WorldWideScience

Sample records for regulations requiring statistical

  1. STATISTICAL LITERACY: EXCESSIVE REQUIREMENT OR TODAY'S NECESSITY

    Directory of Open Access Journals (Sweden)

    M. Potapova

    2014-04-01

    Full Text Available The purpose of this paper is to investigate the concept of literacy of population and the evolution of literacy according to the requirements of nowadays. The approaches of scientists to multifaceted literacy of population and its necessity are considered. Special attention is paid to statistical literacy of population and its necessity in the life of every modern person.

  2. New HCFA regulations clarify PSO requirements.

    Science.gov (United States)

    Brock, T H

    1998-06-01

    In March and April of 1998, HCFA promulgated regulations regarding various requirements for provider-sponsored organizations (PSOs). These regulations define what constitutes an affiliated provider to a PSO, identify what percentage of services must be provided directly to beneficiaries by PSO affiliated providers, define what constitutes provider ownership in a PSO, and set minimum capitalization and liquidity standards for PSOs.

  3. Statistical benchmarking in utility regulation: Role, standards and methods

    International Nuclear Information System (INIS)

    Newton Lowry, Mark; Getachew, Lullit

    2009-01-01

    Statistical benchmarking is being used with increasing frequency around the world in utility rate regulation. We discuss how and where benchmarking is in use for this purpose and the pros and cons of regulatory benchmarking. We then discuss alternative performance standards and benchmarking methods in regulatory applications. We use these to propose guidelines for the appropriate use of benchmarking in the rate setting process. The standards, which we term the competitive market and frontier paradigms, have a bearing on method selection. These along with regulatory experience suggest that benchmarking can either be used for prudence review in regulation or to establish rates or rate setting mechanisms directly

  4. Statistical modelling of transcript profiles of differentially regulated genes

    Directory of Open Access Journals (Sweden)

    Sergeant Martin J

    2008-07-01

    Full Text Available Abstract Background The vast quantities of gene expression profiling data produced in microarray studies, and the more precise quantitative PCR, are often not statistically analysed to their full potential. Previous studies have summarised gene expression profiles using simple descriptive statistics, basic analysis of variance (ANOVA and the clustering of genes based on simple models fitted to their expression profiles over time. We report the novel application of statistical non-linear regression modelling techniques to describe the shapes of expression profiles for the fungus Agaricus bisporus, quantified by PCR, and for E. coli and Rattus norvegicus, using microarray technology. The use of parametric non-linear regression models provides a more precise description of expression profiles, reducing the "noise" of the raw data to produce a clear "signal" given by the fitted curve, and describing each profile with a small number of biologically interpretable parameters. This approach then allows the direct comparison and clustering of the shapes of response patterns between genes and potentially enables a greater exploration and interpretation of the biological processes driving gene expression. Results Quantitative reverse transcriptase PCR-derived time-course data of genes were modelled. "Split-line" or "broken-stick" regression identified the initial time of gene up-regulation, enabling the classification of genes into those with primary and secondary responses. Five-day profiles were modelled using the biologically-oriented, critical exponential curve, y(t = A + (B + CtRt + ε. This non-linear regression approach allowed the expression patterns for different genes to be compared in terms of curve shape, time of maximal transcript level and the decline and asymptotic response levels. Three distinct regulatory patterns were identified for the five genes studied. Applying the regression modelling approach to microarray-derived time course data

  5. Mourning dove hunting regulation strategy based on annual harvest statistics and banding data

    Science.gov (United States)

    Otis, D.L.

    2006-01-01

    Although managers should strive to base game bird harvest management strategies on mechanistic population models, monitoring programs required to build and continuously update these models may not be in place. Alternatively, If estimates of total harvest and harvest rates are available, then population estimates derived from these harvest data can serve as the basis for making hunting regulation decisions based on population growth rates derived from these estimates. I present a statistically rigorous approach for regulation decision-making using a hypothesis-testing framework and an assumed framework of 3 hunting regulation alternatives. I illustrate and evaluate the technique with historical data on the mid-continent mallard (Anas platyrhynchos) population. I evaluate the statistical properties of the hypothesis-testing framework using the best available data on mourning doves (Zenaida macroura). I use these results to discuss practical implementation of the technique as an interim harvest strategy for mourning doves until reliable mechanistic population models and associated monitoring programs are developed.

  6. A Census of Statistics Requirements at U.S. Journalism Programs and a Model for a "Statistics for Journalism" Course

    Science.gov (United States)

    Martin, Justin D.

    2017-01-01

    This essay presents data from a census of statistics requirements and offerings at all 4-year journalism programs in the United States (N = 369) and proposes a model of a potential course in statistics for journalism majors. The author proposes that three philosophies underlie a statistics course for journalism students. Such a course should (a)…

  7. Why Wait? The Influence of Academic Self-Regulation, Intrinsic Motivation, and Statistics Anxiety on Procrastination in Online Statistics

    Science.gov (United States)

    Dunn, Karee

    2014-01-01

    Online graduate education programs are expanding rapidly. Many of these programs require a statistics course, resulting in an increasing need for online statistics courses. The study reported here grew from experiences teaching online, graduate statistics courses. In seeking answers on how to improve this class, I discovered that research has yet…

  8. Industrial sources in Norway -- Regulations and requirements

    International Nuclear Information System (INIS)

    Saxeboel, G.

    2001-01-01

    On 12 May 2000, a new Act on radiation protection passed the Norwegian parliament. The report explains the requirements for the licensing process of sealed industrial sources and provides information, in particular, on the national inventory of industrial gauges, industrial radiography and logging sources. (author)

  9. 40 CFR 63.312 - Existing regulations and requirements.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Existing regulations and requirements. 63.312 Section 63.312 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... National Emission Standards for Coke Oven Batteries § 63.312 Existing regulations and requirements. (a) The...

  10. Statistical problems in nuclear regulation: introduction and overview

    International Nuclear Information System (INIS)

    Moore, R.H.; Easterling, R.G.

    1978-01-01

    The U.S. Nuclear Regulatory Commission (NRC) was organized formally in January 1975. The Commission's responsibilities can be categorized into four broad areas involving the licensing and use of nuclear materials and facilities: protecting public health and safety; protecting the environment; safeguarding nuclear materials and facilities; and assuring conformity with antitrust laws. A large variety of statistical problems are related to these basic responsibilities. They arise from the data-based nature of many of the issues to be resolved in making regulatory decisions. Hence, they are reflected in interactions among the NRC staff and licensees, vendors, and the public. This paper identifies and outlines some of these problems, providing a spectrum for comparison with the other presentations in this session. These problems are linked by the need for clear and objective treatment of data; their articulation and solution will benefit from insights and contributions from an informed statistical community

  11. NEW INTERNATIONAL FINANCIAL REGULATION: NECESSITY OR REQUIRED BY CRISIS

    Directory of Open Access Journals (Sweden)

    Cojocari Anatol

    2010-07-01

    Full Text Available The global economic and financial crisis showed the limits faced by the international financial system. International financial regulations in general, and especially the banking sector regulations, should be refined and adapted to build a stronger and stable international financial system. We analyze the main trends in international regulations: the proposed amendments on capital requirements, the introduction of a global standard for liquidity and indebtedness, the winding-up directive, as well as their impact on the Romanian financial system.

  12. 77 FR 12754 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2012-03-02

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 Parts 931, 952 and 970 RIN 1990-AA37 Contractor Legal... rulemaking (NOPR) to revise existing regulations covering contractor legal management requirements and make... relating to the DOE notice of proposed rulemaking to revise existing regulations covering contractor legal...

  13. 78 FR 29247 - Contractor Legal Management Requirements; Acquisition Regulations; Correction

    Science.gov (United States)

    2013-05-20

    ... DEPARTMENT OF ENERGY 48 CFR Part 952 RIN 1990-AA37 Contractor Legal Management Requirements; Acquisition Regulations; Correction AGENCY: Department of Energy. ACTION: Final rule; correction. SUMMARY: The... (78 FR 25795). In this document, DOE revised existing regulations covering contractor legal management...

  14. Methods for ensuring compliance with regulatory requirements: regulators and operators

    International Nuclear Information System (INIS)

    Fleischmann, A.W.

    1989-01-01

    Some of the methods of ensuring compliance with regulatory requirements contained in various radiation protection documents such as Regulations, ICRP Recommendations etc. are considered. These include radiation safety officers and radiation safety committees, personnel monitoring services, dissemination of information, inspection services and legislative power of enforcement. Difficulties in ensuring compliance include outmoded legislation, financial and personnel constraints

  15. Statistics

    CERN Document Server

    Hayslett, H T

    1991-01-01

    Statistics covers the basic principles of Statistics. The book starts by tackling the importance and the two kinds of statistics; the presentation of sample data; the definition, illustration and explanation of several measures of location; and the measures of variation. The text then discusses elementary probability, the normal distribution and the normal approximation to the binomial. Testing of statistical hypotheses and tests of hypotheses about the theoretical proportion of successes in a binomial population and about the theoretical mean of a normal population are explained. The text the

  16. Regulation E 69-14. Monitoring requirements for medical devices

    International Nuclear Information System (INIS)

    2015-01-01

    In the 'Regulations for the State Evaluation and Registration of Medical Equipment' force (Hereinafter Rules) set forth in Chapter VII, Articles 79 and 86, the monitoring activity as one of the programs necessary for evaluating the safety and effectiveness of medical monitoring equipment. In the years 2008 and 2011 were approved and implemented by the Center for State Control of Medical Equipment (CCEEM) Regulations and -1.1 ER and ER-1 that support and regulatory requirements 'Control and monitoring of pacemakers and implantable defibrillators' and 'Assessment, recording and control after market surgical silicone implants,' which are specific to these products and have provided a useful result for the performance of the activity. Given the number and diversity of high-risk medical devices as implantable or sustain human life that are brought into our National Health System (SNS), a regulation establishing control over the behavior becomes necessary safety and effectiveness of this equipment during use, which provide inputs to risk management. The objective of this regulation is to establish the regulatory requirements for tracking medical equipment introduced in the NHS. The provisions of this Regulation is aimed at health institutions, to CECMED as manufacturers, suppliers, distributors and importers of medical equipment.

  17. Review of orders and regulations requiring environmental protection

    International Nuclear Information System (INIS)

    Kelly, E.; Cunningham, R.; Michael, D.

    1996-01-01

    With the increased awareness of and interest in potential ecological risks associated with past, current, and future Department of Energy (DOE) activities, DOE's Defense Programs (DP) Office of Technical and Environmental Support sponsored a study to (1) evaluate the effectiveness of the current compliance-driven environmental protection and assessment efforts relative to ecological concerns; (2) explore the need for a more focused, integrated approach to address ecological impacts; and (3) identify the requirements for an integrated approach. The study explored four questions. (a) Which federal regulations and DOE orders either explicitly require ecological assessments or implicitly require them through environmental protection language? (b) What currently is being done at selected DOE facilities to implement these regulations and orders? (c) What are private sector industries doing in terms of ecological risk assessments and how do industry approaches and issues compare with those of DOE? (d) What, if anything, in addition to current efforts is needed to ensure the protection of ecological resources associated with DOE facilities, to support defensible decision making, and to improve efficiency? The results of this study are presented in a report titled open-quotes Integrated, Comprehensive Ecological Impact Assessments In Support of Department of Energy Decision Makingclose quotes. This report is a companion document to that report. This report provides a more detailed discussion of the document reviews of the relevant environmental protection regulations and current and pending DOE orders. The main goal of the document reviews was to understand existing requirements for ecological data collection and impact assessments

  18. Cellular growth in plants requires regulation of cell wall biochemistry.

    Science.gov (United States)

    Chebli, Youssef; Geitmann, Anja

    2017-02-01

    Cell and organ morphogenesis in plants are regulated by the chemical structure and mechanical properties of the extracellular matrix, the cell wall. The two primary load bearing components in the plant cell wall, the pectin matrix and the cellulose/xyloglucan network, are constantly remodelled to generate the morphological changes required during plant development. This remodelling is regulated by a plethora of loosening and stiffening agents such as pectin methyl-esterases, calcium ions, expansins, and glucanases. The tight spatio-temporal regulation of the activities of these agents is a sine qua non condition for proper morphogenesis at cell and tissue levels. The pectin matrix and the cellulose-xyloglucan network operate in concert and their behaviour is mutually dependent on their chemical, structural and mechanical modifications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. GENERAL CONSIDERATIONS ON REGULATIONS AND SAFETY REQUIREMENTS FOR QUADRICYCLES

    Directory of Open Access Journals (Sweden)

    Ana Pavlovic

    2015-12-01

    Full Text Available In recent years, a new class of compact vehicles has been emerging and wide-spreading all around Europe: the quadricycle. These four-wheeled motor vehicles, originally derived from motorcycles, are a small and fuel-efficient mean of transportation used in rural or urban areas as an alternative to motorbikes or city cars. In some countries, they are also endorsed by local authorities and institutions which support small and environmentally-friendly vehicles. In this paper, several general considerations on quadricycles will be provided including the vehicle classification, evolution of regulations (as homologation, driver licence, emissions, etc, technical characteristics, safety requirements, most relevant investigations, and other additional useful information (e.g. references, links. It represents an important and actual topic of investigation for designers and manufacturers considering that the new EU regulation on the approval and market surveillance of quadricycles will soon enter in force providing conclusive requirements for functional safety environmental protection of these promising vehicles.

  20. Statistics

    Science.gov (United States)

    Links to sources of cancer-related statistics, including the Surveillance, Epidemiology and End Results (SEER) Program, SEER-Medicare datasets, cancer survivor prevalence data, and the Cancer Trends Progress Report.

  1. Statistical Study to Check the Conformity of Aggregate in Kirkuk City to Requirement of Iraqi Specification

    OpenAIRE

    Ammar Saleem Khazaal; Nizar N Ismeel; Abdel fattah K. Hussein

    2018-01-01

    This research reviews a statistical study to check the conformity of aggregates (Coarse and Fine) was used in Kirkuk city to the requirements of the Iraqi specifications. The data of sieve analysis (215 samples) of aggregates being obtained from of National Central Construction Laboratory and Technical College Construction Laboratory in Kirkuk city have analyzed using the statistical program SAS. The results showed that 5%, 17%, and 18% of fine aggregate samples are passing sieve sizes 10 mm,...

  2. Statistics

    International Nuclear Information System (INIS)

    2005-01-01

    For the years 2004 and 2005 the figures shown in the tables of Energy Review are partly preliminary. The annual statistics published in Energy Review are presented in more detail in a publication called Energy Statistics that comes out yearly. Energy Statistics also includes historical time-series over a longer period of time (see e.g. Energy Statistics, Statistics Finland, Helsinki 2004.) The applied energy units and conversion coefficients are shown in the back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO 2 -emissions, Supplies and total consumption of electricity GWh, Energy imports by country of origin in January-June 2003, Energy exports by recipient country in January-June 2003, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes, precautionary stock fees and oil pollution fees

  3. Statistics

    International Nuclear Information System (INIS)

    2001-01-01

    For the year 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g. Energiatilastot 1999, Statistics Finland, Helsinki 2000, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions from the use of fossil fuels, Total energy consumption by source and CO 2 -emissions, Electricity supply, Energy imports by country of origin in 2000, Energy exports by recipient country in 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

  4. Statistics

    International Nuclear Information System (INIS)

    2000-01-01

    For the year 1999 and 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g., Energiatilastot 1998, Statistics Finland, Helsinki 1999, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions, Total energy consumption by source and CO 2 -emissions, Electricity supply, Energy imports by country of origin in January-March 2000, Energy exports by recipient country in January-March 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

  5. Statistics

    International Nuclear Information System (INIS)

    1999-01-01

    For the year 1998 and the year 1999, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period (see e.g. Energiatilastot 1998, Statistics Finland, Helsinki 1999, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions, Total energy consumption by source and CO 2 -emissions, Electricity supply, Energy imports by country of origin in January-June 1999, Energy exports by recipient country in January-June 1999, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

  6. Infrastructure requirement of knowledge management system model of statistical learning tool (SLT) for education community

    Science.gov (United States)

    Abdullah, Rusli; Samah, Bahaman Abu; Bolong, Jusang; D'Silva, Jeffrey Lawrence; Shaffril, Hayrol Azril Mohamed

    2014-09-01

    Today, teaching and learning (T&L) using technology as tool is becoming more important especially in the field of statistics as a part of the subject matter in higher education system environment. Eventhough, there are many types of technology of statistical learnig tool (SLT) which can be used to support and enhance T&L environment, however, there is lack of a common standard knowledge management as a knowledge portal for guidance especially in relation to infrastructure requirement of SLT in servicing the community of user (CoU) such as educators, students and other parties who are interested in performing this technology as a tool for their T&L. Therefore, there is a need of a common standard infrastructure requirement of knowledge portal in helping CoU for managing of statistical knowledge in acquiring, storing, desseminating and applying of the statistical knowedge for their specific purposes. Futhermore, by having this infrastructure requirement of knowledge portal model of SLT as a guidance in promoting knowledge of best practise among the CoU, it can also enhance the quality and productivity of their work towards excellence of statistical knowledge application in education system environment.

  7. Statistics

    International Nuclear Information System (INIS)

    2003-01-01

    For the year 2002, part of the figures shown in the tables of the Energy Review are partly preliminary. The annual statistics of the Energy Review also includes historical time-series over a longer period (see e.g. Energiatilastot 2001, Statistics Finland, Helsinki 2002). The applied energy units and conversion coefficients are shown in the inside back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO 2 -emissions, Supply and total consumption of electricity GWh, Energy imports by country of origin in January-June 2003, Energy exports by recipient country in January-June 2003, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Excise taxes, precautionary stock fees on oil pollution fees on energy products

  8. Statistics

    International Nuclear Information System (INIS)

    2004-01-01

    For the year 2003 and 2004, the figures shown in the tables of the Energy Review are partly preliminary. The annual statistics of the Energy Review also includes historical time-series over a longer period (see e.g. Energiatilastot, Statistics Finland, Helsinki 2003, ISSN 0785-3165). The applied energy units and conversion coefficients are shown in the inside back cover of the Review. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in GDP, energy consumption and electricity consumption, Carbon dioxide emissions from fossile fuels use, Coal consumption, Consumption of natural gas, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices in heat production, Fuel prices in electricity production, Price of electricity by type of consumer, Average monthly spot prices at the Nord pool power exchange, Total energy consumption by source and CO 2 -emissions, Supplies and total consumption of electricity GWh, Energy imports by country of origin in January-March 2004, Energy exports by recipient country in January-March 2004, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Price of natural gas by type of consumer, Price of electricity by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Excise taxes, precautionary stock fees on oil pollution fees

  9. Statistics

    International Nuclear Information System (INIS)

    2000-01-01

    For the year 1999 and 2000, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy also includes historical time series over a longer period (see e.g., Energiatilastot 1999, Statistics Finland, Helsinki 2000, ISSN 0785-3165). The inside of the Review's back cover shows the energy units and the conversion coefficients used for them. Explanatory notes to the statistical tables can be found after tables and figures. The figures presents: Changes in the volume of GNP and energy consumption, Changes in the volume of GNP and electricity, Coal consumption, Natural gas consumption, Peat consumption, Domestic oil deliveries, Import prices of oil, Consumer prices of principal oil products, Fuel prices for heat production, Fuel prices for electricity production, Carbon dioxide emissions, Total energy consumption by source and CO 2 -emissions, Electricity supply, Energy imports by country of origin in January-June 2000, Energy exports by recipient country in January-June 2000, Consumer prices of liquid fuels, Consumer prices of hard coal, natural gas and indigenous fuels, Average electricity price by type of consumer, Price of district heating by type of consumer, Excise taxes, value added taxes and fiscal charges and fees included in consumer prices of some energy sources and Energy taxes and precautionary stock fees on oil products

  10. Sample Size Requirements for Assessing Statistical Moments of Simulated Crop Yield Distributions

    NARCIS (Netherlands)

    Lehmann, N.; Finger, R.; Klein, T.; Calanca, P.

    2013-01-01

    Mechanistic crop growth models are becoming increasingly important in agricultural research and are extensively used in climate change impact assessments. In such studies, statistics of crop yields are usually evaluated without the explicit consideration of sample size requirements. The purpose of

  11. 45 CFR 309.170 - What statistical and narrative reporting requirements apply to Tribal IV-D programs?

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false What statistical and narrative reporting... (IV-D) PROGRAM Statistical and Narrative Reporting Requirements § 309.170 What statistical and narrative reporting requirements apply to Tribal IV-D programs? (a) Tribes and Tribal organizations...

  12. Radioactive materials and nuclear fuel transport requirements in Poland in the light of international regulations

    International Nuclear Information System (INIS)

    Musialowicz, T.

    1977-01-01

    National regulations for the transport of radioactive materials and nuclear fuel in Poland are discussed. Basic transport requirements and regulations, transport experience including transport accidents and emergency service are described. The comparison with international regulations is given

  13. Statistical Requirements For Pass-Fail Testing Of Contraband Detection Systems

    International Nuclear Information System (INIS)

    Gilliam, David M.

    2011-01-01

    Contraband detection systems for homeland security applications are typically tested for probability of detection (PD) and probability of false alarm (PFA) using pass-fail testing protocols. Test protocols usually require specified values for PD and PFA to be demonstrated at a specified level of statistical confidence CL. Based on a recent more theoretical treatment of this subject [1], this summary reviews the definition of CL and provides formulas and spreadsheet functions for constructing tables of general test requirements and for determining the minimum number of tests required. The formulas and tables in this article may be generally applied to many other applications of pass-fail testing, in addition to testing of contraband detection systems.

  14. translin Is Required for Metabolic Regulation of Sleep.

    Science.gov (United States)

    Murakami, Kazuma; Yurgel, Maria E; Stahl, Bethany A; Masek, Pavel; Mehta, Aradhana; Heidker, Rebecca; Bollinger, Wesley; Gingras, Robert M; Kim, Young-Joon; Ja, William W; Suter, Beat; DiAngelo, Justin R; Keene, Alex C

    2016-04-04

    Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Present state of nuclear regulation organizations of main countries in the world. Importance of regulation staffs and requirements

    International Nuclear Information System (INIS)

    Nishida, Naoki

    2013-01-01

    After Fukushima accident, NRA (Nuclear Regulation Authority) was established in Japan as an independent organization from promotion. In order to perform effective and reliable nuclear regulation, it was important management organization such as nuclear regulation commission worked efficiently, and also requirements for nuclear regulation staffs engaged in actual regulatory works were of importance so as for appropriate decision making or judgments of management organization. Since regulation staffs needed professional expertise and technical judgment capabilities in wide areas including other than nuclear energy, various efforts had been done to get able regulation staffs in US, France and UK nuclear regulation organizations concerned, which became clarified after overseas investigation for this article. Since knowledge in nuclear industry could be used for effective regulation, mid-career recruitment had been employed in regulation organization of each country so as to take such knowledge and so it was important how to utilize industrial knowledge under appropriate conditions compatible with independence of regulation organization. (T. Tanaka)

  16. Discovery of a Splicing Regulator Required for Cell Cycle Progression

    Energy Technology Data Exchange (ETDEWEB)

    Suvorova, Elena S.; Croken, Matthew; Kratzer, Stella; Ting, Li-Min; Conde de Felipe, Magnolia; Balu, Bharath; Markillie, Lye Meng; Weiss, Louis M.; Kim, Kami; White, Michael W.

    2013-02-01

    In the G1 phase of the cell division cycle, eukaryotic cells prepare many of the resources necessary for a new round of growth including renewal of the transcriptional and protein synthetic capacities and building the machinery for chromosome replication. The function of G1 has an early evolutionary origin and is preserved in single and multicellular organisms, although the regulatory mechanisms conducting G1 specific functions are only understood in a few model eukaryotes. Here we describe a new G1 mutant from an ancient family of apicomplexan protozoans. Toxoplasma gondii temperature-sensitive mutant 12-109C6 conditionally arrests in the G1 phase due to a single point mutation in a novel protein containing a single RNA-recognition-motif (TgRRM1). The resulting tyrosine to asparagine amino acid change in TgRRM1 causes severe temperature instability that generates an effective null phenotype for this protein when the mutant is shifted to the restrictive temperature. Orthologs of TgRRM1 are widely conserved in diverse eukaryote lineages, and the human counterpart (RBM42) can functionally replace the missing Toxoplasma factor. Transcriptome studies demonstrate that gene expression is downregulated in the mutant at the restrictive temperature due to a severe defect in splicing that affects both cell cycle and constitutively expressed mRNAs. The interaction of TgRRM1 with factors of the tri-SNP complex (U4/U6 & U5 snRNPs) indicate this factor may be required to assemble an active spliceosome. Thus, the TgRRM1 family of proteins is an unrecognized and evolutionarily conserved class of splicing regulators. This study demonstrates investigations into diverse unicellular eukaryotes, like the Apicomplexa, have the potential to yield new insights into important mechanisms conserved across modern eukaryotic kingdoms.

  17. 78 FR 60898 - Regulation on Definition and Requirements for a Nationally Recognized Testing Laboratory...

    Science.gov (United States)

    2013-10-02

    ...] Regulation on Definition and Requirements for a Nationally Recognized Testing Laboratory; Revision of the Office of Management and Budget's (OMB) Approval of Information Collection (Paperwork) Requirements... collection requirements specified by its Regulation at 29 CFR 1910.7, ``definition and requirements for a...

  18. Statistical Study to Check the Conformity of Aggregate in Kirkuk City to Requirement of Iraqi Specification

    Directory of Open Access Journals (Sweden)

    Ammar Saleem Khazaal

    2018-01-01

    Full Text Available This research reviews a statistical study to check the conformity of aggregates (Coarse and Fine was used in Kirkuk city to the requirements of the Iraqi specifications. The data of sieve analysis (215 samples of aggregates being obtained from of National Central Construction Laboratory and Technical College Construction Laboratory in Kirkuk city have analyzed using the statistical program SAS. The results showed that 5%, 17%, and 18% of fine aggregate samples are passing sieve sizes 10 mm, 4.75 mm, and 2.36 mm, respectively, which were less than the minimum limit allowed by the Iraqi specifications for each sieve. The percentages passing sieve sizes 1.18mm, 600micrometers, and 300micrometers were more than the upper limit of specification by 5%, 20%, and 30% respectively. The samples were passing sieve sizes 1.18mm, and 600micrometers less than the minimum limit of specification by 17%, and 4%, respectively. The results showed that the deviation in a sieve size of 150 micrometers for the upper limit of the specification performs 2% of the total number of samples. For Coarse aggregate, the samples passing sieves size 37.5mm and 20mm were comforting the Iraqi specifications by 100% and 83% respectively, it has found that the samples were passing sieve sizes 10 mm was 5% was more than the higher limit of Iraqi specifications, and 27% of these samples were less than the minimum limit, whereas sample passing sieve size 5mm was 1% which is more than the upper limit of the Iraqi specification. As a result of statistical analysis of data for fine aggregate, it has found that the samples were passing sieve sizes 10 mm, 2.36 mm, 1.18 mm and 150micrometers conforming from statistical point of view the Iraqi specifications, whereas the samples were passing sieve sizes 4.75 mm, 600micrometers and 300 micrometers didn’t conform. Statistical analysis of the results of the coarse aggregates also showed that conforming to sieve sizes of 37.5 mm and 20 mm and

  19. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  20. Identification of chilling and heat requirements of cherry trees--a statistical approach.

    Science.gov (United States)

    Luedeling, Eike; Kunz, Achim; Blanke, Michael M

    2013-09-01

    Most trees from temperate climates require the accumulation of winter chill and subsequent heat during their dormant phase to resume growth and initiate flowering in the following spring. Global warming could reduce chill and hence hamper the cultivation of high-chill species such as cherries. Yet determining chilling and heat requirements requires large-scale controlled-forcing experiments, and estimates are thus often unavailable. Where long-term phenology datasets exist, partial least squares (PLS) regression can be used as an alternative, to determine climatic requirements statistically. Bloom dates of cherry cv. 'Schneiders späte Knorpelkirsche' trees in Klein-Altendorf, Germany, from 24 growing seasons were correlated with 11-day running means of daily mean temperature. Based on the output of the PLS regression, five candidate chilling periods ranging in length from 17 to 102 days, and one forcing phase of 66 days were delineated. Among three common chill models used to quantify chill, the Dynamic Model showed the lowest variation in chill, indicating that it may be more accurate than the Utah and Chilling Hours Models. Based on the longest candidate chilling phase with the earliest starting date, cv. 'Schneiders späte Knorpelkirsche' cherries at Bonn exhibited a chilling requirement of 68.6 ± 5.7 chill portions (or 1,375 ± 178 chilling hours or 1,410 ± 238 Utah chill units) and a heat requirement of 3,473 ± 1,236 growing degree hours. Closer investigation of the distinct chilling phases detected by PLS regression could contribute to our understanding of dormancy processes and thus help fruit and nut growers identify suitable tree cultivars for a future in which static climatic conditions can no longer be assumed. All procedures used in this study were bundled in an R package ('chillR') and are provided as Supplementary materials. The procedure was also applied to leaf emergence dates of walnut (cv. 'Payne') at Davis, California.

  1. Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

    NARCIS (Netherlands)

    Mittag, J.; Lyons, D.J.; Sällström, J.; Vujoviv, M.; Dudazy-Gralla, S.; Warner, A.; Wallis, K.; Alkemade, A.; Nordström, K.; Monyer, H.; Broberger, C.; Arner, A.; Vennström, B.

    2013-01-01

    Thyroid hormone is well known for its profound direct effects on cardiovascular function and metabolism. Recent evidence, however, suggests that the hormone also regulates these systems indirectly through the central nervous system. While some of the molecular mechanisms underlying the hormone’s

  2. 76 FR 81408 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2011-12-28

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 CFR Parts 931, 952 and 970 RIN 1990-AA37 Contractor Legal... Energy (DOE or Department) is proposing to revise existing regulations covering contractor legal... costs by certain contractors whose contracts exceed $100,000,000 as well as legal counsel retained...

  3. 78 FR 25795 - Contractor Legal Management Requirements; Acquisition Regulations

    Science.gov (United States)

    2013-05-03

    ... DEPARTMENT OF ENERGY 10 CFR Part 719 48 CFR Parts 931, 952, and 970 RIN 1990-AA37 Contractor Legal.... ACTION: Final rule. SUMMARY: The Department of Energy revises existing regulations covering contractor... costs by certain contractors whose contracts exceed $100,000,000 as well as legal counsel retained...

  4. Financial Market Regulation in Germany - Capital Requirements of Financial Institutions

    Directory of Open Access Journals (Sweden)

    Daniel Karl Detzer

    2015-03-01

    Full Text Available This paper examines capital adequacy regulation in Germany. The first part reviews capital adequacy regulation from the 1930s up to the financial crisis and identifies two main trends: a gradual softening of the eligibility criteria for equity and increasing reliance on internal risk models. While the first trend has been reversed following the financial crisis, internal risk models still play a central role. Therefore, the second part discusses the problems with the use of internal risk models and discusses the potentials of Basel 2.5 and Basel III to alleviate the identified problems. It is concluded that the relevant problems are not resolved. Therefore, in the final part some suggestions of how the problems could be addressed properly are given.

  5. Cost regulation on the inspection of plants requiring supervision

    International Nuclear Information System (INIS)

    Anon.

    1981-01-01

    According to annexes I to VI of this regulation, TUeVs (technical control authorities) (2nd sentence of para. 1 of sect. 24 c of the trade law) collect fees for inspections ordered by the authorities for the following plants and installations: 1. steam boiler plants, 2. pressure vessels, high-pressure gas vessels, feeders, 3. lifts, 4. acetylene plants, 5. plants for the storage, racking and transport of combustile liquids, 6. electrical installations on hazardous location. (orig.) [de

  6. Appropriate statistical methods are required to assess diagnostic tests for replacement, add-on, and triage

    NARCIS (Netherlands)

    Hayen, Andrew; Macaskill, Petra; Irwig, Les; Bossuyt, Patrick

    2010-01-01

    To explain which measures of accuracy and which statistical methods should be used in studies to assess the value of a new binary test as a replacement test, an add-on test, or a triage test. Selection and explanation of statistical methods, illustrated with examples. Statistical methods for

  7. 76 FR 78933 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-12-20

    ..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA), is announcing a public workshop. The public workshop on FDA's...

  8. Proper joint analysis of summary association statistics requires the adjustment of heterogeneity in SNP coverage pattern.

    Science.gov (United States)

    Zhang, Han; Wheeler, William; Song, Lei; Yu, Kai

    2017-07-07

    As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

  9. 78 FR 80369 - Federal Acquisition Regulation; Service Contracts Reporting Requirements

    Science.gov (United States)

    2013-12-31

    ... (e.g., cost-reimbursement, time-and- materials, and labor-hour contracts), which already require... contract costs and labor can significantly fluctuate each year or how this type of labor can be comingled... of direct labor hours expended on the services performed is extremely concerning, particularly in a...

  10. 76 FR 35218 - Federal Acquisition Regulation; Information Collection; Cost or Pricing Data Requirements and...

    Science.gov (United States)

    2011-06-16

    ... Pricing Data, by any of the following methods: Regulations.gov : http://www.regulations.gov . Submit...; Information Collection; Cost or Pricing Data Requirements and Information Other Than Cost or Pricing Data... concerning cost or pricing data requirements and information other than cost or pricing data. Public comments...

  11. Time integration and statistical regulation applied to mobile objects detection in a sequence of images

    International Nuclear Information System (INIS)

    Letang, Jean-Michel

    1993-01-01

    This PhD thesis deals with the detection of moving objects in monocular image sequences. The first section presents the inherent problems of motion analysis in real applications. We propose a method robust to perturbations frequently encountered during acquisition of outdoor scenes. It appears three main directions for investigations, all of them pointing out the importance of the temporal axis, which is a specific dimension for motion analysis. In the first part, the image sequence is considered as a set of temporal signals. The temporal multi-scale decomposition enables the characterization of various dynamical behaviors of the objects being in the scene at a given instant. A second module integrates motion information. This elementary trajectography of moving objects provides a temporal prediction map, giving a confidence level of motion presence. Interactions between both sets of data are expressed within a statistical regularization. Markov random field models supply a formal framework to convey a priori knowledge of the primitives to be evaluated. A calibration method with qualitative boxes is presented to estimate model parameters. Our approach requires only simple computations and leads to a rather fast algorithm, that we evaluate in the last section over various typical sequences. (author) [fr

  12. New Standards Require Teaching More Statistics: Are Preservice Secondary Mathematics Teachers Ready?

    Science.gov (United States)

    Lovett, Jennifer N.; Lee, Hollylynne S.

    2017-01-01

    Mathematics teacher education programs often need to respond to changing expectations and standards for K-12 curriculum and accreditation. New standards for high school mathematics in the United States include a strong emphasis in statistics. This article reports results from a mixed methods cross-institutional study examining the preparedness of…

  13. Establishing Reusable Requirements Derived from Laws and Regulations for Medical Device Development

    DEFF Research Database (Denmark)

    Hauksdóttir, Dagný; Mortensen, Niels Henrik; Ritsing, Brian

    2016-01-01

    skills and consumes significant effort in product development. Therefore initiating reuse from the analysis and elicitation of requirements from standards and regulations may provide promising potential for gaining efficiency in development and also for assuring sufficient quality of the work...

  14. 7 CFR 330.200 - Movement of plant pests regulated; permits required.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of plant pests regulated; permits required... AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE FEDERAL PLANT PEST REGULATIONS; GENERAL; PLANT PESTS; SOIL, STONE, AND QUARRY PRODUCTS; GARBAGE Movement of Plant Pests § 330.200 Movement of...

  15. ER-16 regulation. Requirements for granting the permit exceptional use of medical devices in humans

    International Nuclear Information System (INIS)

    2015-01-01

    The purpose of this regulation is to establish requirements for applying for a permit exceptional use of medical equipment in Human Beings, the procedures for the evaluation process and bestowal. This regulation is aimed at researchers and designers of medical equipment, related to or associated with National Health Service's priority programs of interest to health.

  16. Greater-than-Class C low-level radioactive waste transportation regulations and requirements study

    International Nuclear Information System (INIS)

    Tyacke, M.; Schmitt, R.

    1993-07-01

    The purpose of this report is to identify the regulations and requirements for transporting greater-than-Class C (GTCC) low-level radioactive waste (LLW) and to identify planning activities that need to be accomplished in preparation for transporting GTCC LLW. The regulations and requirements for transporting hazardous materials, of which GTCC LLW is included, are complex and include several Federal agencies, state and local governments, and Indian tribes. This report is divided into five sections and three appendices. Section 1 introduces the report. Section 2 identifies and discusses the transportation regulations and requirements. The regulations and requirements are divided into Federal, state, local government, and Indian tribes subsections. This report does not identify the regulations or requirements of specific state, local government, and Indian tribes, since the storage, treatment, and disposal facility locations and transportation routes have not been specifically identified. Section 3 identifies the planning needed to ensure that all transportation activities are in compliance with the regulations and requirements. It is divided into (a) transportation packaging; (b) transportation operations; (c) system safety and risk analysis, (d) route selection; (e) emergency preparedness and response; and (f) safeguards and security. This section does not provide actual planning since the details of the Department of Energy (DOE) GTCC LLW Program have not been finalized, e.g., waste characterization and quantity, storage, treatment and disposal facility locations, and acceptance criteria. Sections 4 and 5 provide conclusions and referenced documents, respectively

  17. Regulations for the Safe Transport of Radioactive Material, 2009 ed. Safety Requirements

    International Nuclear Information System (INIS)

    2009-01-01

    This publication establishes the regulations that are applied to the transport of radioactive material by all modes of transport on land, water or in the air, including transport that is incidental to the use of the radioactive material. The objective and scope of the regulations are described in detail as well as the range of their application. The publication provides requirements useful to governments, regulators, operators of nuclear and radiation facilities, carriers, users of radiation sources and cargo handling personnel. Contents: 1. Introduction; 2. Definitions; 3. General provisions; 4. Activity limits and classification; 5. Requirements and controls for transport; 6. Requirements for radioactive materials and for packagings and packages; 7. Test procedures; 8. Approval and administrative requirements; Annex I: Summary of approval and prior notification requirements; Annex II: Conversion factors and prefixes.

  18. Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe

    DEFF Research Database (Denmark)

    Ziemann, Alexandra; Rosenkötter, Nicole; Riesgo, Luis Garcia-Castrillo

    2015-01-01

    BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing...... public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross...... effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)....

  19. 75 FR 14448 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-03-25

    ... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Society of Clinical Research Associates, Inc. (SoCRA) is announcing a public workshop entitled ``FDA...

  20. 77 FR 8886 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2012-02-15

    ..., electronic record requirements, and investigator initiated research. Topics for discussion include the...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical trial...

  1. 76 FR 51040 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-08-17

    ... requirements, and investigator initiated research. Topics for discussion include the following: (1) What FDA...] Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good Clinical... Clinical Research Associates (SoCRA) is announcing a public workshop. The public workshop on FDA's clinical...

  2. Statistical state dynamics-based analysis of the physical mechanisms sustaining and regulating turbulence in Couette flow

    Science.gov (United States)

    Farrell, Brian F.; Ioannou, Petros J.

    2017-08-01

    This paper describes a study of the self-sustaining process in wall turbulence. The study is based on a second order statistical state dynamics model of Couette flow in which the state variables are the streamwise mean flow (first cumulant) and perturbation covariance (second cumulant). This statistical state dynamics model is closed by either setting the third cumulant to zero or by replacing it with a stochastic parametrization. Statistical state dynamics models with this form are referred to as S3T models. S3T models have been shown to self-sustain turbulence with a mean flow and second order perturbation structure similar to that obtained by direct numerical simulation of the equations of motion. The use of a statistical state dynamics model to study the physical mechanisms underlying turbulence has important advantages over the traditional approach of studying the dynamics of individual realizations of turbulence. One advantage is that the analytical structure of S3T statistical state dynamics models isolates the interaction between the mean flow and the perturbation components of the turbulence. Isolation of the interaction between these components reveals how this interaction underlies both the maintenance of the turbulence variance by transfer of energy from the externally driven flow to the perturbation components as well as the enforcement of the observed statistical mean turbulent state by feedback regulation between the mean and perturbation fields. Another advantage of studying turbulence using statistical state dynamics models of S3T form is that the analytical structure of S3T turbulence can be completely characterized. For example, the perturbation component of turbulence in the S3T system is demonstrably maintained by a parametric perturbation growth mechanism in which fluctuation of the mean flow maintains the perturbation field which in turn maintains the mean flow fluctuations in a synergistic interaction. Furthermore, the equilibrium

  3. EUROPEAN INTEGRATION: A MULTILEVEL PROCESS THAT REQUIRES A MULTILEVEL STATISTICAL ANALYSIS

    Directory of Open Access Journals (Sweden)

    Roxana-Otilia-Sonia HRITCU

    2015-11-01

    Full Text Available A process of market regulation and a system of multi-level governance and several supranational, national and subnational levels of decision making, European integration subscribes to being a multilevel phenomenon. The individual characteristics of citizens, as well as the environment where the integration process takes place, are important. To understand the European integration and its consequences it is important to develop and test multi-level theories that consider individual-level characteristics, as well as the overall context where individuals act and express their characteristics. A central argument of this paper is that support for European integration is influenced by factors operating at different levels. We review and present theories and related research on the use of multilevel analysis in the European area. This paper draws insights on various aspects and consequences of the European integration to take stock of what we know about how and why to use multilevel modeling.

  4. Liberalization, Moral Hazard in Banking, and Prudential Regulation: Are Capital Requirements Enough?

    OpenAIRE

    Kevin C. Murdock; Thomas F. Hellmann; Joseph E. Stiglitz

    2000-01-01

    In a dynamic model of moral hazard, competition can undermine prudent bank behavior. While capital-requirement regulation can induce prudent behavior, the policy yields Pareto-inefficient outcomes. Capital requirements reduce gambling incentives by putting bank equity at risk. However, they also have a perverse effect of harming banks' franchise values, thus encouraging gambling. Pareto-efficient outcomes can be achieved by adding deposit-rate controls as a regulatory instrument, since they f...

  5. Casein kinase 1-Like 3 is required for abscisic acid regulation of ...

    African Journals Online (AJOL)

    Casein kinase 1-Like 3 is required for abscisic acid regulation of seed germination, root growth, and gene expression in Arabidopsis. M Wang, D Yu, X Guo, X Li, J Zhang, L Zhao, H Chang, S Hu, C Zhang, J Shi, X Liu ...

  6. 13 CFR 120.1511 - Certification and other reporting and notification requirements for Other Regulated SBLCs.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Certification and other reporting and notification requirements for Other Regulated SBLCs. 120.1511 Section 120.1511 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Risk-Based Lender Oversight Enforcement Actions § 120...

  7. 78 FR 63462 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2013-10-24

    ... Relating to Organizational Conflict of Interest-Major Defense Acquisition Program; OMB Control Number 0704...] Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Organizational Conflict... submit comments, identified by OMB Control Number 0704-0477, using any of the following methods: [cir...

  8. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance and equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  9. 78 FR 65218 - Defense Federal Acquisition Regulation Supplement: Private Sector Notification Requirements of In...

    Science.gov (United States)

    2013-10-31

    ... Federal Acquisition Regulation Supplement: Private Sector Notification Requirements of In-Sourcing Actions... Supplement (DFARS) to implement a section of the National Defense Authorization Act regarding private sector... section 938 of the National Defense Authorization Act (NDAA) for Fiscal Year 2012 regarding private sector...

  10. Capital Regulation, Liquidity Requirements and Taxation in a Dynamic Model of Banking

    NARCIS (Netherlands)

    Di Nicolo, G.; Gamba, A.; Lucchetta, M.

    2011-01-01

    This paper formulates a dynamic model of a bank exposed to both credit and liquidity risk, which can resolve financial distress in three costly forms: fire sales, bond issuance ad equity issuance. We use the model to analyze the impact of capital regulation, liquidity requirements and taxation on

  11. 75 FR 26165 - Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra...

    Science.gov (United States)

    2010-05-11

    ... Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra-Low Sulfur... refiners, importers, distributors, and retailers of highway diesel fuel the option to use an alternative affirmative defense if the Agency finds highway diesel fuel samples above the specified sulfur standard at...

  12. New requirements, rules and regulations, and vested rights of nuclear power plants

    International Nuclear Information System (INIS)

    Raetzke, C.

    2006-01-01

    The article deals with the question whether new requirements can be imposed on existing nuclear power plants. It was promoted by the fact that the German Federal Ministry for the Environment currently is working on a thorough revision of German nuclear regulations. When looking at backfitting requirements, the all-important question is whether new findings show that the provisions taken in the license to guarantee the 'necessary precautions' (as defined in the German Atomic Energy Act) contain errors or omissions; only in this case can the authority demand that remedial measures, including backfitting, be taken. Beyond that, German nuclear law contains no obligation for operators to improve and develop safety still further. This applies regardless of whether new requirements are justified by new technical possibilities or new scientific analyses or whether they are prompted by a mere abstract re-evaluation of the safety level to be achieved. In the former case, if there are good technical or scientific reasons, the operators, as a rule, will perform backfitting voluntarily. Pursuant to these criteria, the article covers three categories of backfitting requirements and illustrates them by examples. These general principles are also valid when a new set of regulations - as planned by the BMU - are put into effect and applied. They may lead to existing plants not having to comply fully with the requirements contained in new regulations. (orig.)

  13. Long-term energy efficiency analysis requires solid energy statistics: The case of the German basic chemical industry

    International Nuclear Information System (INIS)

    Saygin, D.; Worrell, E.; Tam, C.; Trudeau, N.; Gielen, D.J.; Weiss, M.; Patel, M.K.

    2012-01-01

    Analyzing the chemical industry’s energy use is challenging because of the sector’s complexity and the prevailing uncertainty in energy use and production data. We develop an advanced bottom-up model (PIE-Plus) which encompasses the energy use of the 139 most important chemical processes. We apply this model in a case study to analyze the German basic chemical industry’s energy use and energy efficiency improvements in the period between 1995 and 2008. We compare our results with data from the German Energy Balances and with data published by the International Energy Agency (IEA). We find that our model covers 88% of the basic chemical industry’s total final energy use (including non-energy use) as reported in the German Energy Balances. The observed energy efficiency improvements range between 2.2 and 3.5% per year, i.e., they are on the higher side of the values typically reported in literature. Our results point to uncertainties in the basic chemical industry’s final energy use as reported in the energy statistics and the specific energy consumption values. More efforts are required to improve the quality of the national and international energy statistics to make them useable for reliable monitoring of energy efficiency improvements of the chemical industry. -- Highlights: ► An advanced model was developed to estimate German chemical industry’s energy use. ► For the base year (2000), model covers 88% of the sector’s total final energy use. ► Sector’s energy efficiency improved between 2.2 and 3.5%/yr between 1995 and 2008. ► Improved energy statistics are required for accurate monitoring of improvements.

  14. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    DEFF Research Database (Denmark)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate......-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin...... ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together...

  15. An assessment of the fire protection requirements throughout a NPP life related to current IAEA regulations and American, Canadian and UE regulations

    International Nuclear Information System (INIS)

    Branzeu, N.; Necula, D.; Badea, M.; Teodorescu, D.; Peteu, M.

    2006-01-01

    Statistics on fires has surprisingly shown that the frequency of fires in a nuclear power plant are as high as in the conventional industrial units. The analyses on fires occurred in a NPP need to consider both their well-known severe damages and the nuclear consequences. In 1975 a severe fire occurred in BROWNS FERRY NPP due to the ignition of the polyurethane foam used in the electric cable penetration sealings. The fire propagated to the cable channels and damaged over 1600 cables. The fire event revealed important shortcomings in the fire protection design and procedures. The fire represented a crucial event that changed fundamentally the fire protection regulation in the United States nuclear industry. The fire protection programs, standards and guides currently applied, have been developed on basis of this fire analysis and gained conclusions/experience. The purpose of the article is to be a short presentation of the fire protection requirements for all NPP life stages (i.e. design, construction, commissioning, operation and decommissioning), including the most recent issues of the standards, codes, guides and regulations in US, Canada, IAEA and some European countries. Such documentation represented the main technical support in establishing the national fire protection standard design regarding all the stages of a CANDU-6 NPP life, all the types of operational NPPs, particularly for Cernavoda NPP Unit 1 and Unit 2 (now in an advanced stage of construction). In order to satisfy the requirements provided by this documentation, as practically as possible, a list of analyses and fire protection improvement measures for Cernavoda NPP is presented. (authors)

  16. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  17. Regulation EM-ER-6. Requirements for the realization of clinical essays to the medical equipments

    International Nuclear Information System (INIS)

    2015-01-01

    This regulation applies to the medical equipment that become incorporated to the stage of clinical trial required for its evaluation and record, for which they are subdued to clinical investigation for the sake of verifying, in conditions specified of use, its functioning, identifying besides any undesirable defect. It extends to manufacturers of medical equipments, Public Health's units where the clinical investigations with those equipments take place and to the rest of the entities of the MINSAP . Its objective is to protect the participating subjects in the clinical investigations; Assuring the conduction of the clinical investigation and specifying the requirements for the conduction of the clinical investigations and the documentation required for it.

