WorldWideScience

Sample records for current regulatory approach

  1. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  2. Relevance of animal studies in regulatory toxicology : current approaches and future opportunities

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Feron, V.J.

    1996-01-01

    With rapidly increasing knowledge of toxicological processes, the scientific value and relevance of toxicity studies for risk assessment must be re-evaluated. In this paper, it is proposed that the rigid risk evaluation currently required should be replaced by a more flexible, case-by-case approach,

  3. Current Regulations and Regulatory Actions

    Science.gov (United States)

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  4. Regulatory approaches to obesity prevention: A systematic overview of current laws addressing diet-related risk factors in the European Union and the United States.

    Science.gov (United States)

    Sisnowski, Jana; Handsley, Elizabeth; Street, Jackie M

    2015-06-01

    High prevalence of overweight and obesity remains a significant international public health problem. Law has been identified as a tool for obesity prevention and selected high-profile measures have been reported. However, the nature and extent of enacted legislation internationally are unclear. This research provides an overview of regulatory approaches enacted in the United States, the European Union, and EU Member States since 2004. To this end, relevant databases of primary and secondary legislation were systematically searched to identify and explore laws addressing dietary risk factors for obesity. Across jurisdictions, current regulatory approaches to obesity prevention are limited in reach and scope. Target groups are rarely the general population, but instead sub-populations in government-supported settings. Consumer information provision is preferred over taxation and marketing restrictions other than the regulation of health and nutrition claims. In the EU in particular, product reformulation with industry consent has also emerged as a popular small-scale measure. While consistent and widespread use of law is lacking, governments have employed a range of regulatory measures in the name of obesity prevention, indicating that there is, in principle, political will. Results from this study may serve as a starting point for future research and policy development. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Current Scientific and Regulatory Approaches for Development of Orally Inhaled and Nasal Drug Products: Overview of the IPAC-RS/University of Florida Orlando Inhalation Conference.

    Science.gov (United States)

    Hochhaus, Guenther; Davis-Cutting, Craig; Oliver, Martin; Lee, Sau L; Lyapustina, Svetlana

    2015-09-01

    This article summarizes discussions at the March 2014 conference organized by the University of Florida (UF) and International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS), entitled "Orlando Inhalation Conference: Approaches in International Regulation." The special focus of the conference was on global scientific and regulatory issues associated with the testing and demonstration of equivalence for the registration of orally inhaled drug products (OIDPs) in the United States, Europe, Brazil, China, and India. The scope included all types of OIDPs throughout their lifecycle, e.g., innovator/brand-name products, generics, modifications due to lifecycle management, device changes, etc. Details were presented for the U.S. "weight of evidence approach" for registration of generic products (which includes demonstration of in vitro and in vivo equivalence, as well as quantitative and qualitative sameness, and device similarity). The European "stepwise" approach was elucidated, and the thinking of regulatory agencies in the major emerging markets was clarified. The conference also highlighted a number of areas that would benefit from further research and discussion, especially around patient/device interface and human factor studies, statistical methods and criteria for demonstrating equivalence, the relative roles of in vivo and in vitro tests, and appropriate designs and metrics for in vivo studies of inhaled drugs.

  6. Electricity distribution networks: Changing regulatory approaches

    Science.gov (United States)

    Cambini, Carlo

    2016-09-01

    Increasing the penetration of distributed generation and smart grid technologies requires substantial investments. A study proposes an innovative approach that combines four regulatory tools to provide economic incentives for distribution system operators to facilitate these innovative practices.

  7. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    . Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...... in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US...

  8. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

  9. 76 FR 24836 - Regulatory Approach for Commercial Orbital Human Spaceflight

    Science.gov (United States)

    2011-05-03

    ... Federal Aviation Administration 14 CFR Part 460 Regulatory Approach for Commercial Orbital Human... regulatory approach to commercial orbital human spaceflight by the FAA. This public meeting is intended to... 1200 New Jersey Avenue, SE., Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday,...

  10. Nanorobotics current approaches and techniques

    CERN Document Server

    Ferreira, Antoine

    2013-01-01

    Nanorobot devices now perform a wide variety of tasks at the nanoscale in a wide variety of fields including but not limited to fields such as manufacturing, medicine, supply chain, biology, and outer space. Nanorobotics: Current Approaches and Techniques is a comprehensive overview of this interdisciplinary field with a wide ranging discussion that includes nano-manipulation and industrial nanorobotics, nanorobotics in biology and medicine, nanorobotic sensing, navigation and swarm behavior, and protein and DNA-based nanorobotics. Also included is the latest on topics such as bio-nano-actuators and propulsion and navigation of nanorobotic systems using magnetic fields. Nanorobotics: Current Approaches and Techniques is an ideal book for scientists, researchers, and engineers actively involved in applied and robotic research and development.

  11. Current and future applications of PRA in regulatory activities

    Energy Technology Data Exchange (ETDEWEB)

    Speis, T.P.; Murphy, J.A.; Cunningham, M.A. [Nuclear Regulatory Commission, Washington, DC (United States)] [and others

    1995-04-01

    Probabilistic Risk Assessments (PRAs) have proven valuable in providing the regulators, the nuclear plant operators, and the reactor designers insights into plant safety, reliability, design and operation. Both the NRC Commissioners and the staff have grown to appreciate the valuable contributions PRAs can have in the regulatory arena, though I will admit the existence of some tendencies for strict adherence to the deterministic approach within the agency and the public at large. Any call for change, particularly one involving a major adjustment in approach to the regulation of nuclear power, will meet with a certain degree of resistance and retrenchment. Change can appear threatening and can cause some to question whether the safety mission is being fulfilled. This skepticism is completely appropriate and is, in fact, essential to a proper transition towards risk and performance-based approaches. Our task in the Office of Nuclear Regulatory Research is to increase the PRA knowledge base within the agency and develop appropriate guidance and methods needed to support the transitioning process.

  12. Liquid Biopsies in Oncology and the Current Regulatory Landscape.

    Science.gov (United States)

    Strotman, Lindsay N; Millner, Lori M; Valdes, Roland; Linder, Mark W

    2016-10-01

    There is a profound need in oncology to detect cancer earlier, guide individualized therapies, and better monitor progress during treatment. Currently, some of this information can be achieved through solid tissue biopsy and imaging. However, these techniques are limited because of the invasiveness of the procedure and the size of the tumor. A liquid biopsy can overcome these barriers as its non-invasive nature allows samples to be collected over time. Liquid biopsies may also allow earlier detection than traditional imaging. Liquid biopsies include the analysis of circulating tumor cells (CTCs), cell-free nucleic acid (cfNA), or extracellular vesicles obtained from a variety of biofluids, such as peripheral blood. In this review, we discuss different liquid biopsy types and how they fit into the current regulatory landscape.

  13. Bruxism and Current Treatment Approaches

    Directory of Open Access Journals (Sweden)

    Selin Eren

    2016-06-01

    Full Text Available Among the mastication system disorders bruxism is a parafunctional behavior that comes from psychophysiological origin. Epidemiologic studies have reported great variability of bruxism prevalence. The factors that could cause bruxism is highly controversial. There are different opinions on this issue. The etiologic factors of bruxism include stress, malnutrition, allergic and endocrinologic diseases, central nervous system disorders, genetic factors, medicines, malocclusion, and wrong dental treatment. The aim of treatment of bruxism is to prevent damage that may occur on teeth and in the temporomandibular joint and to eliminate pain. Dental treatment, physical therapy, pharmacological treatment and behavioral and cognitive therapy can be considered for this purpose of treatment. This review summarizes the etiologic factors, epidemiology, diagnosis, and current treatment approaches of patient with bruxism. [Archives Medical Review Journal 2016; 25(2.000: 241-258

  14. Data Integrity-A Study of Current Regulatory Thinking and Action.

    Science.gov (United States)

    Shafiei, Nader; De Montardy, Regis; Rivera-Martinez, Edwin

    2015-01-01

    In reaction to breaches of data integrity in the pharmaceutical industry, regulatory authorities have introduced inspection approaches or initiatives with the aim of reducing occurrences of data integrity problems. This review article-based on study of 65 cases of regulatory action from 2002 to 2014-provides an overview of current regulatory thinking and action on breaches of data integrity affecting GxP (health-related regulations) processes supporting non-clinical studies, clinical studies, laboratory controls, and production controls. These case studies largely represent position of the U.S. Food and Drug Administration and the regulatory agencies affiliated with the European Medicines Agency. Also discussed is the role of human factors as a potential source of data integrity problems. The article concludes by recommending some remedial controls that could be established to avoid or reduce occurrences of data integrity problems.Lay Abstract: In fulfilling their mission to protect public health, regulatory agencies (e.g., U.S. Food and Drug Administration, European Medicines Agency) must establish confidence that medical products they approve are fit for their intended use. In so doing they rely on scientific and operational data generated during research, development, manufacturing, sales, marketing, distribution, and post-marketing surveillance activities. The level of confidence they build is directly proportional to the scientific validity and integrity of data presented to them by the sponsors of medical products. In this article we present analysis of 65 case studies that document regulatory action taken by various regulatory agencies on breach of data integrity between 2002 and 2014. The ensuing discussion on current trends largely represents position of the U.S. Food and Drug Administration and European Medicines Agency. The article concludes by proposing some remedial controls that could be established by pharmaceutical companies to avoid or reduce

  15. [Current Approaches in Cancer Immunotherapy].

    Science.gov (United States)

    Otáhal, P; Trněný, M

    2015-01-01

    Methods of cancer immunotherapy have finally entered clinical medicine after years of preclinical research. Currently, there are several methods, which have proven to be very effective even in cases of incurable cancer. Antitumor monoclonal antibodies are among major therapeutic anti-cancer drugs and have been successfully used for many ears. Novel group of antibodies are immunomodulatory antibodies which can break tumor -specific immune tolerance and induce regression of tumors by nonspecific activation of immune system. Bispecific antibodies represent a novel class of anticancer agents which can induce expansion of T cells in vivo, blinatumomab is an example of such agents and is currently available for the treatment of acute B -cell leukemia. Cellular immunotherapy is also very effective, especially the use of Chimeric receptor modified T-cells for the therapy of B- cell lymphoproliferative diseases. Although it is a very complicated and expensive method, it is highly effective approach which can induce remission even in previously hopeless conditions. The goal of this article is to explain the basic principles of cancer immunotherapy and summarize the newest findings in this field.

  16. Approach of Czech regulatory body to LBB

    Energy Technology Data Exchange (ETDEWEB)

    Tendera, P.

    1997-04-01

    At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany, NPP is about ten years in operation (four units 440 MW - WWBFL model 213) and Tomelin NPP is under construction (two units 1000 MW - WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufacturers. The objective of the Czech LBB program is to prove the LBB status of the primary piping systems of there NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety Facilities too. For both Dukovany and Tomelin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement, {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASMF CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quote} and consist of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

  17. Approach for Czech regulatory body to LBB

    Energy Technology Data Exchange (ETDEWEB)

    Tendera, P. [State Office for Nuclear Safety (SONS), Prague (Czech Republic)

    1997-04-01

    At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany NPP is about ten years in operation (four units 440 MW - WWER model 213) and Temelin NPP is under construction (two units 1000 MW-WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufactures. The objective for the Czech LBB programme is to prove the LBB status of the primary piping systems of these NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety facilities, too. For both Dukovany and Temolin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASME, CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No. 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quotes} and consists of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

  18. Discovery of regulatory elements is improved by a discriminatory approach

    DEFF Research Database (Denmark)

    Valen, Eivind; Sandelin, Albin; Winther, Ole;

    2009-01-01

    A major goal in post-genome biology is the complete mapping of the gene regulatory networks for every organism. Identification of regulatory elements is a prerequisite for realizing this ambitious goal. A common problem is finding regulatory patterns in promoters of a group of co-expressed genes...... present a new computational method for identifying transcription factor binding sites in promoters using a discriminatory approach with a large negative set encompassing a significant sample of the promoters from the relevant genome. The sequences are described by a probabilistic model and the most...

  19. Current clinical approach to achalasia

    Institute of Scientific and Technical Information of China (English)

    Alexander J Eckardt; Volker F Eckardt

    2009-01-01

    Idiopathic achalasia is a rare primary motility disorder of the esophagus.The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus.These motor abnormalities lead to dysphagia,stasis,regurgitation,weight loss,or secondary respiratory complications.Although major strides have been made in understanding the pathogenesis of this rare disorder,including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals,a definite trigger has not been identified.The diagnosis of achalasia is suggested by clinical features and confirmed by further diagnostic tests,such as esophagogastroduodenoscopy (EGD),manometry or barium swallow.These studies are not only used to exclude pseudoachalasia,but also might help to categorize the disease by severity or clinical subtype.Recent advances in diagnostic methods,including high resolution manometry (HRM),might allow prediction of treatment responses.The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods.Although limited high-quality data exist,it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients.However,the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease,but also on local expertise and patient preferences.

  20. Reconciling current approaches to blindsight

    DEFF Research Database (Denmark)

    Overgaard, Morten; Mogensen, Jesper

    2015-01-01

    After decades of research, blindsight is still a mysterious and controversial topic in consciousness research. Currently, many researchers tend to think of it as an ideal phenomenon to investigate neural correlates of consciousness, whereas others believe that blindsight is in fact a kind...

  1. Reconciling current approaches to blindsight

    DEFF Research Database (Denmark)

    Overgaard, Morten; Mogensen, Jesper

    2015-01-01

    After decades of research, blindsight is still a mysterious and controversial topic in consciousness research. Currently, many researchers tend to think of it as an ideal phenomenon to investigate neural correlates of consciousness, whereas others believe that blindsight is in fact a kind...

  2. Carious dentine removal: current approach

    Directory of Open Access Journals (Sweden)

    Germana Coeli de Farias Sales

    2008-01-01

    Full Text Available Dentistry is renewed day after day through the results of qualified researches. The approach as regards carious dentin removal is goingthrough questioning and innovation. The scope of this study was to perform a literature review in the sense of elucidating questions pertaining to the problem of whether or not it is necessary to completely remove carious dentin, and the possibility of performing restoration in a single session, in addition to a discussion about which type of material should be applied in this type of substrate. After analyzing the referenced articles, it was concluded that the stepwise treatment controls caries progression; there is a trend in the literature to partially remove the carious dentin in deep lesions and perform definitive restoration; Calcium hydroxide cement is a classical liner in these situations, while glass ionomer cement and resinous materials are other possibilities of materials that can be in close contact with the remaining dentin.

  3. Evolving PBPK applications in regulatory risk assessment: current situation and future goals

    Science.gov (United States)

    The presentation includes current applications of PBPK modeling in regulatory risk assessment and discussions on conflicts between assuring consistency with experimental data in current situation and the desire for animal-free model development.

  4. A novel parametric approach to mine gene regulatory relationship from microarray datasets

    Directory of Open Access Journals (Sweden)

    Zhu Yunping

    2010-12-01

    Full Text Available Abstract Background Microarray has been widely used to measure the gene expression level on the genome scale in the current decade. Many algorithms have been developed to reconstruct gene regulatory networks based on microarray data. Unfortunately, most of these models and algorithms focus on global properties of the expression of genes in regulatory networks. And few of them are able to offer intuitive parameters. We wonder whether some simple but basic characteristics of microarray datasets can be found to identify the potential gene regulatory relationship. Results Based on expression correlation, expression level variation and vectors derived from microarray expression levels, we first introduced several novel parameters to measure the characters of regulating gene pairs. Subsequently, we used the naïve Bayesian network to integrate these features as well as the functional co-annotation between transcription factors and their target genes. Then, based on the character of time-delay from the expression profile, we were able to predict the existence and direction of the regulatory relationship respectively. Conclusions Several novel parameters have been proposed and integrated to identify the regulatory relationship. This new model is proved to be of higher efficacy than that of individual features. It is believed that our parametric approach can serve as a fast approach for regulatory relationship mining.

  5. Regulatory approaches for addressing dissolved oxygen concerns at hydropower facilities

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Mark J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Cada, Glenn F. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sale, Michael J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Eddlemon, Gerald K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2003-03-01

    Low dissolved oxygen (DO) concentrations are a common water quality problem downstream of hydropower facilities. At some facilities, structural improvements (e.g. installation of weir dams or aerating turbines) or operational changes (e.g., spilling water over the dam) can be made to improve DO levels. In other cases, structural and operational approaches are too costly for the project to implement or are likely to be of limited effectiveness. Despite improvements in overall water quality below dams in recent years, many hydropower projects are unable to meet state water quality standards for DO. Regulatory agencies in the U.S. are considering or implementing dramatic changes in their approach to protecting the quality of the Nation’s waters. New policies and initiatives have emphasized flexibility, increased collaboration and shared responsibility among all parties, and market-based, economic incentives. The use of new regulatory approaches may now be a viable option for addressing the DO problem at some hydropower facilities. This report summarizes some of the regulatory-related options available to hydropower projects, including negotiation of site-specific water quality criteria, use of biological monitoring, watershed-based strategies for the management of water quality, and watershed-based trading. Key decision points center on the health of the local biological communities and whether there are contributing impacts (i.e., other sources of low DO effluents) in the watershed. If the biological communities downstream of the hydropower project are healthy, negotiation for site-specific water quality standards or biocriteria (discharge performance criteria based on characteristics of the aquatic biota) might be pursued. If there are other effluent dischargers in the watershed that contribute to low DO problems, watershed-scale strategies and effluent trading may be effective. This report examines the value of regulatory approaches by reviewing their use in

  6. 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...

  7. A study on the regulatory approach of major technical issues

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Choi, J. T.; Kim, I. J. [Sunmoon Univ., Asan (Korea, Republic of); Lee, S. H.; Baek, W. P.; Yang, S. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

    1998-06-15

    This project is to provide the regulatory direction of 4 major technical issues for the Korean Next Generation Reactors, which are parts of major technical issues resulted from the safety regulation R and D on the KNGR. The outstanding results are as follows : reliability of risk significant SSCs established during design stage must be maintained through the operating life of the plant, currently used classification method of plant conditions and safety requirement were reviewed, and a quantitative classification method is needed to be developed further, the basic regulatory directions are proposed for multiple failures such as SBO, TLOFW, multiple SGTR and ATWS, safety requirements are proposed for survivability/availability of severe accident mitigation design features by 5 items if basic requirements, selection of initial event, identification of available equipment and instruments, identification of environmental conditions and verification methods.

  8. 77 FR 52887 - Regulatory Capital Rules: Standardized Approach for Risk-Weighted Assets; Market Discipline and...

    Science.gov (United States)

    2012-08-30

    ... Regulatory Capital Rules: Standardized Approach for Risk-Weighted Assets; Market Discipline and Disclosure... 12 CFR Part 324 RIN 3064-AD96 Regulatory Capital Rules: Standardized Approach for Risk-Weighted... possible. Please use the title ``Regulatory Capital Rules: Standardized Approach for Risk- weighted...

  9. Clinical development of gene therapy needs a tailored approach: a regulatory perspective from the European Union.

    Science.gov (United States)

    Narayanan, Gopalan; Cossu, Giulio; Galli, Maria Cristina; Flory, Egbert; Ovelgonne, Hans; Salmikangas, Paula; Schneider, Christian K; Trouvin, Jean-Hugues

    2014-03-01

    Gene therapy is a rapidly evolving field that needs an integrated approach, as acknowledged in the concept article on the revision of the guideline on gene transfer medicinal products. The first gene therapy application for marketing authorization was approved in the International Conference on Harmonisation (ICH) region in 2012, the product being Alipogene tiparvovec. The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology. Here, as current or previous members of the Committee for Advanced Therapies, we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the European Union to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful marketing authorization.

  10. Current Status of Regulatory Science Education in Faculties of Pharmaceutical Science in Japan.

    Science.gov (United States)

    Tohkin, Masahiro

    2017-01-01

     I introduce the current pharmaceutical education system in Japan, focusing on regulatory science. University schools or faculties of pharmaceutical science in Japan offer two courses: a six-year course for pharmacists and a four-year course for scientists and technicians. Students in the six-year pharmaceutical course receive training in hospitals and pharmacies during their fifth year, and those in the four-year life science course start research activities during their third year. The current model core curriculum for pharmaceutical education requires them to "explain the necessity and significance of regulatory science" as a specific behavior object. This means that pharmacists should understand the significance of "regulatory science", which will lead to the proper use of pharmaceuticals in clinical practice. Most regulatory science laboratories are in the university schools or faculties of pharmaceutical sciences; however, there are too few to conduct regulatory science education. There are many problems in regulatory science education, and I hope that those problems will be resolved not only by university-based regulatory science researchers but also by those from the pharmaceutical industry and regulatory authorities.

  11. A study on the regulatory approach of major technical issues

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Oh, S. H.; Kang, H. J.; Kim, G. S. [Sunmoon Univ., Asan (Korea, Republic of); Lee, S. H.; Baek, W. P.; Yang, S. H.; Jeong, Y. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

    1999-02-15

    This project is to provide the regulatory direction of 4 major technical issues for the Korean Next Generation Reactors, which are parts of major technical issues resulted from the safety regulation R and D on the KNGR. The outstanding results are are as follows : related to the classification and acceptance criteria of plant conditions, currently used classification and safety requirement were reviewed and regulatory direction was proposed. Among multiple failures, it is identified that SBO, TLOFW, multiple SGTR and ATWS are basically to be considered for additional requirements for advanced reactors. This study reviewed risk aspects, design consideration, and trends of safety requirements, and proposed fundamental safety requirements to be applied for KNGR. Multiple steam generator tube failure is a significant safety concern because of the possibility of release of radionuclides to the environment through containment bypass. Proposed safety requirement for this event can be categorized mainly as analysis requirement, design evaluation requirement and PSA requirement; For protection of containment failure, a reasonable safety position is necessary through and integrated review of possibility of severe accident occurrence, effects of sever accident mitigation features and cost effects of these design features. With this consideration safety requirements developed are the analysis requirement, provision of protective measures and survivability/availability of protective measures.

  12. Regulatory hurdles for genome editing: process- vs. product-based approaches in different regulatory contexts.

    Science.gov (United States)

    Sprink, Thorben; Eriksson, Dennis; Schiemann, Joachim; Hartung, Frank

    2016-07-01

    Novel plant genome editing techniques call for an updated legislation regulating the use of plants produced by genetic engineering or genome editing, especially in the European Union. Established more than 25 years ago and based on a clear distinction between transgenic and conventionally bred plants, the current EU Directives fail to accommodate the new continuum between genetic engineering and conventional breeding. Despite the fact that the Directive 2001/18/EC contains both process- and product-related terms, it is commonly interpreted as a strictly process-based legislation. In view of several new emerging techniques which are closer to the conventional breeding than common genetic engineering, we argue that it should be actually interpreted more in relation to the resulting product. A legal guidance on how to define plants produced by exploring novel genome editing techniques in relation to the decade-old legislation is urgently needed, as private companies and public researchers are waiting impatiently with products and projects in the pipeline. We here outline the process in the EU to develop a legislation that properly matches the scientific progress. As the process is facing several hurdles, we also compare with existing frameworks in other countries and discuss ideas for an alternative regulatory system.

  13. Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties.

    Science.gov (United States)

    Marx-Stoelting, P; Niemann, L; Ritz, V; Ulbrich, B; Gall, A; Hirsch-Ernst, K I; Pfeil, R; Solecki, R

    2014-12-01

    Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation

  14. Electronic cigarettes: A comparison of national regulatory approaches.

    Science.gov (United States)

    Rose, Adam; Filion, Kristian B; Eisenberg, Mark J; Franck, Caroline

    2015-10-03

    E-cigarettes have been readily available to global markets since 2004. However, regulations have lagged behind popular use and availability. As policies emerging from national health agencies have an important role to play in shaping consumer health, we examined the existing and upcoming national regulations surrounding e-cigarette availability and use in a convenience sample of English- and French-speaking countries, including Canada, the United States, the United Kingdom, France, Australia and New Zealand. There is substantial international variation in regulatory policies and the extent to which these are enforced. Of the countries considered in this review, the US has regulations that remain the most permissive, whereas those in Canada and New Zealand are the most conservative. However, regulations in Canada, Australia and New Zealand are easily bypassed through Internet imports and lenient enforcement. European health agencies are paving the way for Member States to take appropriate steps to regulate e-cigarettes according to their own jurisdictions. Currently, national regulations of e-cigarettes appear to be ill-defined in terms of shaping the future of e-cigarette availability and use. National regulations should be strengthened to reflect the public health implications of e-cigarettes and to emphasize their difference from consumer products.

  15. Drug interaction studies on new drug applications: current situations and regulatory views in Japan.

    Science.gov (United States)

    Nagai, Naomi

    2010-01-01

    Drug interaction studies on new drug applications (NDAs) for new molecular entities (NMEs) approved in Japan between 1997 and 2008 are examined in the Pharmaceuticals and Medical Devices Agency (PMDA). The situations of drug interaction studies in NDAs have changed over the past 12 years, especially in metabolizing enzyme and transporter-based drug interactions. Materials and approaches to study drug-metabolizing enzyme-based drug interactions have improved, and become more rational based on mechanistic theory and new technologies. On the basis of incremental evidence of transporter roles in human pharmacokinetics, transporter-based drug interactions have been increasingly studied during drug development and submitted in recent NDAs. Some recently approved NMEs include transporter-based drug interaction information in their package inserts (PIs). The regulatory document "Methods of Drug Interaction Studies," in addition to recent advances in science and technology, has also contributed to plan and evaluation of drug interaction studies in recent new drug development. This review summarizes current situations and further discussion points on drug interaction studies in NDAs in Japan.

  16. 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.

  17. Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

    Science.gov (United States)

    Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

    2016-05-01

    Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

  18. Comparing Teaching Approaches About Maxwell's Displacement Current

    Science.gov (United States)

    Karam, Ricardo; Coimbra, Debora; Pietrocola, Maurício

    2014-08-01

    Due to its fundamental role for the consolidation of Maxwell's equations, the displacement current is one of the most important topics of any introductory course on electromagnetism. Moreover, this episode is widely used by historians and philosophers of science as a case study to investigate several issues (e.g. the theory-experiment relationship). Despite the consensus among physics educators concerning the relevance of the topic, there are many possible ways to interpret and justify the need for the displacement current term. With the goal of understanding the didactical transposition of this topic more deeply, we investigate three of its domains: (1) The historical development of Maxwell's reasoning; (2) Different approaches to justify the term insertion in physics textbooks; and (3) Four lectures devoted to introduce the topic in undergraduate level given by four different professors. By reflecting on the differences between these three domains, significant evidence for the knowledge transformation caused by the didactization of this episode is provided. The main purpose of this comparative analysis is to assist physics educators in developing an epistemological surveillance regarding the teaching and learning of the displacement current.

  19. Computational approaches to analogical reasoning current trends

    CERN Document Server

    Richard, Gilles

    2014-01-01

    Analogical reasoning is known as a powerful mode for drawing plausible conclusions and solving problems. It has been the topic of a huge number of works by philosophers, anthropologists, linguists, psychologists, and computer scientists. As such, it has been early studied in artificial intelligence, with a particular renewal of interest in the last decade. The present volume provides a structured view of current research trends on computational approaches to analogical reasoning. It starts with an overview of the field, with an extensive bibliography. The 14 collected contributions cover a large scope of issues. First, the use of analogical proportions and analogies is explained and discussed in various natural language processing problems, as well as in automated deduction. Then, different formal frameworks for handling analogies are presented, dealing with case-based reasoning, heuristic-driven theory projection, commonsense reasoning about incomplete rule bases, logical proportions induced by similarity an...

  20. A recursive network approach can identify constitutive regulatory circuits in gene expression data

    Science.gov (United States)

    Blasi, Monica Francesca; Casorelli, Ida; Colosimo, Alfredo; Blasi, Francesco Simone; Bignami, Margherita; Giuliani, Alessandro

    2005-03-01

    The activity of the cell is often coordinated by the organisation of proteins into regulatory circuits that share a common function. Genome-wide expression profiles might contain important information on these circuits. Current approaches for the analysis of gene expression data include clustering the individual expression measurements and relating them to biological functions as well as modelling and simulation of gene regulation processes by additional computer tools. The identification of the regulative programmes from microarray experiments is limited, however, by the intrinsic difficulty of linear methods to detect low-variance signals and by the sensitivity of the different approaches. Here we face the problem of recognising invariant patterns of correlations among gene expression reminiscent of regulation circuits. We demonstrate that a recursive neural network approach can identify genetic regulation circuits from expression data for ribosomal and genome stability genes. The proposed method, by greatly enhancing the sensitivity of microarray studies, allows the identification of important aspects of genetic regulation networks and might be useful for the discrimination of the different players involved in regulation circuits. Our results suggest that the constitutive regulatory networks involved in the generic organisation of the cell display a high degree of clustering depending on a modular architecture.

  1. Regulatory approaches to worker protection in nanotechnology industry in the USA and European union.

    Science.gov (United States)

    Murashov, Vladimir; Schulte, Paul; Geraci, Charles; Howard, John

    2011-01-01

    A number of reports have been published regarding the applicability of existing regulatory frameworks to protect consumers and the environment from potentially adverse effects related to introduction of nanomaterials into commerce in the United States and the European Union. However, a detailed comparison of the regulatory approaches to worker safety and health in the USA and in the EU is lacking. This report aims to fill this gap by reviewing regulatory frameworks designed to protect workers and their possible application to nanotechnology.

  2. Iterative reconstruction of transcriptional regulatory networks: an algorithmic approach.

    Directory of Open Access Journals (Sweden)

    Christian L Barrett

    2006-05-01

    Full Text Available The number of complete, publicly available genome sequences is now greater than 200, and this number is expected to rapidly grow in the near future as metagenomic and environmental sequencing efforts escalate and the cost of sequencing drops. In order to make use of this data for understanding particular organisms and for discerning general principles about how organisms function, it will be necessary to reconstruct their various biochemical reaction networks. Principal among these will be transcriptional regulatory networks. Given the physical and logical complexity of these networks, the various sources of (often noisy data that can be utilized for their elucidation, the monetary costs involved, and the huge number of potential experiments approximately 10(12 that can be performed, experiment design algorithms will be necessary for synthesizing the various computational and experimental data to maximize the efficiency of regulatory network reconstruction. This paper presents an algorithm for experimental design to systematically and efficiently reconstruct transcriptional regulatory networks. It is meant to be applied iteratively in conjunction with an experimental laboratory component. The algorithm is presented here in the context of reconstructing transcriptional regulation for metabolism in Escherichia coli, and, through a retrospective analysis with previously performed experiments, we show that the produced experiment designs conform to how a human would design experiments. The algorithm is able to utilize probability estimates based on a wide range of computational and experimental sources to suggest experiments with the highest potential of discovering the greatest amount of new regulatory knowledge.

  3. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  4. Narcolepsy: current treatment options and future approaches

    Directory of Open Access Journals (Sweden)

    Michel Billiard

    2008-06-01

    Full Text Available Michel BilliardDepartment of Neurology, Gui de Chauliac Hospital, Montpellier, FranceAbstract: The management of narcolepsy is presently at a turning point. Three main avenues are considered in this review: 1 Two tendencies characterize the conventional treatment of narcolepsy. Modafinil has replaced methylphenidate and amphetamine as the first-line treatment of excessive daytime sleepiness (EDS and sleep attacks, based on randomized, double blind, placebo-controlled clinical trials of modafinil, but on no direct comparison of modafinil versus traditional stimulants. For cataplexy, sleep paralysis, and hypnagogic hallucinations, new antidepressants tend to replace tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs in spite of a lack of randomized, double blind, placebo-controlled clinical trials of these compounds; 2 The conventional treatment of narcolepsy is now challenged by sodium oxybate, the sodium salt of gammahydroxybutyrate, based on a series of randomized, double-blind, placebo-controlled clinical trials and a long-term open label study. This treatment has a fairly good efficacy and is active on all symptoms of narcolepsy. Careful titration up to an adequate level is essential both to obtain positive results and avoid adverse effects; 3 A series of new treatments are currently being tested, either in animal models or in humans, They include novel stimulant and anticataplectic drugs, endocrine therapy, and, more attractively, totally new approaches based on the present state of knowledge of the pathophysiology of narcolepsy with cataplexy, hypocretine-based therapies, and immunotherapy.Keywords: narcolepsy, treatment, conventional drugs, modafinil, sodium oxybate, future treatments

  5. E-learning tools for education: regulatory aspects, current applications in radiology and future prospects.

    Science.gov (United States)

    Pinto, A; Selvaggi, S; Sicignano, G; Vollono, E; Iervolino, L; Amato, F; Molinari, A; Grassi, R

    2008-02-01

    E-learning, an abbreviation of electronic learning, indicates the provision of education and training on the Internet or the World Wide Web. The impact of networks and the Internet on radiology is undoubtedly important, as it is for medicine as a whole. The Internet offers numerous advantages compared with other mass media: it provides access to a large amount of information previously known only to individual specialists; it is flexible, permitting the use of images or video; and it allows linking to Web sites on a specific subject, thus contributing to further expand knowledge. Our purpose is to illustrate the regulatory aspects (including Internet copyright laws), current radiological applications and future prospects of e-learning. Our experience with the installation of an e-learning platform is also presented. We performed a PubMed search on the published literature (without time limits) dealing with e-learning tools and applications in the health sector with specific reference to radiology. The search included all study types in the English language with the following key words: e-learning, education, teaching, online exam, radiology and radiologists. The Fiaso study was referred to for the regulatory aspects of e-learning. The application of e-learning to radiology requires the development of a model that involves selecting and creating e-learning platforms, creating and technologically adapting multimedia teaching modules, creating and managing a unified catalogue of teaching modules, planning training actions, defining training pathways and Continuing Education in Medicine (CME) credits, identifying levels of teaching and technological complexity of support tools, sharing an organisational and methodological model, training the trainers, operators' participation and relational devices, providing training, monitoring progress of the activities, and measuring the effectiveness of training. Since 2004, a platform--LiveLearning--has been used at our

  6. Prebiotics and the health benefits of fiber: current regulatory status, future research, and goals.

    Science.gov (United States)

    Brownawell, Amy M; Caers, Wim; Gibson, Glenn R; Kendall, Cyril W C; Lewis, Kara D; Ringel, Yehuda; Slavin, Joanne L

    2012-05-01

    First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.

  7. Mindfulness buffers retaliatory responses to injustice: A regulatory approach.

    Science.gov (United States)

    Long, Erin Cooke; Christian, Michael S

    2015-09-01

    We investigate the role of mindfulness as a regulatory factor by examining whether it mitigates the relationship between justice and retaliation. Drawing on theories of self-regulation, we integrate work on justice with emerging frameworks that identify mindfulness as an important work-related regulatory variable (Glomb, Duffy, Bono, & Yang, 2011). Specifically, we identify the role of mindfulness as a buffer of the ruminative thoughts and negative emotions that link injustice to retaliation. We test mediated moderation hypotheses in 2 samples. In Sample 1, two behavioral measures of retaliation are assessed in an experiment that manipulated both injustice and mindfulness. In Sample 2, we generalize our model to the field, examining employee responses regarding experiences with workplace injustice and retaliation. Results of both studies converge to support the proposed mediated moderation model that mindfulness buffers the effect of injustice on rumination and negative emotions, thus reducing retaliation. Our findings contribute to the broader literatures on self-regulation, organizational justice, and retaliation. (c) 2015 APA, all rights reserved).

  8. Integrated Approach to Reconstruction of Microbial Regulatory Networks

    Energy Technology Data Exchange (ETDEWEB)

    Rodionov, Dmitry A [Sanford-Burnham Medical Research Institute; Novichkov, Pavel S [Lawrence Berkeley National Laboratory

    2013-11-04

    This project had the goal(s) of development of integrated bioinformatics platform for genome-scale inference and visualization of transcriptional regulatory networks (TRNs) in bacterial genomes. The work was done in Sanford-Burnham Medical Research Institute (SBMRI, P.I. D.A. Rodionov) and Lawrence Berkeley National Laboratory (LBNL, co-P.I. P.S. Novichkov). The developed computational resources include: (1) RegPredict web-platform for TRN inference and regulon reconstruction in microbial genomes, and (2) RegPrecise database for collection, visualization and comparative analysis of transcriptional regulons reconstructed by comparative genomics. These analytical resources were selected as key components in the DOE Systems Biology KnowledgeBase (SBKB). The high-quality data accumulated in RegPrecise will provide essential datasets of reference regulons in diverse microbes to enable automatic reconstruction of draft TRNs in newly sequenced genomes. We outline our progress toward the three aims of this grant proposal, which were: Develop integrated platform for genome-scale regulon reconstruction; Infer regulatory annotations in several groups of bacteria and building of reference collections of microbial regulons; and Develop KnowledgeBase on microbial transcriptional regulation.

  9. Current Cognitive Approaches to Childhood Psychopathology.

    Science.gov (United States)

    Garfield, Sol L., Ed.

    1984-01-01

    Presents six developmentally oriented articles on childhood psychopathology. Reviews research dealing with autism, social isolation, interpersonal understanding, sociomoral reasoning, cognitive controls, and aggression and includes an overview of progress and problems in the cognitive approach to clinical child psychology. (JAC)

  10. Current approach to burn critical care.

    Science.gov (United States)

    Sakallioglu, A E; Haberal, M

    2007-10-01

    Burn trauma is a frequent cause of morbidity and mortality all over the world. Advancements in resuscitation, surgical tecniques, infection control and nutritional/metaolic support decreased mortality and morbidity. This article intends to review current outlines for initial treatment and resuscitation nutritional/metabolic support and wound management peculiar to burn patients.

  11. iSLIM: a comprehensive approach to mapping and characterizing gene regulatory networks.

    Science.gov (United States)

    Rockel, Sylvie; Geertz, Marcel; Hens, Korneel; Deplancke, Bart; Maerkl, Sebastian J

    2013-02-01

    Mapping gene regulatory networks is a significant challenge in systems biology, yet only a few methods are currently capable of systems-level identification of transcription factors (TFs) that bind a specific regulatory element. We developed a microfluidic method for integrated systems-level interaction mapping of TF-DNA interactions, generating and interrogating an array of 423 full-length Drosophila TFs. With integrated systems-level interaction mapping, it is now possible to rapidly and quantitatively map gene regulatory networks of higher eukaryotes.

  12. Teaching Negotiation in the Context of Environmental Regulatory Enforcement: An Experiential Learning Approach

    Science.gov (United States)

    Choy, Marisa S.; Johnson, Stephen A.; Ortolano, Leonard

    2011-01-01

    This article describes a simulation-based teaching approach that helps university students learn about negotiation in the context of environmental regulatory enforcement. The approach centers on negotiation of a penalty between government agencies and a fictitious corporation that has violated provisions of the U.S. Clean Water Act. The exercise…

  13. Thalassemia: current approach to an old disease.

    Science.gov (United States)

    Lo, Louise; Singer, Sylvia Titi

    2002-12-01

    This article discusses the approach for recognition, diagnosis, and management of the thalassemias, and reviews new prospects of therapy, focusing mostly on the beta-thalassemias--the more severe and clinically important type, beta-thalassemia major is typically treated with regular transfusion and chelation therapy. New strategies for specific therapy including monitoring of iron induced organ damage, fetal hemoglobin augmentation as an alternative for transfusions, bone marrow transplantation offer hope for prevention of complications and better care of the beta-thalassemias.

  14. Regulatory hurdles for genome editing: process- vs. product-based approaches in different regulatory contexts

    OpenAIRE

    Sprink, Thorben; Eriksson, Dennis; Schiemann, Joachim; Hartung, Frank

    2016-01-01

    Novel plant genome editing techniques call for an updated legislation regulating the use of plants produced by genetic engineering or genome editing, especially in the European Union. Established more than 25?years ago and based on a clear distinction between transgenic and conventionally bred plants, the current EU Directives fail to accommodate the new continuum between genetic engineering and conventional breeding. Despite the fact that the Directive 2001/18/EC contains both process- and p...

  15. Current Approaches in the Treatment of Prostatitis

    Directory of Open Access Journals (Sweden)

    Volkan Izol

    2013-02-01

    Full Text Available Prostatitis is an infection or inflammation of the prostate gland that presents as several syndromes with varying clinical features. This painful condition mostly affects young and middle-aged men and diminishes their quality of life. With the recent introduction of a new classification for this disease, more effective approach for the evaluation and management of the patients with chronic pelvic pain syndrome has emerged. Nonetheless, no definitely effective treatment regime has yet been described in the literature. [Archives Medical Review Journal 2013; 22(1.000: 130-140

  16. Current approaches in atrial fibrillation treatment

    Directory of Open Access Journals (Sweden)

    Cenk Sarı

    2014-09-01

    Full Text Available Atrial fibrillation (AF is the most common sustained arrhythmia encountered in clinical practice. Its incidence increases with age. AF is classified into subtypes according to the duration and/or able to provide sinus rhytym. İnitially, patients should be evaluated for rhythm or rate control for appropriate treatment. Second stage of strategy aimed to investigate the feasibility of anticoagulation therapy. Recently, due to the progress made in treatment with rhythm control and anticoagulation therapy, either American or European guidelines have been renovated. These developments have taken place in the newly published guide. In this article, the current change in the management of AF is discussed.

  17. A Framework for Organizing Current and Future Electric Utility Regulatory and Business Models

    Energy Technology Data Exchange (ETDEWEB)

    Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fadrhonc, Emily Martin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-06-01

    Many regulators, utilities, customer groups, and other stakeholders are reevaluating existing regulatory models and the roles and financial implications for electric utilities in the context of today’s environment of increasing distributed energy resource (DER) penetrations, forecasts of significant T&D investment, and relatively flat or negative utility sales growth. When this is coupled with predictions about fewer grid-connected customers (i.e., customer defection), there is growing concern about the potential for serious negative impacts on the regulated utility business model. Among states engaged in these issues, the range of topics under consideration is broad. Most of these states are considering whether approaches that have been applied historically to mitigate the impacts of previous “disruptions” to the regulated utility business model (e.g., energy efficiency) as well as to align utility financial interests with increased adoption of such “disruptive technologies” (e.g., shareholder incentive mechanisms, lost revenue mechanisms) are appropriate and effective in the present context. A handful of states are presently considering more fundamental changes to regulatory models and the role of regulated utilities in the ownership, management, and operation of electric delivery systems (e.g., New York “Reforming the Energy Vision” proceeding).

  18. An efficient approach of attractor calculation for large-scale Boolean gene regulatory networks.

    Science.gov (United States)

    He, Qinbin; Xia, Zhile; Lin, Bin

    2016-11-07

    Boolean network models provide an efficient way for studying gene regulatory networks. The main dynamics of a Boolean network is determined by its attractors. Attractor calculation plays a key role for analyzing Boolean gene regulatory networks. An approach of attractor calculation was proposed in this study, which improved the predecessor-based approach. Furthermore, the proposed approach combined with the identification of constant nodes and simplified Boolean networks to accelerate attractor calculation. The proposed algorithm is effective to calculate all attractors for large-scale Boolean gene regulatory networks. If the average degree of the network is not too large, the algorithm can get all attractors of a Boolean network with dozens or even hundreds of nodes.

  19. MEMS Packaging - Current Issues and Approaches

    Energy Technology Data Exchange (ETDEWEB)

    DRESSENDORFER,PAUL V.; PETERSON,DAVID W.; REBER,CATHLEEN ANN

    2000-01-19

    The assembly and packaging of MEMS (Microelectromechanical Systems) devices raise a number of issues over and above those normally associated with the assembly of standard microelectronic circuits. MEMS components include a variety of sensors, microengines, optical components, and other devices. They often have exposed mechanical structures which during assembly require particulate control, space in the package, non-contact handling procedures, low-stress die attach, precision die placement, unique process schedules, hermetic sealing in controlled environments (including vacuum), and other special constraints. These constraints force changes in the techniques used to separate die on a wafer, in the types of packages which can be used in the assembly processes and materials, and in the sealing environment and process. This paper discusses a number of these issues and provides information on approaches being taken or proposed to address them.

  20. Current endoscopic approach to indeterminate biliary strictures

    Institute of Scientific and Technical Information of China (English)

    David W Victor; Stuart Sherman; Tarkan Karakan; Mouen A Khashab

    2012-01-01

    Biliary strictures are considered indeterminate when basic work-up,including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing,are non-diagnostic.Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome.Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery,but also potential timely targeted chemotherapies.A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is,thus,paramount to avoid unnecessary surgery.Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy.Emerging data on other diagnostic modalities,such as ancillary cytology techniques,single operator cholangioscopy,and endoscopic ultrasonography-guided fine needle aspiration,revealed promising results with much improved sensitivity.

  1. Current approach to cutaneous mastocytosis in childhood.

    Science.gov (United States)

    Tamay, Zeynep; Özçeker, Deniz

    2016-09-01

    Mastocytosis is a heterogeneous disorder characterized by clonal proliferation and accumulation of mast cells in one of more organs which may lead to different clinical pictures. Pathological increase and activation of mast cells in various tissues can cause different clinical pictures. Cutaneous mastocytosis limited to the skin is the most typical clinical picture observed in children and systemic mastocytosis is very rare in the pediatric age group. The diagnosis of cutaneous mastocytosis is based on clinical findings, but is often delayed due to lack of clinical awareness of the disease and lack of its consideration in the differential diagnosis. This article focuses on the current diagnosis, management and treatment of cutaneous mastocytosis in children in order to increase awareness about this issue.

  2. Catastrophic antiphospholipid syndrome: The current management approach.

    Science.gov (United States)

    Rodriguez-Pintó, Ignasi; Espinosa, Gerard; Cervera, Ricard

    2016-04-01

    The current recommendation for catastrophic antiphospholipid syndrome (CAPS) management is the standard triple therapy with anticoagulation (AC), glucocorticoids (GCs), plasma exchange (PE), and/or intravenous immunoglobulins (IVIGs). Of note, only AC has a significant effect on the prognosis of these patients. However, from the experimental or basic point of view, there is only indirect evidence to advocate the use of these immunomodulatory therapies (GC, PE, and IVIG) in CAPS. Recently, there have been reports of severe or refractory CAPS patients treated with the monoclonal antibodies rituximab and eculizumab. The first blocks CD20, a surface protein expressed on the cytoplasmic membrane of B cells, and decreases the generation of pathogenic autoantibodies such as antiphospholipid (aPL) antibodies. The second binds with high affinity to C5 complement protein, inhibiting its cleavage and thus preventing the generation of C5b-C9 complex. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Current therapeutic approaches for plantar fasciitis

    Directory of Open Access Journals (Sweden)

    Martinelli N

    2014-03-01

    Full Text Available Nicolò Martinelli, Carlo Bonifacini, Giovanni RomeoDepartment of Ankle and Foot Surgery, IRCCS Galeazzi Orthopaedic Institute, Milan, ItalyAbstract: Almost 1 million Americans are affected by plantar fasciitis (PF, which is the commonest cause of chronic heel pain. This condition is often managed conservatively, and many rehabilitation protocols, some with the aid of orthoses, have been adopted, with good-to-excellent clinical results. Although most cases of chronic PF can be successfully managed with a conservative approach, alternative treatments, including high-energy shock wave therapy and corticosteroid injections, are commonly accepted as second-line treatment when traditional conservative therapy fails. However, surgery is still an important mode of treatment. Recently, new minimally invasive surgical techniques that offer numerous advantages (faster recovery time, early weight-bearing, lower postoperative pain over standard surgical approaches have been proposed, with good results and low complication rates. The purpose of this review is to report new conservative and surgical techniques for the treatment of PF. A literature search for articles about plantar fasciitis was conducted on the PubMed database in order to identify publications addressing the treatments of PF. The literature suggests that, initially, traditional conservative treatments consisting of rest, oral nonsteroidal anti-inflammatory drugs, foot orthotics, and stretching exercises can be tried for several weeks. In patients with chronic recalcitrant PF, extracorporeal shock wave therapy or corticosteroid injection can be considered. Surgery (minimally invasive techniques should be considered only after failure of the conservative treatments.Keywords: heel pain, surgery, plantar fasciosis

  4. Validation of an entirely in vitro approach for rapid prototyping of DNA regulatory elements for synthetic biology

    Science.gov (United States)

    Chappell, James; Jensen, Kirsten; Freemont, Paul S.

    2013-01-01

    A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology. PMID:23371936

  5. CURRENT APPROACHES TO CHEMORADIOTHERAPY FOR MALIGNANT GLIOMAS

    Directory of Open Access Journals (Sweden)

    Ye. L. Choinzonov

    2014-01-01

    Full Text Available High-grade malignant gliomas (WHO grade G III–IV account for more than 50% of all primary brain tumors. Despite aggressive treatment, survival rates are still very low with a median reported survival of no more than 1.5 years.Radiation therapy is an integral part of the combined treatment, but often does not influence lethally on resistant tumor cells. Thereby, in recent decades there has been an active search for novel approaches to the treatment of malignant gliomas (chemotherapeutic drugs, biological modifiers, local hyperthermia. Experimental data showed that the effect of high temperatures has both a direct damaging effect on tumor cells and a sensitizing effect. Significant advantages are achieved when the complex treatment of different malignant tumorsincludes local hyperthermia. However data on the treatment of patients with primary and recurrent gliomas G III–IV using local hyperthermia are scarce.The literature review is given in the article provides an overview of the existing treatment methods for brain tumors.

  6. Pulp regeneration: Current approaches and future challenges

    Directory of Open Access Journals (Sweden)

    Jingwen eYANG

    2016-03-01

    Full Text Available Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α, basic Fibroblast Growth Factor (bFGF, Platelet Derived Growth Factor (PDGF, stem cell factor (SCF, and Granulocyte Colony-Stimulating Factor (G-CSF were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration.

  7. Pulp Regeneration: Current Approaches and Future Challenges.

    Science.gov (United States)

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), stem cell factor (SCF), and Granulocyte Colony-Stimulating Factor (G-CSF) were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration.

  8. Pulp Regeneration: Current Approaches and Future Challenges

    Science.gov (United States)

    Yang, Jingwen; Yuan, Guohua; Chen, Zhi

    2016-01-01

    Regenerative endodontics aims to replace inflamed/necrotic pulp tissues with regenerated pulp-like tissues to revitalize teeth and improve life quality. Pulp revascularization case reports, which showed successful clinical and radiographic outcomes, indicated the possible clinical application of pulp regeneration via cell homing strategy. From a clinical point of view, functional pulp-like tissues should be regenerated with the characterization of vascularization, re-innervation, and dentin deposition with a regulated rate similar to that of normal pulp. Efficient root canal disinfection and proper size of the apical foramen are the two requisite preconditions for pulp regeneration. Progress has been made on pulp regeneration via cell homing strategies. This review focused on the requisite preconditions and cell homing strategies for pulp regeneration. In addition to the traditionally used mechanical preparation and irrigation, antibiotics, irrigation assisted with EndoVac apical negative-pressure system, and ultrasonic and laser irradiation are now being used in root canal disinfection. In addition, pulp-like tissues could be formed with the apical foramen less than 1 mm, although more studies are needed to determine the appropriate size. Moreover, signaling molecules including stromal cell derived factor (SDF-1α), basic Fibroblast Growth Factor (bFGF), Platelet Derived Growth Factor (PDGF), stem cell factor (SCF), and Granulocyte Colony-Stimulating Factor (G-CSF) were used to achieve pulp-like tissue formation via a cell homing strategy. Studies on the cell sources of pulp regeneration might give some indications on the signaling molecular selection. The active recruitment of endogenous cells into root canals to regenerate pulp-like tissues is a novel concept that may offer an unprecedented opportunity for the near-term clinical translation of current biology-based therapies for dental pulp regeneration. PMID:27014076

  9. Regulatory risk assessment approaches for synthetic mineral fibres.

    Science.gov (United States)

    Harrison, Paul; Holmes, Philip; Bevan, Ruth; Kamps, Klaus; Levy, Leonard; Greim, Helmut

    2015-10-01

    Exposure to synthetic mineral fibres (SMF) may occur in a number of workplace scenarios. To protect worker health, a number of different organisations worldwide have assessed the health risk of these materials and established workplace exposure limits. This paper outlines the basic principles of risk assessment and the scientific methods used to derive valid (justifiable) occupational exposure limits (OELs) and goes on to show how, for SMF, and particularly for refractory ceramic fibre (otherwise known as aluminosilicate wool, RCF/ASW), the methods used and the associated outcomes differ widely. It is argued that the resulting differences in established OELs prevent consistent and appropriate risk management of SMF worldwide, and that development of a transparent and harmonised approach to fibre risk assessment and limit-setting is required.

  10. Beyond the Thumbrule Approach: Regulatory Innovations for Bioprospecting in India

    Directory of Open Access Journals (Sweden)

    Kabir Sanjay Bavikatte and Morten Walløe Tvedt

    2015-06-01

    Full Text Available In the wake of the Nagoya Protocol on Access and Benefit Sharing (ABS, there is unprecedented attention on good Green Governance, which implies the development of resource efficient, rights based and effective domestic frameworks to regulate bioprospecting. India has been pioneering in this regard due to its ABS legislation in 2002 that long preceded the Nagoya Protocol. However much has changed since 2002 and while India has learnt a great deal from its ‘learning by doing’ method, there are valuable lessons that can be learnt from innovations in the ABS frameworks of other countries. The innovations of these countries are a great resource for National Biodiversity Authority (NBA in India that is seeking to make the processing of the bioprospecting applications in India more optimal. The current paper highlights the challenges faced by the NBA in processing the high volumes of bioprospecting applications, analyses the reasons for such challenges and proposes solutions for the same.

  11. California Groundwater Management During Drought: Existing and Future Regulatory Approaches

    Science.gov (United States)

    Ekdahl, E.; Boland-Brien, S.; Vanderburgh, B.; Landau, K.; Bean, J.; Peltier, T.

    2015-12-01

    Groundwater has served as an effective buffer to California's crippling drought of 2012-2015, allowing continued agricultural production in many areas where surface water deliveries have been curtailed. However, over-reliance on groundwater has caused plummeting groundwater levels in much of the state's heavily agricultural regions, with annual groundwater overdraft state-wide estimated in the millions of acre-feet per year. Prior to 2015, California water law did not allow for the effective monitoring or assessment of groundwater use; passage of new state regulations will require development of locally-managed plans that, for the first time, require comprehensive groundwater management and groundwater basin sustainability. Because these plans are not required to be implemented for another 25 years, groundwater levels will likely continue to decrease. Some communities that are 100-percent reliant on groundwater as a source of municipal supply may face shortages and supply issues, which may exacerbate known water quality concerns. Examination of community water systems that are reliant on groundwater, their existing water quality issues, and their response to the current drought (through existing mandatory conservation requirements imposed by California state regulators) can identify areas that are particularly susceptible to continued groundwater overdraft.

  12. Current status and regulatory perspective of chimeric antigen receptor-modified T cell therapeutics.

    Science.gov (United States)

    Kim, Mi-Gyeong; Kim, Dongyoon; Suh, Soo-Kyung; Park, Zewon; Choi, Min Joung; Oh, Yu-Kyoung

    2016-04-01

    Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a new modality for cancer immunotherapy due to their potent efficacy against terminal cancers. CAR-Ts are reported to exert higher efficacy than monoclonal antibodies and antibody-drug conjugates, and act via mechanisms distinct from T cell receptor-engineered T cells. These cells are constructed by transducing genes encoding fusion proteins of cancer antigen-recognizing single-chain Fv linked to intracellular signaling domains of T cell receptors. CAR-Ts are classified as first-, second- and third-generation, depending on the intracellular signaling domain number of T cell receptors. This review covers the current status of CAR-T research, including basic proof-of-concept investigations at the cell and animal levels. Currently ongoing clinical trials of CAR-T worldwide are additionally discussed. Owing to the lack of existing approved products, several unresolved concerns remain with regard to safety, efficacy and manufacturing of CAR-T, as well as quality control issues. In particular, the cytokine release syndrome is the major side-effect impeding the successful development of CAR-T in clinical trials. Here, we have addressed the challenges and regulatory perspectives of CAR-T therapy.

