Quality Management Program

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

Not Available

1991-10-01

According to {section} 35.32, Quality Management Program,'' of 10 CFR Part 35, Medical Use of Byproduct Material,'' applicants or licensees, as applicable, are required to establish a quality management (QM) program. This regulatory guide provides guidance to licensees and applicants for developing policies and procedures for the QM program. This guide does not restrict or limit the licensee from using other guidance that may be equally useful in developing a QM program, e.g., information available from the Joint Commission on Accreditation of Healthcare Organizations or the American College of Radiology. Any information collection activities mentioned in this regulatory guide aremore » contained as requirements in 10 CFR Part 35, which provides the regulatory basis for this guide. This information collection requirements in 10 CFR Part 35 have been cleared under OMB Clearance No. 3150-0010.« less

Silver nanoparticles: Synthesis methods, bio-applications and properties.

PubMed

Abbasi, Elham; Milani, Morteza; Fekri Aval, Sedigheh; Kouhi, Mohammad; Akbarzadeh, Abolfazl; Tayefi Nasrabadi, Hamid; Nikasa, Parisa; Joo, San Woo; Hanifehpour, Younes; Nejati-Koshki, Kazem; Samiei, Mohammad

2016-01-01

Silver nanoparticles size makes wide range of new applications in various fields of industry. Synthesis of noble metal nanoparticles for applications such as catalysis, electronics, optics, environmental and biotechnology is an area of constant interest. Two main methods for Silver nanoparticles are the physical and chemical methods. The problem with these methods is absorption of toxic substances onto them. Green synthesis approaches overcome this limitation. Silver nanoparticles size makes wide range of new applications in various fields of industry. This article summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations with respect to the biomedical applicability and regulatory requirements concerning silver nanoparticles.

77 FR 23109 - Airworthiness Directives; Agusta S.p.A. Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

... contains regulatory documents #0;having general applicability and legal effect, most of which are keyed #0... establishing a revised life limit for each tail rotor (T/R) blade and updating the helicopter's historical... life limit for each T/R blade and updating the helicopter's historical records, repetitively inspecting...

76 FR 74078 - Standard Mail Market Test

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-30

... POSTAL REGULATORY COMMISSION [Docket No. MT2011-3; Order No. 998] Standard Mail Market Test AGENCY... Service application for an exemption from the annual revenue limitation that applies to market tests of... limitation in any year during the test of an experimental market dominant product.\\1\\ Pursuant to 39 U.S.C...

10 CFR 2.102 - Administrative review of application.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF... proceeding to confer with the NRC staff informally. In the case of docketed application for a limited work... completion of its review. (b) The Director, Office of Nuclear Reactor Regulation, Director, Office of New...

75 FR 80097 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-21

... LLC Establishing Strike Price Intervals of $1 and Increasing Position and Exercise Limits With Respect... ``Index'') to (i) establish strike price intervals of $1.00 and (ii) increase the position and exercise... price intervals of $1.00 and (ii) increase the position and exercise limits applicable thereto. The...

Two Decades of WRF/CMAQ simulations over the continental United States: New approaches for performing dynamic model evaluation and determining confidence limits for ozone exceedances

EPA Science Inventory

Confidence in the application of models for forecasting and regulatory assessments is furthered by conducting four types of model evaluation: operational, dynamic, diagnostic, and probabilistic. Operational model evaluation alone does not reveal the confidence limits that can be ...

Regulatory aviation medicine : its philosophies and limitations.

DOT National Transportation Integrated Search

1982-09-01

The application of aviation medicine is relatively standardized throughout the world, both in civil and military operations. Substantial differences exist, however, in the way different countries, or even different agencies in the same country, deter...

Gene network inference and visualization tools for biologists: application to new human transcriptome datasets

PubMed Central

Hurley, Daniel; Araki, Hiromitsu; Tamada, Yoshinori; Dunmore, Ben; Sanders, Deborah; Humphreys, Sally; Affara, Muna; Imoto, Seiya; Yasuda, Kaori; Tomiyasu, Yuki; Tashiro, Kosuke; Savoie, Christopher; Cho, Vicky; Smith, Stephen; Kuhara, Satoru; Miyano, Satoru; Charnock-Jones, D. Stephen; Crampin, Edmund J.; Print, Cristin G.

2012-01-01

Gene regulatory networks inferred from RNA abundance data have generated significant interest, but despite this, gene network approaches are used infrequently and often require input from bioinformaticians. We have assembled a suite of tools for analysing regulatory networks, and we illustrate their use with microarray datasets generated in human endothelial cells. We infer a range of regulatory networks, and based on this analysis discuss the strengths and limitations of network inference from RNA abundance data. We welcome contact from researchers interested in using our inference and visualization tools to answer biological questions. PMID:22121215

Capacity for ethical and regulatory review of herbal trials in developing countries: a case study of Moringa oleifera research in HIV-infected patients.

PubMed

Monera-Penduka, Tsitsi G; Maponga, Charles C; Morse, Gene D; Nhachi, Charles F B

2017-01-01

Lack of regulatory capacity limits the conduct of ethical and rigorous trials of herbal medicines in developing countries. Sharing ethical and regulatory experiences of successful herbal trials may accelerate the field while assuring human subjects protection. The methods and timelines for the ethical and regulatory review processes for the first drug regulatory authority approved herbal trial in Zimbabwe are described in this report. The national drug regulatory authority and ethics committee were engaged for pre-submission discussions. Six applications were submitted. Application procedures and communications with the various regulatory and ethics review boards were reviewed. Key issues raised and timelines for communications were summarized. There was no special framework for the approval of herbal trials. One local institutional review committee granted an exemption. Key issues raised for revision were around pre-clinical efficacy and safety data, standardization and quality assurance of the intervention as well as consenting procedures. Approval timelines ranged between eight and 72 weeks. In the absence of a defined framework for review of herbal trials, approval processes can be delayed. Dialogue between researchers and regulators is important for successful and efficient protocol approval for herbal trials in developing countries. The study was registered prospectively on August 3, 2011 with clinicaltrials.gov (NCT01410058).

78 FR 55117 - Ultimate Heat Sink for Nuclear Power Plants; Draft Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... applicants may use to implement general design criteria (GDC) that are applicable to the ultimate heat sink... only for comments received on or before this date. Although a time limit is given, comments and... published guides are encouraged at any time. ADDRESSES: You may submit comment by any of the following...

10 CFR 2.643 - Acceptance and docketing of application for limited work authorization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... § 2.101(a)(9) is incomplete and not acceptable for processing, the Director of New Reactors or the Director of Nuclear Reactor Regulation will inform the applicant of this determination and the respects in... authorization. 2.643 Section 2.643 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING...

10 CFR 50.64 - Limitations on the use of highly enriched uranium (HEU) in domestic non-power reactors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... domestic non-power reactors. 50.64 Section 50.64 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF... Permits § 50.64 Limitations on the use of highly enriched uranium (HEU) in domestic non-power reactors. (a) Applicability. The requirements of this section apply to all non-power reactors. (b) Requirements. (1) The...

10 CFR 50.64 - Limitations on the use of highly enriched uranium (HEU) in domestic non-power reactors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... domestic non-power reactors. 50.64 Section 50.64 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF... Permits § 50.64 Limitations on the use of highly enriched uranium (HEU) in domestic non-power reactors. (a) Applicability. The requirements of this section apply to all non-power reactors. (b) Requirements. (1) The...

77 FR 27221 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-09

.... ET 5/23/12. Docket Numbers: ER12-1698-000. Applicants: New Mexico Renewable Energy Transmission..., LLC, New Mexico Renewable Energy Transmission Authority. Description: Request for Limited Waiver of... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice...

Effect of Temporal and Spatial Rainfall Resolution on HSPF Predictive Performance and Parameter Estimation

EPA Science Inventory

Watershed scale rainfall‐runoff models are used for environmental management and regulatory modeling applications, but their effectiveness are limited by predictive uncertainties associated with model input data. This study evaluated the effect of temporal and spatial rainfall re...

Probabilistic pipe fracture evaluations for leak-rate-detection applications

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

Rahman, S.; Ghadiali, N.; Paul, D.

1995-04-01

Regulatory Guide 1.45, {open_quotes}Reactor Coolant Pressure Boundary Leakage Detection Systems,{close_quotes} was published by the U.S. Nuclear Regulatory Commission (NRC) in May 1973, and provides guidance on leak detection methods and system requirements for Light Water Reactors. Additionally, leak detection limits are specified in plant Technical Specifications and are different for Boiling Water Reactors (BWRs) and Pressurized Water Reactors (PWRs). These leak detection limits are also used in leak-before-break evaluations performed in accordance with Draft Standard Review Plan, Section 3.6.3, {open_quotes}Leak Before Break Evaluation Procedures{close_quotes} where a margin of 10 on the leak detection limit is used in determining the crackmore » size considered in subsequent fracture analyses. This study was requested by the NRC to: (1) evaluate the conditional failure probability for BWR and PWR piping for pipes that were leaking at the allowable leak detection limit, and (2) evaluate the margin of 10 to determine if it was unnecessarily large. A probabilistic approach was undertaken to conduct fracture evaluations of circumferentially cracked pipes for leak-rate-detection applications. Sixteen nuclear piping systems in BWR and PWR plants were analyzed to evaluate conditional failure probability and effects of crack-morphology variability on the current margins used in leak rate detection for leak-before-break.« less

[Sporulation or competence development? A genetic regulatory network model of cell-fate determination in Bacillus subtilis].

PubMed

Lu, Zhenghui; Zhou, Yuling; Zhang, Xiaozhou; Zhang, Guimin

2015-11-01

Bacillus subtilis is a generally recognized as safe (GRAS) strain that has been widely used in industries including fodder, food, and biological control. In addition, B. subtilis expression system also plays a significant role in the production of industrial enzymes. However, its application is limited by its low sporulation frequency and transformation efficiency. Immense studies have been done on interpreting the molecular mechanisms of sporulation and competence development, whereas only few of them were focused on improving sporulation frequency and transformation efficiency of B. subtilis by genetic modification. The main challenge is that sporulation and competence development, as the two major developmental events in the stationary phase of B. subtilis, are regulated by the complicated intracellular genetic regulatory systems. In addition, mutual regulatory mechanisms also exist in these two developmental events. With the development of genetic and metabolic engineering, constructing genetic regulatory networks is currently one of the most attractive research fields, together with the genetic information of cell growth, metabolism, and development, to guide the industrial application. In this review, the mechanisms of sporulation and competence development of B. subtilis, their interactions, and the genetic regulation of cell growth were interpreted. In addition, the roles of these regulatory networks in guiding basic and applied research of B. subtilis and its related species were discussed.

Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals.

PubMed

Beken, Sonja; Kasper, Peter; van der Laan, Jan-Willem

Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non-clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory acceptance of 3R testing approaches, including a process for collection of real-life data (safe harbour). Pathways for regulatory acceptance of 3R testing approaches are depicted and a new procedure for submission and evaluation of a proposal for regulatory acceptance of 3R testing approaches is described.

77 FR 48134 - Combined Notice of Filings #2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-13

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 2 Take notice that the Commission received the following electric corporate filings: Docket Numbers: EC12-129-000 Applicants: Baja California Power, Inc, Uluru Finance Limited, China Huaneng Group HK Ltd., Upper Horm Investments Ltd., Overseas International Inc....

10 CFR 26.4 - FFD program applicability to categories of individuals.

Code of Federal Regulations, 2011 CFR

2011-01-01

....4 Section 26.4 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Administrative... entity, monitors the fitness of the individuals specified in paragraph (f) of this section; (4) Witnesses... not limited to the MRO; (2) All persons who make determinations of fitness; (3) All persons who make...

Application of Regulatory Focus Theory to Search Advertising

PubMed Central

Mowle, Elyse N.; Georgia, Emily J.; Doss, Brian D.; Updegraff, John A.

2015-01-01

Purpose The purpose of this paper is to test the utility of regulatory focus theory principles in a real-world setting; specifically, Internet hosted text advertisements. Effect of compatibility of the ad text with the regulatory focus of the consumer was examined. Design/methodology/approach Advertisements were created using Google AdWords. Data were collected for the number of views and clicks each ad received. Effect of regulatory fit was measured using logistic regression. Findings Logistic regression analyses demonstrated that there was a strong main effect for keyword, such that users were almost six times as likely to click on a promotion advertisement as a prevention advertisement, as well as a main effect for compatibility, such that users were twice as likely to click on an advertisement with content that was consistent with their keyword. Finally, there was a strong interaction of these two variables, such that the effect of consistent advertisements was stronger for promotion searches than for prevention searches. Research limitations/implications The effect of ad compatibility had medium to large effect sizes, suggesting that individuals’ state may have more influence on advertising response than do individuals’ traits (e.g. personality traits). Measurement of regulatory fit was limited by the constraints of Google AdWords. Practical implications The results of this study provide a possible framework for ad creation for Internet advertisers. Originality/value This paper is the first study to demonstrate the utility of regulatory focus theory in online advertising. PMID:26430293

Novel perspectives for the engineering of abiotic stress tolerance in plants.

PubMed

Cabello, Julieta V; Lodeyro, Anabella F; Zurbriggen, Matias D

2014-04-01

Adverse environmental conditions pose serious limitations to agricultural production. Classical biotechnological approaches towards increasing abiotic stress tolerance focus on boosting plant endogenous defence mechanisms. However, overexpression of regulatory elements or effectors is usually accompanied by growth handicap and yield penalties due to crosstalk between developmental and stress-response networks. Herein we offer an overview on novel strategies with the potential to overcome these limitations based on the engineering of regulatory systems involved in the fine-tuning of the plant response to environmental hardships, including post-translational modifications, small RNAs, epigenetic control of gene expression and hormonal networks. The development and application of plant synthetic biology tools and approaches will add new functionalities and perspectives to genetic engineering programs for enhancing abiotic stress tolerance. Copyright © 2013 Elsevier Ltd. All rights reserved.

Advanced Reactor Technologies - Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne L.

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However,more » it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory importance of key DOE reactor research initiatives should be assessed early in the technology development process. Quality assurance requirements supportive of later licensing activities must also be attached to important research activities to ensure resulting data is usable in that context. Early regulatory analysis and licensing approach planning thus provides a significant benefit to the formulation of research plans and also enables the planning and development of a compatible AdvSMR licensing framework, should significant modification be required.« less

Advanced Reactor Technology -- Regulatory Technology Development Plan (RTDP)

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

Moe, Wayne Leland

This DOE-NE Advanced Small Modular Reactor (AdvSMR) regulatory technology development plan (RTDP) will link critical DOE nuclear reactor technology development programs to important regulatory and policy-related issues likely to impact a “critical path” for establishing a viable commercial AdvSMR presence in the domestic energy market. Accordingly, the regulatory considerations that are set forth in the AdvSMR RTDP will not be limited to any one particular type or subset of advanced reactor technology(s) but rather broadly consider potential regulatory approaches and the licensing implications that accompany all DOE-sponsored research and technology development activity that deal with commercial non-light water reactors. However,more » it is also important to remember that certain “minimum” levels of design and safety approach knowledge concerning these technology(s) must be defined and available to an extent that supports appropriate pre-licensing regulatory analysis within the RTDP. Final resolution to advanced reactor licensing issues is most often predicated on the detailed design information and specific safety approach as documented in a facility license application and submitted for licensing review. Because the AdvSMR RTDP is focused on identifying and assessing the potential regulatory implications of DOE-sponsored reactor technology research very early in the pre-license application development phase, the information necessary to support a comprehensive regulatory analysis of a new reactor technology, and the resolution of resulting issues, will generally not be available. As such, the regulatory considerations documented in the RTDP should be considered an initial “first step” in the licensing process which will continue until a license is issued to build and operate the said nuclear facility. Because a facility license application relies heavily on the data and information generated by technology development studies, the anticipated regulatory importance of key DOE reactor research initiatives should be assessed early in the technology development process. Quality assurance requirements supportive of later licensing activities must also be attached to important research activities to ensure resulting data is usable in that context. Early regulatory analysis and licensing approach planning thus provides a significant benefit to the formulation of research plans and also enables the planning and development of a compatible AdvSMR licensing framework, should significant modification be required.« less

Benefits and Limitations of Protein Hydrolysates as Components of Serum-Free Media for Animal Cell Culture Applications

NASA Astrophysics Data System (ADS)

Lobo-Alfonso, Juliet; Price, Paul; Jayme, David

Increased understanding of influential factors for the cultivation of animal cells, combined with heightened regulatory concern over potential transmission of adventitious contaminants associated with serum and other animal-derived components, has elevated interest in using protein hydrolysates as serum replacements or nutrient supplements. This paper reviews the chemistry and biology of various hydrolysates derived from animal, plant and microbial sources. It provides specific examples of a beneficial selection of plant and yeast hydrolysates as ingredients of serum-free nutrient formulations for bioproduction applications of cultured mammalian and insect cells. Strategies for customizing and optimizing nutrients for specialized applications and general benefits and limitations of protein hydrolysates for biopharmaceutical production are also discussed.

The Application of Electrochemical and Surface Analysis Approaches to Studying Copper Corrosion in Water: Fundamentals, Limitations, and Examples

EPA Science Inventory

Corrosion control is a concern for many drinking water utilities. The Lead and Copper Rule established a regulatory need to maintain a corrosion control program. Other corrosion-related issues such as “red” water resulting from excessive iron corrosion and copper pinhole leaks ...

78 FR 39036 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... applicable non-financial listing standard requirements, including, without limitation, the requirements of... financial statements for a full fiscal year commencing on a date after the date of filing with the...-K, including all required audited financial statements (the ``Reverse Merger Form 8-K'').\\5\\ In...

75 FR 4897 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... $100 million public float requirement to those companies, unless there is only very limited trading...-held shares (``public float'') of $40 million at the time of listing. All other companies must have a... value of the company's offering to demonstrate the company's compliance with the applicable public float...

76 FR 47423 - Aviation Fuel and Oil Operating Limitations; Policy Memorandum

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-05

... #0; #0;Rules and Regulations #0; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER contains regulatory documents #0;having general applicability and legal effect, most of which are keyed #0;to and codified in the Code of Federal Regulations, which is published #0;under 50 titles pursuant to...

Environmental damage schedules: community judgments of importance and assessments of losses

Treesearch

Ratana Chuenpagdee; Jack L. Knetsch; Thomas C. Brown

2001-01-01

Available methods of valuing environmental changes are often limited in their applicability to current issues such as damage assessment and implementing regulatory controls, or may otherwise not provide reliable readings of community preferences. An alternative is to base decisions on predetermined fixed schedules of sanctions, restrictions, damage awards, and other...

10 CFR 40.60 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

10 CFR 40.60 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

10 CFR 40.60 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... to avoid exposures to radiation or radioactive materials that could exceed regulatory limits or... releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The equipment is required to be...

Priority review drugs approved by the FDA and the EMA: time for international regulatory harmonization of pharmaceuticals?

PubMed

Alqahtani, Saad; Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Eguale, Tewodros

2015-07-01

The US Food and Drug Administration (FDA) priority review process applies to a drug that is considered a significant improvement over the available alternatives. The European Medicines Agency (EMA) accelerated approval applies to a product that is of major public health interest. This study assessed differences in the characteristics of priority review new molecular entities and new therapeutic biologic products approved by the FDA and the EMA. This study includes regulatory information on drug applications, approvals, indications, and orphan designations of all priority review drugs approved by the FDA and the EMA in the period 1999-2011. Descriptive statistics, t-tests, and chi-squared and Wilcoxon tests were performed. Overall, 100 FDA priority review new molecular entities and new therapeutic biologics were approved by both agencies; 87.0% of the products were first approved by the FDA. The average FDA review time (9.2 ± 8.4 months) was significantly lower than the EMA average review time (14.6 ± 4.0 months) (p < 0.0001). The FDA and the EMA granted orphan designation to 43.0% and 33.0%, respectively, of the applications. There were differences in the administration route (1.0% of all products), dosage (8.0%), strength (23%), posology (51.0%), indications (30.0%), restrictions of use (52.0%), limitations of use (19.0%), and outcomes limitations (28.0%) approved by both regulatory agencies. Significant differences exist in the characteristics of the priority review drugs approved by the FDA and the EMA. Harmonization of the US and European regulatory frameworks may facilitate timely approval of pharmaceutical products. Copyright © 2015 John Wiley & Sons, Ltd.

Learning from Dioxin & PCBs in meat - problems ahead?

NASA Astrophysics Data System (ADS)

Weber, R.

2017-09-01

Persistent organic pollutants (POPs) including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs; “Dioxins”), or polychlorinated biphenyls (PCBs) are widely recognized environmental and food contaminants. More than 90% of PCDD/Fs and PCB exposure of the average population stem from animal based food including meat. While average PCDD/F and PCB levels have decreased compared to levels 1980s, still contamination above regulatory limits are observed and a share of the population is above the tolerable daily intake recommended by the WHO. For PCBs the contamination of feed and food along the life cycle from production, use, recycling, end of life and related contaminated sites has been documented and can be seen as a model. Furthermore, it has been recently discovered that levels of PCBs in feed and soil below regulatory limits can result in meat contamination above EU regulatory limits. In particular, beef meat and chicken meat/eggs have been found very sensitive towards PCB contamination in the environment (soil and feed) but also in stables (paints and sealants). For PCDD/Fs, the major exposure pathways are feed, feed additives and contaminated sites. Chlorinated paraffins have substituted PCBs the last 40 years in open application and short chain chlorinated paraffins (SCCPs) were recently (05/2017) listed in the Stockholm Convention. Furthermore, brominated and fluorinated POPs have been listed in the Convention. All these POPs groups can accumulate in meat animals. For these new listed POPs no regulatory limits in food including meat has been established yet. Initial information on presence and risk of new listed POPs to food animals is compiled. A more systematic assessment of exposure and risks of POPs to food animals/meat is needed.

[Scientific advice by the national and European approval authorities concerning advanced therapy medicinal products].

PubMed

Jost, Nils; Schüssler-Lenz, Martina; Ziegele, Bettina; Reinhardt, Jens

2015-11-01

The aim of scientific advice is to support pharmaceutical developers in regulatory and scientific questions, thus facilitating the development of safe and efficacious new medicinal products. Recent years have shown that the development of advanced therapy medicinal products (ATMPs) in particular needs a high degree of regulatory support. On one hand, this is related to the complexity and heterogeneity of this group of medicinal products and on the other hand due to the fact that mainly academic research institutions and small- and medium-sized enterprises (SMEs) are developing ATMPs. These often have limited regulatory experience and resources. In 2009 the Paul-Ehrlich-Institut (PEI) initiated the Innovation Office as a contact point for applicants developing ATMPs. The mandate of the Innovation Office is to provide support on regulatory questions and to coordinate national scientific advice meetings concerning ATMPs for every phase in drug development and especially with view to the preparation of clinical trial applications. On the European level, the Scientific Advice Working Party (SAWP) of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicinal Agency (EMA) offers scientific advice. This article describes the concepts of national and EMA scientific advice concerning ATMPs and summarizes the experience of the last six years.

78 FR 62817 - Self-Regulatory Organizations; CBOE Futures Exchange, LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... Related Position Transactions and Block Trades October 4, 2013. Pursuant to Section 19(b)(7) of the...) (``ECRP'') and 415 (Block Trading). The scope of this filing is limited solely to the application of the... ECRP transactions, and CFE Rule 415 sets forth requirements relating to Block Trades. Each of these...

10 CFR 2.603 - Acceptance and docketing of application for early review of site suitability issues in a...

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Additional... Issuance of Limited Work Authorizations Early Partial Decisions on Site Suitability-Construction Permit § 2... processing, the Director of the Office of New Reactors or the Director of the Office of Nuclear Reactor...

10 CFR 2.621 - Acceptance and docketing of application for early review of site suitability issues in a combined...

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Additional... Issuance of Limited Work Authorizations Early Partial Decisions on Site Suitability-Combined License Under... Director of the Office of New Reactors or the Director of the Office of Nuclear Reactor Regulation, as...

78 FR 18280 - Approval and Promulgation of Air Quality Implementation Plans; Nevada; Regional Haze Federal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... emission limits applicable to Units 1, 2, and 3 at RGGS by 18 months from January 1, 2015, to June 30, 2016.... Paperwork Reduction Act C. Regulatory Flexibility Act D. Unfunded Mandates Reform Act E. Executive Order..., or Use I. National Technology Transfer and Advancement Act J. Executive Order 12898: Federal Actions...

The Toxics Geography Exercise: Students Use Inquiry to Uncover Uses and Limits of Data in Policy Analysis

ERIC Educational Resources Information Center

Duke, L. Donald; Schmidt, Diane L.

2011-01-01

The Toxics Geography Exercise was developed as an application-oriented exercise to develop skills in critical analysis in groups of undergraduate students from widely diverse academic backgrounds. Students use publicly available data on industrial activities, history of toxic material disposal, basic chemistry, regulatory approaches of federal and…

Air transport of plutonium metal: content expansion initiative for the plutonium air transportable (PAT01) packaging

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

Caviness, Michael L; Mann, Paul T; Yoshimura, Richard H

2010-01-01

The National Nuclear Security Administration (NNSA) has submitted an application to the Nuclear Regulatory Commission (NRC) for the air shipment of plutonium metal within the Plutonium Air Transportable (PAT-1) packaging. The PAT-1 packaging is currently authorized for the air transport of plutonium oxide in solid form only. The INMM presentation will provide a limited overview of the scope of the plutonium metal initiative and provide a status of the NNSA application to the NRC.

A semi-quantitative approach to GMO risk-benefit analysis.

PubMed

Morris, E Jane

2011-10-01

In many countries there are increasing calls for the benefits of genetically modified organisms (GMOs) to be considered as well as the risks, and for a risk-benefit analysis to form an integral part of GMO regulatory frameworks. This trend represents a shift away from the strict emphasis on risks, which is encapsulated in the Precautionary Principle that forms the basis for the Cartagena Protocol on Biosafety, and which is reflected in the national legislation of many countries. The introduction of risk-benefit analysis of GMOs would be facilitated if clear methodologies were available to support the analysis. Up to now, methodologies for risk-benefit analysis that would be applicable to the introduction of GMOs have not been well defined. This paper describes a relatively simple semi-quantitative methodology that could be easily applied as a decision support tool, giving particular consideration to the needs of regulators in developing countries where there are limited resources and experience. The application of the methodology is demonstrated using the release of an insect resistant maize variety in South Africa as a case study. The applicability of the method in the South African regulatory system is also discussed, as an example of what might be involved in introducing changes into an existing regulatory process.

Passing messages between biological networks to refine predicted interactions.

PubMed

Glass, Kimberly; Huttenhower, Curtis; Quackenbush, John; Yuan, Guo-Cheng

2013-01-01

Regulatory network reconstruction is a fundamental problem in computational biology. There are significant limitations to such reconstruction using individual datasets, and increasingly people attempt to construct networks using multiple, independent datasets obtained from complementary sources, but methods for this integration are lacking. We developed PANDA (Passing Attributes between Networks for Data Assimilation), a message-passing model using multiple sources of information to predict regulatory relationships, and used it to integrate protein-protein interaction, gene expression, and sequence motif data to reconstruct genome-wide, condition-specific regulatory networks in yeast as a model. The resulting networks were not only more accurate than those produced using individual data sets and other existing methods, but they also captured information regarding specific biological mechanisms and pathways that were missed using other methodologies. PANDA is scalable to higher eukaryotes, applicable to specific tissue or cell type data and conceptually generalizable to include a variety of regulatory, interaction, expression, and other genome-scale data. An implementation of the PANDA algorithm is available at www.sourceforge.net/projects/panda-net.

75 FR 14212 - Proposed Generic Communications; Applicability of 10 CFR Part 21 Requirements to Applicants for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0122] Proposed Generic Communications; Applicability of 10 CFR Part 21 Requirements to Applicants for Standard Design Certifications AGENCY: Nuclear Regulatory Commission. ACTION: Notice of opportunity for public comment. SUMMARY: The U.S. Nuclear Regulatory Commission...

Unmanned Aerial Vehicle Systems for Disaster Relief: Tornado Alley

NASA Technical Reports Server (NTRS)

DeBusk, Wesley M.

2009-01-01

Unmanned aerial vehicle systems are currently in limited use for public service missions worldwide. Development of civil unmanned technology in the United States currently lags behind military unmanned technology development in part because of unresolved regulatory and technological issues. Civil unmanned aerial vehicle systems have potential to augment disaster relief and emergency response efforts. Optimal design of aerial systems for such applications will lead to unmanned vehicles which provide maximum potentiality for relief and emergency response while accounting for public safety concerns and regulatory requirements. A case study is presented that demonstrates application of a civil unmanned system to a disaster relief mission with the intent on saving lives. The concept utilizes unmanned aircraft to obtain advanced warning and damage assessments for tornados and severe thunderstorms. Overview of a tornado watch mission architecture as well as commentary on risk, cost, need for, and design tradeoffs for unmanned aerial systems are provided.