  18. Sterol homeostasis requires regulated degradation of squalene monooxygenase by the ubiquitin ligase Doa10/Teb4

    Science.gov (United States)

    Foresti, Ombretta; Ruggiano, Annamaria; Hannibal-Bach, Hans K; Ejsing, Christer S; Carvalho, Pedro

    2013-01-01

    Sterol homeostasis is essential for the function of cellular membranes and requires feedback inhibition of HMGR, a rate-limiting enzyme of the mevalonate pathway. As HMGR acts at the beginning of the pathway, its regulation affects the synthesis of sterols and of other essential mevalonate-derived metabolites, such as ubiquinone or dolichol. Here, we describe a novel, evolutionarily conserved feedback system operating at a sterol-specific step of the mevalonate pathway. This involves the sterol-dependent degradation of squalene monooxygenase mediated by the yeast Doa10 or mammalian Teb4, a ubiquitin ligase implicated in a branch of the endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway. Since the other branch of ERAD is required for HMGR regulation, our results reveal a fundamental role for ERAD in sterol homeostasis, with the two branches of this pathway acting together to control sterol biosynthesis at different levels and thereby allowing independent regulation of multiple products of the mevalonate pathway. DOI: http://dx.doi.org/10.7554/eLife.00953.001 PMID:23898401

  19. The regulation and deregulation requirements for the decommissioning of nuclear installations

    International Nuclear Information System (INIS)

    Wagner, H.

    1993-01-01

    On the basis of a brief outline of the starting point in terms of technical conditions and status, and of the main aspects of application and interpretation of the law, the regulation and deregulation requirements are elaborated in the light of suggestions for change and with regard to their possible concretization in laws and subordinate laws; the strongest need for change undoubtedly is in the field of the technical codes and regulations, which hitherto have been established primarily for the construction and operation of nuclear installations and hence are not necessarily applicable to the activities to be performed for decommissioning. Practice so far has shown, however, that these regulations are applied not analogously, as would be adequate, but in direct manner. The required review and modification of the existing regulatory codes for the purpose of decommissioning will have to concentrate on the following aspects: - Scope and level of specification of application documents; - definition of important, safety-related events (as e.g. accidents); - scope and level of specification of expert opinions, taking into account the reduced risk level. As a long-term objective, it would be desirable to harmonize existing German regulatory provisions for the decommissioning of industrial plants with an environmental impact (as e.g, the Waste Management Act, Atomic Energy Act, mining law, Federal Emission Control Act), and to seek an approach of national regulatory systems and technical codes in this field under the roof of the EC. (orig./HSCH) [de

  20. Effect of increased regulation on capital costs and manual labor requirements of nuclear power plants

    International Nuclear Information System (INIS)

    Paik, S.; Schriver, W.R.

    1981-01-01

    An attempt is made to explain the impact of increasing governmental regulation on capital costs and labor requirements for constructing light water reactor (LWR) electric power plants. The principal factors contributing to these increases are: (1) market conditions and (2) increased regulation. General market conditions include additional costs attributable to price inflation of equipment, material, labor, and the increased cost of money. The central objective of this work is to estimate the impact of increasing regulation on plant costs and, conversely, on output. To do this it is necessary to isolate two opposing sets of forces which have been in operation during the period of major regulatory expansion: learning based upon plant design experience and economies of scale with increasing size (generating capacity) of newer plants. Conceptual models are specified to capture the independent effects of increasing regulation, learning, and economies of scale. Empirical results were obtained by estimating the models on data collected from industry experience during the 1967-1980 period. 23 refs

  1. A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.

    Science.gov (United States)

    Vidaki, Marina; Drees, Frauke; Saxena, Tanvi; Lanslots, Erwin; Taliaferro, Matthew J; Tatarakis, Antonios; Burge, Christopher B; Wang, Eric T; Gertler, Frank B

    2017-08-02

    During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons. We find that translation of dyrk1a, a Down syndrome- and autism spectrum disorders-related gene, is dependent on Mena, both in steady-state conditions and upon BDNF stimulation. We identify hundreds of additional mRNAs that associate with the Mena complex, suggesting that it plays broader role(s) in post-transcriptional gene regulation. Our work establishes a dual role for Mena in neurons, providing a potential link between regulation of actin dynamics and local translation. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Cost-optimal levels of minimum energy performance requirements in the Danish Building Regulations

    Energy Technology Data Exchange (ETDEWEB)

    Aggerholm, S.

    2013-09-15

    The purpose of the report is to analyse the cost optimality of the energy requirements in the Danish Building Regulations 2010, BR10 to new building and to existing buildings undergoing major renovation. The energy requirements in the Danish Building Regulations have by tradition always been based on the cost and benefits related to the private economical or financial perspective. Macro economical calculations have in the past only been made in addition. The cost optimum used in this report is thus based on the financial perspective. Due to the high energy taxes in Denmark there is a significant difference between the consumer price and the macro economical for energy. Energy taxes are also paid by commercial consumers when the energy is used for building operation e.g. heating, lighting, ventilation etc. In relation to the new housing examples the present minimum energy requirements in BR 10 all shows gaps that are negative with a deviation of up till 16 % from the point of cost optimality. With the planned tightening of the requirements to new houses in 2015 and in 2020, the energy requirements can be expected to be tighter than the cost optimal point, if the costs for the needed improvements don't decrease correspondingly. In relation to the new office building there is a gap of 31 % to the point of cost optimality in relation to the 2010 requirement. In relation to the 2015 and 2020 requirements there are negative gaps to the point of cost optimality based on today's prices. If the gaps for all the new buildings are weighted to an average based on mix of building types and heat supply for new buildings in Denmark there is a gap of 3 % in average for the new building. The excessive tightness with today's prices is 34 % in relation to the 2015 requirement and 49 % in relation to the 2020 requirement. The component requirement to elements in the building envelope and to installations in existing buildings adds up to significant energy efficiency

  3. Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

    Science.gov (United States)

    Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

    2014-09-29

    Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

  4. Sweden's radiation protection regulations for spent fuel and nuclear waste: Requirements and compliance

    International Nuclear Information System (INIS)

    Norden, M.; Jensen, M.; Larsson, C.M.; Avila, R.; Bergman, S.S.; Wiebert, A.; Wiklund, A.

    2000-01-01

    The Swedish regulations on radiation protection in connection with spent fuel and nuclear waste disposal concern protection of human health and the environment. The reasoning behind the regulations is in observance with the Rio declaration, in the sense that they take into consideration sustainable development also in continued presence of multiple sources of radioactive effluents. Optimisation and best available technique are used as methods for risk reduction. For human health, a risk concept is used, whereas for environmental protection, focus is set on protection of biological resources and diversity. Compliance with the health and environmental goals is discussed using generic definition of the environment. The hypothetical outflow from a repository takes place in the different compartments and the resulting spread in doses are discussed and compared to the requirements of the individual dose standard, and other environmental effects are assessed. (author)

  5. Successful emotion regulation requires both conviction and skill: beliefs about the controllability of emotions, reappraisal, and regulation success.

    Science.gov (United States)

    Gutentag, Tony; Halperin, Eran; Porat, Roni; Bigman, Yochanan E; Tamir, Maya

    2017-09-01

    To succeed in self-regulation, people need to believe that it is possible to change behaviour and they also need to use effective means to enable such a change. We propose that this also applies to emotion regulation. In two studies, we found that people were most successful in emotion regulation, the more they believed emotions can be controlled and the more they used an effective emotion regulation strategy - namely, cognitive reappraisal. Cognitive reappraisal moderated the link between beliefs about the controllability of emotion and success in emotion regulation, when reappraisal was measured as a trait (Study 1) or manipulated (Study 2). Such moderation was found when examining the regulation of disgust elicited by emotion-inducing films (Study 1), and the regulation of anger elicited by real political events (Study 2). We discuss the implications of our findings for research and practice in emotion regulation.

  6. Eph receptor interclass cooperation is required for the regulation of cell proliferation

    International Nuclear Information System (INIS)

    Jurek, Aleksandra; Genander, Maria; Kundu, Parag; Catchpole, Timothy; He, Xiao; Strååt, Klas; Sabelström, Hanna; Xu, Nan-Jie; Pettersson, Sven; Henkemeyer, Mark; Frisén, Jonas

    2016-01-01

    Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signaling clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells. - Highlights: • We demonstrate that ephrin-B1 and ephrin-B2 have largely non-overlapping functions in the intestinal stem cell niche. • Ephrin-B1 regulates cell positioning and ephrin-B2 regulates cell proliferation in the intestinal stem cell niche. • EphA4/B2 receptor cooperation in response to ephrin-B2 binding is obligatory to convey mitogenic signals in the intestine. • EphA4 facilitates EphB2 phosphorylation in response to ephrin-B2 in SW480 adenocarcinoma cells. • Ephrin-B1 and ephrin-B2 induce phosphorylation and degradation of the EphB2 receptor with different kinetics.

  7. Eph receptor interclass cooperation is required for the regulation of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Jurek, Aleksandra; Genander, Maria [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Kundu, Parag [Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Catchpole, Timothy [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); He, Xiao; Strååt, Klas; Sabelström, Hanna [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Xu, Nan-Jie [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); Pettersson, Sven [Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Singapore Centre on Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); The National Cancer Centre, Singapore General Hospital (Singapore); Henkemeyer, Mark [Department of Developmental Biology, University of Texas Southwestern Medical Center, Dallas TX 75390 (United States); Frisén, Jonas, E-mail: jonas.frisen@ki.se [Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden)

    2016-10-15

    Cancer often arises by the constitutive activation of mitogenic pathways by mutations in stem cells. Eph receptors are unusual in that although they regulate the proliferation of stem/progenitor cells in many adult organs, they typically fail to transform cells. Multiple ephrins and Eph receptors are often co-expressed and are thought to be redundant, but we here describe an unexpected dichotomy with two homologous ligands, ephrin-B1 and ephrin-B2, regulating specifically migration or proliferation in the intestinal stem cell niche. We demonstrate that the combined activity of two different coexpressed Eph receptors of the A and B class assembled into common signaling clusters in response to ephrin-B2 is required for mitogenic signaling. The requirement of two different Eph receptors to convey mitogenic signals identifies a new type of cooperation within this receptor family and helps explain why constitutive activation of a single receptor fails to transform cells. - Highlights: • We demonstrate that ephrin-B1 and ephrin-B2 have largely non-overlapping functions in the intestinal stem cell niche. • Ephrin-B1 regulates cell positioning and ephrin-B2 regulates cell proliferation in the intestinal stem cell niche. • EphA4/B2 receptor cooperation in response to ephrin-B2 binding is obligatory to convey mitogenic signals in the intestine. • EphA4 facilitates EphB2 phosphorylation in response to ephrin-B2 in SW480 adenocarcinoma cells. • Ephrin-B1 and ephrin-B2 induce phosphorylation and degradation of the EphB2 receptor with different kinetics.

  8. Self-Organization of Genome Expression from Embryo to Terminal Cell Fate: Single-Cell Statistical Mechanics of Biological Regulation

    Directory of Open Access Journals (Sweden)

    Alessandro Giuliani

    2017-12-01

    Full Text Available A statistical mechanical mean-field approach to the temporal development of biological regulation provides a phenomenological, but basic description of the dynamical behavior of genome expression in terms of autonomous self-organization with a critical transition (Self-Organized Criticality: SOC. This approach reveals the basis of self-regulation/organization of genome expression, where the extreme complexity of living matter precludes any strict mechanistic approach. The self-organization in SOC involves two critical behaviors: scaling-divergent behavior (genome avalanche and sandpile-type critical behavior. Genome avalanche patterns—competition between order (scaling and disorder (divergence reflect the opposite sequence of events characterizing the self-organization process in embryo development and helper T17 terminal cell differentiation, respectively. On the other hand, the temporal development of sandpile-type criticality (the degree of SOC control in mouse embryo suggests the existence of an SOC control landscape with a critical transition state (i.e., the erasure of zygote-state criticality. This indicates that a phase transition of the mouse genome before and after reprogramming (immediately after the late 2-cell state occurs through a dynamical change in a control parameter. This result provides a quantitative open-thermodynamic appreciation of the still largely qualitative notion of the epigenetic landscape. Our results suggest: (i the existence of coherent waves of condensation/de-condensation in chromatin, which are transmitted across regions of different gene-expression levels along the genome; and (ii essentially the same critical dynamics we observed for cell-differentiation processes exist in overall RNA expression during embryo development, which is particularly relevant because it gives further proof of SOC control of overall expression as a universal feature.

  9. Extracellular Matrix-Regulated Gene Expression RequiresCooperation of SWI/SNF and Transcription Factors

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ren; Spencer, Virginia A.; Bissell, Mina J.

    2006-05-25

    Extracellular cues play crucial roles in the transcriptional regulation of tissue-specific genes, but whether and how these signals lead to chromatin remodeling is not understood and subject to debate. Using chromatin immunoprecipitation (ChIP) assays and mammary-specific genes as models, we show here that extracellular matrix (ECM) molecules and prolactin cooperate to induce histone acetylation and binding of transcription factors and the SWI/SNF complex to the {beta}- and ?-casein promoters. Introduction of a dominant negative Brg1, an ATPase subunit of SWI/SNF complex, significantly reduced both {beta}- and ?-casein expression, suggesting that SWI/SNF-dependent chromatin remodeling is required for transcription of mammary-specific genes. ChIP analyses demonstrated that the ATPase activity of SWI/SNF is necessary for recruitment of RNA transcriptional machinery, but not for binding of transcription factors or for histone acetylation. Coimmunoprecipitation analyses showed that the SWI/SNF complex is associated with STAT5, C/EBP{beta}, and glucocorticoid receptor (GR). Thus, ECM- and prolactin-regulated transcription of the mammary-specific casein genes requires the concerted action of chromatin remodeling enzymes and transcription factors.

  10. Identification of two gene clusters and a transcriptional regulator required for Pseudomonas aeruginosa glycine betaine catabolism.

    Science.gov (United States)

    Wargo, Matthew J; Szwergold, Benjamin S; Hogan, Deborah A

    2008-04-01

    Glycine betaine (GB), which occurs freely in the environment and is an intermediate in the catabolism of choline and carnitine, can serve as a sole source of carbon or nitrogen in Pseudomonas aeruginosa. Twelve mutants defective in growth on GB as the sole carbon source were identified through a genetic screen of a nonredundant PA14 transposon mutant library. Further growth experiments showed that strains with mutations in two genes, gbcA (PA5410) and gbcB (PA5411), were capable of growth on dimethylglycine (DMG), a catabolic product of GB, but not on GB itself. Subsequent nuclear magnetic resonance (NMR) experiments with 1,2-(13)C-labeled choline indicated that these genes are necessary for conversion of GB to DMG. Similar experiments showed that strains with mutations in the dgcAB (PA5398-PA5399) genes, which exhibit homology to genes that encode other enzymes with demethylase activity, are required for the conversion of DMG to sarcosine. Mutant analyses and (13)C NMR studies also confirmed that the soxBDAG genes, predicted to encode a sarcosine oxidase, are required for sarcosine catabolism. Our screen also identified a predicted AraC family transcriptional regulator, encoded by gbdR (PA5380), that is required for growth on GB and DMG and for the induction of gbcA, gbcB, and dgcAB in response to GB or DMG. Mutants defective in the previously described gbt gene (PA3082) grew on GB with kinetics similar to those of the wild type in both the PAO1 and PA14 strain backgrounds. These studies provided important insight into both the mechanism and the regulation of the catabolism of GB in P. aeruginosa.

  11. New requirements embodied in expert knowledge regulations for industrial radiation protection officers

    International Nuclear Information System (INIS)

    Vogt, H.G.

    2001-01-01

    Expert knowledge standards and certification requirements of health physics responsible persons or radiation safety officers in industry or in health care are laid down in Germany in administrative regulations. Now the new Radiation Protection Ordinance (StrlSchV) contains a specific section exclusively devoted to all aspects of expert knowledge in industrial radiation protection, which inter alia demonstrates the special significance of education and further training of radiation protection specialists. It is expected that the forthcoming new X-ray Ordinance (RoeV) will contain a similar amendment. The article explains the implications of the new Radiation Protection Ordinance for the education and further training of industrial radiation protection officers, but does not address specific aspects of nuclear engineering. (orig./CB) [de

  12. Learned stressor resistance requires extracellular signal-regulated kinase in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    John Paul Christianson

    2014-10-01

    Full Text Available Behaviorally controllable stressors confer protection from the neurochemical and behavioral consequences of future uncontrollable stressors, a phenomenon termed behavioral immunization. Recent data implicate neuroplasticity within the ventromedial prefrontal cortex (mPFC as critical to behavioral immunization. Adult, male Sprague-Dawley rats were exposed to a series of controllable tailshocks and one week later to uncontrollable tailshocks, followed 24h later by social exploration and shuttlebox escape tests. To test the involvement of N-methyl-D-aspartate receptors (NMDAR and the extracellular signal-regulated kinase (ERK cascade in behavioral immunization, either D-AP5 or the MEK inhibitor U0126 was injected to the prelimbic (PL or infralimbic (IL mPFC prior to controllable stress exposure. Phosphorylated ERK and P70S6K, regulators of transcription and translation, were quantified by Western blot or immunohistochemistry after controllable or uncontrollable tailshocks. Prior controllable stress prevented the social exploration and shuttlebox performance deficits caused by the later uncontrollable stressor, and this effect was blocked by injections of D-AP5 into mPFC. A significant increase in phosphorylated ERK1 and ERK2, but not P70S6K, occurred within the PL and IL in rats exposed to controllable stress, but not to uncontrollable stress. However, U0126 only prevented behavioral immunization when injected to the PL. We provide evidence that NMDAR and ERK dependent plasticity within the PL region is required for behavioral immunization, a learned form of stressor resistance.

  13. Interdomain allosteric regulation of Polo kinase by Aurora B and Map205 is required for cytokinesis

    Science.gov (United States)

    Kachaner, David; Pinson, Xavier; El Kadhi, Khaled Ben; Normandin, Karine; Talje, Lama; Lavoie, Hugo; Lépine, Guillaume; Carréno, Sébastien; Kwok, Benjamin H.; Hickson, Gilles R.

    2014-01-01

    Drosophila melanogaster Polo and its human orthologue Polo-like kinase 1 fulfill essential roles during cell division. Members of the Polo-like kinase (Plk) family contain an N-terminal kinase domain (KD) and a C-terminal Polo-Box domain (PBD), which mediates protein interactions. How Plks are regulated in cytokinesis is poorly understood. Here we show that phosphorylation of Polo by Aurora B is required for cytokinesis. This phosphorylation in the activation loop of the KD promotes the dissociation of Polo from the PBD-bound microtubule-associated protein Map205, which acts as an allosteric inhibitor of Polo kinase activity. This mechanism allows the release of active Polo from microtubules of the central spindle and its recruitment to the site of cytokinesis. Failure in Polo phosphorylation results in both early and late cytokinesis defects. Importantly, the antagonistic regulation of Polo by Aurora B and Map205 in cytokinesis reveals that interdomain allosteric mechanisms can play important roles in controlling the cellular functions of Plks. PMID:25332165

  14. Computational modeling of allosteric regulation in the hsp90 chaperones: a statistical ensemble analysis of protein structure networks and allosteric communications.

    Directory of Open Access Journals (Sweden)

    Kristin Blacklock

    2014-06-01

    Full Text Available A fundamental role of the Hsp90 chaperone in regulating functional activity of diverse protein clients is essential for the integrity of signaling networks. In this work we have combined biophysical simulations of the Hsp90 crystal structures with the protein structure network analysis to characterize the statistical ensemble of allosteric interaction networks and communication pathways in the Hsp90 chaperones. We have found that principal structurally stable communities could be preserved during dynamic changes in the conformational ensemble. The dominant contribution of the inter-domain rigidity to the interaction networks has emerged as a common factor responsible for the thermodynamic stability of the active chaperone form during the ATPase cycle. Structural stability analysis using force constant profiling of the inter-residue fluctuation distances has identified a network of conserved structurally rigid residues that could serve as global mediating sites of allosteric communication. Mapping of the conformational landscape with the network centrality parameters has demonstrated that stable communities and mediating residues may act concertedly with the shifts in the conformational equilibrium and could describe the majority of functionally significant chaperone residues. The network analysis has revealed a relationship between structural stability, global centrality and functional significance of hotspot residues involved in chaperone regulation. We have found that allosteric interactions in the Hsp90 chaperone may be mediated by modules of structurally stable residues that display high betweenness in the global interaction network. The results of this study have suggested that allosteric interactions in the Hsp90 chaperone may operate via a mechanism that combines rapid and efficient communication by a single optimal pathway of structurally rigid residues and more robust signal transmission using an ensemble of suboptimal multiple

  15. Pressure transmitters: Addressing post-Fukushima regulations and requirements with Bibloc technology by Rolls-Royce

    International Nuclear Information System (INIS)

    Fabbro, Herve; Desgeorge, Romain; Chowanek, Michel

    2013-06-01

    Nuclear power stations are designed to withstand substantial seismic activity and as such represent some of the most robust buildings in the world. However The Fukushima nuclear incident highlighted the potential vulnerability of nuclear power plants when multiple natural events of historic proportions happen simultaneously. Following the incident, the worldwide nuclear industry quite rightly called for an immediate review and a targeted reassessment of the safety margins of nuclear reactors. Several recommendations have been given by international safety authorities, including a significant toughening of the already stringent regulations and requirements, with respect to earthquakes, extreme temperatures, pressure and radiation resistance. In the event of an accident, a quick response is imperative and to act efficiently, a correct knowledge of the situation as well as an accurate estimation of its severity are required. Thus, it is essential to be able to rely on the most reliable sensors possible, in particular for the 50 to 100 classified pressure transmitters. Equipment used in nuclear plants all over the world, such pressure transmitters, are implemented following one of two different types of design: - The Monobloc design where almost all the equipment or system is installed very close to the reactor, within the reactor building. - The Bibloc design where the most sensitive parts (in particular the electronics) are removed from the harsh environment present in the vicinity of the reactor to be placed outside of the reactor building. The paper will present the advantages of the Bibloc technology and will show how this technology meets the 'Post Fukushima' requirements. (authors)

  16. 78 FR 68829 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Contract...

    Science.gov (United States)

    2013-11-15

    ... DFARS 252.232-7007, Limitation of Government's Obligation. DFARS subpart 232.7, Contract [[Page 68830...; Defense Federal Acquisition Regulation Supplement; Contract Financing AGENCY: Defense Acquisition... and OMB Number: Defense Federal Acquisition Regulation Supplement (DFARS) Part 232, Contract Financing...

  17. Experiences in certification of packages for transportation of fresh nuclear fuel in the context of new safety requirements established by IAEA regulations (IAEA-96 regulations, ST-1) for air transportation of nuclear materials (requirements to C-type packages)

    Energy Technology Data Exchange (ETDEWEB)

    Dudai, V.I.; Kovtun, A.D.; Matveev, V.Z.; Morenko, A.I.; Nilulin, V.M.; Shapovalov, V.I.; Yakushev, V.A.; Bobrovsky, V.S.; Rozhkov, V.V.; Agapov, A.M.; Kolesnikov, A.S. [Russian Federal Nuclear Centre - All-Russian Research Inst. of Experimental Physics, Sarov (Russian Federation)]|[JSC ' ' MSZ' ' , Electrostal (Russian Federation)]|[JSC ' ' NPCC' ' , Novosibirsk (Russian Federation)]|[Minatom of Russia, Moscow (Russian Federation)]|[Gosatomnadzor of Russia, Moscow (Russian Federation)

    2004-07-01

    Every year in Russia, a large amount of domestic and international transportation of fresh nuclear fuel (FNF) used in Russian and foreign energy and research atomic reactors and referred to fissile materials based on IAEA Regulations is performed. Here, bulk transportation is performed by air, and it concerns international transportation in particular. According to national ''Main Regulations for Safe Transport and physical Protection of Nuclear Materials (OPBZ- 83)'' and ''Regulations for the Safe Transport of Radioactive Materials'' of the International Atomic Energy Agency (IAEA Regulations), nuclear and radiation security under normal (accident free) and accident conditions of transport must be completely provided by the package design. In this context, high requirements to fissile packages exposed to heat and mechanical loads in transport accidents are imposed. A long-standing experience in accident free transportation of FM has shown that such approach to provide nuclear and radiation security pays for itself completely. Nevertheless, once in 10 years the International Atomic Energy Agency on every revision of the ''Regulations for the Safe Transport of Radioactive Materials'' places more stringent requirements upon the FM and transportation thereof, resulting from the objectively increasing risk associated with constant rise in volume and density of transportation, and also strained social and economical situation in a number of regions in the world. In the new edition of the IAEA Regulations (ST-1), published in 1996 and brought into force in 2001 (IAEA-96 Regulations), the requirements to FM packages conveyed by aircraft were radically changed. These requirements are completely presented in new Russian ''Regulations for the Safe Transport of Radioactive Materials'' (PBTRM- 2004) which will be brought into force in the time ahead.

  18. Vernalization and the Chilling Requirement to Exit Bud Dormancy: Shared or Separate Regulation?

    Directory of Open Access Journals (Sweden)

    Amy M Brunner

    2014-12-01

    Full Text Available Similarities have long been recognized between vernalization, the prolonged exposure to cold temperatures that promotes the floral transition in many plants, and the chilling requirement to release bud dormancy in woody plants of temperate climates. In both cases the extended chilling period occurring during winter is used to coordinate developmental events to the appropriate seasonal time. However, whether or not these processes share common regulatory components and molecular mechanisms remain largely unknown. Both gene function and association genetics studies in Populus are beginning to answer this question. In Populus, studies have revealed that orthologs of the antagonistic flowering time genes FT and CEN/TFL1 might have central roles in both processes. We review Populus seasonal shoot development related to dormancy release and the floral transition and evidence for FT/TFL1-mediated regulation of these processes to consider the question of regulatory overlap. In addition, we discuss the potential for and challenges to integrating functional and population genomics studies to uncover the regulatory mechanisms underpinning these processes in woody plant systems.

  19. CSL protein regulates transcription of genes required to prevent catastrophic mitosis in fission yeast.

    Science.gov (United States)

    Převorovský, Martin; Oravcová, Martina; Zach, Róbert; Jordáková, Anna; Bähler, Jürg; Půta, František; Folk, Petr

    2016-11-16

    For every eukaryotic cell to grow and divide, intricately coordinated action of numerous proteins is required to ensure proper cell-cycle progression. The fission yeast Schizosaccharomyces pombe has been instrumental in elucidating the fundamental principles of cell-cycle control. Mutations in S. pombe 'cut' (cell untimely torn) genes cause failed coordination between cell and nuclear division, resulting in catastrophic mitosis. Deletion of cbf11, a fission yeast CSL transcription factor gene, triggers a 'cut' phenotype, but the precise role of Cbf11 in promoting mitotic fidelity is not known. We report that Cbf11 directly activates the transcription of the acetyl-coenzyme A carboxylase gene cut6, and the biotin uptake/biosynthesis genes vht1 and bio2, with the former 2 implicated in mitotic fidelity. Cbf11 binds to a canonical, metazoan-like CSL response element (GTGGGAA) in the cut6 promoter. Expression of Cbf11 target genes shows apparent oscillations during the cell cycle using temperature-sensitive cdc25-22 and cdc10-M17 block-release experiments, but not with other synchronization methods. The penetrance of catastrophic mitosis in cbf11 and cut6 mutants is nutrient-dependent. We also show that drastic decrease in biotin availability arrests cell proliferation but does not cause mitotic defects. Taken together, our results raise the possibility that CSL proteins play conserved roles in regulating cell-cycle progression, and they could guide experiments into mitotic CSL functions in mammals.

  20. Experimental and statistical requirements for developing a well-defined K/sub IR/ curve. Final report

    International Nuclear Information System (INIS)

    Server, W.L.; Oldfield, W.; Wullaert, R.A.

    1977-05-01

    Further development of a statistically well-defined reference fracture toughness curve to verify and compliment the K/sub IR/ curve presently specified in Appendix G, Section III of the ASME Code was accomplished by performing critical experiments in small specimen fracture mechanics and improving techniques for statistical analysis of the data. Except for cleavage-initiated fracture, crack initiation was observed to occur prior to maximum load for all of the materials investigated. Initiation fracture toughness values (K/sub Jc/) based on R-curve heat-tinting studies were up to 50 percent less than the previously reported equivalent energy values (K*/sub d/). At upper shelf temperatures, the initiation fracture toughness (K/sub Jc/) generally increased with stress intensification rate. Both K/sub Jc/--Charpy V-notch and K/sub Ic/--specimen strength ratio correlations are promising methods for predicting thick-section behavior from small specimens. The previously developed tanh curve fitting procedure was improved to permit estimates of the variances and covariances of the regression coefficients to be computed. The distribution of the fracture toughness data was determined as a function of temperature. Instrumented precracked Charpy results were used to normalize the larger specimen fracture toughness data. The transformed large specimen fracture toughness data are used to generate statistically based lower-bound fracture toughness curves for either static or dynamic test results. A comparison of these lower bound curves with the K/sub IR/ curve shows that the K/sub IR/ curve is more conservative over most of its range. 143 figures, 26 tables

  1. Zinc coordination is required for and regulates transcription activation by Epstein-Barr nuclear antigen 1.

    Directory of Open Access Journals (Sweden)

    Siddhesh Aras

    2009-06-01

    Full Text Available Epstein-Barr Nuclear Antigen 1 (EBNA1 is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO(2. Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO(2 and redox potential.

  2. NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation

    International Nuclear Information System (INIS)

    Adachi, Atsuo; Takahashi, Tomosaburo; Ogata, Takehiro; Imoto-Tsubakimoto, Hiroko; Nakanishi, Naohiko; Ueyama, Tomomi; Matsubara, Hiroaki

    2012-01-01

    Highlights: ► NFAT5 protein expression is downregulated during cardiomyogenesis. ► Inhibition of NFAT5 function suppresses canonical Wnt signaling. ► Inhibition of NFAT5 function attenuates mesodermal induction. ► NFAT5 function is required for cardiomyogenesis. -- Abstract: While nuclear factor of activated T cells 5 (NFAT5), a transcription factor implicated in osmotic stress response, is suggested to be involved in other processes such as migration and proliferation, its role in cardiomyogenesis is largely unknown. Here, we examined the role of NFAT5 in cardiac differentiation of P19CL6 cells, and observed that it was abundantly expressed in undifferentiated P19CL6 cells, and its protein expression was significantly downregulated by enhanced proteasomal degradation during DMSO-induced cardiomyogenesis. Expression of a dominant negative mutant of NFAT5 markedly attenuated cardiomyogenesis, which was associated with the inhibition of mesodermal differentiation. TOPflash reporter assay revealed that the transcriptional activity of canonical Wnt signaling was activated prior to mesodermal differentiation, and this activation was markedly attenuated by NFAT5 inhibition. Pharmacological activation of canonical Wnt signaling by [2′Z, 3′E]-6-bromoindirubin-3′-oxime (BIO) restored Brachyury expression in NFAT5DN-expressing cells. Inhibition of NFAT5 markedly attenuated Wnt3 and Wnt3a induction. Expression of Dkk1 and Cerberus1, which are secreted Wnt antagonists, was also inhibited by NFAT5 inhibition. Thus, endogenous NFAT5 regulates the coordinated expression of Wnt ligands and antagonists, which are essential for cardiomyogenesis through the canonical Wnt pathway. These results demonstrated a novel role of NFAT5 in cardiac differentiation of stem cells.

  3. Novel insights into iron regulation and requirement in marine medaka Oryzias melastigma.

    Science.gov (United States)

    Wang, Jian; Wang, Wen-Xiong

    2016-05-24

    Iron (Fe) is an essential trace element for marine fish. However, our knowledge of Fe requirements at different development stages of marine fish is still limited. Here, we reported the efficient Fe absorption strategies adopted by larval fish under different dietary Fe supplementary levels (i.e., 0-640 mg/kg). Biokinetically, the larval fish controlled their dietary Fe assimilation efficiency (AE, 1.6-18.5%), and enhanced their waterborne Fe uptake (ca. 2.5 fold change of uptake rate constant) once the dietary Fe was deficient (i.e., 27.4 mg Fe/kg feed). Transcriptionally, the expression of hepcidin1 (hep1; Fe regulator; i.e., 2.3-15.7 fold change) in larval fish was positively correlated with the Fe supplementary levels. Comparatively, the female adult fish were poor in assimilating the added Fe source (i.e., ferric form) with similar life-sustainable levels of Fe (i.e., 0.046-0.12 μg/g/d assimilated for Fe supplementary levels of 27.4, 162 and 657 mg Fe/kg feed). The overall feeding experiments suggested that dietary net Fe flux sufficient for the normal growth of larval medaka was 0.71-1.75 μg/g/d (i.e., 83.9 mg Fe/kg feed), consistent with the modeled value (i.e., 1.09-2.16 μg/g/d). In female adults, the estimated essential net Fe flux was 0.88-0.90 μg/g/d.

  4. 25 CFR 518.7 - If a tribe holds a certificate of self-regulation, is it required to report information to the...

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false If a tribe holds a certificate of self-regulation, is it... REGULATION OF CLASS II GAMING § 518.7 If a tribe holds a certificate of self-regulation, is it required to... certificate of self-regulation shall be required to submit a self-regulation report annually to the Commission...

  5. Melanocortin 4 receptor is not required for estrogenic regulations on energy homeostasis and reproduction

    Science.gov (United States)

    Brain estrogen receptor-a (ERa) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERa expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic–pituitary–gonadal...

  6. 9 CFR 201.4 - Bylaws, rules and regulations, and requirements of exchanges, associations, or other...

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Bylaws, rules and regulations, and... 201.4 Animals and Animal Products GRAIN INSPECTION, PACKERS AND STOCKYARDS ADMINISTRATION (PACKERS AND... of any exchange, association, or other organization, or any other valid law, rule or regulation, or...

  7. Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

    Science.gov (United States)

    Tate, Jennifer J.; Cooper, Terrance G.

    2013-01-01

    Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

  8. Does bisphenol A induce superfeminization in Marisa cornuarietis? Part II: toxicity test results and requirements for statistical power analyses.

    Science.gov (United States)

    Forbes, Valery E; Aufderheide, John; Warbritton, Ryan; van der Hoeven, Nelly; Caspers, Norbert

    2007-03-01

    This study presents results of the effects of bisphenol A (BPA) on adult egg production, egg hatchability, egg development rates and juvenile growth rates in the freshwater gastropod, Marisa cornuarietis. We observed no adult mortality, substantial inter-snail variability in reproductive output, and no effects of BPA on reproduction during 12 weeks of exposure to 0, 0.1, 1.0, 16, 160 or 640 microg/L BPA. We observed no effects of BPA on egg hatchability or timing of egg hatching. Juveniles showed good growth in the control and all treatments, and there were no significant effects of BPA on this endpoint. Our results do not support previous claims of enhanced reproduction in Marisa cornuarietis in response to exposure to BPA. Statistical power analysis indicated high levels of inter-snail variability in the measured endpoints and highlighted the need for sufficient replication when testing treatment effects on reproduction in M. cornuarietis with adequate power.

  9. 77 FR 33635 - Amendment to the Bank Secrecy Act Regulations-Requirement That Clerks of Court Report Certain...

    Science.gov (United States)

    2012-06-07

    ... business rule reflects that the definition of currency used therein is slightly different from the... Amendment to the Bank Secrecy Act Regulations--Requirement That Clerks of Court Report Certain Currency...: FinCEN is amending the rules relating to the reporting of certain currency transactions consistent...

  10. 77 FR 16196 - Delaying the Compliance Date for Certain Requirements of the Regulations Implementing Titles II...

    Science.gov (United States)

    2012-03-20

    ... be received. The constraints imposed by the Regulations.gov/FDMS system do not apply to U.S. postal... pools, wading pools, and spas in compliance with the 2010 Standards. The proposed extension would run...

  11. 76 FR 17138 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2011-03-28

    ... initiated research. Topics for discussion include the following: (1) What FDA Expects in a Pharmaceutical Clinical Trial; (2) Adverse Event Reporting--Science, Regulation, Error, and Safety; (3) Part 11 Compliance...

  12. 75 FR 51824 - Food and Drug Administration Clinical Trial Requirements, Regulations, Compliance, and Good...

    Science.gov (United States)

    2010-08-23

    ... discussion include the following: (1) What FDA expects in a pharmaceutical clinical trial; (2) adverse event reporting--science, regulation, error, and safety; (3) Part 11 Compliance--Electronic signatures; (4...

  13. 14 CFR 11.61 - May I ask FAA to adopt, amend, or repeal a regulation, or grant relief from the requirements of a...

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false May I ask FAA to adopt, amend, or repeal a regulation, or grant relief from the requirements of a current regulation? 11.61 Section 11.61 Aeronautics... to adopt, amend, or repeal a regulation, or grant relief from the requirements of a current...

  14. Dissecting Sequences of Regulation and Cognition: Statistical Discourse Analysis of Primary School Children's Collaborative Learning

    Science.gov (United States)

    Molenaar, Inge; Chiu, Ming Ming

    2014-01-01

    Extending past research showing that regulative activities (metacognitive and relational) can aid learning, this study tests whether sequences of cognitive, metacognitive and relational activities affect subsequent cognition. Scaffolded by a computer avatar, 54 primary school students (working in 18 groups of 3) discussed writing a report about a…

  15. Rhetoric and Realities: What Independence of the Bar Requires of Lawyer Regulation

    Directory of Open Access Journals (Sweden)

    Alice Woolley

    2011-06-01

    Full Text Available The Canadian legal profession is largely self-regulating. Provincial law societies governed by lawyers elected by their peers set the standards for admission to the profession and for ethical conduct, and investigate, prosecute and adjudicate allegations of professional misconduct by lawyers. Advocates for this regulatory structure rely on the concept of “independence of the bar”, the idea that lawyers must be free from any external interference with their representation of clients. Critics of the regulatory structure, meanwhile, argue that independence has a broader meaning than the advocates suppose and that, in any event, the self-regulatory structure of the Canadian profession is not necessary to ensure independence. This paper presents the varying interpretations of independence of the bar and suggests that while the advocates for self-regulation have a more justifiable understanding of independence than do critics, the concept of independence of the bar is not itself central to assessing the validity of any particular regulatory scheme. Rather, the things that independence should protect – the ability of lawyers to be zealous advocates for clients within the bounds of legality – should be used to assess the adequacies of any regulatory scheme. Does regulation ensure that lawyers fulfill their duty of zealous advocacy? Does regulation ensure that lawyers remain within the bounds of legality? Does regulation ensure access to justice? With these criteria in mind, and using recent changes to the regulation of lawyers in England and Wales as a comparator, the paper then analyzes the adequacy of regulation of Canadian lawyers with respect to competence, the general structure of professional regulation and access to justice. Based on this analysis, the author proposes changes to improve lawyer regulation in Canada. These changes do not abandon self-regulation. However, they include separating the adjudicative function of the law societies

  16. Understanding Statistics - Cancer Statistics

    Science.gov (United States)

    Annual reports of U.S. cancer statistics including new cases, deaths, trends, survival, prevalence, lifetime risk, and progress toward Healthy People targets, plus statistical summaries for a number of common cancer types.

  17. 78 FR 11279 - Loan Originator Compensation Requirements Under the Truth in Lending Act (Regulation Z)

    Science.gov (United States)

    2013-02-15

    .... Fin., Mortgage Originations by Product, in 1 The 2011 Mortgage Market Statistical Annual 20 (2011). So.... When housing prices began to decline in 2005, refinancing became more difficult and delinquency rates..., respectively. In addition, as the economy worsened, the rates of serious delinquency (90 or more days past due...

  18. WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

    KAUST Repository

    Abdallah, Abdallah

    2018-04-09

    The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

  19. WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

    KAUST Repository

    Abdallah, Abdallah; Weerdenburg, Eveline; Guan, Qingtian; Ummels, Roy; Borggreve, S; Adroub, Sabir; Malas, Tareq; Naeem, Raeece; Zhang, Huoming; Otto, Thomas; Bitter, Wilbert; Pain, Arnab

    2018-01-01

    The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

  20. Profiles of Motivated Self-Regulation in College Computer Science Courses: Differences in Major versus Required Non-Major Courses

    Science.gov (United States)

    Shell, Duane F.; Soh, Leen-Kiat

    2013-12-01

    The goal of the present study was to utilize a profiling approach to understand differences in motivation and strategic self-regulation among post-secondary STEM students in major versus required non-major computer science courses. Participants were 233 students from required introductory computer science courses (194 men; 35 women; 4 unknown) at a large Midwestern state university. Cluster analysis identified five profiles: (1) a strategic profile of a highly motivated by-any-means good strategy user; (2) a knowledge-building profile of an intrinsically motivated autonomous, mastery-oriented student; (3) a surface learning profile of a utility motivated minimally engaged student; (4) an apathetic profile of an amotivational disengaged student; and (5) a learned helpless profile of a motivated but unable to effectively self-regulate student. Among CS majors and students in courses in their major field, the strategic and knowledge-building profiles were the most prevalent. Among non-CS majors and students in required non-major courses, the learned helpless, surface learning, and apathetic profiles were the most prevalent. Students in the strategic and knowledge-building profiles had significantly higher retention of computational thinking knowledge than students in other profiles. Students in the apathetic and surface learning profiles saw little instrumentality of the course for their future academic and career objectives. Findings show that students in STEM fields taking required computer science courses exhibit the same constellation of motivated strategic self-regulation profiles found in other post-secondary and K-12 settings.

  1. 75 FR 26121 - Regulation of Fuels and Fuel Additives: Alternative Affirmative Defense Requirements for Ultra...

    Science.gov (United States)

    2010-05-11

    ... standard at retail facilities. This alternative defense consists of a comprehensive program of quality... without change and may be made available online at http://www.regulations.gov , including any personal..., import, sell, store or transport ULSD highway diesel fuel to meet the standards specified in the diesel...

  2. 78 FR 20624 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Science.gov (United States)

    2013-04-05

    ... Identification Advance Shipment Notices AGENCY: Defense Acquisition Regulations System, Department of Defense (Do...) Whether the proposed collection of information is necessary for the proper performance of the functions of... at 252.211; Radio Frequency Identification Advance Shipment Notices, OMB Control Number 0704-0434...

  3. 78 FR 27308 - Loan Originator Compensation Requirements Under the Truth In Lending Act (Regulation Z...

    Science.gov (United States)

    2013-05-10

    ... consumer financial laws, to consider the potential benefits and costs of regulation to consumers and... effective date of Sec. 1026.36(i) would also delay the consumer benefit that would result from allowing the..., 2013 / Proposed Rules#0;#0; [[Page 27308

  4. 27 CFR 70.411 - Imposition of taxes, qualification requirements, and regulations.

    Science.gov (United States)

    2010-04-01

    ... (including activities incident thereto) of distilled spirits plants for the production and/or warehousing... use in making the necessary computation from gauge data. (5) Rules of practice in permit proceedings... regulations relating to the production, bonded warehousing, and withdrawal of distilled spirits, and denatured...

  5. Franchise Values, Regulatory Monitoring, and Capital Requirements in Optimal Bank Regulation

    DEFF Research Database (Denmark)

    Andersen, Thomas Barnebeck; Harr, Thomas

    2008-01-01

    This paper demonstrates that financial deregulation is likely to make standard prudential regulatory instruments less effective in curbing excessive risk-taking incentives among banks. This has interesting implications for optimal bank regulation. When there is an increase in competition, the opt...

  6. 75 FR 33271 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Foreign...

    Science.gov (United States)

    2010-06-11

    ... Certain Contracts with Foreign Entities for the Conduct of Ballistic Missile Defense Research, Development..., development, test, or evaluation in connection with the Ballistic Missile Defense Program. The provision... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System [OMB Control Number 0704-0229...

  7. 78 FR 69267 - Defense Federal Acquisition Regulation Supplement: Requirements Relating to Supply Chain Risk...

    Science.gov (United States)

    2013-11-18

    ... payroll, finance, logistics, and personnel management applications; or (2) Is protected at all times by... recommendation from the Under Secretary of Defense for Acquisition, Technology, and Logistics (USD(AT&L)) and the... assess all costs and benefits of available regulatory alternatives and, if regulation is necessary, to...

  8. 78 FR 15935 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Science.gov (United States)

    2013-03-13

    ... automated collection techniques or other forms of information technology. The Office of Management and... construction contract in Spain has adequate insurance coverage. Affected Public: Businesses or other for profit... construction contract in Spain. Kortnee Stewart, Editor, Defense Acquisition Regulations System. [FR Doc. 2013...

  9. 76 FR 78126 - Disclosure Requirements for Depository Institutions Lacking Federal Deposit Insurance (Regulation I)

    Science.gov (United States)

    2011-12-16

    ..., Office of Regulations, at (202) 435-7700. SUPPLEMENTARY INFORMATION: I. Background The Federal Deposit... products or services or information otherwise promoting the institution; and (2) Small utilitarian items.... SUMMARY: Title X of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act...

  10. 76 FR 65411 - Specialty Crops; Import Regulations; Proposed Pistachio Import Requirements

    Science.gov (United States)

    2011-10-21

    ..., or E-mail: [email protected] or [email protected] . Small businesses may request... the proposed regulations, ``pistachio'' would mean the nut of the pistachio tree, Pistachia vera.... Pages 326-359. \\5\\ Eaton, David L.; Jennifer E. Hobden; and Bruce J. Kelman. 2002. Aflatoxin in...

  11. 77 FR 51686 - Specialty Crops; Import Regulations; New Pistachio Import Requirements

    Science.gov (United States)

    2012-08-27

    ... the new regulation, ``pistachio'' means the nut of the pistachio tree, Pistachia vera, whether inshell... Order No. 983. 2002. Pages 326-359. \\5\\ Eaton, David L.; Jennifer E. Hobden; and Bruce J. Kelman. 2002..., and New Mexico. AMS is committed to complying with the E-Government Act, to promote the use of the...

  12. 77 FR 43076 - Federal Acquisition Regulation; Information Collection; Value Engineering Requirements

    Science.gov (United States)

    2012-07-23

    ... respond, through the use of appropriate technological collection techniques or other forms of information... collection. All comments received will be posted without change to http://www.regulations.gov , including any personal and/or business confidential information provided. FOR FURTHER INFORMATION CONTACT: Mr. Curtis E...

  13. 75 FR 26739 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Part 244...

    Science.gov (United States)

    2010-05-12

    ... Control Number 0704-0253) AGENCY: Defense Acquisition Regulations System, Department of Defense. ACTION... proposed information collection; (c) ways to enhance the quality, utility, and clarity of the information..., withhold, or withdraw purchasing system approval at the conclusion of a purchasing system review...

  14. 78 FR 70025 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2013-11-22

    ... and Procedures AGENCY: Defense Acquisition Regulations System, Department of Defense (DoD). ACTION... proposed information collection; (c) ways to enhance the quality, utility, and clarity of the information..., withhold, or withdraw purchasing system approval at the conclusion of a purchasing system review...

  15. 78 FR 4032 - Prompt Corrective Action, Requirements for Insurance, and Promulgation of NCUA Rules and Regulations

    Science.gov (United States)

    2013-01-18

    ... interest rate risk requirements. The amended IRPS increases the asset threshold that identifies credit... asset threshold used to define a ``complex'' credit union for determining whether risk-based net worth... or credit unions) with assets of $50 million or less from interest rate risk rule requirements. To...

  16. 76 FR 72916 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2011-11-28

    ... information collection requires contractors to comply with the notification process at DFARS clause 252.204... purposes. The U.S.-IAEA Additional Protocol permits the United States unilaterally to declare exclusions from inspection requirements for activities with direct national security significance. The clause at...

  17. 75 FR 34277 - Federal Acquisition Regulation; FAR Case 2008-007, Additional Requirements for Market Research

    Science.gov (United States)

    2010-06-16

    ... executive agencies. Specifically, the head of the agency must conduct market research before issuing an... million for the procurement of items other than commercial items is required to conduct market research... 10 U.S.C. 2377(c), ``Preliminary Market Research'', to require the head of an agency to conduct...

  18. Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation

    Directory of Open Access Journals (Sweden)

    Oliver Todt

    2016-05-01

    Full Text Available Objective. To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Materials and methods. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. Results. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim autho- rizations. Conclusions. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

  19. Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in ß-cells from mice and humans

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram; Cortese, Giuliana; Eliasson, Lena

    2011-01-01

    Insulin is released from pancreatic ß-cells as a result of Ca2+-evoked exocytosis of dense-core granules. Secretion is biphasic, which has been suggested to correspond to the release of different granule pools. Here we review and carefully reanalyze previously published patch-clamp data on depola......Insulin is released from pancreatic ß-cells as a result of Ca2+-evoked exocytosis of dense-core granules. Secretion is biphasic, which has been suggested to correspond to the release of different granule pools. Here we review and carefully reanalyze previously published patch-clamp data...... on depolarization-evoked Ca2+-currents and corresponding capacitance measurements. Using a statistical mixed-effects model, we show that the data indicate that pool depletion is negligible in response to short depolarizations in mouse ß-cells. We then review mathematical models of granule dynamics and exocytosis...