  13. Towards a single European electricity market: A structured approach to regulatory mode decision-making

    NARCIS (Netherlands)

    De Jong, H.M.

    2009-01-01

    This study focuses on the processes through which the rules and regulations that govern European electricity markets - and inherently, their integration process - are established. So far, European policy makers have largely followed a 'trial-and-error' approach to finding an appropriate regulatory

  14. 77 FR 63763 - Regulatory Capital Rules: Standardized Approach for Risk-Weighted Assets; Market Discipline and...

    Science.gov (United States)

    2012-10-17

    ... Country Risk Classification ratings produced by the Organization for Economic Co-Operation and Development... Approach for Risk-Weighted Assets; Market Discipline and Disclosure Requirements; Initial Regulatory... analysis. SUMMARY: On August 30, 2012, the Federal Deposit Insurance Corporation (FDIC), together with the...

  15. Towards a single European electricity market: A structured approach to regulatory mode decision-making

    NARCIS (Netherlands)

    De Jong, H.M.

    2009-01-01

    This study focuses on the processes through which the rules and regulations that govern European electricity markets - and inherently, their integration process - are established. So far, European policy makers have largely followed a 'trial-and-error' approach to finding an appropriate regulatory m

  16. Resting in peace?- regulatory approaches to the geological storage of radioactive waste and carbon dioxide

    Energy Technology Data Exchange (ETDEWEB)

    Langlet, David (School of Business, Economics and Law, Univ. of Goeteborg, Goeteborg (Sweden))

    2010-09-15

    An emerging and much heralded technology for fighting climate change by reducing anthropogenic greenhouse gas emissions is carbon capture and storage (CCS). The final stage of CCS is the storage (or disposal) of the carbon dioxide (CO{sub 2}) away from the atmosphere, typically in a deep geological formation. Although the risks posed by CO{sub 2} differ from those presented by nuclear waste and spent fuel, the similarities - most noticeably the vast time scales involved and the preference for concentration and containment - make a comparison of regulatory approaches to such risks relevant and informative. The intention of the current paper is to carry out such a comparison. Using Sweden as a focal point, applicable legal frameworks for the management of captured CO{sub 2} and spent nuclear fuel and nuclear waste will be juxtaposed. Two aspects in particular will be chosen for closer scrutiny: requirements pertaining to the selection of sites for disposal/storage of nuclear material and captured CO{sub 2} respectively, and the nature and allocation of economic responsibility for handling and minimizing long-term hazards associated with those substances. In the case of nuclear residues, responsibility for spent fuel will be the main focus. However, the same principles mostly apply to other radioactive waste from the nuclear industry, such as parts of decommissioned nuclear reactors

  17. Parsing regulatory DNA: General tasks, techniques, and the PhyloGibbs approach

    Indian Academy of Sciences (India)

    Rahul Siddharthan

    2007-08-01

    In this review, we discuss the general problem of understanding transcrip tional regulation from DNA sequence and prior information. The main tasks we discuss are predicting local regions of DNA, cis-regulatory modules (CRMs) that contain binding sites for transcription factors (TFs), and predicting individ ual binding sites. We review various existing methods, and then describe the approach taken by PhyloGibbs, a recent motif-finding algorithm that we developed to predict TF binding sites, and PhyloGibbs-MP, an extension to PhyloGibbs that tackles other tasks in regulatory genomics, particularly prediction of CRMs.

  18. Current approaches in evolution: from molecules to cells and organisms.

    Science.gov (United States)

    Thattai, Mukund; Peisajovich, Sergio G

    2014-11-01

    This is an exciting time to be an evolutionary biologist. Indeed, it is difficult to keep up with all the studies that fall under the broad category of "Evolution" since they span species, traits, and scales of organization. This special issue gives a flavor of exciting new approaches in evolutionary biology, but also emphasizes universal themes. The reviews contained here discuss important aspects of molecular evolution at multiple scales, from individual proteins to complex regulatory networks, as well as from unicellular organisms to macroscopic traits in animals. Though the model systems are diverse, the issues addressed are fundamental: the origin of evolutionary novelties, and the forces that drive them to fixation.

  19. Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs) in Taiwan

    Science.gov (United States)

    Tsai, Wen-Tien

    2010-01-01

    Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years. PMID:21139852

  20. Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs in Taiwan

    Directory of Open Access Journals (Sweden)

    Wen-Tien Tsai

    2010-10-01

    Full Text Available Organochlorine pesticides (OCPs are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs and even as endocrine disrupting chemicals (EDCs. The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs. The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years.

  1. From System-Wide Differential Gene Expression to Perturbed Regulatory Factors: A Combinatorial Approach.

    Directory of Open Access Journals (Sweden)

    Gaurang Mahajan

    Full Text Available High-throughput experiments such as microarrays and deep sequencing provide large scale information on the pattern of gene expression, which undergoes extensive remodeling as the cell dynamically responds to varying environmental cues or has its function disrupted under pathological conditions. An important initial step in the systematic analysis and interpretation of genome-scale expression alteration involves identification of a set of perturbed transcriptional regulators whose differential activity can provide a proximate hypothesis to account for these transcriptomic changes. In the present work, we propose an unbiased and logically natural approach to transcription factor enrichment. It involves overlaying a list of experimentally determined differentially expressed genes on a background regulatory network coming from e.g. literature curation or computational motif scanning, and identifying that subset of regulators whose aggregated target set best discriminates between the altered and the unaffected genes. In other words, our methodology entails testing of all possible regulatory subnetworks, rather than just the target sets of individual regulators as is followed in most standard approaches. We have proposed an iterative search method to efficiently find such a combination, and benchmarked it on E. coli microarray and regulatory network data available in the public domain. Comparative analysis carried out on artificially generated differential expression profiles, as well as empirical factor overexpression data for M. tuberculosis, shows that our methodology provides marked improvement in accuracy of regulatory inference relative to the standard method that involves evaluating factor enrichment in an individual manner.

  2. From System-Wide Differential Gene Expression to Perturbed Regulatory Factors: A Combinatorial Approach.

    Science.gov (United States)

    Mahajan, Gaurang; Mande, Shekhar C

    2015-01-01

    High-throughput experiments such as microarrays and deep sequencing provide large scale information on the pattern of gene expression, which undergoes extensive remodeling as the cell dynamically responds to varying environmental cues or has its function disrupted under pathological conditions. An important initial step in the systematic analysis and interpretation of genome-scale expression alteration involves identification of a set of perturbed transcriptional regulators whose differential activity can provide a proximate hypothesis to account for these transcriptomic changes. In the present work, we propose an unbiased and logically natural approach to transcription factor enrichment. It involves overlaying a list of experimentally determined differentially expressed genes on a background regulatory network coming from e.g. literature curation or computational motif scanning, and identifying that subset of regulators whose aggregated target set best discriminates between the altered and the unaffected genes. In other words, our methodology entails testing of all possible regulatory subnetworks, rather than just the target sets of individual regulators as is followed in most standard approaches. We have proposed an iterative search method to efficiently find such a combination, and benchmarked it on E. coli microarray and regulatory network data available in the public domain. Comparative analysis carried out on artificially generated differential expression profiles, as well as empirical factor overexpression data for M. tuberculosis, shows that our methodology provides marked improvement in accuracy of regulatory inference relative to the standard method that involves evaluating factor enrichment in an individual manner.

  3. Self-regulatory Behaviors and Approaches to Learning of Arts Students: A Comparison Between Professional Training and English Learning.

    Science.gov (United States)

    Tseng, Min-Chen; Chen, Chia-Cheng

    2016-11-17

    This study investigated the self-regulatory behaviors of arts students, namely memory strategy, goal-setting, self-evaluation, seeking assistance, environmental structuring, learning responsibility, and planning and organizing. We also explored approaches to learning, including deep approach (DA) and surface approach (SA), in a comparison between students' professional training and English learning. The participants consisted of 344 arts majors. The Academic Self-Regulation Questionnaire and the Revised Learning Process Questionnaire were adopted to examine students' self-regulatory behaviors and their approaches to learning. The results show that a positive and significant correlation was found in students' self-regulatory behaviors between professional training and English learning. The results indicated that increases in using self-regulatory behaviors in professional training were associated with increases in applying self-regulatory behaviors in learning English. Seeking assistance, self-evaluation, and planning and organizing were significant predictors for learning English. In addition, arts students used the deep approach more often than the surface approach in both their professional training and English learning. A positive correlation was found in DA, whereas a negative correlation was shown in SA between students' self-regulatory behaviors and their approaches to learning. Students with high self-regulation adopted a deep approach, and they applied the surface approach less in professional training and English learning. In addition, a SEM model confirmed that DA had a positive influence; however, SA had a negative influence on self-regulatory behaviors.

  4. Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

    Science.gov (United States)

    Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

    2015-08-26

    The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme.

  5. Adaptive modelling of gene regulatory network using Bayesian information criterion-guided sparse regression approach.

    Science.gov (United States)

    Shi, Ming; Shen, Weiming; Wang, Hong-Qiang; Chong, Yanwen

    2016-12-01

    Inferring gene regulatory networks (GRNs) from microarray expression data are an important but challenging issue in systems biology. In this study, the authors propose a Bayesian information criterion (BIC)-guided sparse regression approach for GRN reconstruction. This approach can adaptively model GRNs by optimising the l1-norm regularisation of sparse regression based on a modified version of BIC. The use of the regularisation strategy ensures the inferred GRNs to be as sparse as natural, while the modified BIC allows incorporating prior knowledge on expression regulation and thus avoids the overestimation of expression regulators as usual. Especially, the proposed method provides a clear interpretation of combinatorial regulations of gene expression by optimally extracting regulation coordination for a given target gene. Experimental results on both simulation data and real-world microarray data demonstrate the competent performance of discovering regulatory relationships in GRN reconstruction.

  6. Risk assessment of GM trees in the EU: current regulatory framework and guidance

    Directory of Open Access Journals (Sweden)

    Aguilera J

    2013-04-01

    Full Text Available The use of genetically modified organisms - their release into the environment, import, and utilisation as food/feed or food/feed ingredients - is regulated in the European Union (EU. For placing onto the market, current legislations require a comprehensive and science-based risk assessment. This risk assessment (RA is performed by applicants and then evaluated by national authorities in close cooperation with the European Food Safety Authority (EFSA. The EFSA Panel on Genetically Modified Organisms (GMO has published a comprehensive set of guidance documents for applicants and risk assessors for the RA of GM plants (GMP, their products for food and/or feed use, and their cultivation. In those documents, the strategy and the criteria to conduct the assessment are explained, as well as the scientific data to be provided by the applicant. The assessment starts with the molecular characterisation of the GMP. If the GMP or products derived from it are to be consumed, the evaluation of its composition, potential toxicity and/or allergenicity, and nutritional value constitute further cornerstones of the process. The environmental risk assessment (ERA considers biotic and abiotic interactions and the impacts of the management of the GM plant when it is intended for cultivation. In the case of GM trees special emphasis would be placed on assessing their characteristic features such as their longevity, ability to disperse and their ecological significance in a range of environments. The outcome of the assessment is reflected in a published opinion from the EFSA GMO panel that indicates whether the GMP and its products raise any safety issues. This scientific opinion constitutes one of the elements taken into account by the different European regulatory authorities prior to a decision regarding authorisation to commercialise the product.

  7. [Regulatory Program for Medical Devices in Cuba: experiences and current challenges].

    Science.gov (United States)

    Pereira, Dulce María Martínez; Rodríguez, Yadira Álvarez; Valdés, Yamila Cedeño; Ribas, Silvia Delgado

    2016-05-01

    Regulatory control of medical devices in Cuba is conducted through a system based on the Regulatory Program for Medical Devices as a way to ensure the safety, efficacy, and effectiveness of these technologies, which are in use by the National Health System. This program was launched in 1992, when the Regulations for State Evaluation and Registration of Medical Devices were approved. Its successive stages and the merging of regulatory activities for drugs and medical equipment have meant progress toward stronger, more transparent strategies and greater control of industry and the National Health System. Throughout its course the Cuban program has met with challenges and difficulties that it has addressed by drawing on its own experiences. During the new period, the greatest challenges revolve around ensuring that regulatory systems incorporate scientific evaluation, risk levels, maximum rigor through the use of technical standards, and the implementation of international recommendations, together with the application of the ISO 13485 certification scheme, enhanced market monitoring, and classification of medical devices in accordance with their relevance to the country's national health policies. From the regional standpoint, the greatest challenge lies in working toward regulatory convergence. The Collaborating Centre for the Regulation of Health Technologies will support the proposed regulatory strategy and established regional priorities, in particular in connection with the implementation of actions involving medical devices.

  8. Basel II Approaches for the Calculation of the Regulatory Capital for Operational Risk

    Directory of Open Access Journals (Sweden)

    Ivana Valová

    2011-01-01

    Full Text Available The final version of the New Capital Accord, which includes operational risk, was released by the Basel Committee on Banking Supervision in June 2004. The article “Basel II approaches for the calculation of the regulatory capital for operational risk” is devoted to the issue of operational risk of credit financial institutions. The paper talks about methods of operational risk calculation, advantages and disadvantages of particular methods.

  9. A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Xin Lai

    2013-01-01

    Full Text Available MicroRNAs (miRNAs are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.

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

    Directory of Open Access Journals (Sweden)

    Pawandeep Dhami

    Full Text Available The SCL (TAL1 transcription factor is a critical regulator of haematopoiesis and its expression is tightly controlled by multiple cis-acting regulatory elements. To elaborate further the DNA elements which control its regulation, we used genomic tiling microarrays covering 256 kb of the human SCL locus to perform a concerted analysis of chromatin structure and binding of regulatory proteins in human haematopoietic cell lines. This approach allowed us to characterise further or redefine known human SCL regulatory elements and led to the identification of six novel elements with putative regulatory function both up and downstream of the SCL gene. They bind a number of haematopoietic transcription factors (GATA1, E2A LMO2, SCL, LDB1, CTCF or components of the transcriptional machinery and are associated with relevant histone modifications, accessible chromatin and low nucleosomal density. Functional characterisation shows that these novel elements are able to enhance or repress SCL promoter activity, have endogenous promoter function or enhancer-blocking insulator function. Our analysis opens up several areas for further investigation and adds new layers of complexity to our understanding of the regulation of SCL expression.

  11. A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

    Science.gov (United States)

    White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

    2017-08-01

    Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

  12. Systematic Approach to Computational Design of Gene Regulatory Networks with Information Processing Capabilities.

    Science.gov (United States)

    Moskon, Miha; Mraz, Miha

    2014-01-01

    We present several measures that can be used in de novo computational design of biological systems with information processing capabilities. Their main purpose is to objectively evaluate the behavior and identify the biological information processing structures with the best dynamical properties. They can be used to define constraints that allow one to simplify the design of more complex biological systems. These measures can be applied to existent computational design approaches in synthetic biology, i.e., rational and automatic design approaches. We demonstrate their use on a) the computational models of several basic information processing structures implemented with gene regulatory networks and b) on a modular design of a synchronous toggle switch.

  13. Cancer of the cervix: current management and new approaches.

    Science.gov (United States)

    Shivnani, Anand T; Rimel, B J; Schink, Julian; Small, William

    2006-11-01

    This article summarizes the current management of patients with newly diagnosed cervical cancer. The topics range from the management of early-stage disease to the phase III randomized studies that have established the current standard of care for patients with locally advanced cancer of the cervix. New approaches to combined-modality therapy with the goal of improving outcomes and decreasing complications are also described.

  14. Use of Biosensors as Alternatives to Current Regulatory Methods for Marine Biotoxins

    Directory of Open Access Journals (Sweden)

    Luis M. Botana

    2009-11-01

    Full Text Available Marine toxins are currently monitored by means of a bioassay that requires the use of many mice, which poses a technical and ethical problem in many countries. With the exception of domoic acid, there is a legal requirement for the presence of other toxins (yessotoxin, saxitoxin and analogs, okadaic acid and analogs, pectenotoxins and azaspiracids in seafood to be controlled by bioassay, but other toxins, such as palytoxin, cyclic imines, ciguatera and tetrodotoxin are potentially present in European food and there are no legal requirements or technical approaches available to identify their presence. The need for alternative methods to the bioassay is clearly important, and biosensors have become in recent years a feasible alternative to animal sacrifice. This review will discuss the advantages and disadvantages of using biosensors as alternatives to animal assays for marine toxins, with particular focus on surface plasmon resonance (SPR technology.

  15. [Valences of self-evaluation and approach-avoidance tendencies: research based on regulatory focus theory].

    Science.gov (United States)

    Ozaki, Yuka; Karasawa, Kaori

    2011-12-01

    Four studies were conducted to investigate the relationship between valences of self-evaluation and approach-avoidance tendencies. Based on regulatory focus theory (Higgins, 1997, 1998), we predicted that positivity of self-evaluation is related to the tendency to approach gains, while negativity of self-evaluation is related to the tendency to avoid losses. In Study 1, a self-report measure of behavioral tendencies for approaching gains and avoiding losses was developed. In Studies 2 to 4, correlations between these approach/avoidance tendencies and various kinds of self-evaluations were examined. Overall, the authors' predictions were supported. The results suggest that the self-evaluation system and the self-regulation system work in close cooperation with each other in controlling human behavior.

  16. The European Model Company Act: How to choose an efficient regulatory approach?

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    European Company Law regulation is currently undergoing a reform. These reforms raise a number of regulatory questions, such as what the aims of companies legislation should be, and how these aims should best be met by regulation. Many of the reforms and discussions (both on EU and national level......) on the organization of company laws reflect an interesting paradigm shift. Whereas, previously company law was primarily focused on preventing abuse, there is now a trend towards legislation that promote commerce and satisfy the needs of business. This means that the goal of economic efficiency is having...... an increasing influence on the framing of company legislation, such as the choice between mandatory or default rules. This article introduces the project "European Company Law and the choice of Regulatory Method" which is carried out in collaboration with the European Model Company Act Group. The project aims...

  17. Predicting how individuals approach enrichment: regulatory focus in cotton-top tamarins (Sanguinus oedipus).

    Science.gov (United States)

    Franks, Becca; Reiss, Diana; Cole, Patricia; Friedrich, Volney; Thompson, Nicole; Higgins, E Tory

    2013-01-01

    Evidence is mounting that personality is associated with health and well-being in humans and other animals. In a step towards increasing our understanding of this link, we applied regulatory focus theory, a motivational perspective from social psychology, to the behavior of zoo-housed cotton top tamarins. We tested whether regulatory focus "personality," that is stable differences in whether an individual is motivated by gains versus safety, would 1) produce individual differences in behavior and 2) predict how individuals interact with enrichment. First, we characterized individuals with respect to several key behaviors: eating in the open, hiding, and time spent near the front of the exhibit. The monkeys were consistent in their behavioral tendencies across the 6-month study, allowing regulatory focus classification. One monkey showed evidence of being a promotion-individual, that is, more motivated by gains than safety. One monkey showed evidence of being a prevention-individual, that is, more motivated by safety than gains. The other monkeys were stable in their behavior and showed evidence of being intermediate-individuals, that is, they favored neither gains nor safety. Using these characterizations, we predicted distinct patterns of individual-object interactions with enrichment. For example, we predicted that a promotion-individual (favoring gains over safety) would approach potential gains faster than a prevention-individual (favoring safety over gains). Counter-intuitively, however, we also predicted that a promotion-individual would approach non-gains slower than a prevention-individual concerned with safety. We found support for our predictions, which suggests that regulatory focus theory could be a useful tool for understanding how and why individuals interact with environmental enrichment.

  18. Non-human primate regulatory T cells: Current biology and implications for transplantation

    NARCIS (Netherlands)

    E.M. Dons (Eefje); G. Raimondi (Giorgio); D.K.C. Cooper (David); A.W. Thomson (Angus)

    2010-01-01

    textabstractRegulatory T cells (Treg) offer potential for improving long-term outcomes in cell and organ transplantation. The non-human primate model is a valuable resource for addressing issues concerning the transfer of Treg therapy to the clinic. Herein, we discuss the properties of non-human pri

  19. Alternative approaches for identifying acute systemic toxicity: Moving from research to regulatory testing.

    Science.gov (United States)

    Hamm, Jon; Sullivan, Kristie; Clippinger, Amy J; Strickland, Judy; Bell, Shannon; Bhhatarai, Barun; Blaauboer, Bas; Casey, Warren; Dorman, David; Forsby, Anna; Garcia-Reyero, Natàlia; Gehen, Sean; Graepel, Rabea; Hotchkiss, Jon; Lowit, Anna; Matheson, Joanna; Reaves, Elissa; Scarano, Louis; Sprankle, Catherine; Tunkel, Jay; Wilson, Dan; Xia, Menghang; Zhu, Hao; Allen, David

    2017-06-01

    Acute systemic toxicity testing provides the basis for hazard labeling and risk management of chemicals. A number of international efforts have been directed at identifying non-animal alternatives for in vivo acute systemic toxicity tests. A September 2015 workshop, Alternative Approaches for Identifying Acute Systemic Toxicity: Moving from Research to Regulatory Testing, reviewed the state-of-the-science of non-animal alternatives for this testing and explored ways to facilitate implementation of alternatives. Workshop attendees included representatives from international regulatory agencies, academia, nongovernmental organizations, and industry. Resources identified as necessary for meaningful progress in implementing alternatives included compiling and making available high-quality reference data, training on use and interpretation of in vitro and in silico approaches, and global harmonization of testing requirements. Attendees particularly noted the need to characterize variability in reference data to evaluate new approaches. They also noted the importance of understanding the mechanisms of acute toxicity, which could be facilitated by the development of adverse outcome pathways. Workshop breakout groups explored different approaches to reducing or replacing animal use for acute toxicity testing, with each group crafting a roadmap and strategy to accomplish near-term progress. The workshop steering committee has organized efforts to implement the recommendations of the workshop participants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Current approaches for detection of carcinoma in situ testis

    DEFF Research Database (Denmark)

    Hoei-Hansen, Christina E; Olesen, Inge A; Jørgensen, Niels

    2007-01-01

    of carcinoma in situ (CIS). This review describes current possible approaches for the detection of CIS. At present, an open testicular biopsy is the only definitive way of establishing the presence of CIS. The tissue section should be of an adequate size, be properly fixed, and evaluation be supported...

  1. LIMITATIONS OF CURRENT APPROACHES FOR THE TREATMENT OF ACROMEGALY.

    Science.gov (United States)

    Shanik, Michael H

    2016-02-01

    Acromegaly is a rare disease characterized by hypersecretion of growth hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients with acromegaly have an increased risk of mortality and progressive worsening of comorbidities. Surgery, medical therapy, and radiotherapy are currently available treatment approaches for patients with acromegaly, with overall therapeutic goals of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size, improving comorbidities, and minimizing mortality risk. Although surgery can lead to biochemical remission in some patients with acromegaly, many patients will continue to have uncontrolled disease and require additional treatment. We reviewed recently published reports and present a summary of the safety and efficacy of current treatment modalities for patients with acromegaly. A substantial proportion of patients who receive medical therapy or radiotherapy will have persistently elevated GH and/or IGF-1. Because of the serious health consequences of continued elevation of GH and IGF-1, there is a need to improve therapeutic approaches to optimize biochemical control, particularly in high-need patient populations for whom current treatment options provide limited benefit. This review discusses current treatment options for patients with acromegaly, limitations associated with each treatment approach, and areas within the current treatment algorithm, as well as patient populations for which improved therapeutic options are needed. Novel agents in development were also highlighted, which have the potential to improve management of patients with uncontrolled or persistent acromegaly.

  2. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    Directory of Open Access Journals (Sweden)

    Sai Vikram Vemula

    2016-04-01

    Full Text Available Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans.

  3. The wider use of fixed-dose combinations emphasizes the need for a global approach to regulatory guideline development

    DEFF Research Database (Denmark)

    Gautam, Yvonne; Bjerrum, Ole Jannik; Schmiegelow, Merete

    2015-01-01

    face the regulatory world: how to improve the role of regulatory science and provide clear quantification in assessment decisions; the role of guidelines and their impact on innovation; and, most important, the question of globalization and how to move toward a more harmonized regulatory system....... in the EU and US. A review of the FDC guidelines set forth by the EMA, FDA, and ICH, followed by interviews of key informants in industry, identified 5 main industry concerns related to development of FDCs. These concerns were presented to key informants from both the EU and US regulatory authorities....... It was clear from the results that the current regulatory environment for FDCs lacks consistency. This may create a barrier to innovation moving from the laboratory to the clinic, as companies cannot clearly see the development path requirements. This project also highlighted certain challenges that currently...

  4. A Framework for Organizing Current and Future Electric Utility Regulatory and Business Models

    Energy Technology Data Exchange (ETDEWEB)

    Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Schwartz, Lisa [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Fadrhonc, Emily Martin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-06-01

    In this report, we will present a descriptive and organizational framework for incremental and fundamental changes to regulatory and utility business models in the context of clean energy public policy goals. We will also discuss the regulated utility's role in providing value-added services that relate to distributed energy resources, identify the "openness" of customer information and utility networks necessary to facilitate change, and discuss the relative risks, and the shifting of risks, for utilities and customers.

  5. The Effects of Rising Interest Rates on Electric Utility Stock Prices: Regulatory Considerations and Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Kihm, Steve [Seventhwave, Madison, WI (United States); Satchwell, Andrew [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Cappers, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-07-26

    This technical brief identifies conditions under which utility regulators should consider implementing policy approaches that seek to mitigate negative outcomes due to an increase in interest rates. Interest rates are a key factor in determining a utility’s cost of equity and investors find value when returns exceed the cost of equity. Through historical observations of periods of rising and falling interest rates and application of a pro forma financial tool, we identify the key drivers of utility stock valuations and estimate the degree to which those valuations might be affected by increasing interest rates.3 We also analyze the efficacy of responses by utility regulators to mitigate potential negative financial impacts. We find that regulators have several possible approaches to mitigate a decline in value in an environment of increasing interest rates, though regulators must weigh the tradeoffs of improving investor value with potential increases in customer costs. Furthermore, the range of approaches reflects today’s many different electric utility regulatory models and regulatory responses to a decline in investor value will fit within state-specific models.

  6. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Science.gov (United States)

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies. PMID:24216993

  7. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Kosei, E-mail: andokercgv@gmail.com [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Heymann, Marie-Françoise [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France); Stresing, Verena [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Nantes University Hospital, Nantes 44035 (France); Mori, Kanji [Department of Orthopaedic Surgery, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192 (Japan); Rédini, Françoise; Heymann, Dominique [INSERM, UMR 957, 1 Rue Gaston Veil, 44035 Nantes (France); Physiopathologie de la Résorption Osseuse et Therapie des Tumeurs Osseuses Primitives, Université de Nantes, Nantes Atlantique Universités, 1 Rue Gaston Veil, 44035 Nantes (France); Equipe Labellisee Ligue 2012, Nantes, 44035 (France); Nantes University Hospital, Nantes 44035 (France)

    2013-05-24

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies.

  8. Limits of the current EU regulatory framework on GMOs: risk of not authorized GM event-traces in imports

    Directory of Open Access Journals (Sweden)

    Roïz Julie

    2014-11-01

    Full Text Available Since their first commercialization in the 1990’s, the number of genetically modified organisms (GMOs cultivated around the world has steadily increased. This development has been accompanied by the development of regulatory and policy environments which vary from one country to another. Today, the European food and feed sectors are faced with the increasing risk of finding traces of not authorized GMOs in imports. Under the EU zero tolerance for unapproved GMOs, this situation may lead to trade disruptions with important cost implications. A regulatory environment which minimizes the risk of such disruption is therefore indispensable. To address this issue, the EU has adopted the “technical solution” but this remains insufficient to provide the necessary legal certainty which is needed to operate in such context. More comprehensive approaches are considered globally through low level presence policies.

  9. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

    Directory of Open Access Journals (Sweden)

    Yoshikazu Nakayama

    2015-03-01

    Full Text Available Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region.

  10. Chiral lagrangian approach to exchange vector currents in nuclei

    CERN Document Server

    Park, T S; Rho, M; Park, Tae Sun; Min, Dong Pil; Rho, Mannque

    1995-01-01

    Exchange vector currents are calculated up to one-loop order (corresponding to next-to-next-to-leading order) in chiral perturbation theory. As an illustration of the power of the approach, we apply the formalism to the classic nuclear process n+p\\rightarrow d +\\gamma at thermal energy. The exchange current correction comes out to be (4.5 \\pm 0.3) \\% in amplitude giving a predicted cross section \\sigma= (334\\pm 3)\\ {\\mbox mb} in excellent agreement with the experimental value (334.2\\pm 0.5)\\ {\\mbox mb}. Together with the axial charge transitions computed previously, this result provides a strong support for the power of chiral Lagrangians in nuclear physics. As a by-product of our results, we suggest an open problem in the application of chiral Lagrangian approach to nuclear processes that has to do with giving a physical meaning to the short-range correlations that play an important role in nuclei.

  11. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

    Science.gov (United States)

    Jeffery, Hannah C.; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID:27656181

  12. Clinical potential of regulatory T cell therapy in liver diseases: An overview and current perspectives

    Directory of Open Access Journals (Sweden)

    Hannah Claire Jeffery

    2016-09-01

    Full Text Available The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes, that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg. The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients.Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment and Good Manufacturing Practice (GMP facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases, chronic rejection and post-transplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases (GVHD and solid organ transplantations. There have not been any new therapies for the autoimmune liver diseases for more than three decades; thus the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior and microenvironment of Treg before applying the cells to the patients.

  13. Current nutritional approaches in managing autism spectrum disorder: A review.

    Science.gov (United States)

    Cekici, Hande; Sanlier, Nevin

    2017-08-01

    The link between nutrition and autism spectrum disorder (ASD), which is a complex developmental disorder manifesting itself in significant delays or deviation in interaction and communication, has provided a fresh point of view and signals that nutrition may have a role in the aetiology of ASD, as well as play an active role in treatment by alleviating symptoms. In this review study aimed at evaluating, with scientific and concrete proof, the current medical nutrition implementations on ASD, existing medical nutrition therapies have been addressed and their effects on ASD symptoms have been discussed in light of current research. We reviewed articles regarding the medical nutritional therapy of autism on current nutritional approaches selected from PubMed, Science Direct, EBSCO, and databases about autism and nutrition. The research put forward that in individuals with ASD, while gluten-free/casein-free and ketogenic diets, camel milk, curcumin, probiotics, and fermentable foods can play a role in alleviating ASD symptoms, consumption of sugar, additives, pesticides, genetically modified organisms, inorganic processed foods, and hard-to-digest starches may aggravate symptoms. Further prospective controlled trials with large sample sizes are needed before recommendations can be made regarding the ideal ASD diet. This review emphasizes the value of identifying current nutritional approaches specific to individuals with ASD and integrating their effects on symptoms to the conversation and presents suggestions for future research designed to identify medical nutrition therapies targeting this population to better understand the link between ASD and nutrition.

  14. Lymphopenia is detrimental to therapeutic approaches to type 1 diabetes using regulatory T cells.

    Science.gov (United States)

    Ash, Shifra; Yarkoni, Shai; Askenasy, Nadir

    2014-01-01

    One of the therapeutic approaches to type 1 diabetes (T1D) focuses on enhancement of regulatory T cell (Treg) activity, either by adoptive transfer or supplementation of supporting cytokines such as interleukin-2 (IL-2). In principle, this therapeutic design would greatly benefit of concomitant reduction in pathogenic cell burden. Experimental evidence indicates that physiological recovery from lymphopenia is dominated by evolution of effector and cytotoxic cells, which abolishes the therapeutic efficacy of Treg cells. Targeted and selective depletion of effector T cells has been achieved with killer Treg using Fas ligand protein and a fusion protein composed of IL-2 and caspase-3, which showed remarkable efficacy in modulating the course of inflammatory insulitis in NOD mice. We emphasize a critical consideration in design of therapeutic approaches to T1D, immunomodulation without lymphoreduction to avoid the detrimental consequences of rebound recovery from lymphopenia.

  15. Advancing the 3Rs in regulatory ecotoxicology: A pragmatic cross-sector approach.

    Science.gov (United States)

    Burden, Natalie; Benstead, Rachel; Clook, Mark; Doyle, Ian; Edwards, Peter; Maynard, Samuel K; Ryder, Kathryn; Sheahan, Dave; Whale, Graham; van Egmond, Roger; Wheeler, James R; Hutchinson, Thomas H

    2016-07-01

    The ecotoxicity testing of chemicals for prospective environmental safety assessment is an area in which a high number of vertebrates are used across a variety of industry sectors. Refining, reducing, and replacing the use of animals such as fish, birds, and amphibians for this purpose addresses the ethical concerns and the increasing legislative requirements to consider alternative test methods. Members of the UK-based National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) Ecotoxicology Working Group, consisting of representatives from academia, government organizations, and industry, have worked together over the past 6 y to provide evidence bases to support and advance the application of the 3Rs in regulatory ecotoxicity testing. The group recently held a workshop to identify the areas of testing, demands, and drivers that will have an impact on the future of animal use in regulatory ecotoxicology. As a result of these discussions, we have developed a pragmatic approach to prioritize and realistically address key opportunity areas, to enable progress toward the vision of a reduced reliance on the use of animals in this area of testing. This paper summarizes the findings of this exercise and proposes a pragmatic strategy toward our key long-term goals-the incorporation of reliable alternatives to whole-organism testing into regulations and guidance, and a culture shift toward reduced reliance on vertebrate toxicity testing in routine environmental safety assessment. Integr Environ Assess Manag 2016;12:417-421. © 2015 SETAC.

  16. Review of various approaches for assessing public health risks in regulatory decision making: choosing the right approach for the problem.

    Science.gov (United States)

    Dearfield, Kerry L; Hoelzer, Karin; Kause, Janell R

    2014-08-01

    Stakeholders in the public health risk analysis community can possess differing opinions about what is meant by "conduct a risk assessment." In reality, there is no one-size-fits-all risk assessment that can address all public health issues, problems, and regulatory needs. Although several international and national organizations (e.g., Codex Alimentarius Commission, Office International des Epizooties, Food and Agricultural Organization, World Health Organization, National Research Council, and European Food Safety Authority) have addressed this issue, confusion remains. The type and complexity of a risk assessment must reflect the risk management needs to appropriately inform a regulatory or nonregulatory decision, i.e., a risk assessment is ideally "fit for purpose" and directly applicable to risk management issues of concern. Frequently however, there is a lack of understanding by those not completely familiar with risk assessment regarding the specific utility of different approaches for assessing public health risks. This unfamiliarity can unduly hamper the acceptance of risk assessment results by risk managers and may reduce the usefulness of such results for guiding public health policies, practices, and operations. Differences in interpretation of risk assessment terminology further complicate effective communication among risk assessors, risk managers, and stakeholders. This article provides an overview of the types of risk assessments commonly conducted, with examples primarily from the food and agricultural sectors, and a discussion of the utility and limitations of these specific approaches for assessing public health risks. Clarification of the risk management issues and corresponding risk assessment design needs during the formative stages of the risk analysis process is a key step for ensuring that the most appropriate assessment of risk is developed and used to guide risk management decisions.

  17. Personalized medicine and treatment approaches in hypertension: current perspectives

    Directory of Open Access Journals (Sweden)

    Byrd JB

    2016-04-01

    Full Text Available James Brian Byrd Division of Cardiovascular Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA Abstract: In the US, hypertension affects one in three adults. Current guideline-based treatment of hypertension involves little diagnostic testing. A more personalized approach to the treatment of hypertension might be of use. Several methods of personalized treatment have been proposed and vetted to varying degrees. The purpose of this narrative review is to discuss the rationale for personalized therapy in hypertension, barriers to its development and implementation, some influential examples of proposed personalization measures, and a view of future efforts. Keywords: hypertension, blood pressure, personalized medicine

  18. Electrostatic discharge current linear approach and circuit design method

    Energy Technology Data Exchange (ETDEWEB)

    Katsivelis, P. K.; Fotis, G. P.; Gonos, I. F.; Koussiouris, T. G.; Stathopulos, I. A. [School of Electrical and Computer Engineering, National Technical University of Athens, 9 Iroon Polytechniou Str., Zographou 157 80, Athens (Greece)

    2010-11-15

    The electrostatic discharge (ESD) phenomenon is a great threat to all electronic devices and ICs. An electric charge passing rapidly from a charged body to another can seriously harm the last one. However, there is a lack in a linear mathematical approach which will make it possible to design a circuit capable of producing such a sophisticated current waveform. The commonly accepted electrostatic discharge current waveform is the one set by the IEC 61000-4-2. However, the over-simplified circuit included in the same standard is incapable of producing such a waveform. Treating the electrostatic discharge current waveform of the IEC 61000-4-2 as reference, an approximation method, based on Prony's method, is developed and applied in order to obtain a linear system's response. Considering a known input, a method to design a circuit, able to generate this ESD current waveform in presented. The circuit synthesis assumes ideal active elements. A simulation is carried out using the PSpice software. (authors)

  19. Application of the LBB regulatory approach to the steamlines of advanced WWER 1000 reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kiselyov, V.A.; Sokov, L.M.

    1997-04-01

    The LBB regulatory approach adopted in Russia in 1993 as an extra safety barrier is described for advanced WWER 1000 reactor steamline. The application of LBB concept requires the following additional protections. First, the steamline should be a highly qualified piping, performed in accordance with the applicable regulations and guidelines, carefully screened to verify that it is not subjected to any disqualifying failure mechanism. Second, a deterministic fracture mechanics analysis and leak rate evaluation have been performed to demonstrate that postulated through-wall crack that yields 95 1/min at normal operation conditions is stable even under seismic loads. Finally, it has been verified that the leak detection systems are sufficiently reliable, diverse and sensitive, and that adequate margins exist to detect a through wall crack smaller than the critical size. The obtained results are encouraging and show the possibility of the application of the LBB case to the steamline of advanced WWER 1000 reactor.

  20. Data control and digital regulatory space(s: towards a new European approach

    Directory of Open Access Journals (Sweden)

    Roxana Radu

    2015-06-01

    Full Text Available Data control, among the newest forms of power fostered by information and communication technologies (ICTs, triggers a continuous (renegotiation of public and private orderings, with direct implications on both regulators and intermediaries. This article examines the stance of the European Union (EU regarding the position of Google - the world’s largest internet services company as per its 2014 market value - in two controversial instances: the ‘right to be forgotten’ and the implementation of EU competition rules. It provides an analysis of these evolving debates and their meaning for EU regulatory thrust more broadly, discussing the shift in the approach to digital markets and the proactive development of a European framework influential beyond continental boundaries.

  1. Managing Carbon Regulatory Risk in Utility Resource Planning:Current Practices in the Western United States

    Energy Technology Data Exchange (ETDEWEB)

    Barbose, Galen; Wiser, Ryan; Phadke, Amol; Goldman, Charles

    2008-05-16

    Concerns about global climate change have substantially increased the likelihood that future policy will seek to minimize carbon dioxide emissions. Assuch, even today, electric utilities are making resource planning and investment decisions that consider the possible implications of these future carbon regulations. In this article, we examine the manner in which utilities assess the financial risks associated with future carbon regulations within their long-term resource plans. We base our analysis on a review of the most recent resource plans filed by fifteen electric utilities in the Western United States. Virtually all of these utilities made some effort to quantitatively evaluate the potential cost of future carbon regulations when analyzing alternate supply- and demand-side resource options for meeting customer load. Even without Federal climate regulation in the U.S., the prospect of that regulation is already having an impact on utility decision-making and resource choices. That said, the methods and assumptions used by utilities to analyze carbon regulatory risk, and the impact of that analysis on their choice of a particular resource strategy, vary considerably, revealing a number of opportunities for analytic improvement. Though our review focuses on a subset of U.S. electric utilities, this work holds implications for all electric utilities and energy policymakers who are seeking to minimize the compliance costs associated with future carbon regulations

  2. Managing Carbon Regulatory Risk in Utility Resource Planning: Current Practices in the Western United States

    Energy Technology Data Exchange (ETDEWEB)

    Barbose, Galen; Wiser, Ryan; Phadke, Amol; Goldman, Charles

    2008-07-11

    Concerns about global climate change have substantially increased the likelihood that future policy will seek to minimize carbon dioxide emissions. As such, even today, electric utilities are making resource planning and investment decisions that consider the possible implications of these future carbon regulations. In this article, we examine the manner in which utilities assess the financial risks associated with future carbon regulations within their long-term resource plans. We base our analysis on a review of the most recent resource plans filed by fifteen electric utilities in the Western United States. Virtually all of these utilities made some effort to quantitatively evaluate the potential cost of future carbon regulations when analyzing alternate supply- and demand-side resource options for meeting customer load. Even without Federal climate regulation in the U.S., the prospect of that regulation is already having an impact on utility decision-making and resource choices. That said, the methods and assumptions used by utilities to analyze carbon regulatory risk, and the impact of that analysis on their choice of a particular resource strategy, vary considerably, revealing a number of opportunities for analytic improvement. Though our review focuses on a subset of U.S. electric utilities, this work holds implications for all electric utilities and energy policymakers who are seeking to minimize the compliance costs associated with future carbon regulations.

  3. Current Approaches to the Establishment of Credit Risk Specific Provisions

    Directory of Open Access Journals (Sweden)

    Ion Nitu

    2008-10-01

    Full Text Available The aim of the new Basel II and IFRS approaches is to make the operations of financial institutions more transparent and thus to create a better basis for the market participants and supervisory authorities to acquire information and make decisions. In the banking sector, a continuous debate is being led, related to the similarities and differences between IFRS approach on loan loss provisions and Basel II approach on calculating the capital requirements, judging against the classical method regarding loan provisions, currently used by the Romanian banks following the Central Bank’s regulations.Banks must take into consideration that IFRS and Basel II objectives are fundamentally different. While IFRS aims to ensure that the financial papers reflect adequately the losses recorded at each balance sheet date, the Basel II objective is to ensure that the bank has enough provisions or capital in order to face expected losses in the next 12 months and eventual unexpected losses.Consequently, there are clear differences between the objectives of the two models. Basel II works on statistical modeling of expected losses while IFRS, although allowing statistical models, requires a trigger event to have occurred before they can be used. IAS 39 specifically states that losses that are expected as a result of future events, no matter how likely, are not recognized. This is a clear and fundamental area of difference between the two frameworks.

  4. Towards an Airframe Noise Prediction Methodology: Survey of Current Approaches

    Science.gov (United States)

    Farassat, Fereidoun; Casper, Jay H.

    2006-01-01

    In this paper, we present a critical survey of the current airframe noise (AFN) prediction methodologies. Four methodologies are recognized. These are the fully analytic method, CFD combined with the acoustic analogy, the semi-empirical method and fully numerical method. It is argued that for the immediate need of the aircraft industry, the semi-empirical method based on recent high quality acoustic database is the best available method. The method based on CFD and the Ffowcs William- Hawkings (FW-H) equation with penetrable data surface (FW-Hpds ) has advanced considerably and much experience has been gained in its use. However, more research is needed in the near future particularly in the area of turbulence simulation. The fully numerical method will take longer to reach maturity. Based on the current trends, it is predicted that this method will eventually develop into the method of choice. Both the turbulence simulation and propagation methods need to develop more for this method to become useful. Nonetheless, the authors propose that the method based on a combination of numerical and analytical techniques, e.g., CFD combined with FW-H equation, should also be worked on. In this effort, the current symbolic algebra software will allow more analytical approaches to be incorporated into AFN prediction methods.

  5. Development of neuroleptic agents: pharmacogenetics and current safety issues of regulatory concern.

    Science.gov (United States)

    Shah, Rashmi

    2002-12-01

    The development of safe and effective new drug treatments for schizophrenia poses a challenging task. This class of drugs is known to be associated with a wide range of serious and troublesome safety problems that include neurological, cardiac, endocrine, and metabolic side effects. Many of these drugs have a narrow therapeutic index and generate metabolites that often have their own unique pharmacological profile different from the parent compound. These features make it imperative that the optimal dose schedules for neuroleptic drugs are carefully characterized. Many of these drugs are metabolized by cytochrome P450 enzymes, which show genetic polymorphism and a bi modal distribution within the population, A significant subset of the population cannot eliminate these drugs as effectively as the majority. This brings an added dimension of complexity in characterizing the dose and individualizing therapy. Many neuroleptic agents are proarrhythmic with an adverse effect on cardiac repolarization. They are prone to prolonging the QT interval and inducing torsade de pointes. Given the potentially fatal outcome of this ventricular tachyarrhythmia, drug development programs need to ensure that the proarrhythmic potential of any new neuroleptic agent is thoroughly explored and its proarrhythmic risk characterized. The clinical use of many of these drugs is further troubled by their high potential for drug-drug interactions. These too need to be adequately investigated during development The approval and the labeling of a new neuroleptic agent require a careful regulatory assessment of its risk/benefit ratio in comparison with the available alternatives. Their safe and effective use in routine clinical practice depends on careful attention to prescribing information, especially the contraindications, precautions, and patient-monitoring requirements.

  6. Layers of epistasis: genome-wide regulatory networks and network approaches to genome-wide association studies

    Science.gov (United States)

    Cowper-Sal·lari, Richard; Cole, Michael D.; Karagas, Margaret R.; Lupien, Mathieu; Moore, Jason H.

    2010-01-01

    The conceptual foundation of the genome-wide association study (GWAS) has advanced unchecked since its conception. A revision might seem premature as the potential of GWAS has not been fully realized. Multiple technical and practical limitations need to be overcome before GWAS can be fairly criticized. But with the completion of hundreds of studies and a deeper understanding of the genetic architecture of disease, warnings are being raised. The results compiled to date indicate that risk-associated variants lie predominantly in non-coding regions of the genome. Additionally, alternative methodologies are uncovering large and heterogeneous sets of rare variants underlying disease. The fear is that, even in its fulfilment, the current GWAS paradigm might be incapable of dissecting all kinds of phenotypes. In the following text we review several initiatives that aim to overcome these limitations. The overarching theme of these studies is the inclusion of biological knowledge to both the analysis and interpretation of genotyping data. GWAS is uninformed of biology by design and although there is some virtue in its simplicity it is also its most conspicuous deficiency. We propose a framework in which to integrate these novel approaches, both empirical and theoretical, in the form of a genome-wide regulatory network (GWRN). By processing experimental data into networks, emerging data types based on chromatin-immunoprecipitation are made computationally tractable. This will give GWAS re-analysis efforts the most current and relevant substrates, and root them firmly on our knowledge of human disease. PMID:21197657

  7. Using graphical adaptive lasso approach to construct transcription factor and microRNA's combinatorial regulatory network in breast cancer.

    Science.gov (United States)

    Su, Naifang; Dai, Ding; Deng, Chao; Qian, Minping; Deng, Minghua

    2014-06-01

    Discovering the regulation of cancer-related gene is of great importance in cancer biology. Transcription factors and microRNAs are two kinds of crucial regulators in gene expression, and they compose a combinatorial regulatory network with their target genes. Revealing the structure of this network could improve the authors' understanding of gene regulation, and further explore the molecular pathway in cancer. In this article, the authors propose a novel approach graphical adaptive lasso (GALASSO) to construct the regulatory network in breast cancer. GALASSO use a Gaussian graphical model with adaptive lasso penalties to integrate the sequence information as well as gene expression profiles. The simulation study and the experimental profiles verify the accuracy of the authors' approach. The authors further reveal the structure of the regulatory network, and explore the role of feedforward loops in gene regulation. In addition, the authors discuss the combinatorial regulatory effect between transcription factors and microRNAs, and select miR-155 for detailed analysis of microRNA's role in cancer. The proposed GALASSO approach is an efficient method to construct the combinatorial regulatory network. It also provides a new way to integrate different data sources and could find more applications in meta-analysis problem.

  8. Two complementary approaches to right-handed currents

    Energy Technology Data Exchange (ETDEWEB)

    Gemmler, Katrin M.

    2012-04-17

    Flavour observables impose strong constraints on models of new physics. We study whether right-handed currents can provide a realistic extension to the Standard Model. We analyse two complementary models. These setups lead to new flavour violating interactions in the right-handed sector. We first consider a bottom-up approach assuming a left-right symmetric flavour group broken only by the Yukawa couplings. In this model the vertical stroke V{sub ub} vertical stroke problem can be solved. Secondly we study the Left-Right Model. We perform a comprehensive numerical analysis, including all known experimental constraints from {Delta}F=2 observables and the decay B {yields}X{sub s}{gamma} simultaneously. We observe that there exist regions in parameter space in accordance with the all data. In this model all flavour anomalies can be resolved except the vertical stroke V{sub ub} vertical stroke problem.

  9. DIABETIC POLYNEUROPATHY: CURRENT APPROACHES TO DIAGNOSIS AND PATHOGENETIC THERAPY

    Directory of Open Access Journals (Sweden)

    O. S. Levin

    2013-01-01

    Full Text Available The paper considers the current views of the prevalence, clinical picture, approaches to the diagnosis and treatment of one of the most commonneurological complications of diabetes mellitus – diabetic polyneuropathy, and both its somatic and autonomous manifestations. Neuropathy ismost common in diabetic patients and its clinical forms reflect the severe course of diabetes mellitus and serve as an unfavorable prognostic signthat is associated with an approximately 5-fold increase in mortality. At the same time, the timely detection and adequate correction of the manifestations of neuropathy may substantially improve quality of life in the patients. The possibilities of pathogenetic therapy for diabetic polyneuropathy associated mainly with the use of benfotiamine and alpha-lipoic acid, as well as symptomatic therapy for its individual manifestationsare considered.

  10. Stochastic Boolean networks: An efficient approach to modeling gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Liang Jinghang

    2012-08-01

    network inferred from a T cell immune response dataset. An SBN can also implement the function of an asynchronous PBN and is potentially useful in a hybrid approach in combination with a continuous or single-molecule level stochastic model. Conclusions Stochastic Boolean networks (SBNs are proposed as an efficient approach to modelling gene regulatory networks (GRNs. The SBN approach is able to recover biologically-proven regulatory behaviours, such as the oscillatory dynamics of the p53-Mdm2 network and the dynamic attractors in a T cell immune response network. The proposed approach can further predict the network dynamics when the genes are under perturbation, thus providing biologically meaningful insights for a better understanding of the dynamics of GRNs. The algorithms and methods described in this paper have been implemented in Matlab packages, which are attached as Additional files.

  11. 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)

  12. An integer linear programming approach for finding deregulated subgraphs in regulatory networks.

    Science.gov (United States)

    Backes, Christina; Rurainski, Alexander; Klau, Gunnar W; Müller, Oliver; Stöckel, Daniel; Gerasch, Andreas; Küntzer, Jan; Maisel, Daniela; Ludwig, Nicole; Hein, Matthias; Keller, Andreas; Burtscher, Helmut; Kaufmann, Michael; Meese, Eckart; Lenhof, Hans-Peter

    2012-03-01

    Deregulation of cell signaling pathways plays a crucial role in the development of tumors. The identification of such pathways requires effective analysis tools that facilitate the interpretation of expression differences. Here, we present a novel and highly efficient method for identifying deregulated subnetworks in a regulatory network. Given a score for each node that measures the degree of deregulation of the corresponding gene or protein, the algorithm computes the heaviest connected subnetwork of a specified size reachable from a designated root node. This root node can be interpreted as a molecular key player responsible for the observed deregulation. To demonstrate the potential of our approach, we analyzed three gene expression data sets. In one scenario, we compared expression profiles of non-malignant primary mammary epithelial cells derived from BRCA1 mutation carriers and of epithelial cells without BRCA1 mutation. Our results suggest that oxidative stress plays an important role in epithelial cells of BRCA1 mutation carriers and that the activation of stress proteins may result in avoidance of apoptosis leading to an increased overall survival of cells with genetic alterations. In summary, our approach opens new avenues for the elucidation of pathogenic mechanisms and for the detection of molecular key players.

  13. New approaches to the electromagnetic monitoring for improving the regulatory framework “green” building

    Directory of Open Access Journals (Sweden)

    Grafkina Marina

    2016-01-01

    Full Text Available In the regulatory legal base of a “green” construction existing now in the Russian Federation for assessment of an ecological safety of rooms of residential and public buildings criteria of electromagnetic comfort aren’t used. Its completion with obligatory assessment of indicators of electromagnetic safety is reasonable. Suggestions for improvement of the existing documents regulating assessment of conformity of real estate objects to ecological requirements are given in article. For the purpose of further development of system of regulation of negative factors of the habitat and electromagnetic safety, authors offer new approach to environmental control of low-frequency electromagnetic fields – transition from measurement of amplitude characteristics to determination of energy parameters. Sanitary and hygienic assessment and regulation of low-frequency electromagnetic fields it is performed separately on intensity of electric and magnetic field that doesn’t give an idea of an overall picture of spatial distribution of energy. The energy approach offered by authors will allow to estimate total energy impact of electromagnetic fields per capita, and also to develop new system of regulation of low-frequency electromagnetic fields in energy parameters.

  14. Training in clinical forensic medicine in the UK--perceptions of current regulatory standards.

    Science.gov (United States)

    Stark, Margaret M; Norfolk, Guy A

    2011-08-01

    As clinical forensic medicine (CFM) is not currently recognised as a speciality in the UK there are no nationally agreed mandatory standards for training forensic physicians in either general forensic (GFM) or sexual offence medicine (SOM). The General Medical Council (GMC), the medical regulator in the UK, has issued clear standards for training in all specialities recommending that "trainees must be supported to acquire the necessary skills and experience through induction, effective educational supervision, an appropriate workload and time to learn". In order to evaluate the current situation in the field of clinical forensic medicine, doctors who have recently (within the last two years) started working in the field "trainees" (n = 38), and trainers (n = 61) with responsibility for clinical and educational supervision of new trainees, were surveyed by questionnaire to gather their perceptions of how the relevant GMC standards are being met in initial on-the-job training. Telephone interviews were performed with eleven doctors working as clinical or medical directors to determine their views. It is clear that currently the quality of training in CFM is sub-standard and inconsistent and that the published standards, as to the minimum requirement for training that must be met by post-graduate medical and training providers at all levels, are not being met. The Faculty of Forensic and Legal Medicine (FFLM) needs to set explicit minimum standards which will comply with the regulator and work to pilot credentialing for forensic physicians. A number of recommendations are made for urgent FFLM development.

  15. Public Economy versus Planned Economy. Current Approaches and Problems

    Directory of Open Access Journals (Sweden)

    Ani Matei

    2006-03-01

    Full Text Available he present paper proposes a review of the current object and problems facing the public economy. For the past decade and a half, public economy has clearly come back in the attention of the research interests of specialists from the Central and Eastern European countries. Among these, the scientific research encompassed by the public economy area interrelates with the international trends. At a closer look, public economy appears to be a science, particularly interdisciplinary, with sociological, political, econometrical or systemic approaches possible to prevail. To continue, the author makes reference to four pillars of the public economy: optimum, welfare, social choice and economic justice that allow different approaches to develop. A science branch, equally theoretical and practical, public economy will stress its connections with the economic and mathematic modeling, systemic analysis or sociological and political research. Still, seve¬ral problems in public economy remain open. These concentrate on the public interest, intervention and decision. Conceptualization, understanding and description of the mechanisms that allow the operationalisation may form the basis for further developments on both theoretical and practical level. A clear distinction in order to justify the title of this article needs to be made. Public economy is not to be confused with planning economy. The state remains but one of the producers and delivery agents of public goods and services.