The impact of biotechnology on agricultural worker safety and health.

PubMed

Shutske, J M; Jenkins, S M

2002-08-01

Biotechnology applications such as the use and production of genetically modified organisms (GMOs) have been widely promoted, adopted, and employed by agricultural producers throughout the world. Yet, little research exists that examines the implications of agricultural biotechnology on the health and safety of workers involved in agricultural production and processing. Regulatory frameworks do exist to examine key issues related to food safety and environmental protection in GMO applications. However, based on the lack of research and regulatory oversight, it would appear that the potential impact on the safety and health of workers is of limited interest. This article examines some of the known worker health and safety implications related to the use and production of GMOs using the host, agent, and environment framework. The characteristics of employers, workers, inputs, production practices, and socio-economic environments in which future agricultural workers perform various tasks is likely to change based on the research summarized here.

OBSERVABLE INDICATORS OF THE SENSITIVITY OF PM2.5 NITRATE TO EMISSION REDUCTIONS PART I: DERIVATION OF THE ADJUSTED GAS RATIO AND APPLICABILITY AT REGULATORY-RELEVANT TIME SCALES

EPA Science Inventory

Chemical transport models have frequently been used to evaluate the impacts of emission reductions on inorganic PM2.5. However, such models are limited in their accuracy by uncertain estimates of the spatial and temporal characterization of emissions and meteorology. Site-speci...

76 FR 77859 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... only be applicable to PSOs that remove liquidity from the NYSE and that a PSO that provides liquidity...(kk). A PSO is a Primary Only (``PO'') Order that initially sweeps the Exchange's Book before being routed to the security's primary market. \\11\\ In limited circumstances where a PSO in a Tape A security...

75 FR 81704 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-28

... algorithm \\5\\ for HOSS and to make related changes to Interpretation and Policy .03. Currently, there are... applicable allocation algorithm for the HOSS and modified HOSS rotation procedures. Paragraph (c)(iv) of the... allocation algorithm in effect for the option class pursuant to Rule 6.45A or 6.45B), then to limit orders...

Inter-laboratory validation of an inexpensive streamlined method to measure inorganic arsenic in rice grain

USDA-ARS?s Scientific Manuscript database

With the establishment by CODEX of a 200 ng/g limit of inorganic arsenic (iAs) in polished rice grain, more analyses of iAs will be necessary to ensure compliance in regulatory and trade applications, to assess quality control in commercial rice production, and to conduct research involving iAs in r...

The effectiveness of municipal sewage sludge application on the stabilization of Pb, Zn, and Cd in a soil contaminated from mining activities.

PubMed

Xenidis, A; Stouraiti, C; Moirou, A

2001-01-01

The effectiveness of municipal sewage sludge for the stabilisation of Pb, Zn and Cd in a heavily contaminated soil was evaluated by performing pot experiments on soil-sludge mixtures. The soil sample originated from the Montevecchio mining district, Sardinia, Italy, and presented high Pb, Zn and Cd content, as well as US EPA TCLP solubility values for Pb and Cd, which exceeded the respective regulatory limits. Sewage sludge application increased the soil pH. Stabilisation experiments showed that 10% w/w sewage sludge addition effectively reduced Pb and Cd solubilities below the TCLP regulatory limits. At the same addition rate, the EDTA extractable fraction of Pb, Zn, Cd in the treated soil was reduced by 12, 47 and 50% respectively compared with the untreated sample. The five-stage sequential extraction procedure applied on the untreated and treated soil samples, showed a remarkable shift of the metals towards more stable forms. The reducible fractions of Zn and Cd and the residual fraction of Pb were increased by 12, 20 and 18% respectively, while a corresponding decrease in the mobile fractions (exchangeable and carbonate) occurred which accounted for 14, 23 and 25% respectively.

SAFEGUARD: An Assured Safety Net Technology for UAS

NASA Technical Reports Server (NTRS)

Dill, Evan T.; Young, Steven D.; Hayhurst, Kelly J.

2016-01-01

As demands increase to use unmanned aircraft systems (UAS) for a broad spectrum of commercial applications, regulatory authorities are examining how to safely integrate them without loss of safety or major disruption to existing airspace operations. This work addresses the development of the Safeguard system as an assured safety net technology for UAS. The Safeguard system monitors and enforces conformance to a set of rules defined prior to flight (e.g., geospatial stay-out or stay-in regions, speed limits, altitude limits). Safeguard operates independently of the UAS autopilot and is strategically designed in a way that can be realized by a small set of verifiable functions to simplify compliance with regulatory standards for commercial aircraft. A framework is described that decouples the system from any other devices on the UAS as well as introduces complementary positioning source(s) for applications that require integrity and availability beyond what the Global Positioning System (GPS) can provide. Additionally, the high level logic embedded within the software is presented, as well as the steps being taken toward verification and validation (V&V) of proper functionality. Next, an initial prototype implementation of the described system is disclosed. Lastly, future work including development, testing, and system V&V is summarized.

Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy.

PubMed

Kim, Hyun Ah; Rhim, Taiyoun; Lee, Minhyung

2011-07-18

Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Regulation mechanisms in mixed and pure culture microbial fermentation.

PubMed

Hoelzle, Robert D; Virdis, Bernardino; Batstone, Damien J

2014-11-01

Mixed-culture fermentation is a key central process to enable next generation biofuels and biocommodity production due to economic and process advantages over application of pure cultures. However, a key limitation to the application of mixed-culture fermentation is predicting culture product response, related to metabolic regulation mechanisms. This is also a limitation in pure culture bacterial fermentation. This review evaluates recent literature in both pure and mixed culture studies with a focus on understanding how regulation and signaling mechanisms interact with metabolic routes and activity. In particular, we focus on how microorganisms balance electron sinking while maximizing catabolic energy generation. Analysis of these mechanisms and their effect on metabolism dynamics is absent in current models of mixed-culture fermentation. This limits process prediction and control, which in turn limits industrial application of mixed-culture fermentation. A key mechanism appears to be the role of internal electron mediating cofactors, and related regulatory signaling. This may determine direction of electrons towards either hydrogen or reduced organics as end-products and may form the basis for future mechanistic models. © 2014 Wiley Periodicals, Inc.

Task 2 - Limits for High-Frequency Conducted Susceptibility Testing - CS114 (NRC-HQ-60-14-D-0015)

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

Wood, Richard Thomas; Ewing, Paul D.; Moses, Rebecca J.

2015-09-01

A principal focus of Task 2 under this project was for ORNL to evaluate the basis for susceptibility testing against high-frequency conducted interference and to establish recommendations to resolve concerns about the severity of test limits for the conducted susceptibility (CS) test, CS114, from MIL-STD-461. The primary concern about the test limit has been characterized by the EPRI EMI Working Group in the following terms: Demonstrating compliance with the CS114 test limits recommended in TR-102323 has proven to be problematic, even for components that have been tested to commercial standards and demonstrated proper operation in industrial applications [6]. Specifically, EPRImore » notes that the CS114 limits approved in regulatory documents are significantly higher than those invoked by the US military and similar commercial standards in the frequency range below 200 kHz. For this task, ORNL evaluated the original approach to establishing the test limit, EPRI technical findings from a review of the limit, and the regulatory basis through which the currently approved limits were accepted. Based on this analysis, strategies have been developed regarding changes to the CS114 limit that can resolve the technical concerns raised by the industry. Guided by the principles that reasonable assurance of safety must not be compromised but excessive conservatism should be reduced, recommendations on a suitable basis for a revised limit have been developed and can be incorporated into the planned Revision 2 of RG 1.180.« less

[Evaluation of phosphate-containing amendments on remediation effect and influential factors in a lead/zinc mining tailings contaminated soil using TCLP and forms].

PubMed

Chen, Jian-Jun; Yu, Tian-Ming; Wang, Bi-Ling; Xie, Zheng-Miao

2010-01-01

A pot experiment was conducted to evaluate the effects of phosphate-containing (P) amendments on the toxicity and bioavailability of Pb and Zn in a soil contaminated by mining tailings using toxicity characteristic leaching procedure (TCLP) and water soluble, exchangeable leaching procedures in order to find out the appropriate P application rates to reduce the soil TCLP extractable Pb to below the USA EPA's regulatory limit levels. The results showed that TCLP extractable Pb concentrations were significantly decreased by up to 93.3% for MPP treatments and up to 68.5% for SSP treatments after P application. The dose required to reduce leachable Pb below the EPA's regulatory limit level was found to be around the molar ratio of v(P/Pb) = 0.6 for MPP and 1.8 for SSP. It was also found both MPP and SSP could reduce the exchangeable Pb and Zn concentrations that all bio-available Zn forms including water soluble, exchangeable, and TCLP extractable forms in soil were significantly and negatively correlated to soil pH values, indicating that the content of Zn in the soil was mostly controlled by soil pH value even after P application. These results suggest that P as MPP and SSP could successfully decrease the toxicity and bioavailability of Pb and Zn in the contaminated soil.

Optimizing the European regulatory framework for sustainable bacteriophage therapy in human medicine.

PubMed

Verbeken, Gilbert; Pirnay, Jean-Paul; De Vos, Daniel; Jennes, Serge; Zizi, Martin; Lavigne, Rob; Casteels, Minne; Huys, Isabelle

2012-06-01

For practitioners at hospitals seeking to use natural (not genetically modified, as appearing in nature) bacteriophages for treatment of antibiotic-resistant bacterial infections (bacteriophage therapy), Europe's current regulatory framework for medicinal products hinders more than it facilitates. Although many experts consider bacteriophage therapy to be a promising complementary (or alternative) treatment to antibiotic therapy, no bacteriophage-specific framework for documentation exists to date. Decades worth of historical clinical data on bacteriophage therapy (from Eastern Europe, particularly Poland, and the former Soviet republics, particularly Georgia and Russia, as well as from today's 27 EU member states and the US) have not been taken into account by European regulators because these data have not been validated under current Western regulatory standards. Consequently, applicants carrying out standard clinical trials on bacteriophages in Europe are obliged to initiate clinical work from scratch. This paper argues for a reduced documentation threshold for Phase 1 clinical trials of bacteriophages and maintains that bacteriophages should not be categorized as classical medicinal products for at least two reasons: (1) such a categorization is scientifically inappropriate for this specific therapy and (2) such a categorization limits the marketing authorization process to industry, the only stakeholder with sufficient financial resources to prepare a complete dossier for the competent authorities. This paper reflects on the current regulatory framework for medicines in Europe and assesses possible regulatory pathways for the (re-)introduction of bacteriophage therapy in a way that maintains its effectiveness and safety as well as its inherent characteristics of sustainability and in situ self-amplification and limitation.

12 CFR 1263.15 - Recent merger or acquisition applicants.

Code of Federal Regulations, 2014 CFR

2014-01-01

... section. (a) Financial condition requirement—(1) Regulatory financial reports. For purposes of § 1263.11(a... its application for membership, has not yet filed regulatory financial reports with its appropriate... regulatory financial reports that the applicant has filed with its appropriate regulator. (2) Performance...

12 CFR 1263.15 - Recent merger or acquisition applicants.

Code of Federal Regulations, 2013 CFR

2013-01-01

... section. (a) Financial condition requirement—(1) Regulatory financial reports. For purposes of § 1263.11(a... its application for membership, has not yet filed regulatory financial reports with its appropriate... regulatory financial reports that the applicant has filed with its appropriate regulator. (2) Performance...

12 CFR 1263.15 - Recent merger or acquisition applicants.

Code of Federal Regulations, 2011 CFR

2011-01-01

... section. (a) Financial condition requirement—(1) Regulatory financial reports. For purposes of § 1263.11(a... its application for membership, has not yet filed regulatory financial reports with its appropriate... regulatory financial reports that the applicant has filed with its appropriate regulator. (2) Performance...

12 CFR 1263.15 - Recent merger or acquisition applicants.

Code of Federal Regulations, 2012 CFR

2012-01-01

... section. (a) Financial condition requirement—(1) Regulatory financial reports. For purposes of § 1263.11(a... its application for membership, has not yet filed regulatory financial reports with its appropriate... regulatory financial reports that the applicant has filed with its appropriate regulator. (2) Performance...

Impact assessment of WHO TobReg proposals for mandated lowering of selected mainstream cigarette smoke toxicants.

PubMed

Eldridge, Alison C; McAdam, Kevin G; Betson, Tatiana R; Gama, Marcos V; Proctor, Christopher J

2017-06-01

The WHO Tobacco Product Regulation Study Group (TobReg) has proposed three regulatory models for cigarettes, each creating mandatory limits for emissions of nine smoke toxicants. One approach proposes country-specific limits, using median or 1.25× median toxicant/nicotine emission ratios. A second model provides fixed toxicant-ratio limits. The third model limits were three times the lowest toxicant emission on a market. Currently, the practical implications of these models are largely unknown. An impact assessment was conducted using cigarette data from 79 countries to identify four diverse test markets. We sampled all products from each market but limited product availability led to incomplete (80-97%) sourcing. Analysis showed that the country-specific model led to diverse (up to threefold) toxicant limits across the four markets. 70%-80% of products were non-compliant, rising to 100% in some countries with the second and the third models. With each regulatory model the main drivers of non-compliance were the tobacco-specific nitrosamines, the simultaneous application of limits for nine poorly correlated smoke toxicants, and analytical variability. Use of nicotine ratios led to compliance of some high toxicant emission products due to high nicotine emissions. Our findings suggest that these proposals would have greater impact on global markets than TobReg's stated aims. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Regulatory requirements for clinical trial and marketing authorisation application for cell-based medicinal products.

PubMed

Salmikangas, P; Flory, E; Reinhardt, J; Hinz, T; Maciulaitis, R

2010-01-01

The new era of regenerative medicine has led to rapid development of new innovative therapies especially for diseases and tissue/organ defects for which traditional therapies and medicinal products have not provided satisfactory outcome. Although the clinical use and developments of cell-based medicinal products (CBMPs) could be witnessed already for a decade, robust scientific and regulatory provisions for these products have only recently been enacted. The new Regulation for Advanced Therapies (EC) 1394/2007 together with the revised Annex I, Part IV of Directive 2001/83/EC provides the new legal framework for CBMPs. The wide variety of cell-based products and the foreseen limitations (small sample sizes, short shelf life) vs. particular risks (microbiological purity, variability, immunogenicity, tumourigenicity) associated with CBMPs have called for a flexible, case-by-case regulatory approach for these products. Consequently, a risk-based approach has been developed to allow definition of the amount of scientific data needed for a Marketing Authorisation Application (MAA) of each CBMP. The article provides further insight into the initial risk evaluation, as well as to the quality, non-clinical, and clinical requirements of CBMPs. Special somatic cell therapies designed for active immunotherapy are also addressed.

Innovations in vaccine development: can regulatory authorities keep up?

PubMed

Cox, Manon M J; Onraedt, Annelies

2012-10-01

Vaccine Production Summit San Francisco, CA, USA, 4-6 June 2012 IBC's 3rd Vaccine Production Summit featured 28 presentations discussing regulatory challenges in vaccine development, including the use of adjuvants, vaccine manufacturing and technology transfer, process development for vaccines and the role of quality by design, how to address vaccine stability, and how vaccine development timelines can be improved. The conference was run in parallel with the single-use applications for Biopharmaceutical Manufacturing conference. Approximately 250 attendees from large pharmaceutical companies, large and small biotech companies, vendors and a more limited number from academia were allowed to access sessions of either conference, including one shared session. This article summarizes the recurring themes across various presentations.

Advancing environmental toxicology through chemical dosimetry: External exposures versus tissue residues

USGS Publications Warehouse

McCarty, L.S.; Landrum, P.F.; Luoma, S.N.; Meador, J.P.; Merten, A.A.; Shephard, B.K.; van Wezelzz, A.P.

2011-01-01

The tissue residue dose concept has been used, although in a limited manner, in environmental toxicology for more than 100 y. This review outlines the history of this approach and the technical background for organic chemicals and metals. Although the toxicity of both can be explained in tissue residue terms, the relationship between external exposure concentration, body and/or tissues dose surrogates, and the effective internal dose at the sites of toxic action tends to be more complex for metals. Various issues and current limitations related to research and regulatory applications are also examined. It is clear that the tissue residue approach (TRA) should be an integral component in future efforts to enhance the generation, understanding, and utility of toxicity testing data, both in the laboratory and in the field. To accomplish these goals, several key areas need to be addressed: 1) development of a risk-based interpretive framework linking toxicology and ecology at multiple levels of biological organization and incorporating organism-based dose metrics; 2) a broadly applicable, generally accepted classification scheme for modes/mechanisms of toxic action with explicit consideration of residue information to improve both single chemical and mixture toxicity data interpretation and regulatory risk assessment; 3) toxicity testing protocols updated to ensure collection of adequate residue information, along with toxicokinetics and toxicodynamics information, based on explicitly defined toxicological models accompanied by toxicological model validation; 4) continued development of residueeffect databases is needed ensure their ongoing utility; and 5) regulatory guidance incorporating residue-based testing and interpretation approaches, essential in various jurisdictions. ??:2010 SETAC.

12 CFR 562.2 - Regulatory reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

76 FR 40755 - Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0279] Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment AGENCY: Nuclear Regulatory Commission. ACTION: Solicitation of public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or Commission) is seeking public...

Analysis of environmental regulatory proposals: Its your chance to influence policy

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

Veil, J.A.

1994-03-02

As part of the regulatory development process, the US Envirorunental Protection Agency (EPA) collects data, makes various assumptions about the data, and analyzes the data. Although EPA acts in good faith, the agency cannot always be aware of all relevant data, make only appropriate assumptions, and use applicable analytical methods. Regulated industries must carefully must carefully review every component of the regulatory decision-making process to identify misunderstandings and errors and to supply additional data that is relevant to the regulatory action. This paper examines three examples of how EPA`s data, assumptions, and analytical methods have been critiqued. The first twomore » examples involve EPA`s cost-effectiveness (CE) analyses prepared for the offshore oil and gas effluent limitations guidelines and as part of EPA Region 6`s general permit for coastal waters of Texas and Louisiana. A CE analysis regulations to the incremental amount of pollutants that would be removed by the recommended treatment processes. The third example, although not involving a CE analysis, demonstrates how the use of non-representative data can influence the outcome of an analysis.« less

Passing Messages between Biological Networks to Refine Predicted Interactions

PubMed Central

Glass, Kimberly; Huttenhower, Curtis; Quackenbush, John; Yuan, Guo-Cheng

2013-01-01

Regulatory network reconstruction is a fundamental problem in computational biology. There are significant limitations to such reconstruction using individual datasets, and increasingly people attempt to construct networks using multiple, independent datasets obtained from complementary sources, but methods for this integration are lacking. We developed PANDA (Passing Attributes between Networks for Data Assimilation), a message-passing model using multiple sources of information to predict regulatory relationships, and used it to integrate protein-protein interaction, gene expression, and sequence motif data to reconstruct genome-wide, condition-specific regulatory networks in yeast as a model. The resulting networks were not only more accurate than those produced using individual data sets and other existing methods, but they also captured information regarding specific biological mechanisms and pathways that were missed using other methodologies. PANDA is scalable to higher eukaryotes, applicable to specific tissue or cell type data and conceptually generalizable to include a variety of regulatory, interaction, expression, and other genome-scale data. An implementation of the PANDA algorithm is available at www.sourceforge.net/projects/panda-net. PMID:23741402

75 FR 45677 - Draft Regulatory Guide, DG-1216,”Plant-Specific Applicability of Transition Break Size Specified...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0229] Draft Regulatory Guide, DG-1216,''Plant-Specific... Commission (NRC) is extending the public comment period for DG-1216 from August 25, 2010 to November 8, 2010... [email protected] . The Draft Regulatory Guide, DG-1216, ``Plant- Specific Applicability of...

78 FR 51753 - AUC, LLC Reno Creek, In Situ Project, New Source Material License Application

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... NUCLEAR REGULATORY COMMISSION [Docket No. 040-09092; [NRC-2013-0164] AUC, LLC Reno Creek, In Situ Project, New Source Material License Application AGENCY: Nuclear Regulatory Commission. ACTION: Notice of..., AUC, LLC (AUC) submitted to the U.S. Nuclear Regulatory Commission (NRC) an application for a new...

An integrative and applicable phylogenetic footprinting framework for cis-regulatory motifs identification in prokaryotic genomes.

PubMed

Liu, Bingqiang; Zhang, Hanyuan; Zhou, Chuan; Li, Guojun; Fennell, Anne; Wang, Guanghui; Kang, Yu; Liu, Qi; Ma, Qin

2016-08-09

Phylogenetic footprinting is an important computational technique for identifying cis-regulatory motifs in orthologous regulatory regions from multiple genomes, as motifs tend to evolve slower than their surrounding non-functional sequences. Its application, however, has several difficulties for optimizing the selection of orthologous data and reducing the false positives in motif prediction. Here we present an integrative phylogenetic footprinting framework for accurate motif predictions in prokaryotic genomes (MP(3)). The framework includes a new orthologous data preparation procedure, an additional promoter scoring and pruning method and an integration of six existing motif finding algorithms as basic motif search engines. Specifically, we collected orthologous genes from available prokaryotic genomes and built the orthologous regulatory regions based on sequence similarity of promoter regions. This procedure made full use of the large-scale genomic data and taxonomy information and filtered out the promoters with limited contribution to produce a high quality orthologous promoter set. The promoter scoring and pruning is implemented through motif voting by a set of complementary predicting tools that mine as many motif candidates as possible and simultaneously eliminate the effect of random noise. We have applied the framework to Escherichia coli k12 genome and evaluated the prediction performance through comparison with seven existing programs. This evaluation was systematically carried out at the nucleotide and binding site level, and the results showed that MP(3) consistently outperformed other popular motif finding tools. We have integrated MP(3) into our motif identification and analysis server DMINDA, allowing users to efficiently identify and analyze motifs in 2,072 completely sequenced prokaryotic genomes. The performance evaluation indicated that MP(3) is effective for predicting regulatory motifs in prokaryotic genomes. Its application may enhance progress in elucidating transcription regulation mechanism, thus provide benefit to the genomic research community and prokaryotic genome researchers in particular.

78 FR 28896 - Design Limits and Loading Combinations for Metal Primary Reactor Containment System Components

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0095] Design Limits and Loading Combinations for Metal... Regulatory Guide (RG) 1.57, ``Design Limits and Loading Combinations for Metal Primary Reactor Containment... the NRC staff considers acceptable for design limits and loading combinations for metal primary...

Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.

PubMed

Krackhardt, Angela M; Anliker, Brigitte; Hildebrandt, Martin; Bachmann, Michael; Eichmüller, Stefan B; Nettelbeck, Dirk M; Renner, Matthias; Uharek, Lutz; Willimsky, Gerald; Schmitt, Michael; Wels, Winfried S; Schüssler-Lenz, Martina

2018-04-01

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

78 FR 59401 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

...\\ directs the Commission to approve a proposed rule change of a self-regulatory organization if it finds... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70464; File No. SR-ICEEU-2013-11] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change Related To Enhanced...

Bentonite toxicology and epidemiology - a review.

PubMed

Maxim, L Daniel; Niebo, Ron; McConnell, Ernest E

2016-11-01

Bentonite, a clay with numerous industrial and consumer applications, is mined and processed in many countries of the world. Its many beneficial uses also create the potential for widespread occupational and consumer exposure. The available studies on toxicity and epidemiology indicate that the principal exposure pathway of concern is inhalation of respirable dust by occupationally exposed cohorts. Bentonite itself is probably not more toxic than any other particulate not otherwise regulated and is not classified as a carcinogen by any regulatory or advisory body, but some bentonite may contain variable amounts of respirable crystalline silica, a recognized human carcinogen. Therefore, prudent management and adherence to occupational exposure limits is appropriate. This review summarizes the literature available on production, applications, exposure, toxicity, and epidemiology of bentonite and identifies data gaps and limitations.

BeReTa: a systematic method for identifying target transcriptional regulators to enhance microbial production of chemicals.

PubMed

Kim, Minsuk; Sun, Gwanggyu; Lee, Dong-Yup; Kim, Byung-Gee

2017-01-01

Modulation of regulatory circuits governing the metabolic processes is a crucial step for developing microbial cell factories. Despite the prevalence of in silico strain design algorithms, most of them are not capable of predicting required modifications in regulatory networks. Although a few algorithms may predict relevant targets for transcriptional regulator (TR) manipulations, they have limited reliability and applicability due to their high dependency on the availability of integrated metabolic/regulatory models. We present BeReTa (Beneficial Regulator Targeting), a new algorithm for prioritization of TR manipulation targets, which makes use of unintegrated network models. BeReTa identifies TR manipulation targets by evaluating regulatory strengths of interactions and beneficial effects of reactions, and subsequently assigning beneficial scores for the TRs. We demonstrate that BeReTa can predict both known and novel TR manipulation targets for enhanced production of various chemicals in Escherichia coli Furthermore, through a case study of antibiotics production in Streptomyces coelicolor, we successfully demonstrate its wide applicability to even less-studied organisms. To the best of our knowledge, BeReTa is the first strain design algorithm exclusively designed for predicting TR manipulation targets. MATLAB code is available at https://github.com/kms1041/BeReTa (github). byungkim@snu.ac.krSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Machine Learning Approach to Predict Gene Regulatory Networks in Seed Development in Arabidopsis

PubMed Central

Ni, Ying; Aghamirzaie, Delasa; Elmarakeby, Haitham; Collakova, Eva; Li, Song; Grene, Ruth; Heath, Lenwood S.

2016-01-01

Gene regulatory networks (GRNs) provide a representation of relationships between regulators and their target genes. Several methods for GRN inference, both unsupervised and supervised, have been developed to date. Because regulatory relationships consistently reprogram in diverse tissues or under different conditions, GRNs inferred without specific biological contexts are of limited applicability. In this report, a machine learning approach is presented to predict GRNs specific to developing Arabidopsis thaliana embryos. We developed the Beacon GRN inference tool to predict GRNs occurring during seed development in Arabidopsis based on a support vector machine (SVM) model. We developed both global and local inference models and compared their performance, demonstrating that local models are generally superior for our application. Using both the expression levels of the genes expressed in developing embryos and prior known regulatory relationships, GRNs were predicted for specific embryonic developmental stages. The targets that are strongly positively correlated with their regulators are mostly expressed at the beginning of seed development. Potential direct targets were identified based on a match between the promoter regions of these inferred targets and the cis elements recognized by specific regulators. Our analysis also provides evidence for previously unknown inhibitory effects of three positive regulators of gene expression. The Beacon GRN inference tool provides a valuable model system for context-specific GRN inference and is freely available at https://github.com/BeaconProjectAtVirginiaTech/beacon_network_inference.git. PMID:28066488

Knowledge enabled plan of care and documentation prototype.

PubMed

DaDamio, Rebecca; Gugerty, Brian; Kennedy, Rosemary

2006-01-01

There exist significant challenges in integrating the plan of care into documentation and point of care operational processes. A plan of care is often a static artifact that meets regulatory standards with limited influence on supporting goal-directed care delivery processes. Although this prototype is applicable to many clinical disciplines, we will highlight nursing processes in demonstrating a knowledge-driven computerized solution that fully integrates the plan of care within documentation. The knowledge-driven solution reflects evidenced-based practice; is an effective tool for managing problems, orders/interventions, and the patient's progress towards expected outcomes; meets regulatory standards; and drives quality and process improvement. The knowledge infrastructure consists of fully represented terminology, structured clinical expressions utilizing the controlled terminology and clinical knowledge representing evidence-based practice.

Application of Regulatory Focus Theory to Search Advertising.

PubMed

Mowle, Elyse N; Georgia, Emily J; Doss, Brian D; Updegraff, John A

The purpose of this paper is to test the utility of regulatory focus theory principles in a real-world setting; specifically, Internet hosted text advertisements. Effect of compatibility of the ad text with the regulatory focus of the consumer was examined. Advertisements were created using Google AdWords. Data were collected for the number of views and clicks each ad received. Effect of regulatory fit was measured using logistic regression. Logistic regression analyses demonstrated that there was a strong main effect for keyword, such that users were almost six times as likely to click on a promotion advertisement as a prevention advertisement, as well as a main effect for compatibility, such that users were twice as likely to click on an advertisement with content that was consistent with their keyword. Finally, there was a strong interaction of these two variables, such that the effect of consistent advertisements was stronger for promotion searches than for prevention searches. The effect of ad compatibility had medium to large effect sizes, suggesting that individuals' state may have more influence on advertising response than do individuals' traits (e.g. personality traits). Measurement of regulatory fit was limited by the constraints of Google AdWords. The results of this study provide a possible framework for ad creation for Internet advertisers. This paper is the first study to demonstrate the utility of regulatory focus theory in online advertising.