  20. Oligomerization of Bacillus subtilis DesR is required for fine tuning regulation of membrane fluidity.

    Science.gov (United States)

    Najle, Sebastián R; Inda, María E; de Mendoza, Diego; Cybulski, Larisa E

    2009-10-01

    The DesK-DesR two-component system regulates the order of membrane lipids in the bacterium Bacillus subtilis by controlling the expression of the des gene coding for the delta 5-acyl-lipid desaturase. To activate des transcription, the membrane-bound histidine kinase DesK phosphorylates the response regulator DesR. This covalent modification of the regulatory domain of dimeric DesR promotes, in a cooperative fashion, the hierarchical occupation of two adjacent, non-identical, DesR-P binding sites, so that there is a shift in the equilibrium toward the tetrameric active form of the response regulator. However, the mechanism of regulation of DesR activity by phosphorylation and oligomerization is not well understood. We employed deletion analysis and reporter fusions to study the role of the N-terminal domain on DesR activity. In addition, electromobility shift assays were used to analyze the binding capacity of the transcription factor to deletion mutants of the des promoter. We show that DesR lacking the N-terminal domain is still able to bind to the des promoter. We also demonstrate that if the RA site is moved closer to the -35 region of Pdes, the adjacent site RB is dispensable for activation. Our results indicate that the unphosphorylated regulatory domain of DesR obstructs the access of the recognition helix of DesR to its DNA target. In addition, we present evidence showing that RB is physiologically relevant to control the activation of the des gene when the levels of DesR-P reach a critical threshold.

  1. Wnt9a signaling is required for joint integrity and regulation of Ihh during chondrogenesis.

    Science.gov (United States)

    Später, Daniela; Hill, Theo P; O'sullivan, Roderick J; Gruber, Michaela; Conner, David A; Hartmann, Christine

    2006-08-01

    Joints, which separate skeleton elements, serve as important signaling centers that regulate the growth of adjacent cartilage elements by controlling proliferation and maturation of chondrocytes. Accurate chondrocyte maturation is crucial for endochondral ossification and for the ultimate size of skeletal elements, as premature or delayed maturation results predominantly in shortened elements. Wnt9a has previously been implicated as being a player in joint induction, based on gain-of function experiments in chicken and mouse. We show that loss of Wnt9a does not affect joint induction, but results to synovial chondroid metaplasia in some joints. This phenotype can be enhanced by removal of an additional Wnt gene, Wnt4, suggesting that Wnts are playing a crucial role in directing bi-potential chondro-synovioprogenitors to become synovial connective tissue, by actively suppressing their chondrogenic potential. Furthermore, we show that Wnt9a is a temporal and spatial regulator of Indian hedgehog (Ihh), a central player of skeletogenesis. Loss of Wnt9a activity results in transient downregulation of Ihh and reduced Ihh-signaling activity at E12.5-E13.5. The canonical Wnt/beta-catenin pathway probably mediates regulation of Ihh expression in prehypertrophic chondrocytes by Wnt9a, because embryos double-heterozygous for Wnt9a and beta-catenin show reduced Ihh expression, and in vivo chromatin immunoprecipitation demonstrates a direct interaction between the beta-catenin/Lef1 complex and the Ihh promoter.

  2. Regulation requirements for the protection of workers against electromagnetic fields occurring in the work environment

    International Nuclear Information System (INIS)

    Aniolczyk, H.; Zmyslony, M.

    2006-01-01

    In Poland, electromagnetic fields (EMF), one of potentially hazardous physical factors occurring in the work environment, are subjected to compulsory surveillance. In 2001, the Directive issued by the Minister of Labor and Social Policy substantially changed the approach towards the protection of workers against EMF. The Directive regulates the whole range of EMF frequencies and electromagnetic radiation, namely from 0 Hz to 300 GHz, which means the possibility of assessing workers EMF exposure, determined by exposure index, along with the hygiene assessment of EMF sources, defined by protection zones. In 2003 - 2005, a number of amended executive and supplementary regulations were issued. However, it should be emphasized that in the process of their elaboration, striving after perfection, numerous incoherent and ambiguous provisions were adopted, which finally created difficulties in the interpretation of individual regulations. This is also linked with doubts and discussions on their practical application by services responsible for control, measurements and monitoring of working conditions under the exposure to EMF. In this work an attempt was made to clarify all issues and arrange them according to the faced problems. The authors also present proposals how to solve all these problems. (author)

  3. Regulations for the safe transport of radioactive material, 2005 edition. Safety requirements

    International Nuclear Information System (INIS)

    2005-01-01

    This publication includes amendments to the 1996 Edition (As Amended 2003) arising from the second cycle of the biennial review and revision process, as agreed by the Transport Safety Standards Committee (TRANSSC) at its ninth meeting in March 2004, as endorsed by the Commission on Safety Standards at its meeting in June 2004 and as approved by the IAEA Board of Governors in November 2004. Although this publication is identified as a new edition, there are no changes that affect the administrative and approval requirements in Section VIII. The fields covered are General Provisions (radiation protection; emergency response; quality assurance; compliance assurance; non-compliance; special arrangement and training); Activity Limits and Materials Restrictions, Requirement and Controls for Transport , Requirements for Radioactive Materials and for Packagings and Packages, Test Procedures, Approval and Administrative Requirements

  4. Regulation of mtl operon promoter of Bacillus subtilis: requirements of its use in expression vectors

    Directory of Open Access Journals (Sweden)

    Altenbuchner Josef

    2011-10-01

    Full Text Available Abstract Background Several vector systems have been developed to express any gene desired to be studied in Bacillus subtilis. Among them, the transcriptionally regulated promoters involved in carbohydrate utilization are a research priority. Expression systems based on Bacillus promoters for xylose, maltose, and mannose utilization, as well as on the heterologous E. coli lactose promoter, have been successfully constructed. The promoter of the mtlAFD operon for utilization of mannitol is another promising candidate for its use in expression vectors. In this study, we investigated the regulation of the mtl genes in order to identify the elements needed to construct a strong mannitol inducible expression system in B. subtilis. Results Regulation of the promoters of mtlAFD operon (PmtlA and mtlR (PmtlR encoding the activator were investigated by fusion to lacZ. Identification of the PmtlA and PmtlR transcription start sites revealed the σA like promoter structures. Also, the operator of PmtlA was determined by shortening, nucleotide exchange, and alignment of PmtlA and PmtlR operator regions. Deletion of the mannitol-specific PTS genes (mtlAF resulted in PmtlA constitutive expression demonstrating the inhibitory effect of EIICBMtl and EIIAMtl on MtlR in the absence of mannitol. Disruption of mtlD made the cells sensitive to mannitol and glucitol. Both PmtlA and PmtlR were influenced by carbon catabolite repression (CCR. However, a CcpA deficient mutant showed only a slight reduction in PmtlR catabolite repression. Similarly, using PgroE as a constitutive promoter, putative cre sites of PmtlA and PmtlR slightly reduced the promoter activity in the presence of glucose. In contrast, glucose repression of PmtlA and PmtlR was completely abolished in a ΔptsG mutant and significantly reduced in a MtlR (H342D mutant. Conclusions The mtl operon promoter (PmtlA is a strong promoter that reached a maximum of 13,000 Miller units with lacZ as a reporter on

  5. Requirements for Ion and Solute Transport, and pH Regulation During Enamel Maturation

    Science.gov (United States)

    LACRUZ, RODRIGO S.; SMITH, CHARLES E.; MOFFATT, PIERRE; CHANG, EUGENE H.; BROMAGE, TIMOTHY G.; BRINGAS, PABLO; NANCI, ANTONIO; BANIWAL, SANJEEV K.; ZABNER, JOSEPH; WELSH, MICHAEL J.; KURTZ, IRA; PAINE, MICHAEL L.

    2012-01-01

    Transcellular bicarbonate transport is suspected to be an important pathway used by ameloblasts to regulate extracellular pH and support crystal growth during enamel maturation. Proteins that play a role in amelogenesis include members of the ABC transporters (SLC gene family and CFTR). A number of carbonic anhydrases (CAs) have also been identified. The defined functions of these genes are likely interlinked during enamel mineralization. The purpose of this study is to quantify relative mRNA levels of individual SLC, Cftr, and CAs in enamel cells obtained from secretory and maturation stages on rat incisors. We also present novel data on the enamel phenotypes for two animal models, amutant porcine(CFTR-ΔF508) and the NBCe1-null mouse.Our data show that two SLCs(AE2 and NBCe1),Cftr,and Car2, Car3,Car6,and Car12 are all significantly up-regulated at the onset of the maturation stage of amelogenesis when compared to the secretory stage. The remaining SLCs and CA gene transcripts showed negligible expression or no significant change in expression from secretory to maturation stages. The enamel of Cftr-ΔF508 adult pigs was hypomineralized and showed abnormal crystal growth. NBCe1-null mice enamel was structurally defective and had a marked decrease in mineral content relative to wild-type. These data demonstrate the importance of many non-matrix proteins to amelogenesis and that the expression levels of multiple genes regulating extracellular pH are modulated during enamel maturation in response to an increased need for pH buffering during hydroxyapatite crystal growth. PMID:21732355

  6. Measurement and assessment of doses from external radiations required for revised radiation protection regulations

    International Nuclear Information System (INIS)

    Tsujimura, Norio; Kojima, Noboru; Hayashi, Naomi

    2001-01-01

    Radiation protection regulations based on the 1990 recommendations of ICRP have been revised and will take effect from Apr., 2001. The major changes concerning on the measurement and assessment of doses from external radiations are as follows. (1) Personal dose equivalent and ambient dose equivalent stated in ICRP Publication 74 are introduced as quantities to be measured with personal dosimeters and survey instruments, respectively. (2) For multiple dosimetry for workers, the compartment weighting factors used for a realistic assessment of effective dose are markedly changed. In advance of the introduction of the new radiation protection regulations, the impacts on workplace and personal monitoring for external radiations by these revisions were investigated. The following results were obtained. (1) A new ambient dose equivalent to neutrons is higher with a factor of 1.2 than the old one for moderated fission neutron spectra. Therefore, neutron dose equivalent monitors for workplace monitoring at MOX fuel for facilities should be recalibrated for measurement of the new ambient dose equivalent. (2) Annual effective doses of workers were estimated by applying new calibration factors to readings of personal dosimeters, worn by workers. Differences between effective doses and effective dose equivalents are small for workers engaged in the fabrication process of MOX fuel. (author)

  7. Measurement and assessment of doses from external radiations required for revised radiation protection regulations

    Energy Technology Data Exchange (ETDEWEB)

    Tsujimura, Norio; Kojima, Noboru; Hayashi, Naomi [Japan Nuclear Cycle Development Inst., Tokai, Ibaraki (Japan)

    2001-06-01

    Radiation protection regulations based on the 1990 recommendations of ICRP have been revised and will take effect from Apr., 2001. The major changes concerning on the measurement and assessment of doses from external radiations are as follows. (1) Personal dose equivalent and ambient dose equivalent stated in ICRP Publication 74 are introduced as quantities to be measured with personal dosimeters and survey instruments, respectively. (2) For multiple dosimetry for workers, the compartment weighting factors used for a realistic assessment of effective dose are markedly changed. In advance of the introduction of the new radiation protection regulations, the impacts on workplace and personal monitoring for external radiations by these revisions were investigated. The following results were obtained. (1) A new ambient dose equivalent to neutrons is higher with a factor of 1.2 than the old one for moderated fission neutron spectra. Therefore, neutron dose equivalent monitors for workplace monitoring at MOX fuel for facilities should be recalibrated for measurement of the new ambient dose equivalent. (2) Annual effective doses of workers were estimated by applying new calibration factors to readings of personal dosimeters, worn by workers. Differences between effective doses and effective dose equivalents are small for workers engaged in the fabrication process of MOX fuel. (author)

  8. Challenges of the growing African cement market – environmental issues, regulative framework, and quality infrastructure requirements

    Directory of Open Access Journals (Sweden)

    Schmidt Wolfram

    2018-01-01

    Full Text Available The African cement, concrete and construction business is growing at rapid pace. The cement sales are expected to grow rapidly until 2050. The number of newly built cement plants increases dramatically and in addition more cements are being imported from outside the continent, e.g. from Turkey, Pakistan, Indonesia, and China, driven by overcapacities in the countries of origin. This causes a high number of potentials and challenges at the same time. Newly built cement plants can operate directly at best technological state of the art and thus incorporate more sustainable technologies as well as produce new and more sustainable products such as cements blended with sustainable supplementary cementitious materials such as calcined clays, and industrial or agricultural by products. At the same time the new variety of binding agent as well as the international imports, which are driven by price considerations, make the cement market prone to quality scatter. This puts pressure on the quality control regulations and institutions to ensure safety of construction, healthy application, and environmental safety for the population. The paper presents possible solutions to build up the rapidly increasing African cement production more sustainably than in the rest of the world as well as the related challenges and obstacles that need to be overcome. Based on experiences with a series of pan-African cement testing laboratory proficiency schemes conclusions are made on technical, regulative and political level.

  9. 77 FR 58817 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement (DFARS...

    Science.gov (United States)

    2012-09-24

    ... automated collection techniques or other forms of information technology. The Office of Management and... 252.232-7002, Progress Payments for Foreign Military Sales Acquisitions; OMB Control Number 0704-0321.... The clause at 252.232- 7002, Progress Payments for Foreign Military Sales Acquisitions, requires each...

  10. 78 FR 68830 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Service...

    Science.gov (United States)

    2013-11-15

    ... or other forms of information technology. The Office of Management and Budget (OMB) has approved this... Services. The provision at DFARS 252.237- 7024 requires offerors to submit with its offer a written plan describing how it will continue to perform essential contractor services during periods of crisis. The...

  11. 78 FR 73104 - Federal Travel Regulation (FTR); Agency Requirements for Payment of Expenses Connected With the...

    Science.gov (United States)

    2013-12-05

    ... the approval of the Office of Management and Budget under 44 U.S.C. 3501, et seq. E. Small Business... for Payment of Expenses Connected With the Death of Certain Employees and Family Members AGENCY... requirements for payment of expenses connected with the death of certain employees and family members. This...

  12. 78 FR 25445 - Federal Acquisition Regulation; Submission for OMB Review; Quality Assurance Requirements

    Science.gov (United States)

    2013-05-01

    ..., Sr., Procurement Analyst, Contract Policy Division, GSA (202) 501-1448 or email [email protected] . SUPPLEMENTARY INFORMATION: A. Purpose Supplies and services acquired under Government contracts must conform to..., warranty, and other measures associated with quality requirements. Standard clauses related to inspection...

  13. 77 FR 67366 - Federal Acquisition Regulation; Information Collection; Quality Assurance Requirements

    Science.gov (United States)

    2012-11-09

    .... Glover, Sr., Procurement Analyst, Contract Policy Division, GSA (202) 501-1448 or email [email protected] . SUPPLEMENTARY INFORMATION: A. Purpose Supplies and services acquired under Government contracts..., acceptance, warranty, and other measures associated with quality requirements. Standard clauses related to...

  14. Determining the requirements for e-selection in a small recruitment company - using the regulative cycle

    NARCIS (Netherlands)

    Bondarouk, Tatiana; Ruel, Hubertus Johannes Maria; Timmermans, P.; Buragga, K.A.; Zaman, N.

    2013-01-01

    The requirements for e-selection technology to be of practical use for Company T have been investigated. Company T’s main business is in identifying and seconding personnel, especially in the technical sector, and it had been anticipating a shortage in the supply of candidates. This served as the

  15. 76 FR 14562 - Federal Acquisition Regulation; Additional Requirements for Market Research

    Science.gov (United States)

    2011-03-16

    ... and small disadvantaged business, should be exempt from market research requirements because the... subcontracting opportunities for small- business concerns. Careful attention to market-research strategies is an effective method for creating contract opportunities for small- business concerns. It provides them with an...

  16. 78 FR 63461 - Information Collection Requirement; Defense Federal Acquisition Regulation Supplement; Foreign...

    Science.gov (United States)

    2013-10-24

    ... 252.225-7010, Commercial Derivative Military Article-- Specialty Metals Compliance Certificate, as... commercial derivative military articles to the Government. DFARS 252.225-7013, Duty-Free Entry, as prescribed... of origin. DFARS 252.225-7020, Trade Agreements Certificate, as prescribed in 225.1101(5), requires...

  17. 77 FR 34315 - National Pollutant Discharge Elimination System-Proposed Regulations to Establish Requirements...

    Science.gov (United States)

    2012-06-11

    ... on information collection provisions to the Office of Information and Regulatory Affairs, Office of... holidays. The telephone number for the Public Reading Room is 202-566-1744, and the telephone number for... requiring this. EPA's proposed IM limits are expressed as a monthly average and an annual average. A...

  18. 78 FR 16365 - Foreign Trade Regulations: Mandatory Automated Export System Filing for All Shipments Requiring...

    Science.gov (United States)

    2013-03-14

    ... Bureau revised this definition to clarify that the FPPI is the party that purchases the goods. Foreign... the EAR that provides requirements for a license exception for gift parcels and humanitarian donations... interest (FPPI)'' to clarify that the FPPI is the party that purchases the goods for export or to whom...

  19. 75 FR 61653 - Advance Notice of Proposed Rulemaking Regarding Authority To Require Supervision and Regulation...

    Science.gov (United States)

    2010-10-06

    ...? Should the type of asset management activity (e.g., hedge fund, private equity fund, mutual fund) being... contractual arrangements that require the nonbank financial firm either to fund or to satisfy an obligation in connection with managed assets be considered? d. During the financial crisis, some firms provided financial...

  20. Wdr18 is required for Kupffer's vesicle formation and regulation of body asymmetry in zebrafish.

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available Correct specification of the left-right (L-R axis is important for organ morphogenesis. Conserved mechanisms involving cilia rotation inside node-like structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM, which are important symmetry-breaking events, have been intensively studied. In zebrafish, the clustering and migration of dorsal forerunner cells (DFCs is critical for the formation of the Kuppfer's vesicle (KV. However, molecular events underlying DFC clustering and migration are less understood. The WD-repeat proteins function in a variety of biological processes, including cytoskeleton assembly, intracellular trafficking, mRNA splicing, transcriptional regulation and cell migration. However, little is known about the function of WD-repeat proteins in L-R asymmetry determination. Here, we report the identification and functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat protein that is highly conserved among vertebrate species. wdr18 was identified from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18 mRNA expression showed that it was detected in DFCs or the KV progenitor cells and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18 resulted in laterality defects in the visceral organs, which were preceded by the mis-expression of Nodal-related genes, including spaw and pitx2. Examination of morphants at earlier stages revealed that the KV had fewer and shorter cilia which are immotile and a smaller cavity. We further investigated the organization of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and found that the clustering and migration of DFC was altered, leading to a disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino injections, we provided evidence that wdr18 and itgb1b genetically interact in the laterality determination process. Thus, we reveal a new and essential role for WD

  1. Regulation amending the mandatory reporting requirements for emissions of certain contaminants into the atmosphere : economic impact study

    International Nuclear Information System (INIS)

    Menard, R.; Turgeon, M.L.; Dumais, M.; Bernier, A.G.; Leblond, V.; Benoit, J.Y.

    2010-01-01

    Quebec's proposal to amend regulations regarding pollutants responsible for the increase in greenhouse gases, acid rain, smog and toxic pollution will ensure improved monitoring of the state of the environment. The proposed amendments are designed to harmonize with the Western Climate Initiative (WCI) to lower greenhouse gas (GHG) emissions and determine certain methods of calculation. The WCI includes seven U.S. states, including California, and 4 Canadian provinces including Quebec, Ontario, British Columbia and Manitoba. By joining WCI in 2008, Quebec agreed to a cap and trade of GHG emissions. One of the first steps of the process leading to the creation of a common carbon market is to ensure the thoroughness of the information collected on these emissions. Once established, the system of cap and trade will become an important instrument of the provincial strategy to address climate change. The current regulations require Quebec businesses to report GHG emissions that equal or exceed 50,000 tonnes of carbon dioxide (CO 2 ) equivalent. According to the rules of the WCI, the new threshold for reporting will be 10,000 tonnes of CO 2 equivalent. To date, companies did not have any requirements as to how to quantify their emissions. With the amended regulation, calculation methods for GHG emissions will be required for most emission sources. These methods have been adapted for Quebec businesses and were first developed by WCI partners from existing techniques used by international organizations such as the Intergovernmental Panel on Climate Change (IPCC) and the United States Environmental Protection Agency (EPA). They will standardize how issuers calculate their GHG emissions. In addition, the reporting of 25,000 tonnes of CO 2 equivalent or more, will have to be verified by an accredited organization to ensure that the prescribed methods of calculation have been followed and that the statements contain all required data. 1 tab.

  2. The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation.

    Science.gov (United States)

    Henry, Romain; Bruneau, Emmanuelle; Gardan, Rozenn; Bertin, Stéphane; Fleuchot, Betty; Decaris, Bernard; Leblond-Bourget, Nathalie

    2011-10-07

    Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Δrgg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature.

  3. The rgg0182 gene encodes a transcriptional regulator required for the full Streptococcus thermophilus LMG18311 thermal adaptation

    Directory of Open Access Journals (Sweden)

    Bertin Stéphane

    2011-10-01

    Full Text Available Abstract Background Streptococcus thermophilus is an important starter strain for the production of yogurt and cheeses. The analysis of sequenced genomes of four strains of S. thermophilus indicates that they contain several genes of the rgg familly potentially encoding transcriptional regulators. Some of the Rgg proteins are known to be involved in bacterial stress adaptation. Results In this study, we demonstrated that Streptococcus thermophilus thermal stress adaptation required the rgg0182 gene which transcription depends on the culture medium and the growth temperature. This gene encoded a protein showing similarity with members of the Rgg family transcriptional regulator. Our data confirmed that Rgg0182 is a transcriptional regulator controlling the expression of its neighboring genes as well as chaperones and proteases encoding genes. Therefore, analysis of a Δrgg0182 mutant revealed that this protein played a role in the heat shock adaptation of Streptococcus thermophilus LMG18311. Conclusions These data showed the importance of the Rgg0182 transcriptional regulator on the survival of S. thermophilus during dairy processes and more specifically during changes in temperature.

  4. Position Cross-Checking on ECDIS in View of International Regulations Requirements and OCIMF Recommendations

    Directory of Open Access Journals (Sweden)

    Wojciech Legiec

    2016-04-01

    Full Text Available In this paper author suggest methods for position cross-checking on modern bridge equipped with ECDIS. Terrestrial navigation techniques in relation to newly implemented technology are adopted to fulfil international requirements and recommendations. Author proposes voyage recording procedures conforming to IMO requirements ready to be used as navigational procedures in Safety Management System. Vessel Inspection Questionnaire of Ship Inspection Report Programme is used to systematize the needs. Differences in approach between paper charts and ECDIS navigation are exposed and clarified serving as a guide for ships liable to undergo vetting inspection. Author shows both, advantages and weak points of various ECDIS features using as an example ECDIS manufactured by Japan Radio Company.

  5. Basic Requirements Of The Basel Committee On Regulating Capital Adequacy And Liquidity Of Commercial Banks

    OpenAIRE

    Bahriddin Berdiyarov

    2012-01-01

    The current paper highlights theBaselI, Basel II & Basel III requirements on capital adequacy and liquidity of commercial banks.  In the paper, Basel II structure, methods of loan risk assessment, coefficients of loan risk assessment, credit risk measurement for counterparty banks are discussed.  Moreover, assessments of Basel III on bank chances against crisis driven from financial and economic crunches, risk management, performance quality and bank transparency improvement measures are ...

  6. 75 FR 3617 - Outer Continental Shelf Air Regulations Update To Include New Jersey State Requirements

    Science.gov (United States)

    2010-01-22

    ... control requirements N.J.A.C. 7:27-16.18. Leak detection and repair N.J.A.C. 7:27-16.19. Application of cutback and emulsified asphalts N.J.A.C. 7:27-16.21. Natural gas pipelines N.J.A.C. 7:27-16.22. Emission... compound leaks N.J.A.C. 7:27B-3.15. Procedures for the direct detection of fugitive volatile organic...

  7. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (Arabic Edition)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

  8. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (Chinese Edition)

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-01

    The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

  9. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-10-15

    The IAEA's Statute authorizes the Agency to 'establish or adopt... standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the

  10. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements

    International Nuclear Information System (INIS)

    2012-01-01

    The IAEA's Statute authorizes the Agency to 'establish or adopt... standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the

  11. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (French Edition)

    International Nuclear Information System (INIS)

    2013-01-01

    The IAEA's Statute authorizes the Agency to ''establish or adopt standards of safety for protection of health and minimization of danger to life and property'' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the

  12. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (Chinese Edition)

    International Nuclear Information System (INIS)

    2013-01-01

    The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

  13. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (Arabic Edition)

    International Nuclear Information System (INIS)

    2012-01-01

    The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

  14. Statistical physics

    CERN Document Server

    Guénault, Tony

    2007-01-01

    In this revised and enlarged second edition of an established text Tony Guénault provides a clear and refreshingly readable introduction to statistical physics, an essential component of any first degree in physics. The treatment itself is self-contained and concentrates on an understanding of the physical ideas, without requiring a high level of mathematical sophistication. A straightforward quantum approach to statistical averaging is adopted from the outset (easier, the author believes, than the classical approach). The initial part of the book is geared towards explaining the equilibrium properties of a simple isolated assembly of particles. Thus, several important topics, for example an ideal spin-½ solid, can be discussed at an early stage. The treatment of gases gives full coverage to Maxwell-Boltzmann, Fermi-Dirac and Bose-Einstein statistics. Towards the end of the book the student is introduced to a wider viewpoint and new chapters are included on chemical thermodynamics, interactions in, for exam...

  15. Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis.

    Science.gov (United States)

    Gray, Lawrence R; Sultana, Mst Rasheda; Rauckhorst, Adam J; Oonthonpan, Lalita; Tompkins, Sean C; Sharma, Arpit; Fu, Xiaorong; Miao, Ren; Pewa, Alvin D; Brown, Kathryn S; Lane, Erin E; Dohlman, Ashley; Zepeda-Orozco, Diana; Xie, Jianxin; Rutter, Jared; Norris, Andrew W; Cox, James E; Burgess, Shawn C; Potthoff, Matthew J; Taylor, Eric B

    2015-10-06

    Gluconeogenesis is critical for maintenance of euglycemia during fasting. Elevated gluconeogenesis during type 2 diabetes (T2D) contributes to chronic hyperglycemia. Pyruvate is a major gluconeogenic substrate and requires import into the mitochondrial matrix for channeling into gluconeogenesis. Here, we demonstrate that the mitochondrial pyruvate carrier (MPC) comprising the Mpc1 and Mpc2 proteins is required for efficient regulation of hepatic gluconeogenesis. Liver-specific deletion of Mpc1 abolished hepatic MPC activity and markedly decreased pyruvate-driven gluconeogenesis and TCA cycle flux. Loss of MPC activity induced adaptive utilization of glutamine and increased urea cycle activity. Diet-induced obesity increased hepatic MPC expression and activity. Constitutive Mpc1 deletion attenuated the development of hyperglycemia induced by a high-fat diet. Acute, virally mediated Mpc1 deletion after diet-induced obesity decreased hyperglycemia and improved glucose tolerance. We conclude that the MPC is required for efficient regulation of gluconeogenesis and that the MPC contributes to the elevated gluconeogenesis and hyperglycemia in T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Comparison of requirements for location, maintenance and removal of road advertising between polish and foreign regulations

    Directory of Open Access Journals (Sweden)

    Żukowska Joanna

    2017-01-01

    Full Text Available The article gives an overview of Polish and international formal and legal requirements for roadside advertising and the relevant road safety impacts. The analysis focussed on outdoor advertising life cycle consisting of three stages: location, operation and removal of advertising. Experience of road authorities from Australia (Queensland, Republic of South Africa and the United Kingdom was collected. The article is part of a joint project “Development of Road Innovations” funded by the National Centre for Development and Innovation and the General Directorate For National Roads and Motorways.

  17. Strengthening global health security by embedding the International Health Regulations requirements into national health systems.

    Science.gov (United States)

    Kluge, Hans; Martín-Moreno, Jose Maria; Emiroglu, Nedret; Rodier, Guenael; Kelley, Edward; Vujnovic, Melitta; Permanand, Govin

    2018-01-01

    The International Health Regulations (IHR) 2005, as the overarching instrument for global health security, are designed to prevent and cope with major international public health threats. But poor implementation in countries hampers their effectiveness. In the wake of a number of major international health crises, such as the 2014 Ebola and 2016 Zika outbreaks, and the findings of a number of high-level assessments of the global response to these crises, it has become clear that there is a need for more joined-up thinking between health system strengthening activities and health security efforts for prevention, alert and response. WHO is working directly with its Member States to promote this approach, more specifically around how to better embed the IHR (2005) core capacities into the main health system functions. This paper looks at how and where the intersections between the IHR and the health system can be best leveraged towards developing greater health system resilience. This merging of approaches is a key component in pursuit of Universal Health Coverage and strengthened global health security as two mutually reinforcing agendas.

  18. cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

    Directory of Open Access Journals (Sweden)

    Ghania Ramdani

    2015-05-01

    Full Text Available Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites.

  19. DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

    Science.gov (United States)

    Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

    2017-07-20

    Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

  20. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    International Nuclear Information System (INIS)

    Shimada, Midori; Yamamoto, Ayumu; Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi; Aiba, Hirofumi; Murakami, Hiroshi

    2009-01-01

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2 + . The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  1. Impacts and Compliance Implementation Plans and Required Deviations for Toxic Substance Control Act (TSCA) Regulation of Double Shell Tanks (DST)

    International Nuclear Information System (INIS)

    MULKEY, C.H.

    2000-01-01

    In May 2000, the U.S. Department of Energy, Office of River Protection (DOE-ORP) and the U.S. Environmental Protection Agency (EPA) held meetings regarding the management of polychlorinated biphenyls (PCBs) in the Hanford tank waste. It was decided that the radioactive waste currently stored in the double-shell tanks (DSTs) contain waste which will become subject to the Toxic Substance Control Act (TSCA) (40 CFR 761). As a result, DOE-ORP directed the River Protection Project tank farm contractor (TFC) to prepare plans for managing the PCB inventory in the DSTs. Two components of the PCB management plans are this assessment of the operational impacts of TSCA regulation and the identifications of deviations from TSCA that are required to accommodate tank farm unique limitations. This plan provides ORP and CH2M HILL Hanford Group, Inc. (CHG) with an outline of TSCA PCB requirements and their applicability to tank farm activities, and recommends a compliance/implementation approach. Where strict compliance is not possible, the need for deviations from TSCA PCB requirements is identified. The purpose of assembling this information is to enhance the understanding of PCB management requirements, identify operational impacts and select impact mitigation strategies. This information should be useful in developing formal agreements with EPA where required

  2. Survival of Listeria monocytogenes in Soil Requires AgrA-Mediated Regulation.

    Science.gov (United States)

    Vivant, Anne-Laure; Garmyn, Dominique; Gal, Laurent; Hartmann, Alain; Piveteau, Pascal

    2015-08-01

    In a recent paper, we demonstrated that inactivation of the Agr system affects the patterns of survival of Listeria monocytogenes (A.-L. Vivant, D. Garmyn, L. Gal, and P. Piveteau, Front Cell Infect Microbiol 4:160, http://dx.doi.org/10.3389/fcimb.2014.00160). In this study, we investigated whether the Agr-mediated response is triggered during adaptation in soil, and we compared survival patterns in a set of 10 soils. The fate of the parental strain L. monocytogenes L9 (a rifampin-resistant mutant of L. monocytogenes EGD-e) and that of a ΔagrA deletion mutant were compared in a collection of 10 soil microcosms. The ΔagrA mutant displayed significantly reduced survival in these biotic soil microcosms, and differential transcriptome analyses showed large alterations of the transcriptome when AgrA was not functional, while the variations in the transcriptomes between the wild type and the ΔagrA deletion mutant were modest under abiotic conditions. Indeed, in biotic soil environments, 578 protein-coding genes and an extensive repertoire of noncoding RNAs (ncRNAs) were differentially transcribed. The transcription of genes coding for proteins involved in cell envelope and cellular processes, including the phosphotransferase system and ABC transporters, and proteins involved in resistance to antimicrobial peptides was affected. Under sterilized soil conditions, the differences were limited to 86 genes and 29 ncRNAs. These results suggest that the response regulator AgrA of the Agr communication system plays important roles during the saprophytic life of L. monocytogenes in soil. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. Bioclim Deliverable D6b: application of statistical down-scaling within the BIOCLIM hierarchical strategy: methods, data requirements and underlying assumptions

    International Nuclear Information System (INIS)

    2004-01-01

    The overall aim of BIOCLIM is to assess the possible long term impacts due to climate change on the safety of radioactive waste repositories in deep formations. The coarse spatial scale of the Earth-system Models of Intermediate Complexity (EMICs) used in BIOCLIM compared with the BIOCLIM study regions and the needs of performance assessment creates a need for down-scaling. Most of the developmental work on down-scaling methodologies undertaken by the international research community has focused on down-scaling from the general circulation model (GCM) scale (with a typical spatial resolution of 400 km by 400 km over Europe in the current generation of models) using dynamical down-scaling (i.e., regional climate models (RCMs), which typically have a spatial resolution of 50 km by 50 km for models whose domain covers the European region) or statistical methods (which can provide information at the point or station scale) in order to construct scenarios of anthropogenic climate change up to 2100. Dynamical down-scaling (with the MAR RCM) is used in BIOCLIM WP2 to down-scale from the GCM (i.e., IPSL C M4 D ) scale. In the original BIOCLIM description of work, it was proposed that UEA would apply statistical down-scaling to IPSL C M4 D output in WP2 as part of the hierarchical strategy. Statistical down-scaling requires the identification of statistical relationships between the observed large-scale and regional/local climate, which are then applied to large-scale GCM output, on the assumption that these relationships remain valid in the future (the assumption of stationarity). Thus it was proposed that UEA would investigate the extent to which it is possible to apply relationships between the present-day large-scale and regional/local climate to the relatively extreme conditions of the BIOCLIM WP2 snapshot simulations. Potential statistical down-scaling methodologies were identified from previous work performed at UEA. Appropriate station data from the case

  4. Regulation of pyruvate oxidation in blowfly flight muscle mitochondria: requirement for ADP.

    Science.gov (United States)

    Bulos, B A; Thomas, B J; Shukla, S P; Sacktor, B

    1984-11-01

    Blowfly (Phormia regina) flight muscle mitochondria oxidized pyruvate ( + proline) in the presence of either ADP (coupled respiration) or carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP-uncoupled respiration). There was an absolute requirement for ADP (Km = 8.0 microM) when pyruvate oxidation was stimulated by FCCP in the presence of oligomycin. This requirement for ADP was limited to the oxidation of pyruvate; uncoupled alpha-glycerolphosphate oxidation proceeded maximally even in the absence of added ADP. Atractylate inhibited uncoupled pyruvate oxidation whether added before (greater than 99%) or after (95%) initiation of respiration with FCCP. In the presence of FCCP, oligomycin, and limiting concentrations of ADP (less than 110 microM), there was a shutoff in the uptake of oxygen. This inhibition of respiration was completely reversed by the addition of more ADP. Plots of net oxygen uptake as a function of the limiting ADP concentration were linear; the observed ADP/O ratio was 0.22 +/- 0.025. An ADP/O ratio of 0.2 was predicted if phosphorylation occurred only at the succinyl-CoA synthetase step of the tricarboxylate cycle. Experiments performed in the presence of limiting concentrations of ADP, and designed to monitor changes in the mitochondrial content of ADP and ATP, demonstrated that the shutoff in oxygen uptake was not due to the presence of a high intramitochondrial concentration of ATP. Indeed, ATP, added to the medium prior to the addition of FCCP, inhibited uncoupled pyruvate oxidation; the apparent KI was 0.8 mM. These results are consistent with the hypothesis that it is the intramitochondrial ATP/ADP ratio that is one of the controlling factors in determining the rate of flux through the tricarboxylate cycle. Changes in the mitochondrial content of citrate, isocitrate, alpha-ketoglutarate, and malate during uncoupled pyruvate oxidation in the presence of a limiting concentration of ADP were consistent with the hypothesis that the

  5. PPARα Is Required for PPARδ Action in Regulation of Body Weight and Hepatic Steatosis in Mice

    Directory of Open Access Journals (Sweden)

    Wojciech G. Garbacz

    2015-01-01

    Full Text Available Peroxisome proliferator activated receptors alpha (PPARα and delta (PPARδ belong to the nuclear receptor superfamily. PPARα is a target of well established lipid-lowering drugs. PPARδ (also known as PPARβ/δ has been investigated as a promising antidiabetic drug target; however, the evidence in the literature on PPARδ effect on hepatic lipid metabolism is inconsistent. Mice conditionally expressing human PPARδ demonstrated pronounced weight loss and promoted hepatic steatosis when treated with GW501516 (PPARδ-agonist when compared to wild type mice. This effect was completely absent in mice with either a dominant negative form of PPARδ or deletion of the DNA binding domain of PPARδ. This confirmed the absolute requirement for PPARδ in the physiological actions of GW501516 and confirmed the potential utility against the human form of this receptor. Surprisingly the genetic deletion of PPARα also abrogated the effect of GW501516 in terms of both weight loss and hepatic lipid accumulation. Also the levels of the PPARα endogenous agonist 16:0/18:1-GPC were shown to be modulated by PPARδ in wild type mice. Our results show that both PPARδ and PPARα receptors are essential for GW501516-driven adipose tissue reduction and subsequently hepatic steatosis, with PPARα working downstream of PPARδ.

  6. Differential requirement for the CD45 splicing regulator hnRNPLL for accumulation of NKT and conventional T cells.

    Directory of Open Access Journals (Sweden)

    Mehmet Yabas

    Full Text Available Natural killer T (NKT cells represent an important regulatory T cell subset that develops in the thymus and contains immature (NK1.1(lo and mature (NK1.1(hi cell subsets. Here we show in mice that an inherited mutation in heterogeneous ribonucleoprotein L-like protein (hnRNPLL(thunder, that shortens the survival of conventional T cells, has no discernible effect on NKT cell development, homeostasis or effector function. Thus, Hnrpll deficiency effectively increases the NKT∶T cell ratio in the periphery. However, Hnrpll mutation disrupts CD45RA, RB and RC exon silencing of the Ptprc mRNA in both NKT and conventional T cells, and leads to a comparably dramatic shift to high molecular weight CD45 isoforms. In addition, Hnrpll mutation has a cell intrinsic effect on the expression of the developmentally regulated cell surface marker NK1.1 on NKT cells in the thymus and periphery but does not affect cell numbers. Therefore our results highlight both overlapping and divergent roles for hnRNPLL between conventional T cells and NKT cells. In both cell subsets it is required as a trans-acting factor to regulate alternative splicing of the Ptprc mRNA, but it is only required for survival of conventional T cells.

  7. ZMS regulation of M2 muscarinic receptor mRNA stability requires protein factor

    International Nuclear Information System (INIS)

    Zhang Yongfang; Xia Zongqin; Hu Ya'er

    2010-01-01

    Aim The aim of this work is to study the elevation mechanism of ZMS on muscarinic M2 receptor mRNA expression. Methods Actinomycin D was added to cultured CHOm2 cells to stop the de novo synthesis of M2 receptor mRNA and samples were taken at various times to determine the time course of mRNA of M2 receptor with real-time quantitative RT-PCR. Half-life of M2 receptor mRNA and the effect of ZMS on the half-life was obtained from the slope of the exponential curves. Cycloheximide was added at 4 h prior to and 24 h after the addition of ZMS to examine the effect of de novo protein synthesis on the action of ZMS. Results The half-life of m2 mRNA was prolonged by ZMS treatment without cycloheximide (4.75±0.54 h and 2.13 h±0.23 h for ZMS and vehicle treated groups, respectively, P<0.05). When cycloheximide was added to the culture medium 4h prior to the addition of ZMS, the effect of ZMS in prolonging the half-life of m2 mRNA disappeared (3.06 h±0.23 h and 3.00 h±l.20 h for cells with and without ZMS, respectively). However, when the ZMS was added to the medium 24h prior to the addition of cycloheximide, the action of ZMS was not abolished by cycloheximide (half-life was 5.43 h±1.13 h and 2.46 h±0.09 h for cells with and without ZMS, respectively). Conclusion These data suggest that de novo protein synthesis was required for the increase in M2 mRNA stability induced by ZMS. (authors)

  8. High power valve regulated lead-acid batteries for new vehicle requirements

    Science.gov (United States)

    Trinidad, Francisco; Sáez, Francisco; Valenciano, Jesús

    The performance of high power VRLA ORBITAL™ batteries is presented. These batteries have been designed with isolated cylindrical cells, providing high reliability to the recombination process, while maintaining, at the same time, a very high compression (>80 kPa) over the life of the battery. Hence, the resulting VRLA modules combine a high rate capability with a very good cycle performance. Two different electrochemically active material compositions have been developed: high porosity and low porosity for starting and deep cycle applications, respectively (depending on the power demand and depth of discharge). Although, the initial performance of the starting version is higher, after a few cycles the active material of the deep cycle version is fully developed, and this achieves the same high rate capability. Both types are capable of supplying the necessary reliability for cranking at the lowest temperature (-40°C). Specific power of over 500 W/kg is achievable at a much lower cost than for nickel-metal hydride systems. Apart from the initial performance, an impressive behaviour of the cycling version has been found in deep cycle applications, due to the highly compressed and high density active material. When submitted to continuous discharge-charge cycles at 75% (IEC 896-2 specification) and 100% (BCI deep cycle) DoD, it has been found that the batteries are still healthy after more than 1000 and 700 cycles, respectively. However, it has been proven that the application of an IUi algorithm (up to 110% of overcharging) with a small constant current charging period at the end of the charge is absolutely necessary to achieve the above results. Without the final boosting period, the cycle life of the battery could be substantially shortened. The high specific power and reliability observed in the tests carried out, would allow ORBITAL™ batteries to comply with the more demanding requirements that are being introduced in conventional and future hybrid electric

  9. Identification of Two Gene Clusters and a Transcriptional Regulator Required for Pseudomonas aeruginosa Glycine Betaine Catabolism▿ †

    Science.gov (United States)

    Wargo, Matthew J.; Szwergold, Benjamin S.; Hogan, Deborah A.

    2008-01-01

    Glycine betaine (GB), which occurs freely in the environment and is an intermediate in the catabolism of choline and carnitine, can serve as a sole source of carbon or nitrogen in Pseudomonas aeruginosa. Twelve mutants defective in growth on GB as the sole carbon source were identified through a genetic screen of a nonredundant PA14 transposon mutant library. Further growth experiments showed that strains with mutations in two genes, gbcA (PA5410) and gbcB (PA5411), were capable of growth on dimethylglycine (DMG), a catabolic product of GB, but not on GB itself. Subsequent nuclear magnetic resonance (NMR) experiments with 1,2-13C-labeled choline indicated that these genes are necessary for conversion of GB to DMG. Similar experiments showed that strains with mutations in the dgcAB (PA5398-PA5399) genes, which exhibit homology to genes that encode other enzymes with demethylase activity, are required for the conversion of DMG to sarcosine. Mutant analyses and 13C NMR studies also confirmed that the soxBDAG genes, predicted to encode a sarcosine oxidase, are required for sarcosine catabolism. Our screen also identified a predicted AraC family transcriptional regulator, encoded by gbdR (PA5380), that is required for growth on GB and DMG and for the induction of gbcA, gbcB, and dgcAB in response to GB or DMG. Mutants defective in the previously described gbt gene (PA3082) grew on GB with kinetics similar to those of the wild type in both the PAO1 and PA14 strain backgrounds. These studies provided important insight into both the mechanism and the regulation of the catabolism of GB in P. aeruginosa. PMID:17951379

  10. Intracellular pH regulation in unstimulated Calliphora salivary glands is Na+ dependent and requires V-ATPase activity.

    Science.gov (United States)

    Schewe, Bettina; Blenau, Wolfgang; Walz, Bernd

    2012-04-15

    Salivary gland cells of the blowfly Calliphora vicina have a vacuolar-type H(+)-ATPase (V-ATPase) that lies in their apical membrane and energizes the secretion of a KCl-rich primary saliva upon stimulation with serotonin (5-hydroxytryptamine). Whether and to what extent V-ATPase contributes to intracellular pH (pH(i)) regulation in unstimulated gland cells is unknown. We used the fluorescent dye BCECF to study intracellular pH(i) regulation microfluorometrically and show that: (1) under resting conditions, the application of Na(+)-free physiological saline induces an intracellular alkalinization attributable to the inhibition of the activity of a Na(+)-dependent glutamate transporter; (2) the maintenance of resting pH(i) is Na(+), Cl(-), concanamycin A and DIDS sensitive; (3) recovery from an intracellular acid load is Na(+) sensitive and requires V-ATPase activity; (4) the Na(+)/H(+) antiporter is not involved in pH(i) recovery after a NH(4)Cl prepulse; and (5) at least one Na(+)-dependent transporter and the V-ATPase maintain recovery from an intracellular acid load. Thus, under resting conditions, the V-ATPase and at least one Na(+)-dependent transporter maintain normal pH(i) values of pH 7.5. We have also detected the presence of a Na(+)-dependent glutamate transporter, which seems to act as an acid loader. Despite this not being a common pH(i)-regulating transporter, its activity affects steady-state pH(i) in C. vicina salivary gland cells.

  11. Mycobacterium tuberculosis Universal Stress Protein Rv2623 Regulates Bacillary Growth by ATP Binding: Requirement for Establishing Chronic Persistent Infection

    Energy Technology Data Exchange (ETDEWEB)

    Drumm, J.; Mi, K; Bilder, P; Sun, M; Lim, J; Bielefeldt-Ohmann, H; Basaraba, R; So, M; Zhu, G; et. al.

    2009-01-01

    Tuberculous latency and reactivation play a significant role in the pathogenesis of tuberculosis, yet the mechanisms that regulate these processes remain unclear. The Mycobacterium tuberculosisuniversal stress protein (USP) homolog, rv2623, is among the most highly induced genes when the tubercle bacillus is subjected to hypoxia and nitrosative stress, conditions thought to promote latency. Induction of rv2623 also occurs when M. tuberculosis encounters conditions associated with growth arrest, such as the intracellular milieu of macrophages and in the lungs of mice with chronic tuberculosis. Therefore, we tested the hypothesis that Rv2623 regulates tuberculosis latency. We observed that an Rv2623-deficient mutant fails to establish chronic tuberculous infection in guinea pigs and mice, exhibiting a hypervirulence phenotype associated with increased bacterial burden and mortality. Consistent with this in vivo growth-regulatory role, constitutive overexpression of rv2623 attenuates mycobacterial growth in vitro. Biochemical analysis of purified Rv2623 suggested that this mycobacterial USP binds ATP, and the 2.9-A-resolution crystal structure revealed that Rv2623 engages ATP in a novel nucleotide-binding pocket. Structure-guided mutagenesis yielded Rv2623 mutants with reduced ATP-binding capacity. Analysis of mycobacteria overexpressing these mutants revealed that the in vitro growth-inhibitory property of Rv2623 correlates with its ability to bind ATP. Together, the results indicate that i M. tuberculosis Rv2623 regulates mycobacterial growth in vitro and in vivo, and ii Rv2623 is required for the entry of the tubercle bacillus into the chronic phase of infection in the host; in addition, iii Rv2623 binds ATP; and iv the growth-regulatory attribute of this USP is dependent on its ATP-binding activity. We propose that Rv2623 may function as an ATP-dependent signaling intermediate in a pathway that promotes persistent infection.

  12. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  13. Pdlim7 Regulates Arf6-Dependent Actin Dynamics and Is Required for Platelet-Mediated Thrombosis in Mice.