  16. Public Economy versus Planned Economy. Current Approaches and Problems

    Directory of Open Access Journals (Sweden)

    Ani Matei

    2006-01-01

    Full Text Available The present paper proposes a review of the current object and problems facing the public economy. For the past decade and a half, public economy has clearly come back in the attention of the research interests of specialists from the Central and Eastern European countries. Among these, the scientific research encompassed by the public economy area interrelates with the international trends. At a closer look, public economy appears to be a science, particularly interdisciplinary, with sociological, political, econometrical or systemic approaches possible to prevail. To continue, the author makes reference to four pillars of the public economy: optimum, welfare, social choice and economic justice that allow different approaches to develop. A science branch, equally theoretical and practical, public economy will stress its connections with the economic and mathematic modeling, systemic analysis or sociological and political research. Still, seve¬ral problems in public economy remain open. These concentrate on the public interest, intervention and decision. Conceptualization, understanding and description of the mechanisms that allow the operationalisation may form the basis for further developments on both theoretical and practical level. A clear distinction in order to justify the title of this article needs to be made. Public economy is not to be confused with planning economy. The state remains but one of the producers and delivery agents of public goods and services.

  17. Are better sleepers more engaged workers? A self-regulatory approach to sleep hygiene and work engagement.

    Science.gov (United States)

    Barber, Larissa; Grawitch, Matthew J; Munz, David C

    2013-10-01

    Previous research has emphasized facets of both the organizational environment and individual differences as predictors of work engagement. This study explored sleep hygiene as another important behavioural factor that may be related to work engagement. With a sample of 328 adult workers, we tested a multiple mediator model in which sleep hygiene predicts work engagement through one's appraisals of resource depletion stemming from demands (psychological strain) and general self-regulatory capacity (self-control). Results indicated that individuals who frequently engaged in poor sleep hygiene behaviours had lower self-regulatory capacity, experienced higher subjective depletion and were less engaged at work. Additionally, the path from poor sleep hygiene to decreased work engagement was attributed to perceptions of personal resources that are needed to exert self-regulatory energy at work. This is consistent with current self-regulatory theories suggesting that individuals have a limited amount of resources to allocate to demands and that the depletion of these resources can lead to stress and lower self-regulatory functioning in response to other demands. Specifically, poor sleep hygiene results in the loss of self-regulatory resources needed to be engaged in work tasks by impairing the after-work recovery process. Practical and research implications regarding sleep hygiene interventions for well-being and productivity improvement are discussed.

  18. Neuropsychiatric involvement in systemic lupus erythematosus: current therapeutic approach.

    Science.gov (United States)

    Sanna, Giovanni; Bertolaccini, Maria Laura; Khamashta, Munther A

    2008-01-01

    The involvement of the central nervous system (CNS) is one of the major causes of morbidity and mortality in systemic lupus erythematosus (SLE) patients and the less understood aspect of the disease. Its recognition and treatment continue to represent a major diagnostic and therapeutic challenge. Due to the lack of controlled randomized trials, current therapeutic approach is still empirical and based on clinical experience. The therapeutic choice depends on accurate diagnosis, identification of underlying pathogenic mechanism, severity of the presenting neuropsychiatric symptoms, and on prompt identification and management of contributing causes of CNS disease. Mild neuropsychiatric manifestations may need symptomatic treatment only. In more severe CNS disease it is important to distinguish between thrombotic and non-thrombotic mechanisms. Focal CNS manifestations, particularly TIA and stroke, are associated with the presence of antiphospholipid antibodies (aPL). Anticoagulation is warranted in patients with thrombotic disease, particularly in those with the antiphospholipid (Hughes) syndrome (APS). Other CNS manifestations, such as demyelinating syndrome, transverse myelitis, chorea, seizures, migraine and/or cognitive dysfunction, when associated with persistent positivity for aPL, may also benefit from anticoagulation in selected patients. Severe diffuse CNS manifestations, such as acute confusional state, generalised seizures, mood disorders and psychosis, generally require corticosteroids in the first instance. Pulse intravenous cyclophosphamide therapy may help when more severe manifestations are refractory to corticosteroids and other immunosuppressive agents, generally when response is not seen in 3-5 days. Plasmapheresis may also be added in severe cases of symptoms refractory to conventional treatment. Intravenous immunoglobulins, mycophenolate mofetil, rituximab, intratecal methotrexate and dexametasone deserve further studies to confirm their

  19. CURRENT APPROACHES TO UNIVERSAL VACCINE AGAINST INFLUENZA VIRUS

    Directory of Open Access Journals (Sweden)

    I. B. Esmagambetov

    2016-01-01

    Full Text Available Influenza is a seasonal infectious disease widespread across the globe. In Russia the share of influenza and other acute respiratory viral infections account for up to 90% of all infectious diseases. Scientific and reasonable method of influenza prevention is vaccination. However, traditional current influenza vaccines can’t induce protection against various virus strains that differ substantially in terms of their antigenic structure, and thus require periodic updates to its immunogenic components. In addition, there is the risk of a pandemic caused by an entirely new antigen in relation to variants of influenza virus A. Attempts to improve on traditional approaches to vaccination have focused primarily on improving production technologies and to increase immunogenicity of vaccines. Therefore, the urgent task is the creation of vaccines able to induce immune response a broad spectrum against different influenza virus strains and human strains of avian influenza, also can cause disease in humans. Protective effect of universal vaccine should be the induction of integrated immune response, based on the formulation of cross-reactive antibodies and T cells. The development of such universal vaccine could remove the need for periodical strain composition update of existing vaccines and, accor dingly, will be able to give the vaccine manufacturer itself, production planning regardless of epidemic seasons. Currently, the most widely studied antigens as key components of flu vaccines are proteins M2 and NP as well as the hemagglutinin of influenza virus. This review summarizes and lists some data of domestic and foreign research on a universal influenza virus vaccine.

  20. Affinity Density: a novel genomic approach to the identification of transcription factor regulatory targets.

    Science.gov (United States)

    Hazelett, Dennis J; Lakeland, Daniel L; Weiss, Joseph B

    2009-07-01

    A new method was developed for identifying novel transcription factor regulatory targets based on calculating Local Affinity Density. Techniques from the signal-processing field were used, in particular the Hann digital filter, to calculate the relative binding affinity of different regions based on previously published in vitro binding data. To illustrate this approach, the complete genomes of Drosophila melanogaster and D.pseudoobscura were analyzed for binding sites of the homeodomain proteinc Tinman, an essential heart development gene in both Drosophila and Mouse. The significant binding regions were identified relative to genomic background and assigned to putative target genes. Valid candidates common to both species of Drosophila were selected as a test of conservation. The new method was more sensitive than cluster searches for conserved binding motifs with respect to positive identification of known Tinman targets. Our Local Affinity Density method also identified a significantly greater proportion of Tinman-coexpressed genes than equivalent, optimized cluster searching. In addition, this new method predicted a significantly greater than expected number of genes with previously published RNAi phenotypes in the heart. Algorithms were implemented in Python, LISP, R and maxima, using MySQL to access locally mirrored sequence data from Ensembl (D.melanogaster release 4.3) and flybase (D.pseudoobscura). All code is licensed under GPL and freely available at http://www.ohsu.edu/cellbio/dev_biol_prog/affinitydensity/.

  1. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Directory of Open Access Journals (Sweden)

    Scott Okuno

    2011-08-01

    Full Text Available Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  2. Current Approach to the Evaluation and Management of Microscopic Colitis.

    Science.gov (United States)

    Cotter, Thomas G; Pardi, Darrell S

    2017-02-01

    Microscopic colitis is a common cause of chronic watery diarrhea, particularly in the elderly. The accompanying symptoms, which include abdominal pain and fatigue, can markedly impair patients' quality of life. Diagnosis is based upon characteristic histologic findings of the colonic mucosa. This review focuses on the current approach to evaluation and management of patients with microscopic colitis. Although the incidence of microscopic colitis has been increasing over time, recent epidemiological studies show stabilization at 21.0-24.7 cases per 100,000 person-years. Recent research has further expanded our knowledge of the underlying pathophysiology and emphasized the entity of drug-induced microscopic colitis and the association with celiac disease. Two recent randomized studies have confirmed the effectiveness of oral budesonide for both induction and maintenance treatment of microscopic colitis and is now endorsed by the American Gastroenterological Association as first-line treatment. The incidence of microscopic colitis has stabilized at just over 20 cases per 100,000 person-years. Celiac disease and drug-induced microscopic colitis should be considered in all patients diagnosed with microscopic colitis. There are a number of treatments available for patients with microscopic colitis; however, budesonide is the only option well studied in controlled trials and is effective for both induction and maintenance treatment.

  3. Current Approaches and Future Trends to Promote Tendon Repair.

    Science.gov (United States)

    Morais, D S; Torres, J; Guedes, R M; Lopes, M A

    2015-09-01

    Tendons are composed by extracellular collagen fibres arranged in regular arrays and are responsible to transmit tensile forces from a muscle to a bone. Due to their poor healing ability, in some cases tendons injuries are debilitating impairments that affect life quality among adult population worldwide. In the last years, attending to the social and economic concern associated to the high prevalence of tendons injuries and the limited success of the available current treatments, several scaffolds have been developed. Some of these scaffolds are intended to be used as graft-augmentation devices and others to fully replace a damaged tendon. The synthetic ones present superior mechanical characteristics compared to biological scaffolds. However, attending to the specific tendons physiology, even the synthetic scaffolds still don´t present the ideal mechanical properties to accomplish a complete and long-term functional tissue repair. Therefore, to enhance tendogenesis when using a tendon engineering approach, several methodologies have been developed to associate with scaffolds, including surface modification and cell seeding.

  4. Current approaches for the treatment of autoimmune hemolytic anemia.

    Science.gov (United States)

    Jaime-Pérez, José Carlos; Rodríguez-Martínez, Marisol; Gómez-de-León, Andrés; Tarín-Arzaga, Luz; Gómez-Almaguer, David

    2013-10-01

    Autoimmune hemolytic anemia (AIHA) is an infrequent group of diseases defined by autoantibody mediated red blood cell destruction. Correct diagnosis and classification of this condition are essential to provide appropriate treatment. AIHA is divided into warm and cold types according to the characteristics of the autoantibody involved and by the presence of an underlying or associated disorder into primary and secondary AIHA. Due to its low frequency, treatment for AIHA is largely based on small prospective trials, case series, and empirical observations. This review describes in detail the different treatment approaches for autoimmune hemolytic anemia. Warm antibody type AIHA should be treated with steroids, to which most patients respond, although relapse can occur and maintenance doses are frequently required. Splenectomy is an effective second line treatment and can provide long-term remission without medication. Rituximab is a useful alternative for steroid refractory patients, those requiring high maintenance doses and unfavorable candidates for surgery. Promising therapeutic modifications with this monoclonal antibody are emerging including drug combinations, lower doses, and long-term use. Primary cold agglutinin disease has been recognized as having a lymphoproliferative monoclonal origin. It is unresponsive to both steroids and splenectomy. Rituximab is currently the best therapeutic alternative for this condition, and several treatment regimens are available with variable responses.

  5. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Joglekar, Siddharth B. [Musculoskeletal Oncology, Mayo Clinic, Rochester, MN55905 (United States); Rose, Peter S.; Sim, Franklin, E-mail: sim.franklin@mayo.edu [Department of Orthopedics, Mayo Clinic, 200 1st ST SW, Rochester, MN 55905 (United States); Okuno, Scott [Department of Oncology, Mayo Clinic, Rochester, MN55905 (United States); Petersen, Ivy [Department of Radiation Oncology, Mayo Clinic, Rochester, MN55905 (United States)

    2011-08-08

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation.

  6. Robotic surgery for gastric tumor: current status and new approaches.

    Science.gov (United States)

    Lim, Seung Hyun; Lee, Hae Min; Son, Taeil; Hyung, Woo Jin; Kim, Hyoung-Il

    2016-01-01

    Surgical techniques have evolved tremendously over this past century. To maximize the efficacy and minimize the invasiveness of laparoscopic surgery, researchers have sought to implement wider application of robotics. Nevertheless, both optimism without sound evidence and fear of new technology obscure the appropriate uses of robotic surgery. In the present review, we attempted to provide a balanced perspective on the current state of robotic gastrectomy, outlining evidence and opportunities for the use thereof. Although evidence is limited, the use of robotics is feasible for gastric cancer surgery, and less than 10 cases of robotic surgery are needed to become proficient therein. Compared to the clinical impact of laparoscopy on gastric cancer surgery, the additional benefits of robotic surgery to patients seem to be limited. Despite additional costs and longer surgeries, robotic surgery reportedly does not offer surgical outcomes superior to those for laparoscopic surgery, according to a recent multicenter study. Meanwhile, however, our in-depth review of retrospective and prospective reports revealed that robots could expand the indications of minimally invasive gastrectomy for patients requiring total gastrectomy and D2 lymph node dissection. Moreover, we found that robotic gastrectomy is associated with a higher number of retrieved lymph nodes, less bleeding, fewer complications, and shorter hospital stay, compared to laparoscopic gastrectomy. Accordingly, new surgical approaches using advanced technologies, such as near infrared detectors, the Tilepro(®) multi-input display, dual consoles, and the Single-Site(®) system, are under investigation. In conclusion, measuring the additional benefits of robotic over laparoscopic surgery would be difficult and clinically insignificant. Thus, developing new surgical procedures that extend the benefits of conventional laparoscopic surgery to patients in whom minimally invasive surgery would not be possible is

  7. Diagnostic approach and current treatment options in childhood vasculitis.

    Science.gov (United States)

    Barut, Kenan; Şahin, Sezgin; Adroviç, Amra; Kasapçopur, Özgür

    2015-12-01

    All inflammatory changes in the vessel wall are defined as vasculitis. Pediatric vasculitis may present with different clinical findings. Although Henoch-Schönlein purpura which is the most common pediatric vasculitis generally recovers spontaneously, it should be monitorized closely because of the risk of renal failure. Although Kawasaki disease is easy to diagnose with its classical findings, the diagnosis may be delayed in case of incomplete Kawasaki disease. Kawasaki disease should be considered especially in infants in case of prolonged fever even if the criteria are not fully met and intravenous immunoglobulin treatment should be administered without delay in order to prevent development of coronary artery aneurism. Reaction at the site of administration of Bacillus Calmette-Guerin (BCG) vaccine may be observed as commonly as cervical lymphadenopathy in Kawasaki disease and may be used as a valuable finding in suspicious cases. Although anti-neutrophil cytoplasmic antibody-associated vasculitides are rare in children, renal involvement is more common and progression is more severe compared to adults. Hence, efficient and aggressive treatment is required. Takayasu's arteritis is observed commonly in young adult women and rarely in adolescent girls. Therefore, a careful physical examination and blood pressure measurement should be performed in addition to a detailed history in daily practice. In children with unexplained neurological findings, cerebral vasculitis should be considered in the absence of other systemic vasculitides and necessary radiological investigations should be performed in this regard. This review will provide an insight into the understanding of pediatric vasculitis, current diagnostic approaches and prognosis by the aid of new studies.

  8. Robotic surgery for gastric tumor: current status and new approaches

    Science.gov (United States)

    Lim, Seung Hyun; Lee, Hae Min; Son, Taeil; Hyung, Woo Jin

    2016-01-01

    Surgical techniques have evolved tremendously over this past century. To maximize the efficacy and minimize the invasiveness of laparoscopic surgery, researchers have sought to implement wider application of robotics. Nevertheless, both optimism without sound evidence and fear of new technology obscure the appropriate uses of robotic surgery. In the present review, we attempted to provide a balanced perspective on the current state of robotic gastrectomy, outlining evidence and opportunities for the use thereof. Although evidence is limited, the use of robotics is feasible for gastric cancer surgery, and less than 10 cases of robotic surgery are needed to become proficient therein. Compared to the clinical impact of laparoscopy on gastric cancer surgery, the additional benefits of robotic surgery to patients seem to be limited. Despite additional costs and longer surgeries, robotic surgery reportedly does not offer surgical outcomes superior to those for laparoscopic surgery, according to a recent multicenter study. Meanwhile, however, our in-depth review of retrospective and prospective reports revealed that robots could expand the indications of minimally invasive gastrectomy for patients requiring total gastrectomy and D2 lymph node dissection. Moreover, we found that robotic gastrectomy is associated with a higher number of retrieved lymph nodes, less bleeding, fewer complications, and shorter hospital stay, compared to laparoscopic gastrectomy. Accordingly, new surgical approaches using advanced technologies, such as near infrared detectors, the Tilepro® multi-input display, dual consoles, and the Single-Site® system, are under investigation. In conclusion, measuring the additional benefits of robotic over laparoscopic surgery would be difficult and clinically insignificant. Thus, developing new surgical procedures that extend the benefits of conventional laparoscopic surgery to patients in whom minimally invasive surgery would not be possible is necessary

  9. CURRENT APPROACHES FOR RESEARCH OF MULTIPLE SCLEROSIS BIOMARKERS

    Directory of Open Access Journals (Sweden)

    Kolyada T.I

    2016-12-01

    Full Text Available Current data concerning features of multiple sclerosis (MS etiology, pathogenesis, clinical course and treatment of disease indicate the necessity of personalized approach to the management of MS patients. These features are the variety of possible etiological factors and mechanisms that trigger the development of MS, different courses of disease, and significant differences in treatment efficiency. Phenotypic and pathogenetic heterogeneity of MS requires, on the one hand, the stratification of patients into groups with different treatment depending on a number of criteria including genetic characteristics, disease course, stage of the pathological process, and forms of the disease. On the other hand, it requires the use of modern methods for assessment of individual risk of developing MS, its early diagnosis, evaluation and prognosis of the disease course and the treatment efficiency. This approach is based on the identification and determination of biomarkers of MS including the use of systems biology technology platforms such as genomics, proteomics, metabolomics and bioinformatics. Research and practical use of biomarkers of MS in clinical and laboratory practice requires the use of a wide range of modern medical and biological, mathematical and physicochemical methods. The group of "classical" methods used to study MS biomarkers includes physicochemical and immunological methods aimed at the selection and identification of single molecular biomarkers, as well as methods of molecular genetic analysis. This group of methods includes ELISA, western blotting, isoelectric focusing, immunohistochemical methods, flow cytometry, spectrophotometric and nephelometric methods. These techniques make it possible to carry out both qualitative and quantitative assay of molecular biomarkers. The group of "classical methods" can also include methods based on polymerase chain reaction (including multiplex and allele-specific PCR and genome sequencing

  10. Beyond (eco)design: current approaches to sustainable packaging design

    OpenAIRE

    Wever, R.

    2014-01-01

    Packaging has always received a lot of attention within the field of design for sustainability. The classical approach has been to mainly focus on reducing the impact of the packaging. This approach stems from the ill-informed position that packaging is superfluous, or at best there only for marketing reasons. This is a rather guild-based approach that, if taken to extremes, would lead to complete elimination of packaging, or at most a quintessential brown paper bag. In industry reality thoug...

  11. MELiSSA Food Characterization general approach and current status

    Science.gov (United States)

    Weihreter, Martin; Chaerle, Laury; Secco, Benjamin; Molders, Katrien; van der Straeten, Dominique; Duliere, Eric; Pieters, Serge; Maclean, Heather; Dochain, Denis; Quinet, Muriel; Lutts, Stanley; Graham, Thomas; Stasiak, Michael; Rondeau Vuk, Theresa; Zheng, Youbin; Dixon, Mike; Laniau, Martine; Larreture, Alain; Timsit, Michel; Aronne, Giovanna; Barbieri, Giancarlo; Buonomo, Roberta; Veronica; Paradiso, Roberta; de Pascale, Stafania; Galbiati, Massimo; Troia, A. R.; Nobili, Matteo; Bucchieri, Lorenzo; Page, Valérie; Feller, Urs; Lasseur, Christophe

    . Available MELiSSA closed environment crop growth data were used to develop a first photosynthetic model representing the basic carbon fixation mechanisms. This model will be further elaborated in the course of this study to predict yield, oxygen production and transpi-ration. As an ultimate goal the model is intended to simulate the composition of the different plant organs (root, shoot, fruit/seed or tuber) for each crop under various conditions. For the validation of this model an extensive amount of data sets are needed. Current plant growth bench test setups will provide part of the required data. To gain more precise and detailed datasets, a highly closed plant growth chamber (Plant Characterization Unit, PCU) is under development. The PCU will provide accurate mass balances for carbon, water, oxygen and other elements with statistical reliability. This reliability is achieved through a high degree of closure and environment homogeneity. The PCU will also provide data for the above described plant characterization studies. The general work approach, the current status and future steps will be illustrated.

  12. Beyond (eco)design: current approaches to sustainable packaging design

    NARCIS (Netherlands)

    Wever, R.

    2014-01-01

    Packaging has always received a lot of attention within the field of design for sustainability. The classical approach has been to mainly focus on reducing the impact of the packaging. This approach stems from the ill-informed position that packaging is superfluous, or at best there only for marketi

  13. Beyond (eco)design: current approaches to sustainable packaging design

    NARCIS (Netherlands)

    Wever, R.

    2014-01-01

    Packaging has always received a lot of attention within the field of design for sustainability. The classical approach has been to mainly focus on reducing the impact of the packaging. This approach stems from the ill-informed position that packaging is superfluous, or at best there only for

  14. Hierarchical structure and modules in the Escherichia coli transcriptional regulatory network revealed by a new top-down approach

    Directory of Open Access Journals (Sweden)

    Buer Jan

    2004-12-01

    Full Text Available Abstract Background Cellular functions are coordinately carried out by groups of genes forming functional modules. Identifying such modules in the transcriptional regulatory network (TRN of organisms is important for understanding the structure and function of these fundamental cellular networks and essential for the emerging modular biology. So far, the global connectivity structure of TRN has not been well studied and consequently not applied for the identification of functional modules. Moreover, network motifs such as feed forward loop are recently proposed to be basic building blocks of TRN. However, their relationship to functional modules is not clear. Results In this work we proposed a top-down approach to identify modules in the TRN of E. coli. By studying the global connectivity structure of the regulatory network, we first revealed a five-layer hierarchical structure in which all the regulatory relationships are downward. Based on this regulatory hierarchy, we developed a new method to decompose the regulatory network into functional modules and to identify global regulators governing multiple modules. As a result, 10 global regulators and 39 modules were identified and shown to have well defined functions. We then investigated the distribution and composition of the two basic network motifs (feed forward loop and bi-fan motif in the hierarchical structure of TRN. We found that most of these network motifs include global regulators, indicating that these motifs are not basic building blocks of modules since modules should not contain global regulators. Conclusion The transcriptional regulatory network of E. coli possesses a multi-layer hierarchical modular structure without feedback regulation at transcription level. This hierarchical structure builds the basis for a new and simple decomposition method which is suitable for the identification of functional modules and global regulators in the transcriptional regulatory network of E

  15. A robust approach to identifying tissue-specific gene expression regulatory variants using personalized human induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Je-Hyuk Lee

    2009-11-01

    Full Text Available Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells.

  16. HEADROOM APPROACH TO DEVICE DEVELOPMENT: CURRENT AND FUTURE DIRECTIONS

    OpenAIRE

    Girling, A; Lilford, R; Cole, A; Young, T

    2015-01-01

    OBJECTIVES: The headroom approach to medical device development relies on the estimation of a value-based price ceiling at different stages of the development cycle. Such price-ceilings delineate the commercial opportunities for new products in many healthcare systems. We apply a simple model to obtain critical business information as the product proceeds along a development pathway, and indicate some future directions for the development of the approach. METHODS: Health economic modelling in...

  17. A study on the regulatory approach of safety issues for Korean next generation reactor

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Seon; Choi, Jeong Tae; Kim, In Joon [Sunmoon Univ., Asan (Korea, Republic of); Lee, Sang Hoon [Korea Association of Nuclear Technology, Taejon (Korea, Republic of); Kang, Gee Sik [Korea Power Engineering Co., Inc., Seoul (Korea, Republic of); Kim, Han Gon [Korea Electric Power Corporation, Seoul (Korea, Republic of); Park, Jae Uk; Kim, Yun Il; Yang, Soo Hyeong [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1997-10-15

    The project aims to provide the regulatory direction of major technical issues related to the quantitative criteria for probabilistic risk analysis, establishment of containment performance criteria, design of additional water source for long-term corium cooling of core debris, protection against common mode failure of digital I and C system, criteria for safety-related operator action, quantitative reliability targets, classification of plant conditions and acceptance criteria and development of graded QA. These issues are parts of major technical issues resulted from the safety regulation R and D on the next generation reactor. Regulatory directions to be applied to the Korea Next Generation Reactors in this study are developed by analyzing the state-of-the-art of the development of local and foreign regulatory requirements, research trends, and the design features and safety goals of advanced reactors.

  18. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Directory of Open Access Journals (Sweden)

    Melissa A Metzler

    Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  19. Current approaches to model extracellular electrical neural microstimulation

    Directory of Open Access Journals (Sweden)

    Sébastien eJoucla

    2014-02-01

    Full Text Available Nowadays, high-density microelectrode arrays provide unprecedented possibilities to precisely activate spatially well-controlled central nervous system (CNS areas. However, this requires optimizing stimulating devices, which in turn requires a good understanding of the effects of microstimulation on cells and tissues. In this context, modeling approaches provide flexible ways to predict the outcome of electrical stimulation in terms of CNS activation. In this paper, we present state-of-the-art modeling methods with sufficient details to allow the reader to rapidly build numerical models of neuronal extracellular microstimulation. These include 1 the computation of the electrical potential field created by the stimulation in the tissue, and 2 the response of a target neuron to this field. Two main approaches are described: First we describe the classical hybrid approach that combines the finite element modeling of the potential field with the calculation of the neuron’s response in a cable equation framework (compartmentalized neuron models. Then, we present a whole finite element approach allows the simultaneous calculation of the extracellular and intracellular potentials, by representing the neuronal membrane with a thin-film approximation. This approach was previously introduced in the frame of neural recording, but has never been implemented to determine the effect of extracellular stimulation on the neural response at a sub-compartment level. Here, we show on an example that the latter modeling scheme can reveal important sub-compartment behavior of the neural membrane that cannot be resolved using the hybrid approach. The goal of this paper is also to describe in detail the practical implementation of these methods to allow the reader to easily build new models using standard software packages. These modeling paradigms, depending on the situation, should help build more efficient high-density neural prostheses for CNS rehabilitation.

  20. The Intertemporal Approach to the Current Account: Evidence for Chile

    Directory of Open Access Journals (Sweden)

    Sergio A. Salas Landeau

    2002-03-01

    Full Text Available This paper studies the existence of "excess" current-account imbalances in Chile in the 1960-1999 period. This phenomenon is modelled using present value tests that allow for variable interest rates and exchange rate fluctuations. Despite its simplicity, most of the observed imbalances in the current account are accounted for by the model. Results suggest that using models where agents behave as forward-looking rational agents, is a valid framework. Moreover, the analysis highlights the rel-evance of variable interest rates and exchange rates. Results also imply that capital controls, that were widely used in the period under study, were not effective.

  1. Knowing your customer better: the strengths of a self-regulatory value approach

    NARCIS (Netherlands)

    Förster, J.

    2009-01-01

    Regulatory engagement theory's strength over alternative accounts of consumer attitudes is highlighted. In line with the theory, it is argued that in order to predict behavior, one needs to understand the processes involved in goal pursuit, including the dynamic processes of value creation. The

  2. 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...

  3. Knowing your customer better: the strengths of a self-regulatory value approach

    NARCIS (Netherlands)

    J. Förster

    2009-01-01

    Regulatory engagement theory's strength over alternative accounts of consumer attitudes is highlighted. In line with the theory, it is argued that in order to predict behavior, one needs to understand the processes involved in goal pursuit, including the dynamic processes of value creation. The pape

  4. Current Approaches to the Understanding of Early Infantile Autism.

    Science.gov (United States)

    Rickman, David L.

    This review of the literature provides summaries of the genetic, neurophysiological, and biochemical approaches to understanding autism, with special reference to neuroanatomic, cognitive, and neuropsychological studies of this disorder. Available instruments for the assessment of autism and various treatment alternatives including drug therapy,…

  5. Automatic object recognition: critical issues and current approaches

    Science.gov (United States)

    Sadjadi, Firooz A.

    1991-08-01

    Automatic object recognition, with its diverse applications in numerous fields of science and technology, is permeating many aspects of military and civilian industries. This paper gives an overview of the issues confronting the automatic object recognition field and the approaches being used to address these issues.

  6. Current Approaches to Improving Access to Government Documents.

    Science.gov (United States)

    Turner, Carol; Latta, Ann

    Based on the responses of 77 Association of Research Libraries (ARL) member libraries to a December 1986 survey of 106 ARL libraries (a 73% response rate), this report profiles the current state of bibliographic access to federal publications. Following a brief discussion of survey background and methodology, a summary of survey results indicates…

  7. Methodological Approaches in Conducting Overviews: Current State in HTA Agencies

    Science.gov (United States)

    Pieper, Dawid; Antoine, Sunya-Lee; Morfeld, Jana-Carina; Mathes, Tim; Eikermann, Michaela

    2014-01-01

    Objectives: Overviews search for reviews rather than for primary studies. They might have the potential to support decision making within a shorter time frame by reducing production time. We aimed to summarize available instructions for authors intending to conduct overviews as well as the currently applied methodology of overviews in…

  8. Experimental typography : reviewing the modernist and the current approaches

    OpenAIRE

    Makal, Eray

    1993-01-01

    Ankara : The Department of Graphic Design and Institute of Fine Arts, Bilkent Univ., 1993. Thesis (Master's) -- Bilkent University, 1993. Includes bibliographical references leaves 65-66. The intention of this study is to evaluate the experimental typography within the history of graphic design by taking in consideration of two epochs. The Modernist and The Current. Makal, Eray M.S.

  9. 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.

  10. Current Approaches for Management of Postpenetrating Keratoplasty Astigmatism

    Directory of Open Access Journals (Sweden)

    Sepehr Feizi

    2011-01-01

    Full Text Available A successful corneal graft requires both clarity and an acceptable refraction. A clear corneal graft may be an optical failure if high astigmatism limits visual acuity. Intraoperative measures to reduce postkeratoplasty astigmatism include round and central trephination of cornea with an adequate size, appropriate sutures with evenly distributed tension, and perfect graft-host apposition. Suture manipulation has been described for minimising early postoperative astigmatism. If significant astigmatism remains after suture removal, which cannot be corrected by optical means, then further surgical procedures containing relaxing incisions, compression sutures, laser refractive surgery, insertion of intrastromal corneal ring segments, wedge resection, and toric intraocular lens implantation can be performed. When astigmatism cannot be reduced using one or more abovementioned approaches, repeat penetrating keratoplasty should inevitably be considered. However, none of these techniques has emerged as an ideal one, and corneal surgeons may require combining two or more approaches to exploit the maximum advantages.

  11. Current treatment approaches in patients with ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Bilal Elbey

    2015-03-01

    Full Text Available Ankylosing spondylitis (AS is a chronic, inflammatory, rheumatic disease that mainly affects sacroiliac joints and spine. AS predominantly occurs more often in males and typically begins in the second or third decade. The mainstay of therapy in AS are nonsteroidal anti-inflammatory drugs, which reduce inflammation and pain. Disease modifying antirheumatic drugs (DMARD did not have enough evidence to prove their effect in AS treatment. The use of DMARD may not sufficient to improve the treatment and symptoms. Currently, TNF-blockers such as, Golimumab Etanersept Adalimumab İnfliksimab have promising results in the treatment of AS. TNF-blockers improve the clinical signs and symptoms, and improve the patients’ physical function and quality of life. This manuscript is focused that Current pharmacological treatments in patients with ankylosing spondylitis.

  12. Modification of Current Feedback Strategies: A Text Synthesis Approach.

    Science.gov (United States)

    1984-03-01

    f c o lorad I Technic Report No. 127 This research was aponsored byiwtut ot Cogniive Science The Air Force Office of Scienlbc Uriverulty of Cooado...SYNTHESIS APPROACH(UA COLORADO ANIA AT BOXLDEN INST OF COONITXE SCIENCE P LANGEB ET AL MAN 84 N6 SIID AORT-408 FS-304 / /0 N EA-1216 OIIATOh E CR E...ADDRESS 10. PROGRAM ELEMENT, PROJECT. TASK AREA & WORK( UNIT NUMIERS Institute of Cognitive Science University of Colorado 61103F Boulder, CO 80309

  13. Current approaches and problems in social crime prevention

    OpenAIRE

    Vuković, Slaviša

    2011-01-01

    In this paper the topic of consideration focuses on current methods and forms of implementation social crime prevention, as well as problems that often arise in practice during its implementation. This is one of the most important areas in crime prevention, which is also known as crime prevention through social development, and often includes legal activities of state and non-state actors aimed at preventing delinquency of children and minors through the weakening and, if possible, eliminatin...

  14. Direct current stimulation : new approach to enhancing heavy oil production

    Energy Technology Data Exchange (ETDEWEB)

    Whittle, J.K. [Electro-Petroleum Inc., Wayne, PA (United States); Hill, D.G. [Southern California Univ., Los Angeles, CA (United States)

    2006-07-01

    The limited recovery of heavy crude oil can be attributed to the high viscosity of the liquids in the oil reservoirs. A viable technology has been lacking for the economic recovery of heavy oil. This paper discussed the advantages of direct current electrical stimulation or electro-enhanced oil recovery (EEOR). The paper outlined the advantages, including data produced from field demonstrations as well as the results of recent laboratory studies. The paper provided a historical and electro-chemical background of EEOR. Field operations that were discussed included electric field maps and a comparison of direct current versus alternating current electrical power. A series of EEOR field demonstrations were presented for the Santa Maria basin in California and the eastern Alberta plains. The paper also discussed produced fluid chemical changes and electro-osmosis and effective permeability. Last, the paper provided a comparison of EEOR to other existing and emerging technologies including steam flood; surfactant flood; co-solvent flood; carbon dioxide flood; and fire flood. It was concluded that the biggest EEOR limitation is its limited field application portfolio. EEOR has produced encouraging field demonstrations to date and has facilitated beneficial chemical changes in the produced fluids. 26 refs., 5 tabs., 10 figs.

  15. Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

    Directory of Open Access Journals (Sweden)

    Gidrol Xavier

    2008-02-01

    Full Text Available Abstract Background Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge. Results We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC devoted to BN structure learning. Conclusion We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.

  16. Current approach for urinary system stone disease in pregnant women

    Directory of Open Access Journals (Sweden)

    Orcun Celik

    2016-01-01

    Full Text Available Urinary system stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence. Especially urolithiasis during pregnancy is a diagnostic and therapeutic challenge. In most cases, it becomes symptomatic in the second or third trimester. Diagnostic options in pregnant women are limited due to the possible teratogenic, carcinogenic, and mutagenic risk of foetal radiation exposure. Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between patient, obstetrician and urologist. We would like to review current diagnosis and treatment modalities of stone disease of pregnant woman.

  17. Current approach for urinary system stone disease in pregnant women.

    Science.gov (United States)

    Celik, Orcun; Türk, Hakan; Cakmak, Ozgur; Budak, Salih; Ekin, Rahmi Gokhan; Keskin, Mehmet Zeynel; Yildiz, Guner; Ilbey, Yusuf Ozlem

    2016-01-14

    Urinary system stones can be classified according to size, location, X-ray characteristics, aetiology of formation, composition, and risk of recurrence. Especially urolithiasis during pregnancy is a diagnostic and therapeutic challenge. In most cases, it becomes symptomatic in the second or third trimester. Diagnostic options in pregnant women are limited due to the possible teratogenic, carcinogenic, and mutagenic risk of foetal radiation exposure. Clinical management of a pregnant urolithiasis patient is complex and demands close collaboration between patient, obstetrician and urologist. We would like to review current diagnosis and treatment modalities of stone disease of pregnant woman.

  18. Study on the regulatory approach of KNGR multiple steam generator tube rupture events

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Kweon, Y. C.; Lee, S. J.; Lee, Y. S.; Cheong, D. Y.; Park, T. J.; Lee, M. G.; Cheon, Y. H. [Sunmoon Univ., Asan (Korea, Republic of); Cheong, J. H. [Baekseok College of Cultural Studies, Cheonan (Korea, Republic of)

    2001-10-15

    The scope and contents performed in this project are as follows : firstly, reviews of the structure and contents of local and foreign regulatory requirements as well as analysis of design features related to safety improvement and containment bypass during multiple steam generator tube failure of advanced reactors of domestic and foreign countries. Secondly, analyses of the state-of-the-art of the development of local and foreign regulatory requirements, research trends, design features and safety goals of advanced reactors, especially for technical issues related to the containment bypass during MSGTR event. Thirdly, analyses of the event of MSGTR for the KNGR using MAS 1.4 which is the best-estimate system code developed by Korea Atomic Energy Research Institute. Errors in input-decks established last year have been corrected during this analysis. Fourthly, assessment of the effects of several parameters on the consequences following a MSGTR event. Tube rupture location, selection of affected steam generator, tube modeling method, discharge coefficient (C{sub D}) are examined. Fifthly, establishment of regulatory direction of technical issues related to the containment bypass during MSGTR event.

  19. Current approach in the diagnosis and management of panuveitis

    Directory of Open Access Journals (Sweden)

    Bansal Reema

    2010-01-01

    Full Text Available Panuveitis is a generalized inflammation of not only the whole of the uveal tract but also involves the retina and vitreous humor. It differs from other anatomical sites of inflammation in terms of causes as well as distribution. The common causes of panuveitis in our population are tuberculosis, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, Behcet′s disease and sarcoidosis. A large number of cases still remain idiopathic. A stepwise approach is essential while evaluating these patients to be able to identify and treat the disease timely and correctly. Ancillary tests can be appropriately applied once the anatomic site of inflammation is identified. An exhaustive approach comprising a full battery of tests is obsolete. Only specific tailored investigations are ordered as suggested by the preliminary clinical and ocular examination. The mainstay of the treatment of uveitis is corticosteroids. Immunosuppressive agents are administered if the inflammation is not adequately controlled with corticosteroids. One of the recent breakthroughs in the treatment of refractory uveitis includes the introduction of immunomodulating drugs: Tumor necrosis factor-alpha antagonist and Interferon-alpha. Vitrectomy has been used in uveitis for over a few decades for diagnostic and therapeutic purposes. When compared to other anatomical sites of inflammation, panuveitis has poor visual outcome due to more widespread inflammation. The side-effects of the chronic treatment that these patients receive cannot be overlooked and should be specifically monitored under the supervision of an internist with special interest in inflammatory diseases.

  20. Current Approaches in Implementing Citizen Science in the Classroom.

    Science.gov (United States)

    Shah, Harsh R; Martinez, Luis R

    2016-03-01

    Citizen science involves a partnership between inexperienced volunteers and trained scientists engaging in research. In addition to its obvious benefit of accelerating data collection, citizen science has an unexplored role in the classroom, from K-12 schools to higher education. With recent studies showing a weakening in scientific competency of American students, incorporating citizen science initiatives in the curriculum provides a means to address deficiencies in a fragmented educational system. The integration of traditional and innovative pedagogical methods to reform our educational system is therefore imperative in order to provide practical experiences in scientific inquiry, critical thinking, and problem solving for school-age individuals. Citizen science can be used to emphasize the recognition and use of systematic approaches to solve problems affecting the community.

  1. Ebola virus vaccines: an overview of current approaches.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Heinz

    2014-04-01

    Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible.

  2. Cognitive enrichment and welfare: Current approaches and future directions

    Directory of Open Access Journals (Sweden)

    Fay E. Clark

    2017-02-01

    Full Text Available “Cognitive enrichment” is a subset of enrichment that has gained interest from researchers over the past decade, particularly those working in zoos. This review explores the forms of cognitive enrichment that have been attempted for laboratory, farmed and zoo animals with a focus on the latter, including various definitions, aims, and approaches. This review reveals the fundamental theoretical and practical problems associated with cognitive enrichment, leading to recommendations for further research in this field. Critically, more research is needed to elucidate what makes challenges appropriate for certain taxa, acknowledging that individual differences exist. Going forward, we should be prepared to incorporate more computer technology into cognitive tasks, and examine novel welfare indicators such as flow, competence, and agency.

  3. Current Approaches in Implementing Citizen Science in the Classroom

    Directory of Open Access Journals (Sweden)

    Harsh R. Shah

    2015-12-01

    Full Text Available Citizen science involves a partnership between inexperienced volunteers and trained scientists engaging in research. In addition to its obvious benefit of accelerating data collection, citizen science has an unexplored role in the classroom, from K–12 schools to higher education. With recent studies showing a weakening in scientific competency of American students, incorporating citizen science initiatives in the curriculum provides a means to address deficiencies in a fragmented educational system. The integration of traditional and innovative pedagogical methods to reform our educational system is therefore imperative in order to provide practical experiences in scientific inquiry, critical thinking, and problem solving for school-age individuals. Citizen science can be used to emphasize the recognition and use of systematic approaches to solve problems affecting the community.

  4. Current approaches on viral infection: proteomics and functional validations

    Directory of Open Access Journals (Sweden)

    Jie eZheng

    2012-11-01

    Full Text Available Viruses could manipulate cellular machinery to ensure their continuous survival and thus become parasites of living organisms. Delineation of sophisticated host responses upon virus infection is a challenging task. It lies in identifying the repertoire of host factors actively involved in the viral infectious cycle and characterizing host responses qualitatively and quantitatively during viral pathogenesis. Mass spectrometry based proteomics could be used to efficiently study pathogen-host interactions and virus-hijacked cellular signaling pathways. Moreover, direct host and viral responses upon infection could be further investigated by activity based functional validation studies. These approaches involve drug inhibition of secretory pathway, immunofluorescence staining, dominant negative mutation of protein target, real time PCR, small interfering siRNA-mediated knockdown, and molecular cloning studies. In this way, functional validation could gain novel insights into the high-content proteomic dataset in an unbiased and comprehensive way.

  5. Current approaches and future directions in the treatment of leprosy

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    Worobec SM

    2012-08-01

    Full Text Available Sophie M WorobecDepartment of Dermatology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USAAbstract: This review surveys current treatments and future treatment trends in leprosy from a clinical perspective. The World Health Organization provides a multidrug treatment regimen that targets the Mycobacterium leprae bacillus which causes leprosy. Several investigational drugs are available for the treatment of drug-resistant M. leprae. Future directions in leprosy treatment will focus on: the molecular signaling mechanism M. leprae uses to avoid triggering an immune response; prospective studies of the side effects experienced during multiple-drug therapy; recognition of relapse rates post-completion of designated treatments; combating multidrug resistance; vaccine development; development of new diagnostic tests; and the implications of the recent discovery of a genetically distinct leprosy-causing bacillus, Mycobacterium lepromatosis.Keywords: epidemiology, leprosy, Hansen’s disease, multidrug resistance, multidrug therapy

  6. A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

    Directory of Open Access Journals (Sweden)

    Lan Chung-Yu

    2008-09-01

    Full Text Available Abstract Background Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions. Results In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs such as NF-κB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin. Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network

  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. 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.

  10. COST EFFECTIVE REGULATORY APPROACHES TO ENHANCE DOMESTIC OIL & GAS PRODUCTION AND ENSURE THE PROTECTION OF THE ENVIRONMENT

    Energy Technology Data Exchange (ETDEWEB)

    Ben Grunewald; Paul Jehn; Tom Gillespie; Ben Binder

    2004-12-21

    The Environmental Information Management Suite/Risk Based Data Management System (EIMS/RBDMS) and Cost Effective Regulatory Approach (CERA) programs continue to be successful. All oil and gas state regulatory programs participate in these efforts. Significant accomplishments include: streamline regulatory approaches, enhancing environmental protection, and making oil and gas data available via the Internet. Oil and gas companies worldwide now have access to data on state web sites. This reduces the cost of exploration and enables companies to develop properties in areas that would have been cost prohibited for exploration. Early in project, GWPC and State Oil and Gas agencies developed the EIMS and CERA strategic plan to prioritize long term development and implementation. The planning process identifies electronic commerce and coal bed methane as high priorities. The group has involved strategic partners in industry and government to develop a common data exchange process. Technical assistance to Alaska continues to improve their program management capabilities. New initiatives in Alaska include the development of an electronic permit tracking system. This system allows managers to expedite the permitting process. Nationwide, the RBDMS system is largely completed with 22 states and one Indian Nation now using this nationally accepted data management system. Additional remaining tasks include routine maintenance and the installation of the program upon request for the remaining oil and gas states. The GWPC in working with the BLM and MMS to develop an XML schema to facilitate electronic permitting and reporting (Appendix A, B, and C). This is a significant effort and, in years to come, will increase access to federal lands by reducing regulatory barriers. The new initiatives are coal bed methane and e-commerce. The e-commerce program will provide industry and BLM/MMS access to the millions of data points housed in the RBDMS system. E-commerce will streamline

  11. A systematic review of current and emergent manipulator control approaches

    Science.gov (United States)

    Ajwad, Syed Ali; Iqbal, Jamshed; Ullah, Muhammad Imran; Mehmood, Adeel

    2015-06-01

    Pressing demands of productivity and accuracy in today's robotic applications have highlighted an urge to replace classical control strategies with their modern control counterparts. This recent trend is further justified by the fact that the robotic manipulators have complex nonlinear dynamic structure with uncertain parameters. Highlighting the authors' research achievements in the domain of manipulator design and control, this paper presents a systematic and comprehensive review of the state-of-the-art control techniques that find enormous potential in controlling manipulators to execute cuttingedge applications. In particular, three kinds of strategies, i.e., intelligent proportional-integral-derivative (PID) scheme, robust control and adaptation based approaches, are reviewed. Future trend in the subject area is commented. Open-source simulators to facilitate controller design are also tabulated. With a comprehensive list of references, it is anticipated that the review will act as a firsthand reference for researchers, engineers and industrialinterns to realize the control laws for multi-degree of freedom (DOF) manipulators.

  12. RECURRENT ORAL CANCER: CURRENT AND EMERGING THERAPEUTIC APPROACHES

    Directory of Open Access Journals (Sweden)

    Sabrina Daniela Silva

    2012-07-01

    Full Text Available Oral cancer cavity (OCC is associated with high incidence of loco-regional recurrences, which account for the majority of treatment failures post-surgery and radiotherapy. The time-course of relapse manifestation and metastasis are unpredictable. Relapsed OCC represents a major clinical challenge in part due to their aggressive and invasive behaviors. Chemotherapy remains the only option for advanced OCC whenever salvage surgery or re-irradiation is not feasible, but its efficacy is limited as a result of the drug resistance development. Alternatives to use of different permutations of standard cytotoxic drugs or combinations with modulators of drug resistance have led to incremental therapeutic benefits. The introduction of targeted agents and biologics against selective targets that drive cancer progression has opened-up optimism to achieve superior therapeutic activity and overcome drug resistance because, unlike the non-selective cytotoxic, the target can be monitored at molecular levels to identify patients who can benefit from the drug. This review discusses the multifactorial aspects of clinical drug resistance and emerging therapeutic approaches in recurrent OCC, emphasizing recent advances in targeted therapies, immunotherapy, and potential relevance of new concepts such as epithelial-mesenchymal transition and cancer stem cell hypothesis to drug resistance.

  13. Current Approaches Toward Quantitative Mapping of the Interactome.

    Science.gov (United States)

    Buntru, Alexander; Trepte, Philipp; Klockmeier, Konrad; Schnoegl, Sigrid; Wanker, Erich E

    2016-01-01

    Protein-protein interactions (PPIs) play a key role in many, if not all, cellular processes. Disease is often caused by perturbation of PPIs, as recently indicated by studies of missense mutations. To understand the associations of proteins and to unravel the global picture of PPIs in the cell, different experimental detection techniques for PPIs have been established. Genetic and biochemical methods such as the yeast two-hybrid system or affinity purification-based approaches are well suited to high-throughput, proteome-wide screening and are mainly used to obtain qualitative results. However, they have been criticized for not reflecting the cellular situation or the dynamic nature of PPIs. In this review, we provide an overview of various genetic methods that go beyond qualitative detection and allow quantitative measuring of PPIs in mammalian cells, such as dual luminescence-based co-immunoprecipitation, Förster resonance energy transfer or luminescence-based mammalian interactome mapping with bait control. We discuss the strengths and weaknesses of different techniques and their potential applications in biomedical research.

  14. Current approaches to fine mapping of antigen-antibody interactions.

    Science.gov (United States)

    Abbott, W Mark; Damschroder, Melissa M; Lowe, David C

    2014-08-01

    A number of different methods are commonly used to map the fine details of the interaction between an antigen and an antibody. Undoubtedly the method that is now most commonly used to give details at the level of individual amino acids and atoms is X-ray crystallography. The feasibility of undertaking crystallographic studies has increased over recent years through the introduction of automation, miniaturization and high throughput processes. However, this still requires a high level of sophistication and expense and cannot be used when the antigen is not amenable to crystallization. Nuclear magnetic resonance spectroscopy offers a similar level of detail to crystallography but the technical hurdles are even higher such that it is rarely used in this context. Mutagenesis of either antigen or antibody offers the potential to give information at the amino acid level but suffers from the uncertainty of not knowing whether an effect is direct or indirect due to an effect on the folding of a protein. Other methods such as hydrogen deuterium exchange coupled to mass spectrometry and the use of short peptides coupled with ELISA-based approaches tend to give mapping information over a peptide region rather than at the level of individual amino acids. It is quite common to use more than one method because of the limitations and even with a crystal structure it can be useful to use mutagenesis to tease apart the contribution of individual amino acids to binding affinity.

  15. Cytotherapies in multiple myeloma: a complementary approach to current treatments?

    Science.gov (United States)

    Ciavarella, Sabino; Caselli, Anna; Savonarola, Annalisa; Tamma, Antonella Valentina; Tucci, Marco; Silvestris, Franco

    2013-06-01

    Based on their tumor tropism, mesenchymal stem cells (MSCs) have been proposed as carriers of cytotoxic molecules in pioneering strategies of anti-cancer gene therapy. Similar to solid tumors, MSCs, genetically modified to stably express the TNF-related apoptosis-inducing ligand (TRAIL), have been applied to counter-attack multiple myeloma (MM) in vitro and envisioned as a promising strategy for future anti-MM treatments. Accumulating evidence based on the detection of genetic and functional abnormalities in MSCs from MM patients points to the supportive function of MSCs in both the development and progression of MM, driven by chronic interplays with malignant cells within the marrow milieu. In this review, we revisit the function of MSCs in the pathophysiology of MM and explore the pivotal mechanisms of their interaction with myeloma cells. We also discuss the therapeutic significance of novel strategies using TRAIL-engineered MSCs in this cancer model, dissecting their role as new tools for future treatments against MM. A cytotherapy based on TRAIL-engineered MSCs against MM may be successfully combined with either conventional approaches of autologous stem cell transplantation or with novel anti-MM drugs. Intensive preclinical investigations are required to identify the best sources as well as modalities of MSC administration, thus defining the translational suitability of this strategy in the clinical setting.

  16. Current approaches towards quantitative mapping of the interactome

    Directory of Open Access Journals (Sweden)

    Alexander eBuntru

    2016-05-01

    Full Text Available Protein-protein interactions (PPIs play a key role in many, if not all, cellular processes. Disease is often caused by perturbation of PPIs, as recently indicated by studies of missense mutations. To understand the associations of proteins and to unravel the global picture of PPIs in the cell, different experimental detection techniques for PPIs have been established. Genetic and biochemical methods such as the yeast two-hybrid (Y2H system or affinity purification-based approaches are well suited to high-throughput, proteome-wide screening and are mainly used to obtain qualitative results. However, they have been criticized for not reflecting the cellular situation or the dynamic nature of PPIs. In this review, we provide an overview of various genetic methods that go beyond qualitative detection and allow quantitative measuring of PPIs in mammalian cells, such as DULIP, FRET or LUMIER with BACON. We discuss the strengths and weaknesses of different techniques and their potential applications in biomedical research.

  17. Treatment of preeclampsia: current approach and future perspectives.

    Science.gov (United States)

    Berzan, Ecaterina; Doyle, Ross; Brown, Catherine M

    2014-09-01

    Hypertension is the most common medical disorder encountered during pregnancy, occurring in about 6-8 % of pregnancies. Preeclampsia is a pregnancy-specific disorder that occurs after 20 weeks' gestation, characterized by hypertension and proteinuria. Preeclampsia can also occur superimposed upon chronic hypertension. Eclampsia is the convulsive form of preeclampsia, and affects 0.1 % of all pregnancies. In low-income and middle-income countries, preeclampsia and eclampsia are associated with 10-15 % of direct maternal deaths. Women who develop preeclampsia in pregnancy are at greater risk of cardiovascular and cerebrovascular events even years after their pregnancies. There is significant progress in the elucidation of the underlying mechanisms and pathophysiology of preeclampsia, although its therapeutics remains challenging; delivery of the fetus is still the definitive treatment. Different international societies have produced recommendations and guidelines for clinicians treating preeclampsia, with an overall goal of improving maternal and fetal outcomes. In this review, we focus on the level of blood pressure at which to commence treatment and the current clinical management strategies available to treat and possibly prevent preeclampsia. We also briefly outline some newer perspectives on management of the disorder.

  18. New approaches to business cycle theory in current economic science

    Directory of Open Access Journals (Sweden)

    Monica DOBRESCU

    2012-07-01

    Full Text Available In modern economies, current research generally acknowledges that the central issues in macroeconomics are essentially the same as those identified by Keynes in the General Theory of Employment, Interest and Money. One way or the other, economists are trying to address the same macroeconomic issues that they did seven decades ago: How can we account for the different growth rates and various fluctuations observed in national economies? Which are the economic policies most suitable to solve the issues of growth and cyclic behavior? Both the new classicals and the new Keynesians have made considerable progress within their research paradigms: to explain economic fluctuations, the new classicals focus on technological perturbations, the intertemporal substitution of leisure and real business cycles; on the other hand, the new Keynesians speak in terms of monopolistic competition, menu costs or efficiency wages. On the whole, the new classicals believe that the business cycle can best be understood within the market-clearing model, whereas the new keynesians believe that business fluctuations are due to certain market failures of various sorts.The present paper focuses on the main directions of research of the new classical school on the business cycle, given that the theoretical progress in this field has been significant and relevant for economic policy during the past four decades.

  19. Ocular Behçet disease: current therapeutic approaches.

    Science.gov (United States)

    Evereklioglu, Cem

    2011-11-01

    To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.

  20. Amyotrophic lateral sclerosis: clinical features and current treatment approaches

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-06-01

    Full Text Available Amyotrophic lateral sclerosis also known as Lou Gehring's disease, is the most common motor neuron disease characterized by motor neuron degeneration in the primary cortex, brainstem and spinal cord. This leads to widespread paralysis, respiratory insufficiency and death within an average of 3-5 years from disease onset. Majority of cases is sporadic and only 10% have a family story. One of the most interesting discovery in the field of neurodegeneration in recent years is genetic mutation in the C9orf72 (chromosome 9 open reading frame 72 gene, the most common mutation found to be causative of frontotemporal dementia, amyotrophic lateral sclerosis and concomitant of these two diseases. Currently curative therapy for amyotrophic lateral sclerosis is lacking. To date, one medication, Riluzole, has been proved to prolong survival, approximately 3-5 months, in amyotrophic lateral sclerosis. Researches aim to slow disease progression by targeting known pathophysiological pathways or genetics defects. Only symptomatic care to improve quality of life and survival is suggested. These includes respiratory and nutrition support; dysphagia and gastrostomy management; communication and mobility programs; spasticity prevention; pain medication; management of cognitive dysfunction, depression, mood dysorders (especially apathy, fatigue, sleep disturbance and prevention of deep venous thrombosis. [Archives Medical Review Journal 2015; 24(2.000: 182-194

  1. The aetiology ofautism spectrum disorders. An overview of current approaches

    Directory of Open Access Journals (Sweden)

    Paulina Gołaska

    2013-03-01

    Full Text Available Despite the great popularity of autism among researchers, its main cause still remains unknown. However, there are many theories which describe the mechanisms of this disorder. On the other hand, one who tries to integrate them seems to be helpless according to their contradictory and – in most cases – hypothetical status. In a context of this inac‑ curacy, focusing only on one of the concepts would be probably very disadvantageous. As many researchers suggest, the etiology of autism is complex and it is the interaction of multiple factors which implies the disorder appears. It seems that the nature of autism is equifinal and heterogeneous. Thus, the aim of this article is to present a review of current biological theories of autism etiology and to indicate the environmental as well as innate risk factors which may disturb the natural pathway of child development: prenatal (which increase the probability of autism emergence as early as in the first or second year of life or perinatal ones (low birth weight, hypoxia, age of the mother, her educational sta‑ tus. The foetal testosterone theory of autism and its general consequences for the child development will be described also. Finally, the neurological, neurochemical and neuroanatomical dysfunctions in autism will be presented.