Use of noise attenuation modeling in managing missile motor detonation activities.

PubMed

McFarland, Michael J; Watkins, Jeffrey W; Kordich, Micheal M; Pollet, Dean A; Palmer, Glenn R

2004-03-01

The Sound Intensity Prediction System (SIPS) and Blast Operation Overpressure Model (BOOM) are semiempirical sound models that are employed by the Utah Test and Training Range (UTTR) to predict whether noise levels from the detonation of large missile motors will exceed regulatory thresholds. Field validation of SIPS confirmed that the model was effective in limiting the number of detonations of large missile motors that could potentially result in a regulatory noise exceedance. Although the SIPS accurately predicted the impact of weather on detonation noise propagation, regulators have required that the more conservative BOOM model be employed in conjunction with SIPS in evaluating peak noise levels in populated areas. By simultaneously considering the output of both models, in 2001, UTTR detonated 104 missile motors having net explosive weights (NEW) that ranged between 14,960 and 38,938 lb without a recorded public noise complaint. Based on the encouraging results, the U.S. Department of Defense is considering expanding the application of these noise models to support the detonation of missile motors having a NEW of 81,000 lb. Recent modeling results suggest that, under appropriate weather conditions, missile motors containing up to 96,000 lb NEW can be detonated at the UTTR without exceeding the regulatory noise limit of 134 decibels (dB).

Department of Defense Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... Register is mandated for the regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U... the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because... Flexibility Act. Printing of these entries is limited to fields that contain information required by the...

17 CFR 240.19d-2 - Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory...

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory organization. 240.19d-2 Section 240.19d-2... summary suspensions by a self-regulatory organization. If any self-regulatory organization imposes any...

17 CFR 240.19d-2 - Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory organization. 240.19d-2 Section 240.19d-2... summary suspensions by a self-regulatory organization. If any self-regulatory organization imposes any...

17 CFR 240.19d-2 - Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory...

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory organization. 240.19d-2 Section 240.19d-2... summary suspensions by a self-regulatory organization. If any self-regulatory organization imposes any...

17 CFR 240.19d-2 - Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory...

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory organization. 240.19d-2 Section 240.19d-2... summary suspensions by a self-regulatory organization. If any self-regulatory organization imposes any...

17 CFR 240.19d-2 - Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory...

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Applications for stays of disciplinary sanctions or summary suspensions by a self-regulatory organization. 240.19d-2 Section 240.19d-2... summary suspensions by a self-regulatory organization. If any self-regulatory organization imposes any...

Unmanned aircraft systems in wildlife research: Current and future applications of a transformative technology

USGS Publications Warehouse

Christie, Katherine S.; Gilbert, Sophie L.; Brown, Casey L.; Hatfield, Michael; Hanson, Leanne

2016-01-01

Unmanned aircraft systems (UAS) – also called unmanned aerial vehicles (UAVs) or drones – are an emerging tool that may provide a safer, more cost-effective, and quieter alternative to traditional research methods. We review examples where UAS have been used to document wildlife abundance, behavior, and habitat, and illustrate the strengths and weaknesses of this technology with two case studies. We summarize research on behavioral responses of wildlife to UAS, and discuss the need to understand how recreational and commercial applications of this technology could disturb certain species. Currently, the widespread implementation of UAS by scientists is limited by flight range, regulatory frameworks, and a lack of validation. UAS are most effective when used to examine smaller areas close to their launch sites, whereas manned aircraft are recommended for surveying greater distances. The growing demand for UAS in research and industry is driving rapid regulatory and technological progress, which in turn will make them more accessible and effective as analytical tools.

Advancing the Adverse Outcome Pathway Framework - an ...

EPA Pesticide Factsheets

The ability of scientists to conduct whole organism toxicity tests to understand chemical safety has been significantly outpaced by the rapid synthesis of new chemicals. Therefore, to increase efficiencies in chemical risk assessment, scientists are turning to mechanistic-based studies, making greater use of in vitro and in silico methods, to screen for potential environmental and human health hazards. A framework that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP). A number of international activities have focused on AOP development and plausible applications to regulatory decision-making. These interactions have prompted dialog between research scientists and regulatory communities to consider how best to use the AOP framework in risk assessment. While expert-facilitated discussions have been instrumental in moving the science of AOPs forward, it was recognized that a survey of the broader scientific community would aid in identifying shortcomings and guiding future initiatives for the AOP framework. To that end, a ?‘Horizon Scanning’ exercise was conducted to solicit questions from the global scientific and regulatory communities concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. The m

Regulatory assessment of chemical mixtures: Requirements, current approaches and future perspectives.

PubMed

Kienzler, Aude; Bopp, Stephanie K; van der Linden, Sander; Berggren, Elisabet; Worth, Andrew

2016-10-01

This paper reviews regulatory requirements and recent case studies to illustrate how the risk assessment (RA) of chemical mixtures is conducted, considering both the effects on human health and on the environment. A broad range of chemicals, regulations and RA methodologies are covered, in order to identify mixtures of concern, gaps in the regulatory framework, data needs, and further work to be carried out. Also the current and potential future use of novel tools (Adverse Outcome Pathways, in silico tools, toxicokinetic modelling, etc.) in the RA of combined effects were reviewed. The assumptions made in the RA, predictive model specifications and the choice of toxic reference values can greatly influence the assessment outcome, and should therefore be specifically justified. Novel tools could support mixture RA mainly by providing a better understanding of the underlying mechanisms of combined effects. Nevertheless, their use is currently limited because of a lack of guidance, data, and expertise. More guidance is needed to facilitate their application. As far as the authors are aware, no prospective RA concerning chemicals related to various regulatory sectors has been performed to date, even though numerous chemicals are registered under several regulatory frameworks. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

PubMed

Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

2014-12-01

Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of physiologically relevant biopharmaceutics tools within the pharmaceutical industry and in regulatory sciences: Where are we now and what are the gaps?

PubMed

Flanagan, Talia; Van Peer, Achiel; Lindahl, Anders

2016-08-25

Regulatory interactions are an important part of the drug development and licensing process. A survey on the use of biopharmaceutical tools for regulatory purposes has been carried out within the industry community of the EU project OrBiTo within Innovative Medicines Initiative (IMI). The aim was to capture current practice and experience in using in vitro and in silico biopharmaceutics tools at various stages of development, what barriers exist or are perceived, and to understand the current gaps in regulatory biopharmaceutics. The survey indicated that biorelevant dissolution testing and physiologically based modelling and simulation are widely applied throughout development to address a number of biopharmaceutics issues. However, data from these in vitro and in silico predictive biopharmaceutics tools are submitted to regulatory authorities far less often than they are used for internal risk assessment and decision making. This may prevent regulators from becoming familiar with these tools and how they are applied in industry, and limits the opportunities for biopharmaceutics scientists working in industry to understand the acceptability of these tools in the regulatory environment. It is anticipated that the advanced biopharmaceutics tools and understanding delivered in the next years by OrBiTo and other initiatives in the area of predictive tools will also be of value in the regulatory setting, and provide a basis for more informed and confident biopharmaceutics risk assessment and regulatory decision making. To enable the regulatory potential of predictive biopharmaceutics tools to be realized, further scientific dialogue is needed between industry, regulators and scientists in academia, and more examples need to be published to demonstrate the applicability of these tools. Copyright © 2016 Elsevier B.V. All rights reserved.

78 FR 73566 - Standard Format and Content for a License Application for an Independent Spent Fuel Storage...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-06

...The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment draft regulatory guide (DG), DG-3042, ``Standard Format and Content for a License Application for an Independent Spent Fuel Storage Installation or a Monitored Retrievable Storage Facility.'' This draft regulatory guide is proposed revision 2 of Regulatory Guide 3.50, which provides a format that the NRC considers acceptable for submitting the information for license applications to store spent nuclear fuel, high-level radioactive waste, and/or reactor-related Greater than Class C waste.

Agro-economic impact of cattle cloning.

PubMed

Faber, D C; Ferre, L B; Metzger, J; Robl, J M; Kasinathan, P

2004-01-01

The purpose of this paper is to review the economic and social implications of cloned cattle, their products, and their offspring as related to production agriculture. Cloning technology in cattle has several applications outside of traditional production agriculture. These applications can include bio-medical applications, such as the production of pharmaceuticals in the blood or milk of transgenic cattle. Cloning may also be useful in the production of research models. These models may or may not include genetic modifications. Uses in agriculture include many applications of the technology. These include making genetic copies of elite seed stock and prize winning show cattle. Other purposes may range from "insurance" to making copies of cattle that have sentimental value, similar to cloning of pets. Increased selection opportunities available with cloning may provide for improvement in genetic gain. The ultimate goal of cloning has often been envisioned as a system for producing quantity and uniformity of the perfect dairy cow. However, only if heritability were 100%, would clone mates have complete uniformity. Changes in the environment may have significant impact on the productivity and longevity of the resulting clones. Changes in consumer preferences and economic input costs may all change the definition of the perfect cow. The cost of producing such animals via cloning must be economically feasible to meet the intended applications. Present inefficiencies limit cloning opportunities to highly valued animals. Improvements are necessary to move the applications toward commercial application. Cloning has additional obstacles to conquer. Social and regulatory acceptance of cloning is paramount to its utilization in production agriculture. Regulatory acceptance will need to address the animal, its products, and its offspring. In summary, cloning is another tool in the animal biotechnology toolbox, which includes artificial insemination, sexing of semen, embryo sexing and in vitro fertilization. While it will not replace any of the above mentioned, its degree of utilization will depend on both improvement in efficiency as well as social and regulatory acceptance.

ReNE: A Cytoscape Plugin for Regulatory Network Enhancement

PubMed Central

Politano, Gianfranco; Benso, Alfredo; Savino, Alessandro; Di Carlo, Stefano

2014-01-01

One of the biggest challenges in the study of biological regulatory mechanisms is the integration, americanmodeling, and analysis of the complex interactions which take place in biological networks. Despite post transcriptional regulatory elements (i.e., miRNAs) are widely investigated in current research, their usage and visualization in biological networks is very limited. Regulatory networks are commonly limited to gene entities. To integrate networks with post transcriptional regulatory data, researchers are therefore forced to manually resort to specific third party databases. In this context, we introduce ReNE, a Cytoscape 3.x plugin designed to automatically enrich a standard gene-based regulatory network with more detailed transcriptional, post transcriptional, and translational data, resulting in an enhanced network that more precisely models the actual biological regulatory mechanisms. ReNE can automatically import a network layout from the Reactome or KEGG repositories, or work with custom pathways described using a standard OWL/XML data format that the Cytoscape import procedure accepts. Moreover, ReNE allows researchers to merge multiple pathways coming from different sources. The merged network structure is normalized to guarantee a consistent and uniform description of the network nodes and edges and to enrich all integrated data with additional annotations retrieved from genome-wide databases like NCBI, thus producing a pathway fully manageable through the Cytoscape environment. The normalized network is then analyzed to include missing transcription factors, miRNAs, and proteins. The resulting enhanced network is still a fully functional Cytoscape network where each regulatory element (transcription factor, miRNA, gene, protein) and regulatory mechanism (up-regulation/down-regulation) is clearly visually identifiable, thus enabling a better visual understanding of its role and the effect in the network behavior. The enhanced network produced by ReNE is exportable in multiple formats for further analysis via third party applications. ReNE can be freely installed from the Cytoscape App Store (http://apps.cytoscape.org/apps/rene) and the full source code is freely available for download through a SVN repository accessible at http://www.sysbio.polito.it/tools_svn/BioInformatics/Rene/releases/. ReNE enhances a network by only integrating data from public repositories, without any inference or prediction. The reliability of the introduced interactions only depends on the reliability of the source data, which is out of control of ReNe developers. PMID:25541727

Advancing the adverse outcome pathway framework and its ...

EPA Pesticide Factsheets

Regulatory agencies worldwide are confronted with the challenging task of assessing the risks of thousands of chemicals to protect both human health and the environment. Traditional toxicity testing largely relies on apical endpoints from whole animal studies, which, in addition to ethical concerns, is costly and time prohibitive. As a result, the utility of mechanism-based in silico, in vitro, and in vivo approaches to support chemical safety evaluations have increasingly been explored. An approach that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP) framework. A number of international workshops and expert meetings have been held over the past years focusing on the AOP framework and its applications to chemical risk assessment. Although, these interactions have illustrated the necessity of expert guidance in moving the science of AOPs and their applications forward, there is also the recognition that a broader survey of the scientific community could be useful in guiding future initiatives in the AOP arena. To that end, a Horizon Scanning exercise was conducted to solicit questions from the global scientific community concerning the challenges or limitations that must be addressed in order to realize the full potential of the AOP framework in research and regulatory decision making. Over a 4 month ques

Allowance trading activity and state regulatory rulings: Evidence from the US Acid Rain Program

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

Bailey, E.M.

1997-12-31

The US Acid Rain Program is one of the first, and by far the most extensive, applications of a market based approach to pollution control. From the beginning, there has been concern whether utilities would participate in allowance trading, and whether regulatory activity at the state level would further complicate utilities` decision to trade allowances. This paper finds that public utility commission regulation has encouraged allowance trading activity in states with regulatory rulings, but that allowance trading activity has not been limited to states issuing regulations. Until there is evidence suggesting that significant additional cost savings could have been obtainedmore » if additional allowance trading activity had occurred in states without regulations or that utilities in states with regulations are still not taking advantage of all cost saving trading opportunities, this analysis suggests that there is little reason to believe that allowance trading activity is impeded by public utility commission regulations.« less

78 FR 25129 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-29

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule Change Regarding Central Counterparty Resolution and Recovery Procedures April 22, 2013. On March 7, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission...

78 FR 75579 - License Renewal Application for Grand Gulf Nuclear Station, Unit 1

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-416; NRC-2011-0262] License Renewal Application for Grand Gulf Nuclear Station, Unit 1 AGENCY: Nuclear Regulatory Commission. ACTION: Draft supplemental....S. Nuclear Regulatory Commission (NRC) is issuing for public comment a draft, plant-specific...

77 FR 43620 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... self-regulatory organization consents, the Commission shall either approve the proposed rule change...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to the Handling of Stop and Stop Limit...

75 FR 21773 - Improving Government Regulations; Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... Register is mandated for the regulatory flexibility agendas required by the Regulatory Flexibility Act (5 U... the Agency's regulatory flexibility agenda, in accordance with the Regulatory Flexibility Act, because... Flexibility Act. Printing of these entries is limited to fields that contain information required by the...

77 FR 26066 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

...-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change to Provide for a T+1 Settlement of the Initial Payment Related to the CDS Contracts Cleared by ICE Clear Europe Limited April 26, 2012. I. Introduction On March 6, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the...

Regulatory T cells in the control of host-microorganism interactions (*).

PubMed

Belkaid, Yasmine; Tarbell, Kristin

2009-01-01

Each microenvironment requires a specific set of regulatory elements that are finely and constantly tuned to maintain local homeostasis. Various populations of regulatory T cells contribute to the maintenance of this equilibrium and establishment of controlled immune responses. In particular, regulatory T cells limit the magnitude of effector responses, which may result in failure to adequately control infection. However, regulatory T cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses against pathogenic microbes as well as commensals. In this review, we describe various situations in which the balance between regulatory T cells and effector immune functions influence the outcome of host-microorganism coexistence and discuss current hypotheses and points of polemic associated with the origin, target, and antigen specificity of both endogenous and induced regulatory T cells during these interactions.

78 FR 63501 - Request To Submit a Two-Part Application-Northwest Medical Isotopes, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... NUCLEAR REGULATORY COMMISSION [Project No. 0803; NRC-2013-0235] Request To Submit a Two-Part Application--Northwest Medical Isotopes, LLC AGENCY: Nuclear Regulatory Commission. ACTION: Exemption. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is issuing an exemption in response to an August 9, 2013...

75 FR 39610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... Effectiveness of Proposed Rule Change Amending Financial Industry Regulatory Authority, Inc. Online Form NMA... Substance of the Proposed Rule Change FINRA is proposing to amend online Form NMA, the standardized... Proposed Rule Change 1. Purpose Form NMA is the standardized online membership application form applicants...

Regulatory challenges associated with conducting multicountry clinical trials in resource-limited settings.

PubMed

Ndebele, Paul; Blanchard-Horan, Christina; Shahkolahi, Akbar; Sanne, Ian

2014-01-01

International public health and infectious diseases research has expanded to become a global enterprise transcending national and continental borders in organized networks addressing high-impact diseases. In conducting multicountry clinical trials, sponsors and investigators have to ensure that they meet regulatory requirements in all countries in which the clinical trials will be conducted. Some of these requirements include review and approval by national drug regulatory authorities and recognized research ethics committees. A limiting factor to the efficient conduct of multicountry clinical trials is the regulatory environment in each collaborating country, with significant differences determined by various factors including the laws and the procedures used in each country. The long regulatory processes in resource-limited countries may hinder the efficient implementation of multisite clinical trials, delaying research important to the health of populations in these countries and costing millions of dollars a year.

Establishment of Application Guidance for OTC non-Kampo Crude Drug Extract Products in Japan

PubMed Central

Somekawa, Layla; Maegawa, Hikoichiro; Tsukada, Shinsuke; Nakamura, Takatoshi

2017-01-01

Currently, there are no standardized regulatory systems for herbal medicinal products worldwide. Communication and sharing of knowledge between different regulatory systems will lead to mutual understanding and might help identify topics which deserve further discussion in the establishment of common standards. Regulatory information on traditional herbal medicinal products in Japan is updated by the establishment of Application Guidance for over-the-counter non-Kampo Crude Drug Extract Products. We would like to report on updated regulatory information on the new Application Guidance. Methods for comparison of Crude Drug Extract formulation and standard decoction and criteria for application and the key points to consider for each criterion are indicated in the guidance. Establishment of the guidance contributes to improvements in public health. We hope that the regulatory information about traditional herbal medicinal products in Japan will be of contribution to tackling the challenging task of regulating traditional herbal products worldwide. PMID:28894633

75 FR 1830 - Final Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

... review of applications for permits and licenses. RG 5.71, ``Cyber Security Programs for Nuclear... NUCLEAR REGULATORY COMMISSION [NRC-2010-0009] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

WhatsApp in Stroke Systems: Current Use and Regulatory Concerns.

PubMed

Calleja-Castillo, Juan M; Gonzalez-Calderon, Gina

2018-01-01

Smartphone use is extremely common. Applications such as WhatsApp have billions of users and physicians are no exception. Stroke Medicine is a field where instant communication among fairly large groups is essential. In developing countries, economic limitations preclude the possibility of acquiring proper communication platforms. Thus, WhatsApp has been used as an organizational tool, for sharing clinical data, and for real time guidance of clinical care decisions. It has evolved into a cheap, accessible tool for telemedicine. Nevertheless, regulatory and privacy issues must be addressed. Some countries have implemented legislation to address this issue, while others lag behind. In this article, we present an overview on the different roles WhatsApp has acquired as a clinical tool in stroke systems and the potential privacy concerns of its use.

WhatsApp in Stroke Systems: Current Use and Regulatory Concerns

PubMed Central

Calleja-Castillo, Juan M.; Gonzalez-Calderon, Gina

2018-01-01

Smartphone use is extremely common. Applications such as WhatsApp have billions of users and physicians are no exception. Stroke Medicine is a field where instant communication among fairly large groups is essential. In developing countries, economic limitations preclude the possibility of acquiring proper communication platforms. Thus, WhatsApp has been used as an organizational tool, for sharing clinical data, and for real time guidance of clinical care decisions. It has evolved into a cheap, accessible tool for telemedicine. Nevertheless, regulatory and privacy issues must be addressed. Some countries have implemented legislation to address this issue, while others lag behind. In this article, we present an overview on the different roles WhatsApp has acquired as a clinical tool in stroke systems and the potential privacy concerns of its use. PMID:29904369

The use of biopharmaceutic classification of drugs in drug discovery and development: current status and future extension.

PubMed

Lennernäs, Hans; Abrahamsson, Bertil

2005-03-01

Bioavailability (BA) and bioequivalence (BE) play a central role in pharmaceutical product development and BE studies are presently being conducted for New Drug Applications (NDAs) of new compounds, in supplementary NDAs for new medical indications and product line extensions, in Abbreviated New Drug Applications (ANDAs) of generic products and in applications for scale-up and post-approval changes. The Biopharmaceutics Classification System (BCS) has been developed to provide a scientific approach for classifying drug compounds based on solubility as related to dose and intestinal permeability in combination with the dissolution properties of the oral immediaterelease (IR) dosage form. The aim of the BCS is to provide a regulatory tool for replacing certain BE studies by accurate in-vitro dissolution tests. The aim of this review is to present the status of the BCS and discuss its future application in pharmaceutical product development. The future application of the BCS is most likely increasingly important when the present framework gains increased recognition, which will probably be the case if the BCS borders for certain class II and III drugs are extended. The future revision of the BCS guidelines by the regulatory agencies in communication with academic and industrial scientists is exciting and will hopefully result in an increased applicability in drug development. Finally, we emphasize the great use of the BCS as a simple tool in early drug development to determine the rate-limiting step in the oral absorption process, which has facilitated the information between different experts involved in the overall drug development process. This increased awareness of a proper biopharmaceutical characterization of new drugs may in the future result in drug molecules with a sufficiently high permeability, solubility and dissolution rate, and that will automatically increase the importance of the BCS as a regulatory tool over time.

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

NASA Technical Reports Server (NTRS)

Duda, Kristen; Scroggins, Sharon

2008-01-01

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

76 FR 76153 - Allco Renewable Energy Limited v. Massachusetts Electric Company d/b/a National Grid; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL12-12-000] Allco Renewable Energy Limited v. Massachusetts Electric Company d/b/a National Grid; Notice of Complaint Take notice... Public Utilities Regulatory Policies Act (PURPA), Allco Renewable Energy Limited filed a formal complaint...

78 FR 51248 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change Related to... August 14, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange... been prepared primarily by ICE Clear Europe. The Commission is publishing this notice to solicit...

78 FR 19057 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing Proposed Rule Changes...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing Proposed Rule Changes Regarding Central..., 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission... prepared primarily by ICE Clear Europe. The Commission is publishing this notice to solicit comments on the...

78 FR 7844 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-04

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Withdrawal of Proposed Rule Change To Clear Western European Sovereign CDS Contracts January 29, 2013. On October 15, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission''), pursuant to...

78 FR 54718 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-05

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed... given that on August 20, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities..., which Items have been prepared primarily by ICE Clear Europe. ICE Clear Europe filed the proposal...

78 FR 28680 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend Delivery Procedures To Reflect the Clearing Relationship for ICE Futures Europe... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 24, 2013, ICE Clear Europe Limited...

78 FR 333 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-03

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission'') the...

Regulatory cross-cutting topics for fuel cycle facilities.

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

Denman, Matthew R.; Brown, Jason; Goldmann, Andrew Scott

This report overviews crosscutting regulatory topics for nuclear fuel cycle facilities for use in the Fuel Cycle Research & Development Nuclear Fuel Cycle Evaluation and Screening study. In particular, the regulatory infrastructure and analysis capability is assessed for the following topical areas: Fire Regulations (i.e., how applicable are current Nuclear Regulatory Commission (NRC) and/or International Atomic Energy Agency (IAEA) fire regulations to advance fuel cycle facilities) Consequence Assessment (i.e., how applicable are current radionuclide transportation tools to support risk-informed regulations and Level 2 and/or 3 PRA) While not addressed in detail, the following regulatory topic is also discussed: Integrated Security,more » Safeguard and Safety Requirement (i.e., how applicable are current Nuclear Regulatory Commission (NRC) regulations to future fuel cycle facilities which will likely be required to balance the sometimes conflicting Material Accountability, Security, and Safety requirements.)« less

Liposome Technology for Industrial Purposes

PubMed Central

Wagner, Andreas; Vorauer-Uhl, Karola

2011-01-01

Liposomes, spherical vesicles consisting of one or more phospholipid bilayers, were first described in the mid 60s by Bangham and coworkers. Since then, liposomes have made their way to the market. Today, numerous lab scale but only a few large-scale techniques are available. However, a lot of these methods have serious limitations in terms of entrapment of sensitive molecules due to their exposure to mechanical and/or chemical stress. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability. An additional point of view was taken to regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents. PMID:21490754

Invited review current progress and limitations of spider silk for biomedical applications.

PubMed

Widhe, Mona; Johansson, Jan; Hedhammar, My; Rising, Anna

2012-06-01

Spider silk is a fascinating material combining remarkable mechanical properties with low density and biodegradability. Because of these properties and historical descriptions of medical applications, spider silk has been proposed to be the ideal biomaterial. However, overcoming the obstacles to produce spider silk in sufficient quantities and in a manner that meets regulatory demands has proven to be a difficult task. Also, there are relatively few studies of spider silk in biomedical applications available, and the methods and materials used vary a lot. Herein we summarize cell culture- and in vivo implantation studies of natural and synthetic spider silk, and also review the current status and future challenges in the quest for a large scale production of spider silk for medical applications. Copyright © 2011 Wiley Periodicals, Inc.

Issues and approaches for ensuring effective communication on acceptable daily exposure (ADE) values applied to pharmaceutical cleaning.

PubMed

Olson, Michael J; Faria, Ellen C; Hayes, Eileen P; Jolly, Robert A; Barle, Ester Lovsin; Molnar, Lance R; Naumann, Bruce D; Pecquet, Alison M; Shipp, Bryan K; Sussman, Robert G; Weideman, Patricia A

2016-08-01

This manuscript centers on communication with key stakeholders of the concepts and program goals involved in the application of health-based pharmaceutical cleaning limits. Implementation of health-based cleaning limits, as distinct from other standards such as 1/1000th of the lowest clinical dose, is a concept recently introduced into regulatory domains. While there is a great deal of technical detail in the written framework underpinning the use of Acceptable Daily Exposures (ADEs) in cleaning (for example ISPE, 2010; Sargent et al., 2013), little is available to explain how to practically create a program which meets regulatory needs while also fulfilling good manufacturing practice (GMP) and other expectations. The lack of a harmonized approach for program implementation and communication across stakeholders can ultimately foster inappropriate application of these concepts. Thus, this period in time (2014-2017) could be considered transitional with respect to influencing best practice related to establishing health-based cleaning limits. Suggestions offered in this manuscript are intended to encourage full and accurate communication regarding both scientific and administrative elements of health-based ADE values used in pharmaceutical cleaning practice. This is a large and complex effort that requires: 1) clearly explaining key terms and definitions, 2) identification of stakeholders, 3) assessment of stakeholders' subject matter knowledge, 4) formulation of key messages fit to stakeholder needs, 5) identification of effective and timely means for communication, and 6) allocation of time, energy, and motivation for initiating and carrying through with communications. Copyright © 2016 Elsevier Inc. All rights reserved.

77 FR 33331 - Regulatory Guidance on the Applicability of Property-Carrier Hours-of-Service Rules to the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-06

... Regulatory Guidance on the Applicability of Property-Carrier Hours-of-Service Rules to the Driveaway Operation of Vehicles Designed to Transport Passengers AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: The property-carrier hours-of-service (HOS...

Ballast water regulations and the move toward concentration-based numeric discharge limits.

PubMed

Albert, Ryan J; Lishman, John M; Saxena, Juhi R

2013-03-01

Ballast water from shipping is a principal source for the introduction of nonindigenous species. As a result, numerous government bodies have adopted various ballast water management practices and discharge standards to slow or eliminate the future introduction and dispersal of these nonindigenous species. For researchers studying ballast water issues, understanding the regulatory framework is helpful to define the scope of research needed by policy makers to develop effective regulations. However, for most scientists, this information is difficult to obtain because it is outside the standard scientific literature and often difficult to interpret. This paper provides a brief review of the regulatory framework directed toward scientists studying ballast water and aquatic invasive species issues. We describe different approaches to ballast water management in international, U.S. federal and state, and domestic ballast water regulation. Specifically, we discuss standards established by the International Maritime Organization (IMO), the U.S. Coast Guard and U.S. Environmental Protection Agency, and individual states in the United States including California, New York, and Minnesota. Additionally, outside the United States, countries such as Australia, Canada, and New Zealand have well-established domestic ballast water regulatory regimes. Different approaches to regulation have recently resulted in variations between numeric concentration-based ballast water discharge limits, particularly in the United States, as well as reliance on use of ballast water exchange pending development and adoption of rigorous science-based discharge standards. To date, numeric concentration-based discharge limits have not generally been based upon a thorough application of risk-assessment methodologies. Regulators, making decisions based on the available information and methodologies before them, have consequently established varying standards, or not established standards at all. The review and refinement of ballast water discharge standards by regulatory agencies will benefit from activity by the scientific community to improve and develop more precise risk-assessment methodologies.