    Directory of Open Access Journals (Sweden)

    Alexander E Urban

    Full Text Available Upon vessel injury, platelets become activated and rapidly reorganize their actin cytoskeleton to adhere to the site of endothelial damage, triggering the formation of a fibrin-rich plug to prevent further blood loss. Inactivation of Pdlim7 provides the new perspective that regulation of actin cytoskeletal changes in platelets is dependent on the encoded PDZ-LIM protein. Loss-of-function of Pdlim7 triggers hypercoagulopathy and causes significant perinatal lethality in mice. Our in vivo and in vitro studies reveal that Pdlim7 is dynamically distributed along actin fibers, and lack of Pdlim7 leads to a marked inability to rearrange the actin cytoskeleton. Specifically, the absence of Pdlim7 prevents platelets from bundling actin fibers into a concentric ring that defines the round spread shape of activated platelets. Similarly, in mouse embryonic fibroblasts, loss of Pdlim7 abolishes the formation of stress fibers needed to adopt the typical elongated fibroblast shape. In addition to revealing a fundamental cell biological role in actin cytoskeletal organization, we also demonstrate a function of Pdlim7 in regulating the cycling between the GTP/GDP-bound states of Arf6. The small GTPase Arf6 is an essential factor required for actin dynamics, cytoskeletal rearrangements, and platelet activation. Consistent with our findings of significantly elevated initial F-actin ratios and subsequent morphological aberrations, loss of Pdlim7 causes a shift in balance towards an increased Arf6-GTP level in resting platelets. These findings identify a new Pdlim7-Arf6 axis controlling actin dynamics and implicate Pdlim7 as a primary endogenous regulator of platelet-dependent hemostasis.

  14. Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Midori [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Yamamoto, Ayumu [Department of Chemistry, Shizuoka University, 836 Ohya, Suruga-ku, Sizuoka 422-8529 (Japan); Murakami-Tonami, Yuko; Nakanishi, Makoto; Yoshida, Takashi [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aiba, Hirofumi [Laboratory of Molecular Microbiology, School of Agriculture, Nagoya University, Chikusa-ku, Nagoya 464-8601 (Japan); Murakami, Hiroshi, E-mail: hmura@med.nagoya-cu.ac.jp [Department of Biochemistry and Cell Biology, Graduate School of Medicine, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2009-10-23

    The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2{sup +}. The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint by regulating Mad2p.

  15. Phytophthora capsici homologue of the cell cycle regulator SDA1 is required for sporangial morphology, mycelial growth and plant infection.

    Science.gov (United States)

    Zhu, Chunyuan; Yang, Xiaoyan; Lv, Rongfei; Li, Zhuang; Ding, Xiaomeng; Tyler, Brett M; Zhang, Xiuguo

    2016-04-01

    SDA1 encodes a highly conserved protein that is widely distributed in eukaryotic organisms. SDA1 is essential for cell cycle progression and organization of the actin cytoskeleton in yeasts and humans. In this study, we identified a Phytophthora capsici orthologue of yeast SDA1, named PcSDA1. In P. capsici, PcSDA1 is strongly expressed in three asexual developmental states (mycelium, sporangia and germinating cysts), as well as late in infection. Silencing or overexpression of PcSDA1 in P. capsici transformants affected the growth of hyphae and sporangiophores, sporangial development, cyst germination and zoospore release. Phalloidin staining confirmed that PcSDA1 is required for organization of the actin cytoskeleton. Moreover, 4',6-diamidino-2-phenylindole (DAPI) staining and PcSDA1-green fluorescent protein (GFP) fusions revealed that PcSDA1 is involved in the regulation of nuclear distribution in hyphae and sporangia. Both silenced and overexpression transformants showed severely diminished virulence. Thus, our results suggest that PcSDA1 plays a similar role in the regulation of the actin cytoskeleton and nuclear division in this filamentous organism as in non-filamentous yeasts and human cells. © 2015 BSPP and John Wiley & Sons Ltd.

  16. Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth

    Science.gov (United States)

    Low, Malcolm J.; Otero-Corchon, Veronica; Parlow, Albert F.; Ramirez, Jose L.; Kumar, Ujendra; Patel, Yogesh C.; Rubinstein, Marcelo

    2001-01-01

    Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst–/–) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst–/– compared with Smst+/+ mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst–/– mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst-/- mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth. PMID:11413165

  17. Nontranscriptional regulation of SYK by the coactivator OCA-B is required at multiple stages of B cell development.

    Science.gov (United States)

    Siegel, Rachael; Kim, Unkyu; Patke, Alina; Yu, Xin; Ren, Xiaodi; Tarakhovsky, Alexander; Roeder, Robert G

    2006-05-19

    OCA-B was originally identified as a nuclear transcriptional coactivator that is essential for antigen-driven immune responses. The later identification of a membrane bound, myristoylated form of OCA-B suggested additional, unique functions in B cell signaling pathways. This study has shown that OCA-B also functions in the pre-B1-to-pre-B2 cell transition and, most surprisingly, that it directly interacts with SYK, a tyrosine kinase critical for pre-BCR and BCR signaling. This unprecedented type of interaction-a transcriptional coactivator with a signaling kinase-occurs in the cytoplasm and directly regulates SYK stability. This study indicates that OCA-B is required for pre-BCR and BCR signaling at multiple stages of B cell development through its nontranscriptional regulation of SYK. Combined with the deregulation of OCA-B target genes, this may help explain the multitude of defects observed in B cell development and immune responses of Oca-b-/- mice.

  18. The bifunctional abiotic stress signalling regulator and endogenous RNA silencing suppressor FIERY1 is required for lateral root formation

    KAUST Repository

    Chen, Hao

    2010-09-28

    The Arabidopsis FIERY1 (FRY1) locus was originally identified as a negative regulator of stress-responsive gene expression and later shown to be required for suppression of RNA silencing. In this study we discovered that the FRY1 locus also regulates lateral root formation. Compared with the wild type, fry1 mutant seedlings generated significantly fewer lateral roots under normal growth conditions and also exhibited a dramatically reduced sensitivity to auxin in inducing lateral root initiation. Using transgenic plants that overexpress a yeast homolog of FRY1 that possesses only the 3\\', 5\\'-bisphosphate nucleotidase activity but not the inositol 1-phosphatase activity, we demonstrated that the lateral root phenotypes in fry1 result from loss of the nucleotidase activity. Furthermore, a T-DNA insertion mutant of another RNA silencing suppressor, XRN4 (but not XRN2 or XRN3), which is an exoribonuclease that is inhibited by the substrate of the FRY1 3\\', 5\\'-bisphosphate nucleotidase, exhibits similar lateral root defects. Although fry1 and xrn4 exhibited reduced sensitivity to ethylene, our experiments demonstrated that restoration of ethylene sensitivity in the fry1 mutant is not sufficient to rescue the lateral root phenotypes of fry1. Our results indicate that RNA silencing modulated by FRY1 and XRN4 plays an important role in shaping root architecture. © 2010 Blackwell Publishing Ltd.

  19. Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival.

    Science.gov (United States)

    Omori, Yoshihiro; Chaya, Taro; Katoh, Kimiko; Kajimura, Naoko; Sato, Shigeru; Muraoka, Koichiro; Ueno, Shinji; Koyasu, Toshiyuki; Kondo, Mineo; Furukawa, Takahisa

    2010-12-28

    Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

  20. Regulation No. 56/2006 Coll. of the Nuclear Regulatory Authority of the Slovak Republic dated as of January 12, 2006 on details concerning requirements for quality system documentation of authorisation holder, as well as details concerning quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details concerning the scope of their approval

    International Nuclear Information System (INIS)

    2006-01-01

    This Regulation provides details of the requirements for quality system documentation holder, details of the quality requirements for nuclear installations, details concerning quality requirements for classified equipment and details of the scope of their approval. This Regulation came into force on March 1, 2006.

  1. Statistical thermodynamics

    International Nuclear Information System (INIS)

    Lim, Gyeong Hui

    2008-03-01

    This book consists of 15 chapters, which are basic conception and meaning of statistical thermodynamics, Maxwell-Boltzmann's statistics, ensemble, thermodynamics function and fluctuation, statistical dynamics with independent particle system, ideal molecular system, chemical equilibrium and chemical reaction rate in ideal gas mixture, classical statistical thermodynamics, ideal lattice model, lattice statistics and nonideal lattice model, imperfect gas theory on liquid, theory on solution, statistical thermodynamics of interface, statistical thermodynamics of a high molecule system and quantum statistics

  2. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  3. The ciliogenic transcription factor RFX3 regulates early midline distribution of guidepost neurons required for corpus callosum development.

    Directory of Open Access Journals (Sweden)

    Carine Benadiba

    Full Text Available The corpus callosum (CC is the major commissure that bridges the cerebral hemispheres. Agenesis of the CC is associated with human ciliopathies, but the origin of this default is unclear. Regulatory Factor X3 (RFX3 is a transcription factor involved in the control of ciliogenesis, and Rfx3-deficient mice show several hallmarks of ciliopathies including left-right asymmetry defects and hydrocephalus. Here we show that Rfx3-deficient mice suffer from CC agenesis associated with a marked disorganisation of guidepost neurons required for axon pathfinding across the midline. Using transplantation assays, we demonstrate that abnormalities of the mutant midline region are primarily responsible for the CC malformation. Conditional genetic inactivation shows that RFX3 is not required in guidepost cells for proper CC formation, but is required before E12.5 for proper patterning of the cortical septal boundary and hence accurate distribution of guidepost neurons at later stages. We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8 at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene family zinc finger 3 (GLI3 repressor to activator forms. We demonstrate on brain explant cultures that ectopic FGF8 reproduces the guidepost neuronal defects observed in Rfx3 mutants. This study unravels a crucial role of RFX3 during early brain development by indirectly regulating GLI3 activity, which leads to FGF8 upregulation and ultimately to disturbed distribution of guidepost neurons required for CC morphogenesis. Hence, the RFX3 mutant mouse model brings novel understandings of the mechanisms that underlie CC agenesis in ciliopathies.

  4. A voltage-gated calcium channel regulates lysosomal fusion with endosomes and autophagosomes and is required for neuronal homeostasis.

    Directory of Open Access Journals (Sweden)

    Xuejun Tian

    2015-03-01

    Full Text Available Autophagy helps deliver sequestered intracellular cargo to lysosomes for proteolytic degradation and thereby maintains cellular homeostasis by preventing accumulation of toxic substances in cells. In a forward mosaic screen in Drosophila designed to identify genes required for neuronal function and maintenance, we identified multiple cacophony (cac mutant alleles. They exhibit an age-dependent accumulation of autophagic vacuoles (AVs in photoreceptor terminals and eventually a degeneration of the terminals and surrounding glia. cac encodes an α1 subunit of a Drosophila voltage-gated calcium channel (VGCC that is required for synaptic vesicle fusion with the plasma membrane and neurotransmitter release. Here, we show that cac mutant photoreceptor terminals accumulate AV-lysosomal fusion intermediates, suggesting that Cac is necessary for the fusion of AVs with lysosomes, a poorly defined process. Loss of another subunit of the VGCC, α2δ or straightjacket (stj, causes phenotypes very similar to those caused by the loss of cac, indicating that the VGCC is required for AV-lysosomal fusion. The role of VGCC in AV-lysosomal fusion is evolutionarily conserved, as the loss of the mouse homologues, Cacna1a and Cacna2d2, also leads to autophagic defects in mice. Moreover, we find that CACNA1A is localized to the lysosomes and that loss of lysosomal Cacna1a in cerebellar cultured neurons leads to a failure of lysosomes to fuse with endosomes and autophagosomes. Finally, we show that the lysosomal CACNA1A but not the plasma-membrane resident CACNA1A is required for lysosomal fusion. In summary, we present a model in which the VGCC plays a role in autophagy by regulating the fusion of AVs with lysosomes through its calcium channel activity and hence functions in maintaining neuronal homeostasis.

  5. Up-regulation of insulin-like growth factor 2 by ketamine requires glycogen synthase kinase-3 inhibition

    Science.gov (United States)

    Grieco, Steven F.; Cheng, Yuyan; Eldar-Finkelman, Hagit; Jope, Richard S.; Beurel, Eléonore

    2016-01-01

    An antidepressant dose of the rapidly-acting ketamine inhibits glycogen synthase kinase-3 (GSK3) in mouse hippocampus, and this inhibition is required for the antidepressant effect of ketamine in learned helplessness depression-like behavior. Here we report that treatment with an antidepressant dose of ketamine (10 mg/kg) increased expression of insulin-like growth factor 2 (IGF2) in mouse hippocampus, an effect that required ketamine-induced inhibition of GSK3. Ketamine also inhibited hippocampal GSK3 and increased expression of hippocampal IGF2 in mice when administered after the induction of learned helplessness. Treatment with the specific GSK3 inhibitor L803-mts was sufficient to up-regulate hippocampal IGF2 expression. Administration of IGF2 siRNA reduced ketamine's antidepressant effect in the learned helplessness paradigm. Mice subjected to the learned helplessness paradigm were separated into two groups, those that were resilient (non-depressed) and those that were susceptible (depressed). Non-depressed resilient mice displayed higher expression of IGF2 than susceptible mice. These results indicate that IGF2 contributes to ketamine's antidepressant effect and that IGF2 may confer resilience to depression-like behavior. PMID:27542584

  6. Renyi statistics in equilibrium statistical mechanics

    International Nuclear Information System (INIS)

    Parvan, A.S.; Biro, T.S.

    2010-01-01

    The Renyi statistics in the canonical and microcanonical ensembles is examined both in general and in particular for the ideal gas. In the microcanonical ensemble the Renyi statistics is equivalent to the Boltzmann-Gibbs statistics. By the exact analytical results for the ideal gas, it is shown that in the canonical ensemble, taking the thermodynamic limit, the Renyi statistics is also equivalent to the Boltzmann-Gibbs statistics. Furthermore it satisfies the requirements of the equilibrium thermodynamics, i.e. the thermodynamical potential of the statistical ensemble is a homogeneous function of first degree of its extensive variables of state. We conclude that the Renyi statistics arrives at the same thermodynamical relations, as those stemming from the Boltzmann-Gibbs statistics in this limit.

  7. Development of guidance on applications of regulatory requirements for regulating large, contaminated equipment and large decommissioning and decontamination (D and D) components

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Cook, J.R.; Boyle, R.W.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant were major changes to requirements for Low Specific Activity (LSA) material and Surface Contaminated Objects (SCOs). As these requirements were adopted into regulations in the United States, it was recognised that guidance on how to apply these requirements to large, contaminated/activated pieces of equipment and decommissioning and decontamination (D and D) objects would be needed both by the regulators and those regulated to clarify technical uncertainties and ensure implementation. Thus, the US Department of Transportation and the US Nuclear Regulatory Commission, with assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance which will present examples of acceptable methods for demonstrating compliance with the revised rules for large items. Concepts being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment before final issuance in 1997. (Author)

  8. Development of guidance on applications of regulatory requirements for regulating large, contaminated equipment and large decommissioning and decontamination (D and D) components

    International Nuclear Information System (INIS)

    Pope, R.B.; Easton, E.P.; Cook, J.R.; Boyle, R.W.

    1997-01-01

    In 1985, the International Atomic Energy Agency issued revised regulations for the safe transport of radioactive material. Significant were major changes to requirements for Low Specific Activity material and Surface Contaminated Objects. As these requirements were adopted into regulations in the US, it was recognized that guidance on how to apply these requirements to large, contaminated/activated pieces of equipment and decommissioning and decontamination objects would be needed both by the regulators and those regulated to clarify technical uncertainties and ensure implementation. Thus, the US Department of Transportation and the US Nuclear Regulatory Commission, with assistance of staff from Oak Ridge National Laboratory, are preparing regulatory guidance which will present examples of acceptable methods for demonstrating compliance with the revised rules for large items. Concepts being investigated for inclusion in the pending guidance are discussed in this paper. Under current plans, the guidance will be issued for public comment before final issuance in 1997

  9. Development of full sweet, umami, and bitter taste responsiveness requires Regulator of G protein Signaling-21 (RGS21).

    Science.gov (United States)

    Schroer, Adam B; Gross, Joshua D; Kaski, Shane W; Wix, Kim; Siderovski, David P; Vandenbeuch, Aurelie; Setola, Vincent

    2018-04-26

    The mammalian tastes of sweet, umami, and bitter are initiated by activation of G protein-coupled receptors (GPCRs) of the T1R and T2R families on taste receptor cells. GPCRs signal via nucleotide exchange and hydrolysis, the latter hastened by GTPase-accelerating proteins (GAPs) that include the Regulators of G protein Signaling (RGS) protein family. We previously reported that RGS21, uniquely expressed in Type II taste receptor cells, decreases the potency of bitter-stimulated T2R signaling in cultured cells, consistent with its in vitro GAP activity. However, the role of RGS21 in organismal responses to GPCR-mediated tastants was not established. Here, we characterized mice lacking the Rgs21 fifth exon. Eliminating Rgs21 expression had no effect on body mass accumulation (a measure of alimentation), fungiform papillae number and morphology, circumvallate papillae morphology, and taste bud number. Two-bottle preference tests, however, revealed that Rgs21-null mice have blunted aversion to quinine and denatonium, and blunted preference for monosodium glutamate, the sweeteners sucrose and SC45647, and (surprisingly) NaCl. Observed reductions in GPCR-mediated tastant responses upon Rgs21 loss are opposite to original expectations, given that loss of RGS21 -- a GPCR signaling negative regulator -- should lead to increased responsiveness to tastant-mediated GPCR signaling (all else being equal). Yet, reduced organismal tastant responses are consistent with observations of reduced chorda tympani nerve recordings in Rgs21-null mice. Reduced tastant-mediated responses and behaviors exhibited by adult mice lacking Rgs21 expression since birth have thus revealed an underappreciated requirement for a GPCR GAP to establish the full character of tastant signaling.

  10. Historical background of the development of various requirements in the international regulations for the safe packaging and transport of radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Pope, R.B.

    2004-07-01

    Questions are frequently asked regarding the source of some of the package test requirements in the Transport Regulations, the philosophy behind them and the basis for selecting them. This paper summarizes the results of a review of early historical documents and elaborates on the early philosophy behind the regulatory requirements. To the extent possible, the paper compares the early philosophy with the current structure of the Transport Regulations in key topic areas with a focus on the test requirements for packages that are designed to withstand accident conditions of transport.

  11. Historical background of the development of various requirements in the international regulations for the safe packaging and transport of radioactive material

    International Nuclear Information System (INIS)

    Pope, R.B.

    2004-01-01

    Questions are frequently asked regarding the source of some of the package test requirements in the Transport Regulations, the philosophy behind them and the basis for selecting them. This paper summarizes the results of a review of early historical documents and elaborates on the early philosophy behind the regulatory requirements. To the extent possible, the paper compares the early philosophy with the current structure of the Transport Regulations in key topic areas with a focus on the test requirements for packages that are designed to withstand accident conditions of transport

  12. Cancer Statistics

    Science.gov (United States)

    ... What Is Cancer? Cancer Statistics Cancer Disparities Cancer Statistics Cancer has a major impact on society in ... success of efforts to control and manage cancer. Statistics at a Glance: The Burden of Cancer in ...

  13. Minimum forest cover required for sustainable water flow regulation of a watershed: a case study in Jambi Province, Indonesia

    Directory of Open Access Journals (Sweden)

    S. Tarigan

    2018-01-01

    Full Text Available In many tropical regions, the rapid expansion of monoculture plantations has led to a sharp decline in forest cover, potentially degrading the ability of watersheds to regulate water flow. Therefore, regional planners need to determine the minimum proportion of forest cover that is required to support adequate ecosystem services in these watersheds. However, to date, there has been little research on this issue, particularly in tropical areas where monoculture plantations are expanding at an alarming rate. Therefore, in this study, we investigated the influence of forest cover and oil palm (Elaeis guineensis and rubber (Hevea brasiliensis plantations on the partitioning of rainfall into direct runoff and subsurface flow in a humid, tropical watershed in Jambi Province, Indonesia. To do this, we simulated streamflow with a calibrated Soil and Water Assessment Tool (SWAT model and observed several watersheds to derive the direct runoff coefficient (C and baseflow index (BFI. The model had a strong performance, with Nash–Sutcliffe efficiency values of 0.80–0.88 (calibration and 0.80–0.85 (validation and percent bias values of −2.9–1.2 (calibration and 7.0–11.9 (validation. We found that the percentage of forest cover in a watershed was significantly negatively correlated with C and significantly positively correlated with BFI, whereas the rubber and oil palm plantation cover showed the opposite pattern. Our findings also suggested that at least 30 % of the forest cover was required in the study area for sustainable ecosystem services. This study provides new adjusted crop parameter values for monoculture plantations, particularly those that control surface runoff and baseflow processes, and it also describes the quantitative association between forest cover and flow indicators in a watershed, which will help regional planners in determining the minimum proportion of forest and the maximum proportion of plantation to ensure that a

  14. Minimum forest cover required for sustainable water flow regulation of a watershed: a case study in Jambi Province, Indonesia

    Science.gov (United States)

    Tarigan, Suria; Wiegand, Kerstin; Sunarti; Slamet, Bejo

    2018-01-01

    In many tropical regions, the rapid expansion of monoculture plantations has led to a sharp decline in forest cover, potentially degrading the ability of watersheds to regulate water flow. Therefore, regional planners need to determine the minimum proportion of forest cover that is required to support adequate ecosystem services in these watersheds. However, to date, there has been little research on this issue, particularly in tropical areas where monoculture plantations are expanding at an alarming rate. Therefore, in this study, we investigated the influence of forest cover and oil palm (Elaeis guineensis) and rubber (Hevea brasiliensis) plantations on the partitioning of rainfall into direct runoff and subsurface flow in a humid, tropical watershed in Jambi Province, Indonesia. To do this, we simulated streamflow with a calibrated Soil and Water Assessment Tool (SWAT) model and observed several watersheds to derive the direct runoff coefficient (C) and baseflow index (BFI). The model had a strong performance, with Nash-Sutcliffe efficiency values of 0.80-0.88 (calibration) and 0.80-0.85 (validation) and percent bias values of -2.9-1.2 (calibration) and 7.0-11.9 (validation). We found that the percentage of forest cover in a watershed was significantly negatively correlated with C and significantly positively correlated with BFI, whereas the rubber and oil palm plantation cover showed the opposite pattern. Our findings also suggested that at least 30 % of the forest cover was required in the study area for sustainable ecosystem services. This study provides new adjusted crop parameter values for monoculture plantations, particularly those that control surface runoff and baseflow processes, and it also describes the quantitative association between forest cover and flow indicators in a watershed, which will help regional planners in determining the minimum proportion of forest and the maximum proportion of plantation to ensure that a watershed can provide

  15. HIF- and Non-HIF-Regulated Hypoxic Responses Require the Estrogen-Related Receptor in Drosophila melanogaster

    Science.gov (United States)

    Li, Yan; Padmanabha, Divya; Gentile, Luciana B.; Dumur, Catherine I.; Beckstead, Robert B.; Baker, Keith D.

    2013-01-01

    Low-oxygen tolerance is supported by an adaptive response that includes a coordinate shift in metabolism and the activation of a transcriptional program that is driven by the hypoxia-inducible factor (HIF) pathway. The precise contribution of HIF-1a in the adaptive response, however, has not been determined. Here, we investigate how HIF influences hypoxic adaptation throughout Drosophila melanogaster development. We find that hypoxic-induced transcriptional changes are comprised of HIF-dependent and HIF-independent pathways that are distinct and separable. We show that normoxic set-points of carbohydrate metabolites are significantly altered in sima mutants and that these animals are unable to mobilize glycogen in hypoxia. Furthermore, we find that the estrogen-related receptor (dERR), which is a global regulator of aerobic glycolysis in larvae, is required for a competent hypoxic response. dERR binds to dHIFa and participates in the HIF-dependent transcriptional program in hypoxia. In addition, dERR acts in the absence of dHIFa in hypoxia and a significant portion of HIF-independent transcriptional responses can be attributed to dERR actions, including upregulation of glycolytic transcripts. These results indicate that competent hypoxic responses arise from complex interactions between HIF-dependent and -independent mechanisms, and that dERR plays a central role in both of these programs. PMID:23382692

  16. Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation

    Energy Technology Data Exchange (ETDEWEB)

    Tunbak, Hale, E-mail: h.tunbak@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Georgiou, Christiana, E-mail: christiana.georgiou.10@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Guan, Cui, E-mail: c.guan@qmul.ac.uk [School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Richardson, William David, E-mail: w.richardson@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Chittka, Alexandra, E-mail: a.chittka@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom)

    2016-05-27

    PRDM4 is a member of the PRDM family of transcriptional regulators which control various aspects of cellular differentiation and proliferation. PRDM proteins exert their biological functions both in the cytosol and the nucleus of cells. All PRDM proteins are characterised by the presence of two distinct structural motifs, the PR/SET domain and the zinc finger (ZF) motifs. We previously observed that deletion of all six zinc fingers found in PRDM4 leads to its accumulation in the cytosol, whereas overexpressed full length PRDM4 is found predominantly in the nucleus. Here, we investigated the requirements for single zinc fingers in the nuclear localisation of PRDM4. We demonstrate that ZF's 1, 2, 5 and 6 contribute to the accumulation of PRDM4 in the nucleus. Their effect is additive as deleting either ZF1-2 or ZF 5–6 redistributes PRDM4 protein from being almost exclusively nuclear to cytosolic and nuclear. We investigated the potential mechanism of nuclear shuttling of PRDM4 via the importin α/β-mediated pathway and find that PRDM4 nuclear targeting is independent of α/β-mediated nuclear import. -- Highlights: •Zinc fingers 1, 2, 5, and 6 are necessary for efficient nuclear localisation of PRDM4. •Zinc fingers 3 and 4 are dispensable for nuclear localisation of PRDM4. •Zinc knuckle is dispensable for nuclear localisation of PRDM4. •PRDM4 nuclear transport is independent of importin α/β-mediated pathway of nuclear import.

  17. Guide to NRC reporting and recordkeeping requirements. Compiled from requirements in Title 10 of the U.S. Code of Federal Regulations as codified on December 31, 1993; Revision 1

    International Nuclear Information System (INIS)

    Collins, M.; Shelton, B.

    1994-07-01

    This compilation includes in the first two sections the reporting and recordkeeping requirements applicable to US Nuclear Regulatory Commission (NRC) licensees and applicants and to members of the public. It includes those requirements codified in Title 10 of the code of Federal Regulations, Chapter 1, on December 31, 1993. It also includes, in a separate section, any of those requirements that were superseded or discontinued between January 1992 and December 1993. Finally, the appendix lists mailing and delivery addresses for NRC Headquarters and Regional Offices mentioned in the compilation. The Office of Information Resources Management staff compiled this listing of reporting and recordkeeping requirements to briefly describe each in a single document primarily to help licensees readily identify the requirements. The compilation is not a substitute for the regulations, and is not intended to impose any new requirements or technical positions. It is part of NRC's continuing efforts to comply with the Paperwork Reduction Act of 1980 and the Office of Management and Budget regulations that mandate effective and efficient Federal information resources management programs

  18. Supraregional gas transmission systems in a regulated area. EU uniform regulations are required; Ueberregionale Gastransportnetze im regulierten Umfeld. EU-einheitliche Regelungen gefordert

    Energy Technology Data Exchange (ETDEWEB)

    Bahke, Ralph [VNG Gastransport GmbH, Leipzig (Germany). Bereich Netzvermarktung

    2011-07-25

    German rules simplify the transport of gas, but impede the European harmonization. Thus, bundled products only can be commercialized at border crossing points such as Gatrac due to certificates of exemptions of the regulators. Before a single European market can be a reality, the framework conditions should be harmonized. This should enable enough margin for the design.

  19. The chemotaxis regulator pilG of Xylella fastidiosa is required for virulence in Vitis vinifera grapevines

    Science.gov (United States)

    Type IV pili of X. fastidiosa are regulated by pilG, a response regulator protein putatively involved in chemotaxis-like operon sensing stimuli through signal transduction pathways. To elucidate roles of pilG in pathogenicity of X. fastidiosa, the pilG-deletion mutant and complementary strain contai...

  20. 41 CFR 101-1.4902-2053 - GSA Form 2053, Agency Consolidated Requirements for GSA Regulations and Other External Issuances.

    Science.gov (United States)

    2010-07-01

    ...-2053 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.49-Illustrations of Forms § 101-1.4902-2053 GSA... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true GSA Form 2053, Agency...

  1. Nevada Nuclear Waste Storage Investigations: A review of requirements for biological information in federal, state, and local environmental laws and regulations

    International Nuclear Information System (INIS)

    Collins, E.; O'Farrell, T.P.

    1987-01-01

    Biological information concerning Yucca Mountain collected since 1980 is evaluated to determine if it is sufficient to satisfy the requirements of the various federal, state, and local laws and regulations that pertain to environmental protection or to development of waste repositories. The pertinent requirements of each law are summarized, missing information is identified, and recommendations are made for studies to fill these gaps. 11 refs., 2 figs., 1 tab

  2. Usage Statistics

    Science.gov (United States)

    ... this page: https://medlineplus.gov/usestatistics.html MedlinePlus Statistics To use the sharing features on this page, ... By Quarter View image full size Quarterly User Statistics Quarter Page Views Unique Visitors Oct-Dec-98 ...

  3. Mathematical statistics

    CERN Document Server

    Pestman, Wiebe R

    2009-01-01

    This textbook provides a broad and solid introduction to mathematical statistics, including the classical subjects hypothesis testing, normal regression analysis, and normal analysis of variance. In addition, non-parametric statistics and vectorial statistics are considered, as well as applications of stochastic analysis in modern statistics, e.g., Kolmogorov-Smirnov testing, smoothing techniques, robustness and density estimation. For students with some elementary mathematical background. With many exercises. Prerequisites from measure theory and linear algebra are presented.

  4. Frog Statistics

    Science.gov (United States)

    Whole Frog Project and Virtual Frog Dissection Statistics wwwstats output for January 1 through duplicate or extraneous accesses. For example, in these statistics, while a POST requesting an image is as well. Note that this under-represents the bytes requested. Starting date for following statistics

  5. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Yan-Zhuo Yang

    Full Text Available The plant hormone abscisic acid (ABA plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  6. A distal ABA responsive element in AtNCED3 promoter is required for positive feedback regulation of ABA biosynthesis in Arabidopsis.

    Science.gov (United States)

    Yang, Yan-Zhuo; Tan, Bao-Cai

    2014-01-01

    The plant hormone abscisic acid (ABA) plays a crucial role in plant development and responses to abiotic stresses. Recent studies indicate that a positive feedback regulation by ABA exists in ABA biosynthesis in plants under dehydration stress. To understand the molecular basis of this regulation, we analyzed the cis-elements of the AtNCED3 promoter in Arabidopsis. AtNCED3 encodes the first committed and highly regulated dioxygenase in the ABA biosynthetic pathway. Through delineated and mutagenesis analyses in stable-transformed Arabidopsis, we revealed that a distal ABA responsive element (ABRE: GGCACGTG, -2372 to -2364 bp) is required for ABA-induced AtNCED3 expression. By analyzing the AtNCED3 expression in ABRE binding protein ABF3 over-expression transgenic plants and knock-out mutants, we provide evidence that the ABA feedback regulation of AtNCED3 expression is not mediated by ABF3.

  7. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation

    OpenAIRE

    Moreira, Ricardo N.; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M.

    2017-01-01

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms...

  8. Efficient overproduction of membrane proteins in Lactococcus lactis requires the cell envelope stress sensor/regulator couple CesSR

    NARCIS (Netherlands)

    Pinto, Joao P C; Kuipers, Oscar P; Marreddy, Ravi K R; Poolman, Bert; Kok, Jan

    2011-01-01

    BACKGROUND: Membrane proteins comprise an important class of molecules whose study is largely frustrated by several intrinsic constraints, such as their hydrophobicity and added requirements for correct folding. Additionally, the complexity of the cellular mechanisms that are required to insert

  9. Supplement to the approved requirements for the packaging, labelling and carriage of radioactive material by rail. Packaging, Labelling and Carriage of Radioactive Material by Rail Regulations 1996

    International Nuclear Information System (INIS)

    1999-01-01

    The ADR and RID Framework Directives require EC member states' arrangements for the carriage of dangerous goods on domestic road and rail journeys to align with the existing ADR and RID agreements which cover international journeys by road and rail. Because ADR and RID are updated every two years in line with technical and scientific developments, the ADR/RID Framework Directives are also revised on a two-year cycle, to require member states to amend their implementing legislation accordingly. In Great Britain, these two Directives were initially implemented on 1 September 1996 via regulations (usually referred to as the 'carriage regulations'), containing the general legal duties, supported by approved documents, and an Approved Code of Practice containing the detailed technical requirements. The following approved documents have been updated: (a) Approved Vehicle Requirements (AVR) - L89; (b) Approved Requirements and test methods for the classification and packaging of dangerous goods for carriage (ARTM) - L88; (c) Approved Requirements for the packaging, labelling and carriage of radioactive material by rail (ARCRR) - L94; (d) Approved Requirements for the construction of vehicles intended for the carriage of explosives by road (AEVR) - L92; and (e) Approved Carriage List (ACL) - L90

  10. DasR is a pleiotropic regulator required for antibiotic production, pigment biosynthesis, and morphological development in Saccharopolyspora erythraea.

    Science.gov (United States)

    Liao, Cheng-Heng; Xu, Ya; Rigali, Sébastien; Ye, Bang-Ce

    2015-12-01

    The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S. coelicolor, we here identified and characterized the role of DasR to secondary metabolite production and morphological development in industrial erythromycin-producing S. erythraea. The physiological studies have shown that a constructed deletion of dasR in S. erythraea resulted in antibiotic, pigment, and aerial hyphae production deficit in a nutrient-rich condition. DNA microarray assay, combined with quantitative real-time reverse transcription PCR (qRT-PCR), confirmed these results by showing the downregulation of the genes relating to secondary metabolite production in the dasR null mutant. Notably, electrophoretic mobility shift assays (EMSA) showed DasR as being the first identified regulator that directly regulates the pigment biosynthesis rpp gene cluster. In addition, further studies indicated that GlcNAc, the major nutrient signal of DasR-responsed regulation, blocked secondary metabolite production and morphological development. The effects of GlcNAc were shown to be caused by DasR mediation. These findings demonstrated that DasR is an important pleiotropic regulator for both secondary metabolism and morphological development in S. erythraea, providing new insights for the genetic engineering of S. erythraea with increased erythromycin production.

  11. Adjustment of Energy requirements in TEK; TEK= Technical Regulations under the Norwegian Planning and Building Act; Justering av energikrav i TEK

    Energy Technology Data Exchange (ETDEWEB)

    Thyholt, Marit; Dokka, Tor Helge; Schild, Peter; Grini, Catherine; Mysen, Mads; Sartori, Igor

    2008-07-01

    The National Office of Building Technology and Administration (BE) desired to review the consequences of different levels of ambition for requirements for heat gaining from vent air, as well as a possible requirement for energy efficient design of building fronts. In addition the energy scope in the regulation (TEK2007) should be adjusted according to the final establishment of a new calculation standard (Norwegian Standard - NS 3031:2007). A statement on these subjects has been carried out at SINTEF Byggforsk, and is described in this report. Adjustments of framework regulations.There are only minor differences between adjusted calculations according to NS 3031 and the original energy framework calculations, i.e. the difference for net energy need amounts to the size of 0 to 6 percent. Heat gain.The report shows that it is possible - both from techical and financial considerations - to increase the requirement level for heat gain from vent air for most categories of buildings. This implies a sharpening of the annual median temperature efficiency from 70 % to 80 %, for all building categories, except from hospitals, institutions and light industry/workshops. A possible sharpening of regulations for heat gain in houses has not been evaluated. Depending on building category a sharpening of regulations for heat gain from vent air will imply that net energy need will be reduced on a scale of 20 to 30 kWh/m2 per annum. The report demonstrates that despite a possible sharpening of the requirements on energy efficiency for heat recovery devices does not prevent the use of large areas of windows and window panes. Vulnerability analyses show that deviations from the prerequisites in the basis for the energy framework concerning air quantities and air temperatures give the possibility of weakening the building's heating characteristics. Building fronts. Different methods for added requirements for building fronts have been examined. The aim has been to find methods and

  12. Developmentally regulated GTP-binding protein 2 is required for stabilization of Rac1-positive membrane tubules.

    Science.gov (United States)

    Mani, Muralidharan; Lee, Unn Hwa; Yoon, Nal Ae; Yoon, Eun Hye; Lee, Byung Ju; Cho, Wha Ja; Park, Jeong Woo

    2017-11-04

    Previously we have reported that developmentally regulated GTP-binding protein 2 (DRG2) localizes on Rab5 endosomes and plays an important role in transferrin (Tfn) recycling. We here identified DRG2 as a key regulator of membrane tubule stability. At 30 min after Tfn treatment, DRG2 localized to membrane tubules which were enriched with phosphatidylinositol 4-monophosphate [PI(4)P] and did not contain Rab5. DRG2 interacted with Rac1 more strongly with GTP-bound Rac1 and tubular localization of DRG2 depended on Rac1 activity. DRG2 depletion led to destabilization of membrane tubules, while ectopic expression of DRG2 rescued the stability of the membrane tubules in DRG2-depleted cells. Our results reveal a novel mechanism for regulation of membrane tubule stability mediated by DRG2. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Lectures on statistical mechanics

    CERN Document Server

    Bowler, M G

    1982-01-01

    Anyone dissatisfied with the almost ritual dullness of many 'standard' texts in statistical mechanics will be grateful for the lucid explanation and generally reassuring tone. Aimed at securing firm foundations for equilibrium statistical mechanics, topics of great subtlety are presented transparently and enthusiastically. Very little mathematical preparation is required beyond elementary calculus and prerequisites in physics are limited to some elementary classical thermodynamics. Suitable as a basis for a first course in statistical mechanics, the book is an ideal supplement to more convent

  14. Statistical physics

    CERN Document Server

    Sadovskii, Michael V

    2012-01-01

    This volume provides a compact presentation of modern statistical physics at an advanced level. Beginning with questions on the foundations of statistical mechanics all important aspects of statistical physics are included, such as applications to ideal gases, the theory of quantum liquids and superconductivity and the modern theory of critical phenomena. Beyond that attention is given to new approaches, such as quantum field theory methods and non-equilibrium problems.

  15. The transcription factor ABI4 Is required for the ascorbic acid-dependent regulation of growth and regulation of jasmonate-dependent defense signaling pathways in Arabidopsis.

    Science.gov (United States)

    Kerchev, Pavel I; Pellny, Till K; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D; Foyer, Christine H

    2011-09-01

    Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation.

  16. Statistical optics

    CERN Document Server

    Goodman, Joseph W

    2015-01-01

    This book discusses statistical methods that are useful for treating problems in modern optics, and the application of these methods to solving a variety of such problems This book covers a variety of statistical problems in optics, including both theory and applications.  The text covers the necessary background in statistics, statistical properties of light waves of various types, the theory of partial coherence and its applications, imaging with partially coherent light, atmospheric degradations of images, and noise limitations in the detection of light. New topics have been introduced i

  17. Harmonic statistics

    Energy Technology Data Exchange (ETDEWEB)

    Eliazar, Iddo, E-mail: eliazar@post.tau.ac.il

    2017-05-15

    The exponential, the normal, and the Poisson statistical laws are of major importance due to their universality. Harmonic statistics are as universal as the three aforementioned laws, but yet they fall short in their ‘public relations’ for the following reason: the full scope of harmonic statistics cannot be described in terms of a statistical law. In this paper we describe harmonic statistics, in their full scope, via an object termed harmonic Poisson process: a Poisson process, over the positive half-line, with a harmonic intensity. The paper reviews the harmonic Poisson process, investigates its properties, and presents the connections of this object to an assortment of topics: uniform statistics, scale invariance, random multiplicative perturbations, Pareto and inverse-Pareto statistics, exponential growth and exponential decay, power-law renormalization, convergence and domains of attraction, the Langevin equation, diffusions, Benford’s law, and 1/f noise. - Highlights: • Harmonic statistics are described and reviewed in detail. • Connections to various statistical laws are established. • Connections to perturbation, renormalization and dynamics are established.

  18. Harmonic statistics

    International Nuclear Information System (INIS)

    Eliazar, Iddo

    2017-01-01

    The exponential, the normal, and the Poisson statistical laws are of major importance due to their universality. Harmonic statistics are as universal as the three aforementioned laws, but yet they fall short in their ‘public relations’ for the following reason: the full scope of harmonic statistics cannot be described in terms of a statistical law. In this paper we describe harmonic statistics, in their full scope, via an object termed harmonic Poisson process: a Poisson process, over the positive half-line, with a harmonic intensity. The paper reviews the harmonic Poisson process, investigates its properties, and presents the connections of this object to an assortment of topics: uniform statistics, scale invariance, random multiplicative perturbations, Pareto and inverse-Pareto statistics, exponential growth and exponential decay, power-law renormalization, convergence and domains of attraction, the Langevin equation, diffusions, Benford’s law, and 1/f noise. - Highlights: • Harmonic statistics are described and reviewed in detail. • Connections to various statistical laws are established. • Connections to perturbation, renormalization and dynamics are established.

  19. Statistical methods

    CERN Document Server

    Szulc, Stefan

    1965-01-01

    Statistical Methods provides a discussion of the principles of the organization and technique of research, with emphasis on its application to the problems in social statistics. This book discusses branch statistics, which aims to develop practical ways of collecting and processing numerical data and to adapt general statistical methods to the objectives in a given field.Organized into five parts encompassing 22 chapters, this book begins with an overview of how to organize the collection of such information on individual units, primarily as accomplished by government agencies. This text then

  20. Histoplasmosis Statistics

    Science.gov (United States)

    ... Testing Treatment & Outcomes Health Professionals Statistics More Resources Candidiasis Candida infections of the mouth, throat, and esophagus Vaginal candidiasis Invasive candidiasis Definition Symptoms Risk & Prevention Sources Diagnosis ...

  1. BolA Is Required for the Accurate Regulation of c-di-GMP, a Central Player in Biofilm Formation.

    Science.gov (United States)

    Moreira, Ricardo N; Dressaire, Clémentine; Barahona, Susana; Galego, Lisete; Kaever, Volkhard; Jenal, Urs; Arraiano, Cecília M

    2017-09-19

    The bacterial second messenger cyclic dimeric GMP (c-di-GMP) is a nearly ubiquitous intracellular signaling molecule involved in the transition from the motile to the sessile/biofilm state in bacteria. C-di-GMP regulates various cellular processes, including biofilm formation, motility, and virulence. BolA is a transcription factor that promotes survival in different stresses and is also involved in biofilm formation. Both BolA and c-di-GMP participate in the regulation of motility mechanisms leading to similar phenotypes. Here, we establish the importance of the balance between these two factors for accurate regulation of the transition between the planktonic and sessile lifestyles. This balance is achieved by negative-feedback regulation of BolA and c-di-GMP. BolA not only contributes directly to the motility of bacteria but also regulates the expression of diguanylate cyclases and phosphodiesterases. This expression modulation influences the synthesis and degradation of c-di-GMP, while this signaling metabolite has a negative influence in bolA mRNA transcription. Finally, we present evidence of the dominant role of BolA in biofilm, showing that, even in the presence of elevated c-di-GMP levels, biofilm formation is reduced in the absence of BolA. C-di-GMP is one of the most important bacterial second messengers involved in several cellular processes, including virulence, cell cycle regulation, biofilm formation, and flagellar synthesis. In this study, we unravelled a direct connection between the bolA morphogene and the c-di-GMP signaling molecule. We show the important cross-talk that occurs between these two molecular regulators during the transition between the motile/planktonic and adhesive/sessile lifestyles in Escherichia coli This work provides important clues that can be helpful in the development of new strategies, and the results can be applied to other organisms with relevance for human health. IMPORTANCE Bacterial cells have evolved several

  2. Wdpcp, a PCP protein required for ciliogenesis, regulates directional cell migration and cell polarity by direct modulation of the actin cytoskeleton.

    Directory of Open Access Journals (Sweden)

    Cheng Cui

    2013-11-01

    Full Text Available Planar cell polarity (PCP regulates cell alignment required for collective cell movement during embryonic development. This requires PCP/PCP effector proteins, some of which also play essential roles in ciliogenesis, highlighting the long-standing question of the role of the cilium in PCP. Wdpcp, a PCP effector, was recently shown to regulate both ciliogenesis and collective cell movement, but the underlying mechanism is unknown. Here we show Wdpcp can regulate PCP by direct modulation of the actin cytoskeleton. These studies were made possible by recovery of a Wdpcp mutant mouse model. Wdpcp-deficient mice exhibit phenotypes reminiscent of Bardet-Biedl/Meckel-Gruber ciliopathy syndromes, including cardiac outflow tract and cochlea defects associated with PCP perturbation. We observed Wdpcp is localized to the transition zone, and in Wdpcp-deficient cells, Sept2, Nphp1, and Mks1 were lost from the transition zone, indicating Wdpcp is required for recruitment of proteins essential for ciliogenesis. Wdpcp is also found in the cytoplasm, where it is localized in the actin cytoskeleton and in focal adhesions. Wdpcp interacts with Sept2 and is colocalized with Sept2 in actin filaments, but in Wdpcp-deficient cells, Sept2 was lost from the actin cytoskeleton, suggesting Wdpcp is required for Sept2 recruitment to actin filaments. Significantly, organization of the actin filaments and focal contacts were markedly changed in Wdpcp-deficient cells. This was associated with decreased membrane ruffling, failure to establish cell polarity, and loss of directional cell migration. These results suggest the PCP defects in Wdpcp mutants are not caused by loss of cilia, but by direct disruption of the actin cytoskeleton. Consistent with this, Wdpcp mutant cochlea has normal kinocilia and yet exhibits PCP defects. Together, these findings provide the first evidence, to our knowledge, that a PCP component required for ciliogenesis can directly modulate the actin

  3. OsJAR1 is required for JA-regulated floret opening and anther dehiscence in rice

    NARCIS (Netherlands)

    Xiao, Y.; Chen, Y.; Charnikhova, T.; Mulder, P.P.J.; Heijmans, J.; Hoogenboom, A.; Agalou, A.; Michel, C.; Morel, J.B.; Dreni, L.; Kater, M.M.; Bouwmeester, H.; Wang, M.; Zhu, Z.; Ouwerkerk, P.B.F.

    2014-01-01

    Jasmonates are important phytohormones regulating reproductive development. We used two recessive rice Tos17 alleles of OsJAR1, osjar1-2 and osjar1-3, to study the biological function of jasmonates in rice anthesis. The florets of both osjar1 alleles stayed open during anthesis because the

  4. Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

    DEFF Research Database (Denmark)

    Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

    2015-01-01

    The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...

  5. The Serine Protease Inhibitor Neuroserpin Is Required for Normal Synaptic Plasticity and Regulates Learning and Social Behavior

    Science.gov (United States)

    Reumann, Rebecca; Vierk, Ricardo; Zhou, Lepu; Gries, Frederice; Kraus, Vanessa; Mienert, Julia; Romswinkel, Eva; Morellini, Fabio; Ferrer, Isidre; Nicolini, Chiara; Fahnestock, Margaret; Rune, Gabriele; Glatzel, Markus; Galliciotti, Giovanna

    2017-01-01

    The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the…

  6. Quantitative statistical analysis of cis-regulatory sequences in ABA/VP1- and CBF/DREB1-regulated genes of Arabidopsis.

    Science.gov (United States)

    Suzuki, Masaharu; Ketterling, Matthew G; McCarty, Donald R

    2005-09-01

    We have developed a simple quantitative computational approach for objective analysis of cis-regulatory sequences in promoters of coregulated genes. The program, designated MotifFinder, identifies oligo sequences that are overrepresented in promoters of coregulated genes. We used this approach to analyze promoter sequences of Viviparous1 (VP1)/abscisic acid (ABA)-regulated genes and cold-regulated genes, respectively, of Arabidopsis (Arabidopsis thaliana). We detected significantly enriched sequences in up-regulated genes but not in down-regulated genes. This result suggests that gene activation but not repression is mediated by specific and common sequence elements in promoters. The enriched motifs include several known cis-regulatory sequences as well as previously unidentified motifs. With respect to known cis-elements, we dissected the flanking nucleotides of the core sequences of Sph element, ABA response elements (ABREs), and the C repeat/dehydration-responsive element. This analysis identified the motif variants that may correlate with qualitative and quantitative differences in gene expression. While both VP1 and cold responses are mediated in part by ABA signaling via ABREs, these responses correlate with unique ABRE variants distinguished by nucleotides flanking the ACGT core. ABRE and Sph motifs are tightly associated uniquely in the coregulated set of genes showing a strict dependence on VP1 and ABA signaling. Finally, analysis of distribution of the enriched sequences revealed a striking concentration of enriched motifs in a proximal 200-base region of VP1/ABA and cold-regulated promoters. Overall, each class of coregulated genes possesses a discrete set of the enriched motifs with unique distributions in their promoters that may account for the specificity of gene regulation.

  7. 31 CFR 103.120 - Anti-money laundering program requirements for financial institutions regulated by a Federal...

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Anti-money laundering program... Laundering Programs Anti-Money Laundering Programs § 103.120 Anti-money laundering program requirements for... anti-money laundering program that complies with the requirements of §§ 103.176 and 103.178 and the...