  2. Current approaches toward production of secondary plant metabolites

    Directory of Open Access Journals (Sweden)

    Md. Sarfaraj Hussain

    2012-01-01

    Full Text Available Plants are the tremendous source for the discovery of new products with medicinal importance in drug development. Today several distinct chemicals derived from plants are important drugs, which are currently used in one or more countries in the world. Secondary metabolites are economically important as drugs, flavor and fragrances, dye and pigments, pesticides, and food additives. Many of the drugs sold today are simple synthetic modifications or copies of the naturally obtained substances. The evolving commercial importance of secondary metabolites has in recent years resulted in a great interest in secondary metabolism, particularly in the possibility of altering the production of bioactive plant metabolites by means of tissue culture technology. Plant cell and tissue culture technologies can be established routinely under sterile conditions from explants, such as plant leaves, stems, roots, and meristems for both the ways for multiplication and extraction of secondary metabolites. In vitro production of secondary metabolite in plant cell suspension cultures has been reported from various medicinal plants, and bioreactors are the key step for their commercial production. Based on this lime light, the present review is aimed to cover phytotherapeutic application and recent advancement for the production of some important plant pharmaceuticals.

  3. SAPHO Syndrome: Current Developments and Approaches to Clinical Treatment.

    Science.gov (United States)

    Firinu, Davide; Garcia-Larsen, Vanessa; Manconi, Paolo Emilio; Del Giacco, Stefano R

    2016-06-01

    SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare autoimmune disease which, due to its clinical presentation and symptoms, is often misdiagnosed and unrecognized. Its main features are prominent inflammatory cutaneous and articular manifestations. Treatments with immunosuppressive drugs have been used for the management of SAPHO with variable results. To date, the use of anti-TNF-α agents has proved to be an effective alternative to conventional treatment for unresponsive or refractory SAPHO cases. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β, IL-6, and IL-8, involved in inflammation, acute-phase response induction, and chemotaxis. IL-1 inhibition strategies with anakinra have shown efficacy as first and second lines of treatment. In this review, we will describe the main characteristics of biological drugs currently used for SAPHO syndrome. We also describe some of the promising therapeutic effects of ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and anakinra. We discuss the use and impact of the new anti-IL-1 antagonists involved in the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.

  4. A synthetic biology approach to self-regulatory recombinant protein production in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Dragosits Martin

    2012-03-01

    Full Text Available Abstract Background Recombinant protein production is a process of great industrial interest, with products that range from pharmaceuticals to biofuels. Since high level production of recombinant protein imposes significant stress in the host organism, several methods have been developed over the years to optimize protein production. So far, these trial-and-error techniques have proved laborious and sensitive to process parameters, while there has been no attempt to address the problem by applying Synthetic Biology principles and methods, such as integration of standardized parts in novel synthetic circuits. Results We present a novel self-regulatory protein production system that couples the control of recombinant protein production with a stress-induced, negative feedback mechanism. The synthetic circuit allows the down-regulation of recombinant protein expression through a stress-induced promoter. We used E. coli as the host organism, since it is widely used in recombinant processes. Our results show that the introduction of the self-regulatory circuit increases the soluble/insoluble ratio of recombinant protein at the expense of total protein yield. To further elucidate the dynamics of the system, we developed a computational model that is in agreement with the observed experimental data, and provides insight on the interplay between protein solubility and yield. Conclusion Our work introduces the idea of a self-regulatory circuit for recombinant protein products, and paves the way for processes with reduced external control or monitoring needs. It demonstrates that the library of standard biological parts serves as a valuable resource for initial synthetic blocks that needs to be further refined to be successfully applied in practical problems of biotechnological significance. Finally, the development of a predictive model in conjunction with experimental validation facilitates a better understanding of the underlying dynamics and can be

  5. Treatment of cutaneous melanoma: current approaches and future prospects

    Directory of Open Access Journals (Sweden)

    Alain P Algazi

    2010-08-01

    Full Text Available Alain P Algazi1, Christopher W Soon2, Adil I Daud11Department of Medicine, Division of Hematology and Oncology, 2Department of Dermatology, University of California, San Francisco San Francisco, CA, USAAbstract: Melanoma is the most aggressive and deadly type of skin cancer. Surgical resection with or without lymph node sampling is the standard of care for primary cutaneous melanoma. Adjuvant therapy decisions may be informed by careful consideration of prognostic factors. High-dose adjuvant interferon alpha-2b increases disease-free survival and may modestly improve overall survival. Less toxic alternatives for adjuvant therapy are currently under study. External beam radiation therapy is an option for nodal beds where the risk of local recurrence is very high. In-transit melanoma metastases may be treated locally with surgery, immunotherapy, radiation, or heated limb perfusion. For metastatic melanoma, the options include chemotherapy or immunotherapy; targeted anti-BRAF and anti-KIT therapy is under active investigation. Standard chemotherapy yields objective tumor responses in approximately 10%–20% of patients, and sustained remissions are uncommon. Immunotherapy with high-dose interleukin-2 yields objective tumor responses in a minority of patients; however, some of these responses may be durable. Identification of activating mutations of BRAF, NRAS, c-KIT, and GNAQ in distinct clinical subtypes of melanoma suggest that these are molecularly distinct. Emerging data from clinical trials suggest that substantial improvements in the standard of care for melanoma may be possible.Keywords: melanoma, resection, immune modulation, small molecule kinase inhibitors, chemotherapy, clinical trials

  6. [Current approaches to explain the virulence of Acinetobacter baumannii].

    Science.gov (United States)

    Aşık, Gülşah

    2011-04-01

    Acinetobacter baumannii which is one of the most frequent nosocomial pathogens, has drawn attention in the last years owing to multi-drug resistant strains. A.baumannii may give rise to nosocomial epidemics especially in intensive care units and may lead to treatment failure due to its increasing antimicrobial resistance. These gram-negative non-fermentative coccobacilli may be encountered also in community associated infections. However, they are frequently isolated in pneumonia, urinary tract infection, bacteremia, meningitis and wound infections that develop in patients hospitalized for serious diseases. Although detailed data about the epidemiology and antimicrobial resistance patterns related to this bacteria exist, relatively limited data is present about the virulence factors and environmental physiology of A.baumannii. The role of some bacterial virulence factors in the pathogenesis of Acinetobacter infections have been enlightened by recent investigations. Among these virulence factors, production of extracellular enzymes with lipolytic and cytolytic activities, outer membrane protein (AbOmpA) with apoptotic effects on epithelial cells, adhesion molecules (fimbria and AbOmpA) that function during attachment to epithelial cells, K1 type capsular structure, type-1 pili and AbOmpA induced biofilm formation, siderophore (acinetobactin) or hemin mediated iron acquisition mechanisms, quorum sensing system that functions by the help of N-acyl homoserine lacton signal molecules and cellular components that enable Acinetobacter species to live under inappropriate environmental conditions like dryness, low temperature, restricted nutritional elements, can be counted. New information about the virulence factors will help better understanding of the adaptive response of A.baumannii in the host setting. This review is focused on the current information about the virulence factors of of A.baumannii.

  7. Optimal Control of Gene Regulatory Networks with Effectiveness of Multiple Drugs: A Boolean Network Approach

    Science.gov (United States)

    Kobayashi, Koichi; Hiraishi, Kunihiko

    2013-01-01

    Developing control theory of gene regulatory networks is one of the significant topics in the field of systems biology, and it is expected to apply the obtained results to gene therapy technologies in the future. In this paper, a control method using a Boolean network (BN) is studied. A BN is widely used as a model of gene regulatory networks, and gene expression is expressed by a binary value (0 or 1). In the control problem, we assume that the concentration level of a part of genes is arbitrarily determined as the control input. However, there are cases that no gene satisfying this assumption exists, and it is important to consider structural control via external stimuli. Furthermore, these controls are realized by multiple drugs, and it is also important to consider multiple effects such as duration of effect and side effects. In this paper, we propose a BN model with two types of the control inputs and an optimal control method with duration of drug effectiveness. First, a BN model and duration of drug effectiveness are discussed. Next, the optimal control problem is formulated and is reduced to an integer linear programming problem. Finally, numerical simulations are shown. PMID:24058904

  8. 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.

  9. Correlating overrepresented upstream motifs to gene expression a computational approach to regulatory element discovery in eukaryotes

    CERN Document Server

    Caselle, M; Provero, P

    2002-01-01

    Gene regulation in eukaryotes is mainly effected through transcription factors binding to rather short recognition motifs generally located upstream of the coding region. We present a novel computational method to identify regulatory elements in the upstream region of eukaryotic genes. The genes are grouped in sets sharing an overrepresented short motif in their upstream sequence. For each set, the average expression level from a microarray experiment is determined: If this level is significantly higher or lower than the average taken over the whole genome, then the overerpresented motif shared by the genes in the set is likely to play a role in their regulation. The method was tested by applying it to the genome of Saccharomyces cerevisiae, using the publicly available results of a DNA microarray experiment, in which expression levels for virtually all the genes were measured during the diauxic shift from fermentation to respiration. Several known motifs were correctly identified, and a new candidate regulat...

  10. Talus Lex: Regulatory Approaches to Reducing Mercury Concentrations in San Francisco Bay Fish.

    Science.gov (United States)

    Abu-Saba, D. E.; Flegal, D. R.; Ganguli, P. M.; Whyte, D. C.; Mumley, D. E.; Mason, D. P.

    2001-12-01

    The history of mercury in California is recorded in the sediments of San Francisco Bay. The Bay is downstream of 40 percent of the land area of California. Its watershed receives 80 percent of the rainfall in the State, because it rains more in the north. Three billion kilograms of sediments are annually flushed from the Central Valley watershed and deposited in San Francisco Bay. Because mercury preferentially binds to sediments, we calculate mercury loads to the Bay by considering how various sources affect mercury concentrations in Bay sediments. During and after the Gold Rush, over seventy thousand tons of mercury was produced in Coast Range cinnabar mines. Much of this mercury was used as quicksilver to extract gold from placer formations in the Sierra foothills, and later in the production of munitions, electronics, health care and commercial products. Today, we can see the legacy of mining sources, from both remote and local watersheds, superimposed on air deposition, the climate and geography of California, heavily managed water supply and flood control projects, wetland restoration and rehabilitation, urbanization, wastewaster discharge and water reclamation. We already regulate wastewater and urban runoff through issuance of permits and waste discharge requirements. We can regulate mercury inputs from inoperative mines by demonstrating the link between mercury-polluted sediments and violation of existing numeric water quality objectives. We can use the same approach to regulate the disposal of mercury-containing electronic devices. But to reduce mercury levels in fish, we will also have to consider controllable water quality factors that promote mercury methylation in the aquatic ecosystem. Some of these water quality factors are already subject to regulation. For example, we can show that mercury methylation in the northern reach of the Bay increases when dissolved oxygen drops below 6 mg/L; current regulations require dissolved oxygen concentrations of

  11. OVERVIEW OF THE U.S. DEPARTMENT OF ENERGY AND NUCLEAR REGULATORY COMMISSION PERFORMANCE ASSESSMENT APPROACHES: CEMENTITIOUS BARRIERS PARTNERSHIP

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.; Burns, H.

    2009-05-29

    Engineered barriers including cementitious barriers are used at sites disposing or contaminated with low-level radioactive waste to enhance performance of the natural environment with respect to controlling the potential spread of contaminants. Drivers for using cementitious barriers include: high radionuclide inventory, radionuclide characteristics (e.g., long half-live, high mobility due to chemical form/speciation, waste matrix properties, shallow water table, and humid climate that provides water for leaching the waste). This document comprises the first in a series of reports being prepared for the Cementitious Barriers Partnership. The document is divided into two parts which provide a summary of: (1) existing experience in the assessment of performance of cementitious materials used for radioactive waste management and disposal and (2) sensitivity and uncertainty analysis approaches that have been applied for assessments. Each chapter is organized into five parts: Introduction, Regulatory Considerations, Specific Examples, Summary of Modeling Approaches and Conclusions and Needs. The objective of the report is to provide perspective on the state of the practice for conducting assessments for facilities involving cementitious barriers and to identify opportunities for improvements to the existing approaches. Examples are provided in two contexts: (1) performance assessments conducted for waste disposal facilities and (2) performance assessment-like analyses (e.g., risk assessments) conducted under other regulatory regimes. The introductory sections of each section provide a perspective on the purpose of performance assessments and different roles of cementitious materials for radioactive waste management. Significant experience with assessments of cementitious materials associated with radioactive waste disposal concepts exists in the US Department of Energy Complex and the commercial nuclear sector. Recently, the desire to close legacy facilities has created

  12. A genomic approach to identify regulatory nodes in the transcriptional network of systemic acquired resistance in plants.

    Directory of Open Access Journals (Sweden)

    Dong Wang

    2006-11-01

    Full Text Available Many biological processes are controlled by intricate networks of transcriptional regulators. With the development of microarray technology, transcriptional changes can be examined at the whole-genome level. However, such analysis often lacks information on the hierarchical relationship between components of a given system. Systemic acquired resistance (SAR is an inducible plant defense response involving a cascade of transcriptional events induced by salicylic acid through the transcription cofactor NPR1. To identify additional regulatory nodes in the SAR network, we performed microarray analysis on Arabidopsis plants expressing the NPR1-GR (glucocorticoid receptor fusion protein. Since nuclear translocation of NPR1-GR requires dexamethasone, we were able to control NPR1-dependent transcription and identify direct transcriptional targets of NPR1. We show that NPR1 directly upregulates the expression of eight WRKY transcription factor genes. This large family of 74 transcription factors has been implicated in various defense responses, but no specific WRKY factor has been placed in the SAR network. Identification of NPR1-regulated WRKY factors allowed us to perform in-depth genetic analysis on a small number of WRKY factors and test well-defined phenotypes of single and double mutants associated with NPR1. Among these WRKY factors we found both positive and negative regulators of SAR. This genomics-directed approach unambiguously positioned five WRKY factors in the complex transcriptional regulatory network of SAR. Our work not only discovered new transcription regulatory components in the signaling network of SAR but also demonstrated that functional studies of large gene families have to take into consideration sequence similarity as well as the expression patterns of the candidates.

  13. A discussion of regulatory requirements and air dispersion modeling approaches applicable to U.S. chemical demilitarization facilities.

    Science.gov (United States)

    Higgins, B W; Robbins, L B; Litynski, J

    1998-09-01

    Owners of hazardous waste treatment, storage, and disposal facilities, and certain major air pollution sources, must conduct several separate ambient air dispersion modeling analyses before beginning construction of new facilities or modifying existing facilities. These analyses are critical components of the environmental permitting and facility certification processes and must be completed to the satisfaction of federal, state, and local regulatory authorities. The U.S. Army has conducted air dispersion modeling for its proposed chemical agent disposal facilities to fulfill the following environmental regulatory and risk management requirements: (1) Resource Conservation and Recovery Act human health and ecological risk assessment analysis for the hazardous waste treatment and storage permit applications, (2) Quantitative Risk Assessment to support the site-specific risk management programs, and (3) Prevention of Significant Deterioration ambient air impact analysis for the air permit applications. The purpose of these air dispersion modeling studies is to show that the potential impacts on human health and the environment, due to operation of the chemical agent disposal facilities, are acceptable. This paper describes and compares the types of air dispersion models, modeling input data requirements, modeling algorithms, and approaches used to satisfy the three environmental regulatory and risk management requirements listed above. Although this paper discusses only one industry (i.e., chemical demilitarization), the information it contains could help those in other industries who need to communicate to the public the purpose and objectives of each modeling analysis. It may also be useful in integrating the results of each analysis into an overarching summary of compliance and potential risks.

  14. Highly Reliable Organizations in the Onshore Natural Gas Sector: An Assessment of Current Practices, Regulatory Frameworks, and Select Case Studies

    Energy Technology Data Exchange (ETDEWEB)

    Logan, Jeffrey S. [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Paranhos, Elizabeth [Energy Innovation Partners, Seattle, WA (United States); Kozak, Tracy G. [Energy Innovation Partners, Seattle, WA (United States); Boyd, William [Univ. of Colorado, Boulder, CO (United States)

    2017-07-31

    This study focuses on onshore natural gas operations and examines the extent to which oil and gas firms have embraced certain organizational characteristics that lead to 'high reliability' - understood here as strong safety and reliability records over extended periods of operation. The key questions that motivated this study include whether onshore oil and gas firms engaged in exploration and production (E&P) and midstream (i.e., natural gas transmission and storage) are implementing practices characteristic of high reliability organizations (HROs) and the extent to which any such practices are being driven by industry innovations and standards and/or regulatory requirements.

  15. A study on the regulatory approach of KNGR multiple failure events

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Kweon, Y. C.; Kang, H. J.; Lee, S. J.; Cheong, D. Y.; Lee, Y. S.; Lee, M. K. [Sunmoon Univ., Asan (Korea, Republic of); Jeong, Ji Hwan [Baekseok College of Cultural studies, Cheonan (Korea, Republic of)

    2001-01-15

    This project is to provide the regulatory direction of containment bypass during multiple steam generator tube failure issue for the Korean Next Generation Reactors, which is a part of major technical issues resulted from the safety regulation R and D on the KNGR. The outstanding results are as follows : the Multiple Steam Generator Tube Repture(MSGTR) event has never been occurred in the history of commercial nuclear reactor operation but single Steam Generator Tube Rupture(SGTR) event is reported to occur every two years. A probabilistic safety analysis study on MSGTR event, however, show its probability of occurrence is to be the same order as the design basis accidents such as LACA. In this regard, the ability of NPPs to cope with MSGTR event is required. Some requirements on initial and boundary conditions are suggested to be used in the analyses of NPPs during MSGTR events. The items that should be considered in establishing regulatory requirements are summarized as follows : the analyses of MSGTR events should be performed by a best-estimate method with normal full power conditions except initial reactor power of 102%, all safety- and non-safety grade systems and components are assumed to be available only in automatic mode, tube ruptures are assumed to occur at the steam generator which is in the loop connected with a pressurizer, guillotine-type tube raptures are assumed near tube sheet on hot-leg side, the results of 1-5 tube ruptures should be compared, an appropriate break flow model should be used and critical flow model can be compared, an appropriate break flow model should be used and critical flow model can be used if needed, operator response time should be based on ANSI/ANS-51.1-1983 and ANSI/ANS-58.8-1984, acceptance criteria should be stated in terms of MSSV lift time as well as radiological consequences. It is recommended that some analyses should be carried out in order to figure out the effects of tube rupture modelling methods. A single

  16. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production

    Science.gov (United States)

    Walshaw, John; Peck, Michael W.; Barker, Gary C.

    2016-01-01

    Clostridium botulinum produces botulinum neurotoxins (BoNTs), highly potent substances responsible for botulism. Currently, mathematical models of C. botulinum growth and toxigenesis are largely aimed at risk assessment and do not include explicit genetic information beyond group level but integrate many component processes, such as signalling, membrane permeability and metabolic activity. In this paper we present a scheme for modelling neurotoxin production in C. botulinum Group I type A1, based on the integration of diverse information coming from experimental results available in the literature. Experiments show that production of BoNTs depends on the growth-phase and is under the control of positive and negative regulatory elements at the intracellular level. Toxins are released as large protein complexes and are associated with non-toxic components. Here, we systematically review and integrate those regulatory elements previously described in the literature for C. botulinum Group I type A1 into a population dynamics model, to build the very first computational model of toxin production at the molecular level. We conduct a validation of our model against several items of published experimental data for different wild type and mutant strains of C. botulinum Group I type A1. The result of this process underscores the potential of mathematical modelling at the cellular level, as a means of creating opportunities in developing new strategies that could be used to prevent botulism; and potentially contribute to improved methods for the production of toxin that is used for therapeutics. PMID:27855161

  17. Robust control of uncertain nonlinear switched genetic regulatory networks with time delays: A redesign approach.

    Science.gov (United States)

    Moradi, Hojjatullah; Majd, Vahid Johari

    2016-05-01

    In this paper, the problem of robust stability of nonlinear genetic regulatory networks (GRNs) is investigated. The developed method is an integral sliding mode control based redesign for a class of perturbed dissipative switched GRNs with time delays. The control law is redesigned by modifying the dissipativity-based control law that was designed for the unperturbed GRNs with time delays. The switched GRNs are switched from one mode to another based on time, state, etc. Although, the active subsystem is known in any instance, but the switching law and the transition probabilities are not known. The model for each mode is considered affine with matched and unmatched perturbations. The redesigned control law forces the GRN to always remain on the sliding surface and the dissipativity is maintained from the initial time in the presence of the norm-bounded perturbations. The global stability of the perturbed GRNs is maintained if the unperturbed model is globally dissipative. The designed control law for the perturbed GRNs guarantees robust exponential or asymptotic stability of the closed-loop network depending on the type of stability of the unperturbed model. The results are applied to a nonlinear switched GRN, and its convergence to the origin is verified by simulation.

  18. Meson-exchange currents and quasielastic predictions for charged-current neutrino-12C scattering in the superscaling approach

    CERN Document Server

    Megias, G D; Moreno, O; Williamson, C F; Caballero, J A; Gonzalez-Jimenez, R; De Pace, A; Barbaro, M B; Alberico, W M; Nardi, M; Amaro, J E

    2014-01-01

    We evaluate and discuss the impact of meson-exchange currents (MEC) on charged-current quasielastic (QE) neutrino cross sections. We consider the nuclear transverse response arising from 2p-2h states excited by the action of electromagnetic, purely isovector meson-exchange currents in a fully relativistic framework, based on the work by the Torino collaboration [1]. An accurate parametrization of this MEC response as a function of the momentum and energy transfers involved is presented. Results of neutrino-nucleus cross sections using this MEC parametrization together with a recent scaling approach for the 1p-1h contributions (SuSAv2) are compared with experimental data (MiniBooNE, MINERvA, NOMAD and T2K Collaborations).

  19. Do pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery?

    Science.gov (United States)

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2008-06-01

    In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of G-signalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.

  20. Statistical approaches to use a model organism for regulatory sequences annotation of newly sequenced species.

    Directory of Open Access Journals (Sweden)

    Pietro Liò

    Full Text Available A major goal of bioinformatics is the characterization of transcription factors and the transcriptional programs they regulate. Given the speed of genome sequencing, we would like to quickly annotate regulatory sequences in newly-sequenced genomes. In such cases, it would be helpful to predict sequence motifs by using experimental data from closely related model organism. Here we present a general algorithm that allow to identify transcription factor binding sites in one newly sequenced species by performing Bayesian regression on the annotated species. First we set the rationale of our method by applying it within the same species, then we extend it to use data available in closely related species. Finally, we generalise the method to handle the case when a certain number of experiments, from several species close to the species on which to make inference, are available. In order to show the performance of the method, we analyse three functionally related networks in the Ascomycota. Two gene network case studies are related to the G2/M phase of the Ascomycota cell cycle; the third is related to morphogenesis. We also compared the method with MatrixReduce and discuss other types of validation and tests. The first network is well known and provides a biological validation test of the method. The two cell cycle case studies, where the gene network size is conserved, demonstrate an effective utility in annotating new species sequences using all the available replicas from model species. The third case, where the gene network size varies among species, shows that the combination of information is less powerful but is still informative. Our methodology is quite general and could be extended to integrate other high-throughput data from model organisms.

  1. A study on the regulatory approach of KNGR multiple failure events

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Keun Sun; Kweon, Y. C.; Kang, H. J.; Lee, S. J.; Lee, Y. S.; Moon, J. J.; Lee, M. K. [Sumoon Univ., Asan (Korea, Republic of); Jeong, Ji Hwan [Baekseok College, Cheonan (Korea, Republic of); Yang, S. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

    2000-02-15

    This project is to provide the regulatory direction of 3 major technical issues for the Korean Next Generation Reactors, which are parts of major technical issues resulted from the safety regulation R and D on the KNGR. The outstanding results are as follows : through comparison and analysis of domestic/international requirements related to SBO, additional items, which are considered in SSRs, are identified. According to investigation, procedure and training should be included in SSRs, and plant-specific capability analysis requirement contains initial condition, acceptance and addition analysis on the leak rake through RCP seal, etc. In addition, state of the art on the major items related to SBO requirement are described. Several safety analysis requirements are suggested that are needed to be used in the analyses which are aiming to show the ability of the SDVS to cope with TLOFW event. The suggested requirements include suggestions in BE method, reactor thermal power and decay heat, time to reactor trip, time to RCP trip, operator response time, pressurizer and steam generator, and thermal-hydraulic models related to TLOFW event. It is recommended that Moody model mentioned in 10CFR50 appendix K should be excluded in calculation of discharge flow through bleed valves in case of a TLOFW event. Some requirements on initial and boundary conditions are suggested to be used in the analyses of NPPs during MSGTR events. The suggestion includes requirements on analysis method, number of reptured tubes, repture location, operator response time, primary coolant leak flow, and acceptance criteria. As there has been no occurrence of MSGTR event and little literatures reporting analysis results of the event, some items need more study. In addition, some analyses are needed in order to fine the rupture location which gives the most conservative consequence.

  2. Regulatory T cells as a therapeutic tool to induce solid-organ transplant tolerance: current clinical experiences.

    Science.gov (United States)

    Nikoueinejad, Hassan; Sharif, Mohammad Reza; Amirzargar, Aliakbar; Mirshafiey, Abbas; Einollahi, Behzad

    2013-10-01

    Long-term tolerance is potentially an ideal in organ transplant. Achieving this leads us to eliminate immunosuppressive therapies and their associated side effects. Although most succession in this field belongs to mixed chimerism methods of tolerance induction, regulatory T cells and (T-reg)-based methods also have been demonstrated to prevent organ rejection and lead to transplant tolerance through different mechanisms. In contrast to chimeric protocols (which require bone marrow transplant), T-reg-mediated protocols do not aggressively manipulate blood and the immune system. Most treatment has been done for graft-versus-host disease after hematopoietic stem cell transplant. This review describes different types and mechanisms of action and clinical strategies using T-regs to induce transplant tolerance.

  3. An approach to evaluate the topological significance of motifs and other patterns in regulatory networks

    Directory of Open Access Journals (Sweden)

    Wingender Edgar

    2009-05-01

    that enables to evaluate the topological significance of various connected patterns in a regulatory network. Applying this method onto transcriptional networks of three largely distinct organisms we could prove that it is highly suitable to identify most important pattern instances, but that neither motifs nor any pattern in general appear to play a particularly important role per se. From the results obtained so far, we conclude that the pairwise disconnectivity index will most likely prove useful as well in identifying other (higher-order pattern instances in transcriptional and other networks.

  4. Searching for a Cure: The FDA's Regulatory Approach to Traditional Chinese Herbal Medicine

    OpenAIRE

    Kim, Anna L.

    1997-01-01

    I will begin this discussion by describing traditional Chinese medicine and how it compares to the Western medical tradition. Second, I will then examine why regulation is necessary given the impact of Chinese herbal medicine on American healthcare. Then, I will proceed to the problem of trying to fit a square peg into a round hole, namely, the issue of regulating Chinese herbal medicine under current statutory provisions. Fourth, I will analyze state and federal responses to alternative ther...

  5. Not Another Quiz: An Approach to Engage Today's Students in Meaningful Current Events Discussions

    Science.gov (United States)

    Wright, Leigh L.; Shemberger, Melony; Price, Elizabeth

    2016-01-01

    Journalism professors are concerned with how effectively students understand current news events and engage with mainstream news sources. This essay is based on a survey administered to students in a newswriting course and analyzed the kinds of current news that students followed in weekly assignments designed with a digital, interactive approach.…

  6. 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

  7. Innovative Regulatory and Technical Approaches for the U.S. Army Corp of Engineers' Linde FUSRAP Site Remediation

    Energy Technology Data Exchange (ETDEWEB)

    Pitts, J. T.; Coutts, P. W.; Franz, J.; Boyle, J. D.; Rogers, B. C.

    2002-02-27

    The U.S. Department of Energy (USDOE) created the Formerly Utilized Sites Remedial Action Program (FUSRAP) in 1974 to identify, investigate, and cleanup or control radiological contamination at sites used by the Manhattan Engineer District (MED) and the Atomic Energy Commission (AEC) from the 1940s through the 1960s. The USDOE had identified 46 sites in the program and finished remediation at 24 of the smaller ones before the end of 1997. With the passage of the Energy and Water Resources Appropriation Act of 1998 the United States Army Corps of Engineers (USACE) was designated by Congress with responsibility to manage and execute the FUSRAP. The Linde Site located in Tonawanda, New York was operated by the MED from 1942-1946 to extract uranium from several high-grade ores. This natural uranium was subsequently enriched in U-235 elsewhere in the United States and ultimately used to produce energy or weapons. Though in the process of reviewing alternative disposal options by 1995, the USDOE had operated FUSRAP with a strategy requiring virtually all materials remediated be disposed of at only one Nuclear Regulatory Commission licensed facility. The change in management of the FUSRAP in 1997 allowed the disposal policy of low levels of radioactively contaminated materials found at the remaining sites to be reexamined. This paper presents some of the innovative regulatory and technical approaches employed at the Linde Site that are resulting in project cost savings while meeting applicable or relevant and appropriate requirements as well as fulfilling commitments made to the local community.

  8. Mapping knowledge investments in the aftermath of Hurricane Katrina: a new approach for assessing regulatory agency responses to environmental disaster

    Energy Technology Data Exchange (ETDEWEB)

    Frickel, Scott [Department of Sociology, 213 Wilson Hall, Washington State University, Pullman, WA 99164-4020 (United States)], E-mail: frickel@wsu.edu; Campanella, Richard [Center for Bioenvironmental Research, Alcee Fortier Hall, Tulane University, New Orleans, LA 70118 (United States); Vincent, M. Bess [Department of Sociology, 220 Newcomb Hall, Tulane University, New Orleans, LA 70118 (United States)

    2009-04-15

    In the aftermath of large-scale disasters, the public's dependency on federal and state agencies for information about public safety and environmental risk is acute. While formal rules and procedures are in place to guide policy decisions in environmental risk assessment of spatially concentrated hazards such as regulated waste sites or vacant city lots, standard procedures for risk assessment seem potentially less well-suited for urban-scale disaster zones where environmental hazards may be widely dispersed and widely varying. In this paper we offer a new approach for the social assessment of regulatory science in response to large-scale disaster, illustrating our methodology through a socio-spatial analysis of the U.S. Environmental Protection Agency's (EPA) hazard assessment in New Orleans, Louisiana, following Hurricane Katrina in 2005. We find that the agency's commitment of epistemic resources or 'knowledge investments' varied considerably across the flood-impacted portion of the city, concentrating in poorer and disproportionately African American neighborhoods previously known to be heavily contaminated. We address some of the study's social and policy implications, noting the multidimensionality and interactive nature of knowledge investments and the prospects for deepening and extending this approach through comparative research.

  9. Identifying niche-mediated regulatory factors of stem cell phenotypic state: a systems biology approach.

    Science.gov (United States)

    Ravichandran, Srikanth; Del Sol, Antonio

    2017-02-01

    Understanding how the cellular niche controls the stem cell phenotype is often hampered due to the complexity of variegated niche composition, its dynamics, and nonlinear stem cell-niche interactions. Here, we propose a systems biology view that considers stem cell-niche interactions as a many-body problem amenable to simplification by the concept of mean field approximation. This enables approximation of the niche effect on stem cells as a constant field that induces sustained activation/inhibition of specific stem cell signaling pathways in all stem cells within heterogeneous populations exhibiting the same phenotype (niche determinants). This view offers a new basis for the development of single cell-based computational approaches for identifying niche determinants, which has potential applications in regenerative medicine and tissue engineering. © 2017 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  10. OVERVIEW OF THE U.S. DEPARTMENT OF ENERGY AND NUCLEAR REGULATORY COMMISSION PERFORMANCE ASSESSMENT APPROACHES: CEMENTITIOUS BARRIERS PARTNERSHIP

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C.; Burns, H.

    2009-05-29

    Engineered barriers including cementitious barriers are used at sites disposing or contaminated with low-level radioactive waste to enhance performance of the natural environment with respect to controlling the potential spread of contaminants. Drivers for using cementitious barriers include: high radionuclide inventory, radionuclide characteristics (e.g., long half-live, high mobility due to chemical form/speciation, waste matrix properties, shallow water table, and humid climate that provides water for leaching the waste). This document comprises the first in a series of reports being prepared for the Cementitious Barriers Partnership. The document is divided into two parts which provide a summary of: (1) existing experience in the assessment of performance of cementitious materials used for radioactive waste management and disposal and (2) sensitivity and uncertainty analysis approaches that have been applied for assessments. Each chapter is organized into five parts: Introduction, Regulatory Considerations, Specific Examples, Summary of Modeling Approaches and Conclusions and Needs. The objective of the report is to provide perspective on the state of the practice for conducting assessments for facilities involving cementitious barriers and to identify opportunities for improvements to the existing approaches. Examples are provided in two contexts: (1) performance assessments conducted for waste disposal facilities and (2) performance assessment-like analyses (e.g., risk assessments) conducted under other regulatory regimes. The introductory sections of each section provide a perspective on the purpose of performance assessments and different roles of cementitious materials for radioactive waste management. Significant experience with assessments of cementitious materials associated with radioactive waste disposal concepts exists in the US Department of Energy Complex and the commercial nuclear sector. Recently, the desire to close legacy facilities has created

  11. Programmable chemical reaction networks: emulating regulatory functions in living cells using a bottom-up approach.

    Science.gov (United States)

    van Roekel, Hendrik W H; Rosier, Bas J H M; Meijer, Lenny H H; Hilbers, Peter A J; Markvoort, Albert J; Huck, Wilhelm T S; de Greef, Tom F A

    2015-11-07

    Living cells are able to produce a wide variety of biological responses when subjected to biochemical stimuli. It has become apparent that these biological responses are regulated by complex chemical reaction networks (CRNs). Unravelling the function of these circuits is a key topic of both systems biology and synthetic biology. Recent progress at the interface of chemistry and biology together with the realisation that current experimental tools are insufficient to quantitatively understand the molecular logic of pathways inside living cells has triggered renewed interest in the bottom-up development of CRNs. This builds upon earlier work of physical chemists who extensively studied inorganic CRNs and showed how a system of chemical reactions can give rise to complex spatiotemporal responses such as oscillations and pattern formation. Using purified biochemical components, in vitro synthetic biologists have started to engineer simplified model systems with the goal of mimicking biological responses of intracellular circuits. Emulation and reconstruction of system-level properties of intracellular networks using simplified circuits are able to reveal key design principles and molecular programs that underlie the biological function of interest. In this Tutorial Review, we present an accessible overview of this emerging field starting with key studies on inorganic CRNs followed by a discussion of recent work involving purified biochemical components. Finally, we review recent work showing the versatility of programmable biochemical reaction networks (BRNs) in analytical and diagnostic applications.

  12. Adipose-Derived Stem Cells in Aesthetic Surgery: A Mixed Methods Evaluation of the Current Clinical Trial, Intellectual Property, and Regulatory Landscape.

    Science.gov (United States)

    Arshad, Zeeshaan; Halioua-Haubold, Celine-Lea; Roberts, Mackenna; Urso-Baiarda, Fulvio; Branford, Oliver A; Brindley, David A; Davies, Benjamin M; Pettitt, David

    2017-06-07

    Adipose tissue, which can be readily harvested via a number of liposuction techniques, offers an easily accessible and abundant source of adipose-derived stem cells (ASCs). Consequently, ASCs have become an increasingly popular reconstructive option and a novel means of aesthetic soft tissue augmentation. This paper examines recent advances in the aesthetic surgery field, extending beyond traditional review formats to incorporate a comprehensive analysis of current clinical trials, adoption status, and the commercialization pathway. Keyword searches were carried out on clinical trial databases to search for trials using ASCs for aesthetic indications. An intellectual property landscape was created using commercial software (Thomson Reuters Thomson Innovation, New York, NY). Analysis of who is claiming what in respect of ASC use in aesthetic surgery for commercial purposes was analyzed by reviewing the patent landscape in relation to these techniques. Key international regulatory guidelines were also summarized. Completed clinical trials lacked robust controls, employed small sample sizes, and lacked long-term follow-up data. Ongoing clinical trials still do not address such issues. In recent years, claims to intellectual property ownership have increased in the "aesthetic stem cell" domain, reflecting commercial interest in the area. However, significant translational barriers remain including regulatory challenges and ethical considerations. Further rigorous randomized controlled trials are required to delineate long-term clinical efficacy and safety. Providers should consider the introduction of patient reported outcome metrics to facilitate clinical adoption. Robust regulatory and ethical policies concerning stem cells and aesthetic surgery should be devised to discourage further growth of "stem cell tourism."

  13. MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach

    Directory of Open Access Journals (Sweden)

    Yasser Abduallah

    2017-01-01

    Full Text Available Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs. Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

  14. MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach.

    Science.gov (United States)

    Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L

    2017-01-01

    Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

  15. Regulatory Considerations for the Clinical and Research Use of Transcranial Direct Current Stimulation (tDCS): review and recommendations from an expert panel

    Science.gov (United States)

    Fregni, F; Nitsche, MA; Loo, C.K.; Brunoni, AR; Marangolo, P; Leite, J; Carvalho, S; Bolognini, N; Caumo, W; Paik, NJ; Simis, M; Ueda, K; Ekhitari, H; Luu, P; Tucker, DM; Tyler, WJ; Brunelin, J; Datta, A; Juan, CH; Venkatasubramanian, G; Boggio, PS; Bikson, M

    2014-01-01

    The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. We therefore convened a group of research and clinician experts on tDCS to review the research and clinical use of tDCS. In this report, we review the regulatory status of tDCS, and we summarize the results according to research, off-label and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan and United States. Research use, off label treatment and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. PMID:25983531

  16. A frailty model approach for regression analysis of multivariate current status data.

    Science.gov (United States)

    Chen, Man-Hua; Tong, Xingwei; Sun, Jianguo

    2009-11-30

    This paper discusses regression analysis of multivariate current status failure time data (The Statistical Analysis of Interval-censoring Failure Time Data. Springer: New York, 2006), which occur quite often in, for example, tumorigenicity experiments and epidemiologic investigations of the natural history of a disease. For the problem, several marginal approaches have been proposed that model each failure time of interest individually (Biometrics 2000; 56:940-943; Statist. Med. 2002; 21:3715-3726). In this paper, we present a full likelihood approach based on the proportional hazards frailty model. For estimation, an Expectation Maximization (EM) algorithm is developed and simulation studies suggest that the presented approach performs well for practical situations. The approach is applied to a set of bivariate current status data arising from a tumorigenicity experiment.

  17. How to Improve Current Situation of the Communicative Approach in High School EFL Teaching

    Institute of Scientific and Technical Information of China (English)

    张丽芳

    2009-01-01

    The Communicative Approach has been used in EFL teaching of China for years; but still there are some problems centers around it when it is applied in high school English teaching. This paper explores the current situation of the Communicative Approach in Chinese high school EFL teaching by first looking at a simple case study, and then some suggestions are given as to how to improve this situation.

  18. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics

    OpenAIRE

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment...

  19. Systems biology approach to the dissection of the complexity of regulatory networks in the S. scrofa cardiocirculatory system.

    Science.gov (United States)

    Martini, Paolo; Sales, Gabriele; Calura, Enrica; Brugiolo, Mattia; Lanfranchi, Gerolamo; Romualdi, Chiara; Cagnin, Stefano

    2013-11-21

    Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.

  20. Systems Biology Approach to the Dissection of the Complexity of Regulatory Networks in the S. scrofa Cardiocirculatory System

    Directory of Open Access Journals (Sweden)

    Paolo Martini

    2013-11-01

    Full Text Available Genome-wide experiments are routinely used to increase the understanding of the biological processes involved in the development and maintenance of a variety of pathologies. Although the technical feasibility of this type of experiment has improved in recent years, data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. Here, we review strategies used in the gene set approach, and using datasets for the pig cardiocirculatory system as a case study, we demonstrate how the use of a combination of these strategies can enhance the interpretation of results. Gene set analyses are able to distinguish vessels from the heart and arteries from veins in a manner that is consistent with the different cellular composition of smooth muscle cells. By integrating microRNA elements in the regulatory circuits identified, we find that vessel specificity is maintained through specific miRNAs, such as miR-133a and miR-143, which show anti-correlated expression with their mRNA targets.

  1. Ethical and regulatory issues with conducting sexuality research with LGBT adolescents: a call to action for a scientifically informed approach.

    Science.gov (United States)

    Mustanski, Brian

    2011-08-01

    Lesbian, gay, bisexual, and transgender (LGBT) adolescents experience disparities in mental and sexual health. There is also a lack of research on this population relative to other adolescents, which limits our ability to effectively address these health disparities. Researchers may unfortunately avoid conducting research with this population because of anticipated or actual experiences with difficulties in obtaining IRB approval. A case example is provided to illustrate the ethical and regulatory issues related to research with LGBT adolescents. Relevant U.S. federal and local regulations related to research on sexual and mental health with adolescents is then reviewed. Data are presented demonstrating that requiring parental consent for LGBT youth under age 18 would likely alter study result. Data are also presented on participants' appraisals of the risks and discomforts associated with research participation. The provision of such empirical data on the risks of research participation is consistent with the goal of moving the IRB process of risk/benefit assessment from being entirely subjective to being evidence-based. Finally, recommendations are provided on how to approach these issues in IRB applications and investigators are called to help to build a corpus of scholarship that can advance empirical knowledge in this area.

  2. Longitudinal gradient coils with enhanced radial uniformity in restricted diameter: Single-current and multiple-current approaches

    Science.gov (United States)

    Romero, Javier A.; Domínguez, Gabriela A.; Anoardo, Esteban

    2017-03-01

    An important requirement for a gradient coil is that the uniformity of the generated magnetic field gradient should be maximal within the active volume of the coil. For a cylindrical geometry, the radial uniformity of the gradient turns critic, particularly in cases where the gradient-unit has to be designed to fit into the inner bore of a compact magnet of reduced dimensions, like those typically used in fast-field-cycling NMR. In this paper we present two practical solutions aimed to fulfill this requirement. We propose a matrix-inversion optimization algorithm based on the Biot-Savart law, that using a proper cost function, allows maximizing the uniformity of the gradient and power efficiency. The used methodology and the simulation code were validated in a single-current design, by comparing the computer simulated field map with the experimental data measured in a real prototype. After comparing the obtained results with the target field approach, a multiple-element coil driven by independent current sources is discussed, and a real prototype evaluated. Opposed equispaced independent windings are connected in pairs conforming an arrangement of independent anti-Helmholtz units. This last coil seizes 80% of its radial dimension with a gradient uniformity better than 5%. The design also provides an adaptable region of uniformity along with adjustable coil efficiency.

  3. Stormwater Infrastructure in the Los Angeles Region: Are Regulatory Drivers and Opportunism the Best Approach to Clean Water?

    Science.gov (United States)

    Mika, K.; Gold, M.

    2016-12-01

    The Los Angeles region has invested nearly a billion dollars in stormwater infrastructure projects over the last 15 years. The primary drivers for these projects have been regulatory requirements under the Los Angeles County MS4 permit and Total Maximum Daily Loads (TMDLs) for over 150 impaired water bodies in the region. In addition, voters in the state of California have approved five separate water bonds over the last 15 years totaling nearly 21 billion. The City of Los Angeles approved a 500 million stormwater bond in 2004 to construct best management practices (BMPs) to help the city comply with water quality standards. There have also been numerous comprehensive Low Impact Development (LID) ordinances approved in the region that are designed to ensure that new and redevelopment capture for reuse or infiltrate 100% of the runoff generated from the 85th percentile storm. This presentation will overview an assessment of decision-making related to the funding of stormwater BMPs in the region. Specific examples of constructed BMPs, including their performance for meeting water quality standards, will be provided. Among the shortcomings of relying on a bond funding approach to new stormwater infrastructure is a California statutory prohibition on using bond funds for BMP operations and maintenance. The advantages of a systematic structural BMP sizing, designing and siting approach based on optimizing multiple beneficial uses (water quality, flood control, water supply, habitat and recreation) across watersheds or subwatersheds will also be discussed. Integration of stormwater infrastructure construction with transportation improvement projects, as well as building retrofit upon sale requirements, will greatly expedite regional transformation to green stormwater infrastructure.

  4. A Semiconductor Device Noise Model: A Deterministic Approach to Semiconductor Device Current Noise for Semiclassical Transport

    Science.gov (United States)

    Noaman, B. A.; Korman, C. E.

    2009-04-01

    In this paper, we present a deterministic approach to calculate terminal current noise characteristics in semiconductor devices in the framework of semiclassical transport based on the spherical harmonics of the Boltzmann Transport Equation. The model relies on the solution of the Boltzmann equation in the frequency domain with special initial and boundary conditions. The terminal current fluctuation is directly related to scattering without the additional Langevin noise term added to the calculation. Simulation results are presented for the terminal current spectral density for a 1-D n+nn+ structure due to elastic-acoustic and intervally scattering.

  5. Quantum dot as a spin-current diode: A master-equation approach

    DEFF Research Database (Denmark)

    Souza, F.M.; Egues, J.C.; Jauho, Antti-Pekka

    2007-01-01

    We report a study of spin-dependent transport in a system composed of a quantum dot coupled to a normal metal lead and a ferromagnetic lead NM-QD-FM. We use the master equation approach to calculate the spin-resolved currents in the presence of an external bias and an intradot Coulomb interaction....... We find that for a range of positive external biases current flow from the normal metal to the ferromagnet the current polarization =I↑−I↓ / I↑+I↓ is suppressed to zero, while for the corresponding negative biases current flow from the ferromagnet to the normal metal attains a relative maximum value....... The system thus operates as a rectifier for spin-current polarization. This effect follows from an interplay between Coulomb interaction and nonequilibrium spin accumulation in the dot. In the parameter range considered, we also show that the above results can be obtained via nonequilibrium Green functions...

  6. Review of Current Status and Research Approaches to Nitrogen Pollution in Farmlands

    Institute of Scientific and Technical Information of China (English)

    NIE Sheng-wei; GAO Wang-sheng; CHEN Yuan-quan; SUI Peng; A Egrinya Eneji

    2009-01-01

    In this paper, the history, current status, and research approaches to nitrogen pollution were reviewed using systems analysis and deductions. The seriousness of N pollution world-wide was highlighted and recommendations were made to address the situation. A new hypothesis based on phytoremediation, which means the use of plants to directly or indirectly degrade or remove contaminats from soil and water, was proposed.

  7. Current concepts and future approaches to the development of autologous/autogenous vaccines for veterinary use.

    Science.gov (United States)

    Tollis, M

    2004-01-01

    Current classification of autologous/autogenous (A/A) vaccines is commonly based on the concept of strain/antigen specificity associated with targeted treatment of a restricted number of animals. However, fulfilling these two conditions is not sufficient for immune-veterinary immunebiologicals to be excluded from the provisions of Directive 2001/82/EC. Indeed, non-inactivated A/A vaccines are not automatically considered out of the scope of the community code relating to veterinary medicinal products, in particular to immune-biologicals. As a major consequence of the "regulatory" exclusion from the requirements of EU rules, A/A vaccines can be usually manufactured and distributed without having obtained a marketing authorization by the competent authority of a Member State. Furthermore, strain specificity enables veterinarians to consider the use of these vaccines in quite a large variety of epidemiological circumstances where no "conventional" vaccines are yet available or are considered efficacious. In addition, in contrast to "conventional" vaccines, which are considered exclusively as a preventive tool against infectious diseases, A/A vaccines can also be used to treat "continuing" infections. Although the limited scientific value of these products and the poor investigations of the effector mechanisms involved are widely recognized, their use is still claimed in conditions where disorders in the immune system are suspected. Today, a more appropriate definition of A/A vaccines is one that takes into account their historical tradition and practical use, such as stable- or herd-specific vaccines, custom ("..ized") vaccines, therapeutic vaccines, pharmavaccines, vaccines used for biological therapy, etc. Although acknowledging the "regulatory autonomy" of A/A vaccines versus "conventional" vaccines, here it will be presented as an overview of the necessary points to consider, to guarantee an acceptable standard in the development and control of this particular

  8. A Phase Current Reconstruction Approach for Three-Phase Permanent-Magnet Synchronous Motor Drive

    Directory of Open Access Journals (Sweden)

    Hao Yan

    2016-10-01

    Full Text Available Three-phase permanent-magnet synchronous motors (PMSMs are widely used in renewable energy applications such as wind power generation, tidal energy and electric vehicles owing to their merits such as high efficiency, high precision and high reliability. To reduce the cost and volume of the drive system, techniques of reconstructing three-phase current using a single current sensor have been reported for three-phase alternating current (AC control system using the power converts. In existing studies, the reconstruction precision is largely influenced by reconstructing dead zones on the Space Vector Pulse Width Modulation (SVPWM plane, which requires other algorithms to compensate either by modifying PWM modulation or by phase-shifting of the PWM signal. In this paper, a novel extended phase current reconstruction approach for PMSM drive is proposed. Six novel installation positions are obtained by analyzing the sampling results of the current paths between each two power switches. By arranging the single current sensor at these positions, the single current sensor is sampled during zero voltage vectors (ZVV without modifying the PWM signals. This proposed method can reconstruct the three-phase currents without any complex algorithms and is available in the sector boundary region and low modulation region. Finally, this method is validated by experiments.

  9. A transcriptomic approach to identify regulatory genes involved in fruit set of wild-type and parthenocarpic tomato genotypes.

    Science.gov (United States)

    Ruiu, Fabrizio; Picarella, Maurizio Enea; Imanishi, Shunsuke; Mazzucato, Andrea

    2015-10-01

    The tomato parthenocarpic fruit (pat) mutation associates a strong competence for parthenocarpy with homeotic transformation of anthers and aberrancy of ovules. To dissect this complex floral phenotype, genes involved in the pollination-independent fruit set of the pat mutant were investigated by microarray analysis using wild-type and mutant ovaries. Normalized expression data were subjected to one-way ANOVA and 2499 differentially expressed genes (DEGs) displaying a >1.5 log-fold change in at least one of the pairwise comparisons analyzed were detected. DEGs were categorized into 20 clusters and clusters classified into five groups representing transcripts with similar expression dynamics. The "regulatory function" group (685 DEGs) contained putative negative or positive fruit set regulators, "pollination-dependent" (411 DEGs) included genes activated by pollination, "fruit growth-related" (815 DEGs) genes activated at early fruit growth. The last groups listed genes with different or similar expression pattern at all stages in the two genotypes. qRT-PCR validation of 20 DEGs plus other four selected genes assessed the high reliability of microarray expression data; the average correlation coefficient for the 20 DEGs was 0.90. In all the groups were evidenced relevant transcription factors encoding proteins regulating meristem differentiation and floral organ development, genes involved in metabolism, transport and response of hormones, genes involved in cell division and in primary and secondary metabolism. Among pathways related to secondary metabolites emerged genes related to the synthesis of flavonoids, supporting the recent evidence that these compounds are important at the fruit set phase. Selected genes showing a de-regulated expression pattern in pat were studied in other four parthenocarpic genotypes either genetically anonymous or carrying lesions in known gene sequences. This comparative approach offered novel insights for improving the present

  10. 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...

  11. Single-Session Transcranial Direct Current Stimulation Temporarily Improves Symptoms, Mood, and Self-Regulatory Control in Bulimia Nervosa: A Randomised Controlled Trial.

    Science.gov (United States)

    Kekic, Maria; McClelland, Jessica; Bartholdy, Savani; Boysen, Elena; Musiat, Peter; Dalton, Bethan; Tiza, Meyzi; David, Anthony S; Campbell, Iain C; Schmidt, Ulrike

    2017-01-01

    Evidence suggests that pathological eating behaviours in bulimia nervosa (BN) are underpinned by alterations in reward processing and self-regulatory control, and by functional changes in neurocircuitry encompassing the dorsolateral prefrontal cortex (DLPFC). Manipulation of this region with transcranial direct current stimulation (tDCS) may therefore alleviate symptoms of the disorder. This double-blind sham-controlled proof-of-principle trial investigated the effects of bilateral tDCS over the DLPFC in adults with BN. Thirty-nine participants (two males) received three sessions of tDCS in a randomised and counterbalanced order: anode right/cathode left (AR/CL), anode left/cathode right (AL/CR), and sham. A battery of psychological/neurocognitive measures was completed before and after each session and the frequency of bulimic behaviours during the following 24-hours was recorded. AR/CL tDCS reduced eating disorder cognitions (indexed by the Mizes Eating Disorder Cognitions Questionnaire-Revised) when compared to AL/CR and sham tDCS. Both active conditions suppressed the self-reported urge to binge-eat and increased self-regulatory control during a temporal discounting task. Compared to sham stimulation, mood (assessed with the Profile of Mood States) improved after AR/CL but not AL/CR tDCS. Lastly, the three tDCS sessions had comparable effects on the wanting/liking of food and on bulimic behaviours during the 24 hours post-stimulation. These data suggest that single-session tDCS transiently improves symptoms of BN. They also help to elucidate possible mechanisms of action and highlight the importance of selecting the optimal electrode montage. Multi-session trials are needed to determine whether tDCS has potential for development as a treatment for adult BN.

  12. Expanding the reduced-current approach for thermoelectric generators to achieve higher volumetric power density

    DEFF Research Database (Denmark)

    Wijesooriyage, Waruna Dissanayaka; Rosendahl, Lasse

    2015-01-01

    Thermoelectrics are candidate niche electrical generator devices for energy management. At present, scientists are more focused on thermoelectric (TE) material development, but the TE module design procedure is still in a relatively virgin state. One of the most well-known methods is the reduced...... current approach (RCA) for TE module design, where the same current is induced through the p and n legs of the thermoelectric generator (TEG). The current density of each element is manipulated by changing the area of both legs. This technique leads to a TE module architecture based on the most efficient...... configuration of both p and n legs. In the current paper, we apply an extended version of this technique, to show how a TE module with a higher volumetric power density can be designed, compared to the original RCA. Our studies indicate that for some combinations of p and n material properties, optima yielding...

  13. Towards Current Profile Control in ITER: Potential Approaches and Research Needs

    Science.gov (United States)

    Schuster, E.; Barton, J. E.; Wehner, W. P.

    2014-10-01

    Many challenging plasma control problems still need to be addressed in order for the ITER Plasma Control System (PCS) to be able to successfully achieve the ITER project goals. For instance, setting up a suitable toroidal current density profile is key for one possible advanced scenario characterized by noninductive sustainment of the plasma current and steady-state operation. The nonlinearity and high dimensionality exhibited by the plasma demand a model-based current-profile control synthesis procedure that can accommodate this complexity through embedding the known physics within the design. The development of a model capturing the dynamics of the plasma relevant for control design enables not only the design of feedback controllers for regulation or tracking but also the design of optimal feedforward controllers for a systematic model-based approach to scenario planning, the design of state estimators for a reliable real-time reconstruction of the plasma internal profiles based on limited and noisy diagnostics, and the development of a fast predictive simulation code for closed-loop performance evaluation before implementation. Progress towards control-oriented modeling of the current profile evolution and associated control design has been reported following both data-driven and first-principles-driven approaches. An overview of these two approaches will be provided, as well as a discussion on research needs associated with each one of the model applications described above. Supported by the US Department of Energy under DE-SC0001334 and DE-SC0010661.