78 FR 45578 - Application For a License to Export Radioactive Waste

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... NUCLEAR REGULATORY COMMISSION Application For a License to Export Radioactive Waste Pursuant to 10 CFR 110.70 (b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear... requestor or petitioner upon the applicant, the office of the General Counsel, U.S. Nuclear Regulatory...

77 FR 15445 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... Effectiveness of Proposed Rule Change To Amend Online Form NMA, the Standardized Membership Application Form... online Form NMA, the standardized membership application form applicants must file pursuant to NASD Rule...), each applicant for FINRA membership must complete and electronically file the standardized online Form...

[Genome-editing: focus on the off-target effects].

PubMed

He, Xiubin; Gu, Feng

2017-10-25

Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

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

Not Available

These case studies constitute Part II of the ACL Guidance Document. They are intended to assist Regional and State personnel in exercising the discretion conferred by regulation in evaluating applications for alternate concentration limits (ACLs) submitted pursuant to 40 CFR 264.94. The document is not a regulation and should not be used as such. Regional and State personnel must exercise their discretion in using this guidance document as well as other relevant information in determining whether an ACL demonstration meets the regulatory standard.

Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Trial Calculation. Work Plan

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

Grabaskas, David; Bucknor, Matthew; Jerden, James

2016-02-01

The overall objective of the SFR Regulatory Technology Development Plan (RTDP) effort is to identify and address potential impediments to the SFR regulatory licensing process. In FY14, an analysis by Argonne identified the development of an SFR-specific MST methodology as an existing licensing gap with high regulatory importance and a potentially long lead-time to closure. This work was followed by an initial examination of the current state-of-knowledge regarding SFR source term development (ANLART-3), which reported several potential gaps. Among these were the potential inadequacies of current computational tools to properly model and assess the transport and retention of radionuclides duringmore » a metal fuel pool-type SFR core damage incident. The objective of the current work is to determine the adequacy of existing computational tools, and the associated knowledge database, for the calculation of an SFR MST. To accomplish this task, a trial MST calculation will be performed using available computational tools to establish their limitations with regard to relevant radionuclide release/retention/transport phenomena. The application of existing modeling tools will provide a definitive test to assess their suitability for an SFR MST calculation, while also identifying potential gaps in the current knowledge base and providing insight into open issues regarding regulatory criteria/requirements. The findings of this analysis will assist in determining future research and development needs.« less

77 FR 37458 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

...; facilitate the display of customer limit orders under FINRA Rule 6460 (Display of Customer Limit Orders); \\4... the Commission to evaluate the impact of the proposed pilot on the over-the-counter (``OTC'') equity... tiers, facilitate the display of customer limit orders under FINRA Rule 6460,\\15\\ and expand the Rule's...

78 FR 64255 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... Amending Commentary .07 to Rule 904 To Extend the Pilot Program That Eliminated the Position Limits for... that eliminated the position limits for options on SPDR S&P 500 ETF (``SPY'') (``SPY Pilot Program...- regulatory organizations (``SROs'') have adopted similar rules eliminating position limits on SPY and market...

77 FR 7652 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Proposed Rule Change To Revise...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Proposed Rule Change To Revise Rules and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 24, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange Commission (``Commission'') the proposed...

77 FR 11607 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval... \\2\\ notice is hereby given that on February 7, 2012, ICE Clear Europe Limited (``ICE Clear Europe... in Items I, II and III below, which Items have been prepared primarily by ICE Clear Europe. The...

78 FR 15775 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval...\\ notice is hereby given that on February 28, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed... Items I and II below, which Items have been prepared primarily by ICE Clear Europe. The Commission is...

78 FR 58576 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Clear Contracts Traded on ICE Endex September 18, 2013. Pursuant to Section 19(b)(1) of... that on September 18, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities...

77 FR 62289 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-12

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval... thereunder,\\2\\ notice is hereby given that on September 25, 2012, ICE Clear Europe Limited (``ICE Clear... described in Items I and II below, which items have been prepared primarily by ICE Clear Europe. The...

77 FR 76315 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-27

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Delivery Procedures To Reflect the Clearing Relationship for ICE Futures U.S. Inc... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2012, ICE Clear Europe Limited...

International guidelines for bioequivalence of systemically available orally administered generic drug products: a survey of similarities and differences.

PubMed

Davit, Barbara; Braddy, April C; Conner, Dale P; Yu, Lawrence X

2013-10-01

The objective of this article is to discuss the similarities and differences among bioequivalence approaches used by international regulatory authorities when reviewing applications for marketing new generic drug products which are systemically active and intended for oral administration. We focused on the 13 jurisdictions and organizations participating in the International Generic Drug Regulators Pilot. These are Australia, Brazil, Canada, China, Chinese Taipei, the European Medicines Association, Japan, Mexico, Singapore, South Korea, Switzerland, the USA, and the World Health Organization. We began with a comparison of how the various jurisdictions and organizations define a generic product and its corresponding reference product. We then compared the following bioequivalence approaches: recommended bioequivalence study designs, method of pharmacokinetic calculations and bioequivalence acceptance limits, recommendations for modifying bioequivalence study designs and limits for highly variable drugs and narrow therapeutic index drugs, provisions for waiving bioequivalence study requirements (granting biowaivers), and implementation of the Biopharmaceutics Classification System. We observed that, overall, there are more similarities than differences in bioequivalence approaches among the regulatory authorities surveyed.

Use of x-ray fluorescence for in-situ detection of metals

NASA Astrophysics Data System (ADS)

Elam, W. T. E.; Whitlock, Robert R.; Gilfrich, John V.

1995-01-01

X-ray fluorescence (XRF) is a well-established, non-destructive method of determining elemental concentrations at ppm levels in complex samples. It can operate in atmosphere with no sample preparation, and provides accuracies of 1% or better under optimum conditions. This report addresses two sets of issues concerning the use of x-ray fluorescence as a sensor technology for the cone penetrometer, for shipboard waste disposal, or for other in-situ, real- time environmental applications. The first issue concerns the applicability of XRF to these applications, and includes investigation of detection limits and matrix effects. We have evaluated the detection limits and quantitative accuracy of a sensor mock-up for metals in soils under conditions expected in the field. In addition, several novel ways of improving the lower limits of detection to reach the drinking water regulatory limits have been explored. The second issue is the engineering involved with constructing a spectrometer within the 1.75 inch diameter of the penetrometer pipe, which is the most rigorous physical constraint. Only small improvements over current state-of-the-art are required. Additional advantages of XRF are that no radioactive sources or hazardous materials are used in the sensor design, and no reagents or any possible sources of ignition are involved.

77 FR 70515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-26

... Effectiveness of Proposed Rule Change To Establish a Limited Waiver of the TRACE Professional Real-Time Data... limited waiver of the Professional Real-Time Data Display Fee of $60 to access Real-Time Trade Reporting...

10 CFR 30.50 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

10 CFR 70.50 - Reporting requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

10 CFR 70.50 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

10 CFR 30.50 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

10 CFR 70.50 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... event that prevents immediate protective actions necessary to avoid exposures to radiation or... licensee condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

10 CFR 30.50 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... prevents immediate protective actions necessary to avoid exposures to radiation or radioactive materials... license condition to prevent releases exceeding regulatory limits, to prevent exposures to radiation and radioactive materials exceeding regulatory limits, or to mitigate the consequences of an accident; (ii) The...

75 FR 76001 - Southwest Gas Corporation; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-35-000] Southwest Gas Corporation; Notice of Application November 29, 2010. On November 16, 2010, Southwest Gas Corporation (Southwest) filed with the Federal Energy Regulatory Commission (Commission) an application pursuant to...

The ethical landscape: identifying the right way to think about the ethical and societal aspects of synthetic biology research and products

PubMed Central

Yearley, Steven

2009-01-01

Synthetic biology promises to be highly innovative in its contribution to scientific understanding. But it offers other sorts of innovation too: in the variety of applications that could result and in the wide range of practitioners who could become involved. But directly corresponding to each of these is a kind of regulatory concern. If the entry barriers are low for a form of scientific practice with dramatic implications then the need for regulatory control over access is great since no one wants unlicensed operators releasing experimental organisms. If there are likely to be extensive opportunities for application within the human body and in the open environment (for energy production or novel forms of bioremediation) then the release and safety-testing implications are potentially enormous. Proponents of synthetic biology have been quick to realise that these challenges call for reviews of the societal and ethical aspects of synthetic biology. This paper shows that the template commonly adopted for such reviews draws on bioethics. It goes on to show that this template is far from ideal, both because of limitations in the way that bioethics has been institutionalized and because of key differences between the regulatory demands on synthetic biology and on bioethics. The paper concludes that broader models of societal and ethical review of synthetic biology are urgently required. PMID:19447816

Innovative Legal Approaches to Address Obesity

PubMed Central

Pomeranz, Jennifer L; Teret, Stephen P; Sugarman, Stephen D; Rutkow, Lainie; Brownell, Kelly D

2009-01-01

Context: The law is a powerful public health tool with considerable potential to address the obesity issue. Scientific advances, gaps in the current regulatory environment, and new ways of conceptualizing rights and responsibilities offer a foundation for legal innovation. Methods: This article connects developments in public health and nutrition with legal advances to define promising avenues for preventing obesity through the application of the law. Findings: Two sets of approaches are defined: (1) direct application of the law to factors known to contribute to obesity and (2) original and innovative legal solutions that address the weak regulatory stance of government and the ineffectiveness of existing policies used to control obesity. Specific legal strategies are discussed for limiting children's food marketing, confronting the potential addictive properties of food, compelling industry speech, increasing government speech, regulating conduct, using tort litigation, applying nuisance law as a litigation strategy, and considering performance-based regulation as an alternative to typical regulatory actions. Finally, preemption is an overriding issue and can play both a facilitative and a hindering role in obesity policy. Conclusions: Legal solutions are immediately available to the government to address obesity and should be considered at the federal, state, and local levels. New and innovative legal solutions represent opportunities to take the law in creative directions and to link legal, nutrition, and public health communities in constructive ways. PMID:19298420

Enhanced Regulatory Sequence Prediction Using Gapped k-mer Features

PubMed Central

Mohammad-Noori, Morteza; Beer, Michael A.

2014-01-01

Abstract Oligomers of length k, or k-mers, are convenient and widely used features for modeling the properties and functions of DNA and protein sequences. However, k-mers suffer from the inherent limitation that if the parameter k is increased to resolve longer features, the probability of observing any specific k-mer becomes very small, and k-mer counts approach a binary variable, with most k-mers absent and a few present once. Thus, any statistical learning approach using k-mers as features becomes susceptible to noisy training set k-mer frequencies once k becomes large. To address this problem, we introduce alternative feature sets using gapped k-mers, a new classifier, gkm-SVM, and a general method for robust estimation of k-mer frequencies. To make the method applicable to large-scale genome wide applications, we develop an efficient tree data structure for computing the kernel matrix. We show that compared to our original kmer-SVM and alternative approaches, our gkm-SVM predicts functional genomic regulatory elements and tissue specific enhancers with significantly improved accuracy, increasing the precision by up to a factor of two. We then show that gkm-SVM consistently outperforms kmer-SVM on human ENCODE ChIP-seq datasets, and further demonstrate the general utility of our method using a Naïve-Bayes classifier. Although developed for regulatory sequence analysis, these methods can be applied to any sequence classification problem. PMID:25033408

Enhanced regulatory sequence prediction using gapped k-mer features.

PubMed

Ghandi, Mahmoud; Lee, Dongwon; Mohammad-Noori, Morteza; Beer, Michael A

2014-07-01

Oligomers of length k, or k-mers, are convenient and widely used features for modeling the properties and functions of DNA and protein sequences. However, k-mers suffer from the inherent limitation that if the parameter k is increased to resolve longer features, the probability of observing any specific k-mer becomes very small, and k-mer counts approach a binary variable, with most k-mers absent and a few present once. Thus, any statistical learning approach using k-mers as features becomes susceptible to noisy training set k-mer frequencies once k becomes large. To address this problem, we introduce alternative feature sets using gapped k-mers, a new classifier, gkm-SVM, and a general method for robust estimation of k-mer frequencies. To make the method applicable to large-scale genome wide applications, we develop an efficient tree data structure for computing the kernel matrix. We show that compared to our original kmer-SVM and alternative approaches, our gkm-SVM predicts functional genomic regulatory elements and tissue specific enhancers with significantly improved accuracy, increasing the precision by up to a factor of two. We then show that gkm-SVM consistently outperforms kmer-SVM on human ENCODE ChIP-seq datasets, and further demonstrate the general utility of our method using a Naïve-Bayes classifier. Although developed for regulatory sequence analysis, these methods can be applied to any sequence classification problem.

Using Inequality Measures to Incorporate Environmental Justice into Regulatory Analyses

PubMed Central

Harper, Sam; Ruder, Eric; Roman, Henry A.; Geggel, Amelia; Nweke, Onyemaechi; Payne-Sturges, Devon; Levy, Jonathan I.

2013-01-01

Formally evaluating how specific policy measures influence environmental justice is challenging, especially in the context of regulatory analyses in which quantitative comparisons are the norm. However, there is a large literature on developing and applying quantitative measures of health inequality in other settings, and these measures may be applicable to environmental regulatory analyses. In this paper, we provide information to assist policy decision makers in determining the viability of using measures of health inequality in the context of environmental regulatory analyses. We conclude that quantification of the distribution of inequalities in health outcomes across social groups of concern, considering both within-group and between-group comparisons, would be consistent with both the structure of regulatory analysis and the core definition of environmental justice. Appropriate application of inequality indicators requires thorough characterization of the baseline distribution of exposures and risks, leveraging data generally available within regulatory analyses. Multiple inequality indicators may be applicable to regulatory analyses, and the choice among indicators should be based on explicit value judgments regarding the dimensions of environmental justice of greatest interest. PMID:23999551

Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

PubMed

Marx-Stoelting, P; Braeuning, A; Buhrke, T; Lampen, A; Niemann, L; Oelgeschlaeger, M; Rieke, S; Schmidt, F; Heise, T; Pfeil, R; Solecki, R

2015-11-01

Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

Regulatory frameworks for mobile medical applications.

PubMed

Censi, Federica; Mattei, Eugenio; Triventi, Michele; Calcagnini, Giovanni

2015-05-01

A mobile application (app) is a software program that runs on mobile communication devices such as a smartphone. The concept of a mobile medical app has gained popularity and diffusion but its reference regulatory context has raised discussion and concerns. Theoretically, a mobile app can be developed and uploaded easily by any person or entity. Thus, if an app can have some effects on the health of the users, it is mandatory to identify its reference regulatory context and the applicable prescriptions.

75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to the Trade Reporting Facility Limited Liability Company...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

21 CFR 312.86 - Focused FDA regulatory research.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Focused FDA regulatory research. 312.86 Section... Severely-debilitating Illnesses § 312.86 Focused FDA regulatory research. At the discretion of the agency, FDA may undertake focused regulatory research on critical rate-limiting aspects of the preclinical...

Software support in automation of medicinal product evaluations.

PubMed

Juric, Radmila; Shojanoori, Reza; Slevin, Lindi; Williams, Stephen

2005-01-01

Medicinal product evaluation is one of the most important tasks undertaken by government health departments and their regulatory authorities, in every country in the world. The automation and adequate software support are critical tasks that can improve the efficiency and interoperation of regulatory systems across the world. In this paper we propose a software solution that supports the automation of the (i) submission of licensing applications, and (ii) evaluations of submitted licensing applications, according to regulatory authorities' procedures. The novelty of our solution is in allowing licensing applications to be submitted in any country in the world and evaluated according to any evaluation procedure (which can be chosen by either regulatory authorities or pharmaceutical companies). Consequently, submission and evaluation procedures become interoperable and the associated data repositories/databases can be shared between various countries and regulatory authorities.

78 FR 73911 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... 3120 To Extend the Pilot Program That Eliminated the Position Limits for Options on SPDR S&P 500 ETF... extend the pilot program that eliminated the position limits for options on SPDR S&P 500 ETF (``SPY...- regulatory organizations (``SROs'') have adopted similar rules eliminating position limits on SPY and market...

78 FR 35335 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Amendment No. 2 to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Amendment No. 2 to Proposed Rule...\\ notice is hereby given that on June 4, 2013, ICE Clear Europe Limited (``ICE Clear Europe'') filed with... proposed rule changes to implement a clearing relationship in which ICE Clear Europe will clear contracts...

77 FR 75466 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Designation of a Longer Period...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Designation of a Longer Period for Commission... October 15, 2012, ICE Clear Europe Limited (``ICE Clear Europe'') filed with the Securities and Exchange...-day time period. \\5\\ 15 U.S.C. 78s(b)(2). The proposed rule change would permit ICE Clear Europe to...

77 FR 16105 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change To Provide for a T+1 Settlement of the Initial Payment Related to the CDS Contracts Cleared by ICE Clear Europe...\\ and Rule 19b-4 thereunder \\2\\ notice is hereby given that on March 6, 2012, ICE Clear Europe Limited...

77 FR 27254 - Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-09

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66911; File No. SR-ICEEU-2012-05] Self-Regulatory Organizations; ICE Clear Europe Limited; Order Approving Proposed Rule Change To Amend the ICE Clear Europe Limited CDS Procedures, Finance Procedures, and Rules With Respect to the Calculation and Payment of Interest on Mark-To-Market Margin on...

A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs)

PubMed Central

Jones, David R; McBlane, James W; McNaughton, Graham; Rajakumaraswamy, Nishanthan; Wydenbach, Kirsty

2013-01-01

The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines. PMID:23216470

Manipulating regulatory T cells: a promising strategy to treat autoimmunity.

PubMed

Zhang, Dunfang; Tu, Eric; Kasagi, Shimpei; Zanvit, Peter; Chen, Qianming; Chen, WanJun

2015-01-01

CD4(+)CD25(+)Foxp3(+)regulatory T cells (Treg cells) are extremely important in maintaining immune tolerance. Manipulation of Treg cells, especially autoantigen-specific Treg cells is a promising approach for treatments of autoimmune disease since Treg cells may provide the advantage of antigen specificity without overall immune suppression. However, the clinical application of Treg cells has long been limited due to low numbers of Treg cells and the difficulty in identifying their antigen specificity. In this review, we summarize studies that demonstrate regression of autoimmune diseases using Treg cells as therapeutics. We also discuss approaches to generate polyclonal and autoantigen-specific Treg cells in vitro and in vivo. We also discuss our recent study that describes a novel approach of generating autoantigen-specific Treg cells in vivo and restoring immune tolerance by two steps apoptosis-antigen therapy.

Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices

PubMed Central

Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

2015-01-01

While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of underfortified products and enforcement of applicable fortification standards. Only by taking concrete steps to improve the entire regulatory system that is built on a cooperative working relationship between regulatory agencies and food producers will a nutrition strategy that uses fortification see its intended health effects. PMID:26374804

A parallel implementation of the network identification by multiple regression (NIR) algorithm to reverse-engineer regulatory gene networks.

PubMed

Gregoretti, Francesco; Belcastro, Vincenzo; di Bernardo, Diego; Oliva, Gennaro

2010-04-21

The reverse engineering of gene regulatory networks using gene expression profile data has become crucial to gain novel biological knowledge. Large amounts of data that need to be analyzed are currently being produced due to advances in microarray technologies. Using current reverse engineering algorithms to analyze large data sets can be very computational-intensive. These emerging computational requirements can be met using parallel computing techniques. It has been shown that the Network Identification by multiple Regression (NIR) algorithm performs better than the other ready-to-use reverse engineering software. However it cannot be used with large networks with thousands of nodes--as is the case in biological networks--due to the high time and space complexity. In this work we overcome this limitation by designing and developing a parallel version of the NIR algorithm. The new implementation of the algorithm reaches a very good accuracy even for large gene networks, improving our understanding of the gene regulatory networks that is crucial for a wide range of biomedical applications.

Gene transfer strategies in animal transgenesis.

PubMed

Montoliu, Lluís

2002-01-01

Position effects in animal transgenesis have prevented the reproducible success and limited the initial expectations of this technique in many biotechnological projects. Historically, several strategies have been devised to overcome such position effects, including the progressive addition of regulatory elements belonging to the same or to a heterologous expression domain. An expression domain is thought to contain all regulatory elements that are needed to specifically control the expression of a given gene in time and space. The lack of profound knowledge on the chromatin structure of expression domains of biotechnological interest, such as mammary gland-specific genes, explains why most standard expression vectors have failed to drive high-level, position-independent, and copy-number-dependent expression of transgenes in a reproducible manner. In contrast, the application of artificial chromosome-type constructs to animal transgenesis usually ensures optimal expression levels. YACs, BACs, and PACs have become crucial tools in animal transgenesis, allowing the inclusion of distant key regulatory sequences, previously unknown, that are characteristic for each expression domain. These elements contribute to insulating the artificial chromosome-type constructs from chromosomal position effects and are fundamental in order to guarantee the correct expression of transgenes.

BIOSENSORS FOR ENVIRONMENTAL MONITORING: A REGULATORY PERSPECTIVE

EPA Science Inventory

Biosensors show the potential to complement laboratory-based analytical methods for environmental applications. Although biosensors for potential environmental-monitoring applications have been reported for a wide range of environmental pollutants, from a regulatory perspective, ...

A Survey of Social-Regulatory Practices in Selected Michigan Community Colleges.

ERIC Educational Resources Information Center

Hollander, Martin Elliot

This study surveyed social-regulatory practices of selected community colleges in Michigan to find out: origin and extent of written social-regulatory policies and the provisions for change; types of rules of conduct; and communication and enforcement of social-regulatory practices and rules. The study was limited to commuter-type publicly…

76 FR 31599 - Southern Star Central Gas Pipeline, Inc.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-01

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-481-000] Southern Star Central Gas Pipeline, Inc.; Notice of Application On May 13, 2011, Southern Star Central Gas Pipeline, Inc. (Southern Star) filed with the Federal Energy Regulatory Commission (Commission) an application under...

76 FR 46330 - NUREG-1934, Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG); Second Draft...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-02

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0568] NUREG-1934, Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG); Second Draft Report for Comment AGENCY: Nuclear Regulatory Commission... 1023259), ``Nuclear Power Plant Fire Modeling Application Guide (NPP FIRE MAG), Second Draft Report for...

Switching between nitrogen and glucose limitation: Unraveling transcriptional dynamics in Escherichia coli.

PubMed

Löffler, Michael; Simen, Joana Danica; Müller, Jan; Jäger, Günter; Laghrami, Salaheddine; Schäferhoff, Karin; Freund, Andreas; Takors, Ralf

2017-09-20

Transcriptional control under nitrogen and carbon-limitation conditions have been well analyzed for Escherichia coli. However, the transcriptional dynamics that underlie the shift in regulatory programs from nitrogen to carbon limitation is not well studied. In the present study, cells were cultivated at steady state under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose) limitation to monitor changes in transcriptional dynamics. Nitrogen limitation was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the "housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under glucose limitation. During the transition, nitrogen-mediated control was rapidly redeemed and mRNAs that encode active uptake systems, such as ptsG and manXYZ, were quickly amplified. Next, genes encoding facilitators such as lamB were overexpressed, followed by high affinity uptake systems such as mglABC and non-specific porins such as ompF. These regulatory programs are complex and require well-equilibrated and superior control. At the metabolome level, 2-oxoglutarate is the likely component that links carbon- and nitrogen-mediated regulation by interacting with major regulatory elements. In the case of dual glucose and ammonia limitation, sigma 24 (RpoE) appears to play a key role in orchestrating these complex regulatory networks. Copyright © 2017 Elsevier B.V. All rights reserved.

Illicit drugs policy through the lens of regulation.

PubMed

Ritter, Alison

2010-07-01

The application of regulatory theory to the problem of illicit drugs has generally been thought about only in terms of 'command and control'. The international treaties governing global illicit drug control and the use of law enforcement to dissuade and punish offenders have been primary strategies. In this paper I explore the application of other aspects of regulatory theory to illicit drugs-primarily self-regulation and market regulation. There has been an overreliance on strategies from the top of the regulatory pyramid. Two other regulatory strategies--self-regulation and market regulation--can be applied to illicit drugs. Self-regulation, driven by the proactive support of consumer groups may reduce drug-related harms. Market strategies such as pill-testing can change consumer preferences and encourage alternate seller behaviour. Regulatory theory is also concerned with partnerships between the state and third parties: strategies in these areas include partnerships between police and pharmacies regarding sale of potential precursor chemicals. Regulatory theory and practice is a rich and well-developed field in the social sciences. I argue that governments should consider the full array of regulatory strategies. Using regulatory theory provides a rationale and justification to strategies that are currently at the whim of politics, such as funding for user groups. The greater application of regulatory approaches may produce more flexible and structured illicit drug policies. Copyright (c) 2009 Elsevier B.V. All rights reserved.

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

PubMed

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

2017-04-03

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

41 CFR 109-40.102 - Representation before regulatory bodies.

Code of Federal Regulations, 2011 CFR

2011-01-01

... regulatory bodies. 109-40.102 Section 109-40.102 Public Contracts and Property Management Federal Property... Representation before regulatory bodies. Participation in proceedings related to carrier applications to regulatory bodies for temporary or permanent authority to operate in specified geographical locations shall...

41 CFR 109-40.102 - Representation before regulatory bodies.

Code of Federal Regulations, 2010 CFR

2010-07-01

... regulatory bodies. 109-40.102 Section 109-40.102 Public Contracts and Property Management Federal Property... Representation before regulatory bodies. Participation in proceedings related to carrier applications to regulatory bodies for temporary or permanent authority to operate in specified geographical locations shall...

10 CFR 51.35 - Requirement to publish finding of no significant impact; limitation on Commission action.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Requirement to publish finding of no significant impact; limitation on Commission action. 51.35 Section 51.35 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National...

10 CFR 72.75 - Reporting requirements for specific events and conditions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

10 CFR 72.75 - Reporting requirements for specific events and conditions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

10 CFR 72.75 - Reporting requirements for specific events and conditions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

10 CFR 72.75 - Reporting requirements for specific events and conditions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regulatory limits, to prevent exposures to radiation or radioactive materials that could exceed regulatory limits, or to mitigate the consequences of an accident; and (ii) No redundant equipment was available and... waste involved in the event; and (v) Any personnel radiation exposure data. (f) Follow-up notification...

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

EPA Science Inventory

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

47 CFR 1.1910 - Effect of insufficient fee payments, delinquent debts, or debarment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... determine if the applicant has paid the appropriate application fee, appropriate regulatory fees, is... proper application or regulatory fee will be handled pursuant to the rules set forth in 47 CFR part 1... challenge through an administrative appeal or a contested judicial proceeding either to the existence or...

77 FR 16278 - License Renewal Application for Indian Point Nuclear Generating Units 2 and 3; Entergy Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2008-0672] License Renewal Application for Indian Point Nuclear Generating Units 2 and 3; Entergy Nuclear Operations, Inc. AGENCY: Nuclear Regulatory Commission. ACTION: License renewal application; intent to prepare supplement to final...

Links Between Ethylene and Sulfur Nutrition-A Regulatory Interplay or Just Metabolite Association?

PubMed

Wawrzynska, Anna; Moniuszko, Grzegorz; Sirko, Agnieszka

2015-01-01

Multiple reports demonstrate associations between ethylene and sulfur metabolisms, however the details of these links have not yet been fully characterized; the links might be at the metabolic and the regulatory levels. First, sulfur-containing metabolite, methionine, is a precursor of ethylene and is a rate limiting metabolite for ethylene synthesis; the methionine cycle contributes to both sulfur and ethylene metabolism. On the other hand, ethylene is involved in the complex response networks to various stresses and it is known that S deficiency leads to photosynthesis and C metabolism disturbances that might be responsible for oxidative stress. In several plant species, ethylene increases during sulfur starvation and might serve signaling purposes to initiate the process of metabolism reprogramming during adjustment to sulfur deficit. An elevated level of ethylene might result from increased activity of enzymes involved in its synthesis. It has been demonstrated that the alleviation of cadmium stress in plants by application of S seems to be mediated by ethylene formation. On the other hand, the ethylene-insensitive Nicotiana attenuata plants are impaired in sulfur uptake, reduction and metabolism, and they invest their already limited S into methionine needed for synthesis of ethylene constitutively emitted in large amounts to the atmosphere. Regulatory links of EIN3 and SLIM1 (both from the same family of transcriptional factors) involved in the regulation of ethylene and sulfur pathway, respectively, is also quite probable as well as the reciprocal modulation of both pathways on the enzyme activity levels.

ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements.