  8. Statistical Diversions

    Science.gov (United States)

    Petocz, Peter; Sowey, Eric

    2012-01-01

    The term "data snooping" refers to the practice of choosing which statistical analyses to apply to a set of data after having first looked at those data. Data snooping contradicts a fundamental precept of applied statistics, that the scheme of analysis is to be planned in advance. In this column, the authors shall elucidate the…

  9. Statistical Diversions

    Science.gov (United States)

    Petocz, Peter; Sowey, Eric

    2008-01-01

    In this article, the authors focus on hypothesis testing--that peculiarly statistical way of deciding things. Statistical methods for testing hypotheses were developed in the 1920s and 1930s by some of the most famous statisticians, in particular Ronald Fisher, Jerzy Neyman and Egon Pearson, who laid the foundations of almost all modern methods of…

  10. Scan Statistics

    CERN Document Server

    Glaz, Joseph

    2009-01-01

    Suitable for graduate students and researchers in applied probability and statistics, as well as for scientists in biology, computer science, pharmaceutical science and medicine, this title brings together a collection of chapters illustrating the depth and diversity of theory, methods and applications in the area of scan statistics.

  11. Practical Statistics

    CERN Document Server

    Lyons, L.

    2016-01-01

    Accelerators and detectors are expensive, both in terms of money and human effort. It is thus important to invest effort in performing a good statistical anal- ysis of the data, in order to extract the best information from it. This series of five lectures deals with practical aspects of statistical issues that arise in typical High Energy Physics analyses.

  12. Descriptive statistics.

    Science.gov (United States)

    Nick, Todd G

    2007-01-01

    Statistics is defined by the Medical Subject Headings (MeSH) thesaurus as the science and art of collecting, summarizing, and analyzing data that are subject to random variation. The two broad categories of summarizing and analyzing data are referred to as descriptive and inferential statistics. This chapter considers the science and art of summarizing data where descriptive statistics and graphics are used to display data. In this chapter, we discuss the fundamentals of descriptive statistics, including describing qualitative and quantitative variables. For describing quantitative variables, measures of location and spread, for example the standard deviation, are presented along with graphical presentations. We also discuss distributions of statistics, for example the variance, as well as the use of transformations. The concepts in this chapter are useful for uncovering patterns within the data and for effectively presenting the results of a project.

  13. Molecular analysis of mxbD and mxbM, a putative sensor-regulator pair required for oxidation of methanol in Methylobacterium extorquens AM1.

    Science.gov (United States)

    Springer, A L; Morris, C J; Lidstrom, M E

    1997-05-01

    Five genes are thought to be required for transcription of methanol oxidation genes in Methylobacterium strains. These putative regulatory genes include mxcQE, which encode a putative sensor-regulator pair, and mxbDM and mxaB, whose functions are less well-understood. In this study, mxbDM in Methylobacterium extorquens AM1 were shown to be required for expression of a xylE transcriptional fusion to the structural gene for the large subunit of methanol dehydrogenase (mxaF), confirming the role of these genes in transcriptional regulation of mxaF. The nucleotide sequence suggests that mxbD encodes a histidine protein kinase with two transmembrane domains and that mxbM encodes a DNA-binding response regulator. A xylE transcriptional fusion to the putative mxbD promoter showed low-level expression in wild-type cells grown on one-carbon (C1) compounds and no detectable expression in cells grown on succinate. Deletion analysis of this promoter construct showed that the region 229-129 bp upstream of the start of mxbD is required for expression. The expression of the mxbD-xylE fusion was examined in each of the five known regulatory mutant classes. xylE expression was reduced to non-detectable levels in MxcQ and MxcE mutants, but was not affected in the other regulatory mutants or in non-regulatory mutants defective in methanol oxidation. These results suggest a regulatory hierarchy in which the sensor-regulator pair MxcQE control expression of the sensor-regulator pair MxbDM, and MxbDM in turn control expression of a number of genes involved in methanol oxidation.

  14. Suppressor of fusion, a Fusarium oxysporum homolog of Ndt80, is required for nutrient-dependent regulation of anastomosis.

    Science.gov (United States)

    Shahi, Shermineh; Fokkens, Like; Houterman, Petra M; Rep, Martijn

    2016-10-01

    Heterokaryon formation is an essential step in asexual recombination in Fusarium oxysporum. Filamentous fungi have an elaborate nonself recognition machinery to prevent formation and proliferation of heterokaryotic cells, called heterokaryon incompatibility (HI). In F. oxysporum the regulation of this machinery is not well understood. In Neurospora crassa, Vib-1, a putative transcription factor of the p53-like Ndt80 family of transcription factors, has been identified as global regulator of HI. In this study we investigated the role of the F. oxysporum homolog of Vib-1, called Suf, in vegetative hyphal and conidial anastomosis tube (CAT) fusion and HI. We identified a novel function for an Ndt80 homolog as a nutrient-dependent regulator of anastomosis. Strains carrying the SUF deletion mutation display a hyper-fusion phenotype during vegetative growth as well as germling development. In addition, conidial paring of incompatible SUF deletion strains led to more heterokaryon formation, which is independent of suppression of HI. Our data provides further proof for the divergence in the functions of different members Ndt80 family. We propose that Ndt80 homologs mediate responses to nutrient quality and quantity, with specific responses varying between species. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Human regulator of telomere elongation helicase 1 (RTEL1) is required for the nuclear and cytoplasmic trafficking of pre-U2 RNA

    OpenAIRE

    Schertzer , Michael; Jouravleva , Karina; Perderiset , Mylène; Dingli , Florent; Loew , Damarys; Le Guen , Tangui; Bardoni , Barbara; De Villartay , Jean-Pierre; Revy , Patrick; Londono-Vallejo , Arturo

    2015-01-01

    International audience; Hoyeraal-Hreidarsson syndrome (HHS) is a severe form of Dyskeratosis congenita characterized by developmental defects, bone marrow failure and im-munodeficiency and has been associated with telom-ere dysfunction. Recently, mutations in Regulator of Telomere ELongation helicase 1 (RTEL1), a helicase first identified in Mus musculus as being responsible for the maintenance of long telomeres, have been identified in several HHS patients. Here we show that RTEL1 is require...

  16. Semiconductor statistics

    CERN Document Server

    Blakemore, J S

    1962-01-01

    Semiconductor Statistics presents statistics aimed at complementing existing books on the relationships between carrier densities and transport effects. The book is divided into two parts. Part I provides introductory material on the electron theory of solids, and then discusses carrier statistics for semiconductors in thermal equilibrium. Of course a solid cannot be in true thermodynamic equilibrium if any electrical current is passed; but when currents are reasonably small the distribution function is but little perturbed, and the carrier distribution for such a """"quasi-equilibrium"""" co

  17. Statistical Physics

    CERN Document Server

    Wannier, Gregory Hugh

    1966-01-01

    Until recently, the field of statistical physics was traditionally taught as three separate subjects: thermodynamics, statistical mechanics, and kinetic theory. This text, a forerunner in its field and now a classic, was the first to recognize the outdated reasons for their separation and to combine the essentials of the three subjects into one unified presentation of thermal physics. It has been widely adopted in graduate and advanced undergraduate courses, and is recommended throughout the field as an indispensable aid to the independent study and research of statistical physics.Designed for

  18. Statistics Clinic

    Science.gov (United States)

    Feiveson, Alan H.; Foy, Millennia; Ploutz-Snyder, Robert; Fiedler, James

    2014-01-01

    Do you have elevated p-values? Is the data analysis process getting you down? Do you experience anxiety when you need to respond to criticism of statistical methods in your manuscript? You may be suffering from Insufficient Statistical Support Syndrome (ISSS). For symptomatic relief of ISSS, come for a free consultation with JSC biostatisticians at our help desk during the poster sessions at the HRP Investigators Workshop. Get answers to common questions about sample size, missing data, multiple testing, when to trust the results of your analyses and more. Side effects may include sudden loss of statistics anxiety, improved interpretation of your data, and increased confidence in your results.

  19. Image Statistics

    Energy Technology Data Exchange (ETDEWEB)

    Wendelberger, Laura Jean [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-08-08

    In large datasets, it is time consuming or even impossible to pick out interesting images. Our proposed solution is to find statistics to quantify the information in each image and use those to identify and pick out images of interest.

  20. Accident Statistics

    Data.gov (United States)

    Department of Homeland Security — Accident statistics available on the Coast Guard’s website by state, year, and one variable to obtain tables and/or graphs. Data from reports has been loaded for...

  1. CMS Statistics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Center for Strategic Planning produces an annual CMS Statistics reference booklet that provides a quick reference for summary information about health...

  2. WPRDC Statistics

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — Data about the usage of the WPRDC site and its various datasets, obtained by combining Google Analytics statistics with information from the WPRDC's data portal.

  3. Multiparametric statistics

    CERN Document Server

    Serdobolskii, Vadim Ivanovich

    2007-01-01

    This monograph presents mathematical theory of statistical models described by the essentially large number of unknown parameters, comparable with sample size but can also be much larger. In this meaning, the proposed theory can be called "essentially multiparametric". It is developed on the basis of the Kolmogorov asymptotic approach in which sample size increases along with the number of unknown parameters.This theory opens a way for solution of central problems of multivariate statistics, which up until now have not been solved. Traditional statistical methods based on the idea of an infinite sampling often break down in the solution of real problems, and, dependent on data, can be inefficient, unstable and even not applicable. In this situation, practical statisticians are forced to use various heuristic methods in the hope the will find a satisfactory solution.Mathematical theory developed in this book presents a regular technique for implementing new, more efficient versions of statistical procedures. ...

  4. Gonorrhea Statistics

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search the CDC Gonorrhea Note: Javascript is disabled or is not supported ... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Gonorrhea Statistics Recommend on Facebook Tweet Share Compartir Gonorrhea ...

  5. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  6. Proteolytic cleavage and PKA phosphorylation of α1C subunit are not required for adrenergic regulation of CaV1.2 in the heart.

    Science.gov (United States)

    Katchman, Alexander; Yang, Lin; Zakharov, Sergey I; Kushner, Jared; Abrams, Jeffrey; Chen, Bi-Xing; Liu, Guoxia; Pitt, Geoffrey S; Colecraft, Henry M; Marx, Steven O

    2017-08-22

    Calcium influx through the voltage-dependent L-type calcium channel (Ca V 1.2) rapidly increases in the heart during "fight or flight" through activation of the β-adrenergic and protein kinase A (PKA) signaling pathway. The precise molecular mechanisms of β-adrenergic activation of cardiac Ca V 1.2, however, are incompletely known, but are presumed to require phosphorylation of residues in α 1C and C-terminal proteolytic cleavage of the α 1C subunit. We generated transgenic mice expressing an α 1C with alanine substitutions of all conserved serine or threonine, which is predicted to be a potential PKA phosphorylation site by at least one prediction tool, while sparing the residues previously shown to be phosphorylated but shown individually not to be required for β-adrenergic regulation of Ca V 1.2 current (17-mutant). A second line included these 17 putative sites plus the five previously identified phosphoregulatory sites (22-mutant), thus allowing us to query whether regulation requires their contribution in combination. We determined that acute β-adrenergic regulation does not require any combination of potential PKA phosphorylation sites conserved in human, guinea pig, rabbit, rat, and mouse α 1C subunits. We separately generated transgenic mice with inducible expression of proteolytic-resistant α 1C Prevention of C-terminal cleavage did not alter β-adrenergic stimulation of Ca V 1.2 in the heart. These studies definitively rule out a role for all conserved consensus PKA phosphorylation sites in α 1C in β-adrenergic stimulation of Ca V 1.2, and show that phosphoregulatory sites on α 1C are not redundant and do not each fractionally contribute to the net stimulatory effect of β-adrenergic stimulation. Further, proteolytic cleavage of α 1C is not required for β-adrenergic stimulation of Ca V 1.2.

  7. Vital statistics

    CERN Document Server

    MacKenzie, Dana

    2004-01-01

    The drawbacks of using 19th-century mathematics in physics and astronomy are illustrated. To continue with the expansion of the knowledge about the cosmos, the scientists will have to come in terms with modern statistics. Some researchers have deliberately started importing techniques that are used in medical research. However, the physicists need to identify the brand of statistics that will be suitable for them, and make a choice between the Bayesian and the frequentists approach. (Edited abstract).

  8. SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production.

    Science.gov (United States)

    Chen, Gang; Korfhagen, Thomas R; Xu, Yan; Kitzmiller, Joseph; Wert, Susan E; Maeda, Yutaka; Gregorieff, Alexander; Clevers, Hans; Whitsett, Jeffrey A

    2009-10-01

    Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.

  9. Safety evaluations required in the safety regulations for Monju and the validity confirmation of safety evaluation methods

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The purposes of this study are to perform the safety evaluations of the fast breeder reactor 'Monju' and to confirm the validity of the safety evaluation methods. In JFY 2012, the following results were obtained. As for the development of safety evaluation methods needed in the safety examination achieved for the reactor establishment permission, development of the analysis codes, such as a core damage analysis code, were carried out according to the plan. As for the development of the safety evaluation method needed for the risk informed safety regulation, the quantification technique of the event tree using the Continuous Markov chain Monte Carlo method (CMMC method) were studied. (author)

  10. Unique C-terminal region of Hap3 is required for methanol-regulated gene expression in the methylotrophic yeast Candida boidinii.

    Science.gov (United States)

    Oda, Saori; Yurimoto, Hiroya; Nitta, Nobuhisa; Sakai, Yasuyoshi

    2016-05-01

    The Hap complex of the methylotrophic yeast Candida boidinii was found to be required for methanol-regulated gene expression. In this study, we performed functional characterization of CbHap3p, one of the Hap complex components in C. boidinii. Sequence alignment of Hap3 proteins revealed the presence of a unique extended C-terminal region, which is not present in Hap3p from Saccharomyces cerevisiae (ScHap3p), but is found in Hap3p proteins of methylotrophic yeasts. Deletion of the C-terminal region of CbHap3p (Δ256-292 or Δ107-237) diminished activation of methanol-regulated genes and abolished the ability to grow on methanol, but did not affect nuclear localization or DNA-binding ability. However, deletion of the N-terminal region of CbHap3p (Δ1-20) led to not only a growth defect on methanol and a decreased level of methanol-regulated gene expression, but also impaired nuclear localization and binding to methanol-regulated gene promoters. We also revealed that CbHap3p could complement the growth defect of the Schap3Δ strain on glycerol, although ScHap3p could not complement the growth defect of a Cbhap3Δ strain on methanol. We conclude that the unique C-terminal region of CbHap3p contributes to maximum activation of methanol-regulated genes, whilst the N-terminal region is required for nuclear localization and binding to DNA.

  11. Environmental regulation of lateral root emergence in Medicago truncatula requires the HD-Zip I transcription factor HB1.

    Science.gov (United States)

    Ariel, Federico; Diet, Anouck; Verdenaud, Marion; Gruber, Véronique; Frugier, Florian; Chan, Raquel; Crespi, Martin

    2010-07-01

    The adaptation of root architecture to environmental constraints is a major agricultural trait, notably in legumes, the third main crop worldwide. This root developmental plasticity depends on the formation of lateral roots (LRs) emerging from primary roots. In the model legume Medicago truncatula, the HD-Zip I transcription factor HB1 is expressed in primary and lateral root meristems and induced by salt stress. Constitutive expression of HB1 in M. truncatula roots alters their architecture, whereas hb1 TILLING mutants showed increased lateral root emergence. Electrophoretic mobility shift assay, promoter mutagenesis, and chromatin immunoprecipitation-PCR assays revealed that HB1 directly recognizes a CAATAATTG cis-element present in the promoter of a LOB-like (for Lateral Organ Boundaries) gene, LBD1, transcriptionally regulated by auxin. Expression of these genes in response to abscisic acid and auxin and their behavior in hb1 mutants revealed an HB1-mediated repression of LBD1 acting during LR emergence. M. truncatula HB1 regulates an adaptive developmental response to minimize the root surface exposed to adverse environmental stresses.

  12. Requirements for the approval of dosimetry services under the Ionising Radiations Regulations 1985: Pt. 2: Internal radiations

    International Nuclear Information System (INIS)

    1991-01-01

    Guidance for dosimetry services on the requirements for approval by the Health and Safety Executive (HSE) is provided in three parts. This part sets out the procedures and criteria that will be used by HSE in the assessment of dosimetry services seeking approval in relation to internal radiations (including radon decay products). (author)

  13. Requirements for the approval of dosimetry services under the Ionising Radiations Regulations 1985: Pt. 3: Coordination and record-keeping

    International Nuclear Information System (INIS)

    1991-01-01

    Guidance for dosimetry services on the requirements for approval by the Health and Safety Executive (HSE) is provided in three parts. This part sets out the procedures and criteria that will be used by HSE in the assessment of dosimetry services seeking approval for coordination and record keeping. (author)

  14. 75 FR 77561 - Regulations Issued Under the Export Grape and Plum Act; Revision to the Minimum Requirements

    Science.gov (United States)

    2010-12-13

    ... amount of product sold and an increase in returns to producers, shippers, exporters, and carriers... additional 2 percent tolerance for sealed berry cracks on the Exotic grape variety. This action was... minimum size and quality requirements for export shipments of any variety of vinifera species table grapes...

  15. 7 CFR 319.5 - Requirements for submitting requests to change the regulations in 7 CFR part 319.

    Science.gov (United States)

    2010-01-01

    ... required in order to complete a pest risk analysis in accordance with international standards for pest risk... efficiency of monitoring implementation. (8) Existing documentation: Relevant pest risk analyses... Analysis and Operations, PPQ, APHIS, 4700 River Road Unit 140, Riverdale, MD 20737. (d) Information. The...

  16. Requirements for the approval of dosimetry services under the Ionising Radiations Regulations 1985: Pt. 1: External radiations

    International Nuclear Information System (INIS)

    1991-01-01

    Guidance for dosimetry services on the requirements for approval by the Health and Safety Executive (HSE) is provided in three parts. This part sets out the procedures and criteria that will be used by HSE in the assessment of dosimetry services seeking approval in relation to external radiations (including accidents). (author)

  17. Concerning major items in government ordinance requiring modification of part of enforcement regulation for law relating to control of nuclear material, nuclear fuel and nuclear reactor

    International Nuclear Information System (INIS)

    1989-01-01

    The report describes major items planned to be incorporated into the enforcement regulations for laws relating to control of nuclear material, nuclear fuel and nuclear reactor. The modifications have become necessary for the nation to conclude a nuclear material protection treaty with other countries. The modification include the definitions of 'special nuclear fuel substances' and 'special nuclear fuel substances' and 'special nuclear fuel substances subject to protection'. The modifications require that protective measures be taken when handling and transporting special nuclear fuel substances subject to protection. Transport of special nuclear fuel substances requires approval from the Prime Minister or Transport Minister. Transport of special nuclear fuel substances subject to protection should be conducted after notifying the prefectural Public Safety Commission. Transport of special nuclear fuel substances subject to protection requires the conclusion of arrangements among responsible persons and approval of them from the Prime Minister. (N.K.)

  18. Arabidopsis ACA7, encoding a putative auto-regulated Ca(2+)-ATPase, is required for normal pollen development.

    Science.gov (United States)

    Lucca, Noel; León, Gabriel

    2012-04-01

    Microgametogenesis is a complex process that involves numerous well-coordinated cell activities, ending with the production of pollen grains. Pollen development has been studied at the cytological level in Arabidopsis and other plant species, where its temporal time course has been defined. However, the molecular mechanism underlying this process is still unclear, since a relative small number of genes and/or processes have been identified as essential for pollen development. We have designed a methodology to select candidate genes for functional analysis, based on transcriptomic data obtained from different stages of pollen development. From our analyses, we selected At2g22950 as a candidate gene; this gene encodes a protein belonging to the auto-regulated Ca(2+)-ATPase family, ACA7. Microarray data indicate that ACA7 is expressed exclusively in developing pollen grains, with the highest level of mRNA at the time of the second pollen mitosis. Our RT-PCR experiments showed that ACA7 mRNA is detected exclusively in developing flowers. Confocal microscopy experiments showed a plasma membrane localization for the recombinant GFP:ACA7 protein. We identified two different insertional mutant lines, aca7-1 and aca7-2; plants from both mutant lines displayed a normal vegetative development but showed large amounts of dead pollen grains in mature flowers assayed by Alexander's staining. Histological analysis indicated that abnormalities are detected after the first pollen mitosis and we found a strong correlation between ACA7 mRNA accumulation and the severity of the phenotype. Our results indicate that ACA7 is a plasma membrane protein that has an important role during pollen development, possibly through regulation of Ca(2+) homeostasis. © Springer-Verlag 2011

  19. Aminoacyl-tRNA quality control is required for efficient activation of the TOR pathway regulator Gln3p.

    Science.gov (United States)

    Mohler, Kyle; Mann, Rebecca; Kyle, Amanda; Reynolds, Noah; Ibba, Michael

    2017-09-14

    The aminoacylation status of the cellular tRNA pool regulates both general amino acid control (GAAC) and target of rapamycin (TOR) stress response pathways in yeast. Consequently, fidelity of translation at the level of aminoacyl-tRNA synthesis plays a central role in determining accuracy and sensitivity of stress responses. To investigate effects of translational quality control (QC) on cell physiology under stress conditions, phenotypic microarray analyses were used to identify changes in QC deficient cells. Nitrogen source growth assays showed QC deficient yeast grew differently compared to WT. The QC deficient strain was more tolerant to caffeine treatment than wild type through altered interactions with the TOR and GAAC pathways. Increased caffeine tolerance of the QC deficient strain was consistent with the observation that the activity of Gln3p, a transcription factor controlled by the TOR pathway, is decreased in the QC deficient strain compared to WT. GCN4 translation, which is typically repressed in the absence of nutritional stress, was enhanced in the QC deficient strain through TOR inhibition. QC did not impact cell cycle regulation; however, the chronological lifespan of QC deficient yeast strains decreased compared to wild type, likely due to translational errors and alteration of the TOR-associated regulon. These findings support the idea that changes in translational fidelity provide a mechanism of cellular adaptation by modulating TOR activity. This, in turn, supports a central role for aminoacyl-tRNA synthesis QC in the integrated stress response by maintaining the proper aa-tRNA pools necessary to coordinate the GAAC and TOR.

  20. Statistical optics

    Science.gov (United States)

    Goodman, J. W.

    This book is based on the thesis that some training in the area of statistical optics should be included as a standard part of any advanced optics curriculum. Random variables are discussed, taking into account definitions of probability and random variables, distribution functions and density functions, an extension to two or more random variables, statistical averages, transformations of random variables, sums of real random variables, Gaussian random variables, complex-valued random variables, and random phasor sums. Other subjects examined are related to random processes, some first-order properties of light waves, the coherence of optical waves, some problems involving high-order coherence, effects of partial coherence on imaging systems, imaging in the presence of randomly inhomogeneous media, and fundamental limits in photoelectric detection of light. Attention is given to deterministic versus statistical phenomena and models, the Fourier transform, and the fourth-order moment of the spectrum of a detected speckle image.

  1. Statistical mechanics

    CERN Document Server

    Schwabl, Franz

    2006-01-01

    The completely revised new edition of the classical book on Statistical Mechanics covers the basic concepts of equilibrium and non-equilibrium statistical physics. In addition to a deductive approach to equilibrium statistics and thermodynamics based on a single hypothesis - the form of the microcanonical density matrix - this book treats the most important elements of non-equilibrium phenomena. Intermediate calculations are presented in complete detail. Problems at the end of each chapter help students to consolidate their understanding of the material. Beyond the fundamentals, this text demonstrates the breadth of the field and its great variety of applications. Modern areas such as renormalization group theory, percolation, stochastic equations of motion and their applications to critical dynamics, kinetic theories, as well as fundamental considerations of irreversibility, are discussed. The text will be useful for advanced students of physics and other natural sciences; a basic knowledge of quantum mechan...

  2. Statistical mechanics

    CERN Document Server

    Jana, Madhusudan

    2015-01-01

    Statistical mechanics is self sufficient, written in a lucid manner, keeping in mind the exam system of the universities. Need of study this subject and its relation to Thermodynamics is discussed in detail. Starting from Liouville theorem gradually, the Statistical Mechanics is developed thoroughly. All three types of Statistical distribution functions are derived separately with their periphery of applications and limitations. Non-interacting ideal Bose gas and Fermi gas are discussed thoroughly. Properties of Liquid He-II and the corresponding models have been depicted. White dwarfs and condensed matter physics, transport phenomenon - thermal and electrical conductivity, Hall effect, Magneto resistance, viscosity, diffusion, etc. are discussed. Basic understanding of Ising model is given to explain the phase transition. The book ends with a detailed coverage to the method of ensembles (namely Microcanonical, canonical and grand canonical) and their applications. Various numerical and conceptual problems ar...

  3. Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Möbius, Wiebke; Wehr, Michael C; Krämer-Albers, Eva-Maria; Brügger, Britta; Nave, Klaus-Armin

    2009-05-13

    Rapid impulse conduction requires electrical insulation of axons by myelin, a cholesterol-rich extension of the glial cell membrane with a characteristic composition of proteins and lipids. Mutations in several myelin protein genes cause endoplasmic reticulum (ER) retention and disease, presumably attributable to failure of misfolded proteins to pass the ER quality control. Because many myelin proteins partition into cholesterol-rich membrane rafts, their interaction with cholesterol could potentially be part of the ER quality control system. Here, we provide in vitro and in vivo evidence that the major peripheral myelin protein P0 requires cholesterol for exiting the ER and reaching the myelin compartment. Cholesterol dependency of P0 trafficking in heterologous cells is mediated by a cholesterol recognition/interaction amino acid consensus (CRAC) motif. Mutant mice lacking cholesterol biosynthesis in Schwann cells suffer from severe hypomyelination with numerous uncompacted myelin stretches. This demonstrates that high-level cholesterol coordinates P0 export with myelin membrane synthesis, which is required for the correct stoichiometry of myelin components and for myelin compaction.

  4. Statistical Physics

    CERN Document Server

    Mandl, Franz

    1988-01-01

    The Manchester Physics Series General Editors: D. J. Sandiford; F. Mandl; A. C. Phillips Department of Physics and Astronomy, University of Manchester Properties of Matter B. H. Flowers and E. Mendoza Optics Second Edition F. G. Smith and J. H. Thomson Statistical Physics Second Edition E. Mandl Electromagnetism Second Edition I. S. Grant and W. R. Phillips Statistics R. J. Barlow Solid State Physics Second Edition J. R. Hook and H. E. Hall Quantum Mechanics F. Mandl Particle Physics Second Edition B. R. Martin and G. Shaw The Physics of Stars Second Edition A. C. Phillips Computing for Scient

  5. Statistical inference

    CERN Document Server

    Rohatgi, Vijay K

    2003-01-01

    Unified treatment of probability and statistics examines and analyzes the relationship between the two fields, exploring inferential issues. Numerous problems, examples, and diagrams--some with solutions--plus clear-cut, highlighted summaries of results. Advanced undergraduate to graduate level. Contents: 1. Introduction. 2. Probability Model. 3. Probability Distributions. 4. Introduction to Statistical Inference. 5. More on Mathematical Expectation. 6. Some Discrete Models. 7. Some Continuous Models. 8. Functions of Random Variables and Random Vectors. 9. Large-Sample Theory. 10. General Meth

  6. AP statistics

    CERN Document Server

    Levine-Wissing, Robin

    2012-01-01

    All Access for the AP® Statistics Exam Book + Web + Mobile Everything you need to prepare for the Advanced Placement® exam, in a study system built around you! There are many different ways to prepare for an Advanced Placement® exam. What's best for you depends on how much time you have to study and how comfortable you are with the subject matter. To score your highest, you need a system that can be customized to fit you: your schedule, your learning style, and your current level of knowledge. This book, and the online tools that come with it, will help you personalize your AP® Statistics prep

  7. Statistical mechanics

    CERN Document Server

    Davidson, Norman

    2003-01-01

    Clear and readable, this fine text assists students in achieving a grasp of the techniques and limitations of statistical mechanics. The treatment follows a logical progression from elementary to advanced theories, with careful attention to detail and mathematical development, and is sufficiently rigorous for introductory or intermediate graduate courses.Beginning with a study of the statistical mechanics of ideal gases and other systems of non-interacting particles, the text develops the theory in detail and applies it to the study of chemical equilibrium and the calculation of the thermody

  8. Is the risk for soil arthropods covered by new data requirements under the EU PPP Regulation No. 1107/2009?

    Science.gov (United States)

    Kohlschmid, E; Ruf, D

    2016-12-01

    Testing of effects on earthworms and non-target foliar arthropods is an integral part of the ecotoxicological risk assessment for the authorization of plant protection products. According to the new data requirements, which came into force in 2014 for active substances and in 2016 for plant protection products, the chronic earthworm toxicity test with Eisenia fetida based on reproductive, growth, and behavioral effects instead of the acute earthworm toxicity test based on mortality, has to be conducted routinely. Additional testing of effects on soil arthropods (Folsomia candida, Hyposaspis aculeifer) is required if the risk assessment of foliar applications raises concerns regarding non-target foliar arthropods (Aphidius rhopalosiphi, Typhlodromus pyri) or if the product is applied directly on or into the soil. Thus, it was investigated whether the sublethal earthworm endpoint is more sensitive than the sublethal soil arthropod endpoint for different types of pesticides and whether the risk assessment for non-target arthropods would trigger the testing of effects on soil arthropods in the cases where soil arthropods are more sensitive than earthworms. Toxicity data were obtained from Swiss ecotoxicological database, EFSA Conclusions and scientific literature. For insecticides and herbicides, no general conclusion regarding differences in sensitivity of either earthworms or soil arthropods based on sublethal endpoints were possible. For fungicides, the data indicated that in general, earthworms seemed to be more sensitive than soil arthropods. In total, the sublethal F. candida or H. aculeifer endpoint was lower than the sublethal E. fetida endpoint for 23 (34 %) out of 68 active substances. For 26 % of these 23 active substances, testing of soil arthropods would not have been triggered due to the new data requirement. These results based on sublethal endpoints show that earthworms and soil arthropods differ in sensitivity toward certain active substances and

  9. Requirement for the eIF4E binding proteins for the synergistic down-regulation of protein synthesis by hypertonic conditions and mTOR inhibition.

    Science.gov (United States)

    Clemens, Michael J; Elia, Androulla; Morley, Simon J

    2013-01-01

    The protein kinase mammalian target of rapamycin (mTOR) regulates the phosphorylation and activity of several proteins that have the potential to control translation, including p70S6 kinase and the eIF4E binding proteins 4E-BP1 and 4E-BP2. In spite of this, in exponentially growing cells overall protein synthesis is often resistant to mTOR inhibitors. We report here that sensitivity of wild-type mouse embryonic fibroblasts (MEFs) to mTOR inhibitors can be greatly increased when the cells are subjected to the physiological stress imposed by hypertonic conditions. In contrast, protein synthesis in MEFs with a double knockout of 4E-BP1 and 4E-BP2 remains resistant to mTOR inhibitors under these conditions. Phosphorylation of p70S6 kinase and protein kinase B (Akt) is blocked by the mTOR inhibitor Ku0063794 equally well in both wild-type and 4E-BP knockout cells, under both normal and hypertonic conditions. The response of protein synthesis to hypertonic stress itself does not require the 4E-BPs. These data suggest that under certain stress conditions: (i) translation has a greater requirement for mTOR activity and (ii) there is an absolute requirement for the 4E-BPs for regulation by mTOR. Importantly, dephosphorylation of p70S6 kinase and Akt is not sufficient to affect protein synthesis acutely.

  10. Statistical Computing

    Indian Academy of Sciences (India)

    inference and finite population sampling. Sudhakar Kunte. Elements of statistical computing are discussed in this series. ... which captain gets an option to decide whether to field first or bat first ... may of course not be fair, in the sense that the team which wins ... describe two methods of drawing a random number between 0.

  11. Statistical thermodynamics

    CERN Document Server

    Schrödinger, Erwin

    1952-01-01

    Nobel Laureate's brilliant attempt to develop a simple, unified standard method of dealing with all cases of statistical thermodynamics - classical, quantum, Bose-Einstein, Fermi-Dirac, and more.The work also includes discussions of Nernst theorem, Planck's oscillator, fluctuations, the n-particle problem, problem of radiation, much more.

  12. Extracellular signal-regulated kinase activation is required for consolidation and reconsolidation of memory at an early stage of ontogenesis.

    Science.gov (United States)

    Languille, Solène; Davis, Sabrina; Richer, Paulette; Alcacer, Cristina; Laroche, Serge; Hars, Bernard

    2009-11-01

    The ability to form long-term memories exists very early during ontogeny; however, the properties of early memory processes, brain structures involved and underlying cellular mechanisms are poorly defined. Here, we examine the role of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase/ERK signaling cascade, which is crucial for adult memory, in the consolidation and reconsolidation of an early memory using a conditioned taste aversion paradigm in 3-day-old rat pups. We show that intraperitoneal injection of SL327, the upstream mitogen-activated protein kinase kinase inhibitor, impairs both consolidation and reconsolidation of early memory, leaving short-term memory after acquisition and after reactivation intact. The amnesic effect of SL327 diminishes with increasing delays after acquisition and reactivation. Biochemical analyses revealed ERK hyperphosphorylation in the amygdala but not the hippocampus following acquisition, suggesting functional activation of the amygdala as early as post-natal day 3, although there was no clear evidence for amygdalar ERK activation after reactivation. These results indicate that, despite an immature brain, the basic properties of memory and at least some of the molecular mechanisms and brain structures implicated in aversion memory share a number of similarities with the adult and emerge very early during ontogeny.

  13. Cytoplasmic vacuolation in cultured rat astrocytes induced by an organophosphorus agent requires extracellular signal-regulated kinase activation

    International Nuclear Information System (INIS)

    Isobe, Ichiro; Maeno, Yoshitaka; Nagao, Masataka; Iwasa, Mineo; Koyama, Hiroyoshi; Seko-Nakamura, Yoshimi; Monma-Ohtaki, Jun

    2003-01-01

    There are various toxic chemicals that cause cell death. However, in certain cases deleterious agents elicit various cellular responses prior to cell death. To determine the cellular mechanisms by which such cellular responses are induced is important, but sufficient attention has not been paid to this issue to date. In this study, we showed the characteristic effects of an organophosphorus (OP) agent, bis(pinacolyl methyl)phosphonate (BPMP), which we synthesized for the study of OP nerve agents, on cultured rat astrocytes. Morphologically, BPMP induced cytoplasmic vacuolation and stellation in the rat astrocytes. Cytoplasmic vacuolation is a cell pathological change observed, for example, in vacuolar degeneration, and stellation has been reported in astrocytic reactions against various stimuli. By pretreatment with cycloheximide, a protein synthesis inhibitor, stellation was inhibited, although vacuolation was not. Cell staining with a mitochondrion-selective dye indicated that the vacuolation probably occurs in the mitochondria that are swollen and vacuolatred in the center. Interestingly, the extracellular signal-regulated kinase (ERK) cascade inhibitor inhibited vacuolation and, to some extent, stellation. These results suggest that the ERK signaling cascade is important for the induction of mitochondrial vacuolation. We expect that a detailed study of these astrocytic reactions will provide us new perspectives regarding the variation and pathological significance of cell morphological changes, such as vacuolar degeneration, and also the mechanisms underlying various neurological disorders

  14. The plant cuticle is required for osmotic stress regulation of abscisic acid biosynthesis and osmotic stress tolerance in Arabidopsis

    KAUST Repository

    Wang, Zhenyu

    2011-05-01

    Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 genee xpression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxy genase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol)treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly thatCED1 encodes a putative a/b hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cut in biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling. © 2011 American Society of Plant Biologists. All rights reserved.

  15. Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization.

    Science.gov (United States)

    Muntean, Andrew G; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F; Blobel, Gerd A; Crispino, John D

    2007-06-15

    Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1-deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1-deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity.

  16. Cyclin D–Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization

    Science.gov (United States)

    Muntean, Andrew G.; Pang, Liyan; Poncz, Mortimer; Dowdy, Steven F.; Blobel, Gerd A.

    2007-01-01

    Endomitosis is a unique form of cell cycle used by megakaryocytes, in which the latter stages of mitosis are bypassed so that the cell can increase its DNA content and size. Although several transcription factors, including GATA-1 and RUNX-1, have been implicated in this process, the link between transcription factors and polyploidization remains undefined. Here we show that GATA-1–deficient megakaryocytes, which display reduced size and polyploidization, express nearly 10-fold less cyclin D1 and 10-fold increased levels of p16 compared with their wild-type counterparts. We further demonstrate that cyclin D1 is a direct GATA-1 target in megakaryocytes, but not erythroid cells. Restoration of cyclin D1 expression, when accompanied by ectopic overexpression of its partner Cdk4, resulted in a dramatic increase in megakaryocyte size and DNA content. However, terminal differentiation was not rescued. Of note, polyploidization was only modestly reduced in cyclin D1–deficient mice, likely due to compensation by elevated cyclin D3 expression. Finally, consistent with an additional defect conferred by increased levels of p16, inhibition of cyclin D-Cdk4 complexes with a TAT-p16 fusion peptide significantly blocked polyploidization of wild-type megakaryocytes. Together, these data show that GATA-1 controls growth and polyploidization by regulating cyclin D-Cdk4 kinase activity. PMID:17317855

  17. Formation of the sacrum requires down-regulation of sonic hedgehog signaling in the sacral intervertebral discs.

    Science.gov (United States)

    Bonavita, Raffaella; Vincent, Kathleen; Pinelli, Robert; Dahia, Chitra Lekha

    2018-05-21

    In humans, the sacrum forms an important component of the pelvic arch, and it transfers the weight of the body to the lower limbs. The sacrum is formed by collapse of the intervertebral discs (IVDs) between the five sacral vertebrae during childhood, and their fusion to form a single bone. We show that collapse of the sacral discs in the mouse is associated with the down-regulation of sonic hedgehog (SHH) signaling in the nucleus pulposus (NP) of the disc, and many aspects of this phenotype can be reversed by experimental postnatal activation of HH signaling. We have previously shown that SHH signaling is essential for the normal postnatal growth and differentiation of intervertebral discs elsewhere in the spine, and that loss of SHH signaling leads to pathological disc degeneration, a very common disorder of aging. Thus, loss of SHH is pathological in one region of the spine but part of normal development in another. © 2018. Published by The Company of Biologists Ltd.

  18. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae.

    Science.gov (United States)

    Wang, Yonglin; Hu, Xiaoping; Fang, Yulin; Anchieta, Amy; Goldman, Polly H; Hernandez, Gustavo; Klosterman, Steven J

    2018-04-01

    Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.

  20. ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

    Science.gov (United States)

    Berezniuk, Iryna; Rodriguiz, Ramona M; Zee, Michael L; Marcus, David J; Pintar, John; Morgan, Daniel J; Wetsel, William C; Fricker, Lloyd D

    2017-11-01

    To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or saline for 7 days. A total of 102 distinct peptides were identified in one or more of the following brain regions: nucleus accumbens, caudate putamen, frontal cortex, and ventral tegmental area. None of the peptides detected in the caudate putamen or frontal cortex were altered by cocaine administration. Three peptides in the nucleus accumbens and seven peptides in the ventral tegmental area were significantly decreased in cocaine-treated mice. Five of these ten peptides are derived from proSAAS, a secretory pathway protein and neuropeptide precursor. To investigate whether proSAAS peptides contribute to the physiological effects of psychostimulants, we examined acute responses to cocaine and amphetamine in the open field with wild-type (WT) and proSAAS knockout (KO) mice. Locomotion was stimulated more robustly in the WT compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was not maintained in proSAAS KO mice and these mutants failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were altered, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. Taken together, these results suggest that proSAAS-derived peptides contribute differentially to the behavioral sensitization to psychostimulants, while the rewarding effects of cocaine appear intact in mice lacking proSAAS. © 2017 International Society for Neurochemistry.

  1. The nature of statistics

    CERN Document Server

    Wallis, W Allen

    2014-01-01

    Focusing on everyday applications as well as those of scientific research, this classic of modern statistical methods requires little to no mathematical background. Readers develop basic skills for evaluating and using statistical data. Lively, relevant examples include applications to business, government, social and physical sciences, genetics, medicine, and public health. ""W. Allen Wallis and Harry V. Roberts have made statistics fascinating."" - The New York Times ""The authors have set out with considerable success, to write a text which would be of interest and value to the student who,

  2. Statistical Pattern Recognition

    CERN Document Server

    Webb, Andrew R

    2011-01-01

    Statistical pattern recognition relates to the use of statistical techniques for analysing data measurements in order to extract information and make justified decisions.  It is a very active area of study and research, which has seen many advances in recent years. Applications such as data mining, web searching, multimedia data retrieval, face recognition, and cursive handwriting recognition, all require robust and efficient pattern recognition techniques. This third edition provides an introduction to statistical pattern theory and techniques, with material drawn from a wide range of fields,

  3. Energy Statistics

    International Nuclear Information System (INIS)

    Anon.

    1994-01-01

    For the years 1992 and 1993, part of the figures shown in the tables of the Energy Review are preliminary or estimated. The annual statistics of the Energy Review appear in more detail from the publication Energiatilastot - Energy Statistics issued annually, which also includes historical time series over a longer period. The tables and figures shown in this publication are: Changes in the volume of GNP and energy consumption; Coal consumption; Natural gas consumption; Peat consumption; Domestic oil deliveries; Import prices of oil; Price development of principal oil products; Fuel prices for power production; Total energy consumption by source; Electricity supply; Energy imports by country of origin in 1993; Energy exports by recipient country in 1993; Consumer prices of liquid fuels; Consumer prices of hard coal and natural gas, prices of indigenous fuels; Average electricity price by type of consumer; Price of district heating by type of consumer and Excise taxes and turnover taxes included in consumer prices of some energy sources

  4. Statistical Optics

    Science.gov (United States)

    Goodman, Joseph W.

    2000-07-01

    The Wiley Classics Library consists of selected books that have become recognized classics in their respective fields. With these new unabridged and inexpensive editions, Wiley hopes to extend the life of these important works by making them available to future generations of mathematicians and scientists. Currently available in the Series: T. W. Anderson The Statistical Analysis of Time Series T. S. Arthanari & Yadolah Dodge Mathematical Programming in Statistics Emil Artin Geometric Algebra Norman T. J. Bailey The Elements of Stochastic Processes with Applications to the Natural Sciences Robert G. Bartle The Elements of Integration and Lebesgue Measure George E. P. Box & Norman R. Draper Evolutionary Operation: A Statistical Method for Process Improvement George E. P. Box & George C. Tiao Bayesian Inference in Statistical Analysis R. W. Carter Finite Groups of Lie Type: Conjugacy Classes and Complex Characters R. W. Carter Simple Groups of Lie Type William G. Cochran & Gertrude M. Cox Experimental Designs, Second Edition Richard Courant Differential and Integral Calculus, Volume I RIchard Courant Differential and Integral Calculus, Volume II Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume I Richard Courant & D. Hilbert Methods of Mathematical Physics, Volume II D. R. Cox Planning of Experiments Harold S. M. Coxeter Introduction to Geometry, Second Edition Charles W. Curtis & Irving Reiner Representation Theory of Finite Groups and Associative Algebras Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume I Charles W. Curtis & Irving Reiner Methods of Representation Theory with Applications to Finite Groups and Orders, Volume II Cuthbert Daniel Fitting Equations to Data: Computer Analysis of Multifactor Data, Second Edition Bruno de Finetti Theory of Probability, Volume I Bruno de Finetti Theory of Probability, Volume 2 W. Edwards Deming Sample Design in Business Research

  5. Statistical utilitarianism

    OpenAIRE

    Pivato, Marcus

    2013-01-01

    We show that, in a sufficiently large population satisfying certain statistical regularities, it is often possible to accurately estimate the utilitarian social welfare function, even if we only have very noisy data about individual utility functions and interpersonal utility comparisons. In particular, we show that it is often possible to identify an optimal or close-to-optimal utilitarian social choice using voting rules such as the Borda rule, approval voting, relative utilitarianism, or a...

  6. Experimental statistics

    CERN Document Server

    Natrella, Mary Gibbons

    1963-01-01

    Formulated to assist scientists and engineers engaged in army ordnance research and development programs, this well-known and highly regarded handbook is a ready reference for advanced undergraduate and graduate students as well as for professionals seeking engineering information and quantitative data for designing, developing, constructing, and testing equipment. Topics include characterizing and comparing the measured performance of a material, product, or process; general considerations in planning experiments; statistical techniques for analyzing extreme-value data; use of transformations

  7. Calcium Regulates Molecular Interactions of Otoferlin with Soluble NSF Attachment Protein Receptor (SNARE) Proteins Required for Hair Cell Exocytosis*

    Science.gov (United States)

    Ramakrishnan, Neeliyath A.; Drescher, Marian J.; Morley, Barbara J.; Kelley, Philip M.; Drescher, Dennis G.

    2014-01-01

    Mutations in otoferlin, a C2 domain-containing ferlin family protein, cause non-syndromic hearing loss in humans (DFNB9 deafness). Furthermore, transmitter secretion of cochlear inner hair cells is compromised in mice lacking otoferlin. In the present study, we show that the C2F domain of otoferlin directly binds calcium (KD = 267 μm) with diminished binding in a pachanga (D1767G) C2F mouse mutation. Calcium was found to differentially regulate binding of otoferlin C2 domains to target SNARE (t-SNARE) proteins and phospholipids. C2D–F domains interact with the syntaxin-1 t-SNARE motif with maximum binding within the range of 20–50 μm Ca2+. At 20 μm Ca2+, the dissociation rate was substantially lower, indicating increased binding (KD = ∼10−9) compared with 0 μm Ca2+ (KD = ∼10−8), suggesting a calcium-mediated stabilization of the C2 domain·t-SNARE complex. C2A and C2B interactions with t-SNAREs were insensitive to calcium. The C2F domain directly binds the t-SNARE SNAP-25 maximally at 100 μm and with reduction at 0 μm Ca2+, a pattern repeated for C2F domain interactions with phosphatidylinositol 4,5-bisphosphate. In contrast, C2F did not bind the vesicle SNARE protein synaptobrevin-1 (VAMP-1). Moreover, an antibody targeting otoferlin immunoprecipitated syntaxin-1 and SNAP-25 but not synaptobrevin-1. As opposed to an increase in binding with increased calcium, interactions between otoferlin C2F domain and intramolecular C2 domains occurred in the absence of calcium, consistent with intra-C2 domain interactions forming a “closed” tertiary structure at low calcium that “opens” as calcium increases. These results suggest a direct role for otoferlin in exocytosis and modulation of calcium-dependent membrane fusion. PMID:24478316

  8. Regulation of EphA4 kinase activity is required for a subset of axon guidance decisions suggesting a key role for receptor clustering in Eph function

    DEFF Research Database (Denmark)

    Egea, Joaquim; Nissen, Ulla Vig; Dufour, Audrey

    2005-01-01

    Signaling by receptor tyrosine kinases (RTKs) is mediated by their intrinsic kinase activity. Typically, kinase-activating mutations result in ligand-independent signaling and gain-of-function phenotypes. Like other RTKs, Ephs require kinase activity to signal, but signaling by Ephs in vitro also...... requires clustering by their membrane bound ephrin ligands. The relative importance of Eph kinase activity and clustering for in vivo functions is unknown. We find that knockin mice expressing a mutant form of EphA4 (EphA4 EE), whose kinase is constitutively activated in the absence of ephrinB ligands......, are deficient in the development of thalamocortical projections and some aspects of central pattern generator rhythmicity. Surprisingly, other functions of EphA4 were regulated normally by EphA4EE, including midline axon guidance, hindlimb locomotion, in vitro growth cone collapse, and phosphorylation...

  9. Development and application of a permit information system for shale oil (PERMISSO). Final report appendix: summary sheets of regulations required for oil shale development, June 1978--May 1979

    Energy Technology Data Exchange (ETDEWEB)

    1979-07-01

    This appendix is comprised of summaries of various governmental permits, licenses and other approvals required for oil shale development. The summaries were completed during the period June--October 1978, and are current as of July 1, 1978, although more recent authority was cited in some cases. One of the major purposes of Phase II of the project will be to update these summaries as statutes and regulations are added, changed or eliminated. This updating will be particularly important in the case of environmental permits and approvals. Many legislative and regulatory changes affecting environmental requirements are pending at this time and will alter many of the summaries herein. In addition, many regulatory proposals have been or likely will be challenged in the courts. When such conflicts are resolved further changes may be in order.