  14. Efficient non-hydrostatic modelling of 3D wave-induced currents using a subgrid approach

    Science.gov (United States)

    Rijnsdorp, Dirk P.; Smit, Pieter B.; Zijlema, Marcel; Reniers, Ad J. H. M.

    2017-08-01

    Wave-induced currents are an ubiquitous feature in coastal waters that can spread material over the surf zone and the inner shelf. These currents are typically under resolved in non-hydrostatic wave-flow models due to computational constraints. Specifically, the low vertical resolutions adequate to describe the wave dynamics - and required to feasibly compute at the scales of a field site - are too coarse to account for the relevant details of the three-dimensional (3D) flow field. To describe the relevant dynamics of both wave and currents, while retaining a model framework that can be applied at field scales, we propose a two grid approach to solve the governing equations. With this approach, the vertical accelerations and non-hydrostatic pressures are resolved on a relatively coarse vertical grid (which is sufficient to accurately resolve the wave dynamics), whereas the horizontal velocities and turbulent stresses are resolved on a much finer subgrid (of which the resolution is dictated by the vertical scale of the mean flows). This approach ensures that the discrete pressure Poisson equation - the solution of which dominates the computational effort - is evaluated on the coarse grid scale, thereby greatly improving efficiency, while providing a fine vertical resolution to resolve the vertical variation of the mean flow. This work presents the general methodology, and discusses the numerical implementation in the SWASH wave-flow model. Model predictions are compared with observations of three flume experiments to demonstrate that the subgrid approach captures both the nearshore evolution of the waves, and the wave-induced flows like the undertow profile and longshore current. The accuracy of the subgrid predictions is comparable to fully resolved 3D simulations - but at much reduced computational costs. The findings of this work thereby demonstrate that the subgrid approach has the potential to make 3D non-hydrostatic simulations feasible at the scale of a

  15. Current-induced forces in mesoscopic systems: A scattering-matrix approach

    Directory of Open Access Journals (Sweden)

    Niels Bode

    2012-02-01

    Full Text Available Nanoelectromechanical systems are characterized by an intimate connection between electronic and mechanical degrees of freedom. Due to the nanoscopic scale, current flowing through the system noticeably impacts upons the vibrational dynamics of the device, complementing the effect of the vibrational modes on the electronic dynamics. We employ the scattering-matrix approach to quantum transport in order to develop a unified theory of nanoelectromechanical systems out of equilibrium. For a slow mechanical mode the current can be obtained from the Landauer–Büttiker formula in the strictly adiabatic limit. The leading correction to the adiabatic limit reduces to Brouwer’s formula for the current of a quantum pump in the absence of a bias voltage. The principal results of the present paper are the scattering-matrix expressions for the current-induced forces acting on the mechanical degrees of freedom. These forces control the Langevin dynamics of the mechanical modes. Specifically, we derive expressions for the (typically nonconservative mean force, for the (possibly negative damping force, an effective “Lorentz” force that exists even for time-reversal-invariant systems, and the fluctuating Langevin force originating from Nyquist and shot noise of the current flow. We apply our general formalism to several simple models that illustrate the peculiar nature of the current-induced forces. Specifically, we find that in out-of-equilibrium situations the current-induced forces can destabilize the mechanical vibrations and cause limit-cycle dynamics.

  16. Are Current Accounts of Asian Economies Mean-reverting?: Nonlinear Unit Root Test Approach

    Directory of Open Access Journals (Sweden)

    Bonghan Kim

    2005-12-01

    Full Text Available This paper tests the mean reverting property of current account in the financial crisis-affected 5 counties of southeast Asia using nonlinear unit root tests of Park and shintani(2004. Our approach is based on the idea that a conventional unit root test has lower power in detecting the nonlinear mean reverting behavior if the current account follows a nonlinear mean reversion process. We obtained following empirical results. First, for the pre-crisis period (1981Q1-1996Q4, the current accounts of Indonesia, Malaysia and Philippines are mean-reverting but those of Korea and Thailand are not mean-reverting. Second, for the full sample period (1981Q1-2003Q4, the ADF test fails to reject the unit root of the current account in all countries except Philippines. However, unit root is rejected in favor of nonlinear mean reversion except Thailand. This nonlinear unit root test result implies that crisis-affected Asian countries except Thailand have sustainable paths of current accounts. Third, when the current accounts of East Asian countries are nonlinear mean-reverting, the mean reverting process can be well described by the ESTAR model, instead of the DTAR or DLSTAR model. The nonlinear unit root test results imply smooth nonlinear mean-reversion behaviors of East Asian current accounts. Finally, the shape of estimated impulse response functions becomes steeper as the size of shock increases, which is the very characteristic of the nonlinear process.

  17. Current opinion in Alzheimer's disease therapy by nanotechnology-based approaches.

    Science.gov (United States)

    Ansari, Shakeel Ahmed; Satar, Rukhsana; Perveen, Asma; Ashraf, Ghulam Md

    2017-03-01

    Nanotechnology typically deals with the measuring and modeling of matter at nanometer scale by incorporating the fields of engineering and technology. The most prominent feature of these engineered materials involves their manipulation/modification for imparting new functional properties. The current review covers the most recent findings of Alzheimer's disease (AD) therapeutics based on nanoscience and technology. Current studies involve the application of nanotechnology in developing novel diagnostic and therapeutic tools for neurological disorders. Nanotechnology-based approaches can be exploited for limiting/reversing these diseases for promoting functional regeneration of damaged neurons. These strategies offer neuroprotection by facilitating the delivery of drugs and small molecules more effectively across the blood-brain barrier. Nanotechnology based approaches show promise in improving AD therapeutics. Further replication work on synthesis and surface modification of nanoparticles, longer-term clinical trials, and attempts to increase their impact in treating AD are required.

  18. Current Approaches of Photothermal Therapy in Treating Cancer Metastasis with Nanotherapeutics.

    Science.gov (United States)

    Zou, Lili; Wang, Hong; He, Bin; Zeng, Lijuan; Tan, Tao; Cao, Haiqiang; He, Xinyu; Zhang, Zhiwen; Guo, Shengrong; Li, Yaping

    2016-01-01

    Cancer metastasis accounts for the high mortality of many types of cancer. Owing to the unique advantages of high specificity and minimal invasiveness, photothermal therapy (PTT) has been evidenced with great potential in treating cancer metastasis. In this review, we outline the current approaches of PTT with respect to its application in treating metastatic cancer. PTT can be used alone, guided with multimodal imaging, or combined with the current available therapies for effective treatment of cancer metastasis. Numerous types of photothermal nanotherapeutics (PTN) have been developed with encouraging therapeutic efficacy on metastatic cancer in many preclinical animal experiments. We summarize the design and performance of various PTN in PTT alone and their combinational therapy. We also point out the lacking area and the most promising approaches in this challenging field. In conclusion, PTT or their combinational therapy can provide an essential promising therapeutic modality against cancer metastasis.

  19. Expectation values of flavor-neutrino currents in field theoretical approach to oscillation problem -- formulation

    CERN Document Server

    Fujii, Kanji; Fujii, Kanji; Shimomura, Takashi

    2004-01-01

    As a possible approach to the neutrino oscillation on the basis of quantum field theory, the expectation values of the flavor-neutrino currents are investigated by employing the finite-time transition matrix in the interaction representation. Such expectation values give us in the simplest form a possible way of treating the neutrino oscillation without recourse to any one flavor-neutrino states. The present paper is devoted to presenting the formulation and the main structures of the relevant expectation values.

  20. Expectation values of flavor-neutrino currents in field theoretical approach to oscillation problem -- formulation

    OpenAIRE

    FUJII, Kanji; Shimomura, Takashi

    2004-01-01

    As a possible approach to the neutrino oscillation on the basis of quantum field theory, the expectation values of the flavor-neutrino currents are investigated by employing the finite-time transition matrix in the interaction representation. Such expectation values give us in the simplest form a possible way of treating the neutrino oscillation without recourse to any one flavor-neutrino states. The present paper is devoted to presenting the formulation and the main structures of the relevan...

  1. Toxicogenomics in regulatory ecotoxicology

    Science.gov (United States)

    Ankley, Gerald T.; Daston, George P.; Degitz, Sigmund J.; Denslow, Nancy D.; Hoke, Robert A.; Kennedy, Sean W.; Miracle, Ann L.; Perkins, Edward J.; Snape, Jason; Tillitt, Donald E.; Tyler, Charles R.; Versteeg, Donald

    2006-01-01

    Recently, we have witnessed an explosion of different genomic approaches that, through a combination of advanced biological, instrumental, and bioinformatic techniques, can yield a previously unparalleled amount of data concerning the molecular and biochemical status of organisms. Fueled partially by large, well-publicized efforts such as the Human Genome Project, genomic research has become a rapidly growing topical area in multiple biological disciplines. Since 1999, when the term “toxicogenomics” was coined to describe the application of genomics to toxicology (1), a rapid increase in publications on the topic has occurred (Figure 1). The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions and, as with any new technology, has evoked a wide range of opinion (2–6). VIEWPOINT © 2006 american chemical Society july 1, 2006 / EnvironmEntal SciEncE & tEchnology n 4055 The purpose of this feature article is to consider the roles of toxicogenomics in the field of regulatory ecotoxicology, explore current limitations in the science and practice of genomics, and propose possible avenues to approach and resolve some of the major challenges. A significant amount of input to our analysis came from a workshop sponsored by the Society of Environmental Toxicology and Chemistry (SETAC) in Pellston, Mich., in September 2005. A complete list of names and affiliations of the experts participating in that workshop is provided online in Table 1 of the Supporting Information for this paper.

  2. An adaptive finite element approach to modelling sediment laden density currents

    Science.gov (United States)

    Parkinson, S.; Hill, J.; Allison, P. A.; Piggott, M. D.

    2012-04-01

    Modelling sediment-laden density currents at real-world scales is a challenging task. Here we present Fluidity, which uses dynamic adaptive re-meshing to reduce computational costs whilst maintaining sufficient resolution where and when it is required. This allows small-scale processes to be captured in large scale simulations. Density currents, also known as gravity or buoyancy currents, occur wherever two fluids with different densities meet. They can occur at scales of up to hundred kilometres in the ocean when continental shelves collapse. This process releases large quantities of sediment into the ocean which increase the bulk density of the fluid to form a density current. These currents can carry sediment hundreds of kilometres, at speeds of up to a hundred kilometres per hour, over the sea bed. They can be tsunamigenic and they have the potential to cause significant damage to submarine infrastructure, such as submarine telecommunications cables or oil and gas infrastructure. They are also a key process for movement of organic material into the depths of the ocean. Due to this, they play an important role in the global carbon cycle on the Earth, forming a significant component of the stratigraphic record, and their deposits can form useful sources of important hydrocarbons. Modelling large scale sediment laden density currents is a very challenging problem. Particles within the current are suspended by turbulence that occurs at length scales that are several orders of magnitude smaller than the size of the current. Models that resolve the vertical structure of the flow require a very large, highly resolved mesh, and substantial computing power to solve. Here, we verify our adaptive model by comparison with a set of laboratory experiments by Gladstone et al. [1998] on the propagation and sediment deposition of bidisperse gravity currents. Comparisons are also made with fixed mesh solutions, and it is shown that accuracy can be maintained with fewer elements

  3. Ionic channel current burst analysis by a machine learning based approach.

    Science.gov (United States)

    Rauch, Giuseppe; Bertolini, Simona; Sacile, Roberto; Giacomini, Mauro; Ruggiero, Carmelina

    2011-09-01

    A new method to analyze single ionic channel current conduction is presented. It is based on an automatic classification by K-means algorithm and on the concept of information entropy. This method is used to study the conductance of multistate ion current jumps induced by tetanus toxin in planar lipid bilayers. A comparison is presented with the widely used Gaussian best fit approach, whose main drawback is the fact that it is based on the manual choice of the base line and of meaningful fragments of current signal. On the contrary, the proposed method is able to automatically process a great amount of information and to remove spurious transitions and multichannels. The number of levels and their amplitudes do not have to be known a priori. In this way the presented method is able to produce a reliable evaluation of the conductance levels and their characteristic parameters in a short time.

  4. Limitations Of The Current State Space Modelling Approach In Multistage Machining Processes Due To Operation Variations

    Science.gov (United States)

    Abellán-Nebot, J. V.; Liu, J.; Romero, F.

    2009-11-01

    The State Space modelling approach has been recently proposed as an engineering-driven technique for part quality prediction in Multistage Machining Processes (MMP). Current State Space models incorporate fixture and datum variations in the multi-stage variation propagation, without explicitly considering common operation variations such as machine-tool thermal distortions, cutting-tool wear, cutting-tool deflections, etc. This paper shows the limitations of the current State Space model through an experimental case study where the effect of the spindle thermal expansion, cutting-tool flank wear and locator errors are introduced. The paper also discusses the extension of the current State Space model to include operation variations and its potential benefits.

  5. Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Nestor R. Ramos

    2015-04-01

    Full Text Available The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for “complete” remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or refractory AML is generally poor. In this review, we outline the commonly utilized salvage cytotoxic therapy interventions and then highlight novel investigational efforts currently in clinical trials using both pathway-targeted agents and immunotherapy based approaches. We conclude that there is no current standard of care for adult relapsed or refractory AML other than offering referral to an appropriate clinical trial.

  6. Quark flavour mixing with right-handed currents: an effective theory approach

    CERN Document Server

    Buras, Andrzej J; Isidori, Gino

    2010-01-01

    The impact of right-handed currents in both charged- and neutral-current flavour-violating processes is analysed by means of an effective theory approach. More explicitly, we analyse the structure of dimension-six operators assuming a left-right symmetric flavour group, commuting with an underlying $SU(2)_L \\times SU(2)_R \\times U(1)_{B-L}$ global symmetry, broken only by two Yukawa couplings. The model contains a new unitary matrix controlling flavour-mixing in the right-handed sector. We determine the structure of this matrix by charged-current data, where the tension between inclusive and exclusive determinations of $|V_{ub}|$ can be solved. Having determined the size and the flavour structure of right-handed currents, we investigate how they would manifest themselves in neutral current processes, including particle-antiparticle mixing, $Z\\to b \\bar b$, $B_{s,d}\\to \\mu^+\\mu^-$, $B\\to {Xs,K,K*} \

  7. Current insights into the molecular systems pharmacology of lncRNA-miRNA regulatory interactions and implications in cancer translational medicine

    Directory of Open Access Journals (Sweden)

    Sujit Nair

    2016-04-01

    Full Text Available In recent times, the role(s of microRNAs (miRNAs and long noncoding RNAs (lncRNAs in the pathogenesis of various cancers has received great attention. Indeed, there is also a growing recognition of regulatory RNA cross-talk, i.e., lncRNA-miRNA interactions, that may modulate various events in carcinogenesis and progression to metastasis. This review summarizes current evidence in the literature of lncRNA-miRNA interactions in various cancers such as breast, liver, stomach, lung, prostate, bladder, colorectal, blood, brain, skin, kidney, cervical, laryngeal, gall bladder, and bone. Further, the potential prognostic and theragnostic clinical applications of lncRNA-miRNA interactions in cancer are discussed along with an overview of noncoding RNA (ncRNA-based studies that were presented at the American Society of Clinical Oncology (ASCO 2015. Interestingly, the last decade has seen tremendous innovation, as well as increase in complexity, of the cancer biological network(s from mRNA- to miRNA- and lncRNA-based networks. Thus, biological networks devoted to understanding regulatory interactions between these ncRNAs would be the next frontier in better elucidating the contributions of lncRNA-miRNA interactions in cancer. Herein, a cancer biological network of lncRNA-miRNA interactions is presented wherein “edges” connect interacting lncRNA-miRNA pairs, with each ncRNA serving as a discrete “node” of the network. In conclusion, the untapped potential of lncRNA-miRNA interactions in terms of its diagnostic, prognostic and therapeutic potential as targets for clinically actionable intervention as well as biomarker validation in discovery pipelines remains to be explored. Future research will likely harness this potential so as to take us closer to the goal of “precision” and “personalized medicine” which is tailor-made to the unique needs of each cancer patient, and is clearly the way forward going into the future.

  8. An interdisciplinary review of current and future approaches to improving human-predator relations.

    Science.gov (United States)

    Pooley, S; Barua, M; Beinart, W; Dickman, A; Holmes, G; Lorimer, J; Loveridge, A J; Macdonald, D W; Marvin, G; Redpath, S; Sillero-Zubiri, C; Zimmermann, A; Milner-Gulland, E J

    2017-06-01

    In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for

  9. Person-centred health care: a critical assessment of current and emerging research approaches.

    Science.gov (United States)

    Martin, Carmel M; Félix-Bortolotti, Margot

    2014-12-01

    Person-centred health care is prominent in international health care reforms. A shift to understanding and improving personal care at the point of delivery has generated debates about the nature of the person-centred research agenda. This paper purviews research paradigms that influence current person-centred research approaches and traditions that influence knowledge foundations in the field. It presents a synthesis of the emergent approaches and methodologies and highlights gaps between static academic research and the increasing accessibility of evaluation, informatics and big data from health information systems. Paradigms in health services research range from theoretical to atheoretical, including positivist, interpretive, postmodern and pragmatic. Interpretivist (subjective) and positivist (objectivist) paradigms have been historically polarized. Yet, integrative and pragmatic approaches have emerged. Nevertheless, there is a tendency to reductionism, and to reduce personal experiences to metrics in the positivist paradigm. Integrating personalized information into clinical systems is increasingly driven by the pervasive health information technology, which raises many issues about the asymmetry and uncertainty in the flow of information to support personal health journeys. The flux and uncertainty of knowledge between and within paradigmatic or pragmatic approaches highlights the uncertainty and the 'unorder and disorder' in what is known and what it means. Transdisciplinary, complex adaptive systems theory with multi-ontology sense making provides an overarching framework for making sense of the complex dynamics in research progress. A major challenge to current research paradigms is focus on the individualizing of care and enhancing experiences of persons in health settings. There is an urgent need for person-centred research to address this complex process. A transdisciplinary and complex systems approach provides a sense-making framework. © 2014 John

  10. When is success not satisfying? Integrating regulatory focus and approach/avoidance motivation theories to explain the relation between core self-evaluation and job satisfaction.

    Science.gov (United States)

    Ferris, D Lance; Johnson, Russell E; Rosen, Christopher C; Djurdjevic, Emilija; Chang, Chu-Hsiang Daisy; Tan, James A

    2013-03-01

    Integrating implications from regulatory focus and approach/avoidance motivation theories, we present a framework wherein motivational orientations toward positive (approach motivation orientation) or negative (avoidance motivation orientation) stimuli interact with workplace success to mediate the relation of core self-evaluation (CSE) with job satisfaction. Using data collected from supervisor-subordinate dyads (Sample 1) and time-lagged data (Sample 2), we found that the results from two studies indicated that the interaction of workplace success and avoidance motivation orientation mediated relations of CSE with job satisfaction. Although approach motivation orientation did not interact with workplace success, it did mediate the CSE-job satisfaction relation on its own. Implications for the CSE and approach/avoidance literatures are discussed.

  11. A multi-faceted treatment approach for anterior reconstructions using current ceramics, implants, and adhesive systems.

    Science.gov (United States)

    Hajtó, Jan; Gehringer, Uwe; Ozcan, Mutlu

    2010-01-01

    Of all developments in dental technology, fulfilling the esthetic and functional demands of the patient, especially regarding anterior reconstructions, is still a challenge for both dentists and dental technicians. This becomes more difficult for patients with a previous treatment history that is not ideal. This case presentation demonstrates reconstruction of an anterior zirconia resin-bonded fixed dental prosthesis (RBFDP) for the mandible with a combined approach utilizing veneers for harmonized space distribution on the abutment teeth and an implant-supported zirconia fixed dental prosthesis in the anterior segment of the maxilla. Adhesive cementation of the restorations is also presented in a step-by-step approach based on the current state of the art.

  12. Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses.

    Science.gov (United States)

    Jentsch, Mike C; Van Buel, Erin M; Bosker, Fokko J; Gladkevich, Anatoliy V; Klein, Hans C; Oude Voshaar, Richard C; Ruhé, Eric G; Eisel, Uli L M; Schoevers, Robert A

    2015-01-01

    Major depressive disorder is a heterogeneous disorder, mostly diagnosed on the basis of symptomatic criteria alone. It would be of great help when specific biomarkers for various subtypes and symptom clusters of depression become available to assist in diagnosis and subtyping of depression, and to enable monitoring and prognosis of treatment response. However, currently known biomarkers do not reach sufficient sensitivity and specificity, and often the relation to underlying pathophysiology is unclear. In this review, we evaluate various biomarker approaches in terms of scientific merit and clinical applicability. Finally, we discuss how combined biomarker approaches in both preclinical and clinical studies can help to make the connection between the clinical manifestations of depression and the underlying pathophysiology.

  13. Modelling of eddy-current interaction with cracks in the thin-skin regime. Two approaches

    Energy Technology Data Exchange (ETDEWEB)

    Mastorchio, S. [Electricite de France, 78 - Chatou (France). Research and Development Div.; Harfield, N. [Surrey Univ. (United Kingdom). Dept. of Physics

    1998-02-01

    EDF uses TRIFOU code for eddy current testing modelling. This general electromagnetic code is to be further adapted to Non Destructive Testing applications, not only for nuclear NDT but also in other fields such as aeronautical. This paper compares experimental data for aluminium and steel specimens with two methods of solving the forward problem in the thin-skin regime. The first approach is a 3D Finite Element / Boundary Integral Element method (TRIFOU) developed by EDF/RD Division (France). The second approach is specialized for the treatment of surface cracks in the thin-skin regime developed by the University of Surrey (England). In the thin-skin regime, the electromagnetic skin-depth is small compared with the depth of the crack. Such conditions are common in tests on steels and sometimes on aluminium. (K.A.) 4 refs.

  14. Charged-current neutrino-nucleus reactions within the SuSAv2-MEC approach

    CERN Document Server

    Megias, G D; Barbaro, M B; Caballero, J A; Donnelly, T W; Simo, I Ruiz

    2016-01-01

    We present a detailed study of charged-current (CC) neutrino-nucleus reactions in a fully relativis- tic framework and comparisons with recent experiments spanning an energy range from hundreds of MeV up to 100 GeV within the SuperScaling Approach, which is based on the analysis of electron- nucleus scattering data and has been recently improved with the inclusion of Relativistic Mean Field theory effects. We also evaluate and discuss the impact of two-particle two-hole meson-exchange currents (2p-2h MEC) on neutrino-nucleus interactions through the analysis of two-particle two-hole axial and vector contributions to weak response functions in a fully relativistic Fermi gas. The results show a fairly good agreement with experimental data over the whole range of neutrino energies.

  15. Variational approach to low-frequency kinetic-MHD in the current coupling scheme

    CERN Document Server

    Burby, J W

    2016-01-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which is described by a kinetic equation. When the Vlasov description is adopted for the energetic particles, different Vlasov-MHD models have been shown to lack an exact energy balance, which was recently recovered by the introduction of non-inertial force terms in the kinetic equation. These force terms arise from fundamental approaches based on Hamiltonian and variational methods. In this work we apply Hamilton's variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling hybrid schemes, in which energetic particle dynamics are expressed in either guiding-center or gyrocenter coordinates.

  16. Modelling chloride penetration in concrete using electrical voltage and current approaches

    Directory of Open Access Journals (Sweden)

    Juan Lizarazo-Marriaga

    2011-03-01

    Full Text Available This paper reports a research programme aimed at giving a better understanding of the phenomena involved in the chloride penetration in cement-based materials. The general approach used was to solve the Nernst-Planck equation numerically for two physical ideal states that define the possible conditions under which chlorides will move through concrete. These conditions are named in this paper as voltage control and current control. For each condition, experiments and simulations were carried out in order to establish the importance of electrical variables such as voltage and current in modelling chloride transport in concrete. The results of experiments and simulations showed that if those electrical variables are included as key parameters in the modelling of chloride penetration through concrete, a better understanding of this complex phenomenon can be obtained.

  17. Variational approach to low-frequency kinetic-MHD in the current-coupling scheme

    Science.gov (United States)

    Tronci, Cesare; Burby, Joshua

    2016-10-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which is described by a kinetic equation. When the Vlasov description is adopted for the energetic particles, different Vlasov-MHD models have been shown to lack an exact energy balance, unless non-inertial force terms are inserted in the kinetic equation. These force terms arise from fundamental approaches based on Hamiltonian and variational methods. In this work we apply Hamilton's variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling hybrid schemes, in which energetic particle dynamics are expressed in either guiding-center or gyrocenter coordinates. Financial support by the Leverhulme Trust Research Project Grant No. 2014-112 is greatly acknowledged.

  18. Simple engineering design for complex thermoelectric generators based on reduced current approach

    DEFF Research Database (Denmark)

    Wijesooriyage, Waruna Dissanayaka; Rezaniakolaei, Alireza; Rosendahl, Lasse

    2015-01-01

    Thermoelectric generators (TEGs) are niche candidate for the field of energy management as electrical generator devices. Generally, comprehensive and accurate design techniques for TEGs (thermoelectric generators), such as reduced current approach (RCA), are complex and time consuming processes....... This study develops a simple, comprehensive and accurate TEG designing technique based on RCA. The proposed method can predict the most efficient TEG architecture with more than 97% accuracy comparing to the RCA over wide range of possible temperature and zT for present TEG applications. Moreover...

  19. Future Performance Trend Indicators: A Current Value Approach to Human Resources Accounting. Report V: The Value Attribution Process. Technical Report.

    Science.gov (United States)

    Lapointe, Jean B.; And Others

    The development of future performance trend indicators is based on the current value approach to human resource accounting. The value attribution portion of the current value approach is used to estimate the dollar value of observed changes in the state of the human organization. The procedure for value attribution includes: prediction of changes…

  20. Safeguards inventory and process monitoring regulatory comparison

    Energy Technology Data Exchange (ETDEWEB)

    Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2013-06-27

    Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

  1. (Q)SAR modeling and safety assessment in regulatory review.

    Science.gov (United States)

    Kruhlak, N L; Benz, R D; Zhou, H; Colatsky, T J

    2012-03-01

    The ability to predict clinical safety based on chemical structures is becoming an increasingly important part of regulatory decision making. (Quantitative) structure-activity relationship ((Q)SAR) models are currently used to evaluate late-arising safety concerns and possible nonclinical effects of a drug and its related compounds when adequate safety data are absent or equivocal. Regulatory use will likely increase with the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms.

  2. A review of the current status of endoluminal therapy as a primary approach to obesity management.

    Science.gov (United States)

    Majumder, Shounak; Birk, John

    2013-07-01

    Gastroenterologists are expected to play a pivotal role in the management of the global obesity epidemic in coming years as novel endoscopic approaches become more widely available, safe, and effective. This review focuses on the recent advances in the field of endoluminal therapy as a primary approach to obesity management with the aim of providing the interventional endoscopist an overview of currently available evidence along with an insight into upcoming devices and techniques. The intragastric balloon appears to be safe and effective in the short term, especially as a bridge to bariatric surgery. Although early trials support the safety and feasibility of endoscopic gastroplasty, it is technically demanding and staple-line dehiscence continues to be a problem. Moreover, with ongoing technical innovations, most devices that have been used in published trials are no longer manufactured and results of studies using newer endoscopic suturing systems are currently awaited. The duodenojejunal bypass sleeve mimics the physiology of intestinal bypass and shares the metabolic advantages of intestinal diversion. A high rate of premature device withdrawal has been its major limiting factor. Therapeutic endoscopy may be the next paradigm of bariatric care. Combining restrictive and barrier endoscopic techniques can potentially improve efficacy and should be evaluated in the setting of appropriate clinical trials.

  3. Regenerative endodontics as a tissue engineering approach: past, current and future.

    Science.gov (United States)

    Malhotra, Neeraj; Mala, Kundabala

    2012-12-01

    With the reported startling statistics of high incidence of tooth decay and tooth loss, the current interest is focused on the development of alternate dental tissue replacement therapies. This has led to the application of dental tissue engineering as a clinically relevant method for the regeneration of dental tissues and generation of bioengineered whole tooth. Although, tissue engineering approach requires the three main key elements of stem cells, scaffold and morphogens, a conductive environment (fourth element) is equally important for successful engineering of any tissue and/or organ. The applications of this science has evolved continuously in dentistry, beginning from the application of Ca(OH)(2) in vital pulp therapy to the development of a fully functional bioengineered tooth (mice). Thus, with advances in basic research, recent reports and studies have shown successful application of tissue engineering in the field of dentistry. However, certain practical obstacles are yet to be overcome before dental tissue regeneration can be applied as evidence-based approach in clinics. The article highlights on the past achievements, current developments and future prospects of tissue engineering and regenerative therapy in the field of endodontics and bioengineered teeth (bioteeth). © 2012 The Authors. Australian Endodontic Journal © 2012 Australian Society of Endodontology.

  4. Quark flavour mixing with right-handed currents: An effective theory approach

    Energy Technology Data Exchange (ETDEWEB)

    Buras, Andrzej J. [Physik-Department, Technische Universitaet Muenchen, James-Franck-Strasse, D-85748 Garching (Germany); TUM Institute for Advanced Study, Technische Universitaet Muenchen, Arcisstrasse 21, D-80333 Muenchen (Germany); Gemmler, Katrin [Physik-Department, Technische Universitaet Muenchen, James-Franck-Strasse, D-85748 Garching (Germany); Isidori, Gino, E-mail: isidori@lnf.infn.i [TUM Institute for Advanced Study, Technische Universitaet Muenchen, Arcisstrasse 21, D-80333 Muenchen (Germany); INFN, Laboratori Nazionali di Frascati, I-00044 Frascati (Italy)

    2011-02-01

    The impact of right-handed currents in both charged- and neutral-current flavour-violating processes is analysed by means of an effective theory approach. More explicitly, we analyse the structure of dimension-six operators assuming a left-right symmetric flavour group, commuting with an underlying SU(2){sub L}xSU(2){sub R}xU(1){sub B-L} global symmetry, broken only by two Yukawa couplings. The model contains a new unitary matrix controlling flavour-mixing in the right-handed sector. We determine the structure of this matrix by charged-current data, where the tension between inclusive and exclusive determinations of {vert_bar}V{sub ub}{vert_bar} can be solved. Having determined the size and the flavour structure of right-handed currents, we investigate how they would manifest themselves in neutral current processes, including particle-antiparticle mixing, Z{yields}bb-bar, B{sub s,d}{yields}{mu}{sup +}{mu}{sup -}, B{yields}{l_brace}X{sub s},K,K{sup *}{r_brace}{nu}{nu}-bar, and K{yields}{pi}{nu}{nu}-bar decays. The possibility to explain a non-standard CP-violating phase in B{sub s} mixing in this context, and the comparison with other predictive new-physics frameworks addressing the same problem, is also discussed. While a large S{sub {psi}{phi}} asymmetry can easily be accommodated, we point out a tension in this framework between {vert_bar}V{sub ub}{vert_bar} and S{sub {psi}}K.

  5. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer.

    Science.gov (United States)

    Falahi, Fahimeh; van Kruchten, Michel; Martinet, Nadine; Hospers, Geke A P; Rots, Marianne G

    2014-07-29

    DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alterations have been associated with various diseases, including breast cancer. Since aberrant epigenetic modifications are potentially reversible, they might represent targets for breast cancer therapy. Indeed, several drugs have been designed to inhibit epigenetic enzymes (epi-drugs), thereby reversing epigenetic modifications. US Food and Drug Administration approval has been obtained for some epi-drugs for hematological malignancies. However, these drugs have had very modest anti-tumor efficacy in phase I and II clinical trials in breast cancer patients as monotherapy. Therefore, current clinical trials focus on the combination of epi-drugs with other therapies to enhance or restore the sensitivity to such therapies. This approach has yielded some promising results in early phase II trials. The disadvantage of epi-drugs, however, is genome-wide effects, which may cause unwanted upregulation of, for example, pro-metastatic genes. Development of gene-targeted epigenetic modifications (epigenetic editing) in breast cancer can provide a novel approach to prevent such unwanted events. In this context, identification of crucial epigenetic modifications regulating key genes in breast cancer is of critical importance. In this review, we first describe aberrant DNA methylation and histone modifications as two important classes of epigenetic mutations in breast cancer. Then we focus on the preclinical and clinical epigenetic-based therapies currently being explored for breast cancer. Finally, we describe epigenetic editing as a promising new approach for possible applications towards more targeted breast cancer treatment.

  6. Segmentation and Image Analysis of Abnormal Lungs at CT: Current Approaches, Challenges, and Future Trends

    Science.gov (United States)

    Mansoor, Awais; Foster, Brent; Xu, Ziyue; Papadakis, Georgios Z.; Folio, Les R.; Udupa, Jayaram K.; Mollura, Daniel J.

    2015-01-01

    The computer-based process of identifying the boundaries of lung from surrounding thoracic tissue on computed tomographic (CT) images, which is called segmentation, is a vital first step in radiologic pulmonary image analysis. Many algorithms and software platforms provide image segmentation routines for quantification of lung abnormalities; however, nearly all of the current image segmentation approaches apply well only if the lungs exhibit minimal or no pathologic conditions. When moderate to high amounts of disease or abnormalities with a challenging shape or appearance exist in the lungs, computer-aided detection systems may be highly likely to fail to depict those abnormal regions because of inaccurate segmentation methods. In particular, abnormalities such as pleural effusions, consolidations, and masses often cause inaccurate lung segmentation, which greatly limits the use of image processing methods in clinical and research contexts. In this review, a critical summary of the current methods for lung segmentation on CT images is provided, with special emphasis on the accuracy and performance of the methods in cases with abnormalities and cases with exemplary pathologic findings. The currently available segmentation methods can be divided into five major classes: (a) thresholding-based, (b) region-based, (c) shape-based, (d) neighboring anatomy–guided, and (e) machine learning–based methods. The feasibility of each class and its shortcomings are explained and illustrated with the most common lung abnormalities observed on CT images. In an overview, practical applications and evolving technologies combining the presented approaches for the practicing radiologist are detailed. ©RSNA, 2015 PMID:26172351

  7. Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

    Science.gov (United States)

    Pichavant, Christophe; Aartsma-Rus, Annemieke; Clemens, Paula R; Davies, Kay E; Dickson, George; Takeda, Shin'ichi; Wilton, Steve D; Wolff, Jon A; Wooddell, Christine I; Xiao, Xiao; Tremblay, Jacques P

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article. PMID:21468001

  8. CURRENT APPROACHES TO THE LABORATORY DIAGNOSIS OF RHEUMATIC DISEASES: ROLE OF MOLECULAR AND CELLULAR BIOMARKERS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2016-01-01

    .The alternative therapies of RD include the use of low-molecular-weight chemically synthesized agents that suppress the activity of tyrosine kinases. The important area of this therapy is to restore immunological tolerance and to correct autoimmune disorders by means of autologous hematopoietic stem cells, mesenchymal stromal cells, autologous tolerogenic dendritic cells, regulatory T and B cells, gene therapy, and peptide antigens. The prospects for the laboratory diagnosis of RD are associated with the necessity of harmonizing and standardizing the current methods to determine autoantibodies and with the search for and clinical validation of novel proteomic, transcriptomic, and genomic biomarkers.

  9. Predicting distinct organization of transcription factor binding sites on the promoter regions: a new genome-based approach to expand human embryonic stem cell regulatory network.

    Science.gov (United States)

    Hosseinpour, Batool; Bakhtiarizadeh, Mohammad Reza; Khosravi, Pegah; Ebrahimie, Esmaeil

    2013-12-01

    Self-proliferation and differentiation into distinct cell types have been made stem cell as a promising target for regenerative medicine. Several key genes can regulate self-renewal and pluripotency of embryonic stem cells (hESCs). They work together and build a transcriptional hierarchy. Coexpression and coregulation of genes control by common regulatory elements on the promoter regions. Consequently, distinct organization and combination of transcription factor binding sites (TFBSs modules) on promoter regions, in view of order and distance, lead to a common specific expression pattern within a set of genes. To gain insights into transcriptional regulation of hESCs, we selected promoter regions of eleven common expressed hESC genes including SOX2, LIN28, STAT3, NANOG, LEFTB, TDGF1, POU5F1, FOXD3, TERF1, REX1 and GDF3 to predict activating regulatory modules on promoters and discover key corresponding transcription factors. Then, promoter regions in human genome were explored for modules and 328 genes containing the same modules were detected. Using microarray data, we verified that 102 of 328 genes commonly upregulate in hESCs. Also, using output data of DNA-protein interaction assays, we found that 42 of all predicted genes are targets of SOX2, NANOG and POU5F1. Additionally, a protein interaction network of hESC genes was constructed based on biological processes, and interestingly, 126 downregulated genes along with upregulated ones identified by promoter analysis were predicted in the network. Based on the results, we suggest that the identified genes, coregulating with common hESC genes, represent a novel approach for gene discovery based on whole genome promoter analysis irrespective of gene expression. Altogether, promoter profiling can be used to expand hESC transcriptional regulatory circuitry by analysis of shared functional sequences between genes. This approach provides a clear image on underlying regulatory mechanism of gene expression profile and

  10. 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.

  11. 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.

  12. In Vivo Predictive Dissolution (IPD) and Biopharmaceutical Modeling and Simulation: Future Use of Modern Approaches and Methodologies in a Regulatory Context.

    Science.gov (United States)

    Lennernäs, H; Lindahl, A; Van Peer, A; Ollier, C; Flanagan, T; Lionberger, R; Nordmark, A; Yamashita, S; Yu, L; Amidon, G L; Fischer, V; Sjögren, E; Zane, P; McAllister, M; Abrahamsson, B

    2017-04-03

    The overall objective of OrBiTo, a project within Innovative Medicines Initiative (IMI), is to streamline and optimize the development of orally administered drug products through the creation and efficient application of biopharmaceutics tools. This toolkit will include both experimental and computational models developed on improved understanding of the highly dynamic gastrointestinal (GI) physiology relevant to the GI absorption of drug products in both fasted and fed states. A part of the annual OrBiTo meeting in 2015 was dedicated to the presentation of the most recent progress in the development of the regulatory use of PBPK in silico modeling, in vivo predictive dissolution (IPD) tests, and their application to biowaivers. There are still several areas for improvement of in vitro dissolution testing by means of generating results relevant for the intraluminal conditions in the GI tract. The major opportunity is probably in combining IPD testing and physiologically based in silico models where the in vitro data provide input to the absorption predictions. The OrBiTo project and other current research projects include definition of test media representative for the more distal parts of the GI tract, models capturing supersaturation and precipitation phenomena, and influence of motility waves on shear and other forces of hydrodynamic origin, addressing the interindividual variability in composition and characteristics of GI fluids, food effects, definition of biorelevant buffer systems, and intestinal water volumes. In conclusion, there is currently a mismatch between the extensive industrial usage of modern in vivo predictive tools and very limited inclusion of such data in regulatory files. However, there is a great interest among all stakeholders to introduce recent progresses in prediction of in vivo GI drug absorption into regulatory context.

  13. Current Approach in Surface Plasmons for Thin Film and Wire Array Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Keya Zhou

    2015-07-01

    Full Text Available Surface plasmons, which exist along the interface of a metal and a dielectric, have been proposed as an efficient alternative method for light trapping in solar cells during the past ten years. With unique properties such as superior light scattering, optical trapping, guide mode coupling, near field concentration, and hot-electron generation, metallic nanoparticles or nanostructures can be tailored to a certain geometric design to enhance solar cell conversion efficiency and to reduce the material costs. In this article, we review current approaches on different kinds of solar cells, such as crystalline silicon (c-Si and amorphous silicon (a-Si thin film solar cells, organic solar cells, nanowire array solar cells, and single nanowire solar cells.

  14. Prevention of Overweight and Obesity: How Effective is the Current Public Health Approach

    Directory of Open Access Journals (Sweden)

    Jean Woo

    2010-02-01

    Full Text Available Obesity is a public health problem that has become epidemic worldwide. Substantial literature has emerged to show that overweight and obesity are major causes of co-morbidities, including type II diabetes, cardiovascular diseases, various cancers and other health problems, which can lead to further morbidity and mortality. The related health care costs are also substantial. Therefore, a public health approach to develop population-based strategies for the prevention of excess weight gain is of great importance. However, public health intervention programs have had limited success in tackling the rising prevalence of obesity. This paper reviews the definition of overweight and obesity and the variations with age and ethnicity; health consequences and factors contributing to the development of obesity; and critically reviews the effectiveness of current public health strategies for risk factor reduction and obesity prevention.

  15. Current Approach in Surface Plasmons for Thin Film and Wire Array Solar Cell Applications.

    Science.gov (United States)

    Zhou, Keya; Guo, Zhongyi; Liu, Shutian; Lee, Jung-Ho

    2015-07-22

    Surface plasmons, which exist along the interface of a metal and a dielectric, have been proposed as an efficient alternative method for light trapping in solar cells during the past ten years. With unique properties such as superior light scattering, optical trapping, guide mode coupling, near field concentration, and hot-electron generation, metallic nanoparticles or nanostructures can be tailored to a certain geometric design to enhance solar cell conversion efficiency and to reduce the material costs. In this article, we review current approaches on different kinds of solar cells, such as crystalline silicon (c-Si) and amorphous silicon (a-Si) thin film solar cells, organic solar cells, nanowire array solar cells, and single nanowire solar cells.

  16. Current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis in Europe: the AIR survey

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2014-06-01

    Full Text Available This review presents the results of the 2013 Advancing IPF Research (AIR survey, which assessed current approaches to the diagnosis and treatment of idiopathic pulmonary fibrosis (IPF by experienced physicians. A total of 149 physicians, predominantly from European countries, replied to the 28-question survey. The results of the AIR survey were compared with a similar survey of 509 French pulmonologists conducted by the French National Reference Centre and the Network of Regional Competence Centres for Rare Lung Diseases. A number of positive findings emerged from the AIR survey, including the high level of multidisciplinary team involvement in both diagnosis and management. This survey, when taken together with the French survey, suggests that there is still a need to improve earlier diagnosis of IPF.

  17. Asthma and obesity in children: current evidence and potential systems biology approaches.

    Science.gov (United States)

    Frey, U; Latzin, P; Usemann, J; Maccora, J; Zumsteg, U; Kriemler, S

    2015-01-01

    Both obesity and asthma are highly prevalent, complex diseases modified by multiple factors. Genetic, developmental, lung mechanical, immunological and behavioural factors have all been suggested as playing a causal role between the two entities; however, their complex mechanistic interactions are still poorly understood and evidence of causality in children remains scant. Equally lacking is evidence of effective treatment strategies, despite the fact that imbalances at vulnerable phases in childhood can impact long-term health. This review is targeted at both clinicians frequently faced with the dilemma of how to investigate and treat the obese asthmatic child and researchers interested in the topic. Highlighting the breadth of the spectrum of factors involved, this review collates evidence regarding the investigation and treatment of asthma in obese children, particularly in comparison with current approaches in 'difficult-to-treat' childhood asthma. Finally, the authors propose hypotheses for future research from a systems-based perspective.

  18. Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

    Directory of Open Access Journals (Sweden)

    Stefano Mazzoleni

    2017-01-01

    Full Text Available A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections, modulate neural activity (noninvasive brain stimulation, and enhance motivation (virtual reality in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

  19. NRC regulatory initiatives

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, T.C. [Nuclear Regulatory Commission (United States)

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

  20. Identifying ligands at orphan GPCRs: current status using structure-based approaches.

    Science.gov (United States)

    Ngo, Tony; Kufareva, Irina; Coleman, James Lj; Graham, Robert M; Abagyan, Ruben; Smith, Nicola J

    2016-10-01

    GPCRs are the most successful pharmaceutical targets in history. Nevertheless, the pharmacology of many GPCRs remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore the physiological functions and pharmacological potential of these 'orphan' GPCRs, whether they are endogenous and/or surrogate ligands, are therefore of paramount importance. Rates of receptor deorphanization determined by traditional reverse pharmacology methods have slowed, indicating a need for the development of more sophisticated and efficient ligand screening approaches. Here, we discuss the use of structure-based ligand discovery approaches to identify small molecule modulators for exploring the function of orphan GPCRs. These studies have been buoyed by the growing number of GPCR crystal structures solved in the past decade, providing a broad range of template structures for homology modelling of orphans. This review discusses the methods used to establish the appropriate signalling assays to test orphan receptor activity and provides current examples of structure-based methods used to identify ligands of orphan GPCRs. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.

  1. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation.

    Science.gov (United States)

    Locatelli, Franco; Lucarelli, Barbarella; Merli, Pietro

    2014-01-01

    One significant obstacle to the success of allogeneic hematopoietic stem cell transplantation (HSCT) is represented by graft failure, defined as either lack of initial engraftment of donor cells (primary graft failure) or loss of donor cells after initial engraftment (secondary graft failure). Graft failure mediated by host immune cells attacking donor stem cells is named graft rejection. Factors associated with graft failure include HLA disparity in the donor/recipient pair, underlying disease, viral infections, type of conditioning regimen and stem cell source employed. In this article, the experts summarize current approaches to treat graft failure/rejection after HSCT, and they discuss new strategies of graft manipulation and immune therapy of particular interest for preventing/treating this complication. A limited array of options is available to treat graft failure. The experts believe that re-transplantation from another donor or the same donor (if there is no evidence of immunologically mediated graft failure) is the treatment of choice for patients with primary graft failure or acute graft rejection. The experts think that strategies based on innovative approaches of graft manipulation, new agents or cellular therapies could render in the future graft failure a much less relevant problem for HSCT recipients.

  2. Modeling left and right atrial contributions to the ECG: A dipole-current source approach.

    Science.gov (United States)

    Jacquemet, Vincent

    2015-10-01

    This paper presents the mathematical formulation, the numerical validation and several illustrations of a forward-modeling approach based on dipole-current sources to compute the contribution of a part of the heart to the electrocardiogram (ECG). Clinically relevant applications include identifying in the ECG the contributions from the right and the left atrium. In a Courtemanche-based monodomain computer model of the atria and torso, 1000 dipoles distributed throughout the atrial mid-myocardium are found to be sufficient to reproduce body surface potential maps with a relative error approach enables fast offline computation of the ECG contribution of any anatomical part of the atria by applying the principle of superposition to the dipole sources. In the presence of a right-left activation delay (sinus rhythm), pulmonary vein isolation (sinus rhythm) or left-right differences in refractory period (atrial fibrillation), the decomposition of the ECG is shown to help interpret ECG morphology in relation to the atrial substrate. These tools provide a theoretical basis for a deeper understanding of the genesis of the P wave or fibrillatory waves in normal and pathological cases.

  3. Mite Pests in Plant Crops – Current Issues, Inovative Approaches and Possibilities for Controlling Them (2

    Directory of Open Access Journals (Sweden)

    Radmila Petanović

    2010-01-01

    Full Text Available Part one discusses some principal mite pests in agroecosystems and urban horticulturein European countries, Serbia and its neighbouring countries focusing primarily on issueswith regard to plant production, novel methods and approaches in applied acaralogy. Parttwo displays some major properties of acaricides inhibiting respiration, growth and developmentand other synthetic substances with acaricide action on the market in the last decadeof the 20th century and the first decade of the 21st century. Also some products of naturalorigin (azadirachtin, oils, micoacaricides are said to be gaining in importance. Issues withregard to the fact that mites can readily develop resistance to acardicides are discussed anda survey on the results of biochemical, physiological and genetical causes of resistance areanalyzed. Some basic principles of biological control of phytophagous mites and modernadvances and approaches are discussed as well as current knowledge on host plant resistanceto mites. Eventually, the possibility of using a combination of selective acaricides andbiological control agents is discussed but also the inclusion of other modes of control (agriculturalpractices and physical measures expected to contribute to an integrated managementof pest populations.

  4. Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends.

    Science.gov (United States)

    Oliveira, Sara M; Reis, Rui L; Mano, João F

    2015-11-01

    The design of 3D constructs with adequate properties to instruct and guide cells both in vitro and in vivo is one of the major focuses of tissue engineering. Successful tissue regeneration depends on the favorable crosstalk between the supporting structure, the cells and the host tissue so that a balanced matrix production and degradation are achieved. Herein, the major occurring events and players in normal and regenerative tissue are overviewed. These have been inspiring the selection or synthesis of instructive cues to include into the 3D constructs. We further highlight the importance of a multiscale perception of the range of features that can be included on the biomimetic structures. Lastly, we focus on the current and developing tissue-engineering approaches for the preparation of such 3D constructs: top-down, bottom-up and integrative. Bottom-up and integrative approaches present a higher potential for the design of tissue engineering devices with multiscale features and higher biochemical control than top-down strategies, and are the main focus of this review. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Controllable synthesis of metal particles by a direct current electrochemical approach

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Shapes of copper and silver particles were successfully controlled by using a very simple,effective direct-current electrochemical approach without introducing any additives or templates. A diverse range of shapes and also different inner structures were thus accessible. The products prepared at relatively high potentials have flowerlike morphologies and exhibit flakes as building blocks. The uniformly thick flakes intersect mutually,have smooth surfaces and outwardly wavy edges. The particle diameter and the flake density can be easily controlled by changing potential and/or deposition time. With a decrease of potential,the particles’ shapes changed from flower to bud,to sphere and to octahedron. Surface plasmon resonance (SPR) properties of the supported metal particles were investigated by UV-Vis diffuse reflectance spectra (UV-Vis DRS) and surface enhanced Raman scattering (SERS). It was found that the copper octahedra exhibited three characteristic bands,and SERS effect increases with the number of flakes within individual particles. Based on the experimental results,the mechanism for direct-current electrochemical growth of metal nanostructures was discussed.

  6. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Directory of Open Access Journals (Sweden)

    Ting Gong

    2016-01-01

    Full Text Available Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.

  7. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy.

    Science.gov (United States)

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering-stem cells, scaffolds, and signaling molecules-has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration.

  8. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    Science.gov (United States)

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  9. Ocean Current Energy Conversion System in Wallacea Region Using Variable Speed Control Approach

    Directory of Open Access Journals (Sweden)

    Aditya Sukma Nugraha

    2012-03-01

    Full Text Available Ocean Current Energy Conversion System (OCECS is a promising green energy resource in this globe. The Thermohaline circulation data indicates that the Wallacea region has the potential of ocean current energy resources. This paper is aimed to propose research and development of OCECSs to be implemented in the Wallacea region. Firstly, four types of green energy conversion systems extracted from ocean are reviewed. Their advantages and disadvantages are discussed. Secondly, the potential of OCECS in the Wallacea region is described. Third, many types of turbines used for OCECS are reviewed and the turbine type for OCECS is selected to be implemented in the Wallacea region. Fourth, control strategy is proposed.From the work reported in this paper it is concluded that it is appropriate to implement OCECSs using axial flow water turbines in the Wallacea region, and that to maximize energy conversion variable speed control approach is selected together with control of mechanism to move the turbine vertically as well as to rotate the turbine in yaw direction. 

  10. Marketing of library and information services in global era: A current approach

    Directory of Open Access Journals (Sweden)

    Sanjay Kumar Karn

    2008-06-01

    Full Text Available This paper deals with the marketing of library and information services in the global era. It discusses about the marketing concept of today's library and information centers covering various topics such as management of libraries and commitment to customer's satisfaction. It also defines the marketing and its current approach to library and information services at the global level. It also describes customer/user's topic such as customers' priorities, customers' expectations, individuality responsiveness, relationships, quality of services, professional skills and competencies and value added services. The 5 Ps of marketing mix, i.e. product, pricing, place, promotion and person (staff have been discussed. The marketing should aim at effective library and information services. The "service trinity", i.e. users (customers, the staff (service provider and information resources and system should be taken care of from the view of these services. In the modern age, the library and information services (LIS are customer (user oriented. Therefore, users' priorities, expectations and needs should be taken into account. The services should be value added according to the current requirement of the users. It is concluded that the modern libraries are information markets and the library users are consumers of information. The ultimate objective of the marketing of library and information services should be the dissemination of the right information to the right customer (user at the right time.

  11. Exchange processes at geosphere-biosphere interface. Current SKB approach and example of coupled hydrological-ecological approach

    Energy Technology Data Exchange (ETDEWEB)

    Woerman, Anders [Swedish Univ. of Agricultural Sciences, Uppsala (Sweden). Dept. of Biometry and Technology

    2003-09-01

    The design of the repository for final disposal of spent nuclear fuel proposed by SKB is based on a multi-barrier system, in which the geosphere and biosphere are the utmost barrier surrounding the engineer barriers. This report briefly reviews the current approach taken by SKB to account for hydrological and ecological processes at the geosphere-biosphere interface (GBI) and their future plans in this area. A simple analysis was performed to shift the focus of performance assessment involving geosphere-biosphere interface modelling from the very simplistic assumption that the quaternary sediments are bypassed to one in which a more detailed model for sub-surface flows is included. This study indicated that, for many assumed ecosystem descriptions, the presence of the GBI leads to lower maximum doses to individual humans compared to a case when the GBI is neglected. This effect is due to the additional 'barrier' offered by the GBI. The main exposure pathways were assumed to occur through the food web. However, particularly the leakage on land through the stream-network and lakes can lead to higher doses due to ecosystem interaction with arable land. A scenario that gives particularly long duration of doses occurs due to land rise and with the transformation of the former bay and lake bed sediments into agricultural land. This effect is due to the significant retention or accumulation in aquatic sediment, which causes high activities to build up with time. Particularly, in combination with changing conditions in climate, humans life-style or geographic conditions (land rise, deforestation,etc.) doses to individual humans can be large.

  12. Current and emerging approaches to define intestinal epithelium-specific transcriptional networks

    DEFF Research Database (Denmark)

    Olsen, Anders Krûger; Boyd, Mette; Danielsen, Erik Thomas

    2012-01-01

    Upon developmental or environmental cues, the composition of transcription factors in a transcriptional regulatory network is deeply implicated in controlling the signature of the gene expression and thereby specifies the cell- or tissue-type. Novel methods including ChIP-chip and ChIP-Seq have b...

  13. Current and emerging approaches to define intestinal epithelium-specific transcriptional networks

    DEFF Research Database (Denmark)

    Olsen, Anders Krüger; Boyd, Mette; Danielsen, Erik Thomas

    2012-01-01

    Upon developmental or environmental cues, the composition of transcription factors in a transcriptional regulatory network is deeply implicated in controlling the signature of the gene expression and thereby specifies the cell or tissue type. Novel methods including ChIP-chip and ChIP-Seq have be...