PubMed

Taylor, James; Tyekucheva, Svitlana; King, David C; Hardison, Ross C; Miller, Webb; Chiaromonte, Francesca

2006-12-01

Genomic sequence signals - such as base composition, presence of particular motifs, or evolutionary constraint - have been used effectively to identify functional elements. However, approaches based only on specific signals known to correlate with function can be quite limiting. When training data are available, application of computational learning algorithms to multispecies alignments has the potential to capture broader and more informative sequence and evolutionary patterns that better characterize a class of elements. However, effective exploitation of patterns in multispecies alignments is impeded by the vast number of possible alignment columns and by a limited understanding of which particular strings of columns may characterize a given class. We have developed a computational method, called ESPERR (evolutionary and sequence pattern extraction through reduced representations), which uses training examples to learn encodings of multispecies alignments into reduced forms tailored for the prediction of chosen classes of functional elements. ESPERR produces a greatly improved Regulatory Potential score, which can discriminate regulatory regions from neutral sites with excellent accuracy ( approximately 94%). This score captures strong signals (GC content and conservation), as well as subtler signals (with small contributions from many different alignment patterns) that characterize the regulatory elements in our training set. ESPERR is also effective for predicting other classes of functional elements, as we show for DNaseI hypersensitive sites and highly conserved regions with developmental enhancer activity. Our software, training data, and genome-wide predictions are available from our Web site (http://www.bx.psu.edu/projects/esperr).

Utilizing toxicogenomic data to understand chemical mechanism of action in risk assessment

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

Wilson, Vickie S., E-mail: wilson.vickie@epa.gov; Keshava, Nagalakshmi; Hester, Susan

2013-09-15

The predominant role of toxicogenomic data in risk assessment, thus far, has been one of augmentation of more traditional in vitro and in vivo toxicology data. This article focuses on the current available examples of instances where toxicogenomic data has been evaluated in human health risk assessment (e.g., acetochlor and arsenicals) which have been limited to the application of toxicogenomic data to inform mechanism of action. This article reviews the regulatory policy backdrop and highlights important efforts to ultimately achieve regulatory acceptance. A number of research efforts on specific chemicals that were designed for risk assessment purposes have employed mechanismmore » or mode of action hypothesis testing and generating strategies. The strides made by large scale efforts to utilize toxicogenomic data in screening, testing, and risk assessment are also discussed. These efforts include both the refinement of methodologies for performing toxicogenomics studies and analysis of the resultant data sets. The current issues limiting the application of toxicogenomics to define mode or mechanism of action in risk assessment are discussed together with interrelated research needs. In summary, as chemical risk assessment moves away from a single mechanism of action approach toward a toxicity pathway-based paradigm, we envision that toxicogenomic data from multiple technologies (e.g., proteomics, metabolomics, transcriptomics, supportive RT-PCR studies) can be used in conjunction with one another to understand the complexities of multiple, and possibly interacting, pathways affected by chemicals which will impact human health risk assessment.« less

REGULATORY APPLICATIONS OF POREWATER TOXICITY TESTING

EPA Science Inventory

The purpose of this chapter is to evaluate the use of porewater toxicity tests in regulatory applications, including their potential use in the development of sediment quality guideline (SQG) values. Specifically, the following discussion focuses on the appropriateness and readin...

Fronting Integrated Scientific Web Applications: Design Features and Benefits for Regulatory Environments

EPA Science Inventory

Integrated decision support systems for regulatory applications benefit from standardindustry practices such as code reuse, test-driven development, and modularization. Theseapproaches make meeting the federal government’s goals of transparency, efficiency, and quality assurance ...

Characterization of Endogenous and Reduced Promoters for Oxygen-Limited Processes Using Escherichia coli.

PubMed

Lara, Alvaro R; Jaén, Karim E; Sigala, Juan-Carlos; Mühlmann, Martina; Regestein, Lars; Büchs, Jochen

2017-02-17

Oxygen limitation can be used as a simple environmental inducer for the expression of target genes. However, there is scarce information on the characteristics of microaerobic promoters potentially useful for cell engineering and synthetic biology applications. Here, we characterized the Vitreoscilla hemoglobin promoter (P vgb ) and a set of microaerobic endogenous promoters in Escherichia coli. Oxygen-limited cultures at different maximum oxygen transfer rates were carried out. The FMN-binding fluorescent protein (FbFP), which is a nonoxygen dependent marker protein, was used as a reporter. Fluorescence and fluorescence emission rates under oxygen-limited conditions were the highest when FbFP was under transcriptional control of P adhE , P pfl and P vgb . The lengths of the E. coli endogenous promoters were shortened by 60%, maintaining their key regulatory elements. This resulted in improved promoter activity in most cases, particularly for P adhE , P pfl and P narK . Selected promoters were also evaluated using an engineered E. coli strain expressing Vitreoscilla hemoglobin (VHb). The presence of the VHb resulted in a better repression using these promoters under aerobic conditions, and increased the specific growth and fluorescence emission rates under oxygen-limited conditions. These results are useful for the selection of promoters for specific applications and for the design of modified artificial promoters.

76 FR 71007 - Shetek Wind Inc., Jeffers South, LLC and Allco Renewable Energy Limited, Midwest Independent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-16

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL11-53-000] Shetek Wind Inc., Jeffers South, LLC and Allco Renewable Energy Limited, Midwest Independent Transmission System Operator... an original and 14 copies of the protest or intervention to the Federal Energy Regulatory Commission...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

76 FR 12101 - Jordan Hydroelectric Limited Partnership; Notice of Environmental Assessment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [ Project No. 12737-002] Jordan Hydroelectric Limited Partnership; Notice of Environmental Assessment In accordance with the National Environmental Policy Act of 1969 and the Federal Energy Regulatory Commission's regulations, 18 CFR part 380 (Order No. 486, 52 FR 447897), the Office of...

78 FR 73912 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... Rule Change To Extend the Pilot Program That Eliminated the Position and Exercise Limits for Options on... amend its rules to extend the pilot program that eliminated position and exercise limits for physically..., because not all self- regulatory organizations (``SROs'') have adopted similar rules eliminating position...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2014 CFR

2014-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2012 CFR

2012-04-01

... IN ANIMAL FOOD AND FOOD-PACKAGING MATERIAL General Provisions § 509.4 Establishment of tolerances... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN CONSUMPTION AND FOOD-PACKAGING MATERIAL General Provisions § 109.4 Establishment of tolerances... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

Genomics in the land of regulatory science.

PubMed

Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

2015-06-01

Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making. Published by Elsevier Inc.

Regulatory genes and their roles for improvement of antibiotic biosynthesis in Streptomyces.

PubMed

Lu, Fengjuan; Hou, Yanyan; Zhang, Heming; Chu, Yiwen; Xia, Haiyang; Tian, Yongqiang

2017-08-01

The numerous secondary metabolites in Streptomyces spp. are crucial for various applications. For example, cephamycin C is used as an antibiotic, and avermectin is used as an insecticide. Specifically, antibiotic yield is closely related to many factors, such as the external environment, nutrition (including nitrogen and carbon sources), biosynthetic efficiency and the regulatory mechanisms in producing strains. There are various types of regulatory genes that work in different ways, such as pleiotropic (or global) regulatory genes, cluster-situated regulators, which are also called pathway-specific regulatory genes, and many other regulators. The study of regulatory genes that influence antibiotic biosynthesis in Streptomyces spp. not only provides a theoretical basis for antibiotic biosynthesis in Streptomyces but also helps to increase the yield of antibiotics via molecular manipulation of these regulatory genes. Currently, more and more emphasis is being placed on the regulatory genes of antibiotic biosynthetic gene clusters in Streptomyces spp., and many studies on these genes have been performed to improve the yield of antibiotics in Streptomyces. This paper lists many antibiotic biosynthesis regulatory genes in Streptomyces spp. and focuses on frequently investigated regulatory genes that are involved in pathway-specific regulation and pleiotropic regulation and their applications in genetic engineering.

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.

PubMed

Burcham, Christopher L; Florence, Alastair J; Johnson, Martin D

2018-06-07

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

Groundwater recharge with reclaimed municipal wastewater: health and regulatory considerations.

PubMed

Asano, Takashi; Cotruvo, Joseph A

2004-04-01

Groundwater recharge with reclaimed municipal wastewater presents a wide spectrum of technical and health challenges that must be carefully evaluated prior to undertaking a project. This review will provide a discussion of groundwater recharge and its management with special reference to health and regulatory aspects of groundwater recharge with reclaimed municipal wastewater. At present, some uncertainties with respect to health risk considerations have limited expanding use of reclaimed municipal wastewater for groundwater recharge, especially when a large portion of the groundwater contains reclaimed wastewater that may affect the domestic water supply. The proposed State of California criteria for groundwater recharge are discussed as an illustration of a cautious approach. In addition, a summary is provided of the methodology used in developing the World Health Organization's Guidelines for Drinking Water Quality to illustrate how numerical guideline values are generated for contaminants that may be applicable to groundwater recharge.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.

PubMed

Babak, Tomas; Garrett-Engele, Philip; Armour, Christopher D; Raymond, Christopher K; Keller, Mark P; Chen, Ronghua; Rohl, Carol A; Johnson, Jason M; Attie, Alan D; Fraser, Hunter B; Schadt, Eric E

2010-08-13

Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

Intrinsic limits to gene regulation by global crosstalk

NASA Astrophysics Data System (ADS)

Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

75 FR 43588 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-26

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule... FINRA Rule 4320 in the Consolidated FINRA Rulebook July 20, 2010. On May 21, 2010, the Financial... application by their terms. For more information about the rulebook consolidation process, see Information...

17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... self-regulatory organizations, availability of staff, convenience of location, unnecessary regulatory... cooperation and coordination among self-regulatory organizations, and the development of a national market... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

Code of Federal Regulations, 2011 CFR

2011-04-01

... self-regulatory organizations, availability of staff, convenience of location, unnecessary regulatory... cooperation and coordination among self-regulatory organizations, and the development of a national market... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... self-regulatory organizations, availability of staff, convenience of location, unnecessary regulatory... cooperation and coordination among self-regulatory organizations, and the development of a national market... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

Code of Federal Regulations, 2010 CFR

2010-04-01

... self-regulatory organizations, availability of staff, convenience of location, unnecessary regulatory... cooperation and coordination among self-regulatory organizations, and the development of a national market... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

17 CFR 240.17d-1 - Examination for compliance with applicable financial responsibility rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... self-regulatory organizations, availability of staff, convenience of location, unnecessary regulatory... cooperation and coordination among self-regulatory organizations, and the development of a national market... financial responsibility rules. (a) Where a member of SIPC is a member of more than one self-regulatory...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

17 CFR 201.420 - Appeal of determinations by self-regulatory organizations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... self-regulatory organizations. 201.420 Section 201.420 Commodity and Securities Exchanges SECURITIES... Review § 201.420 Appeal of determinations by self-regulatory organizations. (a) Application for review... by a self-regulatory organization determination as to which a notice is required to be filed with the...

75 FR 33361 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-11

... staff needs in its review of applications for permits and licenses. Revision 4 of Regulatory Guide 1.28... (Design and Construction).'' Proposed RG 1.28, Revision 4, extends the scope of the NRC's endorsement to...: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

Development document for final best conventional technology effluent limitations guidelines for the pharmaceutical manufacturing point source category. Final report

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

O'Farrell, T.; Hund, F.

1986-12-01

The document presents the technical rationale for best conventional technology (BCI) effluent limitations guidelines for the pharmaceutical manufacturing point-source category as required by the Clean Water Act of 1977 (P.L. 95-217, the Act). The document describes the technologies considered as the bases for BCT limitations. Section II of this document summarizes the rulemaking process. Sections III through V describe the technical data and engineering analyses used to develop the regulatory technology options. The costs and removals associated with each technology option for each plant and the application of the BCT cost test methodology are presented in Section VI. BCI limitationsmore » bases on the best conventional pollutant control technology are to be achieved by existing direct-discharging facilities.« less

18 CFR 4.201 - Contents of application.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... 4.201 Section 4.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION... form specified. (a) Initial statement. Before the Federal Energy Regulatory Commission Application for...

18 CFR 4.201 - Contents of application.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... 4.201 Section 4.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION... form specified. (a) Initial statement. Before the Federal Energy Regulatory Commission Application for...

18 CFR 4.201 - Contents of application.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... 4.201 Section 4.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION... form specified. (a) Initial statement. Before the Federal Energy Regulatory Commission Application for...

18 CFR 4.201 - Contents of application.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... 4.201 Section 4.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION... form specified. (a) Initial statement. Before the Federal Energy Regulatory Commission Application for...

18 CFR 4.201 - Contents of application.

Code of Federal Regulations, 2010 CFR

2010-04-01

.... 4.201 Section 4.201 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT LICENSES, PERMITS, EXEMPTIONS, AND DETERMINATION... form specified. (a) Initial statement. Before the Federal Energy Regulatory Commission Application for...

78 FR 29390 - Applications; SHINE Medical Technologies, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-20

... NUCLEAR REGULATORY COMMISSION [Proj-0792; NRC-2013-0053] Applications; SHINE Medical Technologies, Inc. AGENCY: Nuclear Regulatory Commission. ACTION: Notice; receipt and availability. FOR FURTHER... (ADAMS) Accession No. ML13088A192), SHINE Medical Technologies (SHINE) filed with the U.S. Nuclear...

The Benefits and Limitations of Hydraulic Modeling for Ordinary High Water Mark Delineation

DTIC Science & Technology

2016-02-01

ER D C/ CR RE L TR -1 6- 1 Wetland Regulatory Assistance Program (WRAP) The Benefits and Limitations of Hydraulic Modeling for Ordinary...client/default. Wetland Regulatory Assistance Program (WRAP) ERDC/CRREL TR-16-1 February 2016 The Benefits and Limitations of Hydraulic Modeling...Approved for public release; distribution is unlimited. Prepared for Headquarters, U.S. Army Corps of Engineers Washington, DC 20314-1000 Under Wetlands

Translational and regulatory challenges for exon skipping therapies.

PubMed

Aartsma-Rus, Annemieke; Ferlini, Alessandra; Goemans, Nathalie; Pasmooij, Anna M G; Wells, Dominic J; Bushby, Katerine; Vroom, Elizabeth; Balabanov, Pavel

2014-10-01

Several translational challenges are currently impeding the therapeutic development of antisense-mediated exon skipping approaches for rare diseases. Some of these are inherent to developing therapies for rare diseases, such as small patient numbers and limited information on natural history and interpretation of appropriate clinical outcome measures. Others are inherent to the antisense oligonucleotide (AON)-mediated exon skipping approach, which employs small modified DNA or RNA molecules to manipulate the splicing process. This is a new approach and only limited information is available on long-term safety and toxicity for most AON chemistries. Furthermore, AONs often act in a mutation-specific manner, in which case multiple AONs have to be developed for a single disease. A workshop focusing on preclinical development, trial design, outcome measures, and different forms of marketing authorization was organized by the regulatory models and biochemical outcome measures working groups of Cooperation of Science and Technology Action: "Networking towards clinical application of antisense-mediated exon skipping for rare diseases." The workshop included participants from patient organizations, academia, and members of staff from the European Medicine Agency and Medicine Evaluation Board (the Netherlands). This statement article contains the key outcomes of this meeting.

Evaluation of the long-term performance of six alternative disposal methods for LLRW

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

Kossik, R.; Sharp, G.; Chau, T.

1995-12-31

The State of New York has carried out a comparison of six alternative disposal methods for low-level radioactive waste (LLRW). An important part of these evaluations involved quantitatively analyzing the long-term (10,000 yr) performance of the methods with respect to dose to humans, radionuclide concentrations in the environment, and cumulative release from the facility. Four near-surface methods (covered above-grade vault, uncovered above-grade vault, below-grade vault, augered holes) and two mine methods (vertical shaft mine and drift mine) were evaluated. Each method was analyzed for several generic site conditions applicable for the state. The evaluations were carried out using RIP (Repositorymore » Integration Program), an integrated, total system performance assessment computer code which has been applied to radioactive waste disposal facilities both in the U.S. (Yucca Mountain, WIPP) and worldwide. The evaluations indicate that mines in intact low-permeability rock and near-surface facilities with engineered covers generally have a high potential to perform well (within regulatory limits). Uncovered above-grade vaults and mines in highly fractured crystalline rock, however, have a high potential to perform poorly, exceeding regulatory limits.« less

47 CFR 1.1158 - Form of payment for regulatory fees.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regulatory fee payment (including a regulatory fee payment submitted with an application in the wireless radio service) made by credit card or money order must be submitted with a completed FCC Form 159...

47 CFR 1.1158 - Form of payment for regulatory fees.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regulatory fee payment (including a regulatory fee payment submitted with an application in the wireless radio service) made by credit card or money order must be submitted with a completed FCC Form 159...

47 CFR 1.1158 - Form of payment for regulatory fees.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regulatory fee payment (including a regulatory fee payment submitted with an application in the wireless radio service) made by credit card or money order must be submitted with a completed FCC Form 159...

Gene therapy delivery systems for enhancing viral and nonviral vectors for cardiac diseases: current concepts and future applications.

PubMed

Katz, Michael G; Fargnoli, Anthony S; Williams, Richard D; Bridges, Charles R

2013-11-01

Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course.

Reconstruction of gene regulatory modules from RNA silencing of IFN-α modulators: experimental set-up and inference method.

PubMed

Grassi, Angela; Di Camillo, Barbara; Ciccarese, Francesco; Agnusdei, Valentina; Zanovello, Paola; Amadori, Alberto; Finesso, Lorenzo; Indraccolo, Stefano; Toffolo, Gianna Maria

2016-03-12

Inference of gene regulation from expression data may help to unravel regulatory mechanisms involved in complex diseases or in the action of specific drugs. A challenging task for many researchers working in the field of systems biology is to build up an experiment with a limited budget and produce a dataset suitable to reconstruct putative regulatory modules worth of biological validation. Here, we focus on small-scale gene expression screens and we introduce a novel experimental set-up and a customized method of analysis to make inference on regulatory modules starting from genetic perturbation data, e.g. knockdown and overexpression data. To illustrate the utility of our strategy, it was applied to produce and analyze a dataset of quantitative real-time RT-PCR data, in which interferon-α (IFN-α) transcriptional response in endothelial cells is investigated by RNA silencing of two candidate IFN-α modulators, STAT1 and IFIH1. A putative regulatory module was reconstructed by our method, revealing an intriguing feed-forward loop, in which STAT1 regulates IFIH1 and they both negatively regulate IFNAR1. STAT1 regulation on IFNAR1 was object of experimental validation at the protein level. Detailed description of the experimental set-up and of the analysis procedure is reported, with the intent to be of inspiration for other scientists who want to realize similar experiments to reconstruct gene regulatory modules starting from perturbations of possible regulators. Application of our approach to the study of IFN-α transcriptional response modulators in endothelial cells has led to many interesting novel findings and new biological hypotheses worth of validation.

The regulatory framework for preventing cross-contamination of pharmaceutical products: History and considerations for the future.

PubMed

Sargent, Edward V; Flueckiger, Andreas; Barle, Ester Lovsin; Luo, Wendy; Molnar, Lance R; Sandhu, Reena; Weideman, Patricia A

2016-08-01

Cross-contamination in multi-product pharmaceutical manufacturing facilities can impact both product safety and quality. This issue has been recognized by regulators and industry for some time, leading to publication of a number of continually evolving guidelines. This manuscript provides a historical overview of the regulatory framework for managing cross-contamination in multi-product facilities to provide context for current approaches. Early guidelines focused on the types of pharmaceuticals for which dedicated facilities and control systems were needed, and stated the requirements for cleaning validation. More recent guidelines have promoted the idea of using Acceptable Daily Exposures (ADEs) to establish cleaning limits for actives and other potentially hazardous substances. The ADE approach is considered superior to previous methods for setting cleaning limits such as using a predetermined general limit (e.g., 10 ppm or a fraction of the median lethal dose (LD50) or therapeutic dose). The ADEs can be used to drive the cleaning process and as part of the overall assessment of whether dedicated production facilities are required. While great strides have been made in using the ADE approach, work remains to update good manufacturing practices (GMPs) to ensure that the approaches are clear, consistent with the state-of-the-science, and broadly applicable yet flexible enough for adaptation to unique products and situations. Copyright © 2016 Elsevier Inc. All rights reserved.

An effective strategy for decontamination, ex vivo expansion, and storage of human fetal liver hematopoietic stem cells.

PubMed

Rice, H E; Skarsgard, E D; Emani, V R; Zanjani, E D; Harrison, M R; Flake, A W

1994-12-01

The transplantation of human fetal tissue has the potential to cure a variety of life-threatening diseases. The strategy for procurement, quality control, and functional assessment of human fetal liver HSC may prove useful for the transplantation of other fetal tissues. In addition to technical limitations, there are ethical and legal issues which need to be resolved before widespread use of fetal tissue. Further development of regulatory standards for the acquisition and distribution of fetal tissues will foster the application of this novel technology.

Intrinsic limits to gene regulation by global crosstalk

PubMed Central

Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

2016-01-01

Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

Five-year ALARA review of dosimetry results :

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

Paulus, Luke R.

2013-08-01

A review of personnel dosimetry (external and internal) and environmental monitoring results from 1 January 2008 through 31 December 2012 performed at Sandia National Laboratories, New Mexico was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform with the ALARA philosophy. ALARA is the philosophical approach to radiation protection by managing and controlling radiation exposures (individual and collective) to the work force and to the general public to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limitmore » but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

Revisiting phage therapy: new applications for old resources.

PubMed

Nobrega, Franklin L; Costa, Ana Rita; Kluskens, Leon D; Azeredo, Joana

2015-04-01

The success of phage therapy is dependent on the development of strategies able to overcome the limitations of bacteriophages as therapeutic agents, the creation of an adequate regulatory framework, the implementation of safety protocols, and acceptance by the general public. Many approaches have been proposed to circumvent phages' intrinsic limitations but none have proved to be completely satisfactory. In this review we present the major hurdles of phage therapy and the solutions proposed to circumvent them. A thorough discussion of the advantages and drawbacks of these solutions is provided and special attention is given to the genetic modification of phages as an achievable strategy to shape bacteriophages to exhibit desirable biological properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

78 FR 9083 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... FINRA to determine whether Rule 11892 is necessary once the Plan is operational and, if so, whether... in Connection With the Limit Up-Limit Down Plan February 1, 2013. Pursuant to Section 19(b)(1) of the... also proposes to adopt new supplementary material in connection with the upcoming operation of the Plan...

77 FR 27825 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

...-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing and Order Granting Accelerated Approval...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on May 5, 2012, ICE Clear Europe... such as the FSA, CFTC, SEC, Banque de France, Bundesbank, Bundesanstalt f[uuml]r...

78 FR 13922 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-01

... the Regulation NMS Plan to Address Extraordinary Market Volatility. The text of the proposed rule... text of these statements may be examined at the places specified in Item IV below. FINRA has prepared... thereunder.\\6\\ The Limit Up-Limit Down mechanism is intended to address the type of sudden price movements...

21 CFR 509.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 509.4 Section 509.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

21 CFR 109.4 - Establishment of tolerances, regulatory limits, and action levels.

Code of Federal Regulations, 2010 CFR

2010-04-01

... a food additive, may be established to define a level of contamination at which a food may be... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Establishment of tolerances, regulatory limits, and action levels. 109.4 Section 109.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF...

78 FR 15790 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

... Security ``(ABS'') (except ABS traded To Be Announced (``TBA'')), in the limited instances when members... Factor in the limited instances when the member effects a transaction in an ABS (except a TBA transaction...-conforming Factor'').\\13\\ As a result of the proposed rule change, when an ABS transaction (except for a TBA...

Attempting to be active: Self-efficacy and barrier limitation differentiate activity levels of working mothers.

PubMed

Gierc, Madelaine; Locke, Sean; Jung, Mary; Brawley, Lawrence

2016-07-01

Working mothers are less physically active than working women without children and mothers who do not work. The purpose of this study was to examine concurrent self-regulatory efficacy and barriers to physical activity in a sample of working mothers. Women completed a mixed-methods survey which included measures of physical activity, concurrent self-regulatory efficacy, and barriers. Sufficiently active women experienced significantly greater concurrent self-regulatory efficacy and significantly less barrier limitation and frequency. No significant group differences were found for age, domestic duties performed, and children's extracurricular activities. Thematic analysis of barriers revealed six themes of common and unique factors, including limited time and family activities. © The Author(s) 2014.

49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 2 2011-10-01 2011-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 2 2014-10-01 2014-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 2 2010-10-01 2010-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

49 CFR 173.471 - Requirements for U.S. Nuclear Regulatory Commission approved packages.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 2 2013-10-01 2013-10-01 false Requirements for U.S. Nuclear Regulatory...) Materials § 173.471 Requirements for U.S. Nuclear Regulatory Commission approved packages. In addition to the applicable requirements of the U.S. Nuclear Regulatory Commission (NRC) and other requirements of...

Regulatory facility guide for Ohio

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

Anderson, S.S.; Bock, R.E.; Francis, M.W.

1994-02-28

The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

Characterization of the radiation environment for a large-area interim spent-nuclear-fuel storage facility

NASA Astrophysics Data System (ADS)

Fortkamp, Jonathan C.

Current needs in the nuclear industry and movements in the political arena indicate that authorization may soon be given for development of a federal interim storage facility for spent nuclear fuel. The initial stages of the design work have already begun within the Department of Energy and are being reviewed by the Nuclear Regulatory Commission. This dissertation addresses the radiation environment around an interim spent nuclear fuel storage facility. Specifically the dissertation characterizes the radiation dose rates around the facility based on a design basis source term, evaluates the changes in dose due to varying cask spacing configurations, and uses these results to define some applicable health physics principles for the storage facility. Results indicate that dose rates from the facility are due primarily from photons from the spent fuel and Co-60 activation in the fuel assemblies. In the modeled cask system, skyshine was a significant contribution to dose rates at distances from the cask array, but this contribution can be reduced with an alternate cask venting system. With the application of appropriate health physics principles, occupation doses can be easily maintained far below regulatory limits and maintained ALARA.

Challenges in cryopreservation of regulatory T cells (Tregs) for clinical therapeutic applications.

PubMed

Golab, Karolina; Leveson-Gower, Dennis; Wang, Xiao-Jun; Grzanka, Jakub; Marek-Trzonkowska, Natalia; Krzystyniak, Adam; Millis, J Michael; Trzonkowski, Piotr; Witkowski, Piotr

2013-07-01

Promising results of initial studies applying ex-vivo expanded regulatory T cell (Treg) as a clinical intervention have increased interest in this type of the cellular therapy and several new clinical trials involving Tregs are currently on the way. Methods of isolation and expansion of Tregs have been studied and optimized to the extent that such therapy is feasible, and allows obtaining sufficient numbers of Tregs in the laboratory following Good Manufacturing Practice (GMP) guidelines. Nevertheless, Treg therapy could even more rapidly evolve if Tregs could be efficiently cryopreserved and stored for future infusion or expansions rather than utilization of only freshly isolated and expanded cells as it is preferred now. Currently, our knowledge regarding the impact of cryopreservation on Treg recovery, viability, and functionality is still limited. Based on experience with cryopreserved peripheral blood mononuclear cells (PBMCs), cryopreservation may have a detrimental effect on Tregs, can decrease Treg viability, cause abnormal cytokine secretion, and compromise expression of surface markers essential for proper Treg function and processing. Therefore, optimal strategies and conditions for Treg cryopreservation in conjunction with cell culture, expansion, and processing for clinical application still need to be investigated and defined. Copyright © 2013 Elsevier B.V. All rights reserved.

Design of an ectoine-responsive AraC mutant and its application in metabolic engineering of ectoine biosynthesis.

PubMed

Chen, Wei; Zhang, Shan; Jiang, Peixia; Yao, Jun; He, Yongzhi; Chen, Lincai; Gui, Xiwu; Dong, Zhiyang; Tang, Shuang-Yan

2015-07-01

Advanced high-throughput screening methods for small molecules may have important applications in the metabolic engineering of the biosynthetic pathways of these molecules. Ectoine is an excellent osmoprotectant that has been widely used in cosmetics. In this study, the Escherichia coli regulatory protein AraC was engineered to recognize ectoine as its non-natural effector and to activate transcription upon ectoine binding. As an endogenous reporter of ectoine, the mutated AraC protein was successfully incorporated into high-throughput screening of ectoine hyper-producing strains. The ectoine biosynthetic cluster from Halomonas elongata was cloned into E. coli. By engineering the rate-limiting enzyme L-2,4-diaminobutyric acid (DABA) aminotransferase (EctB), ectoine production and the specific activity of the EctB mutant were increased. Thus, these results demonstrated the effectiveness of engineering regulatory proteins into sensitive and rapid screening tools for small molecules and highlighted the importance and efficacy of directed evolution strategies applied to the engineering of genetic components for yield improvement in the biosynthesis of small molecules. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Co-processed excipients: a patent review.