  10. Efficient Overproduction of Membrane Proteins in Lactococcus lactis Requires the Cell Envelope Stress Sensor/Regulator Couple CesSR

    Science.gov (United States)

    Pinto, Joao P. C.; Kuipers, Oscar P.; Marreddy, Ravi K. R.; Poolman, Bert; Kok, Jan

    2011-01-01

    Background Membrane proteins comprise an important class of molecules whose study is largely frustrated by several intrinsic constraints, such as their hydrophobicity and added requirements for correct folding. Additionally, the complexity of the cellular mechanisms that are required to insert membrane proteins functionally in the membrane and to monitor their folding state makes it difficult to foresee the yields at which one can obtain them or to predict which would be the optimal production host for a given protein. Methods and Findings We describe a rational design approach to improve the lactic acid bacterium Lactococcus lactis as a producer of membrane proteins. Our transcriptome data shows that the two-component system CesSR, which senses cell envelope stresses of different origins, is one of the major players when L. lactis is forced to overproduce the endogenous membrane protein BcaP, a branched-chain amino acid permease. Growth of the BcaP-producing L. lactis strain and its capability to produce membrane proteins are severely hampered when the CesSR system itself or particular members of the CesSR regulon are knocked out, notably the genes ftsH, oxaA2, llmg_2163 and rmaB. Overexpressing cesSR reduced the growth defect, thus directly improving the production yield of BcaP. Applying this rationale to eukaryotic proteins, some of which are notoriously more difficult to produce, such as the medically-important presenilin complex, we were able to significantly diminish the growth defect seen in the wild-type strain and improve the production yield of the presenilin variant PS1Δ9-H6 more than 4-fold. Conclusions The results shed light into a key, and perhaps central, membrane protein quality control mechanism in L. lactis. Modulating the expression of CesSR benefited the production yields of membrane proteins from different origins. These findings reinforce L. lactis as a legitimate alternative host for the production of membrane proteins. PMID:21818275

  11. A Myb transcription factor of Phytophthora sojae, regulated by MAP kinase PsSAK1, is required for zoospore development.

    Directory of Open Access Journals (Sweden)

    Meng Zhang

    Full Text Available PsSAK1, a mitogen-activated protein (MAP kinase from Phytophthora sojae, plays an important role in host infection and zoospore viability. However, the downstream mechanism of PsSAK1 remains unclear. In this study, the 3'-tag digital gene expression (DGE profiling method was applied to sequence the global transcriptional sequence of PsSAK1-silenced mutants during the cysts stage and 1.5 h after inoculation onto susceptible soybean leaf tissues. Compared with the gene expression levels of the recipient P. sojae strain, several candidates of Myb family were differentially expressed (up or down in response to the loss of PsSAK1, including of a R2R3-type Myb transcription factor, PsMYB1. qRT-PCR indicated that the transcriptional level of PsMYB1 decreased due to PsSAK1 silencing. The transcriptional level of PsMYB1 increased during sporulating hyphae, in germinated cysts, and early infection. Silencing of PsMYB1 results in three phenotypes: a no cleavage of the cytoplasm into uninucleate zoospores or release of normal zoospores, b direct germination of sporangia, and c afunction in zoospore-mediated plant infection. Our data indicate that the PsMYB1 transcription factor functions downstream of MAP kinase PsSAK1 and is required for zoospore development of P. sojae.

  12. Statistics 101 for Radiologists.

    Science.gov (United States)

    Anvari, Arash; Halpern, Elkan F; Samir, Anthony E

    2015-10-01

    Diagnostic tests have wide clinical applications, including screening, diagnosis, measuring treatment effect, and determining prognosis. Interpreting diagnostic test results requires an understanding of key statistical concepts used to evaluate test efficacy. This review explains descriptive statistics and discusses probability, including mutually exclusive and independent events and conditional probability. In the inferential statistics section, a statistical perspective on study design is provided, together with an explanation of how to select appropriate statistical tests. Key concepts in recruiting study samples are discussed, including representativeness and random sampling. Variable types are defined, including predictor, outcome, and covariate variables, and the relationship of these variables to one another. In the hypothesis testing section, we explain how to determine if observed differences between groups are likely to be due to chance. We explain type I and II errors, statistical significance, and study power, followed by an explanation of effect sizes and how confidence intervals can be used to generalize observed effect sizes to the larger population. Statistical tests are explained in four categories: t tests and analysis of variance, proportion analysis tests, nonparametric tests, and regression techniques. We discuss sensitivity, specificity, accuracy, receiver operating characteristic analysis, and likelihood ratios. Measures of reliability and agreement, including κ statistics, intraclass correlation coefficients, and Bland-Altman graphs and analysis, are introduced. © RSNA, 2015.

  13. Shoreline dynamics of the active Yellow River delta since the implementation of Water-Sediment Regulation Scheme: A remote-sensing and statistics-based approach

    Science.gov (United States)

    Fan, Yaoshen; Chen, Shenliang; Zhao, Bo; Pan, Shunqi; Jiang, Chao; Ji, Hongyu

    2018-01-01

    The Active Yellow River (Huanghe) Delta (AYRD) is a complex landform in which rapid deposition takes place due to its geologic formation and evolution. Continuous monitoring of shoreline dynamics at high-temporal frequency is crucial for understanding the processes and the driving factors behind this rapidly changing coast. Great efforts have been devoted to map the changing shoreline of the Yellow River delta and explain such changes through remote sensing data. However, the temporal frequency of shoreline in the obtained datasets are generally not fine enough to reflect the detailed or subtly variable processes of shoreline retreat and advance. To overcome these limitations, we continuously monitored the dynamics of this shoreline using time series of Landsat data based on tidal-level calibration model and orthogonal-transect method. The Abrupt Change Value (ACV) results indicated that the retreat-advance patterns had a significant impact regardless of season or year. The Water-Sediment Regulation Scheme (WSRS) plays a dominant role in delivering river sediment discharge to the sea and has an impact on the annual average maximum ACV, especially at the mouth of the river. The positive relationship among the average ACV, runoff and sediment load are relatively obvious; however, we found that the Relative Exposure Index (REI) that measures wave energy was able to explain only approximately 20% of the variation in the data. Based on the abrupt change at the shoreline of the AYRD, river flow and time, we developed a binary regression model to calculate the critical sediment load and water discharge for maintaining the equilibrium of the active delta from 2002 to 2015. These values were approximately 0.48 × 108 t/yr and 144.37 × 108 m3/yr. If the current water and sediment proportions released from the Xiaolangdi Reservoir during the WSRS remain stable, the erosion-accretion patterns of the active delta will shift from rapid accretion to a dynamic balance.

  14. The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth Arrest.

    Science.gov (United States)

    Gascoyne, Duncan M; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E; Croucher, Peter I; Banham, Alison H

    2015-01-01

    Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.

  15. Developmentally-Regulated Excision of the SPβ Prophage Reconstitutes a Gene Required for Spore Envelope Maturation in Bacillus subtilis

    Science.gov (United States)

    Abe, Kimihiro; Kawano, Yuta; Iwamoto, Keito; Arai, Kenji; Maruyama, Yuki; Eichenberger, Patrick; Sato, Tsutomu

    2014-01-01

    Temperate phages infect bacteria by injecting their DNA into bacterial cells, where it becomes incorporated into the host genome as a prophage. In the genome of Bacillus subtilis 168, an active prophage, SPβ, is inserted into a polysaccharide synthesis gene, spsM. Here, we show that a rearrangement occurs during sporulation to reconstitute a functional composite spsM gene by precise excision of SPβ from the chromosome. SPβ excision requires a putative site-specific recombinase, SprA, and an accessory protein, SprB. A minimized SPβ, where all the SPβ genes were deleted, except sprA and sprB, retained the SPβ excision activity during sporulation, demonstrating that sprA and sprB are necessary and sufficient for the excision. While expression of sprA was observed during vegetative growth, sprB was induced during sporulation and upon mitomycin C treatment, which triggers the phage lytic cycle. We also demonstrated that overexpression of sprB (but not of sprA) resulted in SPβ prophage excision without triggering the lytic cycle. These results suggest that sprB is the factor that controls the timing of phage excision. Furthermore, we provide evidence that spsM is essential for the addition of polysaccharides to the spore envelope. The presence of polysaccharides on the spore surface renders the spore hydrophilic in water. This property may be beneficial in allowing spores to disperse in natural environments via water flow. A similar rearrangement occurs in Bacillus amyloliquefaciens FZB42, where a SPβ-like element is excised during sporulation to reconstitute a polysaccharide synthesis gene, suggesting that this type of gene rearrangement is common in spore-forming bacteria because it can be spread by phage infection. PMID:25299644

  16. Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Joseph L. Regan

    2017-12-01

    Full Text Available Summary: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs. To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT, we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival. : Colon cancer is a heterogeneous tumor driven by a subpopulation(s of therapy-resistant cancer stem cells (CSCs. Regan et al. use 3D culture models to demonstrate that CSC survival is regulated by non-canonical, SHH-dependent, PTCH1-dependent Hedgehog signaling, which acts as a positive regulator of WNT signaling to block CSC differentiation. Keywords: WNT pathway, non-canonical Hedgehog signaling, cancer stem cell, colon cancer, cancer organoid, PTCH1, HHAT, SHH

  17. Energy statistics

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    World data from the United Nation's latest Energy Statistics Yearbook, first published in our last issue, are completed here. The 1984-86 data were revised and 1987 data added for world commercial energy production and consumption, world natural gas plant liquids production, world LP-gas production, imports, exports, and consumption, world residual fuel oil production, imports, exports, and consumption, world lignite production, imports, exports, and consumption, world peat production and consumption, world electricity production, imports, exports, and consumption (Table 80), and world nuclear electric power production

  18. Statistical Engine Knock Control

    DEFF Research Database (Denmark)

    Stotsky, Alexander A.

    2008-01-01

    A new statistical concept of the knock control of a spark ignition automotive engine is proposed . The control aim is associated with the statistical hy pothesis test which compares the threshold value to the average value of the max imal amplitud e of the knock sensor signal at a given freq uency....... C ontrol algorithm which is used for minimization of the regulation error realizes a simple count-up-count-d own logic. A new ad aptation algorithm for the knock d etection threshold is also d eveloped . C onfi d ence interval method is used as the b asis for ad aptation. A simple statistical mod el...... which includ es generation of the amplitud e signals, a threshold value d etermination and a knock sound mod el is d eveloped for evaluation of the control concept....

  19. Basics of statistical physics

    CERN Document Server

    Müller-Kirsten, Harald J W

    2013-01-01

    Statistics links microscopic and macroscopic phenomena, and requires for this reason a large number of microscopic elements like atoms. The results are values of maximum probability or of averaging. This introduction to statistical physics concentrates on the basic principles, and attempts to explain these in simple terms supplemented by numerous examples. These basic principles include the difference between classical and quantum statistics, a priori probabilities as related to degeneracies, the vital aspect of indistinguishability as compared with distinguishability in classical physics, the differences between conserved and non-conserved elements, the different ways of counting arrangements in the three statistics (Maxwell-Boltzmann, Fermi-Dirac, Bose-Einstein), the difference between maximization of the number of arrangements of elements, and averaging in the Darwin-Fowler method. Significant applications to solids, radiation and electrons in metals are treated in separate chapters, as well as Bose-Eins...

  20. SAPS, Crime statistics

    African Journals Online (AJOL)

    incidents' refer to 'incidents such as labour disputes and dissatisfaction with service delivery in which violence erupted and SAPS action was required to restore peace and order'.26. It is apparent from both the SAPS statistics and those provided by the Municipal IQ Hotspots. Monitor, that public protests and gatherings are.

  1. Regulation of the Osem gene by abscisic acid and the transcriptional activator VP1: analysis of cis-acting promoter elements required for regulation by abscisic acid and VP1.

    Science.gov (United States)

    Hattori, T; Terada, T; Hamasuna, S

    1995-06-01

    Osem, a rice gene homologous to the wheat Em gene, which encodes one of the late-embryogenesis abundant proteins was isolated. The gene was characterized with respect to control of transcription by abscisic acid (ABA) and the transcriptional activator VP1, which is involved in the ABA-regulated gene expression during late embryo-genesis. A fusion gene (Osem-GUS) consisting of the Osem promoter and the bacterial beta-glucuronidase (GUS) gene was constructed and tested in a transient expression system, using protoplasts derived from a suspension-cultured line of rice cells, for activation by ABA and by co-transfection with an expression vector (35S-Osvp1) for the rice VP1 (OSVP1) cDNA. The expression of Osem-GUS was strongly (40- to 150-fold) activated by externally applied ABA and by over-expression of (OS)VP1. The Osem promoter has three ACGTG-containing sequences, motif A, motif B and motif A', which resemble the abscisic acid-responsive element (ABRE) that was previously identified in the wheat Em and the rice Rab16. There is also a CATGCATG sequence, which is known as the Sph box and is shown to be essential for the regulation by VP1 of the maize anthocyanin regulatory gene C1. Focusing on these sequence elements, various mutant derivatives of the Osem promoter in the transient expression system were assayed. The analysis revealed that motif A functions not only as an ABRE but also as a sequence element required for the regulation by (OS)VP1.

  2. Regulation of abiotic stress signalling by Arabidopsis C-terminal domain phosphatase-like 1 requires interaction with a k-homology domain-containing protein.

    Directory of Open Access Journals (Sweden)

    In Sil Jeong

    Full Text Available Arabidopsis thaliana CARBOXYL-TERMINAL DOMAIN (CTD PHOSPHATASE-LIKE 1 (CPL1 regulates plant transcriptional responses to diverse stress signals. Unlike typical CTD phosphatases, CPL1 contains two double-stranded (ds RNA binding motifs (dsRBMs at its C-terminus. Some dsRBMs can bind to dsRNA and/or other proteins, but the function of the CPL1 dsRBMs has remained obscure. Here, we report identification of REGULATOR OF CBF GENE EXPRESSION 3 (RCF3 as a CPL1-interacting protein. RCF3 co-purified with tandem-affinity-tagged CPL1 from cultured Arabidopsis cells and contains multiple K-homology (KH domains, which were predicted to be important for binding to single-stranded DNA/RNA. Yeast two-hybrid, luciferase complementation imaging, and bimolecular fluorescence complementation analyses established that CPL1 and RCF3 strongly associate in vivo, an interaction mediated by the dsRBM1 of CPL1 and the KH3/KH4 domains of RCF3. Mapping of functional regions of CPL1 indicated that CPL1 in vivo function requires the dsRBM1, catalytic activity, and nuclear targeting of CPL1. Gene expression profiles of rcf3 and cpl1 mutants were similar during iron deficiency, but were distinct during the cold response. These results suggest that tethering CPL1 to RCF3 via dsRBM1 is part of the mechanism that confers specificity to CPL1-mediated transcriptional regulation.

  3. Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on.

    Science.gov (United States)

    Bergö, Martin; Wu, Gengshu; Ruge, Toralph; Olivecrona, Thomas

    2002-04-05

    During short term fasting, lipoprotein lipase (LPL) activity in rat adipose tissue is rapidly down-regulated. This down-regulation occurs on a posttranslational level; it is not accompanied by changes in LPL mRNA or protein levels. The LPL activity can be restored within 4 h by refeeding. Previously, we showed that during fasting there is a shift in the distribution of lipase protein toward an inactive form with low heparin affinity. To study the nature of the regulatory mechanism, we determined the in vivo turnover of LPL activity, protein mass, and mRNA in rat adipose tissue. When protein synthesis was inhibited with cycloheximide, LPL activity and protein mass decreased rapidly and in parallel with half-lives of around 2 h, and the effect of refeeding was blocked. This indicates that maintaining high levels of LPL activity requires continuous synthesis of new enzyme protein. When transcription was inhibited by actinomycin, LPL mRNA decreased with half-lives of 13.3 and 16.8 h in the fed and fasted states, respectively, demonstrating slow turnover of the LPL transcript. Surprisingly, when actinomycin was given to fed rats, LPL activity was not down-regulated during fasting, indicating that actinomycin interferes with the transcription of a gene that blocks the activation of newly synthesized LPL protein. When actinomycin was given to fasted rats, LPL activity increased 4-fold within 6 h, even in the absence of refeeding. The same effect was seen with alpha-amanitin, another inhibitor of transcription. The response to actinomycin was much less pronounced in aging rats, which are obese and insulin-resistant. These data suggest a default state where LPL protein is synthesized on a relatively stable mRNA and is processed into its active form. During fasting, a gene is switched on whose product prevents the enzyme from becoming active even though synthesis of LPL protein continues unabated.

  4. Spatiotemporally regulated proteolysis to dissect the role of vegetative proteins during Bacillus subtilis sporulation: cell-specific requirement of σH and σA.

    Science.gov (United States)

    Riley, Eammon P; Trinquier, Aude; Reilly, Madeline L; Durchon, Marine; Perera, Varahenage R; Pogliano, Kit; Lopez-Garrido, Javier

    2018-04-01

    Sporulation in Bacillus subtilis is a paradigm of bacterial development, which involves the interaction between a larger mother cell and a smaller forespore. The mother cell and the forespore activate different genetic programs, leading to the production of sporulation-specific proteins. A critical gap in our understanding of sporulation is how vegetative proteins, made before sporulation initiation, contribute to spore formation. Here we present a system, spatiotemporally regulated proteolysis (STRP), which enables the rapid, developmentally regulated degradation of target proteins, thereby providing a suitable method to dissect the cell- and developmental stage-specific role of vegetative proteins. STRP has been used to dissect the role of two major vegetative sigma factors, σ H and σ A , during sporulation. The results suggest that σ H is only required in predivisional cells, where it is essential for sporulation initiation, but that it is dispensable during subsequent steps of spore formation. However, evidence has been provided that σ A plays different roles in the mother cell, where it replenishes housekeeping functions, and in the forespore, where it plays an unexpected role in promoting spore germination and outgrowth. Altogether, the results demonstrate that STRP has the potential to provide a comprehensive molecular dissection of every stage of sporulation, germination and outgrowth. © 2018 John Wiley & Sons Ltd.

  5. Casein kinase II is required for proper cell division and acts as a negative regulator of centrosome duplication in Caenorhabditis elegans embryos

    Directory of Open Access Journals (Sweden)

    Jeffrey C. Medley

    2017-01-01

    Full Text Available Centrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein kinase II (CK2 in early Caenorhabditis elegans embryos. The catalytic subunit (KIN-3/CK2α of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner.

  6. The Acinetobacter baumannii Two-Component System AdeRS Regulates Genes Required for Multidrug Efflux, Biofilm Formation, and Virulence in a Strain-Specific Manner

    Directory of Open Access Journals (Sweden)

    Grace E. Richmond

    2016-04-01

    Full Text Available The opportunistic pathogen Acinetobacter baumannii is able to persist in the environment and is often multidrug resistant (MDR, causing difficulties in the treatment of infections. Here, we show that the two-component system AdeRS, which regulates the production of the AdeABC multidrug resistance efflux pump, is required for the formation of a protective biofilm in an ex vivo porcine mucosal model, which mimics a natural infection of the human epithelium. Interestingly, deletion of adeB impacted only on the ability of strain AYE to form a biofilm on plastic and only on the virulence of strain Singapore 1 for Galleria mellonella. RNA-Seq revealed that loss of AdeRS or AdeB significantly altered the transcriptional landscape, resulting in the changed expression of many genes, notably those associated with antimicrobial resistance and virulence interactions. For example, A. baumannii lacking AdeRS displayed decreased expression of adeABC, pil genes, com genes, and a pgaC-like gene, whereas loss of AdeB resulted in increased expression of pil and com genes and decreased expression of ferric acinetobactin transport system genes. These data define the scope of AdeRS-mediated regulation, show that changes in the production of AdeABC mediate important phenotypes controlled by AdeRS, and suggest that AdeABC is a viable target for antimicrobial drug and antibiofilm discovery.

  7. MCK1 is a novel regulator of myo-inositol phosphate synthase (MIPS that is required for inhibition of inositol synthesis by the mood stabilizer valproate.

    Directory of Open Access Journals (Sweden)

    Wenxi Yu

    Full Text Available Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS, which catalyzes the rate-limiting step of inositol synthesis. mck1Δ cells exhibited a 50% decrease in MIPS activity and a decreased rate of incorporation of [13C6]glucose into [13C6]-inositol-3-phosphate and [13C6]-inositol compared to WT cells. mck1Δ cells also exhibited decreased growth in the presence of the inositol depleting drug valproate (VPA, which was rescued by supplementation of inositol. However, in contrast to wild type cells, which exhibited more than a 40% decrease in MIPS activity in the presence of VPA, the drug did not significantly decrease MIPS activity in mck1Δ cells. These findings indicate that VPA-induced MIPS inhibition is Mck1-dependent, and suggest a model that unifies two current hypotheses of the mechanism of action of VPA-inositol depletion and GSK3 inhibition.

  8. MCK1 is a novel regulator of myo-inositol phosphate synthase (MIPS) that is required for inhibition of inositol synthesis by the mood stabilizer valproate.

    Science.gov (United States)

    Yu, Wenxi; Daniel, Joshua; Mehta, Dhara; Maddipati, Krishna Rao; Greenberg, Miriam L

    2017-01-01

    Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS), which catalyzes the rate-limiting step of inositol synthesis. mck1Δ cells exhibited a 50% decrease in MIPS activity and a decreased rate of incorporation of [13C6]glucose into [13C6]-inositol-3-phosphate and [13C6]-inositol compared to WT cells. mck1Δ cells also exhibited decreased growth in the presence of the inositol depleting drug valproate (VPA), which was rescued by supplementation of inositol. However, in contrast to wild type cells, which exhibited more than a 40% decrease in MIPS activity in the presence of VPA, the drug did not significantly decrease MIPS activity in mck1Δ cells. These findings indicate that VPA-induced MIPS inhibition is Mck1-dependent, and suggest a model that unifies two current hypotheses of the mechanism of action of VPA-inositol depletion and GSK3 inhibition.

  9. HHR23A, a human homolog of Saccharomyces cerevisiae Rad23, regulates xeroderma pigmentosum C protein and is required for nucleotide excision repair

    International Nuclear Information System (INIS)

    Hsieh, Hui-Chuan; Hsieh, Yi-Hsuan; Huang, Yu-Hsin; Shen, Fan-Ching; Tsai, Han-Ni; Tsai, Jui-He; Lai, Yu-Ting; Wang, Yu-Ting; Chuang, Woei-Jer; Huang, Wenya

    2005-01-01

    HHR23A and hHR23B are the human homologs of Saccharomyces cerevisiae Rad23. hHR23B is associated with the nucleotide excision repair (NER) factor xeroderma pigmentosum C (XPC) protein and is required for global genome repair. The function of hHR23A is not yet clear. In this study, the potential function of the hHR23A protein was investigated using RNA interference techniques. The hHR23A knock-down (KD) construct diminished the RNA level of hHR23A protein by approximately 60%, and it did not interfere with expression of the hHR23B gene. Based on Southwestern immunoblot and host-cell reactivation assays, hHR23A KD cells were found to be deficient in DNA repair activity against the DNA damage caused by UVC irradiation. In these hHR23A KD cells, the XPC gene was not normally induced by UVC irradiation, indicating that the hHR23A protein is involved in NER through regulation of the DNA damage recognition protein XPC. Co-immunoprecipitation experiments revealed that hHR23A was associated with a small portion of hHR23B and the majority of p53 protein, indicating that hHR23A regulates the function of XPC by its association with the NER activator p53

  10. Industrial commodity statistics yearbook 2001. Production statistics (1992-2001)

    International Nuclear Information System (INIS)

    2003-01-01

    This is the thirty-fifth in a series of annual compilations of statistics on world industry designed to meet both the general demand for information of this kind and the special requirements of the United Nations and related international bodies. Beginning with the 1992 edition, the title of the publication was changed to industrial Commodity Statistics Yearbook as the result of a decision made by the United Nations Statistical Commission at its twenty-seventh session to discontinue, effective 1994, publication of the Industrial Statistics Yearbook, volume I, General Industrial Statistics by the Statistics Division of the United Nations. The United Nations Industrial Development Organization (UNIDO) has become responsible for the collection and dissemination of general industrial statistics while the Statistics Division of the United Nations continues to be responsible for industrial commodity production statistics. The previous title, Industrial Statistics Yearbook, volume II, Commodity Production Statistics, was introduced in the 1982 edition. The first seven editions in this series were published under the title The Growth of World industry and the next eight editions under the title Yearbook of Industrial Statistics. This edition of the Yearbook contains annual quantity data on production of industrial commodities by country, geographical region, economic grouping and for the world. A standard list of about 530 commodities (about 590 statistical series) has been adopted for the publication. The statistics refer to the ten-year period 1992-2001 for about 200 countries and areas

  11. Industrial commodity statistics yearbook 2002. Production statistics (1993-2002)

    International Nuclear Information System (INIS)

    2004-01-01

    This is the thirty-sixth in a series of annual compilations of statistics on world industry designed to meet both the general demand for information of this kind and the special requirements of the United Nations and related international bodies. Beginning with the 1992 edition, the title of the publication was changed to industrial Commodity Statistics Yearbook as the result of a decision made by the United Nations Statistical Commission at its twenty-seventh session to discontinue, effective 1994, publication of the Industrial Statistics Yearbook, volume I, General Industrial Statistics by the Statistics Division of the United Nations. The United Nations Industrial Development Organization (UNIDO) has become responsible for the collection and dissemination of general industrial statistics while the Statistics Division of the United Nations continues to be responsible for industrial commodity production statistics. The previous title, Industrial Statistics Yearbook, volume II, Commodity Production Statistics, was introduced in the 1982 edition. The first seven editions in this series were published under the title 'The Growth of World industry' and the next eight editions under the title 'Yearbook of Industrial Statistics'. This edition of the Yearbook contains annual quantity data on production of industrial commodities by country, geographical region, economic grouping and for the world. A standard list of about 530 commodities (about 590 statistical series) has been adopted for the publication. The statistics refer to the ten-year period 1993-2002 for about 200 countries and areas

  12. Industrial commodity statistics yearbook 2000. Production statistics (1991-2000)

    International Nuclear Information System (INIS)

    2002-01-01

    This is the thirty-third in a series of annual compilations of statistics on world industry designed to meet both the general demand for information of this kind and the special requirements of the United Nations and related international bodies. Beginning with the 1992 edition, the title of the publication was changed to industrial Commodity Statistics Yearbook as the result of a decision made by the United Nations Statistical Commission at its twenty-seventh session to discontinue, effective 1994, publication of the Industrial Statistics Yearbook, volume I, General Industrial Statistics by the Statistics Division of the United Nations. The United Nations Industrial Development Organization (UNIDO) has become responsible for the collection and dissemination of general industrial statistics while the Statistics Division of the United Nations continues to be responsible for industrial commodity production statistics. The previous title, Industrial Statistics Yearbook, volume II, Commodity Production Statistics, was introduced in the 1982 edition. The first seven editions in this series were published under the title The Growth of World industry and the next eight editions under the title Yearbook of Industrial Statistics. This edition of the Yearbook contains annual quantity data on production of industrial commodities by country, geographical region, economic grouping and for the world. A standard list of about 530 commodities (about 590 statistical series) has been adopted for the publication. Most of the statistics refer to the ten-year period 1991-2000 for about 200 countries and areas

  13. Calcium-regulation of mitochondrial respiration maintains ATP homeostasis and requires ARALAR/AGC1-malate aspartate shuttle in intact cortical neurons.

    Science.gov (United States)

    Llorente-Folch, Irene; Rueda, Carlos B; Amigo, Ignacio; del Arco, Araceli; Saheki, Takeyori; Pardo, Beatriz; Satrústegui, Jorgina

    2013-08-28

    Neuronal respiration is controlled by ATP demand and Ca2+ but the roles played by each are unknown, as any Ca2+ signal also impacts on ATP demand. Ca2+ can control mitochondrial function through Ca2+-regulated mitochondrial carriers, the aspartate-glutamate and ATP-Mg/Pi carriers, ARALAR/AGC1 and SCaMC-3, respectively, or in the matrix after Ca2+ transport through the Ca2+ uniporter. We have studied the role of Ca2+ signaling in the regulation of mitochondrial respiration in intact mouse cortical neurons in basal conditions and in response to increased workload caused by increases in [Na+]cyt (veratridine, high-K+ depolarization) and/or [Ca2+]cyt (carbachol). Respiration in nonstimulated neurons on 2.5-5 mm glucose depends on ARALAR-malate aspartate shuttle (MAS), with a 46% drop in aralar KO neurons. All stimulation conditions induced increased OCR (oxygen consumption rate) in the presence of Ca2+, which was prevented by BAPTA-AM loading (to preserve the workload), or in Ca2+-free medium (which also lowers cell workload). SCaMC-3 limits respiration only in response to high workloads and robust Ca2+ signals. In every condition tested Ca2+ activation of ARALAR-MAS was required to fully stimulate coupled respiration by promoting pyruvate entry into mitochondria. In aralar KO neurons, respiration was stimulated by veratridine, but not by KCl or carbachol, indicating that the Ca2+ uniporter pathway played a role in the first, but not in the second condition, even though KCl caused an increase in [Ca2+]mit. The results suggest a requirement for ARALAR-MAS in priming pyruvate entry in mitochondria as a step needed to activate respiration by Ca2+ in response to moderate workloads.

  14. The Drosophila nerfin-1 mRNA requires multiple microRNAs to regulate its spatial and temporal translation dynamics in the developing nervous system.

    Science.gov (United States)

    Kuzin, Alexander; Kundu, Mukta; Brody, Thomas; Odenwald, Ward F

    2007-10-01

    The mRNA encoding the Drosophila Zn-finger transcription factor Nerfin-1, required for CNS axon pathfinding events, is subject to post-transcriptional silencing. Although nerfin-1 mRNA is expressed in many neural precursor cells including all early delaminating CNS neuroblasts, the encoded Nerfin-1 protein is detected only in the nuclei of neural precursors that divide just once to generate neurons and then only transiently in nascent neurons. Using a nerfin-1 promoter-controlled reporter transgene, replacement of the nerfin-1 3' UTR with the viral SV-40 3' UTR releases the neuroblast translational block and prolongs reporter protein expression in neurons. Comparative genomics analysis reveals that the nerfin-1 mRNA 3' UTR contains multiple highly conserved sequence blocks that either harbor and/or overlap 21 predicted binding sites for 18 different microRNAs. To determine the functional significance of these microRNA-binding sites and less conserved microRNA target sites, we have studied their ability to block or limit the expression of reporter protein in nerfin-1-expressing cells during embryonic development. Our results indicate that no single microRNA is sufficient to fully inhibit protein expression but rather multiple microRNAs that target different binding sites are required to block ectopic protein expression in neural precursor cells and temporally restrict expression in neurons. Taken together, these results suggest that multiple microRNAs play a cooperative role in the post-transcriptional regulation of nerfin-1 mRNA, and the high degree of microRNA-binding site evolutionary conservation indicates that all members of the Drosophila genus employ a similar strategy to regulate the onset and extinction dynamics of Nerfin-1 expression.

  15. National Statistical Commission and Indian Official Statistics*

    Indian Academy of Sciences (India)

    IAS Admin

    a good collection of official statistics of that time. With more .... statistical agencies and institutions to provide details of statistical activities .... ing several training programmes. .... ful completion of Indian Statistical Service examinations, the.

  16. Cyclic di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation in Staphylococcus aureus but dispensable for viability in anaerobic conditions.

    Science.gov (United States)

    Zeden, Merve S; Schuster, Christopher F; Bowman, Lisa; Zhong, Qiyun; Williams, Huw D; Gründling, Angelika

    2018-03-02

    Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling molecule important for the survival of Firmicutes, a large bacterial group that includes notable pathogens such as Staphylococcus aureus However, the exact role of this molecule has not been identified. dacA , the S. aureus gene encoding the diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted when bacterial cells are grown in rich medium, indicating that c-di-AMP is required for growth in this condition. Here, we report that an S. aureus dacA mutant can be generated in chemically defined medium. Consistent with previous findings, this mutant had a severe growth defect when cultured in rich medium. Using this growth defect in rich medium, we selected for suppressor strains with improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the essentiality of dacA were identified in alsT and opuD, encoding a predicted amino acid and osmolyte transporter, the latter of which we show here to be the main glycine betaine-uptake system in S. aureus. Inactivation of these transporters likely prevents the excessive osmolyte and amino acid accumulation in the cell, providing further evidence for a key role of c-di-AMP in osmotic regulation. Suppressor mutations were also obtained in hepS, hemB, ctaA, and qoxB, coding proteins required for respiration. Furthermore, we show that dacA is dispensable for growth in anaerobic conditions. Together, these findings reveal an essential role for the c-di-AMP signaling network in aerobic, but not anaerobic, respiration in S. aureus . © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Elementary Statistics Tables

    CERN Document Server

    Neave, Henry R

    2012-01-01

    This book, designed for students taking a basic introductory course in statistical analysis, is far more than just a book of tables. Each table is accompanied by a careful but concise explanation and useful worked examples. Requiring little mathematical background, Elementary Statistics Tables is thus not just a reference book but a positive and user-friendly teaching and learning aid. The new edition contains a new and comprehensive "teach-yourself" section on a simple but powerful approach, now well-known in parts of industry but less so in academia, to analysing and interpreting process dat

  18. Stupid statistics!

    Science.gov (United States)

    Tellinghuisen, Joel

    2008-01-01

    The method of least squares is probably the most powerful data analysis tool available to scientists. Toward a fuller appreciation of that power, this work begins with an elementary review of statistics fundamentals, and then progressively increases in sophistication as the coverage is extended to the theory and practice of linear and nonlinear least squares. The results are illustrated in application to data analysis problems important in the life sciences. The review of fundamentals includes the role of sampling and its connection to probability distributions, the Central Limit Theorem, and the importance of finite variance. Linear least squares are presented using matrix notation, and the significance of the key probability distributions-Gaussian, chi-square, and t-is illustrated with Monte Carlo calculations. The meaning of correlation is discussed, including its role in the propagation of error. When the data themselves are correlated, special methods are needed for the fitting, as they are also when fitting with constraints. Nonlinear fitting gives rise to nonnormal parameter distributions, but the 10% Rule of Thumb suggests that such problems will be insignificant when the parameter is sufficiently well determined. Illustrations include calibration with linear and nonlinear response functions, the dangers inherent in fitting inverted data (e.g., Lineweaver-Burk equation), an analysis of the reliability of the van't Hoff analysis, the problem of correlated data in the Guggenheim method, and the optimization of isothermal titration calorimetry procedures using the variance-covariance matrix for experiment design. The work concludes with illustrations on assessing and presenting results.

  19. The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.

    Science.gov (United States)

    Quilty, Douglas; Chan, Calvin J; Yurkiw, Katherine; Bain, Alexandra; Babolmorad, Ghazal; Melançon, Paul

    2018-04-19

    We previously proposed a novel mechanism by which the enzyme Golgi-specific Brefeldin A resistance factor 1 (GBF1) is recruited to the membranes of the cis -Golgi, based on in vivo experiments. Here, we extended our in vivo analysis on the production of regulatory Arf-GDP and observed that ArfGAP2 and ArfGAP3 do not play a role in GBF1 recruitment. We confirm that Arf-GDP localization is critical, as a TGN-localized Arf-GDP mutant protein fails to promote GBF1 recruitment. We also reported the establishment of an in vitro GBF1 recruitment assay that supports the regulation of GBF1 recruitment by Arf-GDP. This in vitro assay yielded further evidence for the requirement of a Golgi-localized protein because heat denaturation or protease treatment of Golgi membranes abrogated GBF1 recruitment. Finally, combined in vivo and in vitro measurements indicated that the recruitment to Golgi membranes via a putative receptor requires only the HDS1 and HDS2 domains in the C-terminal half of GBF1. © 2018. Published by The Company of Biologists Ltd.

  20. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells

    Science.gov (United States)

    Poppensieker, Karola; Otte, David-Marian; Schürmann, Britta; Limmer, Andreas; Dresing, Philipp; Drews, Eva; Schumak, Beatrix; Klotz, Luisa; Raasch, Jennifer; Mildner, Alexander; Waisman, Ari; Scheu, Stefanie; Knolle, Percy; Förster, Irmgard; Prinz, Marco; Maier, Wolfgang; Zimmer, Andreas; Alferink, Judith

    2012-01-01

    Dendritic cells (DCs) are pivotal for the development of experimental autoimmune encephalomyelitis (EAE). However, the mechanisms by which they control disease remain to be determined. This study demonstrates that expression of CC chemokine receptor 4 (CCR4) by DCs is required for EAE induction. CCR4−/− mice presented enhanced resistance to EAE associated with a reduction in IL-23 and GM-CSF expression in the CNS. Restoring CCR4 on myeloid cells in bone marrow chimeras or intracerebral microinjection of CCR4-competent DCs, but not macrophages, restored EAE in CCR4−/− mice, indicating that CCR4+ DCs are cellular mediators of EAE development. Mechanistically, CCR4−/− DCs were less efficient in GM-CSF and IL-23 production and also TH-17 maintenance. Intraspinal IL-23 reconstitution restored EAE in CCR4−/− mice, whereas intracerebral inoculation using IL-23−/− DCs or GM-CSF−/− DCs failed to induce disease. Thus, CCR4-dependent GM-CSF production in DCs required for IL-23 release in these cells is a major component in the development of EAE. Our study identified a unique role for CCR4 in regulating DC function in EAE, harboring therapeutic potential for the treatment of CNS autoimmunity by targeting CCR4 on this specific cell type. PMID:22355103

  1. Statistics and risk philosophy in human activities

    International Nuclear Information System (INIS)

    Failla, L.

    1983-01-01

    Two leading interpretations of the use of statistics exist, the first one considering statistics as a physical law regulating the phenomena studied, and the other considering statistics as a method allowing to achieve exhaustive knowledge of the phenomena. The Author chooses the second theory, applies this concept of statistics to the risk involved in human activities and discusses the different kinds of risk in this field. The Author distinguishes between the risk that can be eliminated or at least reduced, and the risk inherent in the activity itself, that can never be completely eliminated -unless the activity is suppressed-; yet, also this kind of risk can be kept under control. Furthermore, she distinguishes between risks that can or cannot be foreseen. The Author supports the theory according to which the risk foreseen must be prevented through up-to-date techniques: this should be done coherently with the aim of the activity but independently of the economic cost. The theory considering risk probability as a physical law is mainly based on events happened in the past: it uses the occurrence probability as a law. This theory accepts the statistical risk and estimates its costs, including the ''human cost''. The Author examines the different statistical possibilities to study this specific phenomenon: so, the possibility to avoid the risks may arise along with -last but not least- the opportunity to eliminate or reduce the damage connected. On the contrary, statistics used as a physical law implies the acceptable of a given amount of risk compared with the cost of improving the technical conditions required to eliminate damages. In the end, a practical example of this theory is described

  2. CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

    Directory of Open Access Journals (Sweden)

    Anthony Bruce

    Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

  3. Conformity and statistical tolerancing

    Science.gov (United States)

    Leblond, Laurent; Pillet, Maurice

    2018-02-01

    Statistical tolerancing was first proposed by Shewhart (Economic Control of Quality of Manufactured Product, (1931) reprinted 1980 by ASQC), in spite of this long history, its use remains moderate. One of the probable reasons for this low utilization is undoubtedly the difficulty for designers to anticipate the risks of this approach. The arithmetic tolerance (worst case) allows a simple interpretation: conformity is defined by the presence of the characteristic in an interval. Statistical tolerancing is more complex in its definition. An interval is not sufficient to define the conformance. To justify the statistical tolerancing formula used by designers, a tolerance interval should be interpreted as the interval where most of the parts produced should probably be located. This tolerance is justified by considering a conformity criterion of the parts guaranteeing low offsets on the latter characteristics. Unlike traditional arithmetic tolerancing, statistical tolerancing requires a sustained exchange of information between design and manufacture to be used safely. This paper proposes a formal definition of the conformity, which we apply successively to the quadratic and arithmetic tolerancing. We introduce a concept of concavity, which helps us to demonstrate the link between tolerancing approach and conformity. We use this concept to demonstrate the various acceptable propositions of statistical tolerancing (in the space decentring, dispersion).

  4. Detecting Human Hydrologic Alteration from Diversion Hydropower Requires Universal Flow Prediction Tools: A Proposed Framework for Flow Prediction in Poorly-gauged, Regulated Rivers

    Science.gov (United States)

    Kibler, K. M.; Alipour, M.

    2016-12-01

    Achieving the universal energy access Sustainable Development Goal will require great investment in renewable energy infrastructure in the developing world. Much growth in the renewable sector will come from new hydropower projects, including small and diversion hydropower in remote and mountainous regions. Yet, human impacts to hydrological systems from diversion hydropower are poorly described. Diversion hydropower is often implemented in ungauged rivers, thus detection of impact requires flow analysis tools suited to prediction in poorly-gauged and human-altered catchments. We conduct a comprehensive analysis of hydrologic alteration in 32 rivers developed with diversion hydropower in southwestern China. As flow data are sparse, we devise an approach for estimating streamflow during pre- and post-development periods, drawing upon a decade of research into prediction in ungauged basins. We apply a rainfall-runoff model, parameterized and forced exclusively with global-scale data, in hydrologically-similar gauged and ungauged catchments. Uncertain "soft" data are incorporated through fuzzy numbers and confidence-based weighting, and a multi-criteria objective function is applied to evaluate model performance. Testing indicates that the proposed framework returns superior performance (NSE = 0.77) as compared to models parameterized by rote calibration (NSE = 0.62). Confident that the models are providing `the right answer for the right reasons', our analysis of hydrologic alteration based on simulated flows indicates statistically significant hydrologic effects of diversion hydropower across many rivers. Mean annual flows, 7-day minimum and 7-day maximum flows decreased. Frequency and duration of flow exceeding Q25 decreased while duration of flows sustained below the Q75 increased substantially. Hydrograph rise and fall rates and flow constancy increased. The proposed methodology may be applied to improve diversion hydropower design in data-limited regions.

  5. Statistics Anxiety among Postgraduate Students

    Science.gov (United States)

    Koh, Denise; Zawi, Mohd Khairi

    2014-01-01

    Most postgraduate programmes, that have research components, require students to take at least one course of research statistics. Not all postgraduate programmes are science based, there are a significant number of postgraduate students who are from the social sciences that will be taking statistics courses, as they try to complete their…

  6. Lecture notes on quantum statistics

    NARCIS (Netherlands)

    Gill, R.D.

    2000-01-01

    These notes are meant to form the material for an introductory course on quantum statistics at the graduate level aimed at mathematical statisticians and probabilists No background in physics quantum or otherwise is required They are still far from complete

  7. Efficient design and simulation of an expandable hybrid (wind-photovoltaic) power system with MPPT and inverter input voltage regulation features in compliance with electric grid requirements

    Energy Technology Data Exchange (ETDEWEB)

    Skretas, Sotirios B.; Papadopoulos, Demetrios P. [Electrical Machines Laboratory, Department of Electrical and Computer Engineering, Democritos University of Thrace (DUTH), 12 V. Sofias, 67100 Xanthi (Greece)

    2009-09-15

    In this paper an efficient design along with modeling and simulation of a transformer-less small-scale centralized DC - bus Grid Connected Hybrid (Wind-PV) power system for supplying electric power to a single phase of a three phase low voltage (LV) strong distribution grid are proposed and presented. The main components of the hybrid system are: a PV generator (PVG); and an array of horizontal-axis, fixed-pitch, small-size, variable-speed wind turbines (WTs) with direct-driven permanent magnet synchronous generator (PMSG) having an embedded uncontrolled bridge rectifier. An overview of the basic theory of such systems along with their modeling and simulation via Simulink/MATLAB software package are presented. An intelligent control method is applied to the proposed configuration to simultaneously achieve three desired goals: to extract maximum power from each hybrid power system component (PVG and WTs); to guarantee DC voltage regulation/stabilization at the input of the inverter; to transfer the total produced electric power to the electric grid, while fulfilling all necessary interconnection requirements. Finally, a practical case study is conducted for the purpose of fully evaluating a possible installation in a city site of Xanthi/Greece, and the practical results of the simulations are presented. (author)

  8. Human regulator of telomere elongation helicase 1 (RTEL1) is required for the nuclear and cytoplasmic trafficking of pre-U2 RNA.

    Science.gov (United States)

    Schertzer, Michael; Jouravleva, Karina; Perderiset, Mylene; Dingli, Florent; Loew, Damarys; Le Guen, Tangui; Bardoni, Barbara; de Villartay, Jean-Pierre; Revy, Patrick; Londoño-Vallejo, Arturo

    2015-02-18

    Hoyeraal-Hreidarsson syndrome (HHS) is a severe form of Dyskeratosis congenita characterized by developmental defects, bone marrow failure and immunodeficiency and has been associated with telomere dysfunction. Recently, mutations in Regulator of Telomere ELongation helicase 1 (RTEL1), a helicase first identified in Mus musculus as being responsible for the maintenance of long telomeres, have been identified in several HHS patients. Here we show that RTEL1 is required for the export and the correct cytoplasmic trafficking of the small nuclear (sn) RNA pre-U2, a component of the major spliceosome complex. RTEL1-HHS cells show abnormal subcellular partitioning of pre-U2, defects in the recycling of ribonucleotide proteins (RNP) in the cytoplasm and splicing defects. While most of these phenotypes can be suppressed by re-expressing the wild-type protein in RTEL1-HHS cells, expression of RTEL1 mutated variants in immortalized cells provokes cytoplasmic mislocalizations of pre-U2 and other RNP components, as well as splicing defects, thus phenocopying RTEL1-HHS cellular defects. Strikingly, expression of a cytoplasmic form of RTEL1 is sufficient to correct RNP mislocalizations both in RTEL1-HHS cells and in cells expressing nuclear mutated forms of RTEL1. This work unravels completely unanticipated roles for RTEL1 in RNP trafficking and strongly suggests that defects in RNP biogenesis pathways contribute to the pathology of HHS. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Causality Statistical Perspectives and Applications

    CERN Document Server

    Berzuini, Carlo; Bernardinell, Luisa

    2012-01-01

    A state of the art volume on statistical causality Causality: Statistical Perspectives and Applications presents a wide-ranging collection of seminal contributions by renowned experts in the field, providing a thorough treatment of all aspects of statistical causality. It covers the various formalisms in current use, methods for applying them to specific problems, and the special requirements of a range of examples from medicine, biology and economics to political science. This book:Provides a clear account and comparison of formal languages, concepts and models for statistical causality. Addr

  10. All of statistics a concise course in statistical inference

    CERN Document Server

    Wasserman, Larry

    2004-01-01

    This book is for people who want to learn probability and statistics quickly It brings together many of the main ideas in modern statistics in one place The book is suitable for students and researchers in statistics, computer science, data mining and machine learning This book covers a much wider range of topics than a typical introductory text on mathematical statistics It includes modern topics like nonparametric curve estimation, bootstrapping and classification, topics that are usually relegated to follow-up courses The reader is assumed to know calculus and a little linear algebra No previous knowledge of probability and statistics is required The text can be used at the advanced undergraduate and graduate level Larry Wasserman is Professor of Statistics at Carnegie Mellon University He is also a member of the Center for Automated Learning and Discovery in the School of Computer Science His research areas include nonparametric inference, asymptotic theory, causality, and applications to astrophysics, bi...

  11. Childhood Cancer Statistics

    Science.gov (United States)

    ... Watchdog Ratings Feedback Contact Select Page Childhood Cancer Statistics Home > Cancer Resources > Childhood Cancer Statistics Childhood Cancer Statistics – Graphs and Infographics Number of Diagnoses Incidence Rates ...

  12. Transcriptional control of the tissue-specific, developmentally regulated osteocalcin gene requires a binding motif for the Msx family of homeodomain proteins.

    Science.gov (United States)

    Hoffmann, H M; Catron, K M; van Wijnen, A J; McCabe, L R; Lian, J B; Stein, G S; Stein, J L

    1994-12-20

    The OC box of the rat osteocalcin promoter (nt -99 to -76) is the principal proximal regulatory element contributing to both tissue-specific and developmental control of osteocalcin gene expression. The central motif of the OC box includes a perfect consensus DNA binding site for certain homeodomain proteins. Homeodomain proteins are transcription factors that direct proper development by regulating specific temporal and spatial patterns of gene expression. We therefore addressed the role of the homeodomain binding motif in the activity of the OC promoter. In this study, by the combined application of mutagenesis and site-specific protein recognition analysis, we examined interactions of ROS 17/2.8 osteosarcoma cell nuclear proteins and purified Msx-1 homeodomain protein with the OC box. We detected a series of related specific protein-DNA interactions, a subset of which were inhibited by antibodies directed against the Msx-1 homeodomain but which also recognize the Msx-2 homeodomain. Our results show that the sequence requirements for binding the Msx-1 or Msx-2 homeodomain closely parallel those necessary for osteocalcin gene promoter activity in vivo. This functional relationship was demonstrated by transient expression in ROS 17/2.8 osteosarcoma cells of a series of osteocalcin promoter (nt -1097 to +24)-reporter gene constructs containing mutations within and flanking the homeodomain binding site of the OC box. Northern blot analysis of several bone-related cell types showed that all of the cells expressed msx-1, whereas msx-2 expression was restricted to cells transcribing osteocalcin. Taken together, our results suggest a role for Msx-1 and -2 or related homeodomain proteins in transcription of the osteocalcin gene.