  14. Phylogeny based discovery of regulatory elements

    Directory of Open Access Journals (Sweden)

    Cohen Barak A

    2006-05-01

    Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

  15. Current approaches to the management of new-onset ulcerative colitis

    Directory of Open Access Journals (Sweden)

    Marchioni Beery R

    2014-05-01

    Full Text Available Renée Marchioni Beery,1 Sunanda Kane21Division of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USAAbstract: Ulcerative colitis (UC is an idiopathic, inflammatory gastrointestinal disease of the colon. As a chronic condition, UC follows a relapsing and remitting course with medical maintenance during periods of quiescent disease and appropriate escalation of therapy during times of flare. Initial treatment strategies must not only take into account current clinical presentation (with specific regard for extent and severity of disease activity but must also take into consideration treatment options for the long-term. The following review offers an approach to new-onset UC with a focus on early treatment strategies. An introduction to the disease entity is provided along with an approach to initial diagnosis. Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining course of therapy. Frequent assessments are required to determine clinical response, and treatment intensification may be warranted if expected improvement goals are not appropriately reached. Mild-to-moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases. Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents (as initial therapy or in transition from steroids or thiopurines (as bridging therapy. Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure. The authors provide

  16. A data integration approach to mapping OCT4 gene regulatory networks operative in embryonic stem cells and embryonal carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Marc Jung

    Full Text Available It is essential to understand the network of transcription factors controlling self-renewal of human embryonic stem cells (ESCs and human embryonal carcinoma cells (ECs if we are to exploit these cells in regenerative medicine regimes. Correlating gene expression levels after RNAi-based ablation of OCT4 function with its downstream targets enables a better prediction of motif-specific driven expression modules pertinent for self-renewal and differentiation of embryonic stem cells and induced pluripotent stem cells.We initially identified putative direct downstream targets of OCT4 by employing CHIP-on-chip analysis. A comparison of three peak analysis programs revealed a refined list of OCT4 targets in the human EC cell line NCCIT, this list was then compared to previously published OCT4 CHIP-on-chip datasets derived from both ES and EC cells. We have verified an enriched POU-motif, discovered by a de novo approach, thus enabling us to define six distinct modules of OCT4 binding and regulation of its target genes.A selection of these targets has been validated, like NANOG, which harbours the evolutionarily conserved OCT4-SOX2 binding motif within its proximal promoter. Other validated targets, which do not harbour the classical HMG motif are USP44 and GADD45G, a key regulator of the cell cycle. Over-expression of GADD45G in NCCIT cells resulted in an enrichment and up-regulation of genes associated with the cell cycle (CDKN1B, CDKN1C, CDK6 and MAPK4 and developmental processes (BMP4, HAND1, EOMES, ID2, GATA4, GATA5, ISL1 and MSX1. A comparison of positively regulated OCT4 targets common to EC and ES cells identified genes such as NANOG, PHC1, USP44, SOX2, PHF17 and OCT4, thus further confirming their universal role in maintaining self-renewal in both cell types. Finally we have created a user-friendly database (http://biit.cs.ut.ee/escd/, integrating all OCT4 and stem cell related datasets in both human and mouse ES and EC cells.In the current

  17. The current status of the debate on socio-economic regulatory assessments: positions and policies in Canada, the USA, the EU and developing countries

    NARCIS (Netherlands)

    Falck-Zepeda, J.; Wesseler, J.H.H.; Smyth, S.

    2013-01-01

    Article 26.1 of the Cartagena Protocol on Biosafety has the option of considering socio-economic issues in biosafety regulatory approval processes related to genetically engineered organisms. National laws and regulations in some countries have already defined positions and may have enacted policies

  18. Metabolic constraint-based refinement of transcriptional regulatory networks.

    Science.gov (United States)

    Chandrasekaran, Sriram; Price, Nathan D

    2013-01-01

    There is a strong need for computational frameworks that integrate different biological processes and data-types to unravel cellular regulation. Current efforts to reconstruct transcriptional regulatory networks (TRNs) focus primarily on proximal data such as gene co-expression and transcription factor (TF) binding. While such approaches enable rapid reconstruction of TRNs, the overwhelming combinatorics of possible networks limits identification of mechanistic regulatory interactions. Utilizing growth phenotypes and systems-level constraints to inform regulatory network reconstruction is an unmet challenge. We present our approach Gene Expression and Metabolism Integrated for Network Inference (GEMINI) that links a compendium of candidate regulatory interactions with the metabolic network to predict their systems-level effect on growth phenotypes. We then compare predictions with experimental phenotype data to select phenotype-consistent regulatory interactions. GEMINI makes use of the observation that only a small fraction of regulatory network states are compatible with a viable metabolic network, and outputs a regulatory network that is simultaneously consistent with the input genome-scale metabolic network model, gene expression data, and TF knockout phenotypes. GEMINI preferentially recalls gold-standard interactions (p-value = 10(-172)), significantly better than using gene expression alone. We applied GEMINI to create an integrated metabolic-regulatory network model for Saccharomyces cerevisiae involving 25,000 regulatory interactions controlling 1597 metabolic reactions. The model quantitatively predicts TF knockout phenotypes in new conditions (p-value = 10(-14)) and revealed potential condition-specific regulatory mechanisms. Our results suggest that a metabolic constraint-based approach can be successfully used to help reconstruct TRNs from high-throughput data, and highlights the potential of using a biochemically-detailed mechanistic framework to

  19. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  20. Multidisciplinary approach to evaluating immunogenicity of biosimilars: lessons learnt and open questions based on 10 years' experience of the European Union regulatory pathway

    Directory of Open Access Journals (Sweden)

    Chamberlain PD

    2014-06-01

    Full Text Available Paul D Chamberlain NDA Advisory Board, NDA Advisory Services Ltd, Surrey, UK Abstract: Clinical evaluation of comparative immunogenicity represents an important component of the European Union regulatory review process for candidate biosimilar products. The clinical evaluation is part of a multidisciplinary review that cross-refers to product quality attributes as well as preclinical and ongoing risk management considerations. Results from the monitoring of anti-drug antibody formation in relevant populations treated for an adequate period of time are interpreted in relation to clinically relevant endpoints, including pharmacokinetics, pharmacodynamics, efficacy, and safety parameters. The European Union regulatory standard for designation of biosimilarity requires a suitable weight of evidence, determined on a product-specific basis, to demonstrate that the immunogenicity associated with the biosimilar product does not lead to a higher negative impact on clinically relevant outcomes compared with the reference product. The experience gained during the 10-year period following the implementation of the European Union biosimilars pathway indicates that a suitably cautious approach was applied, insofar as no immunogenicity-related issues have emerged for the approved applications of the different biosimilar products. In some cases, product quality-related issues were identified in the preauthorization setting as being potentially relevant for heightened risk of immunogenicity and were duly taken into account for the biosimilarity decision. Some unresolved issues remain, most notably concerning the limitation of noninterventional post-marketing surveillance measures to monitor the potential for changes in immunogenicity over the longer term, eg, following introduction of changes in manufacture, formulation, or primary product container. Lack of standardization of bioanalytical methods precludes comparison of anti-drug antibody formation for

  1. Current and future perspectives on the development, evaluation and application of in silico approaches for predicting toxicity

    Science.gov (United States)

    Safety-related problems continue to be one of the major reasons of attrition in drug development. Non-testing approaches to predict toxicity could form part of the solution. This review provides a perspective of current status of non-testing approaches available for the predictio...

  2. Approaches to Grammar Instruction in Teaching Materials: A Study in Current L2 Beginning-Level Spanish Textbooks

    Science.gov (United States)

    Fernandez, Claudia

    2011-01-01

    This study explores how grammar instruction is conceptualized and applied in published Spanish materials. It sought to answer the following questions: What are the approaches to grammar instruction in current, college-level, beginning Spanish textbooks? How do they reflect current perspectives on grammar teaching? Six widely adopted Spanish…

  3. Approaches to Grammar Instruction in Teaching Materials: A Study in Current L2 Beginning-Level Spanish Textbooks

    Science.gov (United States)

    Fernandez, Claudia

    2011-01-01

    This study explores how grammar instruction is conceptualized and applied in published Spanish materials. It sought to answer the following questions: What are the approaches to grammar instruction in current, college-level, beginning Spanish textbooks? How do they reflect current perspectives on grammar teaching? Six widely adopted Spanish…

  4. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  5. Combined transcranial alternating current stimulation and continuous theta burst stimulation: a novel approach for neuroplasticity induction.

    Science.gov (United States)

    Goldsworthy, Mitchell R; Vallence, Ann-Maree; Yang, Ruiting; Pitcher, Julia B; Ridding, Michael C

    2016-02-01

    Non-invasive brain stimulation can induce functionally relevant plasticity in the human cortex, making it potentially useful as a therapeutic tool. However, the induced changes are highly variable between individuals, potentially limiting research and clinical utility. One factor that might contribute to this variability is the level of cortical inhibition at the time of stimulation. The alpha rhythm (~ 8-13 Hz) recorded with electroencephalography (EEG) is thought to reflect pulsatile cortical inhibition; therefore, targeting non-invasive brain stimulation to particular phases of the alpha rhythm may provide an approach to enhance plasticity induction. Transcranial alternating current stimulation (tACS) has been shown to entrain cortical oscillations in a frequency-specific manner. We investigated whether the neuroplastic response to continuous theta burst stimulation (cTBS) was enhanced by timing bursts of stimuli to the peak or the trough of a tACS-imposed alpha rhythm. While motor evoked potentials (MEPs) were unaffected when cTBS was applied in-phase with the peak of the tACS-imposed oscillation, MEP depression was enhanced when cTBS was applied in-phase with the trough. This enhanced MEP depression was dependent on the individual peak frequency of the endogenous alpha rhythm recorded with EEG prior to stimulation, and was strongest in those participants classified as non-responders to standard cTBS. These findings suggest that tACS may be used in combination with cTBS to enhance the plasticity response. Furthermore, the peak frequency of endogenous alpha, as measured with EEG, may be used as a simple marker to pre-select those individuals likely to benefit from this approach.

  6. Review: Current trends in coral transplantation – an approach to preserve biodiversity

    Directory of Open Access Journals (Sweden)

    ABDELNABY ORABI

    2013-04-01

    Full Text Available Ammar MSA,El-Gammal F, Nassar M, Belal A, Farag W, El-Mesiry G, El-Haddad K, Orabi A, Abdelreheem A, Shaaban A. 2013. Review: Current trends in coral transplantation – an approach to preserve biodiversity. Biodiversitas 14: 43-53. The increasing rates of coral mortality associated with the rise in stress factors and the lack of adequate recovery worldwide have urged recent calls for actions by the scientific, conservation, and reef management communities. This work reviews the current trends in coral transplantation. Transplantation of coral colonies or fragments, whether from aqua-, mariculture or harvesting from a healthy colony, has been the most frequently recommended action for increasing coral abundance on damaged or degraded reefs and for conserving listed or “at-risk” species. Phytoplanktons are important for providing transplanted corals with complex organic compounds through photosynthesis. Artificial surfaces like concrete blocks, wrecks or other purpose-designed structures can be introduced for larval settlement. New surfaces can also be created through electrolysis. Molecular biological tools can be used to select sites for rehabilitation by asexual recruits. Surface chemistry and possible inputs of toxic leachate from artificial substrates are considered as important factors affecting natural recruitment. Transplants should be carefully maintained , revisited and reattached at least weekly in the first month and at least fortnightly in the next three months. Studies on survivorship and the reproductive ability of transplanted coral fragments are important for coral reef restoration. A coral nursery may be considered as a pool for local species that supplies reef-managers with unlimited coral colonies for sustainable management. Transplanting corals for making artificial reefs can be useful for increasing biodiversity, providing tourist diving, fishing and surfing; creating new artisanal and commercial fishing opportunities

  7. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2009-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified t......, such as legislation, self-regulation and technical approaches. It is intended to promote an effective approach to improve consumer privacy in the mobile advertising domain....

  8. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2010-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified......, such as legislation, self-regulation and technical approaches. It is intended to promote an effective approach to improve consumer privacy in the mobile advertising domain....

  9. A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

    Science.gov (United States)

    Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

    2014-08-08

    Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing

  10. Protection of people and environment from radiation risk through good regulatory practice

    Science.gov (United States)

    Jais, Azlina Mohammad; Hassan, Najwa

    2017-01-01

    The term "good regulatory practice" has seen growing frequency of usage worldwide, especially since the 2011 Fukushima nuclear incident. However, the term appears quite ambiguous as it may mean differently to different people. This leads us to the first important question: what does "good regulatory practice" actually mean? When used in conjunction with the Fukushima incident, do we imply that there is an absence of "good regulatory practice" in the Japanese' Nuclear and Industry Safety Agency (NISA)? This is quite troubling. It is clear that the term should be defined formally so that our understanding of "good regulatory practice" can be standardized. There is still another important question beyond agreeing on what "good regulatory practice" is: is "good regulatory practice" specific to a region, or is it global? And is it applicable only to nuclear regulators, or to all types of regulators per se? This paper aims to deliberate on the above mentioned questions. Specifically, we hope to discuss the "good regulatory practice" for atomic energy activities in order to protect the people and the environment from radiation risk of such activities. By understanding what "good regulatory practice" truly means, a newcomer country such as Malaysia can quickly learn and adopt these practices so as to assure a competent national nuclear regulatory authority who will be responsible in ensuring the safety, security and safeguards of peaceful atomic energy activities in the country including nuclear liability. In understanding this concept, a holistic approach will be taken by looking into example of advanced and newcomer countries of various nuclear regulatory authorities all around the world. Then the paper will focus on the challenges that the current nuclear regulatory authority in Malaysia which is Atomic Energy Licensing Board has, its challenges to follow the concept of "good regulatory practice" and its ways to overcome it. This study explore the initiatives could be

  11. Transcription Factor Binding Probabilities in Orthologous Promoters: An Alignment-Free Approach to the Inference of Functional Regulatory Targets

    Science.gov (United States)

    Liu, Xiao; Clarke, Neil D.

    Using a physically principled method of scoring genomic sequences for the potential to be bound by transcription factors, we have developed an algorithm for assessing the conservation of predicted binding occupancy that does not rely on sequence alignment of promoters. The method, which we call ortholog-weighting, assesses the degree to which the predicted binding occupancy of a transcription factor in a reference gene is also predicted in the promoters of orthologous genes. The analysis was performed separately for over 100 different transcription factors in S. cerevisiae. Statistical significance was evaluated by simulation using permuted versions of the position weight matrices. Ortholog-weighting produced about twice as many significantly high scoring genes as were obtained from the S. cerevisiae genome alone. Gene Ontology analysis found a similar two-fold enrichment of genes. Both analyses suggest that ortholog-weighting improves the prediction of true regulatory targets. Interestingly, the method has only a marginal effect on the prediction of binding by chromatin immunoprecipitation (ChIP) assays. We suggest several possibilities for reconciling this result with the improved enrichment that we observe for functionally related promoters and for promoters that are under positive selection.

  12. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management—An Insight into Future Approaches

    Directory of Open Access Journals (Sweden)

    Cecilia Beatrice Chighizola

    2015-01-01

    Full Text Available Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS, which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL. Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.

  13. Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH).

    Science.gov (United States)

    Sobanski, Vincent; Launay, David; Hachulla, Eric; Humbert, Marc

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc-PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management.

  14. Application of Caco-2 Cell Line in Herb-Drug Interaction Studies: Current Approaches and Challenges

    Science.gov (United States)

    Awortwe, C.; Fasinu, P.S.; Rosenkranz, B.

    2015-01-01

    The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions. PMID:24735758

  15. [Current methods in genetic analysis : an approach for genetics-based preventive medicine].

    Science.gov (United States)

    Klein, Hans-Georg; Rost, Imma

    2015-02-01

    Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the "post-genomic era". The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches.

  16. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management-An Insight into Future Approaches.

    Science.gov (United States)

    Chighizola, Cecilia Beatrice; Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control.

  17. Weight management in type 2 diabetes: current and emerging approaches to treatment.

    Science.gov (United States)

    Van Gaal, Luc; Scheen, André

    2015-06-01

    Diabetes is a growing global health concern, as is obesity. Diabetes and obesity are intrinsically linked: obesity increases the risk of diabetes and also contributes to disease progression and cardiovascular disease. Although the benefits of weight loss in the prevention of diabetes and as a critical component of managing the condition are well established, weight reduction remains challenging for individuals with type 2 diabetes due to a host of metabolic and psychological factors. For many patients, lifestyle intervention is not enough to achieve weight loss, and alternative options, such as pharmacotherapy, need to be considered. However, many traditional glucose-lowering medications may lead to weight gain. This article focuses on the potential of currently available pharmacological strategies and on emerging approaches in development to support the glycemic and weight-loss goals of individuals with type 2 diabetes. Two pharmacotherapy types are considered: those developed primarily for blood glucose control that have a favorable effect on body weight and those developed primarily to induce weight loss that have a favorable effect on blood glucose control. Finally, the potential of combination therapies for the management of obese patients with type 2 diabetes is discussed.

  18. Interventions to reduce the risk of violence toward emergency department staff: current approaches

    Directory of Open Access Journals (Sweden)

    Ramacciati N

    2016-04-01

    Full Text Available Nicola Ramacciati,1,2 Andrea Ceccagnoli,2 Beniamino Addey,3 Enrico Lumini,4 Laura Rasero1,5 1Department of Experimental and Clinical Medicine, University of Florence, 2Emergency Department, S. Maria della Misericordia Hospital, 3Emergency Medical System, S. Maria della Misericordia Hospital, Perugia, 4Department of Health Sciences, University of Florence, 5Research and Development Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy Introduction: The phenomenon of workplace violence in health care settings, and especially in the emergency department (ED, has assumed the dimensions of a real epidemic. Many studies highlight the need for methods to ensure the safety of staff and propose interventions to address the problem. Aim: The aim of this review was to propose a narrative of the current approaches to reduce workplace violence in the ED, with a particular focus on evaluating the effectiveness of emergency response programs. Methods: A search was conducted between December 1, 2015 and December 7, 2015, in PubMed and CINAHL. Ten intervention studies were selected and analyzed. Results: Seven of these interventions were based on sectoral interventions and three on comprehensive actions. Conclusion: The studies that have attempted to evaluate the effectiveness of interventions have shown weak evidence to date. Further research is needed to identify effective actions to promote a safe work environment in the ED. Keywords: workplace violence, violence prevention and control, emergency department, aggression, security, review

  19. Old concepts, new molecules and current approaches applied to the bacterial nucleotide signalling field

    Science.gov (United States)

    2016-01-01

    Signalling nucleotides are key molecules that help bacteria to rapidly coordinate cellular pathways and adapt to changes in their environment. During the past 10 years, the nucleotide signalling field has seen much excitement, as several new signalling nucleotides have been discovered in both eukaryotic and bacterial cells. The fields have since advanced quickly, aided by the development of important tools such as the synthesis of modified nucleotides, which, combined with sensitive mass spectrometry methods, allowed for the rapid identification of specific receptor proteins along with other novel genome-wide screening methods. In this review, we describe the principle concepts of nucleotide signalling networks and summarize the recent work that led to the discovery of the novel signalling nucleotides. We also highlight current approaches applied to the research in the field as well as resources and methodological advances aiding in a rapid identification of nucleotide-specific receptor proteins. This article is part of the themed issue ‘The new bacteriology’. PMID:27672152

  20. The past, present, and future of the U.S. electric power sector: Examining regulatory changes using multivariate time series approaches

    Science.gov (United States)

    Binder, Kyle Edwin

    The U.S. energy sector has undergone continuous change in the regulatory, technological, and market environments. These developments show no signs of slowing. Accordingly, it is imperative that energy market regulators and participants develop a strong comprehension of market dynamics and the potential implications of their actions. This dissertation contributes to a better understanding of the past, present, and future of U.S. energy market dynamics and interactions with policy. Advancements in multivariate time series analysis are employed in three related studies of the electric power sector. Overall, results suggest that regulatory changes have had and will continue to have important implications for the electric power sector. The sector, however, has exhibited adaptability to past regulatory changes and is projected to remain resilient in the future. Tests for constancy of the long run parameters in a vector error correction model are applied to determine whether relationships among coal inventories in the electric power sector, input prices, output prices, and opportunity costs have remained constant over the past 38 years. Two periods of instability are found, the first following railroad deregulation in the U.S. and the second corresponding to a number of major regulatory changes in the electric power and natural gas sectors. Relationships among Renewable Energy Credit prices, electricity prices, and natural gas prices are estimated using a vector error correction model. Results suggest that Renewable Energy Credit prices do not completely behave as previously theorized in the literature. Potential reasons for the divergence between theory and empirical evidence are the relative immaturity of current markets and continuous institutional intervention. Potential impacts of future CO2 emissions reductions under the Clean Power Plan on economic and energy sector activity are estimated. Conditional forecasts based on an outlined path for CO2 emissions are

  1. A new approach to study the effect of generation rate on drain-source current of bilayer graphene transistors

    Science.gov (United States)

    Ahmad, H.; Ghadiry, M.; AbdManaf, A.

    2016-10-01

    This paper presents a new approach to study the effect of impact ionization on the current of bilayer graphene field effect transistors. Analytical models for surface potential and current together with a Monte Carlo approach which include the edge effect scattering are used to calculate the current and generation rate in bilayer graphene transistors due to ionization. FlexPDE simulation is also employed for verification of surface potential modeling. Using the approach, the profile of generation rate, surface potential and current are plotted with respect to several structural parameters. We have shown that ignoring this effect in the modeling will result in an error of up to 10 % for a typical 30 nm bilayer graphene field effect transistor. As a result, we conclude that any analytical study ignoring the ionization is incomplete for bilayer graphene field effect transistors. The model presented here can be applied in optimization of photo detectors based on graphene.

  2. Integration of in silico approaches to determination of endocrine-disrupting perfluorinated chemicals binding potency with steroidogenic acute regulatory protein.

    Science.gov (United States)

    Kranthi Kumar, K; Uma Devi, B; Neeraja, P

    2017-09-30

    A myriad of perfluorinated compounds (PFCs) have the ability to interfere with steroidogenic acute regulatory (StAR) protein. Consequently, PFCs breaches cholesterol biotransformation in mitochondria and cause fatal consequences in steroidogenesis, however, these were poorly characterized. In the present study, we have evaluated toxic potencies, nuclear mediated probabilities and interaction profiles with StAR of PFCs using computational system biology tools. Toxicity endpoints revealed that PFCs contain high carcinogenicity, developmental toxicity, skin sensitization effects with low mutagenic activity. Consensus qualitative nuclear receptor agonist models show higher probability rates towards ER and PPAR-γ receptor than AR and AhR models were observed. To poise the subtle fluctuations of actual predictions, balanced accuracy and MCC were computed, and they signify perfect correlation ranges in all models. Screening studies resulting protein-ligand interaction profiles showed that residues Asn148, Asn150, Glu169, Ala171, Arg182, Phe184, Arg188, Trp241, Thr263 and Phe267 were identified as novel hotspots, participated in halogen bonds, H-bonds, atomic π-stacking, π-cation interactions and salt-bridges formation. Thus, the additional bonds contribute conformer stability that holds the protein structure at flexible state, so that PFCs acts as a barrier to cholesterol binding. From docking outcomes, representation space was created, that specifies high and medium StAR binders were occupied in toxic endpoints space with active concern. PFCs restrain molecular features and mitochondrial membrane disruption functions were revealed by efficient toxicogenomics studies. These data indicate toxicity and StAR protein binding levels of PFCs, sorted pinpoints could be useful in a promising way to know the other environmental pollutants and health risks. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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.

  4. EURL ECVAM Status Report on the Development, Validation and Regulatory Acceptance of Alternative Methods and Approaches (2016)

    OpenAIRE

    ZUANG Valerie; ASTURIOL BOFILL DAVID; VIEGAS BARROSO JOAO FILIPE; BELZ SUSANNE; BERGGREN ELISABET; Bernasconi, Camilla; BOPP Stephanie; BOSTROEM Ann-Charlotte; BOUHIFD Mounir; Casati, Silvia; Coecke, Sandra; Cole, Thomas; Corvi, Raffaella; HALDER MARIA ELISABETH; HOLLEY TRACEY

    2016-01-01

    Replacement, Reduction and Refinement of animal testing is anchored in EU legislation. Alternative non-animal approaches facilitate a shift away from animal testing. Cell-based methods and computational technologies are integrated to translate molecular mechanistic understanding of toxicity into safety testing strategies.

  5. Current approaches to treatments for schizophrenia spectrum disorders, part I: an overview and medical treatments

    Directory of Open Access Journals (Sweden)

    Chien WT

    2013-09-01

    Full Text Available Wai Tong Chien, Annie LK Yip School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong Abstract: During the last three decades, an increasing understanding of the etiology, psychopathology, and clinical manifestations of schizophrenia spectrum disorders, in addition to the introduction of second-generation antipsychotics, has optimized the potential for recovery from the illness. Continued development of various models of psychosocial intervention promotes the goal of schizophrenia treatment from one of symptom control and social adaptation to an optimal restoration of functioning and/or recovery. However, it is still questionable whether these new treatment approaches can address the patients' needs for treatment and services and contribute to better patient outcomes. This article provides an overview of different treatment approaches currently used in schizophrenia spectrum disorders to address complex health problems and a wide range of abnormalities and impairments resulting from the illness. There are different treatment strategies and targets for patients at different stages of the illness, ranging from prophylactic antipsychotics and cognitive–behavioral therapy in the premorbid stage to various psychosocial interventions in addition to antipsychotics for relapse prevention and rehabilitation in the later stages of the illness. The use of antipsychotics alone as the main treatment modality may be limited not only in being unable to tackle the frequently occurring negative symptoms and cognitive impairments but also in producing a wide variety of adverse effects to the body or organ functioning. Because of varied pharmacokinetics and treatment responsiveness across agents, the medication regimen should be determined on an individual basis to ensure an optimal effect in its long-term use. This review also highlights that the recent practice guidelines and standards have

  6. Prevalence and Current Approaches of Ebola Virus Disease in ASEAN Countries.

    Science.gov (United States)

    Rajiah, Kingston; San, Kok Pui; Jiun, Ting Wei; May, Tam Ai; Neng, Yap Chan; Seng, Hee Kah; Soon, Lim Jing; Pazooki, Nazanin

    2015-09-01

    As indicated by the World Health Organization as of year 2014, around 10,000 people have been influenced with Ebola infection. The episode of Ebola in African locale is courged with a high death rate. Notwithstanding, in the United States, people influenced by Ebola have been given brilliant wellbeing offices, as the U.S. is one of the highest nations that have taken sterner wellbeing measures and principles against Ebola. Aside from the U.S., individuals in Asia, where billions live in indigence and general wellbeing frameworks are frequently extremely powerless, are under more serious danger of the Ebola infection. Despite the fact that nations like Singapore, Malaysia, South Korea and Japan can take stretched out measures to battle against the infection, nations like Philippines and Indonesia have unfathomable quantities of poor who may be incredibly influenced by a conceivable episode. At this moment, the chances that Asia will take a critical hit from the Ebola infection appear to be genuinely little. Yet, while it is far-fetched that Asia will encounter a real flare-up, genuine concerns stay about the infection coming to urban communities like Hong Kong, Beijing, Shanghai and Singapore through their worldwide airplane terminals. Wellbeing priests from the Association of Southeast Asian Nations (ASEAN) reported key measures not long ago to keep the Ebola plague from coming to the locale and to backing influenced nations. This article accordingly will concentrate on the prevalence and current approaches of Ebola Virus Disease in ASEAN nations which is the need of the hour.

  7. Using a clinical protocol for orthognathic surgery and assessing a 3-dimensional virtual approach: current therapy.

    Science.gov (United States)

    Quevedo, Luis A; Ruiz, Jessica V; Quevedo, Cristobal A

    2011-03-01

    Oral and maxillofacial surgeons who perform orthognathic surgery face major changes in their practices, and these challenges will increase in the near future, because the extraordinary advances in technology applied to our profession are not only amazing but are becoming the standard of care as they promote improved outcomes for our patients. Orthognathic surgery is one of the favorite areas of practicing within the scope of practice of an oral and maxillofacial surgeon. Our own practice in orthognathic surgery has completed over 1,000 surgeries of this type. Success is directly related to the consistency and capability of the surgical-orthodontic team to achieve predictable, stable results, and our hypothesis is that a successful result is directly related to the way we take our records and perform diagnosis and treatment planning following basic general principles. Now that we have the opportunity to plan and treat 3-dimensional (3D) problems with 3D technology, we should enter into this new era with appropriate standards to ensure better results, instead of simply enjoying these new tools, which will clearly show not only us but everyone what we do when we perform orthognathic surgery. Appropriate principles need to be taken into account when implementing this new technology. In other words, new technology is welcome, but we do not have to reinvent the wheel. The purpose of this article is to review the current protocol that we use for orthognathic surgery and compare it with published protocols that incorporate new 3D and virtual technology. This report also describes our approach to this new technology.

  8. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2010-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified t......, such as legislation, self-regulation and technical approaches. It is intended to promote an effective approach to improve consumer privacy in the mobile advertising domain.......This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified...... that should be addressed, so that fair information principles can be applied in the context of m-advertising. It also points out the limitations of these principles. Furthermore, the article discusses a range of models that is available for regulating the collection, use and disclosure of personal data...

  9. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2009-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified t......, such as legislation, self-regulation and technical approaches. It is intended to promote an effective approach to improve consumer privacy in the mobile advertising domain.......This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified...... that should be addressed, so that fair information principles can be applied in the context of m-advertising. It also points out the limitations of these principles. Furthermore, the article discusses a range of models that is available for regulating the collection, use and disclosure of personal data...

  10. 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

  11. Soft and hard computing approaches for real-time prediction of currents in a tide-dominated coastal area

    Digital Repository Service at National Institute of Oceanography (India)

    Charhate, S.B.; Deo, M.C.; SanilKumar, V.

    limited dataarchitecture, namely the feedforward type (Fig. 1), another, called the Jordan–Elman type (Fig. 3), was also are available [39]. Similarly, the feedforward type of network was trained using back propagation,used, since the latter architecture... of coastal current components. All the approaches employed performed muchmethods and architectures in the last 15 years has brought the ANN to its current level of usefulness. better than the traditional statistical method of harmonic analysis.Similar success...

  12. High Tc Superconducting Materials for Strong Current Applications: Approach at the First Stage

    Institute of Scientific and Technical Information of China (English)

    JIN Jian-xun

    2007-01-01

    Strong current and large-scale application is the most important prospect of high Tc superconductors (HTS). Practical HTS samples in various forms have been produced with high critical currents operated at economic cryogenic temperatures. Engineering applications of those HTS materials have been studied with various HTS prototype devices. The applicable HTS materials produced in different forms are verified in this paper with regard to their strong current characterizations, and the HTS applications are summarized along with the HTS prototypes made.

  13. Modulating Endogenous Electric Currents in Human Corneal Wounds—A Novel Approach of Bioelectric Stimulation Without Electrodes

    Science.gov (United States)

    Reid, Brian; Graue-Hernandez, Enrique O.; Mannis, Mark J.; Zhao, Min

    2011-01-01

    Purpose To measure electric current in human corneal wounds and test the feasibility of pharmacologically enhancing the current to promote corneal wound healing. Methods Using a noninvasive vibrating probe, corneal electric current was measured before and after wounding of the epithelium of donated postmortem human corneas. The effects of drug aminophylline and chloride-free solution on wound current were also tested. Results Unwounded cornea had small outward currents (0.07 μA/cm2). Wounding increased the current more than 5 fold (0.41 μA/cm2). Monitoring the wound current over time showed that it seemed to be actively regulated and maintained above normal unwounded levels for at least 6 hours. The time course was similar to that previously measured in rat cornea. Drug treatment or chloride-free solution more than doubled the size of wound currents. Conclusions Electric current at human corneal wounds can be significantly increased with aminophylline or chloride-free solution. Because corneal wound current directly correlates with wound healing rate, our results suggest a role for chloride-free and/or aminophylline eyedrops to enhance healing of damaged cornea in patients with reduced wound healing such as the elderly or diabetic patient. This novel approach offers bioelectric stimulation without electrodes and can be readily tested in patients. PMID:21099404

  14. An Approach for the Analysis of Regulatory Analytes in High Level Radioactive Waste Stored at Hanford, Richland, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Wiemers, K.D.; Miller, M.; Lerchen, M.E.

    1999-01-04

    Radiation levels, salt concentration, and the oxidizing nature of the waste dictates modifications to the SW-846 methods. Modified methods will be used to meet target EQLs and QC currently in SW-846. Method modifications will be validated per SW-846 and HASQARD and will be documented consistent with WAC 173-303-910. The affect of modifications to holding times and storage conditions will be evaluated using techniques developed by Maskarinec and Bayne (1996). After validating the methods and performing the holding time study on a minimum of two Phase 1 candidate feed source tank wastes, DOE and Ecology will assess: whether different methods are needed, whether holding time/storage conditions should be altered, whether the high priority analyte list should be refined, and which additional tank waste needs to be characterized.

  15. Synthesis of the Danish Experience with Combating Nutrient Pollution of Surface Waters: The Old Regulatory Approach and a New Targeted Approach Utilising the Natural Attenuation Capacity in Landscapes

    Science.gov (United States)

    Kronvang, Brian; Windolf, Jørgen; Blicher-Mathiesen, Gitte; Tornbjerg, Henrik; Højberg, Anker; Rieman, Bo

    2016-04-01

    Excess nitrogen (N) and phosphorus (P) emissions to surface waters are a high priority environmental problem worldwide for protection of water resources in times of population growth and climate change. As clean water is a scarce resource the struggle for reducing nutrient emissions are an ongoing issue for many countries and regions. Since the mid1980s a wide range of national regulatory general measures have been implemented to reduce land based nitrogen (N) and phosphorus (P) loadings of the Danish aquatic environment. These measures have addressed both point source emissions and emissions from diffuse sources especially from agricultural production. Following nearly 4 decades of combating nutrient pollution our surface waters such as lakes and estuaries are only slowly responding on the 50% reduction in N and 56% reduction in P. Therefore, the implementation of the EU Water Framework Directive in Danish surface waters still call for further reductions of N and P loadings. Introduction of a new paradigm of targeted implemented measures was the proposed outcome of a Commission on Nature and Agriculture established by the Danish Government in 2013. Their White Book points to the need of increased growth and better environment through more targeted and efficient regulation using advanced technological mitigation methods that are implemented intelligently according to the local natural attenuation capacity for nutrients in the landscape. As a follow up a national consensus model for N was established chaining existing leaching, 3D groundwater and surface water models. The new model concept enables a calculation of the N dynamics and attenuation capacity within a scale of 15 km2. Moreover, several research projects have been conducted to investigate the effect of a suite of targeted mitigation measures such as restored natural wetlands, constructed wetlands, controlled drainage and intelligent buffer zones. The outcome of six Danish management plans for nutrient load

  16. Caustic-based approach to understanding bunching dynamics and current spike formation in particle bunches

    Science.gov (United States)

    Charles, T. K.; Paganin, D. M.; Dowd, R. T.

    2016-10-01

    Current modulations, current spikes, and current horns, are observed in a range of accelerator physics applications including strong bunch compression in Free Electron Lasers and linear colliders, trains of microbunching for terahertz radiation, microbunching instability and many others. This paper considers the fundamental mechanism that drives intense current modulations in dispersive regions, beyond the common explanation of nonlinear and higher-order effects. Under certain conditions, neighboring electron trajectories merge to form caustics, and often result in characteristic current spikes. Caustic lines and surfaces are regions of maximum electron density, and are witnessed in accelerator physics as folds in phase space of accelerated bunches. We identify the caustic phenomenon resulting in cusplike current profiles and derive an expression which describes the conditions needed for particle-bunch caustic formation in dispersive regions. The caustic expression not only reveals the conditions necessary for caustics to form but also where in longitudinal space the caustics will form. Particle-tracking simulations are used to verify these findings. We discuss the broader implications of this work including how to utilize the caustic expression for manipulation of the longitudinal phase space to achieve a desired current profile shape.

  17. A high-throughput metabolomic approach to explore the regulatory effect of mangiferin on metabolic network disturbances of hyperlipidemia rats.

    Science.gov (United States)

    Zhou, Chengyan; Li, Gang; Li, Yanchuan; Gong, Liya; Huang, Yifan; Shi, Zhiping; Du, Shanshan; Li, Ying; Wang, Maoqing; Yin, Jun; Sun, Changhao

    2015-02-01

    This paper was designed to study metabolomic characters of the high-fat diet (HFD)-induced hyperlipidemia and the intervention effects of Mangiferin (MG). In this study, we aimed to investigate the intervention of MG on rats with hyperlipidemia induced by HFD and explore the possible mechanisms of hyperlipidemia. Urine metabolic profiles were analyzed using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) coupled with the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models, Heatmap and metabolism pathway analysis. PCA was applied to study the trajectory of the urinary metabolic phenotype of hyperlipidemia rat after administration of MG. The VIP-plot of orthogonal PLS-DA was used for discovering potential biomarkers to clarify the mechanism of MG. Biochemical analyses indicate that MG can alleviate the hyperlipidemia damage. Twenty significantly changed metabolites (potential biomarkers) were found to be reasonable in explaining the action mechanism of MG. The effectiveness of MG on hyperlipidemia is proved using the established metabolomic method and the regulated metabolic pathways involve the TCA cycle, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine and serine and threonine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis etc. The results indicated that MG has a favourable protective effect on HFD-induced hyperlipidemia by adjusting the metabolic disorders. It also suggests that the metabolomic technology is a powerful approach for elucidation of the action mechanisms of MG.

  18. A diagrammatic description of the equations of motion, current and noise within the second-order von Neumann approach

    DEFF Research Database (Denmark)

    Karlstrom, O.; Emary, C.; Zedler, P.

    2013-01-01

    comparison sheds light on the validity of all these self-consistent second-order approaches. We analyze the discrepancy between the noise calculated by our method and the exact Levitov formula for a simple non-interacting quantum dot model. Furthermore, we study the noise of the canyon of current suppression...

  19. Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers

    NARCIS (Netherlands)

    den Uyl, T.E.; Gladwin, T.E.; Wiers, R.W.

    2016-01-01

    BACKGROUND: Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying

  20. 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....

  1. Evaluation of the Current Status of the Combinatorial Approach for the Study of Phase Diagrams.

    Science.gov (United States)

    Wong-Ng, W

    2012-01-01

    This paper provides an evaluation of the effectiveness of using the high throughput combinatorial approach for preparing phase diagrams of thin film and bulk materials. Our evaluation is based primarily on examples of combinatorial phase diagrams that have been reported in the literature as well as based on our own laboratory experiments. Various factors that affect the construction of these phase diagrams are examined. Instrumentation and analytical approaches needed to improve data acquisition and data analysis are summarized.

  2. A new approach for modeling of dark current characteristics of quantum wire infrared photodetectors

    Institute of Scientific and Technical Information of China (English)

    H. Barickaby; A. Zarifkar; M. H. Sheikhi

    2011-01-01

    In order to study the dark current characteristics in a quantum wire infrared photodetector (QRIP), the average number of electrons in quantum wires (QRs) must be got, which is mostly too complicated. In this paper we give a simple formula to calculate the average number of carriers in a quantum wire (QR) that can be easily evaluated by mathematical softwares, and then we use this formula to study dark current characteristics ora quantum wire infrared photodetector (QRIP).

  3. 78 FR 76973 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-12-20

    ... #0; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER contains regulatory documents #0..., and 225 Regulations H, Q, and Y RIN 7100-AD 87 Regulatory Capital Rules: Regulatory Capital... Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches...

  4. Metalloprotein and metallo-DNA/RNAzyme design: current approaches, success measures, and future challenges.

    Science.gov (United States)

    Lu, Yi

    2006-12-11

    Specific metal-binding sites have been found in not only proteins but also DNA and RNA molecules. Together these metalloenzymes consist of a major portion of the enzyme family and can catalyze some of the most difficult biological reactions. Designing these metalloenzymes can be both challenging and rewarding because it can provide deeper insights into the structure and function of proteins and cheaper and more stable alternatives for biochemical and biotechnological applications. Toward this goal, both rational and combinatorial approaches have been used. The rational approach is good for designing metalloenzymes that are well characterized, such as heme proteins, while the combinatorial approach is better at designing those whose structures are poorly understood, such as metallo-DNA/RNAzymes. Among the rational approaches, de novo design is at its best when metal-binding sites reside in a scaffold whose structure has been designed de novo (e.g., alpha-helical bundles). Otherwise, design using native scaffolds can be equally effective, allowing more choices of scaffolds whose structural stability is often more resistant to multiple mutations. In addition, computational and empirical designs have both enjoyed successes. Because of the limitation in defining structural parameters for metal-binding sites, a computational approach is restricted to mostly metal-binding sites that are well defined, such as mono- or homonuclear centers. An empirical approach, even though it is less restrictive in the metal-binding sites to be designed, depends heavily on one's knowledge and choice of templates and targets. An emerging approach is a combination of both computational and empirical approaches. The success of these approaches can be measured not only by three-dimensional structural comparison between the designed and target enzymes but also by the total amount of insight obtained from the design process and studies of the designed enzymes. One of the biggest advantages of

  5. Approach for Wide Use of Diagnostic Method for XLPE Cables Using Harmonics in AC Loss Current

    Science.gov (United States)

    Tsujimoto, Tomiyuki; Nakade, Masahiko; Yagi, Yukihiro; Ishii, Noboru

    Water tree is one of the degradation aspects of XLPE cables used for under-ground distribution or transmission lines. We have developed the loss current method using 3rd harmonic in AC loss current for cable diagnosis. Harmonic components in loss current arise as a result of the non-linear voltage-current characteristics of water trees. We confirmed that the 3rd harmonic in AC loss current had good correlation with water tree growth and break down strength. After that, we have applied this method to the actual 66kV XLPE cable lines. Up to now, the number of the application results is more than 130 lines. In case of cable lines terminated at gas-insulated switchgear (GIS), we have to remove the lightning arrestor (LA) and the potential transformer (PT) out of the test circuit. The reason is that we are afraid that each of LA and PT disturbs the degradation signal from cable lines. It takes extra time (1 or 2 days) and costs more to remove LA and PT in GIS out of a circuit. In order to achieve easy and reasonable diagnosis, we have developed a new method for cable lines terminated at GIS, by utilizing a technique, which enables to reduce signal of LA and PT from disturbed signal of cable lines. We confirmed the effect of the new method by experiments with actual cables.

  6. Variational approach to low-frequency kinetic-MHD in the current coupling scheme

    Science.gov (United States)

    Burby, Joshua W.; Tronci, Cesare

    2017-04-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which obeys a kinetic equation. In this work we apply Hamilton’s variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling schemes, in which energetic particle dynamics are expressed in either guiding center or gyrocenter coordinates. When guiding center theory is used to model the hot particles, we show how energy conservation requires corrections to the standard magnetization term. On the other hand, charge and momentum conservation in gyrokinetic-MHD lead to extra terms in the usual definition of the hot current density as well as modifications to conventional gyrocenter dynamics. All these new features arise naturally from the underlying variational structure of the proposed models.

  7. Current conservation in electrodisintegration of a bound system in the Bethe-Salpeter approach

    CERN Document Server

    Karmanov, V A

    2014-01-01

    Using our solutions of the Bethe-Salpeter equation with OBE kernel in Minkowski space both for the bound and scattering states, we calculate the transition form factors for electrodisintegration of the bound system which determine the electromagnetic current J of this process. Special emphasis is put on verifying the gauge invariance which should manifest itself in the current conservation. We find that for any value of the momentum transfer q the contributions of the plane wave and the final state interaction to the quantity J.q cancel each other thus providing J.q=0. However, this cancellation is obtained only if the initial Bethe-Salpeter amplitude (bound state), the final one (scattering state) and the current operator are strictly consistent with each other. A reliable result for the transition form factor can be found only in this case.

  8. New approaches in the design of magnetic tweezers-current magnetic tweezers

    Science.gov (United States)

    Bessalova, Valentina; Perov, Nikolai; Rodionova, Valeria

    2016-10-01

    The main advantages of the magnetic tweezers are the low price and simplicity of use. However the range of their application is reduced due to shortcomings like, for example, the remanent induction of the core and interaction between ferromagnetic cores. We present the new design of magnetic tweezers-Current Magnetic Tweezers (CMT) that allow particle manipulation by means of the magnetic field generated by the electric currents flowing through the non-magnetic wires. Arranging wires in different geometric shapes allows the particle movement either in two or three dimensions. Forces acting on the magnetic particles with the magnetic moment of 2·10-11 A m2 at distances up to 1 mm had been experimentally measured. It is established that a current of about 1 A at a 1 mm distance generates force of (approximately) 3 pN which is consistent with theoretical estimates.

  9. Master Equation Approach to Current-Voltage Characteristics of Solar Cells

    Science.gov (United States)

    Oh, Sangchul; Zhang, Yiteng; Alharbi, Fahhad; Kais, Sabre

    2015-03-01

    The current-voltage characteristics of solar cells is obtained using quantum master equations for electrons, holes, and excitons, in which generation, recombination, and transport processes are taken into account. As a first example, we simulate a photocell with a molecular aggregate donor to investigate whether a delocalized quantum state could enhance the efficiency. As a second example, we calculate the current-voltage characteristics of conventional p-n junction solar cells and perovskite solar cells using the master equation. The connection between the drift-diffusion model and the master equation method is established. The short-circuit current and the open-circuit voltage are calculated numerically as a function of the intensity of the sunlight and material properties such as energy gaps, diffusion constants, etc.

  10. An Approach to Model Earth Conductivity Structures with Lateral Changes for Calculating Induced Currents and Geoelectric Fields during Geomagnetic Disturbances

    Directory of Open Access Journals (Sweden)

    Bo Dong

    2015-01-01

    Full Text Available During geomagnetic disturbances, the telluric currents which are driven by the induced electric fields will flow in conductive Earth. An approach to model the Earth conductivity structures with lateral conductivity changes for calculating geoelectric fields is presented in this paper. Numerical results, which are obtained by the Finite Element Method (FEM with a planar grid in two-dimensional modelling and a solid grid in three-dimensional modelling, are compared, and the flow of induced telluric currents in different conductivity regions is demonstrated. Then a three-dimensional conductivity structure is modelled and the induced currents in different depths and the geoelectric field at the Earth’s surface are shown. The geovoltages by integrating the geoelectric field along specific paths can be obtained, which are very important regarding calculations of geomagnetically induced currents (GIC in ground-based technical networks, such as power systems.

  11. New active-only grounded inductance simulator employing current-mode approach suitable for wide band operation

    Science.gov (United States)

    Yamacli, Serhan; Ozcan, Sadri; Kuntman, Hakan

    2011-08-01

    In this paper, an active-only grounded lossless inductance simulator operating in current-mode is presented. The circuit uses only a current operational amplifier (COA) and an operational transconductance amplifier (OTA). The novelty of the proposed circuit is that it uses a COA instead of a voltage operational amplifier (VOA) to take the wider frequency operation advantage of the current-mode approach. The simulation results obtained through SPICE with 0.5 μm standard CMOS technology verify that the designed circuit can be operated up to 30 MHz, which is much higher than the operation frequency of previously reported inductance simulators utilising VOAs. The inductance value of the presented circuit can be adjusted electronically between 3.9 μH and 37 μH via the biasing current of the OTA. A parallel resonance circuit application is also given validating the operation of the proposed inductance simulator.

  12. Regulatory Status of Dissimilar Metal Weld (DMW)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. C.; Hong, J. K.; Shin, H. S.; Kang, S. S.; Song, M. H.; Chung, H. D. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2009-05-15

    In this technical article, the regulatory status for Dissimilar Metal Water (DMW) was discussed. In order to decide the regulatory direction of DMW, the USA's accidents of PWSCC and their regulatory directions were reviewed. By reviewing their experiences, the Korean DMW regulation approach was decided.

  13. Cognitive and Emotion-Regulatory Mediators of the Relationship between Behavioral Approach System Sensitivity and Non-Suicidal Self-Injury Frequency

    Science.gov (United States)

    Burke, Taylor A.; Stange, Jonathan P.; Hamilton, Jessica L.; Cohen, Jonah N.; O’Garro-Moore, Jared; Daryanani, Issar; Abramson, Lyn Y.; Alloy, Lauren B.

    2014-01-01

    Non-suicidal self-injury (NSSI) is highly prevalent among late adolescents and predicts the onset of suicidal ideation and behavior. Although research has established an association between the behavioral approach system (BAS) and NSSI, less research has explored mechanisms underlying this relationship. The authors examined negative and positive emotion regulation patterns, as well as the BAS-relevant cognitive style of self-criticism, as potential mechanisms through which a hypersensitive BAS might be related to NSSI frequency. Late adolescents (N=177) with high and moderate BAS levels completed measures of self-criticism, positive emotion regulation, brooding, and both lifetime and last year frequency of NSSI. Results indicated that self-criticism and positive emotion dampening independently mediated the relationship between BAS and last year frequency of NSSI. Self-criticism also mediated the relationship between BAS and lifetime frequency of NSSI. Results suggest that cognitive and emotion-regulatory styles may help to explain why high BAS individuals are likely to engage in NSSI. PMID:25443691

  14. Current Cognitive Distortion Theory and Research: An Internalist Approach to Cognition

    Science.gov (United States)

    Gannon, Theresa A.

    2009-01-01

    This review examines contemporary cognitive distortion theory and research relating to sexual offenders. In particular, this review highlights that researchers--to date--have tended to adopt an internalist approach to sexual offenders' cognition which views offence-supportive cognitive activity as occurring solely within the mind. This review…

  15. Approaches to Learning with Media and Media Literacy Education--Trends and Current Situation in Germany

    Science.gov (United States)

    Tulodziecki, Gerhard; Grafe, Silke

    2012-01-01

    German approaches to media literacy education are concerned with the questions, how the variety of media can be used in a meaningful way for learning and teaching and what educational tasks result from the extensive use of media. Considering these questions there are various conceptual ideas, research and development projects as well as…

  16. A Phenomenological Approach to Experiences with Technology: Current State, Promise, and Future Directions for Research

    Science.gov (United States)

    Cilesiz, Sebnem

    2011-01-01

    In this paper I conceptualize experiences with technology as an object of study for educational technology research and propose phenomenology as a highly suitable method for studying this construct. I begin by reviewing existing research focusing on the construct of experiences with technology and the approaches utilized for its study. To augment…

  17. Current Cognitive Distortion Theory and Research: An Internalist Approach to Cognition

    Science.gov (United States)

    Gannon, Theresa A.

    2009-01-01

    This review examines contemporary cognitive distortion theory and research relating to sexual offenders. In particular, this review highlights that researchers--to date--have tended to adopt an internalist approach to sexual offenders' cognition which views offence-supportive cognitive activity as occurring solely within the mind. This review…

  18. Overview of current multiparametric magnetic resonance imaging approach in the diagnosis and staging of prostate cancer

    Directory of Open Access Journals (Sweden)

    Hasan Aydın

    2015-04-01

    Full Text Available This article is primarily based on the utility and validity of multiparametric magnetic resonance imaging in the diagnosis and staging of prostate gland tumors. Multiparametric magnetic resonance imaging is an emerging, useful approach for evaluating and detecting prostate cancers. It also aids in the management of a tumor and improve the care and follow-up of patients.

  19. Current training on the basics of robotic surgery in the Netherlands: time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, W.; Angst, I. de; Schreuder, H.; Schout, B.M.A.; Draaisma, W.; Verweij, L.; Hendrikx, A.; Poel, H. van der

    2016-01-01

    Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  20. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    W. Brinkman (Willem); I. de Angst (Isabel); H.W.R. Schreuder (Henk); B. Schout (Barbara); W.A. Draaisma (Werner); L.M. Verweij (Lisanne); A.J.M. Hendrikx (A. J M); H.G. van der Poel (Henk G.)

    2017-01-01

    textabstractIntroduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary

  1. Chronic ischaemic mitral regurgitation. Current treatment results and new mechanism-based surgical approaches

    NARCIS (Netherlands)

    Bouma, Wobbe; van der Horst, Iwan C. C.; Wijdh-den Hamer, Inez J.; Erasmus, Michiel E.; Zijlstra, Felix; Mariani, Massimo A.; Ebels, Tjark

    2010-01-01

    Chronic ischaemic mitral regurgitation (CIMR) remains one of the most complex and unresolved aspects in the management of ischaemic heart disease. This review provides an overview of the present knowledge about the different aspects of CIMR with an emphasis on mechanisms, current surgical treatment

  2. Soft regulations in pharmaceutical policy making : an overview of current approaches and their consequences

    NARCIS (Netherlands)

    Wettermark, B.; Godman, B.; Jacobsson, B.; Haaijer-Ruskamp, F.M.

    2009-01-01

    It is a challenge to improve public health within limited resources. Pharmaceutical policy making is a greater challenge due to conflicting interests between key stakeholder groups. This paper reviews current and future strategies to help improve the quality and efficiency of care, with special emph

  3. Extreme precipitation and temperature responses to circulation patterns in current climate: statistical approaches

    NARCIS (Netherlands)

    Photiadou, C.

    2015-01-01

    Climate change is likely to influence the frequency of extreme extremes - temperature, precipitation and hydrological extremes, which implies increasing risks for flood and drought events in Europe. In current climate, European countries were often not sufficiently prepared to deal with the great so

  4. Current training on the basics of robotic surgery in the Netherlands: time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, W.; Angst, I. de; Schreuder, H.; Schout, B.M.A.; Draaisma, W.; Verweij, L.; Hendrikx, A.; Poel, H. van der

    2016-01-01

    Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  5. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, Willem; de Angst, Isabel; Schreuder, Henk; Schout, Barbara; Draaisma, Werner; Verweij, Lisanne; Hendrikx, Ad; van der Poel, Henk

    Introduction The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  6. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    W. Brinkman (Willem); I. de Angst (Isabel); H.W.R. Schreuder (Henk); B. Schout (Barbara); W.A. Draaisma (Werner); L.M. Verweij (Lisanne); A.J.M. Hendrikx (A. J M); H.G. van der Poel (Henk G.)

    2017-01-01

    textabstractIntroduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary

  7. Characterisation of plastic packaging waste for recycling: problems related to current approaches

    DEFF Research Database (Denmark)

    Götze, Ramona; Astrup, Thomas Fruergaard

    2013-01-01

    criteria of recycling processes. A lack of information in current waste characterisation practise on polymer resin composition, black coloured material content and the influence of surface adherent material on physico-chemical characteristics of plastic packaging waste were identified. These shortcomings...

  8. Current Approaches to the Assessment of Graphic Design in a Higher Education Context

    Science.gov (United States)

    Giloi, Susan; du Toit, Pieter

    2013-01-01

    This article provides an overview of the current trends in assessment practice within the field of graphic design. The demands placed on educators to apply sound assessment practice for Higher Education subjects is as intense in the field of graphic design as in any other. Forcing the assessment of creative visual work into existing assessment…

  9. Random-matrix-theory approach to mesoscopic fluctuations of heat current.

    Science.gov (United States)

    Schmidt, Martin; Kottos, Tsampikos; Shapiro, Boris

    2013-08-01

    We consider an ensemble of fully connected networks of N oscillators coupled harmonically with random springs and show, using random-matrix-theory considerations, that both the average phonon heat current and its variance are scale invariant and take universal values in the large N limit. These anomalous mesoscopic fluctuations is the hallmark of strong correlations between normal modes.

  10. Factitious prey and artificial diets for predatory lady beetles: current situation, obstacles, and approaches for improvement

    Science.gov (United States)

    Predatory lady beetles (Coleoptera: Coccinellidae) are important natural enemies of many pests in crop ecosystems throughout the world. Although several species are currently mass-reared and sold by biocontrol companies, there is an urgent need to reduce rearing costs. Cost effective mass rearing of...

  11. Trade reform, policy uncertainty, and the current account: a non expected-utility approach

    NARCIS (Netherlands)

    van Wijnbergen, S.J.G.

    1992-01-01

    Rapid and comprehensive reduction in barriers to international trade has often been followed by a sharp deterioration in the current account. The macroeconomic counterpart of the deterioration has typically been a decline in private savings; no clear response pattern has been observed for private in

  12. Current training on the basics of robotic surgery in the Netherlands: Time for a multidisciplinary approach?

    NARCIS (Netherlands)

    Brinkman, Willem; de Angst, Isabel; Schreuder, Henk|info:eu-repo/dai/nl/304815977; Schout, Barbara; Draaisma, Werner; Verweij, Lisanne; Hendrikx, Ad; van der Poel, Henk

    2017-01-01

    Introduction The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills

  13. On wind Turbine failure detection from measurements of phase currents: a permutation entropy approach

    CERN Document Server

    Ram, Sumit Kumar; Molinas, Marta

    2016-01-01

    This article presents the applicability of Permutation Entropy based complexity measure of a time series for detection of fault in wind turbines. A set of electrical data from one faulty and one healthy wind turbine were analysed using traditional FastFourier analysis in addition to Permutation Entropy analysis to compare the complexity index of phase currents of the two turbines over time. The 4 seconds length data set did not reveal any low frequency in the spectra of currents, neither did they show any meaningful differences of spectrum between the two turbine currents. Permutation Entropy analysis of the current waveforms of same phases for the two turbines are found to have different complexity values over time, one of them being clearly higher than the other. The work of Yan et. al. in has found that higher entropy values related to thepresence of failure in rotary machines in his study. Following this track, further efforts will be put into relating the entropy difference found in our study to possible...