PubMed

Garg, Nidhi; Dureja, Harish; Kaushik, Deepak

2013-04-01

The introduction of high speed tableting machines and the preference of direct compression as a method of tableting have increased the demands on the functionality of excipients mainly in terms of flowability and compressibility. Co-processed excipients, where in, excipients are combined by virtue of sub-particle level interaction have provided an attractive tool for developing high functionality excipients. The multifold advantages offered by co-processed excipients such as production of synergism in functionality of individual components, reduction of company's regulatory concern because of absence of chemical change during co-processing and improvement in physico-chemical properties have expanded their use in the pharmaceutical industry. In the recent years, there has been a spurt in the number of patents filed on co-processed excipients. Hence, the present review focuses on co-processed excipients and their application in pharmaceutical industry. The worldwide databases of European patent office (http://ep.espacenet.com) and United States patent office (www.uspto.gov) were employed to collect the patents and patent applications. The advantages, limitations, basis for the selection of excipients to be co-processed, methods of co-processing and regulatory perspective of co-processed excipients are also briefly discussed.

78 FR 70965 - Ameren Missouri; Combined License Application for Callaway Plant, Unit 2, Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... NUCLEAR REGULATORY COMMISSION [Docket No. 52-037; NRC-2008-0556] Ameren Missouri; Combined License Application for Callaway Plant, Unit 2, Exemption 1.0 Background Union Electric Company, doing business as Ameren UE, submitted to the U.S. Nuclear Regulatory Commission (NRC) a Combined License (COL) Application for a single unit of AREVA NP's U.S...

77 FR 76539 - Ameren Missouri; Combined License Application For Callaway Plant, Unit 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-28

... NUCLEAR REGULATORY COMMISSION [Docket No. 52-037; NRC-2008-0556] Ameren Missouri; Combined License Application For Callaway Plant, Unit 2; Exemption 1.0 Background Union Electric Company, doing business as Ameren UE, submitted to the U.S. Nuclear Regulatory Commission (NRC) a Combined License (COL) Application for a single unit of AREVA NP's U.S...

75 FR 80854 - Toshiba Corporation; Acceptance for Docketing of an Application for Renewal of the U.S. Advanced...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... NUCLEAR REGULATORY COMMISSION [Docket No. 52-044; NRC-2010-0361] Toshiba Corporation; Acceptance for Docketing of an Application for Renewal of the U.S. Advanced Boiling Water Reactor Design Certification On November 2, 2010, Toshiba Corporation (Toshiba) submitted an application to the U.S. Nuclear Regulatory Commission (NRC) for a design...

Regulatory guidance concerning the applicability of the Federal Motor Carrier Safety regulations to texting by commercial motor vehicle drivers

DOT National Transportation Integrated Search

2010-01-10

The FMCSA announces regulatory guidance concerning texting while driving a commercial motor vehicle (CMV). The guidance is applicable to all interstate drivers of CMVs subject to the Federal Motor Carrier Safety Regulations (FMCSRs).

76 FR 18210 - Texas Eastern Transmission, LP; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-01

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-138-000] Texas Eastern Transmission, LP; Notice of Application On March 15, 2011, Texas Eastern Transmission Corporation (Texas Eastern), 5400 Westheimer Court, Houston, Texas 77056-5310, filed with the Federal Energy Regulatory...

75 FR 45676 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2010-0235] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: U.S. Nuclear Regulatory Commission (NRC). ACTION: Notice of...: Applications for new licenses and amendments may be submitted at any time. Applications for renewal are...

10 CFR 51.12 - Application of subpart to ongoing environmental work.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Application of subpart to ongoing environmental work. 51.12 Section 51.12 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act...

10 CFR 51.12 - Application of subpart to ongoing environmental work.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Application of subpart to ongoing environmental work. 51.12 Section 51.12 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) ENVIRONMENTAL PROTECTION REGULATIONS FOR DOMESTIC LICENSING AND RELATED REGULATORY FUNCTIONS National Environmental Policy Act...

Science in the regulatory setting: a challenging but incompatible mix?

PubMed

Yetley, Elizabeth A

2007-01-01

Regulatory decisions informed by sound science have an important role in many regulatory applications involving drugs and foods, including applications related to dietary supplements. However, science is only one of many factors that must be taken into account in the regulatory decision-making process. In many cases, the scientific input to a regulatory decision must compete with other factors (e.g. economics, legal requirements, stakeholder interests) for impact on the resultant policy decision. Therefore, timely and effective articulation of the available science to support a regulatory decision can significantly affect the relative weight given to science. However, the incorporation of science into the regulatory process for dietary supplements is often fraught with challenges. The available scientific evidence has rarely been designed for the purpose of addressing regulatory questions and is often preliminary and of widely varying scientific quality. To add to the confusion, the same scientific evidence may result in what appears to be different regulatory decisions because the context in which the science is used differs. The underlying assumption is that scientists who have a basic understanding of the interface between science and policy decisions can more effectively provide scientific input into these decisions.

Physico-chemical properties of manufactured nanomaterials - Characterisation and relevant methods. An outlook based on the OECD Testing Programme.

PubMed

Rasmussen, Kirsten; Rauscher, Hubert; Mech, Agnieszka; Riego Sintes, Juan; Gilliland, Douglas; González, Mar; Kearns, Peter; Moss, Kenneth; Visser, Maaike; Groenewold, Monique; Bleeker, Eric A J

2018-02-01

Identifying and characterising nanomaterials require additional information on physico-chemical properties and test methods, compared to chemicals in general. Furthermore, regulatory decisions for chemicals are usually based upon certain toxicological properties, and these effects may not be equivalent to those for nanomaterials. However, regulatory agencies lack an authoritative decision framework for nanomaterials that links the relevance of certain physico-chemical endpoints to toxicological effects. This paper investigates various physico-chemical endpoints and available test methods that could be used to produce such a decision framework for nanomaterials. It presents an overview of regulatory relevance and methods used for testing fifteen proposed physico-chemical properties of eleven nanomaterials in the OECD Working Party on Manufactured Nanomaterials' Testing Programme, complemented with methods from literature, and assesses the methods' adequacy and applications limits. Most endpoints are of regulatory relevance, though the specific parameters depend on the nanomaterial and type of assessment. Size (distribution) is the common characteristic of all nanomaterials and is decisive information for classifying a material as a nanomaterial. Shape is an important particle descriptor. The octanol-water partitioning coefficient is undefined for particulate nanomaterials. Methods, including sample preparation, need to be further standardised, and some new methods are needed. The current work of OECD's Test Guidelines Programme regarding physico-chemical properties is highlighted. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Stochastic Effects in Computational Biology of Space Radiation Cancer Risk

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Pluth, Janis; Harper, Jane; O'Neill, Peter

2007-01-01

Estimating risk from space radiation poses important questions on the radiobiology of protons and heavy ions. We are considering systems biology models to study radiation induced repair foci (RIRF) at low doses, in which less than one-track on average transverses the cell, and the subsequent DNA damage processing and signal transduction events. Computational approaches for describing protein regulatory networks coupled to DNA and oxidative damage sites include systems of differential equations, stochastic equations, and Monte-Carlo simulations. We review recent developments in the mathematical description of protein regulatory networks and possible approaches to radiation effects simulation. These include robustness, which states that regulatory networks maintain their functions against external and internal perturbations due to compensating properties of redundancy and molecular feedback controls, and modularity, which leads to general theorems for considering molecules that interact through a regulatory mechanism without exchange of matter leading to a block diagonal reduction of the connecting pathways. Identifying rate-limiting steps, robustness, and modularity in pathways perturbed by radiation damage are shown to be valid techniques for reducing large molecular systems to realistic computer simulations. Other techniques studied are the use of steady-state analysis, and the introduction of composite molecules or rate-constants to represent small collections of reactants. Applications of these techniques to describe spatial and temporal distributions of RIRF and cell populations following low dose irradiation are described.

76 FR 65544 - Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

...The U.S. Nuclear Regulatory Commission (NRC or Commission) is issuing a revision to regulatory guide (RG) 3.39, ``Standard Format and Content of License Applications for Mixed Oxide Fuel Fabrication Facilities.'' This guide endorses the standard format and content for license applications and integrated safety analysis (ISA) summaries described in the current version of NUREG-1718, ``Standard Review Plan for the Review of an Application for a Mixed Oxide (MOX) Fuel Fabrication Facility,'' as a method that the NRC staff finds acceptable for meeting the regulatory requirements of Title 10 of the Code of Federal Regulations (10 CFR) part 70, ``Domestic Licensing of Special Nuclear Material'' for mixed oxide fuel fabrication facilities.

77 FR 21866 - Safety Zone; Sunken Vessel, Puget Sound, Everett, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

... significant regulatory action due to being limited in size and duration. Small Entities Under the Regulatory... impact on a substantial number of small entities. The term ``small entities'' comprises small businesses... duration. Assistance for Small Entities Under section 213(a) of the Small Business Regulatory Enforcement...

77 FR 7930 - Improving Government Regulations; Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

... the Regulatory Flexibility Act (5 U.S.C. 602), the Department of Defense's printed agenda entries... section 610 of the Regulatory Flexibility Act. Printing of these entries is limited to fields that contain...D Intelligence Interrogations, Detainee Debriefings, and Tactical Questioning. This rule only...

Allergen source materials: state-of-the-art.

PubMed

Esch, Robert E

2009-01-01

A variety of positive outcomes can be realized from validation and risk management activities (see Table 4). They are dependent on the participation of multiple functional groups including the quality unit, regulatory and legal affairs, engineering and production operations, research and development, and sales and marketing. Quality risk management is receiving increased attention in the area of public health, pharmacovigilance, and pharmaceutical manufacturing. Recent examples of its regulatory use in our industry include the assessment of the potential risks of transmissible spongiform encephalopathies (TSE) agents through contaminated products], the risks of precipitates in allergenic extracts, and the revision of the potency limits for standardized dust mite and grass allergen vaccines. Its application to allergen source material process validation activities allowed for a practical strategy, especially in a complex manufacturing environment involving hundreds of products with multiple intended uses. In addition, the use of tools such as FMEA was useful in evaluating proposed changes made to manufacturing procedures and product specifications, new regulatory actions, and customer feedback or complaints. The success of such a quality assurance programs will ultimately be reflected in the elimination or reduction of product failures, improvement in the detection and prediction of potential product failures, and increased confidence in product quality.

Scientific foundation of regulating ionizing radiation: application of metrics for evaluation of regulatory science information.

PubMed

Moghissi, A Alan; Gerraa, Vikrham Kumar; McBride, Dennis K; Swetnam, Michael

2014-11-01

This paper starts by describing the historical evolution of assessment of biologic effects of ionizing radiation leading to the linear non-threshold (LNT) system currently used to regulate exposure to ionizing radiation. The paper describes briefly the concept of Best Available Science (BAS) and Metrics for Evaluation of Scientific Claims (MESC) derived for BAS. It identifies three phases of regulatory science consisting of the initial phase, when the regulators had to develop regulations without having the needed scientific information; the exploratory phase, when relevant tools were developed; and the standard operating phase, when the tools were applied to regulations. Subsequently, an attempt is made to apply the BAS/MESC system to various stages of LNT. This paper then compares the exposure limits imposed by regulatory agencies and also compares them with naturally occurring radiation at several cities. Controversies about LNT are addressed, including judgments of the U.S. National Academies and their French counterpart. The paper concludes that, based on the BAS/MESC system, there is no disagreement between the two academies on the scientific foundation of LNT; instead, the disagreement is based on their judgment or speculation.

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

Wichman, K.; Tsao, J.; Mayfield, M.

The regulatory application of leak before break (LBB) for operating and advanced reactors in the U.S. is described. The U.S. Nuclear Regulatory Commission (NRC) has approved the application of LBB for six piping systems in operating reactors: reactor coolant system primary loop piping, pressurizer surge, safety injection accumulator, residual heat removal, safety injection, and reactor coolant loop bypass. The LBB concept has also been applied in the design of advanced light water reactors. LBB applications, and regulatory considerations, for pressurized water reactors and advanced light water reactors are summarized in this paper. Technology development for LBB performed by the NRCmore » and the International Piping Integrity Research Group is also briefly summarized.« less

Regulatory perspectives on acceptability testing of dosage forms in children.

PubMed

Kozarewicz, Piotr

2014-08-05

Current knowledge about the age-appropriateness of different dosage forms is still fragmented or limited. Applicants are asked to demonstrate that the target age group(s) can manage the dosage form or propose an alternative strategy. However, questions remain about how far the applicant must go and what percentage of patients must find the strategy 'acceptable'. The aim of this overview is to provide an update on current thinking and understanding of the problem, and discuss issues relating to the acceptability testing. This overview should be considered as means to start a wider discussion which hopefully will result in a harmonised, globally acceptable approach for confirmation of the acceptability in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

Assessment of the benefits and impacts in the U.S. Nuclear Power Industry of hypothesized lower occupational dose limits

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

Andersen, R.L.; Schmitt, J.F.

1995-03-01

The International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements have issued recommendations that would limit occupational exposure of individuals to doses lower than regulatory limits contained in the Nuclear Regulatory Commission`s 10 CFR Part 20, {open_quotes}Standards for Protection Against Radiation{close_quotes}. Because of this situation, there is interest in the potential benefits and impacts that would be associated with movement of the NRC regulatory limits toward the advisory bodies recommendations. The records of occupational worker doses in the U.S. commercial nuclear power industry show that the vast majority of these workers have doses that aremore » significantly below the regulatory limit of 50 mSv (5 rem) per year. Some workers doses do approach the limits, however. This is most common in the case of specially skilled workers, especially those with skills utilized in support of plant outage work. Any consideration of the potential benefits and impacts of hypothesized lower dose limits must address these workers as an important input to the overall assessment. There are also, of course, many other areas in which the benefits and impacts must be evaluated. To prepare to provide valid, constructive input on this matter, the U.S. nuclear power industry is undertaking an assessment, facilitated by the Nuclear Energy Institute (NEI), of the potential benefits and impacts at its facilities associated with hypothesized lower occupational dose limits. Some preliminary results available to date from this assessment are provided.« less

77 FR 74687 - Agency Information Collection Activities: Application for Employment Authorization, Form I-765...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... Policy and Strategy, Chief, Regulatory Coordination Division, 20 Massachusetts Avenue NW., Washington, DC... money incurred by applicants for the following aspects of this information collection: The time burden... contacted at: USCIS, Office of Policy and Strategy, Regulatory Coordination Division, 20 Massachusetts...

Approaches for Increasing Acceptance of Physiologically Based Pharmacokinetic Models in Public Health Risk Assessment

EPA Science Inventory

Physiologically based pharmacokinetic (PBPK) models have great potential for application in regulatory and non-regulatory public health risk assessment. The development and application of PBPK models in chemical toxicology has grown steadily since their emergence in the 1980s. Ho...

Summary report of PQRI Workshop on Nanomaterial in Drug Products: current experience and management of potential risks.

PubMed

Bartlett, Jeremy A; Brewster, Marcus; Brown, Paul; Cabral-Lilly, Donna; Cruz, Celia N; David, Raymond; Eickhoff, W Mark; Haubenreisser, Sabine; Jacobs, Abigail; Malinoski, Frank; Morefield, Elaine; Nalubola, Ritu; Prud'homme, Robert K; Sadrieh, Nakissa; Sayes, Christie M; Shahbazian, Hripsime; Subbarao, Nanda; Tamarkin, Lawrence; Tyner, Katherine; Uppoor, Rajendra; Whittaker-Caulk, Margaret; Zamboni, William

2015-01-01

At the Product Quality Research Institute (PQRI) Workshop held last January 14-15, 2014, participants from academia, industry, and governmental agencies involved in the development and regulation of nanomedicines discussed the current state of characterization, formulation development, manufacturing, and nonclinical safety evaluation of nanomaterial-containing drug products for human use. The workshop discussions identified areas where additional understanding of material attributes, absorption, biodistribution, cellular and tissue uptake, and disposition of nanosized particles would continue to inform their safe use in drug products. Analytical techniques and methods used for in vitro characterization and stability testing of formulations containing nanomaterials were discussed, along with their advantages and limitations. Areas where additional regulatory guidance and material characterization standards would help in the development and approval of nanomedicines were explored. Representatives from the US Food and Drug Administration (USFDA), Health Canada, and European Medicines Agency (EMA) presented information about the diversity of nanomaterials in approved and newly developed drug products. USFDA, Health Canada, and EMA regulators discussed the applicability of current regulatory policies in presentations and open discussion. Information contained in several of the recent EMA reflection papers was discussed in detail, along with their scope and intent to enhance scientific understanding about disposition, efficacy, and safety of nanomaterials introduced in vivo and regulatory requirements for testing and market authorization. Opportunities for interaction with regulatory agencies during the lifecycle of nanomedicines were also addressed at the meeting. This is a summary of the workshop presentations and discussions, including considerations for future regulatory guidance on drug products containing nanomaterials.

78 FR 22357 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Order Approving, on...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

... Basis, Proposed Rule Change Relating to Limit Up Limit Down Functionality April 9, 2013. I. Introduction... substance of the proposed rule change or raise any novel regulatory issues, Amendment No. 1 is not subject... defined in Exchange Rule 100 to include orders for the account of a person or entity that is a broker or...

The limits of regulatory toxicology

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

Carrington, Clark D.; Bolger, P. Michael, E-mail: mike.bolger@fda.hhs.go

2010-03-01

The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standardsmore » are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.« less

47 CFR 27.10 - Regulatory status.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply concerning...

47 CFR 27.10 - Regulatory status.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply concerning...

75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... existing paragraph (b)(4) of the Rule, entitled ``Numerical Guidelines Applicable to Volatile Market Opens... existing paragraph (b)(2), which provides flexibility to FINRA to use different Numerical Guidelines or... of paragraph (b)(4) (``Numerical Guidelines Applicable to Volatile Market Opens'') of the existing...

77 FR 31050 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

...-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... threshold qualifications and corresponding rates applicable to Option Trading Permit (``OTP'') Holder and... restructure the threshold qualifications and corresponding rates applicable to OTP Holder and OTP Firm...

76 FR 77219 - Federal Energy Regulatory Commission Combined Notice of Filings #1

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Combined Notice of Filings 1 Take notice.... Applicants: Caney River Wind Project, LLC, Rocky Ridge Wind Project, LLC. Description: Joint Application for..., Request for Expedited Consideration and Confidential Treatment of Caney River Wind Project, LLC, et al...

76 FR 67160 - Southern Star Central Gas Pipeline, Inc.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-481-001] Southern Star Central Gas Pipeline, Inc.; Notice of Application On October 19, 2011, Southern Star Central Gas Pipeline, Inc. (Southern Star) filed with the Federal Energy Regulatory Commission (Commission) an amendment to...

78 FR 45579 - Request for a License to Import Radioactive Waste

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... NUCLEAR REGULATORY COMMISSION Request for a License to Import Radioactive Waste Pursuant to 10 CFR 110.70 (b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear... requestor or petitioner upon the applicant, the office of the General Counsel, U.S. Nuclear Regulatory...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

78 FR 6356 - Notice of Consideration of Approval of Application Regarding Proposed Indirect Transfer of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... NUCLEAR REGULATORY COMMISSION [Docket No. 070-3098; NRC-2011-0081] Notice of Consideration of Approval of Application Regarding Proposed Indirect Transfer of Control of the Construction Authorization for the Mixed Oxide Fuel Fabrication Facility in Aiken, SC; Correction AGENCY: Nuclear Regulatory...

POTENTIAL IMPLICATIONS OF GENOMICS FOR REGULATORY AND RISK ASSESSMENT APPLICATIONS AT EPA

EPA Science Inventory

Benson, W.H., K. Gallagher and K. Dearfield. In press. Potential Implications of Genomics for Regulatory and Risk Assessment Applications at EPA (Abstract). To be presented at the SETAC Fourth World Congress, 14-18 November 2004, Portland, OR. 1 p. (ERL,GB R1002).

Advance...

30 CFR 773.11 - Review of compliance history.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Review of compliance history. 773.11 Section... REGULATORY PROGRAMS REQUIREMENTS FOR PERMITS AND PERMIT PROCESSING § 773.11 Review of compliance history. (a... histories of compliance with the Act or the applicable State regulatory program, and any other applicable...

10 CFR 55.31 - How to apply.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false How to apply. 55.31 Section 55.31 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES Applications § 55.31 How to apply. (a) The applicant... writing the Office of Information Services, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001...

76 FR 38597 - Regulatory Guidance: Applicability of the Federal Motor Carrier Safety Regulations to Operators...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-01

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration 49 CFR Parts 383 and 390 [Docket No. FMCSA-2011-0146] Regulatory Guidance: Applicability of the Federal Motor Carrier Safety Regulations to Operators of Certain Farm Vehicles and Off-Road Agricultural Equipment AGENCY: Federal Motor...

76 FR 50433 - Regulatory Guidance: Applicability of the Federal Motor Carrier Safety Regulations to Operators...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... DEPARTMENT OF TRANSPORTATION Federal Motor Carrier Safety Administration 49 CFR Parts 383 and 390 [Docket No. FMCSA-2011-0146] Regulatory Guidance: Applicability of the Federal Motor Carrier Safety Regulations to Operators of Certain Farm Vehicles and Off-Road Agricultural Equipment AGENCY: Federal Motor...

75 FR 39577 - Draft Supplemental Environmental Impact Statement on the Issuance of Annual Regulations...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-09

... timing of the general regulatory process. (2) Frequency of review and adoption of duck regulatory packages. Duck regulatory packages are the set of framework regulations that apply to the general duck... limits), and closed. In the draft SEIS, we present two alternatives regarding how frequently duck...

The Regulatory Review Process in South Africa: Challenges and Opportunities for a New Improved System.

PubMed

Keyter, Andrea; Gouws, Joey; Salek, Sam; Walker, Stuart

2018-01-01

The aims of this study were to assess the regulatory review process in South Africa from 2015 to 2017, identify the key milestones and timelines; evaluate the effectiveness of measures to ensure consistency, transparency, timeliness, and predictability in the review process; and to provide recommendations for enhanced regulatory practices. A questionnaire was completed by the Medicines Control Council (MCC) to describe the organization of the authority, record key milestones and timelines in the review process and to identify good review practices (GRevPs). Currently, the MCC conducts a full assessment of quality, efficacy, and safety data in the review of all applications. The overall regulatory median approval time decreased by 14% in 2017 (1411 calendar days) compared with that of 2016, despite the 27% increase in the number of applications. However, the MCC has no target for overall approval time of new active substance applications and no targets for key review milestones. Guidelines, standard operating procedures, and review templates are in place, while the formal implementation of GRevPs and the application of an electronic document management system are planned for the near future. As the MCC transitions to the newly established South Africa Health Products Regulatory Authority, it would be crucial for the authority to recognize the opportunities for an enhanced regulatory review and should consider models such as abridged assessment, which encompass elements of risk stratification and reliance. It is hoped that resource constraints may then be alleviated and capacity developed to meet target timelines.

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation.

PubMed

Pietrobon, Ricardo; Shah, Anand; Kuo, Paul; Harker, Matthew; McCready, Mariana; Butler, Christeen; Martins, Henrique; Moorman, C T; Jacobs, Danny O

2006-07-27

Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process. The main objective of DSRC is to streamline regulatory research processes. The application was built using a combination of paper prototyping for system requirements and Java as the primary language for the application, in conjunction with the Model-View-Controller design model. The researcher interface was designed for simplicity so that it could be used by individuals with different computer literacy levels. Analogously, the administrator interface was designed with functionality as its primary goal. DSRC facilitates the exchange of regulatory documents between researchers and research administrators, allowing for tasks to be tracked and documents to be stored in a Web environment accessible from an Intranet. Usability was evaluated using formal usability tests and field observations. Formal usability results demonstrated that DSRC presented good speed, was easy to learn and use, had a functionality that was easily understandable, and a navigation that was intuitive. Additional features implemented upon request by initial users included: extensive variable categorization (in contrast with data capture using free text), searching capabilities to improve how research administrators could search an extensive number of researcher names, warning messages before critical tasks were performed (such as deleting a task), and confirmatory e-mails for critical tasks (such as completing a regulatory task). The current version of DSRC was shown to have excellent overall usability properties in handling research regulatory issues. It is hoped that its release as an open-source application will promote improved and streamlined regulatory processes for individual academic centers as well as larger research networks.

Duke Surgery Research Central: an open-source Web application for the improvement of compliance with research regulation

PubMed Central

Pietrobon, Ricardo; Shah, Anand; Kuo, Paul; Harker, Matthew; McCready, Mariana; Butler, Christeen; Martins, Henrique; Moorman, CT; Jacobs, Danny O

2006-01-01

Background Although regulatory compliance in academic research is enforced by law to ensure high quality and safety to participants, its implementation is frequently hindered by cost and logistical barriers. In order to decrease these barriers, we have developed a Web-based application, Duke Surgery Research Central (DSRC), to monitor and streamline the regulatory research process. Results The main objective of DSRC is to streamline regulatory research processes. The application was built using a combination of paper prototyping for system requirements and Java as the primary language for the application, in conjunction with the Model-View-Controller design model. The researcher interface was designed for simplicity so that it could be used by individuals with different computer literacy levels. Analogously, the administrator interface was designed with functionality as its primary goal. DSRC facilitates the exchange of regulatory documents between researchers and research administrators, allowing for tasks to be tracked and documents to be stored in a Web environment accessible from an Intranet. Usability was evaluated using formal usability tests and field observations. Formal usability results demonstrated that DSRC presented good speed, was easy to learn and use, had a functionality that was easily understandable, and a navigation that was intuitive. Additional features implemented upon request by initial users included: extensive variable categorization (in contrast with data capture using free text), searching capabilities to improve how research administrators could search an extensive number of researcher names, warning messages before critical tasks were performed (such as deleting a task), and confirmatory e-mails for critical tasks (such as completing a regulatory task). Conclusion The current version of DSRC was shown to have excellent overall usability properties in handling research regulatory issues. It is hoped that its release as an open-source application will promote improved and streamlined regulatory processes for individual academic centers as well as larger research networks. PMID:16872540

Perspective: Maximum caliber is a general variational principle for dynamical systems

NASA Astrophysics Data System (ADS)

Dixit, Purushottam D.; Wagoner, Jason; Weistuch, Corey; Pressé, Steve; Ghosh, Kingshuk; Dill, Ken A.

2018-01-01

We review here Maximum Caliber (Max Cal), a general variational principle for inferring distributions of paths in dynamical processes and networks. Max Cal is to dynamical trajectories what the principle of maximum entropy is to equilibrium states or stationary populations. In Max Cal, you maximize a path entropy over all possible pathways, subject to dynamical constraints, in order to predict relative path weights. Many well-known relationships of non-equilibrium statistical physics—such as the Green-Kubo fluctuation-dissipation relations, Onsager's reciprocal relations, and Prigogine's minimum entropy production—are limited to near-equilibrium processes. Max Cal is more general. While it can readily derive these results under those limits, Max Cal is also applicable far from equilibrium. We give examples of Max Cal as a method of inference about trajectory distributions from limited data, finding reaction coordinates in bio-molecular simulations, and modeling the complex dynamics of non-thermal systems such as gene regulatory networks or the collective firing of neurons. We also survey its basis in principle and some limitations.

Perspective: Maximum caliber is a general variational principle for dynamical systems.

PubMed

Dixit, Purushottam D; Wagoner, Jason; Weistuch, Corey; Pressé, Steve; Ghosh, Kingshuk; Dill, Ken A

2018-01-07

We review here Maximum Caliber (Max Cal), a general variational principle for inferring distributions of paths in dynamical processes and networks. Max Cal is to dynamical trajectories what the principle of maximum entropy is to equilibrium states or stationary populations. In Max Cal, you maximize a path entropy over all possible pathways, subject to dynamical constraints, in order to predict relative path weights. Many well-known relationships of non-equilibrium statistical physics-such as the Green-Kubo fluctuation-dissipation relations, Onsager's reciprocal relations, and Prigogine's minimum entropy production-are limited to near-equilibrium processes. Max Cal is more general. While it can readily derive these results under those limits, Max Cal is also applicable far from equilibrium. We give examples of Max Cal as a method of inference about trajectory distributions from limited data, finding reaction coordinates in bio-molecular simulations, and modeling the complex dynamics of non-thermal systems such as gene regulatory networks or the collective firing of neurons. We also survey its basis in principle and some limitations.