  13. Introductory statistics for engineering experimentation

    CERN Document Server

    Nelson, Peter R; Coffin, Marie

    2003-01-01

    The Accreditation Board for Engineering and Technology (ABET) introduced a criterion starting with their 1992-1993 site visits that "Students must demonstrate a knowledge of the application of statistics to engineering problems." Since most engineering curricula are filled with requirements in their own discipline, they generally do not have time for a traditional two semesters of probability and statistics. Attempts to condense that material into a single semester often results in so much time being spent on probability that the statistics useful for designing and analyzing engineering/scientific experiments is never covered. In developing a one-semester course whose purpose was to introduce engineering/scientific students to the most useful statistical methods, this book was created to satisfy those needs. - Provides the statistical design and analysis of engineering experiments & problems - Presents a student-friendly approach through providing statistical models for advanced learning techniques - Cove...

  14. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (∼160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  15. Novelty-induced activity-regulated cytoskeletal-associated protein (Arc) expression in frontal cortex requires serotonin 2A receptor activation

    DEFF Research Database (Denmark)

    Santini, Martin; Klein, A B; El-Sayed, M

    2011-01-01

    environment. As an output of FC activation we measured expression of activity-regulated cytoskeletal-associated protein (Arc). Novelty-exposure (open-field arena) robustly up-regulated FC Arc mRNA expression (~160%) in mice compared to home-cage controls. This response was inhibited with the 5-HT(2A...

  16. MQSA National Statistics

    Science.gov (United States)

    ... Standards Act and Program MQSA Insights MQSA National Statistics Share Tweet Linkedin Pin it More sharing options ... but should level off with time. Archived Scorecard Statistics 2018 Scorecard Statistics 2017 Scorecard Statistics 2016 Scorecard ...

  17. State Transportation Statistics 2014

    Science.gov (United States)

    2014-12-15

    The Bureau of Transportation Statistics (BTS) presents State Transportation Statistics 2014, a statistical profile of transportation in the 50 states and the District of Columbia. This is the 12th annual edition of State Transportation Statistics, a ...

  18. Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions.

    Directory of Open Access Journals (Sweden)

    Kwong Tai Cheng

    2011-03-01

    Full Text Available Store-operated Ca²+ entry (SOCE has been associated with two types of channels: CRAC channels that require Orai1 and STIM1 and SOC channels that involve TRPC1, Orai1, and STIM1. While TRPC1 significantly contributes to SOCE and SOC channel activity, abrogation of Orai1 function eliminates SOCE and activation of TRPC1. The critical role of Orai1 in activation of TRPC1-SOC channels following Ca²+ store depletion has not yet been established. Herein we report that TRPC1 and Orai1 are components of distinct channels. We show that TRPC1/Orai1/STIM1-dependent I(SOC, activated in response to Ca²+ store depletion, is composed of TRPC1/STIM1-mediated non-selective cation current and Orai1/STIM1-mediated I(CRAC; the latter is detected when TRPC1 function is suppressed by expression of shTRPC1 or a STIM1 mutant that lacks TRPC1 gating, STIM1(⁶⁸⁴EE⁶⁸⁵. In addition to gating TRPC1 and Orai1, STIM1 mediates the recruitment and association of the channels within ER/PM junctional domains, a critical step in TRPC1 activation. Importantly, we show that Ca²+ entry via Orai1 triggers plasma membrane insertion of TRPC1, which is prevented by blocking SOCE with 1 µM Gd³+, removal of extracellular Ca²+, knockdown of Orai1, or expression of dominant negative mutant Orai1 lacking a functional pore, Orai1-E106Q. In cells expressing another pore mutant of Orai1, Orai1-E106D, TRPC1 trafficking is supported in Ca²+-containing, but not Ca²+-free, medium. Consistent with this, I(CRAC is activated in cells pretreated with thapsigargin in Ca²+-free medium while I(SOC is activated in cells pretreated in Ca²+-containing medium. Significantly, TRPC1 function is required for sustained K(Ca activity and contributes to NFκB activation while Orai1 is sufficient for NFAT activation. Together, these findings reveal an as-yet unidentified function for Orai1 that explains the critical requirement of the channel in the activation of TRPC1 following Ca²+ store

  19. Key World Energy Statistics

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The IEA produced its first handy, pocket-sized summary of key energy data in 1997. This new edition responds to the enormously positive reaction to the book since then. Key World Energy Statistics produced by the IEA contains timely, clearly-presented data on supply, transformation and consumption of all major energy sources. The interested businessman, journalist or student will have at his or her fingertips the annual Canadian production of coal, the electricity consumption in Thailand, the price of diesel oil in Spain and thousands of other useful energy facts. It exists in different formats to suit our readers' requirements.

  20. Sampling, Probability Models and Statistical Reasoning Statistical

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 5. Sampling, Probability Models and Statistical Reasoning Statistical Inference. Mohan Delampady V R Padmawar. General Article Volume 1 Issue 5 May 1996 pp 49-58 ...

  1. Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases.

    Science.gov (United States)

    Battistone, M A; Da Ros, V G; Salicioni, A M; Navarrete, F A; Krapf, D; Visconti, P E; Cuasnicú, P S

    2013-09-01

    were exposed to SKI606 and OA. Interestingly, different concentrations of inhibitors were required to modulate human and mouse capacitation revealing the species specificity of the molecular mechanisms underlying this process. In conclusion, our results describe for the first time the involvement of both PKA activation and Ser/Thr phosphatase down-regulation in functional human sperm capacitation and provide convincing evidence that early PKA-dependent phosphorylation is the convergent regulatory point between these two signaling pathways.

  2. Statistical methods in nuclear material accountancy: Past, present and future

    International Nuclear Information System (INIS)

    Pike, D.J.; Woods, A.J.

    1983-01-01

    The analysis of nuclear material inventory data is motivated by the desire to detect any loss or diversion of nuclear material, insofar as such detection may be feasible by statistical analysis of repeated inventory and throughput measurements. The early regulations, which laid down the specifications for the analysis of inventory data, were framed without acknowledging the essentially sequential nature of the data. It is the broad aim of this paper to discuss the historical nature of statistical analysis of inventory data including an evaluation of why statistical methods should be required at all. If it is accepted that statistical techniques are required, then two main areas require extensive discussion. First, it is important to assess the extent to which stated safeguards aims can be met in practice. Second, there is a vital need for reassessment of the statistical techniques which have been proposed for use in nuclear material accountancy. Part of this reassessment must involve a reconciliation of the apparent differences in philosophy shown by statisticians; but, in addition, the techniques themselves need comparative study to see to what extent they are capable of meeting realistic safeguards aims. This paper contains a brief review of techniques with an attempt to compare and contrast the approaches. It will be suggested that much current research is following closely similar lines, and that national and international bodies should encourage collaborative research and practical in-plant implementations. The techniques proposed require credibility and power; but at this point in time statisticians require credibility and a greater level of unanimity in their approach. A way ahead is proposed based on a clear specification of realistic safeguards aims, and a development of a unified statistical approach with encouragement for the performance of joint research. (author)

  3. Decision support using nonparametric statistics

    CERN Document Server

    Beatty, Warren

    2018-01-01

    This concise volume covers nonparametric statistics topics that most are most likely to be seen and used from a practical decision support perspective. While many degree programs require a course in parametric statistics, these methods are often inadequate for real-world decision making in business environments. Much of the data collected today by business executives (for example, customer satisfaction opinions) requires nonparametric statistics for valid analysis, and this book provides the reader with a set of tools that can be used to validly analyze all data, regardless of type. Through numerous examples and exercises, this book explains why nonparametric statistics will lead to better decisions and how they are used to reach a decision, with a wide array of business applications. Online resources include exercise data, spreadsheets, and solutions.

  4. Statistical properties of reactor antineutrinos

    CERN Document Server

    Rusov, V D; Tarasov, V O; Shaaban, Y

    2002-01-01

    Based on the properties of the cascade statistics of reactor antineutrinos, the efficient method of searching for neutrino oscillations is offered. The determination of physical parameters of this statistics, i.e. the average number of fissions and the overage number of antineutrinos per fission, requires no a priori knowledge of the geometry and characteristics of the detector, the reactor power, and composition of nuclear fuel.

  5. The Statistical Fermi Paradox

    Science.gov (United States)

    Maccone, C.

    In this paper is provided the statistical generalization of the Fermi paradox. The statistics of habitable planets may be based on a set of ten (and possibly more) astrobiological requirements first pointed out by Stephen H. Dole in his book Habitable planets for man (1964). The statistical generalization of the original and by now too simplistic Dole equation is provided by replacing a product of ten positive numbers by the product of ten positive random variables. This is denoted the SEH, an acronym standing for “Statistical Equation for Habitables”. The proof in this paper is based on the Central Limit Theorem (CLT) of Statistics, stating that the sum of any number of independent random variables, each of which may be ARBITRARILY distributed, approaches a Gaussian (i.e. normal) random variable (Lyapunov form of the CLT). It is then shown that: 1. The new random variable NHab, yielding the number of habitables (i.e. habitable planets) in the Galaxy, follows the log- normal distribution. By construction, the mean value of this log-normal distribution is the total number of habitable planets as given by the statistical Dole equation. 2. The ten (or more) astrobiological factors are now positive random variables. The probability distribution of each random variable may be arbitrary. The CLT in the so-called Lyapunov or Lindeberg forms (that both do not assume the factors to be identically distributed) allows for that. In other words, the CLT "translates" into the SEH by allowing an arbitrary probability distribution for each factor. This is both astrobiologically realistic and useful for any further investigations. 3. By applying the SEH it is shown that the (average) distance between any two nearby habitable planets in the Galaxy may be shown to be inversely proportional to the cubic root of NHab. This distance is denoted by new random variable D. The relevant probability density function is derived, which was named the "Maccone distribution" by Paul Davies in

  6. Statistical mechanics in a nutshell

    CERN Document Server

    Peliti, Luca

    2011-01-01

    Statistical mechanics is one of the most exciting areas of physics today, and it also has applications to subjects as diverse as economics, social behavior, algorithmic theory, and evolutionary biology. Statistical Mechanics in a Nutshell offers the most concise, self-contained introduction to this rapidly developing field. Requiring only a background in elementary calculus and elementary mechanics, this book starts with the basics, introduces the most important developments in classical statistical mechanics over the last thirty years, and guides readers to the very threshold of today

  7. Learning the Language of Statistics: Challenges and Teaching Approaches

    Science.gov (United States)

    Dunn, Peter K.; Carey, Michael D.; Richardson, Alice M.; McDonald, Christine

    2016-01-01

    Learning statistics requires learning the language of statistics. Statistics draws upon words from general English, mathematical English, discipline-specific English and words used primarily in statistics. This leads to many linguistic challenges in teaching statistics and the way in which the language is used in statistics creates an extra layer…

  8. Measuring equipment and regulation of gas consuming appliances. Requirements for measuring equipments and regulation of gas consuming appliances; Maeleudstyr og indregulering af gasforbrugende apparater. Krav til maeleudstyr og indregulering af gasforbrugende apparater. Projektrapport

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, H.

    2004-06-01

    Regulation of gas consuming appliances has so far been regarded as a banality. However, during recent years a number of misunderstandings have arisen in this area. The load to which a gas consuming appliance should be regulated under practical conditions is often unclear. By way of example may be mentioned that the factory typically set the load using G20 reference gas (pure methane). Under practical Danish conditions the load (with Danish natural gas) is approx. 2% higher than the load set from the factory. This report focuses on the problems with varying gas composition in relation to regulation of gas consuming appliances. Furthermore, a number of unclear points concerning measuring equipment are dealt with. The report aims at offering suggestions for practical solutions. (BA)

  9. Calculating the capital contribution required for regulation of incentives in the energy sector; Bestimmung des Eigenkapitalzinssatzes fuer eine Anreizregulierung des Energiesektors

    Energy Technology Data Exchange (ETDEWEB)

    Schaeffner, D. [WIK GmbH, Wissenschaftliches Inst. fuer Infrastruktur und Kommunikationsdienste, Bad Honnef (Germany)

    2006-12-15

    On 30 June 2006, the Federal Regulatory Agency (BNetzA) published its final report on the introduction of regulation by incentives according to Section 21a EnWG. The new regulation regime is to start on 1 January 2008. By this date, a starting value must be defined for the initial cost level and grid use reimbursements. Further, the interest rate for the capital contribution must be redefined (currently: 6.5 percent for the electricity sector and 7.8 percent for the gas sector). The contribution presents a regulation-economic method which takes account of individual parameteres in defining the capital contribution interest rate and of tax parameters and links these to current legal boundary conditions. As an example, the well-known CAPM is presented. (orig.)

  10. The CD3 gamma leucine-based receptor-sorting motif is required for efficient ligand-mediated TCR down-regulation

    DEFF Research Database (Denmark)

    von Essen, Marina; Menné, Charlotte; Nielsen, Bodil L

    2002-01-01

    . The other pathway is dependent on protein kinase C (PKC)-mediated activation of the CD3 gamma di-leucine-based receptor-sorting motif. Previous studies have failed to demonstrate a connection between ligand- and PKC-induced TCR down-regulation. Thus, although an apparent paradox, the dogma has been...... that ligand- and PKC-induced TCR down-regulations are not interrelated. By analyses of a newly developed CD3 gamma-negative T cell variant, freshly isolated and PHA-activated PBMC, and a mouse T cell line, we challenged this dogma and demonstrate in this work that PKC activation and the CD3 gamma di...

  11. The foundations of statistics

    CERN Document Server

    Savage, Leonard J

    1972-01-01

    Classic analysis of the foundations of statistics and development of personal probability, one of the greatest controversies in modern statistical thought. Revised edition. Calculus, probability, statistics, and Boolean algebra are recommended.

  12. State Transportation Statistics 2010

    Science.gov (United States)

    2011-09-14

    The Bureau of Transportation Statistics (BTS), a part of DOTs Research and Innovative Technology Administration (RITA), presents State Transportation Statistics 2010, a statistical profile of transportation in the 50 states and the District of Col...

  13. State Transportation Statistics 2012

    Science.gov (United States)

    2013-08-15

    The Bureau of Transportation Statistics (BTS), a part of the U.S. Department of Transportation's (USDOT) Research and Innovative Technology Administration (RITA), presents State Transportation Statistics 2012, a statistical profile of transportation ...

  14. Adrenal Gland Tumors: Statistics

    Science.gov (United States)

    ... Gland Tumor: Statistics Request Permissions Adrenal Gland Tumor: Statistics Approved by the Cancer.Net Editorial Board , 03/ ... primary adrenal gland tumor is very uncommon. Exact statistics are not available for this type of tumor ...

  15. State transportation statistics 2009

    Science.gov (United States)

    2009-01-01

    The Bureau of Transportation Statistics (BTS), a part of DOTs Research and : Innovative Technology Administration (RITA), presents State Transportation : Statistics 2009, a statistical profile of transportation in the 50 states and the : District ...

  16. State Transportation Statistics 2011

    Science.gov (United States)

    2012-08-08

    The Bureau of Transportation Statistics (BTS), a part of DOTs Research and Innovative Technology Administration (RITA), presents State Transportation Statistics 2011, a statistical profile of transportation in the 50 states and the District of Col...

  17. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 01/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  18. State Transportation Statistics 2013

    Science.gov (United States)

    2014-09-19

    The Bureau of Transportation Statistics (BTS), a part of the U.S. Department of Transportations (USDOT) Research and Innovative Technology Administration (RITA), presents State Transportation Statistics 2013, a statistical profile of transportatio...

  19. BTS statistical standards manual

    Science.gov (United States)

    2005-10-01

    The Bureau of Transportation Statistics (BTS), like other federal statistical agencies, establishes professional standards to guide the methods and procedures for the collection, processing, storage, and presentation of statistical data. Standards an...

  20. Appetitive Cue-Evoked ERK Signaling in the Nucleus Accumbens Requires NMDA and D1 Dopamine Receptor Activation and Regulates CREB Phosphorylation

    Science.gov (United States)

    Kirschmann, Erin K. Z.; Mauna, Jocelyn C.; Willis, Cory M.; Foster, Rebecca L.; Chipman, Amanda M.; Thiels, Edda

    2014-01-01

    Conditioned stimuli (CS) can modulate reward-seeking behavior. This modulatory effect can be maladaptive and has been implicated in excessive reward seeking and relapse to drug addiction. We previously demonstrated that exposure to an appetitive CS causes an increase in the activation of extracellular signal-regulated kinase (ERK) and cyclic-AMP…

  1. Activation of Nrf2 is required for up-regulation of the π class of glutathione S-transferase in rat primary hepatocytes with L-methionine starvation.

    Science.gov (United States)

    Lin, Ai-Hsuan; Chen, Haw-Wen; Liu, Cheng-Tze; Tsai, Chia-Wen; Lii, Chong-Kuei

    2012-07-04

    Numerous genes expression is regulated in response to amino acid shortage, which helps organisms adapt to amino acid limitation. The expression of the π class of glutathione (GSH) S-transferase (GSTP), a highly inducible phase II detoxification enzyme, is regulated mainly by activates activating protein 1 (AP-1) binding to the enhancer I of GSTP (GPEI). Here we show the critical role of nuclear factor erythroid-2-related factor 2 (Nrf2) in up-regulating GSTP gene transcription. Primary rat hepatocytes were cultured in a methionine-restricted medium, and immunoblotting and RT-PCR analyses showed that methionine restriction time-dependently increased GSTP protein and mRNA expression over a 48 h period. Nrf2 translocation to the nucleus, nuclear proteins binding to GPEI, and antioxidant response element (ARE) luciferase reporter activity were increased by methionine restriction as well as by l-buthionine sulfoximine (BSO), a GSH synthesis inhibitor. Transfection with Nrf2 siRNA knocked down Nrf2 expression and reversed the methionine-induced GSTP expression and GPEI binding activity. Chromatin immunoprecipitation assay confirmed the binding of Nrf2 to the GPEI. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells. ERK2 siRNA abolished methionine restriction-induced Nrf2 nuclear translocation, GPEI binding activity, ARE-luciferase reporter activity, and GSTP expression. Our results suggest that the up-regulation of GSTP gene transcription in response to methionine restriction likely occurs via the ERK-Nrf2-GPEI signaling pathway.

  2. 40 CFR 1065.602 - Statistics.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Statistics. 1065.602 Section 1065.602... PROCEDURES Calculations and Data Requirements § 1065.602 Statistics. (a) Overview. This section contains equations and example calculations for statistics that are specified in this part. In this section we use...

  3. 40 CFR 122.34 - As an operator of a regulated small MS4, what will my NPDES MS4 storm water permit require?

    Science.gov (United States)

    2010-07-01

    ... NATIONAL POLLUTANT DISCHARGE ELIMINATION SYSTEM Permit Application and Special NPDES Program Requirements... water impacts. For example, providing information to restaurants on the impact of grease clogging storm... minimum, the relevant requirements of paragraph (b) of this section. (d)(1) In your permit application...

  4. Business Statistics Education: Content and Software in Undergraduate Business Statistics Courses.

    Science.gov (United States)

    Tabatabai, Manouchehr; Gamble, Ralph

    1997-01-01

    Survey responses from 204 of 500 business schools identified most often topics in business statistics I and II courses. The most popular software at both levels was Minitab. Most schools required both statistics I and II. (SK)

  5. Isolation of a novel cell wall architecture mutant of rice with defective Arabidopsis COBL4 ortholog BC1 required for regulated deposition of secondary cell wall components.

    Science.gov (United States)

    Sato, Kanna; Suzuki, Ryu; Nishikubo, Nobuyuki; Takenouchi, Sachi; Ito, Sachiko; Nakano, Yoshimi; Nakaba, Satoshi; Sano, Yuzou; Funada, Ryo; Kajita, Shinya; Kitano, Hidemi; Katayama, Yoshihiro

    2010-06-01

    The plant secondary cell wall is a highly ordered structure composed of various polysaccharides, phenolic components and proteins. Its coordinated regulation of a number of complex metabolic pathways and assembly has not been resolved. To understand the molecular mechanisms that regulate secondary cell wall synthesis, we isolated a novel rice mutant, cell wall architecture1 (cwa1), that exhibits an irregular thickening pattern in the secondary cell wall of sclerenchyma, as well as culm brittleness and reduced cellulose content in mature internodes. Light and transmission electron microscopy revealed that the cwa1 mutant plant has regions of local aggregation in the secondary cell walls of the cortical fibers in its internodes, showing uneven thickness. Ultraviolet microscopic observation indicated that localization of cell wall phenolic components was perturbed and that these components abundantly deposited at the aggregated cell wall regions in sclerenchyma. Therefore, regulation of deposition and assembly of secondary cell wall materials, i.e. phenolic components, appear to be disturbed by mutation of the cwa1 gene. Genetic analysis showed that cwa1 is allelic to brittle culm1 (bc1), which encodes the glycosylphosphatidylinositol-anchored COBRA-like protein specifically in plants. BC1 is known as a regulator that controls the culm mechanical strength and cellulose content in the secondary cell walls of sclerenchyma, but the precise function of BC1 has not been resolved. Our results suggest that CWA1/BC1 has an essential role in assembling cell wall constituents at their appropriate sites, thereby enabling synthesis of solid and flexible internodes in rice.

  6. Beginning R The Statistical Programming Language

    CERN Document Server

    Gardener, Mark

    2012-01-01

    Conquer the complexities of this open source statistical language R is fast becoming the de facto standard for statistical computing and analysis in science, business, engineering, and related fields. This book examines this complex language using simple statistical examples, showing how R operates in a user-friendly context. Both students and workers in fields that require extensive statistical analysis will find this book helpful as they learn to use R for simple summary statistics, hypothesis testing, creating graphs, regression, and much more. It covers formula notation, complex statistics

  7. Statistics in Schools

    Science.gov (United States)

    Information Statistics in Schools Educate your students about the value and everyday use of statistics. The Statistics in Schools program provides resources for teaching and learning with real life data. Explore the site for standards-aligned, classroom-ready activities. Statistics in Schools Math Activities History

  8. Transport Statistics - Transport - UNECE

    Science.gov (United States)

    Sustainable Energy Statistics Trade Transport Themes UNECE and the SDGs Climate Change Gender Ideas 4 Change UNECE Weekly Videos UNECE Transport Areas of Work Transport Statistics Transport Transport Statistics About us Terms of Reference Meetings and Events Meetings Working Party on Transport Statistics (WP.6

  9. Compliance Determination for Inactivation Requirements of the National Primary Drinking Water Regulations when a Public Water Systems Uses Dichlor and Trichlor for Primary Disinfection

    Science.gov (United States)

    This memorandum has been developed to assist SDWA primacy agencies (EPA Regions, states and territories) when considering inactivation/disinfection compliance requirements for those water systems that choose to use Dichlor or Trichlor.

  10. Major Vault Protein, a Candidate Gene in 16p11.2 Microdeletion Syndrome, Is Required for the Homeostatic Regulation of Visual Cortical Plasticity.

    Science.gov (United States)

    Ip, Jacque P K; Nagakura, Ikue; Petravicz, Jeremy; Li, Keji; Wiemer, Erik A C; Sur, Mriganka

    2018-04-18

    Microdeletion of a region in chromosome 16p11.2 increases susceptibility to autism. Although this region contains exons of 29 genes, disrupting only a small segment of the region, which spans five genes, is sufficient to cause autistic traits. One candidate gene in this critical segment is MVP , which encodes for the major vault protein (MVP) that has been implicated in regulation of cellular transport mechanisms. MVP expression levels in MVP +/- mice closely phenocopy those of 16p11.2 mutant mice, suggesting that MVP +/- mice may serve as a model of MVP function in 16p11.2 microdeletion. Here we show that MVP regulates the homeostatic component of ocular dominance (OD) plasticity in primary visual cortex. MVP +/- mice of both sexes show impairment in strengthening of open-eye responses after several days of monocular deprivation (MD), whereas closed-eye responses are weakened as normal, resulting in reduced overall OD plasticity. The frequency of miniature EPSCs (mEPSCs) in pyramidal neurons is decreased in MVP +/- mice after extended MD, suggesting a reduction of functional synapses. Correspondingly, upregulation of surface GluA1 AMPA receptors is reduced in MVP +/- mice after extended MD, and is accompanied by altered expression of STAT1 and phosphorylated ERK, which have been previously implicated in OD plasticity. Normalization of STAT1 levels by introducing STAT1 shRNA rescues surface GluA1 and open-eye responses, implicating STAT1 as a downstream effector of MVP. These findings demonstrate a specific role for MVP as a key molecule influencing the homeostatic component of activity-dependent synaptic plasticity, and potentially the corresponding phenotypes of 16p11.2 microdeletion syndrome. SIGNIFICANCE STATEMENT Major vault protein (MVP), a candidate gene in 16p11.2 microdeletion syndrome, has been implicated in the regulation of several cellular processes including transport mechanisms and scaffold signaling. However, its role in brain function and

  11. Statistical literacy for clinical practitioners

    CERN Document Server

    Holmes, William H

    2014-01-01

    This textbook on statistics is written for students in medicine, epidemiology, and public health. It builds on the important role evidence-based medicine now plays in the clinical practice of physicians, physician assistants and allied health practitioners. By bringing research design and statistics to the fore, this book can integrate these skills into the curricula of professional programs. Students, particularly practitioners-in-training, will learn statistical skills that are required of today’s clinicians. Practice problems at the end of each chapter and downloadable data sets provided by the authors ensure readers get practical experience that they can then apply to their own work.  Topics covered include:   Functions of Statistics in Clinical Research Common Study Designs Describing Distributions of Categorical and Quantitative Variables Confidence Intervals and Hypothesis Testing Documenting Relationships in Categorical and Quantitative Data Assessing Screening and Diagnostic Tests Comparing Mean...

  12. Design research in statistics education : on symbolizing and computer tools

    NARCIS (Netherlands)

    Bakker, A.

    2004-01-01

    The present knowledge society requires statistical literacy-the ability to interpret, critically evaluate, and communicate about statistical information and messages (Gal, 2002). However, research shows that students generally do not gain satisfactory statistical understanding. The research

  13. Computation of the Molenaar Sijtsma Statistic

    Science.gov (United States)

    Andries van der Ark, L.

    The Molenaar Sijtsma statistic is an estimate of the reliability of a test score. In some special cases, computation of the Molenaar Sijtsma statistic requires provisional measures. These provisional measures have not been fully described in the literature, and we show that they have not been implemented in the software. We describe the required provisional measures as to allow the computation of the Molenaar Sijtsma statistic for all data sets.

  14. Statistics in biomedical research

    Directory of Open Access Journals (Sweden)

    González-Manteiga, Wenceslao

    2007-06-01

    Full Text Available The discipline of biostatistics is nowadays a fundamental scientific component of biomedical, public health and health services research. Traditional and emerging areas of application include clinical trials research, observational studies, physiology, imaging, and genomics. The present article reviews the current situation of biostatistics, considering the statistical methods traditionally used in biomedical research, as well as the ongoing development of new methods in response to the new problems arising in medicine. Clearly, the successful application of statistics in biomedical research requires appropriate training of biostatisticians. This training should aim to give due consideration to emerging new areas of statistics, while at the same time retaining full coverage of the fundamentals of statistical theory and methodology. In addition, it is important that students of biostatistics receive formal training in relevant biomedical disciplines, such as epidemiology, clinical trials, molecular biology, genetics, and neuroscience.La Bioestadística es hoy en día una componente científica fundamental de la investigación en Biomedicina, salud pública y servicios de salud. Las áreas tradicionales y emergentes de aplicación incluyen ensayos clínicos, estudios observacionales, fisología, imágenes, y genómica. Este artículo repasa la situación actual de la Bioestadística, considerando los métodos estadísticos usados tradicionalmente en investigación biomédica, así como los recientes desarrollos de nuevos métodos, para dar respuesta a los nuevos problemas que surgen en Medicina. Obviamente, la aplicación fructífera de la estadística en investigación biomédica exige una formación adecuada de los bioestadísticos, formación que debería tener en cuenta las áreas emergentes en estadística, cubriendo al mismo tiempo los fundamentos de la teoría estadística y su metodología. Es importante, además, que los estudiantes de

  15. Generalized quantum statistics

    International Nuclear Information System (INIS)

    Chou, C.

    1992-01-01

    In the paper, a non-anyonic generalization of quantum statistics is presented, in which Fermi-Dirac statistics (FDS) and Bose-Einstein statistics (BES) appear as two special cases. The new quantum statistics, which is characterized by the dimension of its single particle Fock space, contains three consistent parts, namely the generalized bilinear quantization, the generalized quantum mechanical description and the corresponding statistical mechanics

  16. The Regulation of Cytokine Networks in Hippocampal CA1 Differentiates Extinction from Those Required for the Maintenance of Contextual Fear Memory after Recall

    Science.gov (United States)

    Scholz, Birger; Doidge, Amie N.; Barnes, Philip; Hall, Jeremy; Wilkinson, Lawrence S.; Thomas, Kerrie L.

    2016-01-01

    We investigated the distinctiveness of gene regulatory networks in CA1 associated with the extinction of contextual fear memory (CFM) after recall using Affymetrix GeneChip Rat Genome 230 2.0 Arrays. These data were compared to previously published retrieval and reconsolidation-attributed, and consolidation datasets. A stringent dual normalization and pareto-scaled orthogonal partial least-square discriminant multivariate analysis together with a jack-knifing-based cross-validation approach was used on all datasets to reduce false positives. Consolidation, retrieval and extinction were correlated with distinct patterns of gene expression 2 hours later. Extinction-related gene expression was most distinct from the profile accompanying consolidation. A highly specific feature was the discrete regulation of neuroimmunological gene expression associated with retrieval and extinction. Immunity–associated genes of the tyrosine kinase receptor TGFβ and PDGF, and TNF families’ characterized extinction. Cytokines and proinflammatory interleukins of the IL-1 and IL-6 families were enriched with the no-extinction retrieval condition. We used comparative genomics to predict transcription factor binding sites in proximal promoter regions of the retrieval-regulated genes. Retrieval that does not lead to extinction was associated with NF-κB-mediated gene expression. We confirmed differential NF-κBp65 expression, and activity in all of a representative sample of our candidate genes in the no-extinction condition. The differential regulation of cytokine networks after the acquisition and retrieval of CFM identifies the important contribution that neuroimmune signalling plays in normal hippocampal function. Further, targeting cytokine signalling upon retrieval offers a therapeutic strategy to promote extinction mechanisms in human disorders characterised by dysregulation of associative memory. PMID:27224427

  17. Cloning and Characterization of an Outer Membrane Protein of Vibrio vulnificus Required for Heme Utilization: Regulation of Expression and Determination of the Gene Sequence

    Science.gov (United States)

    Litwin, Christine M.; Byrne, Burke L.

    1998-01-01

    Vibrio vulnificus is a halophilic, marine pathogen that has been associated with septicemia and serious wound infections in patients with iron overload and preexisting liver disease. For V. vulnificus, the ability to acquire iron from the host has been shown to correlate with virulence. V. vulnificus is able to use host iron sources such as hemoglobin and heme. We previously constructed a fur mutant of V. vulnificus which constitutively expresses at least two iron-regulated outer membrane proteins, of 72 and 77 kDa. The N-terminal amino acid sequence of the 77-kDa protein purified from the V. vulnificus fur mutant had 67% homology with the first 15 amino acids of the mature protein of the Vibrio cholerae heme receptor, HutA. In this report, we describe the cloning, DNA sequence, mutagenesis, and analysis of transcriptional regulation of the structural gene for HupA, the heme receptor of V. vulnificus. DNA sequencing of hupA demonstrated a single open reading frame of 712 amino acids that was 50% identical and 66% similar to the sequence of V. cholerae HutA and similar to those of other TonB-dependent outer membrane receptors. Primer extension analysis localized one promoter for the V. vulnificus hupA gene. Analysis of the promoter region of V. vulnificus hupA showed a sequence homologous to the consensus Fur box. Northern blot analysis showed that the transcript was strongly regulated by iron. An internal deletion in the V. vulnificus hupA gene, done by using marker exchange, resulted in the loss of expression of the 77-kDa protein and the loss of the ability to use hemin or hemoglobin as a source of iron. The hupA deletion mutant of V. vulnificus will be helpful in future studies of the role of heme iron in V. vulnificus pathogenesis. PMID:9632577

  18. Regulation of protein biosynthesis by non-lymphoid cells requires the participation of receptors, which recognize the same protein through a center analogous to the antibody active center

    International Nuclear Information System (INIS)

    Kul'berg, A.Y.; Ivanovska, N.D.; Tarkhanova, I.A.

    1986-01-01

    This paper studies the mechanism for regulating the biosynthesis of one of the complement components (anti-idiotypic antibodies CI /SUB q/ ) by macrophages. The experiments were conducted on mouse resident peritoneal macrophages cultivated in medium containing C 14-glycine. The synthesis of CI /SUB q/ was evaluated according to the content of protein which was bound by rabbit antibodies against mouse CI /SUB q/ immobilized on bromocyan-Sepharose 4B. The study of the kinetics of the biosynthesis of CI /SUB q/ by propagated macrophages shows that the biosynthesis was initially recorded and in the subsequent period the culture contained no other cells apart from macrophages

  19. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions.

    OpenAIRE

    Pettit, S C; Moody, M D; Wehbie, R S; Kaplan, A H; Nantermet, P V; Klein, C A; Swanstrom, R

    1994-01-01

    The proteolytic processing sites of the human immunodeficiency virus type 1 (HIV-1) Gag precursor are cleaved in a sequential manner by the viral protease. We investigated the factors that regulate sequential processing. When full-length Gag protein was digested with recombinant HIV-1 protease in vitro, four of the five major processing sites in Gag were cleaved at rates that differ by as much as 400-fold. Three of these four processing sites were cleaved independently of the others. The CA/p...

  20. Caveolin-1 down-regulation is required for Wnt5a-Frizzled 2 signalling in Ha-RasV12 -induced cell transformation.

    Science.gov (United States)

    Lin, Hsiu-Kuan; Lin, Hsi-Hui; Chiou, Yu-Wei; Wu, Ching-Lung; Chiu, Wen-Tai; Tang, Ming-Jer

    2018-05-01

    Caveolin-1 (Cav1) is down-regulated during MK4 (MDCK cells harbouring inducible Ha-Ras V12 gene) transformation by Ha-Ras V12 . Cav1 overexpression abrogates the Ha-Ras V12 -driven transformation of MK4 cells; however, the targeted down-regulation of Cav1 is not sufficient to mimic this transformation. Cav1-silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction-related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I-CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha-Ras V12 -inducing MK4 cells increased exosome-like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I-CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I-CM (MK4+I-EXs). Wnt5a, a downstream product of Ha-Ras V12 , was markedly secreted by MK4+I-CM and MK4+I-EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha-Ras V12 - and MK4+I-CM-induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down-regulation, either by Ha-Ras V12 or targeted shRNA, increased frizzled-2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I-EXs in MDCK cells. These data suggest that Cav1-dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha-Ras V12 -Wnt5a-Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha-Ras V12 -driven cell transformation. © 2018 The Authors

  1. National Statistical Commission and Indian Official Statistics

    Indian Academy of Sciences (India)

    Author Affiliations. T J Rao1. C. R. Rao Advanced Institute of Mathematics, Statistics and Computer Science (AIMSCS) University of Hyderabad Campus Central University Post Office, Prof. C. R. Rao Road Hyderabad 500 046, AP, India.

  2. Regulated expression of the human cytomegalovirus pp65 gene: Octamer sequence in the promoter is required for activation by viral gene products

    International Nuclear Information System (INIS)

    Depto, A.S.; Stenberg, R.M.

    1989-01-01

    To better understand the regulation of late gene expression in human cytomegalovirus (CMV)-infected cells, the authors examined expression of the gene that codes for the 65-kilodalton lower-matrix phosphoprotein (pp65). Analysis of RNA isolated at 72 h from cells infected with CMV Towne or ts66, a DNA-negative temperature-sensitive mutant, supported the fact that pp65 is expressed at low levels prior to viral DNA replication but maximally expressed after the initiation of viral DNA replication. To investigate promoter activation in a transient expression assay, the pp65 promoter was cloned into the indicator plasmid containing the gene for chloramphenicol acetyltransferase (CAT). Transfection of the promoter-CAT construct and subsequent superinfection with CMV resulted in activation of the promoter at early times after infection. Cotransfection with plasmids capable of expressing immediate-early (IE) proteins demonstrated that the promoter was activated by IE proteins and that both IE regions 1 and 2 were necessary. These studies suggest that interactions between IE proteins and this octamer sequence may be important for the regulation and expression of this CMV gene

  3. Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2018-03-01

    Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Statistics For Dummies

    CERN Document Server

    Rumsey, Deborah

    2011-01-01

    The fun and easy way to get down to business with statistics Stymied by statistics? No fear ? this friendly guide offers clear, practical explanations of statistical ideas, techniques, formulas, and calculations, with lots of examples that show you how these concepts apply to your everyday life. Statistics For Dummies shows you how to interpret and critique graphs and charts, determine the odds with probability, guesstimate with confidence using confidence intervals, set up and carry out a hypothesis test, compute statistical formulas, and more.Tracks to a typical first semester statistics cou

  5. Industrial statistics with Minitab

    CERN Document Server

    Cintas, Pere Grima; Llabres, Xavier Tort-Martorell

    2012-01-01

    Industrial Statistics with MINITAB demonstrates the use of MINITAB as a tool for performing statistical analysis in an industrial context. This book covers introductory industrial statistics, exploring the most commonly used techniques alongside those that serve to give an overview of more complex issues. A plethora of examples in MINITAB are featured along with case studies for each of the statistical techniques presented. Industrial Statistics with MINITAB: Provides comprehensive coverage of user-friendly practical guidance to the essential statistical methods applied in industry.Explores

  6. JMJD-5/KDM8 regulates H3K36me2 and is required for late steps of homologous recombination and genome integrity

    DEFF Research Database (Denmark)

    Amendola, Pier Giorgio; Zaghet, Nico; Ramalho, João J

    2017-01-01

    recombination. Loss of jmjd-5 results in hypersensitivity to ionizing radiation and in meiotic defects, and it is associated with aberrant retention of RAD-51 at sites of double strand breaks. Analyses of jmjd-5 genetic interactions with genes required for resolving recombination intermediates (rtel-1...

  7. The Heuristics of Statistical Argumentation: Scaffolding at the Postsecondary Level

    Science.gov (United States)

    Pardue, Teneal Messer

    2017-01-01

    Language plays a key role in statistics and, by extension, in statistics education. Enculturating students into the practice of statistics requires preparing them to communicate results of data analysis. Statistical argumentation is one way of providing structure to facilitate discourse in the statistics classroom. In this study, a teaching…

  8. Statistical theory of dynamo

    Science.gov (United States)

    Kim, E.; Newton, A. P.

    2012-04-01

    One major problem in dynamo theory is the multi-scale nature of the MHD turbulence, which requires statistical theory in terms of probability distribution functions. In this contribution, we present the statistical theory of magnetic fields in a simplified mean field α-Ω dynamo model by varying the statistical property of alpha, including marginal stability and intermittency, and then utilize observational data of solar activity to fine-tune the mean field dynamo model. Specifically, we first present a comprehensive investigation into the effect of the stochastic parameters in a simplified α-Ω dynamo model. Through considering the manifold of marginal stability (the region of parameter space where the mean growth rate is zero), we show that stochastic fluctuations are conductive to dynamo. Furthermore, by considering the cases of fluctuating alpha that are periodic and Gaussian coloured random noise with identical characteristic time-scales and fluctuating amplitudes, we show that the transition to dynamo is significantly facilitated for stochastic alpha with random noise. Furthermore, we show that probability density functions (PDFs) of the growth-rate, magnetic field and magnetic energy can provide a wealth of useful information regarding the dynamo behaviour/intermittency. Finally, the precise statistical property of the dynamo such as temporal correlation and fluctuating amplitude is found to be dependent on the distribution the fluctuations of stochastic parameters. We then use observations of solar activity to constrain parameters relating to the effect in stochastic α-Ω nonlinear dynamo models. This is achieved through performing a comprehensive statistical comparison by computing PDFs of solar activity from observations and from our simulation of mean field dynamo model. The observational data that are used are the time history of solar activity inferred for C14 data in the past 11000 years on a long time scale and direct observations of the sun spot

  9. The Transcription Factor ABI4 Is Required for the Ascorbic Acid–Dependent Regulation of Growth and Regulation of Jasmonate-Dependent Defense Signaling Pathways in Arabidopsis[C][W

    Science.gov (United States)

    Kerchev, Pavel I.; Pellny, Till K.; Vivancos, Pedro Diaz; Kiddle, Guy; Hedden, Peter; Driscoll, Simon; Vanacker, Hélène; Verrier, Paul; Hancock, Robert D.; Foyer, Christine H.

    2011-01-01

    Cellular redox homeostasis is a hub for signal integration. Interactions between redox metabolism and the ABSCISIC ACID-INSENSITIVE-4 (ABI4) transcription factor were characterized in the Arabidopsis thaliana vitamin c defective1 (vtc1) and vtc2 mutants, which are defective in ascorbic acid synthesis and show a slow growth phenotype together with enhanced abscisic acid (ABA) levels relative to the wild type (Columbia-0). The 75% decrease in the leaf ascorbate pool in the vtc2 mutants was not sufficient to adversely affect GA metabolism. The transcriptome signatures of the abi4, vtc1, and vtc2 mutants showed significant overlap, with a large number of transcription factors or signaling components similarly repressed or induced. Moreover, lincomycin-dependent changes in LIGHT HARVESTING CHLOROPHYLL A/B BINDING PROTEIN 1.1 expression were comparable in these mutants, suggesting overlapping participation in chloroplast to nucleus signaling. The slow growth phenotype of vtc2 was absent in the abi4 vtc2 double mutant, as was the sugar-insensitive phenotype of the abi4 mutant. Octadecanoid derivative-responsive AP2/ERF-domain transcription factor 47 (ORA47) and AP3 (an ABI5 binding factor) transcripts were enhanced in vtc2 but repressed in abi4 vtc2, suggesting that ABI4 and ascorbate modulate growth and defense gene expression through jasmonate signaling. We conclude that low ascorbate triggers ABA- and jasmonate-dependent signaling pathways that together regulate growth through ABI4. Moreover, cellular redox homeostasis exerts a strong influence on sugar-dependent growth regulation. PMID:21926335

  10. The cholesterol, fatty acid and triglyceride synthesis pathways regulated by site 1 protease (S1P) are required for efficient replication of severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Urata, Shuzo; Uno, Yukiko; Kurosaki, Yohei; Yasuda, Jiro

    2018-06-12

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively. These results enhance our understanding of the SFTSV replication mechanism and may contribute to the development of novel therapies for SFTSV infection. Copyright © 2018. Published by Elsevier Inc.

  11. The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions.

    Science.gov (United States)

    Pettit, S C; Moody, M D; Wehbie, R S; Kaplan, A H; Nantermet, P V; Klein, C A; Swanstrom, R

    1994-12-01

    The proteolytic processing sites of the human immunodeficiency virus type 1 (HIV-1) Gag precursor are cleaved in a sequential manner by the viral protease. We investigated the factors that regulate sequential processing. When full-length Gag protein was digested with recombinant HIV-1 protease in vitro, four of the five major processing sites in Gag were cleaved at rates that differ by as much as 400-fold. Three of these four processing sites were cleaved independently of the others. The CA/p2 site, however, was cleaved approximately 20-fold faster when the adjacent downstream p2/NC site was blocked from cleavage or when the p2 domain of Gag was deleted. These results suggest that the presence of a C-terminal p2 tail on processing intermediates slows cleavage at the upstream CA/p2 site. We also found that lower pH selectively accelerated cleavage of the CA/p2 processing site in the full-length precursor and as a peptide primarily by a sequence-based mechanism rather than by a change in protein conformation. Deletion of the p2 domain of Gag results in released virions that are less infectious despite the presence of the processed final products of Gag. These findings suggest that the p2 domain of HIV-1 Gag regulates the rate of cleavage at the CA/p2 processing site during sequential processing in vitro and in infected cells and that p2 may function in the proper assembly of virions.

  12. Recreational Boating Statistics 2012

    Data.gov (United States)

    Department of Homeland Security — Every year, the USCG compiles statistics on reported recreational boating accidents. These statistics are derived from accident reports that are filed by the owners...

  13. Recreational Boating Statistics 2013

    Data.gov (United States)

    Department of Homeland Security — Every year, the USCG compiles statistics on reported recreational boating accidents. These statistics are derived from accident reports that are filed by the owners...

  14. Statistical data analysis handbook

    National Research Council Canada - National Science Library

    Wall, Francis J

    1986-01-01

    It must be emphasized that this is not a text book on statistics. Instead it is a working tool that presents data analysis in clear, concise terms which can be readily understood even by those without formal training in statistics...

  15. CMS Program Statistics

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CMS Office of Enterprise Data and Analytics has developed CMS Program Statistics, which includes detailed summary statistics on national health care, Medicare...

  16. Recreational Boating Statistics 2011

    Data.gov (United States)

    Department of Homeland Security — Every year, the USCG compiles statistics on reported recreational boating accidents. These statistics are derived from accident reports that are filed by the owners...

  17. Uterine Cancer Statistics

    Science.gov (United States)

    ... Doing AMIGAS Stay Informed Cancer Home Uterine Cancer Statistics Language: English (US) Español (Spanish) Recommend on Facebook ... the most commonly diagnosed gynecologic cancer. U.S. Cancer Statistics Data Visualizations Tool The Data Visualizations tool makes ...

  18. Tuberculosis Data and Statistics

    Science.gov (United States)

    ... Advisory Groups Federal TB Task Force Data and Statistics Language: English (US) Español (Spanish) Recommend on Facebook ... Set) Mortality and Morbidity Weekly Reports Data and Statistics Decrease in Reported Tuberculosis Cases MMWR 2010; 59 ( ...

  19. National transportation statistics 2011

    Science.gov (United States)

    2011-04-01

    Compiled and published by the U.S. Department of Transportation's Bureau of Transportation Statistics : (BTS), National Transportation Statistics presents information on the U.S. transportation system, including : its physical components, safety reco...

  20. National Transportation Statistics 2008

    Science.gov (United States)

    2009-01-08

    Compiled and published by the U.S. Department of Transportations Bureau of Transportation Statistics (BTS), National Transportation Statistics presents information on the U.S. transportation system, including its physical components, safety record...

  1. Mental Illness Statistics

    Science.gov (United States)

    ... News & Events About Us Home > Health Information Share Statistics Research shows that mental illnesses are common in ... of mental illnesses, such as suicide and disability. Statistics Top ı cs Mental Illness Any Anxiety Disorder ...

  2. School Violence: Data & Statistics

    Science.gov (United States)

    ... Social Media Publications Injury Center School Violence: Data & Statistics Recommend on Facebook Tweet Share Compartir The first ... Vehicle Safety Traumatic Brain Injury Injury Response Data & Statistics (WISQARS) Funded Programs Press Room Social Media Publications ...

  3. Caregiver Statistics: Demographics

    Science.gov (United States)

    ... You are here Home Selected Long-Term Care Statistics Order this publication Printer-friendly version What is ... needs and services are wide-ranging and complex, statistics may vary from study to study. Sources for ...

  4. Aortic Aneurysm Statistics

    Science.gov (United States)

    ... Summary Coverdell Program 2012-2015 State Summaries Data & Statistics Fact Sheets Heart Disease and Stroke Fact Sheets ... Roadmap for State Planning Other Data Resources Other Statistic Resources Grantee Information Cross-Program Information Online Tools ...

  5. Alcohol Facts and Statistics

    Science.gov (United States)

    ... Standard Drink? Drinking Levels Defined Alcohol Facts and Statistics Print version Alcohol Use in the United States: ... 1238–1245, 2004. PMID: 15010446 National Center for Statistics and Analysis. 2014 Crash Data Key Findings (Traffic ...

  6. National Transportation Statistics 2009

    Science.gov (United States)

    2010-01-21

    Compiled and published by the U.S. Department of Transportation's Bureau of Transportation Statistics (BTS), National Transportation Statistics presents information on the U.S. transportation system, including its physical components, safety record, ...

  7. National transportation statistics 2010

    Science.gov (United States)

    2010-01-01

    National Transportation Statistics presents statistics on the U.S. transportation system, including its physical components, safety record, economic performance, the human and natural environment, and national security. This is a large online documen...

  8. Statistics for Finance

    DEFF Research Database (Denmark)

    Lindström, Erik; Madsen, Henrik; Nielsen, Jan Nygaard

    Statistics for Finance develops students’ professional skills in statistics with applications in finance. Developed from the authors’ courses at the Technical University of Denmark and Lund University, the text bridges the gap between classical, rigorous treatments of financial mathematics...

  9. Principles of applied statistics

    National Research Council Canada - National Science Library

    Cox, D. R; Donnelly, Christl A

    2011-01-01

    .... David Cox and Christl Donnelly distil decades of scientific experience into usable principles for the successful application of statistics, showing how good statistical strategy shapes every stage of an investigation...