  14. Current Approaches to the Assessment of Graphic Design in a Higher Education Context

    Science.gov (United States)

    Giloi, Susan; du Toit, Pieter

    2013-01-01

    This article provides an overview of the current trends in assessment practice within the field of graphic design. The demands placed on educators to apply sound assessment practice for Higher Education subjects is as intense in the field of graphic design as in any other. Forcing the assessment of creative visual work into existing assessment…

  15. The effectiveness of current approaches to workplace stress management in the nursing profession: an evidence based literature review

    Science.gov (United States)

    Mimura, C; Griffiths, P

    2003-01-01

    The effectiveness of current approaches to workplace stress management for nurses was assessed through a systematic review. Seven randomised controlled trials and three prospective cohort studies assessing the effectiveness of a stress management programmes were identified and reviewed. The quality of research identified was weak. There is more evidence for the effectiveness of programmes based on providing personal support than environmental management to reduce stressors. However, since the number and quality of studies is low, the question as to which, if any, approach is more effective cannot be answered definitively. Further research is required before clear recommendations for the use of particular interventions for nursing work related stress can be made. PMID:12499451

  16. CHOICE OF SURGICAL APPROACH FOR ACETABULAR COMPONENT’S IMPLANTATION USING CURRENT CLASSIFICATION FOR ARTHRITIS FOLLOWING ACETABULAR FRACTURE

    Directory of Open Access Journals (Sweden)

    R. M. Tikhilov

    2011-01-01

    Full Text Available Degenerative-dystrophic changes in hip after treatment of acetabular fracture, over the time, develops about in 60% of affected people. In such cases, total hip replacement is used. Existing classifications (for example AO or Letournel are good for fracture treatment, but not for arthritis following acetabular fracture. The group of patients, with post traumatic arthritis, is heterogeneous with severity of post traumatic anatomic changes. Basis for surgical approach, could be current classification for post traumatic changes – taking into account features of anatomic functional changes in hip and the bone defects of acetabulum. In this article is demonstrated X-ray and clinical basing for current classification.

  17. Risk assessment of mixtures of pesticides. Current approaches and future strategies

    DEFF Research Database (Denmark)

    Reffstrup, Trine Klein; Larsen, John Christian; Meyer, Otto A.

    2010-01-01

    The risk assessment of pesticide residues in food is based on toxicological evaluation of the single compounds and no internationally accepted procedure exists for evaluation of cumulative exposure to multiple residues of pesticides in crops, except for a few groups of pesticides sharing a group...... several approaches are available for the risk assessment of mixtures of pesticides. However, no single simple approach is available to judge upon potential interactions at the low doses that humans are exposed to from pesticide residues in food. In these cases, PBTK models could be useful as tools...... to assess combined tissue doses and to help predict potential interactions including thresholds for such effects. This would improve the quality of the risk assessment....

  18. Overcoming resistance to targeted therapies in NSCLC: current approaches and clinical application.

    Science.gov (United States)

    Maione, Paolo; Sacco, Paola Claudia; Sgambato, Assunta; Casaluce, Francesca; Rossi, Antonio; Gridelli, Cesare

    2015-09-01

    The discovery that a number of aberrant tumorigenic processes and signal transduction pathways are mediated by druggable protein kinases has led to a revolutionary change in nonsmall cell lung cancer (NSCLC) treatment. Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the targets of several tyrosine kinase inhibitors (TKIs), some of them approved for treatment and others currently in clinical development. First-generation agents offer, in target populations, a substantial improvement of outcomes compared with standard chemotherapy in the treatment of advanced NSCLC. Unfortunately, drug resistance develops after initial benefit through a variety of mechanisms. Novel generation EGFR and ALK inhibitors are currently in advanced clinical development and are producing encouraging results in patients with acquired resistance to previous generation agents. The search for new drugs or strategies to overcome the TKI resistance in patients with EGFR mutations or ALK rearrangements is to be considered a priority for the improvement of outcomes in the treatment of advanced NSCLC.

  19. Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

    Science.gov (United States)

    Aschenbroich, Sophie A; Lafontaine, Eric R; Hogan, Robert J

    2016-09-01

    Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.

  20. Transition electromagnetic form factor and current conservation in the Bethe-Salpeter approach

    CERN Document Server

    Carbonell, J

    2015-01-01

    The transition form factor for electrodisintegration of a two-body bound system is calculated in the Bethe-Salpeter framework. For the initial (bound) and the final (scattering) states, we use our solutions of the Bethe-Salpeter equation in Minkowski space which were first obtained recently. The gauge invariance, which manifests itself in the conservation of the transition electromagnetic current Jq = 0, is studied numerically. It results from a cancellation between the plane wave and the final state interaction contributions. This cancellation takes place only if the initial bound state BS amplitude, the final scattering state and the operator of electromagnetic current are strictly consistent with each other, that is if they are found in the same dynamical framework. A reliable result for the transition form factor can be obtained in this case only.

  1. Peripheral T-cell lymphomas: A review of current approaches and hopes for the future.

    Directory of Open Access Journals (Sweden)

    Alan Pierre Skarbnik

    2013-05-01

    Full Text Available Peripheral T-cell lymphomas comprise a heterogeneous group of NHLs, with different clinical and biological behaviors, but with a common denominator of poor overall prognosis and lack of potentially curable approaches outside of the realm of stem cell transplantation. Recent data have elicited renewed hope in the treatment of this disease. The authors review the standard of care in treating PTCL, as well as novel therapeutic modalities.

  2. Current diagnostic approach of bone tumors in childhood; Abordagem diagnostica atual dos tumores osseos na infancia

    Energy Technology Data Exchange (ETDEWEB)

    Torre, Marcia Barbosa; Scatigno Neto, Andre [Sao Paulo Univ., SP (Brazil). Faculdade de Medicina. Hospital das Clinicas

    1995-09-01

    The authors analyze the magnetic resonance imaging (MRI) as the imaging modality of choice for evaluation of patients with bone tumors or soft tissue tumors. The advent of such a sensitive imaging modality is fortuitous and coincides with a recent change in the therapeutic approach to primary bone tumors. MRI is extremely valuable in monitoring the tumor response to the initial chemotherapy and is accurate defining the margins of tumor, facilitating planning of limb salvage surgical procedures. (author). 5 refs., 8 figs.

  3. Our Approach to Toxic Epidermal Necrolysis and Review of Current Treatment Alternatives

    Directory of Open Access Journals (Sweden)

    Fatih Uygur

    2008-09-01

    Full Text Available Toxic epidermal necrolysis (TEN is a clinical entity which has a 30 to 40 % mortality rate, with necrolysis affecting the entire epidermis. Antibiotics, nonsteroidal anti-inflammatory drugs and anticonvulsants are offender drugs in TEN etiology. A standard treatment protocol with proven efficacy is still lacking. In this study, current treatment practice and our treatment strategy for TEN is discussed and eight patients treated in our clinic between the years 2001 and 2008 are reviewed.

  4. The generalized BLM approach to fix scale-dependence in QCD: the current status of investigations

    CERN Document Server

    Kataev, A L

    2014-01-01

    I present a brief review of the generalized Brodsky-Lepage-McKenzie (BLM) approaches to fix the scale-dependence of the renormalization group (RG) invariant quantities in QCD. At first, these approaches are based on the expansions of the coefficients of the perturbative series for the RG-invariant quantities in the products of the coefficients $\\beta_i$ of the QCD $\\beta$-function, which are evaluated in the MS-like schemes. As a next step all $\\beta_i$-dependent terms are absorbed into the BLM-type scale(s) of the powers of the QCD couplings. The difference between two existing formulations of the above mentioned generalizations based on the seBLM approach and the Principle of Maximal Conformality (PMC) are clarified in the case of the Bjorken polarized deep-inelastic scattering sum rule. Using the conformal symmetry-based relations for the non-singlet coefficient functions of the Adler D-function and of Bjorken polarized deep-inelastic scattering sum rules $C^{\\rm Bjp}_{\\rm NS}(a_s)$ the $\\beta_i$-dependent...

  5. New approaches in the design of magnetic tweezers–current magnetic tweezers

    Energy Technology Data Exchange (ETDEWEB)

    Bessalova, Valentina [Lomonosov Moscow State University, Leninskie Gory 1-2, 119991 Moscow (Russian Federation); Perov, Nikolai [Lomonosov Moscow State University, Leninskie Gory 1-2, 119991 Moscow (Russian Federation); Immanuel Kant Baltic Federal University, Nevskogo 14, 236004 Kaliningrad (Russian Federation); Rodionova, Valeria [Immanuel Kant Baltic Federal University, Nevskogo 14, 236004 Kaliningrad (Russian Federation); National University of Science and Technology ' MISiS' , Leninsky Prospect 4, 119049 Moscow (Russian Federation)

    2016-10-01

    The main advantages of the magnetic tweezers are the low price and simplicity of use. However the range of their application is reduced due to shortcomings like, for example, the remanent induction of the core and interaction between ferromagnetic cores. We present the new design of magnetic tweezers–Current Magnetic Tweezers (CMT) that allow particle manipulation by means of the magnetic field generated by the electric currents flowing through the non-magnetic wires. Arranging wires in different geometric shapes allows the particle movement either in two or three dimensions. Forces acting on the magnetic particles with the magnetic moment of 2·10{sup −11} A m{sup 2} at distances up to 1 mm had been experimentally measured. It is established that a current of about 1 A at a 1 mm distance generates force of (approximately) 3 pN which is consistent with theoretical estimates. - Highlights: • We suggest the idea and the results of the test the prototype based on 3 wire's system that allows manipulation of nanoparticles on XY plane.

  6. Society for Maternal-Fetal Medicine (SMFM) Special Report: Current approaches to measuring quality of care in obstetrics.

    Science.gov (United States)

    Bailit, Jennifer L; Gregory, Kimberly D; Srinivas, Sindhu; Westover, Thomas; Grobman, William A; Saade, George R

    2016-09-01

    Heath care measurement and evaluation is an integral piece of the health care system. The creation and assessment of care performance metrics are important and relevant for the obstetric community including both clinicians and patients. Careful deliberation is required to create a measurement system that results in optimal care for women and families. This article reviews the current approaches to measuring quality in obstetrics. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. A Combined EOF/Variational Approach for Mapping Radar-Derived Sea Surface Currents

    Science.gov (United States)

    2011-01-01

    assess the method’s skill and compare it with the conventional 2d variational (2dVar) approach. It is shown that the proposed technique consistently...radial velocities are interpolated on the regular grid. Experiments with simulated and real data are used to assess the method’s skill and compare it...velocities v(x,) observed outside the gap (x, efl \\<u) are expanded in Kr "resolved" eigenfunctions e* of C: find otk: £ v(Xj)- ]T 0Lke"(x,) X, . I/lU

  8. Visão atual da hemocromatose hereditária Current approach to hereditary hemochromatosis

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    2010-01-01

    involved in the iron metabolism. Hepcidin is an iron regulatory hormone that inhibits ferroportin-mediated iron export from enterocytes and macrophages. Defective hepcidin gene expression or function may underlie most forms of hereditary hemochromatosis. Target organs and tissues affected by hereditary hemochromatosis include the liver, heart, pancreas, joints, and skin, with cirrhosis and diabetes melittus representing late signs of disease in patients with very high liver iron concentrations. Patients with an established diagnosis of hereditary hemochromatosis and iron overload should be treated with phlebotomy to achieve body iron depletion followed by maintenance phlebotomy. The most frequent causes of death in hereditary hemochromatosis are liver cancer, cirrhosis, cardiomyopathy, and diabetes. However, patients who undergo successful iron depletion before developing cirrhosis or diabetes can have normal life expectancy.

  9. Current Trends in Psychological and Educational Approaches for Training and Teaching Students with Autism in California

    Directory of Open Access Journals (Sweden)

    Trisha SUGITA

    2016-12-01

    Full Text Available Within the United States, Autism Spectrum Disorder (ASD has seen a dramatic increase over the past twenty years. As the prevalence rate of ASD increases, an increased need for expertise in the field of education has become apparent. Psychological and educational practices for training and teaching students with ASD continue to evolve in California however, a significant gap between theory and practice remains. This article provides a historical perspective of ASD and its prevalence rates. In addition, this article examines the current shifts in teacher training and provides an overview of evidence-based strategies to support students with ASD.

  10. Choosing Wisely: assessment of current US top five list recommendations’ trustworthiness using a pragmatic approach

    Science.gov (United States)

    Horvath, Karl; Semlitsch, Thomas; Jeitler, Klaus; Abuzahra, Muna E; Posch, Nicole; Domke, Andreas; Siebenhofer, Andrea

    2016-01-01

    Objectives Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. Setting Not applicable. Participants All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. Main outcome measures/interventions Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an ‘A’ GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. Results 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an ‘A’ GoR, or a strong recommendation based on strong evidence, and 26 had a ‘B’ or a ‘C’ GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. Conclusions 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number

  11. Choosing Wisely: assessment of current US top five list recommendations' trustworthiness using a pragmatic approach.

    Science.gov (United States)

    Horvath, Karl; Semlitsch, Thomas; Jeitler, Klaus; Abuzahra, Muna E; Posch, Nicole; Domke, Andreas; Siebenhofer, Andrea

    2016-10-07

    Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign. Not applicable. All top 5 list recommendations available from the American Board of Internal Medicine Foundation website. Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an 'A' GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature. 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an 'A' GoR, or a strong recommendation based on strong evidence, and 26 had a 'B' or a 'C' GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory. 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological

  12. Current Research and Classroom Practice: Toward More Inclusive Approaches to Literacy Development in Schools

    Directory of Open Access Journals (Sweden)

    David Booth

    2009-07-01

    Full Text Available This paper offers an exploration of current research and related practice in boys’ literacy development, interprets key findings in the literature, and further explores some of the complex dilemmas and debates related to the ‘gender gap’ – i.e., differences between the achievement of boys and girls in this area. In conclusion, the authors suggest that governments, policy-makers, administrators, teachers and parents all need to closely examine and consider available research-based strategies and classroom interventions that can effectively support both boys and girls in their literacy development. 

  13. Agulhas Current variability determined from space: a multi-sensor approach

    CSIR Research Space (South Africa)

    Rouault, M

    2011-11-01

    Full Text Available ]) or altimetry (de Ruijter et al. [1999]; van Leeuwen et al. [2000]), as well as from numerical modelling experiments (Biastoch et al. [2008b]; Tsugawa and Hasumi [2010]). More recent studies on Natal Pulses have shown that these offshore meanders originate.... In particular, they have been linked to the formation of Agulhas Rings (van Leeuwen et al. [2000]) and on some occasion to early retroflections (Lutjeharms and van Ballegooyen [1988]). In the southern Agulhas, south of 35oS, the Agulhas Current is no longer...

  14. 3D cell culture: a review of current approaches and techniques.

    Science.gov (United States)

    Haycock, John W

    2011-01-01

    Cell culture in two dimensions has been routinely and diligently undertaken in thousands of laboratories worldwide for the past four decades. However, the culture of cells in two dimensions is arguably primitive and does not reproduce the anatomy or physiology of a tissue for informative or useful study. Creating a third dimension for cell culture is clearly more relevant, but requires a multidisciplinary approach and multidisciplinary expertise. When entering the third dimension, investigators need to consider the design of scaffolds for supporting the organisation of cells or the use of bioreactors for controlling nutrient and waste product exchange. As 3D culture systems become more mature and relevant to human and animal physiology, the ability to design and develop co-cultures becomes possible as does the ability to integrate stem cells. The primary objectives for developing 3D cell culture systems vary widely - and range from engineering tissues for clinical delivery through to the development of models for drug screening. The intention of this review is to provide a general overview of the common approaches and techniques for designing 3D culture models.

  15. Current approach to male infertility treatment: sperm selection procedure based on hyaluronic acid binding ability

    Directory of Open Access Journals (Sweden)

    A. V. Zobova

    2015-01-01

    Full Text Available Intracytoplasmic sperm injection into an oocyte is widely used throughout the world in assisted reproductive technologies programs in the presence of male infertility factor. However, this approach can allow selection of a single sperm, which is carrying different types of pathologies. Minimizing of any potential risks, entailing the occurrence of abnormalities in the embryos development (apoptosis, fragmentation of embryos, alterations in gene expression, aneuploidies is a very important condition for reducing the potential negative consequences resulting the manipulation with gametes. Processes that could be influenced by the embryologist must be fulfilled in safe and physiological way as much as it is possible. Data of numerous publications reporting about the positive effects of using the technology of sperm selection by hyaluronic acid binding, let make a conclusion about the high prospects of this approach in the treatment of male infertility by methods of in vitro fertilization. The selection of sperm with improved characteristics, which determine the maturity and genetic integrity, provides an opportunity to improve the parameters of pre-implantation embryogenesis, having thus a positive effect on clinical outcomes of assisted reproductive technologies programs.

  16. Current approaches to managing partial breast defects: the role of conservative breast surgery reconstruction.

    Science.gov (United States)

    Munhoz, Alexandre Mendonça; Montag, Eduardo; Filassi, José Roberto; Gemperli, Rolf

    2014-03-01

    Recently breast surgeons can offer patients a variety of treatment and reconstructive alternatives when early breast cancer is diagnosed. In fact, advances in reconstructive techniques have reduced surgical trauma and thus are capable of preserving the breast form as well as quality of life. Depending on a variety of different factors, including stage, tumor size, location, hystological type, but also breast volume, a reconstructive schedule is established. The main techniques are related to volume displacement or replacement procedures including local flaps, latissimus dorsi myocutaneous flap and reduction mammaplasty/ masthopexy. Regardless of the fact that there are is no consensus over the best approach, the criteria are determined by the surgeon's experience and the size of the defect in relation to the size of the remaining breast. Aim of every reconstructive procedure decision should be breast preservation and an adequate aesthetic outcome. Additionally, reconstruction permits wider excision of the tumor, with a superior mean volume of the specimen and potentially reducing the incidence of margin involvement. The objective of this review is to give an overview of reconstructive modalities for conservative breast surgery, based not only on traditional but also on the latest studies regarding the outcome of the main techniques employed. Surgical approaches, as well as conservative treatment options, such as lumpectomy and quadrantectomy, are further discussed. Surgical planning should include the patients' preferences, while chiefly addressing individual reconstructive requirements, and enabling each patient to receive an individual "custom-made" reconstruction.

  17. Neonatal infections due to multi-resistant strains: Epidemiology, current treatment, emerging therapeutic approaches and prevention.

    Science.gov (United States)

    Tzialla, Chryssoula; Borghesi, Alessandro; Pozzi, Margherita; Stronati, Mauro

    2015-12-07

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units. The benefits of antibiotic therapy when indicated are clearly enormous, but the continued and widespread use of antibiotics has generated over the years a strong selective pressure on microorganisms, favoring the emergence of resistant strains. Health agencies worldwide are galvanizing attention toward antibiotic resistance in gram-positive and gram-negative bacteria. Infections in neonatal units due to multidrug and extensively multidrug resistant bacteria are rising and are already seriously challenging antibiotic treatment options. While there is a growing choice of agents against multi-resistant gram-positive bacteria, new options for multi-resistant gram-negative bacteria in the clinical practice have decreased significantly in the last 20 years making the treatment of infections caused by multidrug-resistant pathogens challenging mostly in neonates. Treatment options are currently limited and will be some years before any new treatment for neonates become available for clinical use, if ever. The aim of the review is to highlight the current knowledge on antibiotic resistance in the neonatal population, the possible therapeutic choices, and the prevention strategies to adopt in order to reduce the emergency and spread of resistant strains.

  18. Current applications and different approaches for microbial L-asparaginase production

    Directory of Open Access Journals (Sweden)

    Jorge Javier Muso Cachumba

    Full Text Available ABSTRACT L-asparaginase (EC 3.5.1.1 is an enzyme that catalysis mainly the asparagine hydrolysis in L-aspartic acid and ammonium. This enzyme is presented in different organisms, such as microorganisms, vegetal, and some animals, including certain rodent's serum, but not unveiled in humans. It can be used as important chemotherapeutic agent for the treatment of a variety of lymphoproliferative disorders and lymphomas (particularly acute lymphoblastic leukemia (ALL and Hodgkin's lymphoma, and has been a pivotal agent in chemotherapy protocols from around 30 years. Also, other important application is in food industry, by using the properties of this enzyme to reduce acrylamide levels in commercial fried foods, maintaining their characteristics (color, flavor, texture, security, etc. Actually, L-asparaginase catalyzes the hydrolysis of L-asparagine, not allowing the reaction of reducing sugars with this aminoacid for the generation of acrylamide. Currently, production of L-asparaginase is mainly based in biotechnological production by using some bacteria. However, industrial production also needs research work aiming to obtain better production yields, as well as novel process by applying different microorganisms to increase the range of applications of the produced enzyme. Within this context, this mini-review presents L-asparaginase applications, production by different microorganisms and some limitations, current investigations, as well as some challenges to be achieved for profitable industrial production.

  19. Upper extremity sarcoma: impact of current practice guidelines and controversies on reconstructive approaches

    Directory of Open Access Journals (Sweden)

    Dobke Marek

    2017-01-01

    Full Text Available The goals of sarcoma management include both a cure and the functional preservation of involved tissues and adjacent critical structures with common opinions favoring immediate reconstruction. The question arises whether these goals are contradictory. This paper discusses the question based on the experience of 28 patients with different types of extremity sarcoma, with 24 surgically treated by the University of California San Diego (UCSD orthopedic and plastic surgery team (2011–2016 and the collection of evidence from published practice guidelines, reviews, case studies, and clinical trials. Included are the impact of limb-sparing and functional reconstructive concepts, efforts regarding the adequacy of surgical margins, and the rationale of immediate versus delayed reconstructive approaches, and the disease-free status of sarcoma management.

  20. Multiple, sclerosis: clinical feature, pathogenesis and current therapeutical approaches; Encephalomyelitis disseminata: Klinik, Pathogenese und aktuelle Therapiekonzepte

    Energy Technology Data Exchange (ETDEWEB)

    Merkelbach, S.; Koelmel, C.; Schimrigk, K. [Universitaet des Saarlandes, Homburg/Saar (Germany). Neurologische Klinik

    2000-11-01

    Multiple sclerosis (MS) is considered as a T-cell mediated autoimmune disease. Caused by central nervous system demyelination and axonal damage varying clinical signs do occur either with relapsing-remitting or with chronic progressive course. Based on pathogenetic considerations immunomodulative and immunosuppressive therapeutical approaches are used to limit the disease progression. Clinical symptoms, diagnostic criteria, pathogenetical considerations, and consecutive therapeutical interventions are summarized. (orig.) [German] Die Encephalomyelitis disseminata oder Multiple Sklerose (ED oder MS) gilt als T-Zell-vermittelte Autoimmunerkrankung. Schubfoermig oder chronisch progredient kommt es im Zentralnervensystem infolge einer Demyelinisierung der weissen Substanz und axonaler Schaedigungen zu einer Vielzahl neurologischer Symptome. Basierend auf pathogenetischen Erkenntnissen werden derzeit immunmodulative und immunsuppressive Therapien eingesetzt, die den Krankheitsverlauf zumindest bremsen. Klinische Symptome, diagnostische Kriterien, pathogenetische Ueberlegungen und sich daraus ableitende Therapiekonzepte werden zusammenfassend dargestellt. (orig.)

  1. Current approach to metastasis of extra-genital system malignancies to the female genital tract

    Directory of Open Access Journals (Sweden)

    Kemal Güngördük

    2015-12-01

    Full Text Available Metastases to the female genital tract from extra-genital malignancies are very uncommon and have a poor prognosis. The most common extra-genital primary sites are breast and gastrointestinal system. The ovaries are frequent targets of metastasis for malignant tumors. Distinction between primary and metastatic tumors is important because misinterpretation of a metastatic tumor as primary tumor may lead to inappropriate management and suboptimal treatment outcome. The routes of tumor spread to the genital system are variable such as lymphatic and hematogenous metastasis or direct extension. Multidisciplinary approach is required to management and follow-up for these patients. J Clin Exp Invest 2015; 6 (4: 406-413

  2. Pharmacological chaperone approaches for rescuing GPCR mutants: Current state, challenges, and screening strategies.

    Science.gov (United States)

    Beerepoot, Pieter; Nazari, Reza; Salahpour, Ali

    2017-03-01

    A substantial number of G-protein coupled receptors (GPCRs) genetic disorders are due to mutations that cause misfolding or dysfunction of the receptor product. Pharmacological chaperoning approaches can rescue such mutant receptors by stabilizing protein conformations that behave similar to the wild type protein. For example, this can be achieved by improving folding efficiency and/or interaction with chaperone proteins. Although efficacy of pharmacological chaperones has been demonstrated in vitro for a variety of GPCRs, translation to clinical use has been limited. In this paper we discuss the history of pharmacological chaperones of GPCR's and other membrane proteins, the challenges in translation to the clinic, and the use of different assays for pharmacological chaperone discovery.

  3. Surpassing the current limitations of biohydrogen production systems: The case for a novel hybrid approach.

    Science.gov (United States)

    Boboescu, Iulian Zoltan; Gherman, Vasile Daniel; Lakatos, Gergely; Pap, Bernadett; Bíró, Tibor; Maróti, Gergely

    2016-03-01

    The steadily increase of global energy requirements has brought about a general agreement on the need for novel renewable and environmentally friendly energy sources and carriers. Among the alternatives to a fossil fuel-based economy, hydrogen gas is considered a game-changer. Certain methods of hydrogen production can utilize various low-priced industrial and agricultural wastes as substrate, thus coupling organic waste treatment with renewable energy generation. Among these approaches, different biological strategies have been investigated and successfully implemented in laboratory-scale systems. Although promising, several key aspects need further investigation in order to push these technologies towards large-scale industrial implementation. Some of the major scientific and technical bottlenecks will be discussed, along with possible solutions, including a thorough exploration of novel research combining microbial dark fermentation and algal photoheterotrophic degradation systems, integrated with wastewater treatment and metabolic by-products usage.

  4. An Overview of Current Screening and Management Approaches for Prostate Cancer.

    Science.gov (United States)

    Akram, Omar N; Mushtaq, Gohar; Kamal, Mohammad Amjad

    2015-01-01

    Prostate cancer is the fourth leading cause of mortality in Australian men. The prevalence and incidence is increasing in both developed and developing nations, thus there is a need for better screening and management of this disorder. While there is no direct known cause of prostate cancer, management is largely focused on early detection and treatment strategies. Of particular concern is advanced prostate cancer which can manifest as castrate resistant prostate cancer characterized by therapy resistance. This short review outlines the global epidemiology of prostate cancer, clinical manifestations, risk factors, current screening strategies including first line clinical screening as well as the use of circulating biomarkers, and treatment of prostate cancer through mainstream therapeutics as well as the cutting edge peptide and nano-technology based therapeutics that are being implemented or in the process of development to overcome therapeutic obstacles in the treatment of prostate cancer.

  5. Hyponatremia in the neurocritical care patient: An approach based on current evidence.

    Science.gov (United States)

    Manzanares, W; Aramendi, I; Langlois, P L; Biestro, A

    2015-05-01

    In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of "cerebral salt wasting", which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  6. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa

    2016-01-01

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures...... are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS...... experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation...

  7. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: Current approaches and future perspectives

    DEFF Research Database (Denmark)

    Bergmann, Til Ole; Karabanov, Anke; Hartwigsen, Gesa

    2016-01-01

    Non-invasive transcranial brain stimulation (NTBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS) are important tools in human systems and cognitive neuroscience because they are able to reveal the relevance of certain brain structures...... are technically demanding. We argue that the benefit from this combination is twofold. Firstly, neuroimaging and electrophysiology can inform subsequent NTBS, providing the required information to optimize where, when, and how to stimulate the brain. Information can be achieved both before and during the NTBS...... experiment, requiring consecutive and concurrent applications, respectively. Secondly, neuroimaging and electrophysiology can provide the readout for neural changes induced by NTBS. Again, using either concurrent or consecutive applications, both "online" NTBS effects immediately following the stimulation...

  8. Characterisation of plastic packaging waste for recycling: problems related to current approaches

    DEFF Research Database (Denmark)

    Götze, Ramona; Astrup, Thomas Fruergaard

    2013-01-01

    were addressed by a resin type-based sorting analysis and a washing test for plastic packaging material from Danish household waste. Preliminary results show that, for a quarter of the hand sorted material, no resin type could be identified and that Polypropylene and Polyethylene terephthalate were...... criteria of recycling processes. A lack of information in current waste characterisation practise on polymer resin composition, black coloured material content and the influence of surface adherent material on physico-chemical characteristics of plastic packaging waste were identified. These shortcomings...... the dominating resin types in plastic packaging. The suggested washing procedure caused a decrease of 70% of the ash content of the plastic material. The analysed metals and nutrients were reduced by up to 24%...

  9. Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

    Science.gov (United States)

    Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

    2012-10-31

    Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Análise comparativa do desenho normativo de instituições reguladoras do presente e do passado Comparative analysis of the normative design of former and current regulatory institutions

    Directory of Open Access Journals (Sweden)

    Antonio Gelis Filho

    2006-08-01

    Full Text Available Este artigo desenvolve um modelo matricial para avaliação do desenho normativo de instituições reguladoras do presente e do passado (autarquias econômicas da república "populista". Desenho normativo é definido como o conjunto de possibilidades de estruturação e de atuação de uma instituição que é delimitado pelas normas jurídicas que a criaram. O modelo é estruturado a partir de dois parâmetros principais: independência em relação ao poder central e transparência em relação à sociedade. Foram testadas cinco hipóteses, concluindo-se que as instituições reguladoras do presente apresentam desenhos normativos heterogêneos e que se distinguem de instituições do passado tanto por maior independência quanto por maior transparência, sendo a diferença mais acentuada em relação ao segundo parâmetro.This article develops a matrix model to assess the normative design of past and current regulatory institutions (economic autarchies of the 'populist' republic. Normative design is defined as a set of possibilities for an institution's structure and actions which is limited by the legal norms that created it. The model is structured based on two main parameters: independence in relation to the central power and transparency in relation to society. Five hypothesis were tested, and the conclusion was that current regulatory institutions have heterogeneous designs and they differ from the former ones for being both more independent and more transparent, and the largest difference is in the second parameter.

  11. Pharmacological approaches to improving cognitive function in Down syndrome: current status and considerations

    Directory of Open Access Journals (Sweden)

    Gardiner KJ

    2014-12-01

    Full Text Available Katheleen J Gardiner Linda Crnic Institute for Down Syndrome, Department of Pediatrics, Department of Biochemistry and Molecular Genetics, Human Medical Genetics and Genomics Program, Neuroscience Program, University of Colorado School of Medicine, Aurora, CO, USA Abstract: Down syndrome (DS, also known as trisomy 21, is the most common genetic cause of intellectual disability (ID. Although ID can be mild, the average intelligence quotient is in the range of 40–50. All individuals with DS will also develop the neuropathology of Alzheimer’s disease (AD by the age of 30–40 years, and approximately half will display an AD-like dementia by the age of 60 years. DS is caused by an extra copy of the long arm of human chromosome 21 (Hsa21 and the consequent elevated levels of expression, due to dosage, of trisomic genes. Despite a worldwide incidence of one in 700–1,000 live births, there are currently no pharmacological treatments available for ID or AD in DS. However, over the last several years, very promising results have been obtained with a mouse model of DS, the Ts65Dn. A diverse array of drugs has been shown to rescue, or partially rescue, DS-relevant deficits in learning and memory and abnormalities in cellular and electrophysiological features seen in the Ts65Dn. These results suggest that some level of amelioration or prevention of cognitive deficits in people with DS may be possible. Here, we review information from the preclinical evaluations in the Ts65Dn, how drugs were selected, how efficacy was judged, and how outcomes differ, or not, among studies. We also summarize the current state of human clinical trials for ID and AD in DS. Lastly, we describe the genetic limitations of the Ts65Dn as a model of DS, and in the preclinical testing of pharmacotherapeutics, and suggest additional targets to be considered for potential pharmacotherapies. Keywords: Ts65Dn, pharmacotherapy, clinical trials, Hsa21

  12. Assessing the reliability of ecotoxicological studies: An overview of current needs and approaches.

    Science.gov (United States)

    Moermond, Caroline; Beasley, Amy; Breton, Roger; Junghans, Marion; Laskowski, Ryszard; Solomon, Keith; Zahner, Holly

    2016-11-21

    In general, reliable studies are well designed and well performed, and enough details on study design and performance are reported to assess the study. For hazard and risk assessment in various legal frameworks, many different types of ecotoxicity studies need to be evaluated for reliability. These studies vary in study design, methodology, quality, and level of detail reported (e.g., reviews, peer-reviewed research papers, or industry-sponsored studies documented under Good Laboratory Practice [GLP] guidelines). Regulators have the responsibility to make sound and verifiable decisions and should evaluate each study for reliability in accordance with scientific principles regardless of whether they were conducted in accordance with GLP and/or standardized methods. Thus, a systematic and transparent approach is needed to evaluate studies for reliability. In this paper, 8 different methods for reliability assessment were compared using a number of attributes: categorical versus numerical scoring methods, use of exclusion and critical criteria, weighting of criteria, whether methods are tested with case studies, domain of applicability, bias toward GLP studies, incorporation of standard guidelines in the evaluation method, number of criteria used, type of criteria considered, and availability of guidance material. Finally, some considerations are given on how to choose a suitable method for assessing reliability of ecotoxicity studies. Integr Environ Assess Manag. ©2016 SETAC.

  13. Missing Data in Substance Abuse Treatment Research: Current Methods and Modern Approaches

    Science.gov (United States)

    McPherson, Sterling; Barbosa-Leiker, Celestina; Burns, G. Leonard; Howell, Donelle; Roll, John

    2013-01-01

    Two common procedures for the treatment of missing information, listwise deletion and positive urine analysis (UA) imputation (e.g., if the participant fails to provide urine for analysis, then score the UA positive), may result in significant biases during the interpretation of treatment effects. To compare these approaches and to offer a possible alternative, these two procedures were compared to the multiple imputation (MI) procedure with publicly available data from a recent clinical trial. Listwise deletion, single imputation (i.e., positive UA imputation), and MI missing data procedures were used to comparatively examine the effect of two different buprenorphine/naloxone tapering schedules (7- or 28-days) for opioid addiction on the likelihood of a positive UA (Clinical Trial Network 0003; Ling et al., 2009). The listwise deletion of missing data resulted in a nonsignificant effect for the taper while the positive UA imputation procedure resulted in a significant effect, replicating the original findings by Ling et al. (2009). Although the MI procedure also resulted in a significant effect, the effect size was meaningfully smaller and the standard errors meaningfully larger when compared to the positive UA procedure. This study demonstrates that the researcher can obtain markedly different results depending on how the missing data are handled. Missing data theory suggests that listwise deletion and single imputation procedures should not be used to account for missing information, and that MI has advantages with respect to internal and external validity when the assumption of missing at random can be reasonably supported. PMID:22329556

  14. IMRT dose fractionation for head and neck cancer: Variation in current approaches will make standardisation difficult

    Energy Technology Data Exchange (ETDEWEB)

    Ho, Kean F. (Academic Dept. of Radiation Oncology, Univ. of Manchester, Manchester (United Kingdom)); Fowler, Jack F. (Dept. of Human Oncology and Medical Physics, Univ. of Wisconsin, Wisconsin (United States)); Sykes, Andrew J.; Yap, Beng K.; Lee, Lip W.; Slevin, Nick J. (Dept. of Clinical Oncology, Christie Hospital NHS Foundation Trust, Manchester (United Kingdom))

    2009-04-15

    Introduction. Altered fractionation has demonstrated clinical benefits compared to the conventional 2 Gy/day standard of 70 Gy. When using synchronous chemotherapy, there is uncertainty about optimum fractionation. IMRT with its potential for Simultaneous Integrated Boost (SIB) adds further to this uncertainty. This survey will examine international practice of IMRT fractionation and suggest possible reasons for diversity in approach. Material and methods. Fourteen international cancer centres were surveyed for IMRT dose/fractionation practised in each centre. Results. Twelve different types of dose fractionation were reported. Conventional 70-72 Gy (daily 2 Gy/fraction) was used in 3/14 centres with concurrent chemotherapy while 11/14 centres used altered fractionation. Two centres used >1 schedule. Reported schedules and number of centres included 6 fractions/week DAHANCA regime (3), modest hypofractionation (=2.2 Gy/fraction) (3), dose-escalated hypofractionation (=2.3 Gy/fraction) (4), hyperfractionation (1), continuous acceleration (1) and concomitant boost (1). Reasons for dose fractionation variability include (i) dose escalation; (ii) total irradiated volume; (iii) number of target volumes; (iv) synchronous systemic treatment; (v) shorter overall treatment time; (vi) resources availability; (vii) longer time on treatment couch; (viii) variable GTV margins; (ix) confidence in treatment setup; (x) late tissue toxicity and (xi) use of lower neck anterior fields. Conclusions. This variability in IMRT fractionation makes any meaningful comparison of treatment results difficult. Some standardization is needed particularly for design of multi-centre randomized clinical trials.

  15. Therapeutic Approach in the Improvement of Endothelial Dysfunction: The Current State of the Art

    Directory of Open Access Journals (Sweden)

    Miroslav Radenković

    2013-01-01

    Full Text Available The endothelium has a central role in the regulation of blood flow through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, or anticoagulant effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation. So far, the pharmacological approach in improving/reversal of endothelial dysfunction was shown to be beneficial in clinical trials that have investigated actions of different cardiovascular drugs. The aim of this paper was to summarize some of the latest clinical findings related to therapeutic possibilities for improving endothelial dysfunction in different pathological conditions. In the majority of presented clinical investigations, the assessment of improvement or reversal of endothelial dysfunction was performed through the flow-mediated dilatation measurement, and in some of those endothelial progenitor cells’ count was used for the same purpose. Still, given the fast and continuous development of this field, the evidence acquisition included the MEDLINE data base screening and the selection of articles published between 2010 and 2012.

  16. Pros and cons of current approaches for detecting peroxynitrite and their applications

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    Xingmiao Chen

    2014-03-01

    Full Text Available Peroxynitrite, a representative of reactive nitrogen species, plays important roles in the physiological and pathological processes of many oxidative stress-related diseases. It is generated from the reaction of nitric oxide (NO and superoxide (O2·– and is far more active than its precursors. Peroxynitrite can be further decomposed into other cytotoxic reactive species. Peroxynitrite and its derivatives can interact with various biomolecules such as DNA and proteins. Due to its high reactivity and short lifetime, accurate detection of peroxynitrite in biological systems is a challenge task. In the last decade, huge efforts have been made to develop reliable techniques to assess the generation of peroxynitrite in various cellular and animal experiments. There are three major approaches for peroxynitrite detection, including electrochemical sensors, detection of nitrotyrosine formation, and fluorescent probes. Particularly, progress has been made in developing novel fluorescent probes to detect peroxynitrite with relatively high sensitivity and specificity. Herein, we review the recent progress made in peroxynitrite detection methods and discuss the advantages and disadvantages of these methods. The development of these techniques will offer new opportunities for understanding the roles of peroxynitrite in the oxidative stress-related physiological and pathological conditions and provide platforms for drug discovery targeting peroxynitrite and other free radicals for therapeutic purposes.

  17. Current approaches of managing microbial diseases:focus on nanosciences technique

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Nanoscience is a fast growing research area that focuses on producing and utilizing nano-sized particles, which are measured in nanometers. Recently, nanoparticles are used in various fields. Therefore, studies on the effect of nanoparticles on microorganisms are worthy of analysis. However, using many antimicrobial agents has been avoided because of their methodical harmful effect. Hence, this review paper focuses on the use of some nanomaterials to manage microbial diseases. The discussed nanomaterials as antimicrobial agents include sliver nanoparticles, gold nanoparticles and copper nanoparticles. This review also explains the mechanisms of action of some nanotechnological products to inhibit microorganisms. There are many problems in the development of an evaluation for the effect of nanomaterials on environment. Nevertheless, the defect of the approaches used to analyze nanomaterials toxicity gives no ground for hampering the development of nanotechnologies for safety using. In order to overcome this problem, ecotoxicological studies should be extended to include the analysis of the biological safety of nanomaterials in environment and accumulate experimental data.

  18. Current Treatment Approaches to HCC with a Special Consideration to Transplantation

    Science.gov (United States)

    Perera, M. T. P. R.; Silva, M. A.

    2016-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients. PMID:27413539

  19. Current Treatment Approaches to HCC with a Special Consideration to Transplantation

    Directory of Open Access Journals (Sweden)

    N. Bhardwaj

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. The mainstay of treatment of HCC has been both resectional and transplantation surgery. It is well known that, in selected, optimized patients, hepatectomy for HCC may be an option, even in patients with underlying cirrhosis. Resectable patients with early HCC and underlying liver disease are however increasingly being considered for transplantation because of potential for better disease-free survival and resolution of underlying liver disease, although this approach is limited by the availability of donor livers, especially in resectable patients. Outcomes following liver transplantation improved dramatically for patients with HCC following the implementation of the Milan criteria in the late 1990s. Ever since, the rather restrictive nature of the Milan criteria has been challenged with good outcomes. There has also been an increase in the donor pool with marginal donors including organs retrieved following cardiac death being used. Even so, patients still continue to die while waiting for a liver transplant. In order to reduce this attrition, bridging techniques and methods for downstaging disease have evolved. Additionally new techniques for organ preservation have increased the prospect of this potentially curative procedure being available for a greater number of patients.

  20. How to measure the international development of palliative care? A critique and discussion of current approaches.

    Science.gov (United States)

    Loucka, Martin; Payne, Sheila; Brearley, Sarah

    2014-01-01

    A number of research projects have been conducted that aim to gather data on the international development of palliative care. These data are important for policy makers and palliative care advocates. The aim of this article was to provide a critical comparative analysis of methodological approaches used to assess the development and status of palliative care services and infrastructure at an international level. A selective literature review that focused on the methodological features of eight identified reports was undertaken. Reviewed reports were found to differ in adopted methodologies and provided uneven amounts of methodological information. Five major methodological limitations were identified (lack of theory, use of experts as source of information, grey literature, difficulties in ranking, and the problematic nature of data on service provision). A set of recommendations on how to deal with these issues in future research is provided. Measuring the international development of palliative care is a difficult and challenging task. The results of this study could be used to improve the validity of future research in this field. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

  1. The "Biogenetic Law" in zoology: from Ernst Haeckel's formulation to current approaches.

    Science.gov (United States)

    Olsson, Lennart; Levit, Georgy S; Hoßfeld, Uwe

    2017-06-01

    150 years ago, in 1866, Ernst Haeckel published a book in two volumes called "Generelle Morphologie der Organismen" (General Morphology of Organisms) in which he formulated his biogenetic law, famously stating that ontogeny recapitulates phylogeny. Here we describe Haeckel's original idea and follow its development in the thinking of two scientists inspired by Haeckel, Alexei Sewertzoff and Adolf Naef. Sewertzoff and Naef initially approached the problem of reformulating Haeckel's law in similar ways, and formulated comparable hypotheses at a purely descriptive level. But their theoretical viewpoints were crucially different. While Sewertzoff laid the foundations for a Darwinian evolutionary morphology and is regarded as a forerunner of the Modern Synthesis, Naef was one of the most important figures in 'idealistic morphology', usually seen as a type of anti-Darwinism. Both Naef and Sewertzoff aimed to revise Haeckel's biogenetic law and came to comparable conclusions at the empirical level. We end our review with a brief look at the present situation in which molecular data are used to test the "hour-glass model", which can be seen as a modern version of the biogenetic law.

  2. Environmental epigenomics: Current approaches to assess epigenetic effects of endocrine disrupting compounds (EDC's) on human health.

    Science.gov (United States)

    Tapia-Orozco, Natalia; Santiago-Toledo, Gerardo; Barrón, Valeria; Espinosa-García, Ana María; García-García, José Antonio; García-Arrazola, Roeb

    2017-04-01

    Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders. Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses. Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Pharmacological Treatment of Idiopathic Pulmonary Fibrosis: Current Approaches, Unsolved Issues, and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Michael Kreuter

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a devastating condition with a 5-year survival of approximately 20%. The disease primarily occurs in elderly patients. IPF is a highly heterogeneous disorder with a clinical course that varies from prolonged periods of stability to episodes of rapid deterioration. In the last decade, improved understanding of disease mechanisms along with a more precise disease definition has allowed the design and completion of a number of high-quality clinical trials. Yet, until recently, IPF was essentially an untreatable disease. Finally, pirfenidone and nintedanib, two compounds with antifibrotic properties, have consistently proven effective in reducing functional decline and disease progression in IPF. This is a major breakthrough for patients and physicians alike, but there is still a long way to go. In fact, neither pirfenidone nor nintedanib is a cure for IPF, and most patients continue to progress despite treatment. As such, comprehensive care of patients with IPF, including management of comorbidities/complications and physical debility and timely referral for palliative care or, in a small number of highly selected patients, lung transplantation, remains essential. Several agents with high potential are currently being tested and many more are ready to be evaluated in clinical trials.

  4. The Metabolism of Anticancer Drugs by the Liver: Current Approaches to the Drug Development Process.

    Science.gov (United States)

    Belka, Mariusz; Bączek, Tomasz

    2015-01-01

    The worldwide scientific community is in agreement that the activities of metabolic enzymes greatly impact the efficacies of anticancer drugs. Elucidation of the influences of these drugs on metabolism, especially that occurring in the liver, appears to be an extremely important step in the development of new anticancer drugs. Considering the continuous need to search for safe and effective chemotherapeutics, studies of the metabolism of new potent drugs are very important and should be included in the modern, innovative drug development pipeline. This article summarizes most of the current metabolic case studies involving anticancer drug development. Firstly, the impacts of diverse metabolic enzymes, particularly cytochrome P450, and the utilities of a few model in vitro enzymatic systems are described. Then, different analytical techniques, with particular emphasis on liquid chromatography- mass spectrometry detection and structural elucidation, are discussed. Finally, some computer-aided strategies for decision making in the drug design process are described. Recent advances in drug development, including microdosing, in vitro-in vivo correlation and pharmacologic audit trail, are also discussed in relation to metabolic studies.

  5. Current and previous eating practices among women recovered from anorexia nervosa: a qualitative approach

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    Mariana Dimitrov Ulian

    2013-12-01

    Full Text Available OBJECTIVE: The aim of this study was to analyze qualitatively how women, who have recovered from anorexia nervosa, perceive and describe their current eating practices, as well as the ones developed during the eating disorder period. METHODS: Seven women were interviewed individually with the objective of investigating their eating practices, transition phases and all relevant aspects that somewhat contributed to the habit-forming; experiences, feelings and perceptions related to mealtime and the influence that food has had over the present subjects' life. The interviews were analyzed by the discourse of the collective subject method. RESULTS: The results brought up the following topics: a control; b concerns and feelings; c deprivation d beauty dictatorship; e eating competence; f importance of food; g food cacophony. CONCLUSIONS: What stands out is a multiplicity of eating practices, which during the eating disorder were similar to and characterized by restriction; however, after recovery, part of the subjects seem to have developed a higher eating competence, whereas others show a practice similar to the one acquired during the anorexia nervosa, such as the difficulty in realizing when they are satisfied and a feeling of discomfort when facing social interactions.

  6. New Approach to Low-Power & Leakage Current Reduction Technique for CMOS Circuit Design

    Directory of Open Access Journals (Sweden)

    Sujata Prajapati

    2014-02-01

    Full Text Available Leakage power dissipation has become major portion of total power consumption in the integrated device and is expected to grow exponentially in the next decade as per International Technology Roadmap for Semiconductors (IRTS. This directly affects the battery operated devices as it has long idle times. Thus by scaling down the threshold voltage has tremendously increased the sub threshold leakage current thereby making the static power dissipation very high. To overcome this problem several techniques has been proposed to overcome this high leakage power dissipation. A comprehensive survey and analysis of various leakage power minimization techniques is presented in this paper. Of the available techniques, eight techniques are considered for the analysis namely, Multi Threshold CMOS (MTCMOS, Super Cut-off CMOS (SCCMOS, Forced Transistor Stacking (FTS and Sleepy Stack (SS, Sleepy keeper (SK, Dual Stack (OS, and LECTOR. From the results, it is observed that Lector techniques produces lower power dissipation than the other techniques due to the ability of power gating.

  7. Efficient Green's-function approach to finding the currents in a random resistor network

    Science.gov (United States)

    Wu, Kang; Bradley, R. Mark

    1994-02-01

    Using Green's functions, we reformulate Kirchhoff's laws for a two-component random resistor network in which a fraction p of the resistors has conductance σ- and the remainder have conductance σ+. In this Green's-function formulation (GFF), the current correlation between any two resistors in the network is explicitly taken into account. The GFF yields a linear system equivalent to Kirchhoff's laws but with a smaller number of variables. In the dilute case (pGFF. For general p, a variety of algorithms can be used to solve the GFF linear system. We present the technical details of solving the GFF linear system using the conjugate gradient method (method A). Our extensive numerical work shows that method A consistently requires fewer iterations than solving Kirchhoff's laws directly using the conjugate gradient method (method B). For example, for a 128×128 grid with p>=0.65 and σ-/σ+<=10-4, the number of iterations needed to achieve a precision of 10-10 is more than 100 times smaller in method A than in method B.

  8. Transport approach to the reconstruction of the neutrino kinematics in current oscillation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Tina; Buss, Oliver; Mosel, Ulrich [Institut fuer Theoretische Physik, Universitaet Giessen (Germany); Alvarez-Ruso, Luis [Departamento de Fisica Teorica and IFIC, Universidad de Valencia - CSIC (Spain)

    2008-07-01

    Neutrino oscillation results depend on the neutrino energy - a quantity which can not be measured directly but has to be reconstructed from the hadronic debris coming out of the neutrino-nucleus reaction inside the detector. A reliable reconstruction of the neutrino kinematics and the initial scattering process has to account for in-medium modifications and, in particular, for final state interactions inside the target nucleus. They can, e.g. through intranuclear rescattering, change particle multiplicities and also redistribute their energy. Those effects can be simulated with our fully coupled channel GiBUU transport model where the neutrino first interacts with a bound nucleon producing secondary particles which are then transported out of the nucleus. We use a relativistic formalism that incorporates recent form factor parametrizations, and apply, besides Fermi motion, full in-medium kinematics, mean-field potentials and in-medium spectral functions. In this talk, we compare the reconstructed quantities obtained within our framework to the ones obtained by the current experiments, which, as e.g. MiniBooNE, mostly rely on simple two-body kinematics. We then discuss how these uncertainties influence not only the cross section measurements but also the oscillation results.

  9. Bacterial Diseases of Bananas and Enset: Current State of Knowledge and Integrated Approaches Toward Sustainable Management

    Directory of Open Access Journals (Sweden)

    Guy Blomme

    2017-07-01

    Full Text Available Bacterial diseases of bananas and enset have not received, until recently, an equal amount of attention compared to other major threats to banana production such as the fungal diseases black leaf streak (Mycosphaerella fijiensis and Fusarium wilt (Fusarium oxysporum f. sp. cubense. However, bacteria cause significant impacts on bananas globally and management practices are not always well known or adopted by farmers. Bacterial diseases in bananas and enset can be divided into three groups: (1 Ralstonia-associated diseases (Moko/Bugtok disease caused by Ralstonia solanacearum and banana blood disease caused by R. syzygii subsp. celebesensis; (2 Xanthomonas wilt of banana and enset, caused by Xanthomonas campestris pv. musacearum and (3 Erwinia-associated diseases (bacterial head rot or tip-over disease Erwinia carotovora ssp. carotovora and E. chrysanthemi, bacterial rhizome and pseudostem wet rot (Dickeya paradisiaca formerly E. chrysanthemi pv. paradisiaca. Other bacterial diseases of less widespread importance include: bacterial wilt of abaca, Javanese vascular wilt and bacterial fingertip rot (probably caused by Ralstonia spp., unconfirmed. This review describes global distribution, symptoms, pathogenic diversity, epidemiology and the state of the art for sustainable disease management of the major bacterial wilts currently affecting banana and enset.

  10. A Review of Current Neuromorphic Approaches for Vision, Auditory, and Olfactory Sensors.

    Science.gov (United States)

    Vanarse, Anup; Osseiran, Adam; Rassau, Alexander

    2016-01-01

    Conventional vision, auditory, and olfactory sensors generate large volumes of redundant data and as a result tend to consume excessive power. To address these shortcomings, neuromorphic sensors have been developed. These sensors mimic the neuro-biological architecture of sensory organs using aVLSI (analog Very Large Scale Integration) and generate asynchronous spiking output that represents sensing information in ways that are similar to neural signals. This allows for much lower power consumption due to an ability to extract useful sensory information from sparse captured data. The foundation for research in neuromorphic sensors was laid more than two decades ago, but recent developments in understanding of biological sensing and advanced electronics, have stimulated research on sophisticated neuromorphic sensors that provide numerous advantages over conventional sensors. In this paper, we review the current state-of-the-art in neuromorphic implementation of vision, auditory, and olfactory sensors and identify key contributions across these fields. Bringing together these key contributions we suggest a future research direction for further development of the neuromorphic sensing field.

  11. Current approaches of the management of mercury poisoning: need of the hour.

    Science.gov (United States)

    Rafati-Rahimzadeh, Mehrdad; Rafati-Rahimzadeh, Mehravar; Kazemi, Sohrab; Moghadamnia, Ali Akbar

    2014-06-02

    Mercury poisoning cases have been reported in many parts of the world, resulting in many deaths every year. Mercury compounds are classified in different chemical types such as elemental, inorganic and organic forms. Long term exposure to mercury compounds from different sources e.g. water, food, soil and air lead to toxic effects on cardiovascular, pulmonary, urinary, gastrointestinal, neurological systems and skin. Mercury level can be measured in plasma, urine, feces and hair samples. Urinary concentration is a good indicator of poisoning of elemental and inorganic mercury, but organic mercury (e.g. methyl mercury) can be detected easily in feces. Gold nanoparticles (AuNPs) are a rapid, cheap and sensitive method for detection of thymine bound mercuric ions. Silver nanoparticles are used as a sensitive detector of low concentration Hg2+ ions in homogeneous aqueous solutions. Besides supportive therapy, British anti lewisite, dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA. succimer) and dimercaptopropanesulfoxid acid (DMPS) are currently used as chelating agents in mercury poisoning. Natural biologic scavengers such as algae, azolla and other aquatic plants possess the ability to uptake mercury traces from the environment.

  12. Approach for removing ghost-images in remote field eddy current testing of ferromagnetic pipes

    Science.gov (United States)

    Luo, Q. W.; Shi, Y. B.; Wang, Z. G.; Zhang, W.; Zhang, Y.

    2016-10-01

    In the non-destructive testing of ferromagnetic pipes based on remote field eddy currents, an array of sensing coils is often used to detect local defects. While testing, the image that is obtained by sensing coils exhibits a ghost-image, which originates from both the transmitter and sensing coils passing over the same defects in pipes. Ghost-images are caused by transmitters and lead to undesirable assessments of defects. In order to remove ghost-images, two pickup coils are coaxially set to each other in remote field. Due to the time delay between differential signals tested by the two pickup coils, a Wiener deconvolution filter is used to identify the artificial peaks that lead to ghost-images. Because the sensing coils and two pickup coils all receive the same signal from one transmitter, they all contain the same artificial peaks. By subtracting the artificial peak values obtained by the two pickup coils from the imaging data, the ghost-image caused by the transmitter is eliminated. Finally, a relatively highly accurate image of local defects is obtained by these sensing coils. With proposed method, there is no need to subtract the average value of the sensing coils, and it is sensitive to ringed defects.