77 FR 17537 - Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-26

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66629; File No. SR-ICEEU-2012-05] Self-Regulatory Organizations; ICE Clear Europe Limited; Notice of Filing of Proposed Rule Change To Amend the ICE Clear Europe CDS Procedures, Finance Procedures, and Rules With Respect to the Calculation and Payment of Interest on Mark-To-Market Margin on CDS...

Current regulatory issues in cell and tissue therapy.

PubMed

Burger, S R

2003-01-01

Cell-based therapies have grown dramatically in power and scope in recent years. Once limited to blood and BM transplantation, these therapies now encompass tissue repair and regeneration, metabolic support, gene replacement, and immune effector functions, with established and investigational clinical applications in disorders affecting nearly every tissue and organ system. The complexity and novel applications of human cells, tissues, and cellular and tissue-based products (HCT/Ps), however, present potential risks for adverse events. The US Food and Drug Administration, responding to these concerns, has established a tiered, risk-based regulatory structure, in which more rigorous controls and safeguards are required for products thought to pose increased risk. The proposed good tissue practices (GTP) rule and existing good manufacturing practices (GMP) requirements form the principal elements of this regulatory framework. The proposed GTPs are intended to prevent HCT/P contamination with infectious disease agents, and to ensure that these cells and tissues maintain their integrity and function. GMPs focus on production of safe, pure, and potent products, and entail a higher level of process control and product characterization. All HCT/Ps will be required to comply with GTPs. HCT/Ps considered to present greater risks of adverse events, however, will be subject to both GTPs and GMPs, and must obtain premarket approval using the Investigational New Drug (IND) mechanism established for biologics. Although these requirements will present significant challenges for clinician- investigators and laboratories producing HCT/Ps, the regulations fundamentally support good clinical care by increasing safety and control, and enable good science by improving the quality and reliability of data.

Review of oncology and hematology drug product approvals at the US Food and Drug Administration between July 2005 and December 2007.

PubMed

Sridhara, Rajeshwari; Johnson, John R; Justice, Robert; Keegan, Patricia; Chakravarty, Aloka; Pazdur, Richard

2010-02-24

The Office of Oncology Drug Products (OODP) in the Center for Drug Evaluation and Research at the US Food and Drug Administration began reviewing marketing applications for oncological and hematologic indications in July 2005. We conducted an overview of products that were reviewed by the OODP for marketing approval and the regulatory actions taken during July 2005 to December 2007. We identified all applications that were reviewed by the OODP from July 1, 2005, through December 31, 2007, and reviewed the actions that OODP took. We also sought the basis for the actions taken, including the clinical trial design, endpoints used, patient accrual in the trial(s) supporting approval, and the type of regulatory approval. During the study period, the OODP reviewed marketing applications for 60 new indications and took regulatory action on 58 indications. Regulatory action was based on a risk-benefit evaluation of the data submitted with each application. Products that demonstrated efficacy and had an acceptable risk-benefit ratio were granted either regular or accelerated marketing approval for use in the specific indication that was studied. Regular approval was based on endpoints that demonstrated that the drug provided clinical benefit as evidenced by a longer or better life or a favorable effect on an established surrogate for a longer or better life. Accelerated approval was based on a less well-established surrogate endpoint that was reasonably likely to predict a longer or better life. Of the 53 new indications that were approved during the study period, 39 received regular approval, nine received accelerated approval, and five were converted from accelerated to regular approval. Five applications were not approved, and two applications were withdrawn before any regulatory action was taken. Eighteen of the 53 indications that were approved were for new molecular entities. During the study period, regulatory action was taken on 58 of the 60 marketing applications. Fifty-three applications were approved. A variety of clinical trial endpoints were used in the approval trials.

Legitimization of regulatory norms: Waterfowl hunter acceptance of changing duck bag limits

USGS Publications Warehouse

Schroeder, Susan A.; Fulton, David C.; Lawrence, Jeffrey S.; Cordts, Steven D.

2014-01-01

Few studies have examined response to regulatory change over time, or addressed hunter attitudes about changes in hunting bag limits. This article explores Minnesota waterfowl hunters’ attitudes about duck bag limits, examining attitudes about two state duck bag limits that were initially more restrictive than the maximum set by the U.S. Fish and Wildlife Service (USFWS), but then increased to match federal limits. Results are from four mail surveys that examined attitudes about bag limits over time. Following two bag limit increases, a greater proportion of hunters rated the new bag limit “too high” and a smaller proportion rated it “too low.” Several years following the first bag limit increase, the proportion of hunters who indicated that the limit was “too high” had declined, suggesting hunter acceptance of the new regulation. Results suggest that waterfowl bag limits may represent legal norms that influence hunter attitudes and gain legitimacy over time.

75 FR 62154 - Carolina Power & Light Company; Notice of Withdrawal of Application for Amendment to Renewed...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-07

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0319; Docket No. 50-400] Carolina Power & Light Company; Notice of Withdrawal of Application for Amendment to Renewed Facility Operating License The U.S. Nuclear Regulatory Commission (NRC, the Commission) has granted the request of the Carolina Power & Light Company...

10 CFR 170.41 - Failure by applicant or licensee to pay prescribed fees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Failure by applicant or licensee to pay prescribed fees. 170.41 Section 170.41 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED...

10 CFR 170.41 - Failure by applicant or licensee to pay prescribed fees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Failure by applicant or licensee to pay prescribed fees. 170.41 Section 170.41 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED...

10 CFR 170.41 - Failure by applicant or licensee to pay prescribed fees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Failure by applicant or licensee to pay prescribed fees. 170.41 Section 170.41 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED...

10 CFR 170.41 - Failure by applicant or licensee to pay prescribed fees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Failure by applicant or licensee to pay prescribed fees. 170.41 Section 170.41 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED...

10 CFR 170.41 - Failure by applicant or licensee to pay prescribed fees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Failure by applicant or licensee to pay prescribed fees. 170.41 Section 170.41 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FEES FOR FACILITIES, MATERIALS, IMPORT AND EXPORT LICENSES, AND OTHER REGULATORY SERVICES UNDER THE ATOMIC ENERGY ACT OF 1954, AS AMENDED...

Report of the State-of-the-Science Workshop: Evaluation of Epidemiological Data Consistency for Application in Regulatory Risk Assessment (Final Report)

EPA Science Inventory

EPA announced the availability of the independent workshop proceedings, Report of the State-of-the-Science Workshop: Evaluation of Epidemiological Data Consistency for Application in Regulatory Risk Assessment. This report provides a summary of selected epidemiology meth...

78 FR 52219 - State of Georgia Relinquishment of Sealed Source and Device Evaluation and Approval Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-22

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0196] State of Georgia Relinquishment of Sealed Source and... evaluate and approve sealed source and device (SS&D) applications in the State of Georgia and approved the... regulatory authority for evaluating and approving sealed source and device applications on August 20, 2013...

77 FR 51581 - Request for a License To Export Nuclear Grade Graphite

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-24

... NUCLEAR REGULATORY COMMISSION Request for a License To Export Nuclear Grade Graphite Pursuant to 10 CFR 110.70 (b) ``Public Notice of Receipt of an Application,'' please take notice that the Nuclear... requestor or petitioner upon the applicant, the office of the General Counsel, U.S. Nuclear Regulatory...

76 FR 12949 - Stingray Pipeline Company, L.L.C.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP11-97-000] Stingray Pipeline Company, L.L.C.; Notice of Application On February 22, 2011, Stingray Pipeline Company, L.L.C...--Regulatory Affairs, Stingray Pipeline Company, L.L.C., 1100 Louisiana, Suite 3300, Houston, Texas 77002, by...

76 FR 71961 - Elba Express Company, L.L.C.; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-21

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. CP12-11-000] Elba Express Company, L.L.C.; Notice of Application Take notice that on October 31, 2011, Elba Express Company, L.L.C... directed to Glenn A. Sheffield, Director, Rates & Regulatory Affairs, Elba Express Company, L.L.C., 569...

RCT: Module 2.04, Dosimetry, Course 8769

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

Hillmer, Kurt T.

This course will introduce the types of instruments used to measure external and internal radiation to people. Dosimetry is the quantitative assessment of radiation received by the human body. Several types of dosimeters are used worldwide. This information is valuable to all radiological control personnel because dosimeters are the only direct method to measure and document personnel radiation exposure and ensure regulatory compliance with applicable limits. This course will cover dosimetry terms, Department of Energy (DOE) limits, Los Alamos National Laboratory (LANL) administrative guidelines, thermoluminescent dosimeters (TLDs), LANL dosimetry, and bioassay assessment methods. This course will prepare the student withmore » the skills necessary for radiological control technician (RCT) qualification by passing quizzes, tests, and the RCT Comprehensive Phase 1, Unit 2 Examination (TEST 27566) and providing in-thefield skills.« less

Emerging ethical perspectives in the clustered regularly interspaced short palindromic repeats genome-editing debate

PubMed Central

Camporesi, Silvia; Cavaliere, Giulia

2016-01-01

This paper provides an overview of the ethical issues in the international clustered regularly interspaced short palindromic repeats (CRISPR) genome editing debate from March 2015 to September 2016. We present the regulatory framework for embryo research in the UK, and explain why CRISPR is not a significant break with the past. We discuss the ethical issues arising from CRISPR applications beyond human embryos, namely the use of gene drive-engineered mosquitoes to eradicate diseases, engineering nonhuman animals to harvest organs for human transplant and engineering crops. We discuss the experiments that have demonstrated the technical feasibility of cultivating embryos in vitro for up to 14 days, and possibly beyond this limit, and the ethical issues arising from the proposal to extend the limit beyond 14 days. PMID:28757883

Emerging ethical perspectives in the clustered regularly interspaced short palindromic repeats genome-editing debate.

PubMed

Camporesi, Silvia; Cavaliere, Giulia

2016-11-01

This paper provides an overview of the ethical issues in the international clustered regularly interspaced short palindromic repeats (CRISPR) genome editing debate from March 2015 to September 2016. We present the regulatory framework for embryo research in the UK, and explain why CRISPR is not a significant break with the past. We discuss the ethical issues arising from CRISPR applications beyond human embryos, namely the use of gene drive-engineered mosquitoes to eradicate diseases, engineering nonhuman animals to harvest organs for human transplant and engineering crops. We discuss the experiments that have demonstrated the technical feasibility of cultivating embryos in vitro for up to 14 days, and possibly beyond this limit, and the ethical issues arising from the proposal to extend the limit beyond 14 days.

JCell--a Java-based framework for inferring regulatory networks from time series data.

PubMed

Spieth, C; Supper, J; Streichert, F; Speer, N; Zell, A

2006-08-15

JCell is a Java-based application for reconstructing gene regulatory networks from experimental data. The framework provides several algorithms to identify genetic and metabolic dependencies based on experimental data conjoint with mathematical models to describe and simulate regulatory systems. Owing to the modular structure, researchers can easily implement new methods. JCell is a pure Java application with additional scripting capabilities and thus widely usable, e.g. on parallel or cluster computers. The software is freely available for download at http://www-ra.informatik.uni-tuebingen.de/software/JCell.

Integrative approach for inference of gene regulatory networks using lasso-based random featuring and application to psychiatric disorders.

PubMed

Kim, Dongchul; Kang, Mingon; Biswas, Ashis; Liu, Chunyu; Gao, Jean

2016-08-10

Inferring gene regulatory networks is one of the most interesting research areas in the systems biology. Many inference methods have been developed by using a variety of computational models and approaches. However, there are two issues to solve. First, depending on the structural or computational model of inference method, the results tend to be inconsistent due to innately different advantages and limitations of the methods. Therefore the combination of dissimilar approaches is demanded as an alternative way in order to overcome the limitations of standalone methods through complementary integration. Second, sparse linear regression that is penalized by the regularization parameter (lasso) and bootstrapping-based sparse linear regression methods were suggested in state of the art methods for network inference but they are not effective for a small sample size data and also a true regulator could be missed if the target gene is strongly affected by an indirect regulator with high correlation or another true regulator. We present two novel network inference methods based on the integration of three different criteria, (i) z-score to measure the variation of gene expression from knockout data, (ii) mutual information for the dependency between two genes, and (iii) linear regression-based feature selection. Based on these criterion, we propose a lasso-based random feature selection algorithm (LARF) to achieve better performance overcoming the limitations of bootstrapping as mentioned above. In this work, there are three main contributions. First, our z score-based method to measure gene expression variations from knockout data is more effective than similar criteria of related works. Second, we confirmed that the true regulator selection can be effectively improved by LARF. Lastly, we verified that an integrative approach can clearly outperform a single method when two different methods are effectively jointed. In the experiments, our methods were validated by outperforming the state of the art methods on DREAM challenge data, and then LARF was applied to inferences of gene regulatory network associated with psychiatric disorders.

Limited output transcranial electrical stimulation (LOTES-2017): Engineering principles, regulatory statutes, and industry standards for wellness, over-the-counter, or prescription devices with low risk.

PubMed

Bikson, Marom; Paneri, Bhaskar; Mourdoukoutas, Andoni; Esmaeilpour, Zeinab; Badran, Bashar W; Azzam, Robin; Adair, Devin; Datta, Abhishek; Fang, Xiao Hui; Wingeier, Brett; Chao, Daniel; Alonso-Alonso, Miguel; Lee, Kiwon; Knotkova, Helena; Woods, Adam J; Hagedorn, David; Jeffery, Doug; Giordano, James; Tyler, William J

We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter)national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulation of the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotherapy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS, tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities, this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public. Copyright © 2017 Elsevier Inc. All rights reserved.

30 CFR 701.2 - Objective.

Code of Federal Regulations, 2011 CFR

2011-07-01

... definitions that apply to the regulation of coal exploration and surface coal mining and reclamation... REGULATORY PROGRAM § 701.2 Objective. The regulations in this part give— (a) A general overview of the regulatory program to be implemented by the State or Federal regulatory authority; (b) The applicability of...

30 CFR 701.2 - Objective.

Code of Federal Regulations, 2014 CFR

2014-07-01

... definitions that apply to the regulation of coal exploration and surface coal mining and reclamation... REGULATORY PROGRAM § 701.2 Objective. The regulations in this part give— (a) A general overview of the regulatory program to be implemented by the State or Federal regulatory authority; (b) The applicability of...

30 CFR 701.2 - Objective.

Code of Federal Regulations, 2010 CFR

2010-07-01

... definitions that apply to the regulation of coal exploration and surface coal mining and reclamation... REGULATORY PROGRAM § 701.2 Objective. The regulations in this part give— (a) A general overview of the regulatory program to be implemented by the State or Federal regulatory authority; (b) The applicability of...

30 CFR 701.2 - Objective.

Code of Federal Regulations, 2013 CFR

2013-07-01

... definitions that apply to the regulation of coal exploration and surface coal mining and reclamation... REGULATORY PROGRAM § 701.2 Objective. The regulations in this part give— (a) A general overview of the regulatory program to be implemented by the State or Federal regulatory authority; (b) The applicability of...

30 CFR 701.2 - Objective.

Code of Federal Regulations, 2012 CFR

2012-07-01

... definitions that apply to the regulation of coal exploration and surface coal mining and reclamation... REGULATORY PROGRAM § 701.2 Objective. The regulations in this part give— (a) A general overview of the regulatory program to be implemented by the State or Federal regulatory authority; (b) The applicability of...

Hours of work and rest in the rail industry.

PubMed

Anderson, C; Grunstein, R R; Rajaratnam, S M W

2013-06-01

Currently, the National Transport Commission is considering four options to form the regulatory framework for rail safety within Australia with respect to fatigue. While the National Transport Commission currently recommends no limitations around hours of work or rest, we provide evidence which suggests regulatory frameworks should incorporate a traditional hours of service regulation over more flexible policies. Our review highlights: Shift durations >12 h are associated with a doubling of risk for accident and injury. Fatigue builds cumulatively with each successive shift where rest in between is inadequate (<12 h). A regulatory framework for fatigue management within the rail industry should prescribe limits on hours of work and rest, including maximum shift duration and successive number of shifts. Appropriately, validated biomathematical models and technologies may be used as a part of a fatigue management system, to augment the protection afforded by limits on hours of work and rest. A comprehensive sleep disorder screening and management programme should form an essential component of any regulatory framework. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications

PubMed Central

Katz, Michael G.; Fargnoli, Anthony S.; Williams, Richard D.

2013-01-01

Abstract Gene therapy is one of the most promising fields for developing new treatments for the advanced stages of ischemic and monogenetic, particularly autosomal or X-linked recessive, cardiomyopathies. The remarkable ongoing efforts in advancing various targets have largely been inspired by the results that have been achieved in several notable gene therapy trials, such as the hemophilia B and Leber's congenital amaurosis. Rate-limiting problems preventing successful clinical application in the cardiac disease area, however, are primarily attributable to inefficient gene transfer, host responses, and the lack of sustainable therapeutic transgene expression. It is arguable that these problems are directly correlated with the choice of vector, dose level, and associated cardiac delivery approach as a whole treatment system. Essentially, a delicate balance exists in maximizing gene transfer required for efficacy while remaining within safety limits. Therefore, the development of safe, effective, and clinically applicable gene delivery techniques for selected nonviral and viral vectors will certainly be invaluable in obtaining future regulatory approvals. The choice of gene transfer vector, dose level, and the delivery system are likely to be critical determinants of therapeutic efficacy. It is here that the interactions between vector uptake and trafficking, delivery route means, and the host's physical limits must be considered synergistically for a successful treatment course. PMID:24164239

Time perspective and social preference in older and younger adults: Effects of self-regulatory fatigue.

PubMed

Segerstrom, Suzanne C; Geiger, Paul J; Combs, Hannah L; Boggero, Ian A

2016-09-01

Socioemotional selectivity theory predicts that when perceived time in life is limited, people will prefer emotionally close social partners over less emotionally rewarding partners. Regulating social choices with regard to time perspective can make the best use of time with regard to well-being. However, doing so may depend on the self-regulatory capacity of the individual. Two studies, 1 with younger adults (N = 101) and 1 with younger (N = 42) and older (N = 39) adults, experimentally tested the effects of time perspective and self-regulatory fatigue on preferences for emotionally close partners and knowledgeable partners. In both studies and across younger and older adults, when self-regulatory fatigue was low, the perception of limited time resulted in a greater preference for close social partners relative to knowledgeable social partners. However, this shift was eliminated by self-regulatory fatigue. In Study 2, when fatigued, younger adults preferred close social partners to knowledgeable partners across time perspectives; older adults preferred close and knowledgeable partners more equally across time perspectives. These findings have implications for social decision-making and satisfaction among people who experience chronic self-regulatory fatigue. They also contradict previous suggestions that only younger adults are susceptible to self-regulatory fatigue. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Time Perspective and Social Preference in Older and Younger Adults: Effects of Self-Regulatory Fatigue

PubMed Central

Segerstrom, Suzanne C.; Geiger, Paul J.; Combs, Hannah L.; Boggero, Ian A.

2016-01-01

Socioemotional selectivity theory predicts that when perceived time in life is limited, people will prefer emotionally close social partners over less emotionally rewarding partners. Regulating social choices with regard to time perspective can make the best use of time with regard to well-being. However, doing so may depend on the self-regulatory capacity of the individual. Two studies, one with younger adults (N = 101) and one with younger (N = 42) and older (N = 39) adults, experimentally tested the effects of time perspective and self-regulatory fatigue on preferences for emotionally close partners and knowledgeable partners. In both studies and across younger and older adults, when self-regulatory fatigue was low, the perception of limited time resulted in a greater preference for close social partners relative to knowledgeable social partners. However, this shift was eliminated by self-regulatory fatigue. In Study 2, when fatigued, younger adults preferred close social partners to knowledgeable partners across time perspectives; older adults preferred close and knowledgeable partners more equally across time perspectives. These findings have implications for social decision-making and satisfaction among people who experience chronic self-regulatory fatigue. They also contradict previous suggestions that only younger adults are susceptible to self-regulatory fatigue. PMID:27243763

Alkali activated solidification/stabilisation of air pollution control residues and co-fired pulverised fuel ash.

PubMed

Shirley, Robin; Black, Leon

2011-10-30

This paper examines the potential treatment by solidification/stabilisation (S/S) of air pollution control (APC) residues using only waste materials otherwise bound for disposal, namely a pulverised fuel ash (PFA) from a co-fired power station and a waste caustic solution. The use of waste materials to stabilise hazardous wastes in order to meet waste acceptance criteria (WAC) would offer an economical and efficient method for reducing the environmental impact of the hazardous waste. The potential is examined against leach limits for chlorides, sulphates and total dissolved solids, and compressive strength performance described in the WAC for stable non-reactive (SNR) hazardous waste landfill cells in England and Wales. The work demonstrates some potential for the treatment, including suitable compressive strengths to meet regulatory limits. Monolithic leach results showed good encapsulation compared to previous work using a more traditional cement binder. However, consistent with previous work, SNR WAC for chlorides was not met, suggesting the need for a washing stage. The potential problems of using a non-EN450 PFA for S/S applications were also highlighted, as well as experimental results which demonstrate the effect of ionic interactions on the mobility of phases during regulatory leach testing. Copyright © 2011 Elsevier B.V. All rights reserved.

[Physically-based model of pesticide application for risk assessment of agricultural workers].

PubMed

Rubino, F M; Mandic-Rajcevic, S; Vianello, G; Brambilla, G; Colosio, C

2012-01-01

Due to their unavoidable toxicity to non-target organisms, including man, the not of Plant Protection Products requires a thorough risk assessment to rationally advise safe use procedures and protection equipment by farmers. Most information on active substances and formulations, such as dermal absorption rates and exposure limits are available in the large body of regulatory data. Physically-based computational models can be used to forecast risk in real-life conditions (preventive assessment by 'exposure profiles'), to drive the cost-effective use of products and equipment and to understand the sources of unexpected exposure.

Induction of virus resistance by exogenous application of double-stranded RNA.

PubMed

Mitter, Neena; Worrall, Elizabeth A; Robinson, Karl E; Xu, Zhi Ping; Carroll, Bernard J

2017-10-01

Exogenous application of double-stranded RNA (dsRNA) for virus resistance in plants represents a very attractive alternative to virus resistant transgenic crops or pesticides targeting virus vectors. However, the instability of dsRNA sprayed onto plants is a major challenge as spraying naked dsRNA onto plants provides protection against homologous viruses for only 5 days. Innovative approaches, such as the use of nanoparticles as carriers of dsRNA for improved stability and sustained release, are emerging as key disruptive technologies. Knowledge is still limited about the mechanism of entry, transport and processing of exogenously applied dsRNA in plants. Cost of dsRNA and regulatory framework will be key influencers towards practical adoption of this technology. Copyright © 2017 Elsevier B.V. All rights reserved.

RCRA, superfund and EPCRA hotline training module. Introduction to: Generators (40 cfr part 262) updated July 1996

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

NONE

1996-07-01

The module presents an overview of regulations applicable to generators of hazardous waste. It defines the terms `generator` and `co-generator,` and lists the three classes of generators, outlines the different generation and accumulation limits, and provides specific regulatory and CFR citations. It defines episodic generation and explains the use of EPA identification numbers and manifests. It outlines the accumulation standards, defines `empty tank` and `start time` for waste accumulation purposes, and identifies regulations pertaining to accumulation in tanks, containers, containment buildings, and on drip pads. It defines `satellite accumulation` and provides applicable federal register citations. It cites the CFR sectionmore » covering recordkeeping and reporting requirements for generators. It explains how to obtain copies of notification forms and manifests.« less

12 CFR 218.701 - Exemption from the definition of “broker” for certain institutional referrals.

Code of Federal Regulations, 2010 CFR

2010-01-01

... rules of any self-regulatory organization; (B) Predominantly engaged in banking activities other than..., in accordance with the qualification standards established by the rules of any self-regulatory... dealer's applicable self-regulatory organization as if the broker or dealer had recommended the...

78 FR 57319 - Children's Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-18

...-AB20 Children's Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines; kidSAFE... proposed self-regulatory guidelines submitted by the kidSAFE Seal Program (``kidSAFE''), owned and operated... part of the SUPPLEMENTARY INFORMATION section below. Write ``kidSAFE Application for Safe Harbor...

Web-based applications for building, managing and analysing kinetic models of biological systems.

PubMed

Lee, Dong-Yup; Saha, Rajib; Yusufi, Faraaz Noor Khan; Park, Wonjun; Karimi, Iftekhar A

2009-01-01

Mathematical modelling and computational analysis play an essential role in improving our capability to elucidate the functions and characteristics of complex biological systems such as metabolic, regulatory and cell signalling pathways. The modelling and concomitant simulation render it possible to predict the cellular behaviour of systems under various genetically and/or environmentally perturbed conditions. This motivates systems biologists/bioengineers/bioinformaticians to develop new tools and applications, allowing non-experts to easily conduct such modelling and analysis. However, among a multitude of systems biology tools developed to date, only a handful of projects have adopted a web-based approach to kinetic modelling. In this report, we evaluate the capabilities and characteristics of current web-based tools in systems biology and identify desirable features, limitations and bottlenecks for further improvements in terms of usability and functionality. A short discussion on software architecture issues involved in web-based applications and the approaches taken by existing tools is included for those interested in developing their own simulation applications.

Telemedicine: legal and licensure issues

NASA Astrophysics Data System (ADS)

Wood, Michael B.; Whelan, Leo J.

1995-10-01

The National Information Infrastructure program offers a great opportunity for the United States to capitalize on remarkable technological advancements over a broad range of applications benefiting society. One such application, telemedicine, has the potential to offer widespread access to sophisticated medical care, curtailed health care delivery costs, and homogeneous health and health-related educational opportunities. However, there are a variety of barriers to widespread application of telemedicine once the technical infrastructure of the information highway is well established and ubiquitous. These barriers include technical limitations, reimbursement issues, equipment and networking costs, and appropriate scientific studies to document efficacy and cost effectiveness. These issues may prove to be only transient disincentives which can be surmounted. Additional barriers exist, however, that may not be as readily resolved by traditional methods of analysis and more widespread practice applications. These political and regulatory obstacles will require clarification of the issues and solutions based on national consensus. It is the purpose of this discussion to amplify on these particular barriers which include licensure and tort jurisdiction.

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

PubMed Central

2010-01-01

Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

[The certification of advanced therapy medicinal products. A quality label for product development in small and medium-sized enterprises].

PubMed

Berger, A; Schüle, S; Flory, E

2011-07-01

Advanced therapy medicinal products (ATMPs) are gene therapy, cell therapy, and tissue engineered products. To gain access to the market within the European Union, ATMPs must be authorized by the European Commission (EC). Especially for small and medium-sized enterprises (SMEs), the European centralized procedure of marketing authorization that is conducted by the European Medicines Agency (EMA) constitutes a major challenge, because SMEs often have little experience with regulatory procedures and many have limited financial possibilities. To tackle these challenges, a certification procedure exclusively for SMEs and their ATMP development was introduced by the EC. Independently from a marketing authorization application, development and/or production processes can be certified. An issued certificate demonstrates that the respective process meets the current regulatory and scientific requirements of the EMA, representing a valuable milestone for putative investors and licensees. This article highlights the background, the detailed procedure, the minimum requirements, as well as the costs of certification, while giving further noteworthy guidance for interested parties.

Implementing the NPDES program: An update on the WET ...

EPA Pesticide Factsheets

The U.S. EPA has utilized the Clean Water Act - National Pollutant Discharge Elimination System permitting program to protect waters of the U.S for over 40 years. NPDES permit effluent limitations serve as the primary mechanism for controlling discharges of pollutants to receiving waters. When developing effluent limitations for an NPDES permit, a permit writer must consider limits based on both the technology available to control the pollutants (i.e., technology-based effluent limits) and limits that are protective of the water quality standards of the receiving water (i.e., water quality-based effluent limits). WET testing is one of the water quality-based effluent limitation mechanisms available to permit writers that is useful in determining how the additive, synergistic and compounding effects of toxic effluents effect streams. This presentation will provide an overview of the current EPA NPDES permit program direction for increasing the efficacy of NPDES permits program administered by the U.S. EPA and States. The training implementation plan is expected to provide permit writers with a clearer understanding of WET requirements as established via the U.S. EPA WET test manuals, NPDES permitting regulatory authorities, and the WET science which has been long established. not applicable

76 FR 64388 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses; Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0241] Biweekly Notice; Applications and Amendments to Facility Operating Licenses; Involving No Significant Hazards Considerations Background Pursuant to section 189a. (2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or NRC) is publishing...

77 FR 22808 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0090] Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses Involving No Significant Hazards Considerations Background Pursuant to Section 189a. (2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or...

78 FR 44167 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0158] Biweekly Notice; Applications and Amendments to Facility Operating Licenses and Combined Licenses Involving No Significant Hazards Considerations Background Pursuant to Section 189a. (2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or...