  10. Regulation of Hxt3 and Hxt7 turnover converges on the Vid30 complex and requires inactivation of the Ras/cAMP/PKA pathway in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Chris Snowdon

    Full Text Available Eukaryotic cells adjust their intracellular protein complement as a mechanism to adapt to changing environmental signals. In Saccharomyces cerevisiae the hexose transporters Hxt3 and Hxt7 are expressed and function on the plasma membrane in high and low glucose abundance, respectively. By contrast, Hxt3 is endocytosed and degraded in the vacuole when cells are starved of glucose and Hxt7 in response to rapamycin treatment or when nitrogen is limiting. Yeast uses several signaling pathways, including the TORC1 and Ras/cAMP/Protein Kinase A (PKA pathways, to adapt to nutrient changes in the environment. The multi-protein Vid30 complex (Vid30c, an E3 ubiquitin ligase required for the degradation of FBPase, assists in this adaptation process in a mechanism that is poorly understood. Here we show the endocytosis and the subsequent degradation of both Hxt3 and Hxt7, in response to different nutrient signals, is dependent on components of the Vid30c. Additionally, we define the signaling events required for the turnover of Hxt3 and Hxt7 by showing that Hxt3 turnover requires Ras2 and PKA inactivation, whereas Hxt7 turnover requires TORC1 and Ras2 inactivation. Further investigation led us to identify Rim15, a kinase that is inhibited by both the TORC1 and Ras/cAMP/PKA pathways, as a key downstream effector in signaling both turnover events. Finally, we show that the turnover of both Hxt3 and Hxt7 is dependent on the essential E3 ubiquitin ligase, Rsp5, indicating that the role of the Vid30c might be indirect of Hxt ubiquitylation.

  11. Applying contemporary statistical techniques

    CERN Document Server

    Wilcox, Rand R

    2003-01-01

    Applying Contemporary Statistical Techniques explains why traditional statistical methods are often inadequate or outdated when applied to modern problems. Wilcox demonstrates how new and more powerful techniques address these problems far more effectively, making these modern robust methods understandable, practical, and easily accessible.* Assumes no previous training in statistics * Explains how and why modern statistical methods provide more accurate results than conventional methods* Covers the latest developments on multiple comparisons * Includes recent advanc

  12. Climate Regulation of Rearing-Related Buildings - Evaluating the Factors Related to the Energy Requirement of Heating/Cooling, and Analysis of Alternative Solutions

    Directory of Open Access Journals (Sweden)

    Toth Laszló

    2017-10-01

    Full Text Available The most notable role in the energy usage of rearing-related buildings belongs to barn climate. For animals, one of the most important climate parameter is the temperature of the barn atmosphere. This can be kept in the proper interval by either heating or cooling. Apart from the operation of technological solutions, the need for airing barns must be taken into consideration. This means there are special technical requirements for airing. Also, they can cause significant energy losses. The temperature limit of heating is mainly influenced by the technological temperature related to keeping the animal in question, its acceptable differences, the heat loss of the barn, and the airing requirement. Energy sources applicable to heating can be traditional sources (coal, oil, gas, renewable sources (solar, biomass, wind, water, or geothermal energy, or transformed energy (electricity. As these have specific operation systems, they also mean further challenges in implementing efficient energy usage. The usage of heating energy can either be optimised by the rational usage of the heating system, or machinery explicitly made for reserving energy. Sparing heating energy via recuperative heating exchange may cut costs significantly, which we also proved in this research with actual calculations. However, we have to state that the efficient usage of heat exchangers requires that the internal and external temperatures differ greatly, which has a huge impact on heat recovery performance.

  13. Statistics: The stethoscope of a thinking urologist

    Directory of Open Access Journals (Sweden)

    Arun S Sivanandam

    2009-01-01

    Full Text Available Understanding statistical terminology and the ability to appraise clinical research findings and statistical tests are critical to the practice of evidence-based medicine. Urologists require statistics in their toolbox of skills in order to successfully sift through increasingly complex studies and realize the drawbacks of statistical tests. Currently, the level of evidence in urology literature is low and the majority of research abstracts published for the American Urological Association (AUA meetings lag behind for full-text publication because of a lack of statistical reporting. Underlying these issues is a distinct deficiency in solid comprehension of statistics in the literature and a discomfort with the application of statistics for clinical decision-making. This review examines the plight of statistics in urology and investigates the reason behind the white-coat aversion to biostatistics. Resources such as evidence-based medicine websites, primers in statistics, and guidelines for statistical reporting exist for quick reference by urologists. Ultimately, educators should take charge of monitoring statistical knowledge among trainees by bolstering competency requirements and creating sustained opportunities for statistics and methodology exposure.

  14. Interactive statistics with ILLMO

    NARCIS (Netherlands)

    Martens, J.B.O.S.

    2014-01-01

    Progress in empirical research relies on adequate statistical analysis and reporting. This article proposes an alternative approach to statistical modeling that is based on an old but mostly forgotten idea, namely Thurstone modeling. Traditional statistical methods assume that either the measured

  15. Ethics in Statistics

    Science.gov (United States)

    Lenard, Christopher; McCarthy, Sally; Mills, Terence

    2014-01-01

    There are many different aspects of statistics. Statistics involves mathematics, computing, and applications to almost every field of endeavour. Each aspect provides an opportunity to spark someone's interest in the subject. In this paper we discuss some ethical aspects of statistics, and describe how an introduction to ethics has been…

  16. Youth Sports Safety Statistics

    Science.gov (United States)

    ... 6):794-799. 31 American Heart Association. CPR statistics. www.heart.org/HEARTORG/CPRAndECC/WhatisCPR/CPRFactsandStats/CPRpercent20Statistics_ ... Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. (January 10, 2013). The DAWN Report: ...

  17. Basic Student Charges at Postsecondary Institutions: Academic Year 1994-95. Tuition and Required Fees and Room and Board Charges at 4-Year, 2-Year, and Public Less-Than-2-Year Institutions. Statistical Analysis Report.

    Science.gov (United States)

    Barbett, Samuel F.; And Others

    This document lists the typical tuition and required fees and room and board charges assessed to college students in 1994-95 based on a national "Institutional Characteristics" survey which is part of the Integrated Postsecondary Education Data System. The data were collected from over 5,000 of the 5,775 4-year, 2-year, and public…

  18. Assumptions used in determining the radiation exposure according to the amended Radiation Protection Ordinance, and required adjustments in the General Administrative Regulation relating to paragraph 45 of the Radiation Protection Ordinance

    International Nuclear Information System (INIS)

    Wirth, E.

    2000-01-01

    Within the framework of the amendment of the Radiation Protection Ordinance, the need arises to also amend the General Administrative Regulation on calculation of the radiation exposure due to radioactivity release with gaseous or liquid effluents, for the purpose of verification of compliance with the dose limits given in section 45 of the Radiation Protection Ordinance. The General Administrative regulation has to be harmonized with European legislation, EURATOM Directive 96/29. The required consultations for decision making have been a task of the working group for 'Anpassung der radiooekologischen Berechnungsgrundlage', of the Radioecology Committee of the SSK. The paper discusses the resulting draft document for amendment presented to and accepted by the SSK Committee. The document is awaiting discussion for final decision among members of the SSK, and between the SSK and representatives of Land governments as well as various bodies representing interests. (orig./CB) [de

  19. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements. (Russian Edition); Pravila bezopasnoj perevozki radioaktivnykh materialov. Izdanie 2012 goda. Konkretnye trebovaniya bezopasnosti

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

  20. Regulations for the Safe Transport of Radioactive Material. 2012 Edition. Specific Safety Requirements (French Edition); Reglement de transport des matieres radioactives. Edition de 2012

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-03-15

    The IAEA's Statute authorizes the Agency to ''establish or adopt standards of safety for protection of health and minimization of danger to life and property'' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the

  1. The Translesion Polymerase Pol η Is Required for Efficient Epstein-Barr Virus Infectivity and Is Regulated by the Viral Deubiquitinating Enzyme BPLF1.

    Science.gov (United States)

    Dyson, Ossie F; Pagano, Joseph S; Whitehurst, Christopher B

    2017-10-01

    Epstein-Barr virus (EBV) infection and lytic replication are known to induce a cellular DNA damage response. We previously showed that the virally encoded BPLF1 protein interacts with and regulates several members of the translesion synthesis (TLS) pathway, a DNA damage tolerance pathway, and that these cellular factors enhance viral infectivity. BPLF1 is a late lytic cycle gene, but the protein is also packaged in the viral tegument, indicating that BPLF1 may function both early and late during infection. The BPLF1 protein expresses deubiquitinating activity that is strictly conserved across the Herpesviridae ; mutation of the active site cysteine results in a loss of enzymatic activity. Infection with an EBV BPLF1 knockout virus results in decreased EBV infectivity. Polymerase eta (Pol η), a specialized DNA repair polymerase, functions in TLS and allows for DNA replication complexes to bypass lesions in DNA. Here we report that BPLF1 interacts with Pol η and that Pol η protein levels are increased in the presence of functional BPLF1. BPLF1 promotes a nuclear relocalization of Pol η molecules which are focus-like in appearance, consistent with the localization observed when Pol η is recruited to sites of DNA damage. Knockdown of Pol η resulted in decreased production of infectious virus, and further, Pol η was found to bind to EBV DNA, suggesting that it may allow for bypass of damaged viral DNA during its replication. The results suggest a mechanism by which EBV recruits cellular repair factors, such as Pol η, to sites of viral DNA damage via BPLF1, thereby allowing for efficient viral DNA replication. IMPORTANCE Epstein-Barr virus is the causative agent of infectious mononucleosis and infects approximately 90% of the world's population. It causes lymphomas in individuals with acquired and innate immune disorders and is strongly associated with Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B-cell lymphomas, nasopharyngeal carcinoma (NPC), and

  2. Practical Statistics for Environmental and Biological Scientists

    CERN Document Server

    Townend, John

    2012-01-01

    All students and researchers in environmental and biological sciences require statistical methods at some stage of their work. Many have a preconception that statistics are difficult and unpleasant and find that the textbooks available are difficult to understand. Practical Statistics for Environmental and Biological Scientists provides a concise, user-friendly, non-technical introduction to statistics. The book covers planning and designing an experiment, how to analyse and present data, and the limitations and assumptions of each statistical method. The text does not refer to a specific comp

  3. TIF-IA-dependent regulation of ribosome synthesis in drosophila muscle is required to maintain systemic insulin signaling and larval growth.

    Directory of Open Access Journals (Sweden)

    Abhishek Ghosh

    2014-10-01

    Full Text Available The conserved TOR kinase signaling network links nutrient availability to cell, tissue and body growth in animals. One important growth-regulatory target of TOR signaling is ribosome biogenesis. Studies in yeast and mammalian cell culture have described how TOR controls rRNA synthesis-a limiting step in ribosome biogenesis-via the RNA Polymerase I transcription factor TIF-IA. However, the contribution of TOR-dependent ribosome synthesis to tissue and body growth in animals is less clear. Here we show in Drosophila larvae that ribosome synthesis in muscle is required non-autonomously to maintain normal body growth and development. We find that amino acid starvation and TOR inhibition lead to reduced levels of TIF-IA, and decreased rRNA synthesis in larval muscle. When we mimic this decrease in muscle ribosome synthesis using RNAi-mediated knockdown of TIF-IA, we observe delayed larval development and reduced body growth. This reduction in growth is caused by lowered systemic insulin signaling via two endocrine responses: reduced expression of Drosophila insulin-like peptides (dILPs from the brain and increased expression of Imp-L2-a secreted factor that binds and inhibits dILP activity-from muscle. We also observed that maintaining TIF-IA levels in muscle could partially reverse the starvation-mediated suppression of systemic insulin signaling. Finally, we show that activation of TOR specifically in muscle can increase overall body size and this effect requires TIF-IA function. These data suggest that muscle ribosome synthesis functions as a nutrient-dependent checkpoint for overall body growth: in nutrient rich conditions, TOR is required to maintain levels of TIF-IA and ribosome synthesis to promote high levels of systemic insulin, but under conditions of starvation stress, reduced muscle ribosome synthesis triggers an endocrine response that limits systemic insulin signaling to restrict growth and maintain homeostasis.

  4. Statistics for Research

    CERN Document Server

    Dowdy, Shirley; Chilko, Daniel

    2011-01-01

    Praise for the Second Edition "Statistics for Research has other fine qualities besides superior organization. The examples and the statistical methods are laid out with unusual clarity by the simple device of using special formats for each. The book was written with great care and is extremely user-friendly."-The UMAP Journal Although the goals and procedures of statistical research have changed little since the Second Edition of Statistics for Research was published, the almost universal availability of personal computers and statistical computing application packages have made it possible f

  5. Statistics in a nutshell

    CERN Document Server

    Boslaugh, Sarah

    2013-01-01

    Need to learn statistics for your job? Want help passing a statistics course? Statistics in a Nutshell is a clear and concise introduction and reference for anyone new to the subject. Thoroughly revised and expanded, this edition helps you gain a solid understanding of statistics without the numbing complexity of many college texts. Each chapter presents easy-to-follow descriptions, along with graphics, formulas, solved examples, and hands-on exercises. If you want to perform common statistical analyses and learn a wide range of techniques without getting in over your head, this is your book.

  6. Statistics & probaility for dummies

    CERN Document Server

    Rumsey, Deborah J

    2013-01-01

    Two complete eBooks for one low price! Created and compiled by the publisher, this Statistics I and Statistics II bundle brings together two math titles in one, e-only bundle. With this special bundle, you'll get the complete text of the following two titles: Statistics For Dummies, 2nd Edition  Statistics For Dummies shows you how to interpret and critique graphs and charts, determine the odds with probability, guesstimate with confidence using confidence intervals, set up and carry out a hypothesis test, compute statistical formulas, and more. Tra

  7. Nonparametric statistical inference

    CERN Document Server

    Gibbons, Jean Dickinson

    2010-01-01

    Overall, this remains a very fine book suitable for a graduate-level course in nonparametric statistics. I recommend it for all people interested in learning the basic ideas of nonparametric statistical inference.-Eugenia Stoimenova, Journal of Applied Statistics, June 2012… one of the best books available for a graduate (or advanced undergraduate) text for a theory course on nonparametric statistics. … a very well-written and organized book on nonparametric statistics, especially useful and recommended for teachers and graduate students.-Biometrics, 67, September 2011This excellently presente

  8. Business statistics for dummies

    CERN Document Server

    Anderson, Alan

    2013-01-01

    Score higher in your business statistics course? Easy. Business statistics is a common course for business majors and MBA candidates. It examines common data sets and the proper way to use such information when conducting research and producing informational reports such as profit and loss statements, customer satisfaction surveys, and peer comparisons. Business Statistics For Dummies tracks to a typical business statistics course offered at the undergraduate and graduate levels and provides clear, practical explanations of business statistical ideas, techniques, formulas, and calculations, w

  9. Head First Statistics

    CERN Document Server

    Griffiths, Dawn

    2009-01-01

    Wouldn't it be great if there were a statistics book that made histograms, probability distributions, and chi square analysis more enjoyable than going to the dentist? Head First Statistics brings this typically dry subject to life, teaching you everything you want and need to know about statistics through engaging, interactive, and thought-provoking material, full of puzzles, stories, quizzes, visual aids, and real-world examples. Whether you're a student, a professional, or just curious about statistical analysis, Head First's brain-friendly formula helps you get a firm grasp of statistics

  10. v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII

    DEFF Research Database (Denmark)

    Disela, C; Glineur, C; Bugge, T

    1991-01-01

    The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte...... of this CAII reporter construct could only be suppressed by very high amounts of v-erbA. Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein....

  11. Extracellular Signal-Regulated Kinase 5 is Required for Low-Concentration H2O2-Induced Angiogenesis of Human Umbilical Vein Endothelial Cells.

    Science.gov (United States)

    Jiang, Shan; Zhang, Dongxin; Huang, Hong; Lei, Yonghong; Han, Yan; Han, Weidong

    2017-01-01

    Background . The aim of this study was to assess the effects of low concentrations of H 2 O 2 on angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and explore the underlying mechanisms. Methods . HUVECs were cultured and stimulated with different concentrations of H 2 O 2 . Flow cytometric analysis was used to select an optimal concentration of H 2 O 2 for the following experiments. Cell proliferation, migration, and tubule formation were evaluated by Cell Counting Kit-8 (CCK-8) assays, scratch wound assays, and Matrigel tubule formation assays, respectively. For gain and loss of function studies, constitutively active MEK5 (CA-MEK5) and ERK5 shRNA lentiviruses were used to activate or knock down extracellular signal-regulated kinase 5 (ERK5). Results . We found that low concentrations of H 2 O 2 promoted HUVECs proliferation, migration, and tubule formation. ERK5 in HUVECs was significantly activated by H 2 O 2 . Enhanced ERK5 activity significantly amplified the proangiogenic effects of H 2 O 2 ; in contrast, ERK5 knock-down abrogated the effects of H 2 O 2 . Conclusions . Our results confirmed that low concentrations of H 2 O 2 promoted HUVECs angiogenesis in vitro, and ERK5 is an essential mediator of this process. Therefore, ERK5 may be a potential therapeutic target for promoting angiogenesis and improving graft survival.

  12. Feedback-regulated poly(ADP-ribosyl)ation by PARP-1 is required for rapid response to DNA damage in living cells

    Science.gov (United States)

    Mortusewicz, Oliver; Amé, Jean-Christophe; Leonhardt, Heinrich

    2007-01-01

    Genome integrity is constantly threatened by DNA lesions arising from numerous exogenous and endogenous sources. Survival depends on immediate recognition of these lesions and rapid recruitment of repair factors. Using laser microirradiation and live cell microscopy we found that the DNA-damage dependent poly(ADP-ribose) polymerases (PARP) PARP-1 and PARP-2 are recruited to DNA damage sites, however, with different kinetics and roles. With specific PARP inhibitors and mutations, we could show that the initial recruitment of PARP-1 is mediated by the DNA-binding domain. PARP-1 activation and localized poly(ADP-ribose) synthesis then generates binding sites for a second wave of PARP-1 recruitment and for the rapid accumulation of the loading platform XRCC1 at repair sites. Further PARP-1 poly(ADP-ribosyl)ation eventually initiates the release of PARP-1. We conclude that feedback regulated recruitment of PARP-1 and concomitant local poly(ADP-ribosyl)ation at DNA lesions amplifies a signal for rapid recruitment of repair factors enabling efficient restoration of genome integrity. PMID:17982172

  13. Modern requirements of legal regulations for transport in the cities and necessity for making sector strategy in order to harmonize with other modes of transport

    Directory of Open Access Journals (Sweden)

    Aleksandra VASILJ

    2010-01-01

    Full Text Available Crucial problem of transport in the cities, as a source of pollution of the environment, are uncontrolled individual motorization, permanently increasing number of motor vehicles on the roads and streets that expels human primary need for walking.Reduced social area is also loaded with vibrations and increased sound pressure which often exceeds recommended 80 dB/A.Accent is on ecological problems caused by: polluted air, which comes from gas emissions (full of aerosol, metals, dust, soot, smoke, cutting and disappearance of green areas in order to provide space for transport, making huge amount of secondary waste (e. g. tyres, metal, used oil, liquids.To improve present sequences and reduce negative effects in the future it is necessary to take different measures: fiscal, administrative, educational, which will restrict use of individual, particularly car traffic. Same measures should be used to encourage users to use public transportation.Transport in the cities, with all weaknesses and comparative advantages, should be separately analyzed mode of road transport and also be an individual part in strategic documents.The most important questions that such strategy of transport in the cities should include are: regulation, privatization or other more efficient mode of organization in public transport of passengers, as well as urban elements of sustainable development of the urban areas and transport.

  14. Lectures on algebraic statistics

    CERN Document Server

    Drton, Mathias; Sullivant, Seth

    2009-01-01

    How does an algebraic geometer studying secant varieties further the understanding of hypothesis tests in statistics? Why would a statistician working on factor analysis raise open problems about determinantal varieties? Connections of this type are at the heart of the new field of "algebraic statistics". In this field, mathematicians and statisticians come together to solve statistical inference problems using concepts from algebraic geometry as well as related computational and combinatorial techniques. The goal of these lectures is to introduce newcomers from the different camps to algebraic statistics. The introduction will be centered around the following three observations: many important statistical models correspond to algebraic or semi-algebraic sets of parameters; the geometry of these parameter spaces determines the behaviour of widely used statistical inference procedures; computational algebraic geometry can be used to study parameter spaces and other features of statistical models.

  15. Statistics for economics

    CERN Document Server

    Naghshpour, Shahdad

    2012-01-01

    Statistics is the branch of mathematics that deals with real-life problems. As such, it is an essential tool for economists. Unfortunately, the way you and many other economists learn the concept of statistics is not compatible with the way economists think and learn. The problem is worsened by the use of mathematical jargon and complex derivations. Here's a book that proves none of this is necessary. All the examples and exercises in this book are constructed within the field of economics, thus eliminating the difficulty of learning statistics with examples from fields that have no relation to business, politics, or policy. Statistics is, in fact, not more difficult than economics. Anyone who can comprehend economics can understand and use statistics successfully within this field, including you! This book utilizes Microsoft Excel to obtain statistical results, as well as to perform additional necessary computations. Microsoft Excel is not the software of choice for performing sophisticated statistical analy...

  16. A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.

    Science.gov (United States)

    Demoulin, J B; Uyttenhove, C; Van Roost, E; DeLestré, B; Donckers, D; Van Snick, J; Renauld, J C

    1996-09-01

    Interleukin-9 (IL-9), a T-cell-derived cytokine, interacts with a specific receptor associated with the IL-2 receptor gamma chain. In this report, we analyze the functional domains of the human IL-9 receptor transfected into mouse lymphoid cell lines. Three different functions were examined: growth stimulation in factor-dependent pro-B Ba/F3 cells, protection against dexamethasone-induced apoptosis, and Ly-6A2 induction in BW5147 lymphoma cells. The results indicated that a single tyrosine, at position 116 in the cytoplasmic domain, was required for all three activities. In addition, we observed that human IL-9 reduced the proliferation rate of transfected BW5147 cells, an effect also dependent on the same tyrosine. This amino acid was necessary for IL-9-mediated tyrosine phosphorylation of the receptor and for STAT activation but not for IRS-2/4PS activation or for JAK1 phosphorylation, which depended on a domain closer to the plasma membrane. We also showed that JAK1 was constitutively associated with the IL-9 receptor. Activated STAT complexes induced by IL-9 were found to contain STAT1, STAT3, and STAT5 transcription factors. Moreover, sequence homologies between human IL-9 receptor tyrosine 116 and tyrosines (of other receptors activating STAT3 and STAT5 were observed. Taken together, these data indicate that a single tyrosine of the IL-9 receptor, required for activation of three different STAT proteins, is necessary for distinct activities of this cytokine, including proliferative responses.

  17. Ste12/Fab1 phosphatidylinositol-3-phosphate 5-kinase is required for nitrogen-regulated mitotic commitment and cell size control.

    Directory of Open Access Journals (Sweden)

    David Cobley

    Full Text Available Tight coupling of cell growth and cell cycle progression enable cells to adjust their rate of division, and therefore size, to the demands of proliferation in varying nutritional environments. Nutrient stress promotes inhibition of Target Of Rapamycin Complex 1 (TORC1 activity. In fission yeast, reduced TORC1 activity advances mitotic onset and switches growth to a sustained proliferation at reduced cell size. A screen for mutants, that failed to advance mitosis upon nitrogen stress, identified a mutant in the PIKFYVE 1-phosphatidylinositol-3-phosphate 5-kinase fission yeast homolog Ste12. Ste12PIKFYVE deficient mutants were unable to advance the cell cycle to reduce cell size after a nitrogen downshift to poor nitrogen (proline growth conditions. While it is well established that PI(3,5P2 signalling is required for autophagy and that Ste12PIKFYVE mutants have enlarged vacuoles (yeast lysosomes, neither a block to autophagy or mutants that independently have enlarged vacuoles had any impact upon nitrogen control of mitotic commitment. The addition of rapamycin to Ste12PIKFYVE deficient mutants reduced cell size at division to suggest that Ste12PIKFYVE possibly functions upstream of TORC1. ste12 mutants display increased Torin1 (TOR inhibitor sensitivity. However, no major impact on TORC1 or TORC2 activity was observed in the ste12 deficient mutants. In summary, Ste12PIKFYVE is required for nitrogen-stress mediated advancement of mitosis to reduce cell size at division.

  18. Modern Thermodynamics with Statistical Mechanics

    CERN Document Server

    Helrich, Carl S

    2009-01-01

    With the aim of presenting thermodynamics in as simple and as unified a form as possible, this textbook starts with an introduction to the first and second laws and then promptly addresses the complete set of the potentials in a subsequent chapter and as a central theme throughout. Before discussing modern laboratory measurements, the book shows that the fundamental quantities sought in the laboratory are those which are required for determining the potentials. Since the subjects of thermodynamics and statistical mechanics are a seamless whole, statistical mechanics is treated as integral part of the text. Other key topics such as irreversibility, the ideas of Ilya Prigogine, chemical reaction rates, equilibrium of heterogeneous systems, and transition-state theory serve to round out this modern treatment. An additional chapter covers quantum statistical mechanics due to active current research in Bose-Einstein condensation. End-of-chapter exercises, chapter summaries, and an appendix reviewing fundamental pr...

  19. Baseline Statistics of Linked Statistical Data

    NARCIS (Netherlands)

    Scharnhorst, Andrea; Meroño-Peñuela, Albert; Guéret, Christophe

    2014-01-01

    We are surrounded by an ever increasing ocean of information, everybody will agree to that. We build sophisticated strategies to govern this information: design data models, develop infrastructures for data sharing, building tool for data analysis. Statistical datasets curated by National

  20. HCN4 ion channel function is required for early events that regulate anatomical left-right patterning in a nodal and lefty asymmetric gene expression-independent manner.

    Science.gov (United States)

    Pai, Vaibhav P; Willocq, Valerie; Pitcairn, Emily J; Lemire, Joan M; Paré, Jean-François; Shi, Nian-Qing; McLaughlin, Kelly A; Levin, Michael

    2017-10-15

    Laterality is a basic characteristic of all life forms, from single cell organisms to complex plants and animals. For many metazoans, consistent left-right asymmetric patterning is essential for the correct anatomy of internal organs, such as the heart, gut, and brain; disruption of left-right asymmetry patterning leads to an important class of birth defects in human patients. Laterality functions across multiple scales, where early embryonic, subcellular and chiral cytoskeletal events are coupled with asymmetric amplification mechanisms and gene regulatory networks leading to asymmetric physical forces that ultimately result in distinct left and right anatomical organ patterning. Recent studies have suggested the existence of multiple parallel pathways regulating organ asymmetry. Here, we show that an isoform of the hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels (hyperpolarization-activated cyclic nucleotide-gated channel 4, HCN4) is important for correct left-right patterning. HCN4 channels are present very early in Xenopus embryos. Blocking HCN channels ( I h currents) with pharmacological inhibitors leads to errors in organ situs. This effect is only seen when HCN4 channels are blocked early (pre-stage 10) and not by a later block (post-stage 10). Injections of HCN4-DN (dominant-negative) mRNA induce left-right defects only when injected in both blastomeres no later than the 2-cell stage. Analysis of key asymmetric genes' expression showed that the sidedness of Nodal , Lefty , and Pitx2 expression is largely unchanged by HCN4 blockade, despite the randomization of subsequent organ situs, although the area of Pitx2 expression was significantly reduced. Together these data identify a novel, developmental role for HCN4 channels and reveal a new Nodal-Lefty-Pitx2 asymmetric gene expression-independent mechanism upstream of organ positioning during embryonic left-right patterning. © 2017. Published by The Company of Biologists Ltd.

  1. Extracellular signal-regulated kinase 1 and 2 are not required for GnRH neuron development and normal female reproductive axis function in mice.

    Science.gov (United States)

    Wierman, Margaret E; Xu, Mei; Pierce, A; Bliesner, B; Bliss, S P; Roberson, M S

    2012-01-01

    Selective deletion of extracellular signal-regulated kinase (ERK) 1 and ERK2 in the pituitary gonadotrope and ovarian granulosa cells disrupts female reproductive axis function. Thus, we asked if ERK1 and ERK2 are critical for GnRH neuron ontogeny or the central control of female reproductive function. GnRH-Cre-recombinase (Cre+) expressing mice were crossed with mice with a global deletion of ERK1 and a floxed ERK2 allele (Erk1-/Erk2fl/fl) to selectively delete ERK2 in GnRH neurons. Cre-recombinase mRNA was selectively expressed in the brain of Cre+ mice. GnRH neuron number and location were determined during embryogenesis and in the adult. GnRH neuron counts at E15 did not differ between experimental and control groups (1,198 ± 65 and 1,160 ± 80 respectively, p = NS). In adults, numbers of GnRH neurons in the GnRHCre+Erk1-/Erk2- mice (741 ± 157) were similar to those in controls (756 ± 7), without alteration in their distribution across the forebrain. ERK1 and 2 deficiency did not alter the timing of vaginal opening, age at first estrus, or estrous cyclicity. Although ERK1 and 2 are components of a dominant signaling pathway in GnRH neuronal cells that modulates survival and control of GnRH gene expression, other signaling pathways compensate for their deletion in vivo to allow GnRH neuron survival and targeting and normal onset of female sexual maturation and reproductive function. In contrast to effects at the pituitary and the ovary, ERK1 and ERK2 are dispensable at the level of the GnRH neuron. Copyright © 2011 S. Karger AG, Basel.

  2. 29 CFR 2201.10 - Maintenance of statistics.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Maintenance of statistics. 2201.10 Section 2201.10 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH REVIEW COMMISSION REGULATIONS IMPLEMENTING THE FREEDOM OF INFORMATION ACT § 2201.10 Maintenance of statistics. (a) The FOIA Disclosure...

  3. FDA & digital mammography: why has FDA required full field digital mammography systems to be regulated as potentially dangerous devices for more than 10 years?

    Science.gov (United States)

    Nields, Morgan W

    2010-05-01

    Digital mammography is routinely used in the US to screen asymptomatic women for breast cancer and currently over 50% of US screening centers employ the technology. In spite of FDAs knowledge that digital mammography requires less radiation than film mammography and that its equivalence has been proven in a prospective randomized trial, the agency has failed to allow the technology market access via the 510(k) pre market clearance pathway. As a result of the restrictive Pre Market Approval process, only four suppliers have received FDA approval. The resulting lack of a competitive market has kept costs high, restricted technological innovation, and impeded product improvements as a result of PMA requirements. Meanwhile, at least twelve companies are on the market in the EU and the resulting competitive market has lowered costs and provided increased technological choice. A cultural change with new leadership occurred in the early 90's at FDA. The historical culture at the Center for Devices and Radiological Health of collaboration and education gave way to one characterized by a lack of reliance on outside scientific expertise, tolerance of decision making by unqualified reviewers, and an emphasis on enforcement and punishment. Digital mammography fell victim to this cultural change and as a result major innovations like breast CT and computer aided detection technologies are also withheld from the market. The medical device law, currently under review by the Institute of Medicine, should be amended by the Congress so that new technologies can be appropriately classified in accordance with the risk based assessment classification system detailed in Chapter V of the Federal Food, Drug, and Cosmetic Act. A panel of scientific experts chartered by the NIH or IOM should determine the classification appropriate for new technologies that have no historical regulatory framework. This would be binding on FDA. Unless the law is changed we will likely again experience

  4. Statistical Physics An Introduction

    CERN Document Server

    Yoshioka, Daijiro

    2007-01-01

    This book provides a comprehensive presentation of the basics of statistical physics. The first part explains the essence of statistical physics and how it provides a bridge between microscopic and macroscopic phenomena, allowing one to derive quantities such as entropy. Here the author avoids going into details such as Liouville’s theorem or the ergodic theorem, which are difficult for beginners and unnecessary for the actual application of the statistical mechanics. In the second part, statistical mechanics is applied to various systems which, although they look different, share the same mathematical structure. In this way readers can deepen their understanding of statistical physics. The book also features applications to quantum dynamics, thermodynamics, the Ising model and the statistical dynamics of free spins.

  5. Statistical symmetries in physics

    International Nuclear Information System (INIS)

    Green, H.S.; Adelaide Univ., SA

    1994-01-01

    Every law of physics is invariant under some group of transformations and is therefore the expression of some type of symmetry. Symmetries are classified as geometrical, dynamical or statistical. At the most fundamental level, statistical symmetries are expressed in the field theories of the elementary particles. This paper traces some of the developments from the discovery of Bose statistics, one of the two fundamental symmetries of physics. A series of generalizations of Bose statistics is described. A supersymmetric generalization accommodates fermions as well as bosons, and further generalizations, including parastatistics, modular statistics and graded statistics, accommodate particles with properties such as 'colour'. A factorization of elements of ggl(n b ,n f ) can be used to define truncated boson operators. A general construction is given for q-deformed boson operators, and explicit constructions of the same type are given for various 'deformed' algebras. A summary is given of some of the applications and potential applications. 39 refs., 2 figs

  6. The statistical stability phenomenon

    CERN Document Server

    Gorban, Igor I

    2017-01-01

    This monograph investigates violations of statistical stability of physical events, variables, and processes and develops a new physical-mathematical theory taking into consideration such violations – the theory of hyper-random phenomena. There are five parts. The first describes the phenomenon of statistical stability and its features, and develops methods for detecting violations of statistical stability, in particular when data is limited. The second part presents several examples of real processes of different physical nature and demonstrates the violation of statistical stability over broad observation intervals. The third part outlines the mathematical foundations of the theory of hyper-random phenomena, while the fourth develops the foundations of the mathematical analysis of divergent and many-valued functions. The fifth part contains theoretical and experimental studies of statistical laws where there is violation of statistical stability. The monograph should be of particular interest to engineers...

  7. Prelimbic cortex extracellular signal-regulated kinase 1/2 activation is required for memory retrieval of long-term inhibitory avoidance.

    Science.gov (United States)

    Luo, Fei; Zheng, Jian; Sun, Xuan; Deng, Wei-Ke; Li, Bao Ming; Liu, Fang

    2017-04-15

    Neural mechanism underlying memory retrieval has been extensively studied in the hippocampus and amygdala. However, little is known about the role of medial prefrontal cortex in long-term memory retrieval. We evaluate this issue in one-trial step-through inhibitory avoidance (IA) paradigm. Our results showed that, 1) inactivation of mPFC by local infusion of GABA A -receptor agonist muscimol caused severe deficits in retrieval of 1-day and 7-day but had no effects on 2-h inhibitory avoidance memory; 2) the protein level of phosphorylated-ERK1/2 in mPFC were significantly increased following retrieval of 1-day and 7-day IA memory, so did the numbers of phosphorylated-ERK (pERK) and phosphorylated-CREB (pCREB) labeled neurons; 3) intra-mPFC infusion of ERK kinase inhibitor PD98095 significantly reduced phosphorylated ERK1/2 levels and phosphorylated-ERK1/2 and phosphorylated-CREB labeled cells, and severely impaired retrieval of 7-day IA memory when the drugs were administrated 30min prior to test. The present study provides evidence that retrieval of long-lasting memory for inhibitory avoidance requires mPFC and involves the ERK-CREB signaling cascade. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Equilibrium statistical mechanics

    CERN Document Server

    Jackson, E Atlee

    2000-01-01

    Ideal as an elementary introduction to equilibrium statistical mechanics, this volume covers both classical and quantum methodology for open and closed systems. Introductory chapters familiarize readers with probability and microscopic models of systems, while additional chapters describe the general derivation of the fundamental statistical mechanics relationships. The final chapter contains 16 sections, each dealing with a different application, ordered according to complexity, from classical through degenerate quantum statistical mechanics. Key features include an elementary introduction t

  9. Applied statistics for economists

    CERN Document Server

    Lewis, Margaret

    2012-01-01

    This book is an undergraduate text that introduces students to commonly-used statistical methods in economics. Using examples based on contemporary economic issues and readily-available data, it not only explains the mechanics of the various methods, it also guides students to connect statistical results to detailed economic interpretations. Because the goal is for students to be able to apply the statistical methods presented, online sources for economic data and directions for performing each task in Excel are also included.

  10. Mineral industry statistics 1975

    Energy Technology Data Exchange (ETDEWEB)

    1978-01-01

    Production, consumption and marketing statistics are given for solid fuels (coal, peat), liquid fuels and gases (oil, natural gas), iron ore, bauxite and other minerals quarried in France, in 1975. Also accident statistics are included. Production statistics are presented of the Overseas Departments and territories (French Guiana, New Caledonia, New Hebrides). An account of modifications in the mining field in 1975 is given. Concessions, exploitation permits, and permits solely for prospecting for mineral products are discussed. (In French)

  11. Introduction to Statistics

    Directory of Open Access Journals (Sweden)

    Mirjam Nielen

    2017-01-01

    Full Text Available Always wondered why research papers often present rather complicated statistical analyses? Or wondered how to properly analyse the results of a pragmatic trial from your own practice? This talk will give an overview of basic statistical principles and focus on the why of statistics, rather than on the how.This is a podcast of Mirjam's talk at the Veterinary Evidence Today conference, Edinburgh November 2, 2016. 

  12. Equilibrium statistical mechanics

    CERN Document Server

    Mayer, J E

    1968-01-01

    The International Encyclopedia of Physical Chemistry and Chemical Physics, Volume 1: Equilibrium Statistical Mechanics covers the fundamental principles and the development of theoretical aspects of equilibrium statistical mechanics. Statistical mechanical is the study of the connection between the macroscopic behavior of bulk matter and the microscopic properties of its constituent atoms and molecules. This book contains eight chapters, and begins with a presentation of the master equation used for the calculation of the fundamental thermodynamic functions. The succeeding chapters highlight t

  13. Contributions to statistics

    CERN Document Server

    Mahalanobis, P C

    1965-01-01

    Contributions to Statistics focuses on the processes, methodologies, and approaches involved in statistics. The book is presented to Professor P. C. Mahalanobis on the occasion of his 70th birthday. The selection first offers information on the recovery of ancillary information and combinatorial properties of partially balanced designs and association schemes. Discussions focus on combinatorial applications of the algebra of association matrices, sample size analogy, association matrices and the algebra of association schemes, and conceptual statistical experiments. The book then examines latt

  14. IAEA news: • Newcomer countries face common challenges in nuclear infrastructure development. • Safety and licensing requirements for small modular reactors: IAEA hosts first workshop for regulators. • IAEA reaches milestone in disposal of radioactive sources

    International Nuclear Information System (INIS)

    Kollar, Lenka; Dyck, Elisabeth; Dixit, Aabha; Gaspar, Miklos; Gil, Laura

    2016-01-01

    • Newcomer countries face common challenges in nuclear infrastructure development: Countries embarking on a nuclear power programme need to make sure that the development of their legal, regulatory and support infrastructure keeps pace with the construction of the power plant itself. This is the only way to ensure that the programme proceeds in a safe, secure and sustainable way, concluded participants of a workshop on nuclear power infrastructure development hosted at the IAEA last February. • Safety and licensing requirements for small modular reactors: IAEA hosts first workshop for regulators: A new generation of advanced, prefab nuclear power reactors called small modular reactors (SMRs) could be licensed and hit the market as early as 2020, and the IAEA is helping regulators prepare for their debut. In a series of workshops that began earlier this year, the IAEA is working closely with regulators on approaches to safety and licensing ahead of potential SMR deployment worldwide. • IAEA reaches milestone in disposal of radioactive sources: Successful tests of a promising technology for moving and storing low level radioactive sealed sources are paving the way for a new disposal method for dealing with small volumes of radioactive waste around the world. The method, which involves placing and covering sealed sources in a narrow hole a few hundred metres deep, would allow countries to safely and securely take charge of their own disused radioactive sources. The proof of concept for the technology was tested in Croatia late last year — without the use of actual radioactive material.

  15. The exemption from the requirement of registration and/or licensing of some sources. machines and devices emitting ionizing and /or on ionizing radiation: a proposed draft for Israeli regulations

    Energy Technology Data Exchange (ETDEWEB)

    Schlesinger, T; Margaliot, M [Israel Atomic Energy Commission, Yavne (Israel). Soreq Nuclear Research Center

    1997-11-16

    The licensing and authorization of the import, purchase, distribution, transportation and application of radioactive materials and devices emitting ionizing and/or non-ionizing radiation are carried out in Israel by the Ministries of the Environment and of Health. The legal basis for file authority of these Ministries in radiation protection matters is file {sup P}harmacists Regulation- Radioactive Elements and Products Thereof, 1981 (revision 1994) (PRREPT). Licenses are issued by the Chief Radiation Executive (CUE) appointed by the Minister of the Environment and the Minister of Health. The Regulations include a clause which enables the CUE to exempt certain amounts of radioactive materials from file requirements laid down in the PRREPT. The exemption clause is general and does not indicate the types and amounts of radioactive material may be exempted. The proposed draft Israeli regulations are related to exemption of some sources, machines and devices emitting ionizing and non-ionizing radiation, wife a suggestion to extend file above mentioned exemption clause to include some machines and devices and to provide an explicit and detailed list of materials, sources and devices to be exempted. Among these are the following: (authors)

  16. The exemption from the requirement of registration and/or licensing of some sources. machines and devices emitting ionizing and /or on ionizing radiation: a proposed draft for Israeli regulations

    International Nuclear Information System (INIS)

    Schlesinger, T.; Margaliot, M.

    1997-01-01

    The licensing and authorization of the import, purchase, distribution, transportation and application of radioactive materials and devices emitting ionizing and/or non-ionizing radiation are carried out in Israel by the Ministries of the Environment and of Health. The legal basis for file authority of these Ministries in radiation protection matters is file P harmacists Regulation- Radioactive Elements and Products Thereof, 1981 (revision 1994) (PRREPT). Licenses are issued by the Chief Radiation Executive (CUE) appointed by the Minister of the Environment and the Minister of Health. The Regulations include a clause which enables the CUE to exempt certain amounts of radioactive materials from file requirements laid down in the PRREPT. The exemption clause is general and does not indicate the types and amounts of radioactive material may be exempted. The proposed draft Israeli regulations are related to exemption of some sources, machines and devices emitting ionizing and non-ionizing radiation, wife a suggestion to extend file above mentioned exemption clause to include some machines and devices and to provide an explicit and detailed list of materials, sources and devices to be exempted. Among these are the following: (authors)

  17. Statistics in a Nutshell

    CERN Document Server

    Boslaugh, Sarah

    2008-01-01

    Need to learn statistics as part of your job, or want some help passing a statistics course? Statistics in a Nutshell is a clear and concise introduction and reference that's perfect for anyone with no previous background in the subject. This book gives you a solid understanding of statistics without being too simple, yet without the numbing complexity of most college texts. You get a firm grasp of the fundamentals and a hands-on understanding of how to apply them before moving on to the more advanced material that follows. Each chapter presents you with easy-to-follow descriptions illustrat

  18. Understanding Computational Bayesian Statistics

    CERN Document Server

    Bolstad, William M

    2011-01-01

    A hands-on introduction to computational statistics from a Bayesian point of view Providing a solid grounding in statistics while uniquely covering the topics from a Bayesian perspective, Understanding Computational Bayesian Statistics successfully guides readers through this new, cutting-edge approach. With its hands-on treatment of the topic, the book shows how samples can be drawn from the posterior distribution when the formula giving its shape is all that is known, and how Bayesian inferences can be based on these samples from the posterior. These ideas are illustrated on common statistic

  19. Annual Statistical Supplement, 2002

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2002 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  20. Annual Statistical Supplement, 2010

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2010 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  1. Annual Statistical Supplement, 2007

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2007 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  2. Annual Statistical Supplement, 2001

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2001 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  3. Annual Statistical Supplement, 2016

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2016 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  4. Annual Statistical Supplement, 2011

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2011 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  5. Annual Statistical Supplement, 2005

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2005 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  6. Annual Statistical Supplement, 2015

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2015 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  7. Annual Statistical Supplement, 2003

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2003 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  8. Annual Statistical Supplement, 2017

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2017 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  9. Annual Statistical Supplement, 2008

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2008 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  10. Annual Statistical Supplement, 2014

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2014 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  11. Annual Statistical Supplement, 2004

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2004 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  12. Annual Statistical Supplement, 2000

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2000 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  13. Annual Statistical Supplement, 2009

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2009 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  14. Annual Statistical Supplement, 2006

    Data.gov (United States)

    Social Security Administration — The Annual Statistical Supplement, 2006 includes the most comprehensive data available on the Social Security and Supplemental Security Income programs. More than...

  15. Principles of statistics

    CERN Document Server

    Bulmer, M G

    1979-01-01

    There are many textbooks which describe current methods of statistical analysis, while neglecting related theory. There are equally many advanced textbooks which delve into the far reaches of statistical theory, while bypassing practical applications. But between these two approaches is an unfilled gap, in which theory and practice merge at an intermediate level. Professor M. G. Bulmer's Principles of Statistics, originally published in 1965, was created to fill that need. The new, corrected Dover edition of Principles of Statistics makes this invaluable mid-level text available once again fo

  16. 100 statistical tests

    CERN Document Server

    Kanji, Gopal K

    2006-01-01

    This expanded and updated Third Edition of Gopal K. Kanji's best-selling resource on statistical tests covers all the most commonly used tests with information on how to calculate and interpret results with simple datasets. Each entry begins with a short summary statement about the test's purpose, and contains details of the test objective, the limitations (or assumptions) involved, a brief outline of the method, a worked example, and the numerical calculation. 100 Statistical Tests, Third Edition is the one indispensable guide for users of statistical materials and consumers of statistical information at all levels and across all disciplines.

  17. Statistical distribution sampling

    Science.gov (United States)

    Johnson, E. S.

    1975-01-01

    Determining the distribution of statistics by sampling was investigated. Characteristic functions, the quadratic regression problem, and the differential equations for the characteristic functions are analyzed.

  18. Basic statistics with Microsoft Excel: a review.

    Science.gov (United States)

    Divisi, Duilio; Di Leonardo, Gabriella; Zaccagna, Gino; Crisci, Roberto

    2017-06-01

    The scientific world is enriched daily with new knowledge, due to new technologies and continuous discoveries. The mathematical functions explain the statistical concepts particularly those of mean, median and mode along with those of frequency and frequency distribution associated to histograms and graphical representations, determining elaborative processes on the basis of the spreadsheet operations. The aim of the study is to highlight the mathematical basis of statistical models that regulate the operation of spreadsheets in Microsoft Excel.

  19. [''R"--project for statistical computing

    DEFF Research Database (Denmark)

    Dessau, R.B.; Pipper, Christian Bressen

    2008-01-01

    An introduction to the R project for statistical computing (www.R-project.org) is presented. The main topics are: 1. To make the professional community aware of "R" as a potent and free software for graphical and statistical analysis of medical data; 2. Simple well-known statistical tests are fai...... are fairly easy to perform in R, but more complex modelling requires programming skills; 3. R is seen as a tool for teaching statistics and implementing complex modelling of medical data among medical professionals Udgivelsesdato: 2008/1/28......An introduction to the R project for statistical computing (www.R-project.org) is presented. The main topics are: 1. To make the professional community aware of "R" as a potent and free software for graphical and statistical analysis of medical data; 2. Simple well-known statistical tests...

  20. Activation of Extracellular Signal-Regulated Kinase but Not of p38 Mitogen-Activated Protein Kinase Pathways in Lymphocytes Requires Allosteric Activation of SOS

    Science.gov (United States)

    Jun, Jesse E.; Yang, Ming; Chen, Hang; Chakraborty, Arup K.

    2013-01-01

    Thymocytes convert graded T cell receptor (TCR) signals into positive selection or deletion, and activation of extracellular signal-related kinase (ERK), p38, and Jun N-terminal protein kinase (JNK) mitogen-activated protein kinases (MAPKs) has been postulated to play a discriminatory role. Two families of Ras guanine nucleotide exchange factors (RasGEFs), SOS and RasGRP, activate Ras and the downstream RAF-MEK-ERK pathway. The pathways leading to lymphocyte p38 and JNK activation are less well defined. We previously described how RasGRP alone induces analog Ras-ERK activation while SOS and RasGRP cooperate to establish bimodal ERK activation. Here we employed computational modeling and biochemical experiments with model cell lines and thymocytes to show that TCR-induced ERK activation grows exponentially in thymocytes and that a W729E allosteric pocket mutant, SOS1, can only reconstitute analog ERK signaling. In agreement with RasGRP allosterically priming SOS, exponential ERK activation is severely decreased by pharmacological or genetic perturbation of the phospholipase Cγ (PLCγ)-diacylglycerol-RasGRP1 pathway. In contrast, p38 activation is not sharply thresholded and requires high-level TCR signal input. Rac and p38 activation depends on SOS1 expression but not allosteric activation. Based on computational predictions and experiments exploring whether SOS functions as a RacGEF or adaptor in Rac-p38 activation, we established that the presence of SOS1, but not its enzymatic activity, is critical for p38 activation. PMID:23589333