  13. Healthcare regulatory concepts in Brazil.

    Science.gov (United States)

    Oliveira, Robson Rocha de; Elias, Paulo Eduardo Mangeon

    2012-06-01

    The healthcare regulatory concepts used in Brazilian scientific publications on healthcare management were reviewed. A typo-logical classification for regulatory concepts was developed from the most current ideas in five disciplines: life sciences, law, economics, sociology and political science. Four ideas stood out: control, balance, adaptation and direction, with greatest emphasis on the technical nature of regulation. The political nature of regulation was secondary. It was considered that dis-cussion of healthcare regulatory concepts was connected with comprehension of the role that the state plays in this sector. De-finition of the forms of state intervention is the key convergence point between the different ways of conceptualizing healthcare regulation.

  14. Current methodological approaches to determining the environmental competitiveness of products and manufacturers

    Directory of Open Access Journals (Sweden)

    S.K. Harichkov

    2013-09-01

    Full Text Available The aim of the article. The aim of the article is to develop methodological approaches to environmental assessments and enterprise competitiveness.The results of the analysis. Ensuring environmental competitiveness of producers and their products should be based on the creation of conditions for access to restricted environmentally friendly natural resources as factors of production. Environmentally friendly products may not be carried out under conditions of companies that pollute the environment. Environmental competitiveness of producers is provided based on two of its constituent factors. First it's impact on the environment: the value of economic - environmental damage inflicted terms of air emissions, discharges into water, waste disposal in water and land facilities, depletion of all natural resources in the process of extraction and application economic-environmental damage to the environment in the extraction of natural resources. The second factor is the production of environmentally viable products. Environmental competitiveness of goods is determined by environmental parameters as a commodity and its price are acceptable to consumers and appropriate to the effective demand for certain markets in certain time periods. An important condition for the formation of the competitive nature of the process is the qualitative state factors of production, which, in turn, depends on the environmental component condition, performance, environment, sustainability of natural resource base of the national economy.To environmental performance include:level (content contaminants in combustion engines of vehicles, equipment, machinery, facilities,the probability of harmful particles, gases emissions during storage, transportation, use or consumption of goods;radioactivity of the final product and others.Methods of assessing the environmental performance of the enterprise should consist of the following steps:Gathering and analyzing baseline information

  15. STUDY OF CURRENT APPROACHES FOR WEB PUBLISHING OF OPEN SCIENTIFIC DATA

    Directory of Open Access Journals (Sweden)

    D. I. Mouromtsev

    2015-11-01

    Full Text Available Subject of Study. The subject of study of this work is closely related to the development of tools and technologies for Internet publishing of open data in machine-readable formats with regard to data of universities, educational and research organizations and scientific laboratories. We analyze the trends in the publishing formats most commonly used including not only popular formats such as pdf, csv, excel, but also the Semantic Web formats such as RDF. The paper describes the way of scientific data publication in semantic formats on the example of import and convertation of the information from University database. Methods. We describe the methods of publication for scientific open data in the network consisting of a set of transformations of the original data sets to the final semantic representation. These transformation steps include data upload from a relational database, data mapping on the ontological model (schema and the generation of a set of RDF-triples corresponding to the initial database fragment. A description is given to the popular open data publishing systems, such as CKAN, VIVO, and others. OpenLink Virtuoso system is selected as the primary storage and data publication. The description of RDF data model is used as a way of presenting open data of ITMO University. Main Results. The authors have described the methods of scientific open data publication and identified their shortcomings. To demonstrate the efficiency of the proposed method of university open data publication, a software prototype has been developed available online at: http://lod.ifmo.ru/. The example of the system usage is also given. Practical Relevance. Implementation of the proposed approach will improve significantly the effect of the publication of university open data and make it available for third-party applications, such as applications for information retrieval about educational activities and research results, analysis of scientific activities in

  16. Crohn`s disease: current imaging approach; Die radiologische Abklaerung des Morbus Crohn

    Energy Technology Data Exchange (ETDEWEB)

    Schober, E.; Turetschek, K. [Klinische Abt. Roentgen fuer konservative Faecher, Universitaetsklinik fuer Radiodiagnostik, Vienna (Austria); Mostbeck, G. [Roentgeninstitut, Krankenhaus der Barmherzigen Brueder, Eisenstadt (Austria)

    1998-01-01

    Purpose: This paper discusses the role of different imaging modalities in the diagnostic work-up of Crohn`s disease (CD). Methods: We present a concept, which emphasizes different diagnostic aspects with regard to primary diagnosis, follow-up and assessment of complications of CD. The most effective imaging approach to various diagnostic problems of CD is discussed in detail. Discussion: With regard to the primary diagnosis barium studies should contribute to differentiate between CD and ulcerative colitis. Beyond that, these studies should evaluate location and extent of disease. During the follow-up bowel sonography provides staging of disease and enables the detection of complications at an early stage. CT is a valuable tool in the preoperative assessment of complications, such as fistuale and abscesses. (orig.) [Deutsch] Die vorliegende Uebersichtsarbeit soll die Rolle bildgebender radiologischer Modalitaeten bei der interdiziplinaeren Betreuung von Patienten mit Morbus Crohn (MC) diskutieren. Es wird ein Konzept vorgestellt, welches die unterschiedlichen Anforderungen an die bildgebende Diagnostik im Rahmen der Erstdiagnose, der Verlaufskontrolle sowie bei der Erfassung von Komplikationen eines MC definiert. Davon ausgehend wird versucht, fuer die einzelnen Fragestellungen die jeweils effektivste radiologische Abklaerung vorzuschlagen. Mehrere Tabellen ermoeglichen einen raschen und komprimierten Ueberblick der diagnostischen Problemstellungen im Rahmen einer schrittweisen Abklaerung der Erkrankung. Im Rahmen der Erstdiagnostik soll die radiologische Duenndarmdarstellung bei der Differentialdiagnose (MC vs. Colitis ulcerosa) hilfreich sein und das genaue Ausmass des Duenndarmbefalles eruieren. Im Rahmen der klinischen Verlaufskontrolle ist die Darmsonographie ideal zur Ueberwachung der Erkrankung sowie zur fruehen Erfassung von Komplikationen geeignet. Bei geringstem Verdacht auf eine Komplikation sollte sofort eine CT durchgefuehrt werden. (orig.)

  17. Where should Momma go? Current nursing home performance measurement strategies and a less ambitious approach

    Directory of Open Access Journals (Sweden)

    Lieberman Trudy

    2007-06-01

    Full Text Available Abstract Background Nursing home performance measurement systems are practically ubiquitous. The vast majority of these systems aspire to rank order all nursing homes based on quantitative measures of quality. However, the ability of such systems to identify homes differing in quality is hampered by the multidimensional nature of nursing homes and their residents. As a result, the authors doubt the ability of many nursing home performance systems to truly help consumers differentiate among homes providing different levels of quality. We also argue that, for consumers, performance measurement models are better at identifying problem facilities than potentially good homes. Discussion In response to these concerns we present a proposal for a less ambitious approach to nursing home performance measurement than previously used. We believe consumers can make better informed choice using a simpler system designed to pinpoint poor-quality nursing homes, rather than one designed to rank hundreds of facilities based on differences in quality-of-care indicators that are of questionable importance. The suggested performance model is based on five principles used in the development of the Consumers Union 2006 Nursing Home Quality Monitor. Summary We can best serve policy-makers and consumers by eschewing nursing home reporting systems that present information about all the facilities in a city, a state, or the nation on a website or in a report. We argue for greater modesty in our efforts and a focus on identifying only the potentially poorest or best homes. In the end, however, it is important to remember that information from any performance measurement website or report is no substitute for multiple visits to a home at different times of the day to personally assess quality.

  18. Phage therapy--history from Twort and d'Herelle through Soviet experience to current approaches.

    Science.gov (United States)

    Chanishvili, Nina

    2012-01-01

    Felix d'Herelle proposed the use of bacteriophages for the therapy of human and animal bacterial infections at the beginning of the 20th century. This approach, however, was not widely accepted in the West. After the emergence of antibiotics in 1940s, phage research was diverted to a more fundamental level. At the same time, phage therapy was widely practiced in the Soviet Union due to collaboration of Felix d'Herelle with his Georgian colleagues. The majority of the articles dedicated to this subject are from the 1930s and 1940s. The old Soviet literature indicates that phage therapy was used extensively to treat a wide range of bacterial infections in the areas of dermatology (Beridze, 1938), ophthalmology (Rodigina, 1938), urology (Tsulukidze, 1938), stomatology (Ruchko and Tretyak, 1936), pediatrics (Alexandrova et al., 1935; Lurie, 1938), otolaryngology (Ermolieva, 1939), and surgery (Tsulukidze, 1940, 1941). These articles were published in Russian and thus were not readily available to Western scientists. The Western skepticism toward phage therapy itself was again followed by renewed interest and reappraisal, mainly due to the emergence of drug-resistant bacteria. Often the experiments described in the old Soviet articles were not designed properly: the use of placebos and the coding of preparations were absent from most of the studies, number of patients in the experimental and control groups was unequal or missing, sometimes no control groups were used at all, or patients treated previously unsuccessfully with antibiotics were employed as an experimental group and as control. The results obtained and the efficiency of phage prophylaxis were estimated by comparing with results obtained in previous years. In most publications, phage titers and descriptions of methods used for evaluation of the results are not specified. Nevertheless, past experience indicates some effectiveness of phage therapy and prophylaxis. Therefore, these clinical results should not

  19. Impact of a board-game approach on current smokers: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Khazaal Yasser

    2013-01-01

    Full Text Available Abstract Background The main objective of our study was to assess the impact of a board game on smoking status and smoking-related variables in current smokers. To accomplish this objective, we conducted a randomized controlled trial comparing the game group with a psychoeducation group and a waiting-list control group. Methods The following measures were performed at participant inclusion, as well as after a 2-week and a 3-month follow-up period: “Attitudes Towards Smoking Scale” (ATS-18, “Smoking Self-Efficacy Questionnaire” (SEQ-12, “Attitudes Towards Nicotine Replacement Therapy” scale (ANRT-12, number of cigarettes smoked per day, stages of change, quit attempts, and smoking status. Furthermore, participants were assessed for concurrent psychiatric disorders and for the severity of nicotine dependence with the Fagerström Test for Nicotine Dependence (FTND. Results A time × group effect was observed for subscales of the ANRT-12, ATS-18 and SEQ-12, as well as for the number of cigarettes smoked per day. At three months follow-up, compared to the participants allocated to the waiting list group, those on Pick-Klop group were less likely to remain smoker. Outcomes at 3 months were not predicted by gender, age, FTND, stage of change, or psychiatric disorders at inclusion. Conclusions The board game seems to be a good option for smokers. The game led to improvements in variables known to predict quitting in smokers. Furthermore, it increased smoking-cessation rates at 3-months follow-up. The game is also an interesting alternative for smokers in the precontemplation stage.

  20. Review of Current Experience on Intermediate Heat Exchanger (IHX) and A Recommended Code Approach

    Energy Technology Data Exchange (ETDEWEB)

    Duane Spencer; Kevin McCoy

    2010-02-02

    The purpose of the ASME/DOE Gen IV Task 7 Part I is to review the current experience on various high temperature reactor intermediate heat exchanger (IHX) concepts. There are several different IHX concepts that could be envisioned for HTR/VHTR applications in a range of temperature from 850C to 950C. The concepts that will be primarily discussed herein are: (1) Tubular Helical Coil Heat Exchanger (THCHE); (2) Plate-Stamped Heat Exchanger (PSHE); (3) Plate-Fin Heat Exchanger (PFHE); and (4) Plate-Machined Heat Exchanger (PMHE). The primary coolant of the NGNP is potentially subject to radioactive contamination by the core as well as contamination from the secondary loop fluid. To isolate the radioactivity to minimize radiation doses to personnel, and protect the primary circuit from contamination, intermediate heat exchangers (IHXs) have been proposed as a means for separating the primary circuit of the NGNP (Next Generation Nuclear Plant) or other process heat application from the remainder of the plant. This task will first review the different concepts of IHX that could be envisioned for HTR/VHTR applications in a range of temperature from 850 to 950 C. This will cover shell-and-tube and compact designs (including the platefin concept). The review will then discuss the maturity of the concepts in terms of design, fabricability and component testing (or feedback from experience when applicable). Particular attention will be paid to the feasibility of developing the IHX concepts for the NGNP with operation expected in 2018-2021. This report will also discuss material candidates for IHX applications and will discuss specific issues that will have to be addressed in the context of the HTR design (thermal aging, corrosion, creep, creep-fatigue, etc). Particular attention will be paid to specific issues associated with operation at the upper end of the creep regime.

  1. Management of Neuropsychiatric Systemic Lupus Erythematosus: Current Approaches and Future Perspectives.

    Science.gov (United States)

    Magro-Checa, César; Zirkzee, Elisabeth J; Huizinga, Tom W; Steup-Beekman, Gerda M

    2016-03-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is a generic definition referring to a series of neurological and psychiatric symptoms directly related to systemic lupus erythematosus (SLE). NPSLE includes heterogeneous and rare neuropsychiatric (NP) manifestations involving both the central and peripheral nervous system. Due to the lack of a gold standard, the attribution of NP symptoms to SLE represents a clinical challenge that obligates the strict exclusion of any other potential cause. In the acute setting, management of these patients does not differ from other non-SLE subjects presenting with the same NP manifestation. Afterwards, an individualized therapeutic strategy, depending on the presenting manifestation and severity of symptoms, must be started. Clinical trials in NPSLE are scarce and most of the data are extracted from case series and case reports. High-dose glucocorticoids and intravenous cyclophosphamide remain the cornerstone for patients with severe symptoms that are thought to reflect inflammation or an underlying autoimmune process. Rituximab, intravenous immunoglobulins, or plasmapheresis may be used if response is not achieved. When patients present with mild to moderate NP manifestations, or when maintenance therapy is warranted, azathioprine and mycophenolate may be considered. When symptoms are thought to reflect a thrombotic underlying process, anticoagulation and antiplatelet agents are the mainstay of therapy, especially if antiphospholipid antibodies or antiphospholipid syndrome are present. Recent trials on SLE using new biologicals, based on newly understood SLE mechanisms, have shown promising results. Based on what we currently know about its pathogenesis, it is tempting to speculate how these new therapies may affect the management of NPSLE patients. This article provides a comprehensive and critical review of the literature on the epidemiology, pathophysiology, diagnosis, and management of NPSLE. We describe the most

  2. Impact of a board-game approach on current smokers: a randomized controlled trial.

    Science.gov (United States)

    Khazaal, Yasser; Chatton, Anne; Prezzemolo, Roberto; Zebouni, Fadi; Edel, Yves; Jacquet, Johan; Ruggeri, Ornella; Burnens, Emilie; Monney, Grégoire; Protti, Anne-Sylvie; Etter, Jean-François; Khan, Riaz; Cornuz, Jacques; Zullino, Daniele

    2013-01-17

    The main objective of our study was to assess the impact of a board game on smoking status and smoking-related variables in current smokers. To accomplish this objective, we conducted a randomized controlled trial comparing the game group with a psychoeducation group and a waiting-list control group. The following measures were performed at participant inclusion, as well as after a 2-week and a 3-month follow-up period: "Attitudes Towards Smoking Scale" (ATS-18), "Smoking Self-Efficacy Questionnaire" (SEQ-12), "Attitudes Towards Nicotine Replacement Therapy" scale (ANRT-12), number of cigarettes smoked per day, stages of change, quit attempts, and smoking status. Furthermore, participants were assessed for concurrent psychiatric disorders and for the severity of nicotine dependence with the Fagerström Test for Nicotine Dependence (FTND). A time × group effect was observed for subscales of the ANRT-12, ATS-18 and SEQ-12, as well as for the number of cigarettes smoked per day. At three months follow-up, compared to the participants allocated to the waiting list group, those on Pick-Klop group were less likely to remain smoker.Outcomes at 3 months were not predicted by gender, age, FTND, stage of change, or psychiatric disorders at inclusion. The board game seems to be a good option for smokers. The game led to improvements in variables known to predict quitting in smokers. Furthermore, it increased smoking-cessation rates at 3-months follow-up. The game is also an interesting alternative for smokers in the precontemplation stage.

  3. The crucial role of habits in energy consumption: an evolutionary approach on changing current patterns

    Energy Technology Data Exchange (ETDEWEB)

    Marechal, Kevin (Centre for Economic and Social Studies on the Environment (CESSE), Univ. Libre de Bruxelles, Univ. d' Europe (Belgium)). e-mail: kevin.marechal@ulb.ac.be

    2009-07-01

    A substantial body of literature has shown that our behaviour is often guided by habits. The existence of habits - not fully conscious forms of behaviour - is important as it contradicts rational choice theory. Their presence thus calls for the setting of new instruments as they make it unlikely that consumers be capable of exercising control over their energy consumption in reaction to given incentives. This is further increased in the evolutionary perspective where the current carbon-based Socio-Technical System constraints and shapes consumers' choices through structural forces. Habits being potentially 'counterintentional', they may explain the 'efficiency paradox' in energy as well as the continued increase of energy consumption despite the rising environmental awareness among the population. Policies aiming at reducing energy consumption should thus specifically address the performance context of habits. For instance, targeting new residents has proven to be more effective given that their preceding habits have been disturbed. The results of our empirical analysis confirm this idea by showing how a change of context makes people more receptive to a proposed measure. Our analysis of the role played by habits also suggests that individuals do not consider the need to change existing habits as an obstacle even though this is contradicted implicitly in the answers they provided to open questions. This 'unconsciousness' is one of the most delicate features of habits and it should thus be accounted for when designing measures. Given the other characteristics of habits, the joint use of feedbacks and commitment strategies appears promising.

  4. Long-term catheterization: current approaches in the diagnosis and treatment of port-related infections

    Directory of Open Access Journals (Sweden)

    Bustos C

    2014-02-01

    Full Text Available Cesar Bustos,1 Aitziber Aguinaga,1 Francisco Carmona-Torre,2 Jose Luis Del Pozo1,3 1Department of Clinical Microbiology, 2Department of Internal Medicine, 3Division of Infectious Diseases, Clinica Universidad de Navarra, Pamplona, Spain Abstract: Since the first description in 1982, totally implanted venous access ports have progressively improved patients' quality of life and medical assistance when a medical condition requires the use of long-term venous access. Currently, they are part of the standard medical care for oncohematologic patients. However, apart from mechanical and thrombotic complications, there are also complications associated with biofilm development inside the catheters. These biofilms increase the cost of medical assistance and extend hospitalization. The most frequently involved micro-organisms in these infections are gram-positive cocci. Many efforts have been made to understand biofilm formation within the lumen catheters, and to resolve catheter-related infection once it has been established. Apart from systemic antibiotic treatment, the use of local catheter treatment (ie, antibiotic lock technique is widely employed. Many different antimicrobial options have been tested, with different outcomes, in clinical and in in vitro assays. The stability of antibiotic concentration in the lock solution once instilled inside the catheter lumen remains unresolved. To prevent infection, it is mandatory to perform hand hygiene before catheter insertion and manipulation, and to disinfect catheter hubs, connectors, and injection ports before accessing the catheter. At present, there are still unresolved questions regarding the best antimicrobial agent for catheter-related bloodstream infection treatment and the duration of concentration stability of the antibiotic solution within the lumen of the port. Keywords: catheter-related infection, bacteremia, biofilm

  5. Using text mining for study identification in systematic reviews: a systematic review of current approaches.

    Science.gov (United States)

    O'Mara-Eves, Alison; Thomas, James; McNaught, John; Miwa, Makoto; Ananiadou, Sophia

    2015-01-14

    The large and growing number of published studies, and their increasing rate of publication, makes the task of identifying relevant studies in an unbiased way for inclusion in systematic reviews both complex and time consuming. Text mining has been offered as a potential solution: through automating some of the screening process, reviewer time can be saved. The evidence base around the use of text mining for screening has not yet been pulled together systematically; this systematic review fills that research gap. Focusing mainly on non-technical issues, the review aims to increase awareness of the potential of these technologies and promote further collaborative research between the computer science and systematic review communities. Five research questions led our review: what is the state of the evidence base; how has workload reduction been evaluated; what are the purposes of semi-automation and how effective are they; how have key contextual problems of applying text mining to the systematic review field been addressed; and what challenges to implementation have emerged? We answered these questions using standard systematic review methods: systematic and exhaustive searching, quality-assured data extraction and a narrative synthesis to synthesise findings. The evidence base is active and diverse; there is almost no replication between studies or collaboration between research teams and, whilst it is difficult to establish any overall conclusions about best approaches, it is clear that efficiencies and reductions in workload are potentially achievable. On the whole, most suggested that a saving in workload of between 30% and 70% might be possible, though sometimes the saving in workload is accompanied by the loss of 5% of relevant studies (i.e. a 95% recall). Using text mining to prioritise the order in which items are screened should be considered safe and ready for use in 'live' reviews. The use of text mining as a 'second screener' may also be used cautiously

  6. Estimation of seismic quality factor: Artificial neural networks and current approaches

    Science.gov (United States)

    Yıldırım, Eray; Saatçılar, Ruhi; Ergintav, Semih

    2017-01-01

    The aims of this study are to estimate soil attenuation using alternatives to traditional methods, to compare results of using these methods, and to examine soil properties using the estimated results. The performances of all methods, amplitude decay, spectral ratio, Wiener filter, and artificial neural network (ANN) methods, are examined on field and synthetic data with noise and without noise. High-resolution seismic reflection field data from Yeniköy (Arnavutköy, İstanbul) was used as field data, and 424 estimations of Q values were made for each method (1,696 total). While statistical tests on synthetic and field data are quite close to the Q value estimation results of ANN, Wiener filter, and spectral ratio methods, the amplitude decay methods showed a higher estimation error. According to previous geological and geophysical studies in this area, the soil is water-saturated, quite weak, consisting of clay and sandy units, and, because of current and past landslides in the study area and its vicinity, researchers reported heterogeneity in the soil. Under the same physical conditions, Q value calculated on field data can be expected to be 7.9 and 13.6. ANN models with various structures, training algorithm, input, and number of neurons are investigated. A total of 480 ANN models were generated consisting of 60 models for noise-free synthetic data, 360 models for different noise content synthetic data and 60 models to apply to the data collected in the field. The models were tested to determine the most appropriate structure and training algorithm. In the final ANN, the input vectors consisted of the difference of the width, energy, and distance of seismic traces, and the output was Q value. Success rate of both ANN methods with noise-free and noisy synthetic data were higher than the other three methods. Also according to the statistical tests on estimated Q value from field data, the method showed results that are more suitable. The Q value can be estimated

  7. The North Atlantic Data Portal: A Current Approach To Improving Marine Geophysical Data Discovery And Access

    Science.gov (United States)

    Jencks, J. H.; Cartwright, J.; Varner, J. D.

    2016-12-01

    Exploring, understanding, and managing the global oceans are a challenge when hydrographic maps are available for only 5% of the world's oceans. Seafloor mapping is expensive and most government and academic budgets continue to tighten. The first step for any mapping program, before setting out to map uncharted waters, should be to identify if data currently exist in the area of interest. There are many reasons why this seemingly simple suggestion is easier said than done.While certain datasets are accessible online (e.g., NOAA's NCEI, EMODnet, IHO-DCDB), many are not. In some cases, data that are publicly available are difficult to discover and access. No single agency can successfully resolve the complex and pressing demands of ocean and coastal mapping and the associated data stewardship. The National Oceanic and Atmospheric Administration (NOAA) is an active participant in numerous campaign mapping projects whose goals are to carry out coordinated and comprehensive ocean mapping efforts. One of these international programs is an outcome of the Galway Statement on Atlantic Ocean Cooperation signed by the European Union, Canada, and the United States in 2013. At NOAA's National Centers for Environmental Information (NCEI), resources are focused on ensuring the security and widespread availability of the Nation's scientific marine geophysical data through long-term stewardship. NCEI draws on a variety of software technologies and adheres to international standards to meet this challenge. The result is a geospatial framework built on spatially-enabled databases, standards-based web services, and International Standards Organization (ISO) metadata. Through the use of industry standards, the services are constructed such that they can be combined and re-used in a variety of contexts. For example, users may leverage the services in desktop analysis tools, web applications created by the hosting organizations (e.g. the North Atlantic Data Portal), or in custom

  8. Bioprinting of artificial blood vessels: current approaches towards a demanding goal.

    Science.gov (United States)

    Hoch, Eva; Tovar, Günter E M; Borchers, Kirsten

    2014-11-01

    Free-form fabrication techniques, often referred to as '3D printing', are currently tested with regard to the processing of biological and biocompatible materials in general and for fabrication of vessel-like structures in particular. Such computer-controlled methods assemble 3D objects by layer-wise deposition or layer-wise cross-linking of materials. They use, for example, nozzle-based deposition of hydrogels and cells, drop-on-demand inkjet-printing of cell suspensions with subsequent cross-linking, layer-by-layer cross-linking of synthetic or biological polymers by selective irradiation with light and even laser-induced deposition of single cells. The need of vessel-like structures has become increasingly crucial for the supply of encapsulated cells for 3D tissue engineering, or even with regard to future application such as vascular grafts. The anticipated potential of providing tubes with tailored branching geometries made of biocompatible or biological materials pushes future visions of patient-specific vascularized tissue substitutions, tissue-engineered blood vessels and bio-based vascular grafts. We review here the early attempts of bringing together innovative free-form manufacturing processes with bio-based and biodegradable materials. The presented studies provide many important proofs of concepts such as the possibility to integrate viable cells into computer-controlled processes and the feasibility of supplying cells in a hydrogel matrix by generation of a network of perfused channels. Several impressive results in the generation of complex shapes and high-aspect-ratio tubular structures demonstrate the potential of additive assembly methods. Yet, it also becomes obvious that there remain major challenges to simultaneously match all material requirements in terms of biological functions (cell function supporting properties), physicochemical functions (mechanical properties of the printed material) and process-related (viscosity, cross

  9. 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.

  10. System approaches to study root hairs as a single cell plant model: current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Md Shakhawat eHossain

    2015-05-01

    Full Text Available Our current understanding of plant functional genomics derives primarily from measurements of gene, protein and/or metabolite levels averaged over the whole plant or multicellular tissues. These approaches risk diluting the response of specific cells that might respond strongly to the treatment but whose signal is diluted by the larger proportion of non-responding cells. For example, if a gene is expressed at a low level, does this mean that it is indeed lowly expressed or is it highly expressed, but only in a few cells? In order to avoid these issues, we adopted the soybean root hair cell, derived from a single, differentiated root epidermal cell, as a single-cell model for functional genomics. Root hair cells are intrinsically interesting since they are major conduits for root water and nutrient uptake and are also the preferred site of infection by nitrogen-fixing rhizobium bacteria. Although a variety of other approaches have been used to study single plant cells or single cell types, the root hair system is perhaps unique in allowing application of the full repertoire of functional genomic and biochemical approaches. In this mini review, we summarize our published work and place this within the broader context of root biology, with a significant focus on understanding the initial events in the soybean-rhizobium interaction.

  11. Rotor Current Control of DFIG for Improving Fault Ride - Through Using a Novel Sliding Mode Control Approach

    Science.gov (United States)

    Cai, Guowei; Liu, Cheng; Yang, Deyou

    2013-11-01

    The doubly fed induction generators (DFIG) have been recognized as the dominant technology used in wind power generation systems with the rapid development of wind power. However, continuous operation of DFIG may cause a serious wind turbine generators tripping accident, due to destructive over-current in the rotor winding which is caused by the power system fault or inefficient fault ride-through (FRT) strategy. A new rotor current control scheme in the rotor-side converter (RSC) ispresented to enhance FRT capacities of grid-connected DFIG. Due to the strongly nonlinear nature of DFIG and insensitive to DFIG parameter's variations, a novel sliding mode controller was designed. The controller combines extended state observer (ESO) with sliding model variable structure control theory. The simulation is carried out to verify the effectiveness of the proposed control approach under various types of grid disturbances. It is shown that the proposed controller provides enhanced transient features than the classic proportional-integral control. The proposed control method can effectively reduce over-current in the RSC, and the transient pulse value of electromagnetic torque is too large under power grid fault.

  12. Electrophysiological and Behavioral Effects of Combined Transcranial Direct Current Stimulation and Alcohol Approach Bias Retraining in Hazardous Drinkers.

    Science.gov (United States)

    den Uyl, Tess E; Gladwin, Thomas E; Wiers, Reinout W

    2016-10-01

    Cognitive bias modification (CBM) can be used to retrain automatic approach tendencies for alcohol. We investigated whether changing cortical excitability with transcranial direct current stimulation (tDCS) could enhance CBM effects in hazardous drinkers. We also studied the underlying mechanisms by including behavioral (craving, implicit associations, approach tendencies) and electrophysiological (event-related potentials) measurements. The analytical sample consisted of 78 hazardous drinkers (Alcohol Use Disorders Identification Test >8) randomly assigned to 4 conditions in a 2-by-2 factorial design (control/active CBM and sham/active tDCS). The intervention consisted of 3 sessions of CBM, specifically alcohol approach bias retraining, combined with 15 minutes 1 mA tDCS over the left dorsolateral prefrontal cortex. There was a pre- and postassessment before and after the intervention that included experimental tasks (Approach Avoidance Task, Implicit Association Task) and an electroencephalogram with an oddball and cue-reactivity task. tDCS decreased cue-induced craving (but not overall craving) on postassessment. CBM did not induce an avoidance bias during assessment. During the training, active and control-CBM only differed in bias score during the first session. We found no enhancement effects of tDCS on CBM. Electrophysiological data showed no clear effects of active tDCS or CBM on the P300. There were no electrophysiological or behavioral effects of repeated CBM and/or tDCS, except for an effect of tDCS on craving. Applied in these specific ways these techniques appear to have limited effects in a hazardous drinking population. Copyright © 2016 by the Research Society on Alcoholism.

  13. General approach for the determination of the magneto-angular dependence of the critical current of YBCO coated conductors

    Science.gov (United States)

    Zhang, X.; Zhong, Z.; Ruiz, H. S.; Geng, J.; Coombs, T. A.

    2017-02-01

    The physical understanding and numerical modelling of superconducting devices which exploit the high performance of second generation high temperature superconducting tapes (2G-HTS), is commonly hindered by the lack of accurate functions which allow the consideration of the in-field dependence of the critical current. This is true regardless of the manufacturer of the superconducting tape. In this paper, we present a general approach for determining a unified function I c(B, θ), ultimately capable of describing the magneto-angular dependence of the in-field critical current of commercial 2G-HTS tapes in the Lorentz configuration. Five widely different superconducting tapes, provided by three different manufacturers, have been tested in a liquid nitrogen bath and external magnetic fields of up to 400 mT. The critical current was recorded at 90 different orientations of the magnetic field ranging from θ = 0°, i.e., with B aligned with the crystallographic ab-planes of the YBCO layer, towards ±90°, i.e., with B perpendicular to the wider surfaces of the 2G-HTS tape. The whole set of experimental data has been analysed using a novel multi-objective model capable of predicting a sole function I c(B, θ). This allows an accurate validation of the experimental data regardless of the fabrication differences and widths of the superconducting tapes. It is shown that, in spite of the wide set of differences between the fabrication and composition of the considered tapes, at liquid nitrogen temperature the magneto-angular dependence of the in-field critical current of YBCO-based 2G-HTS tapes, can be described by a universal function I c(f(B), θ), with a power law field dependence dominated by the Kim’s factor B/B 0, and an angular dependence moderated by the electron mass anisotropy ratio of the YBCO layer.

  14. Current approaches to treatments for schizophrenia spectrum disorders, part II: psychosocial interventions and patient-focused perspectives in psychiatric care

    Directory of Open Access Journals (Sweden)

    Chien WT

    2013-09-01

    functioning, and/or relapse rate. However, the comparative effects between these five approaches have not been well studied; thus, we are not able to clearly understand the superiority of any of these interventions. With the exception of patient relapse, the longer-term (eg, >2 years effects of these approaches on most psychosocial outcomes are not well-established among these patients. Despite the fact that patients' perspectives on treatment and care have been increasingly concerned, not many studies have evaluated the effect of interventions on this perspective, and where they did, the findings were inconclusive. To conclude, current approaches to psychosocial interventions for schizophrenia have their strengths and weaknesses, particularly indicating limited evidence on long-term effects. To improve the longer-term outcomes of people with schizophrenia, future treatment strategies should focus on risk identification, early intervention, person-focused therapy, partnership with family caregivers, and the integration of evidence-based psychosocial interventions into existing services. Keywords: schizophrenia, psychosocial intervention, patient-focused perspectives

  15. Current approaches to treatments for schizophrenia spectrum disorders, part II: psychosocial interventions and patient-focused perspectives in psychiatric care.

    Science.gov (United States)

    Chien, Wai Tong; Leung, Sau Fong; Yeung, Frederick Kk; Wong, Wai Kit

    2013-01-01

    exception of patient relapse, the longer-term (eg, >2 years) effects of these approaches on most psychosocial outcomes are not well-established among these patients. Despite the fact that patients' perspectives on treatment and care have been increasingly concerned, not many studies have evaluated the effect of interventions on this perspective, and where they did, the findings were inconclusive. To conclude, current approaches to psychosocial interventions for schizophrenia have their strengths and weaknesses, particularly indicating limited evidence on long-term effects. To improve the longer-term outcomes of people with schizophrenia, future treatment strategies should focus on risk identification, early intervention, person-focused therapy, partnership with family caregivers, and the integration of evidence-based psychosocial interventions into existing services.

  16. Economic evaluations of pharmacogenetic approaches in infectious diseases: a review of current approaches and evaluation of critical aspects affecting their quality

    Directory of Open Access Journals (Sweden)

    Paolo Meoni

    2013-11-01

    Full Text Available Pharmacogenetics holds great potential for improving the effectiveness of treatment modalities in infectious diseases by taking into account the genetic determinants of both the host and infectious agents’ individuality. Better utilization of resources and improved therapeutic efficiency are the expected outcomes of personalized medicine using pharmacogenetic and pharmacogenomics information made available by technological advances. However, there has been growing concern in the clinical community regarding the evaluation of the true benefits of these approaches. This perception is partly due to the limited number and perceived poor quality of economic evaluations in this field, and initiatives aimed at harmonizing and communicating strategies improving the quality of these studies and their acceptance by the clinical community are greatly needed. This paper reviews current literature of economic evaluations of pharmacogenetics interventions guiding pharmacotherapy in infectious diseases. PubMed and the NHS Centre for Reviews and Dissemination databases were searched using a combination of five broad research terms related to pharmacogenetic approaches, and papers relative to economic evaluations of pharmacogenetic interventions in infectious diseases retained for further analysis. Using these criteria, a total of 14 papers were included in this review. The area of economic evaluation of pharmacogenetic interventions in infectious diseases remains understudied and would benefit from greater harmonization. The main weaknesses of evaluations reviewed in this paper seem to be represented by poor evidence of pharmacogenetic marker validation, inconsistencies in the selection of costs and utility included in the economic models and the choice of sensitivity analysis. All these factors limit the overall transparency of the studies, greater acceptance of their results and applicability to diverse and possibly resourcelimited environments where these

  17. Reforming Financial Regulatory System in China after the Stock Market Turbulence:Problems and the Responses

    Institute of Scientific and Technical Information of China (English)

    Chen Zhenyun

    2016-01-01

    In an age when modern financial companies have become more and more complex,and if not adequately supervised,they can cause lethal harm to the stability of one’ s financial system. In post-financial crisis era,major developed economies have apparently rein-forced the function of the central bank in a country’ s financial regulatory system. Over the past several years,China has witnessed the huge changes in the financial sector but the financial regulatory framework remains the same as before. The Chinese stock market crash that began on June 12 2015 has urged the domestic regulators to restructure its financial regulatory sys-tem. The issue that which modal China should follow has perplexed Chinese policymakers. The governor of People’ s Bank of China,Zhou Xiaochuan,clearly responded to the problem concerning the current financial regulatory system, and indicated that Chinese regulators and policymakers had still studied the regulatory approach China would adopt during the press of People’s Congress of 2016. This paper reviews the development of China’s banking regulato-ry system,points out the deficiencies in its original system and analyzes the recent trends of fi-nancial regulatory reform in UK to learn the international experience for further reform re-garding financial regulatory system in China.

  18. Review of the History and Current Status of Cell-Transplant Approaches for the Management of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Mary J. Eaton

    2012-01-01

    Full Text Available Treatment of sensory neuropathies, whether inherited or caused by trauma, the progress of diabetes, or other disease states, are among the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord would be the logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the transplant of cells or a cell line to treat human disease. The history of the research and development of useful cell-transplant-based approaches offers an understanding of the advantages and problems associated with these technologies, but as an adjuvant or replacement for current pharmacological treatments, cell therapy is a likely near future clinical tool for improved health care.

  19. Current approaches to improve the anticancer chemotherapy with alkylating agents: state of the problem in world and Ukraine.

    Directory of Open Access Journals (Sweden)

    Iatsyshyna A. P.

    2012-01-01

    Full Text Available Alkylating agents are frequently used in many established anticancer chemotherapies. They alkylate the genomic DNA at various sites. Alkylation of the guanine at the O6-position is cytotoxic, it has the strongest mutagenic potential, as well as can cause the tumor development. Alkyl groups at the O6-position of guanine are removed by the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT. The effectiveness of alkylating chemotherapy is limited by MGMT in cancer cells and adverse toxic side effects in normal cells. Different approaches consisting in the modulation of the MGMT expression and activity are under development now to improve the cancer chemotherapy. They include two main directions, in particular, the increase in chemosensitivity of cancer cells to alkylating drugs and the protection of normal cells from the toxic side effects of chemotherapy. This review is focused on current attempts to improve the alkylating chemotherapy of malignant tumours worldwide and state of the issue in Ukraine

  20. A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs) and Future Perspectives

    Science.gov (United States)

    D’Amico, Emanuele; Patti, Francesco; Zanghì, Aurora; Zappia, Mario

    2016-01-01

    Using the term of progressive multiple sclerosis (PMS), we considered a combined population of persons with secondary progressive MS (SPMS) and primary progressive MS (PPMS). These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future. PMID:27763513

  1. Neurocognitive and Social Cognitive Approaches for Improving Functional Outcome in Early Psychosis: Theoretical Considerations and Current State of Evidence

    Directory of Open Access Journals (Sweden)

    Cali F. Bartholomeusz

    2012-01-01

    Full Text Available Improving functional outcome, in addition to alleviating psychotic symptoms, is now a major treatment objective in schizophrenia research. Given the large body of evidence suggesting pharmacological treatments generally have minimal effects on indices of functioning, research has turned to psychosocial rehabilitation programs. Among these, neurocognitive and social cognitive interventions are at the forefront of this field and are argued to target core deficits inherent to the schizophrenia illness. However, to date, research trials have primarily focused on chronic schizophrenia populations, neglecting the early psychosis groups who are often as severely impaired in social and occupational functioning. This theoretical paper will outline the rationale for investigating adjunctive cognitive-based interventions in the early phases of psychotic illness, critically examine the current approach strategies used in these interventions, and assess the evidence supporting certain training programs for improving functional outcome in early psychosis. Potential pathways for future research will be discussed.

  2. A Personalized Approach in Progressive Multiple Sclerosis: The Current Status of Disease Modifying Therapies (DMTs and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Emanuele D’Amico

    2016-10-01

    Full Text Available Using the term of progressive multiple sclerosis (PMS, we considered a combined population of persons with secondary progressive MS (SPMS and primary progressive MS (PPMS. These forms of MS cannot be challenged with efficacy by the licensed therapy. In the last years, several measures of risk estimation were developed for predicting clinical course in MS, but none is specific for the PMS forms. Personalized medicine is a therapeutic approach, based on identifying what might be the best therapy for an individual patient, taking into account the risk profile. We need to achieve more accurate estimates of useful predictors in PMS, including unconventional and qualitative markers which are not yet currently available or practicable routine diagnostics. The evaluation of an individual patient is based on the profile of disease activity.Within the neurology field, PMS is one of the fastest-moving going into the future.

  3. Current Perspectives on Novel Drug Delivery Systems and Approaches for Management of Cervical Cancer: A Comprehensive Review.

    Science.gov (United States)

    Hani, Umme; Osmani, Riyaz Ali M; Bhosale, Rohit R; Shivakumar, Hosakote Gurumallappa; Kulkarni, Parthasarathi K

    2016-01-01

    Cervical cancer is uterine cervix carcinoma, the second deadly cancer and has a high incidence and mortality rate. In the developing world conventional treatment strategies such as surgical intervention and chemoradiotherapy are less widely available. Currently cancer research focuses on improving treatment of cervical cancer using various therapies such as gene therapy, recombinant protein therapy, photodynamic therapy, photothermal therapy and delivery of chemotherapeutic agents using nanoparticles, hydrogel and liposomal based delivery systems and also localized delivery systems which exist in a variety of forms such as intravaginal rings, intravaginal patches, intravaginal films, etc. in order to improve the drug delivery in a controlled manner to the diseased site thereby reducing systemic side effects. The present review encloses existing diverse delivery systems and approaches intended for treatment of cervical cancer.

  4. Problems associated with direct-to-consumer advertising (DTCA) of restricted, implantable medical devices: should the current regulatory approach be changed?

    Science.gov (United States)

    Patsner, Bruce

    2009-01-01

    Advertising and promotion of Food and Drug Administration (FDA)-approved medical products has been one of the most controversial and bitterly litigated areas in food and drug law in the U.S. for more than a decade. Hundreds of newspaper articles and dozens of law review articles have been written on the subject of the risks and benefits of direct to consumer advertising (DTCA) of medical products, but until very recently virtually all of this literature and commentary has focused exclusively on prescription and over-the-counter drugs. Even when FDA has sponsored public hearings to address the issue of DTCA of all medical products, as it did in 2005, review of the content of the speakers' presentations reveals that almost all of the subject matter, nearly all of the data, and the majority of comments concerned DTCA of drugs. Not a single law review article has ever been devoted exclusively to the subject of advertising and promotion of medical devices to consumers--until now.

  5. AIDS-Related Non-Hodgkin's Lymphoma in Sub-Saharan Africa: Current Status and Realities of Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Peter M. Mwamba

    2012-01-01

    Full Text Available Today AIDS-related non-Hodgkin's lymphoma (AR-NHL is a significant cause of morbidity and mortality in HIV-infected patients the world over, and especially in sub-Saharan Africa. While the overall incidence of AR-NHL since the emergence of combination antiretroviral therapy (cART era has declined, the occurrence of this disease appears to have stabilized. In regions where access to cART is challenging, the impact on disease incidence is less clear. In the resource-rich environment it is clinically recognized that it is no longer appropriate to consider AR-NHL as a single disease entity and rather treatment of AIDS lymphoma needs to be tailored to lymphoma subtype. While intensive therapeutic strategies in the resource-rich world are clearly improving outcome, in AIDS epicenters of the world and especially in sub-Saharan Africa there is a paucity of data on treatment and outcomes. In fact, only one prospective study of dose-modified oral chemotherapy and limited retrospective studies with sufficient details provide a window into the natural history and clinical management of this disease. The scarcities and challenges of treatment in this setting provide a backdrop to review the current status and realities of the therapeutic approach to AR-NHL in sub-Saharan Africa. More pragmatic and risk-adapted therapeutic approaches are needed.

  6. Current challenges and innovative approaches in the development of peripheral regions in Bulgaria: The case of Ivaylovgrad municipality

    Directory of Open Access Journals (Sweden)

    Dimitrova Elena

    2010-01-01

    Full Text Available The paper approaches territorial cohesion in SEE from the perspective of social equity with regard to the opportunity to choose to live in one’s native place without compromising the quality of life. It is interested in border areas - both physical and virtual; in real life situations as meeting points of theories and policies influencing human lives; and in the emerging challenges there that often make us question once and again our concepts and actions as experts. Based on the Bulgarian case-study analysis, the authors discuss the effectiveness and current challenges of real-life implementation of EU and national policies aimed at sustainable development of peripheral regions. The rural peripheral municipality of Ivaylovgrad is an indicative case study for the ongoing processes in the peripheral regions of Bulgaria and the efforts to overcome a continuing loss of working places, services, markets and further isolation from the rest of the country since the early 1990s. The paper presents a critical view of initiatives and projects undertaken by interest and local groups in the period 2006-2010. Possible innovative approaches for regional revival are considered and conclusions are drawn about the importance of creating development strategies sensitive to the existing and emerging socio-cultural patterns.

  7. Current status of the SBS PCM approach to self-navigation of lasers on injected IFE pellets

    Science.gov (United States)

    Kalal, Milan; Martinkova, Michaela; Slezak, Ondrej; Kong, Hong Jin; Yoon, Jin Woo; Shin, Jae Sung; Rostislavovna Koresheva, Elena; Aleksandrovich Startsev, Sergei

    2010-08-01

    Current status of SBS PCM based IFE approach proposed recently as an alternative to the IFE classical approach is presented. This technology is of particular importance to the direct drive scheme taking care of automatic self-navigation of every individual laser beam on the injected pellets with no need for any final optics adjustment. Conceptual design of one typical laser driver is shown and its features discussed. In comparison with the earlier design an upgraded scheme was developed with the low energy illumination laser beam (glint) entering the reactor chamber through the same entrance window as used by the corresponding high energy irradiation laser beam. Results of experimental verification of this improved design are reported. In these experiments for the fist time a complete setup including the pellet (realized by the static steel ball) was employed. The pellet survival conditions in the period between its low energy illumination and subsequent high energy irradiation were studied and the upper limits on the allowed energies absorbed were found for both DD and DT fuels.

  8. The emergence of international food safety standards and guidelines: understanding the current landscape through a historical approach.

    Science.gov (United States)

    Ramsingh, Brigit

    2014-07-01

    Following the Second World War, the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) teamed up to construct an International Codex Alimentarius (or 'food code') which emerged in 1963. The Codex Committee on Food Hygiene (CCFH) was charged with the task of developing microbial hygiene standards, although it found itself embroiled in debate with the WHO over the nature these standards should take. The WHO was increasingly relying upon the input of biometricians and especially the International Commission on Microbial Specifications for Foods (ICMSF) which had developed statistical sampling plans for determining the microbial counts in the final end products. The CCFH, however, was initially more focused on a qualitative approach which looked at the entire food production system and developed codes of practice as well as more descriptive end-product specifications which the WHO argued were 'not scientifically correct'. Drawing upon historical archival material (correspondence and reports) from the WHO and FAO, this article examines this debate over microbial hygiene standards and suggests that there are many lessons from history which could shed light upon current debates and efforts in international food safety management systems and approaches.

  9. Tidal currents and mixing in the Gulf of St. Lawrence : an application of the incremental approach to data assimilation

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Y.; Thompson, K.R. [Dalhousie Univ., Halifax, NS (Canada). Inst. of Oceanography; Wright, D.G. [Bedford Inst. of Oceanography, Dartmouth, NS (Canada)

    2001-04-01

    The physical factors that control the distribution and abundance of the planktonic copepod Calanus finmarchicus in the Gulf of St. Lawrence (GSL) were studied. The species is an important component of the region's marine pelagic food web. In this study, the positions of baroclinic fronts formed by tidal mixing in the GSL were studied to determine if the tidal fronts, which are regions of convergence and enhanced biological activity, have important implications for the spatial distribution of biomass. The study also presented a new and effective method of data assimilation that makes it possible to convert standard physical information, (such as tidal heights) into a more biologically meaningful product, such as a map of tidal fronts. The method could be used assimilate sparse measurements of zooplankton abundance into biological models embedded within circulation models. Tidal heights from 19 tide gauges were assimilated into a fully nonlinear, three-dimensional model using the incremental approach to data assimilation. Tidal currents were predicted with good accuracy. The maps of predicted tidal currents can be used to identify regions of mixed and stratified water in the GSL using a version of the Simpson-Hunter stability parameter. 28 refs., 2 tabs., 10 figs.

  10. Regulatory approach of the monitoring the effectiveness of maintenance at nuclear power plants program; Abordagem regulatoria do programa de monitoracao da eficacia da manutencao para usinas nucleoeletricas

    Energy Technology Data Exchange (ETDEWEB)

    Vajgel, Stefan

    2009-03-15

    The electrical power generation using nuclear power plants requires this installation being safety, reliable and available for the working periods. For this purpose, an adequate, effective and well conducted maintenance program makes an essential and useful tool to the owner of the plant. However, it is necessary to follow the regulatory requirements for this program implementation which monitories this maintenance effectiveness. There are Brazilian norms requirements which must be followed. The international regulatory guides establish these requirements in good details but it is necessary to verify if this methodology for implementing can be totally applied here in Brazil. Then, the american guide NUMARC 93-01 which details how can be implemented a program for this monitoring, shows some methods for using. In this thesis, the Delphi and Probabilistic Safety Analysis were briefly included because they were preferred for implementing this monitoring.in a Brazilian plant. The results which are being obtained show that, looking the regulatory aspects, the NUMARC 93-01 follows our regulations and gives good results for the plant management. (author)

  11. 78 FR 62417 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-10-22

    ... Part 324 RIN 3064-AD95 Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy, Transition Provisions, Prompt Corrective Action, Standardized Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches Risk-Based Capital Rule,...

  12. Regulatory system reform of occupational health and safety in China.

    Science.gov (United States)

    Wu, Fenghong; Chi, Yan

    2015-01-01

    With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

  13. Collective action : a regulatory focus perspective

    NARCIS (Netherlands)

    Zaal, Maarten Pieter

    2012-01-01

    In this dissertation I investigate how individuals respond to collective disadvantage from the perspective of regulatory focus theory. Regulatory focus theory distinguishes between two motivational systems: promotion focus, the system in charge of the approach of positive end-states, and prevention

  14. 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...

  15. Exploring Education Culture by Employing Hofstede?s Cultural Dimensions to Evaluate the Effectiveness of the Current ERP Training Approach in Thailand

    Science.gov (United States)

    Chayakonvikom, Monta; Fuangvut, Parin; Cannell, Stephen

    2016-01-01

    ERP training is a critical success factor in ERP implementation. The current ERP training was largely ineffective and caused user resistance and ERP implementation failure. The objective of this paper is to investigate whether the current ERP training approach can accommodate the cultural learning behaviors of end-users. Hofstede's cultural…

  16. Analytical approaches to support current understanding of exposure, uptake and distributions of engineered nanoparticles by aquatic and terrestrial organisms.

    Science.gov (United States)

    Schultz, Carolin; Powell, Kate; Crossley, Alison; Jurkschat, Kerstin; Kille, Peter; Morgan, A John; Read, Daniel; Tyne, William; Lahive, Elma; Svendsen, Claus; Spurgeon, David J

    2015-03-01

    Initiatives to support the sustainable development of the nanotechnology sector have led to rapid growth in research on the environmental fate, hazards and risk of engineered nanoparticles (ENP). As the field has matured over the last 10 years, a detailed picture of the best methods to track potential forms of exposure, their uptake routes and best methods to identify and track internal fate and distributions following assimilation into organisms has begun to emerge. Here we summarise the current state of the field, focussing particularly on metal and metal oxide ENPs. Studies to date have shown that ENPs undergo a range of physical and chemical transformations in the environment to the extent that exposures to pristine well dispersed materials will occur only rarely in nature. Methods to track assimilation and internal distributions must, therefore, be capable of detecting these modified forms. The uptake mechanisms involved in ENP assimilation may include a range of trans-cellular trafficking and distribution pathways, which can be followed by passage to intracellular compartments. To trace toxicokinetics and distributions, analytical and imaging approaches are available to determine rates, states and forms. When used hierarchically, these tools can map ENP distributions to specific target organs, cell types and organelles, such as endosomes, caveolae and lysosomes and assess speciation states. The first decade of ENP ecotoxicology research, thus, points to an emerging paradigm where exposure is to transformed materials transported into tissues and cells via passive and active pathways within which they can be assimilated and therein identified using a tiered analytical and imaging approach.

  17. Single molecule conductivity: the role of junction-orbital degeneracy in the artificially high currents predicted by ab initio approaches.

    Science.gov (United States)

    Solomon, Gemma C; Reimers, Jeffrey R; Hush, Noel S

    2004-10-01

    A priori evaluations, using Hartree-Fock self-consistent-field (SCF) theory or density-functional theory (DFT), of the current passing between two electrodes through a single bridging molecule result in predicted conductivities that may be up to one to two orders of magnitude larger than observed ones. We demonstrate that this is, in part, often due to the improper application of the computational methods. Conductivity is shown to arise from tunneling between junction states of the electrodes through the molecule; these states are inherently either quasi two-fold or four-fold degenerate and always comprise the (highest occupied molecular orbital) HOMO band at the Fermi energy of the system. Frequently, in previous cluster based molecular conduction calculations, closed-shell SCF or Kohn-Sham DFT methods have been applied to systems that we demonstrate to be intrinsically open shell in nature. Such calculations are shown to induce artificial HOMO-LUMO (LUMO-lowest unoccupied molecular orbital) band splittings that Landauer-based formalisms for steady-state conduction interpret as arising from extremely rapid through-molecule tunneling at the Fermi energy, hence, overestimating the low-voltage conductivity. It is demonstrated that these shortcomings can be eliminated, dramatically reducing calculated current magnitudes, through the alternate use of electronic-structure calculations based on the spin-restricted open-shell formalism and related multiconfigurational SCF of DFT approaches. Further, we demonstrate that most anomalies arising in DFT implementations arise through the use of hybrid density functionals such as B3LYP. While the enhanced band-gap properties of these functionals have made them the defacto standard in molecular conductivity calculations, we demonstrate that it also makes them particularly susceptible to open-shell anomalies.

  18. The United States Remains Unprepared for Oil Import Disruptions. Volume II. Detailed Review of Current Emergency Programs and Alternative Approaches.

    Science.gov (United States)

    1981-09-29

    Conservation Act ERA Economic Regulatory Administration ERDO Emergency Reserve Drawdown Obligation ESS Emergency Sharing System ESSD Emergency Strategies and...a fraction of the base period volume. Each prime supplier (a refiner or wholesaler who first transports gasoline into a State) generally must use a...that State. Each prime supplier must set aside 5 percent of supply for this purpose. 1/See U.S. General Accounting Office, "Gasoline Allocation A Chaotic

  19. 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.

  20. Review of decision methodologies for evaluating regulatory actions affecting public health and safety. [Nuclear industry site selection

    Energy Technology Data Exchange (ETDEWEB)

    Hendrickson, P.L.; McDonald, C.L.; Schilling, A.H.

    1976-12-01

    This report examines several aspects of the problems and choices facing the governmental decision maker who must take regulatory actions with multiple decision objectives and attributes. Particular attention is given to the problems facing the U.S. Nuclear Regulatory Commission (NRC) and to the decision attribute of chief concern to NRC, the protection of human health and safety, with emphasis on nuclear power plants. The study was undertaken to provide background information for NRC to use in refining its process of value/impact assessment of proposed regulatory actions. The principal conclusion is that approaches to rationally consider the value and impact of proposed regulatory actions are available. These approaches can potentially improve the decision-making process and enable the agency to better explain and defend its decisions. They also permit consistent examination of the impacts, effects of uncertainty and sensitivity to various assumptions of the alternatives being considered. Finally, these approaches can help to assure that affected parties are heard and that technical information is used appropriately and to the extent possible. The principal aspects of the regulatory decision problem covered in the report are: the legal setting for regulatory decisions which affect human health and safety, elements of the decision-making process, conceptual approaches to decision making, current approaches to decision making in several Federal agencies, and the determination of acceptable risk levels.