77 FR 23766 - Duke Energy Carolinas, LLC; Notice of Withdrawal of Application for Amendment to Facility...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-269, 50-270, and 50-287; NRC-2012-0093] Duke Energy Carolinas, LLC; Notice of Withdrawal of Application for Amendment to Facility Operating License The U.S. Nuclear Regulatory Commission (the Commission) has granted the request of Duke Energy Carolinas, LLC (the...

77 FR 32962 - Gulf Coast LNG Export, LLC; Application for Long-Term Authorization To Export Domestically...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

...: Office of Fossil Energy, DOE. ACTION: Notice of application. SUMMARY: The Office of Fossil Energy (FE) of... Regulatory Activities, Office of Fossil Energy, P.O. Box 44375, Washington, DC 20026-4375. Hand Delivery or... Gas Regulatory Activities, Office of Fossil Energy, Forrestal Building, Room 3E-042, 1000 Independence...

76 FR 81994 - UniStar Nuclear Energy; Combined License Application for Calvert Cliffs Nuclear Power Plant, Unit...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... NUCLEAR REGULATORY COMMISSION [Docket No. 52-016; NRC-2008-0250] UniStar Nuclear Energy; Combined License Application for Calvert Cliffs Nuclear Power Plant, Unit 3; Exemption 1.0 Background: UniStar Nuclear Energy (UNE) submitted to the U.S. Nuclear Regulatory Commission (NRC or the Commission ) a...

76 FR 4948 - GE Hitachi Nuclear Energy; Notice of Receipt and Availability of an Application for Renewal of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-27

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0020] GE Hitachi Nuclear Energy; Notice of Receipt and... December 7, 2010, GE Hitachi Nuclear Energy (GEH) filed with the U.S. Nuclear Regulatory Commission (NRC..., Certifications, and Approvals for Nuclear Power Plants,'' an application for a design certification (DC) renewal...

76 FR 55125 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0205] Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No Significant Hazards Considerations Background Pursuant to Section 189a. (2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or NRC) is publishing thi...

76 FR 9821 - Biweekly Notice Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-22

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0040] Biweekly Notice Applications and Amendments to Facility Operating Licenses Involving No Significant Hazards Considerations I. Background Pursuant to Section 189a.(2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or NRC) is publishing...

76 FR 4381 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0019] Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No Significant Hazards Considerations I. Background Pursuant to section 189a. (2) of the Atomic Energy Act of 1954, as amended (the Act), the U.S. Nuclear Regulatory Commission (the Commission or NRC) is publishing...

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

PubMed

Byrom, Bill; Watson, Chris; Doll, Helen; Coons, Stephen Joel; Eremenco, Sonya; Ballinger, Rachel; Mc Carthy, Marie; Crescioni, Mabel; O'Donohoe, Paul; Howry, Cindy

2018-06-01

Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Inferring Regulatory Networks from Experimental Morphological Phenotypes: A Computational Method Reverse-Engineers Planarian Regeneration

PubMed Central

Lobo, Daniel; Levin, Michael

2015-01-01

Transformative applications in biomedicine require the discovery of complex regulatory networks that explain the development and regeneration of anatomical structures, and reveal what external signals will trigger desired changes of large-scale pattern. Despite recent advances in bioinformatics, extracting mechanistic pathway models from experimental morphological data is a key open challenge that has resisted automation. The fundamental difficulty of manually predicting emergent behavior of even simple networks has limited the models invented by human scientists to pathway diagrams that show necessary subunit interactions but do not reveal the dynamics that are sufficient for complex, self-regulating pattern to emerge. To finally bridge the gap between high-resolution genetic data and the ability to understand and control patterning, it is critical to develop computational tools to efficiently extract regulatory pathways from the resultant experimental shape phenotypes. For example, planarian regeneration has been studied for over a century, but despite increasing insight into the pathways that control its stem cells, no constructive, mechanistic model has yet been found by human scientists that explains more than one or two key features of its remarkable ability to regenerate its correct anatomical pattern after drastic perturbations. We present a method to infer the molecular products, topology, and spatial and temporal non-linear dynamics of regulatory networks recapitulating in silico the rich dataset of morphological phenotypes resulting from genetic, surgical, and pharmacological experiments. We demonstrated our approach by inferring complete regulatory networks explaining the outcomes of the main functional regeneration experiments in the planarian literature; By analyzing all the datasets together, our system inferred the first systems-biology comprehensive dynamical model explaining patterning in planarian regeneration. This method provides an automated, highly generalizable framework for identifying the underlying control mechanisms responsible for the dynamic regulation of growth and form. PMID:26042810

An inventory of ambulance service regulatory programs in California.

PubMed

Narad, R A

1998-01-01

Ambulance regulation in California is the responsibility of numerous agencies on the state and local levels. By identifying and analyzing the variety of programs used in one state, this study establishes a framework for evaluation of state and local regulatory programs elsewhere. This study surveyed all California local EMS agencies (LEMSAs: California's equivalent of regional EMS organizations) to identify the types of regulatory programs used, the foci of these programs (e.g., equipment and personnel), and their application (e.g., public and private providers). All data acquired were analyzed using population parameters rather than inferential statistics. A response rate of 100% was obtained. Among the regulatory tools used are ordinances, contracts, and franchises. Regulatory standards vary widely as do their applications. Large counties and those that operate their own LEMSA have more extensive regulatory programs than do smaller counties and those who participate in multicounty agencies. Many of the enforcement mechanisms available are weak. This study suggests several policy implications for California and other states. The wide variation in the types of regulatory programs and the standards that are used suggest that the purpose and impact of regulatory programs should be studied further. The decentralization of the ambulance regulatory program and the lack of integration of ambulance regulations into EMS system planning also raise policy questions. In addition, the role of multicounty EMS agencies, as it relates to regulation of ambulance services, should be reviewed.

Incident reporting to BfArM - regulatory framework, results and challenges.

PubMed

Seidel, Robin; Stößlein, Ekkehard; Lauer, Wolfgang

2016-04-01

Medical devices are manifold and one of the most innovative fields of technology. As technologies advance, former limits cease to exist and complex devices become reality. Medical devices represent a very dynamic field with high economic relevance. The manufacturer of a medical device is obliged to minimize product-related risks as well as to demonstrate compliance with the so-called "essential requirements" regarding safety and performance before placing the device on the market. Any critical incident in relation to the application of a medical device has to be reported to the competent authority for risk assessment, which in Germany is either the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI) depending on the type of device. In this article, the German regulatory framework for medical devices and the resulting tasks for BfArM are described as well as the topics of its recently installed research and development group on prospective risk identification and application safety for medical devices. Results of failure mode and root cause analyses of incident data are presented as well as further data on cases with the result "root-cause analysis not possible". Finally an outlook is given on future challenges regarding risk assessment for medical devices.

An assessment of the risk of foreign animal disease introduction into the United States of America through garbage from Alaskan cruise ships.

PubMed

McElvaine, M D; McDowell, R M; Fite, R W; Miller, L

1993-12-01

The United States Department of Agriculture, Animal and Plant Health Inspection Service (USDA-APHIS) has been exploring methods of quantitative risk assessment to support decision-making, provide risk management options and identify research needs. With current changes in world trade, regulatory decisions must have a scientific basis which is transparent, consistent, documentable and defensible. These quantitative risk assessment methods are described in an accompanying paper in this issue. In the present article, the authors provide an illustration by presenting an application of these methods. Prior to proposing changes in regulations, USDA officials requested an assessment of the risk of introduction of foreign animal disease to the United States of America through garbage from Alaskan cruise ships. The risk assessment team used a combination of quantitative and qualitative methods to evaluate this question. Quantitative risk assessment methods were used to estimate the amount of materials of foreign origin being sent to Alaskan landfills. This application of quantitative risk assessment illustrates the flexibility of the methods in addressing specific questions. By applying these methods, specific areas were identified where more scientific information and research were needed. Even with limited information, the risk assessment provided APHIS management with a scientific basis for a regulatory decision.

BMDExpress Data Viewer: A Visualization Tool to Analyze ...

EPA Pesticide Factsheets

Regulatory agencies increasingly apply benchmark dose (BMD) modeling to determine points of departure in human risk assessments. BMDExpress applies BMD modeling to transcriptomics datasets and groups genes to biological processes and pathways for rapid assessment of doses at which biological perturbations occur. However, graphing and analytical capabilities within BMDExpress are limited, and the analysis of output files is challenging. We developed a web-based application, BMDExpress Data Viewer, for visualization and graphical analyses of BMDExpress output files. The software application consists of two main components: ‘Summary Visualization Tools’ and ‘Dataset Exploratory Tools’. We demonstrate through two case studies that the ‘Summary Visualization Tools’ can be used to examine and assess the distributions of probe and pathway BMD outputs, as well as derive a potential regulatory BMD through the modes or means of the distributions. The ‘Functional Enrichment Analysis’ tool presents biological processes in a two-dimensional bubble chart view. By applying filters of pathway enrichment p-value and minimum number of significant genes, we showed that the Functional Enrichment Analysis tool can be applied to select pathways that are potentially sensitive to chemical perturbations. The ‘Multiple Dataset Comparison’ tool enables comparison of BMDs across multiple experiments (e.g., across time points, tissues, or organisms, etc.). The ‘BMDL-BM

[The food legislation evaluation of environmental chemicals in freshwater fish].

PubMed

Krüger, K E

1990-07-01

During the last 1 1/2 decades different regulatory limits have been given to value pollutants in fish under food-legal aspects. Their requested target, which consists of an effective consumer's protection however has been missed by various reasons: The production and distribution of environmental pollutants cannot be suppressed by limits for food. The selective elimination of limit-exceeding individuals from a lot is impossible. Treating both, natural pollutants like geogenic mercury and anthropogenic ones similar seems to be indefensible with regard to food law. Therefore proposals are made to rule only anthropogenic pollutants by law, when regulatory limits are planned to be supplemented. In case of natural distribution less stringent advisory limits seem to be more suitable.

Regulatory elements driving the expression of skeletal lineage reporters differ during bone development and adulthood.

PubMed

Stiers, Pieter-Jan; van Gastel, Nick; Moermans, Karen; Stockmans, Ingrid; Carmeliet, Geert

2017-12-01

To improve bone healing or regeneration more insight in the fate and role of the different skeletal cell types is required. Mouse models for fate mapping and lineage tracing of skeletal cells, using stage-specific promoters, have advanced our understanding of bone development, a process that is largely recapitulated during bone repair. However, validation of these models is often only performed during development, whereas proof of the activity and specificity of the used promoters during the bone regenerative process is limited. Here, we show that the regulatory elements of the 6kb collagen type II promoter are not adequate to drive gene expression during bone repair. Similarly, the 2.3kb promoter of collagen type I lacks activity in adult mice, but the 3.2kb promoter is suitable. Furthermore, Cre-mediated fate mapping allows the visualization of progeny, but this label retention may hinder to distinguish these cells from ones with active expression of the marker at later time points. Together, our results show that the lineage-specific regulatory elements driving gene expression during bone development differ from those required later in life and during bone repair, and justify validation of lineage-specific cell tracing and gene silencing strategies during fracture healing and bone regenerative applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Surface receptor Toso controls B cell-mediated regulation of T cell immunity.

PubMed

Yu, Jinbo; Duong, Vu Huy Hoang; Westphal, Katrin; Westphal, Andreas; Suwandi, Abdulhadi; Grassl, Guntram A; Brand, Korbinian; Chan, Andrew C; Föger, Niko; Lee, Kyeong-Hee

2018-05-01

The immune system is tightly controlled by regulatory processes that allow for the elimination of invading pathogens, while limiting immunopathological damage to the host. In the present study, we found that conditional deletion of the cell surface receptor Toso on B cells unexpectedly resulted in impaired proinflammatory T cell responses, which led to impaired immune protection in an acute viral infection model and was associated with reduced immunopathological tissue damage in a chronic inflammatory context. Toso exhibited its B cell-inherent immunoregulatory function by negatively controlling the pool of IL-10-competent B1 and B2 B cells, which were characterized by a high degree of self-reactivity and were shown to mediate immunosuppressive activity on inflammatory T cell responses in vivo. Our results indicate that Toso is involved in the differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor activation thresholds. Furthermore, we showed that during influenza A-induced pulmonary inflammation, the application of Toso-specific antibodies selectively induced IL-10-competent B cells at the site of inflammation and resulted in decreased proinflammatory cytokine production by lung T cells. These findings suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T cell responses via the modulation of IL-10-competent regulatory B cells.

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PubMed

Alonso-Alconada, L; Barbazan, J; Candamio, S; Falco, J L; Anton, C; Martin-Saborido, C; Fuster, G; Sampedro, M; Grande, C; Lado, R; Sampietro-Colom, L; Crego, E; Figueiras, S; Leon-Mateos, L; Lopez-Lopez, R; Abal, M

2018-05-01

Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Transcription Factor Binding Profiles Reveal Cyclic Expression of Human Protein-coding Genes and Non-coding RNAs

PubMed Central

Cheng, Chao; Ung, Matthew; Grant, Gavin D.; Whitfield, Michael L.

2013-01-01

Cell cycle is a complex and highly supervised process that must proceed with regulatory precision to achieve successful cellular division. Despite the wide application, microarray time course experiments have several limitations in identifying cell cycle genes. We thus propose a computational model to predict human cell cycle genes based on transcription factor (TF) binding and regulatory motif information in their promoters. We utilize ENCODE ChIP-seq data and motif information as predictors to discriminate cell cycle against non-cell cycle genes. Our results show that both the trans- TF features and the cis- motif features are predictive of cell cycle genes, and a combination of the two types of features can further improve prediction accuracy. We apply our model to a complete list of GENCODE promoters to predict novel cell cycle driving promoters for both protein-coding genes and non-coding RNAs such as lincRNAs. We find that a similar percentage of lincRNAs are cell cycle regulated as protein-coding genes, suggesting the importance of non-coding RNAs in cell cycle division. The model we propose here provides not only a practical tool for identifying novel cell cycle genes with high accuracy, but also new insights on cell cycle regulation by TFs and cis-regulatory elements. PMID:23874175

Rationalizing context-dependent performance of dynamic RNA regulatory devices.

PubMed

Kent, Ross; Halliwell, Samantha; Young, Kate; Swainston, Neil; Dixon, Neil

2018-06-21

The ability of RNA to sense, regulate and store information is an attractive attribute for a variety of functional applications including the development of regulatory control devices for synthetic biology. RNA folding and function is known to be highly context sensitive, which limits the modularity and reuse of RNA regulatory devices to control different heterologous sequences and genes. We explored the cause and effect of sequence context sensitivity for translational ON riboswitches located in the 5' UTR, by constructing and screening a library of N-terminal synonymous codon variants. By altering the N-terminal codon usage we were able to obtain RNA devices with a broad range of functional performance properties (ON, OFF, fold-change). Linear regression and calculated metrics were used to rationalize the major determining features leading to optimal riboswitch performance, and to identify multiple interactions between the explanatory metrics. Finally, partial least squared (PLS) analysis was employed in order to understand the metrics and their respective effect on performance. This PLS model was shown to provide good explanation of our library. This study provides a novel multi-variant analysis framework by which to rationalize the codon context performance of allosteric RNA-devices. The framework will also serve as a platform for future riboswitch context engineering endeavors.

17 CFR 240.19b-5 - Temporary exemption from the filing requirements of Section 19(b) of the Act.

Code of Federal Regulations, 2013 CFR

2013-04-01

... filing requirement for self-regulatory organizations that file proposed rule changes concerning the... other requirements under the Act that are applicable to self-regulatory organizations continue to apply... term specialist means any member subject to a requirement of a self-regulatory organization that such...

17 CFR 240.19b-5 - Temporary exemption from the filing requirements of Section 19(b) of the Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... filing requirement for self-regulatory organizations that file proposed rule changes concerning the... other requirements under the Act that are applicable to self-regulatory organizations continue to apply... term specialist means any member subject to a requirement of a self-regulatory organization that such...

17 CFR 240.19b-5 - Temporary exemption from the filing requirements of Section 19(b) of the Act.

Code of Federal Regulations, 2014 CFR

2014-04-01

... filing requirement for self-regulatory organizations that file proposed rule changes concerning the... other requirements under the Act that are applicable to self-regulatory organizations continue to apply... term specialist means any member subject to a requirement of a self-regulatory organization that such...

17 CFR 240.19b-5 - Temporary exemption from the filing requirements of Section 19(b) of the Act.

Code of Federal Regulations, 2012 CFR

2012-04-01

... filing requirement for self-regulatory organizations that file proposed rule changes concerning the... other requirements under the Act that are applicable to self-regulatory organizations continue to apply... term specialist means any member subject to a requirement of a self-regulatory organization that such...

17 CFR 240.19b-5 - Temporary exemption from the filing requirements of Section 19(b) of the Act.

Code of Federal Regulations, 2011 CFR

2011-04-01

... filing requirement for self-regulatory organizations that file proposed rule changes concerning the... other requirements under the Act that are applicable to self-regulatory organizations continue to apply... term specialist means any member subject to a requirement of a self-regulatory organization that such...

17 CFR 240.15b2-2 - Inspection of newly registered brokers and dealers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section 15C(b)(1) of the Act. (b) Each self-regulatory organization that has responsibility for examining... conformity with applicable financial responsibility rules. (c) The examining self-regulatory organization is... examining self-regulatory organization determines that a broker or dealer member has not commenced actual...

75 FR 45172 - Withdrawal of Regulatory Guides 3.44 and 3.49

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-02

... Format and Content for the Safety Analysis Report for an Independent Spent Fuel Storage Installation... on the format and content of the safety analysis report that is required as part of an application to...: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 3.44, ``Standard Format and Content...

78 FR 39367 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... effective upon receipt of this filing by the Commission. The Commission is publishing this notice to solicit... FINRA Firm Gateway.\\5\\ As announced in Regulatory Notice 12-40, the Form, an abbreviated version of...\\ FINRA Firm Gateway is an online compliance tool that provides consolidated access to FINRA applications...

17 CFR 41.3 - Application for an exemptive order pursuant to section 4f(a)(4)(B) of the Act.

Code of Federal Regulations, 2010 CFR

2010-04-01

... member of the National Association of Securities Dealers, Inc.) or equivalent self-regulatory... self-regulatory organization may submit an application for an order pursuant to this section on behalf... exemption; (4) Any provision(s) of the securities laws or rules, or of the rules of a securities self...

75 FR 57299 - First Energy Nuclear Operating Company; Notice of Receipt and Availability of Application for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-20

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0298; Docket No. 50-346] First Energy Nuclear Operating Company; Notice of Receipt and Availability of Application for Renewal of Davis Besse Nuclear Power Station, Unit 1, Facility Operating License No. NPF-003 for an Additional 20-Year Period The U.S. Nuclear Regulatory Commission (NRC or Commission) has...

Applicability of the fish embryo acute toxicity (FET) test (OECD 236) in the regulatory context of Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH).

PubMed

Sobanska, Marta; Scholz, Stefan; Nyman, Anna-Maija; Cesnaitis, Romanas; Gutierrez Alonso, Simon; Klüver, Nils; Kühne, Ralph; Tyle, Henrik; de Knecht, Joop; Dang, Zhichao; Lundbergh, Ivar; Carlon, Claudio; De Coen, Wim

2018-03-01

In 2013 the Organisation for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity (FET) was adopted. It determines the acute toxicity of chemicals to embryonic fish. Previous studies show a good correlation of FET with the standard acute fish toxicity (AFT) test; however, the potential of the FET test to predict AFT, which is required by the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) regulation (EC 1907/2006) and the Classification, Labelling and Packaging (CLP) Regulation (EC 1272/2008), has not yet been fully clarified. In 2015 the European Chemicals Agency (ECHA) requested that a consultant perform a scientific analysis of the applicability of FET to predict AFT. The purpose was to compare the toxicity of substances to fish embryos and to adult fish, and to investigate whether certain factors (e.g., physicochemical properties, modes of action, or chemical structures) could be used to define the applicability boundaries of the FET test. Given the limited data availability, the analysis focused on organic substances. The present critical review summarizes the main findings and discusses regulatory application of the FET test under REACH. Given some limitations (e.g., neurotoxic mode of action) and/or remaining uncertainties (e.g., deviation of some narcotic substances), it has been found that the FET test alone is currently not sufficient to meet the essential information on AFT as required by the REACH regulation. However, the test may be used within weight-of-evidence approaches together with other independent, relevant, and reliable sources of information. The present review also discusses further research needs that may overcome the remaining uncertainties and help to increase acceptance of FET as a replacement for AFT in the future. For example, an increase in the availability of data generated according to OECD test guideline 236 may provide evidence of a higher predictive power of the test. Environ Toxicol Chem 2018;37:657-670. © 2017 SETAC. © 2017 SETAC.

Nuclear Regulatory Commission activities to prepare for reviewing license applications and issuing licenses

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

Uleck, R.B.; DeFino, C.V.

1991-12-31

The Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) assigned States the responsibility to provide for disposal of commercial low-level radioactive waste (LLRW) by 1993. The LLRWPAA also required the US Nuclear Regulatory Commission (NRC) to establish procedures and develop the technical review capability to process license applications for new LLRW disposal facilities. Under the LLRWPAA, NRC is required, to the extent practicable, to complete its review of an LLRW disposal facility license application within 15 months of its submittal by a State. This provision of the LLRWPAA helps ensure that NRC, in addition to protecting public health andmore » safety and the environment, facilitates States` achievement of LLRWPAA milestones for new facility development. A timely NRC review is needed for States to accomplish their objective of having new disposal facilities in operation on the dates prescribed in the LLRWPAA. To help assure NRC and States` compliance with the provisions of the LLRWPAA, NRC has developed a licensing review strategy that includes: (1) the further development of regulatory guidance, (2) enhancement of licensing review capability, and (3) prelicensing regulatory consultation with potential applicants.« less

Study of the regulatory issues affecting truck freight movement in the Midwest.

DOT National Transportation Integrated Search

2014-12-01

This project investigated regulatory issues that may affect or limit freight movement in Iowa and other Midwest states: Illinois, Kansas, : Minnesota, Missouri, Nebraska, South Dakota, and Wisconsin. Current state regulations for the following are re...

Particulate matter emissions from combustion of wood in district heating applications

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

Ghafghazi, S.; Sowlati, T.; Sokhansanj, Shahabaddine

2011-01-01

The utilization of wood biomass to generate district heat and power in communities that have access to this energy source is increasing. In this paper the effect of wood fuel properties, combustion condition, and flue gas cleaning system on variation in the amount and formation of particles in the flue gas of typical district heating wood boilers are discussed based on the literature survey. Direct measurements of particulate matter (PM) emissions from wood boilers with district heating applications are reviewed and presented. Finally, recommendations are given regarding the selection of wood fuel, combustion system condition, and flue gas cleaning systemmore » in district heating systems in order to meet stringent air quality standards. It is concluded that utilization of high quality wood fuel, such as wood pellets produced from natural, uncontaminated stem wood, would generate the least PM emissions compared to other wood fuel types. Particulate matter emissions from grate burners equipped with electrostatic precipitators when using wood pellets can be well below stringent regulatory emission limit such as particulate emission limit of Metro Vancouver, Canada.« less

Digital marketing of unhealthy foods to Australian children and adolescents.

PubMed

Boelsen-Robinson, Tara; Backholer, Kathryn; Peeters, Anna

2016-09-01

The emergence of new media-including branded websites, social media and mobile applications-has created additional touch points for unhealthy food and beverage companies to target children and adolescents. The aim of this study was to perform an audit of new media for three top selling food and beverage brands in Australia. The top selling brand in three of the most advertised food and beverage categories was identified. Facebook, websites and mobile phone applications from these three brands were assessed using a combination of descriptive analyses and structured data collection during June and July 2013. Information on target audience, main focus of the activity, marketing strategies employed and connectivity were collected. Promotional activities were assessed against industry self-regulatory codes. McDonald's, Coca-Cola and Cadbury Dairy Milk were audited, with 21 promotional activities identified. These promotional activities appeared to use a number of marketing strategies, with frequent use of indirect product association, engagement techniques and branding. We identified strategic targeting of both children and adolescents. We found that while all promotional activities technically met self-regulatory codes (usually due to media-specific age restrictions) a number appeared to employ unhealthy food or beverage marketing directed to children. Brands are using engaging content via new media aimed at children and adolescents to promote unhealthy food and beverages. Given the limitations of self-regulatory codes in the context of new media, strategies need to be developed to reduce exposure of children and adolescents to marketing of unhealthy food and beverage products via these avenues. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Policy Considerations for Commercializing Natural Gas and Biomass CCUS

NASA Astrophysics Data System (ADS)

Abrahams, L.; Clavin, C.

2017-12-01

Captured CO2 from power generation has been discussed as an opportunity to improve the environmental sustainability of fossil fuel-based electricity generation and likely necessary technological solution necessary for meeting long-term climate change mitigation goals. In our presentation, we review the findings of a study of natural gas CCUS technology research and development and discuss their applications to biomass CCUS technology potential. Based on interviews conducted with key stakeholders in CCUS technology development and operations, this presentation will discuss these technical and economic challenges and potential policy opportunities to support commercial scale CCUS deployment. In current domestic and electricity and oil markets, CCUS faces economic challenges for commercial deployment. In particular, the economic viability of CCUS has been impacted by the sustained low oil prices that have limited the potential for enhanced oil recovery (EOR) to serve as a near-term utilization opportunity for the captured CO2. In addition, large scale commercial adoption of CCUS is constrained by regulatory inconsistencies and uncertainties across the United States, high initial capital costs, achieving familiarity with new technology applications to existing markets, developing a successful performance track record to acquire financing agreements, and competing against well-established incumbent technologies. CCUS also has additional technical hurdles for measurement, verification, and reporting within states that have existing policy and regulatory frameworks for climate change mitigation. In addition to fossil-fuel based CCUS, we will discuss emerging opportunities to utilize CCUS fueled by gasified biomass resulting in carbon negative power generation with expanded economic opportunities associated with the enhanced carbon sequestration. Successful technology development of CCUS technology requires a portfolio of research leading to technical advances, advances in financial instruments to leverage the benefits of multiple commodity markets (e.g. natural gas, oil, biomass), and policy instruments that address regulatory hurdles posed CCUS technology deployment.

Analysis of environmental constraints on expanding reserves in current and future reservoirs in wetlands. Final report

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

Harder, B.J.

1995-03-01

Louisiana wetlands require careful management to allow exploitation of non-renewable resources without destroying renewable resources. Current regulatory requirements have been moderately successful in meeting this goal by restricting development in wetland habitats. Continuing public emphasis on reducing environmental impacts of resource development is causing regulators to reassess their regulations and operators to rethink their compliance strategies. We examined the regulatory system and found that reducing the number of applications required by going to a single application process and having a coherent map of the steps required for operations in wetland areas would reduce regulatory burdens. Incremental changes can be mademore » to regulations to allow one agency to be the lead for wetland permitting at minimal cost to operators. Operators need cost effective means of access that will reduce environmental impacts, decrease permitting time, and limit future liability. Regulators and industry must partner to develop incentive based regulations that can provide significant environmental impact reduction for minimal economic cost. In addition regulators need forecasts of future E&P trends to estimate the impact of future regulations. To determine future activity we attempted to survey potential operators when this approach was unsuccessful we created two econometric models of north and south Louisiana relating drilling activity, success ratio, and price to predict future wetland activity. Results of the econometric models indicate that environmental regulations have a small but statistically significant effect on drilling operations in wetland areas of Louisiana. We examined current wetland practices and evaluated those practices comparing environmental versus economic costs and created a method for ranking the practices.« less

Definition of Small Gram Quantity Contents for Type B Radioactive Material Transportation Packages: Activity-Based Content Limitations

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

Sitaraman, S; Kim, S; Biswas, D

2010-10-27

Since the 1960's, the Department of Transportation Specification (DOT Spec) 6M packages have been used extensively for transportation of Type B quantities of radioactive materials between Department of Energy (DOE) facilities, laboratories, and productions sites. However, due to the advancement of packaging technology, the aging of the 6M packages, and variability in the quality of the packages, the DOT implemented a phased elimination of the 6M specification packages (and other DOT Spec packages) in favor of packages certified to meet federal performance requirements. DOT issued the final rule in the Federal Register on October 1, 2004 requiring that use ofmore » the DOT Specification 6M be discontinued as of October 1, 2008. A main driver for the change was the fact that the 6M specification packagings were not supported by a Safety Analysis Report for Packaging (SARP) that was compliant with Title 10 of the Code of Federal Regulations part 71 (10 CFR 71). Therefore, materials that would have historically been shipped in 6M packages are being identified as contents in Type B (and sometimes Type A fissile) package applications and addenda that are to be certified under the requirements of 10 CFR 71. The requirements in 10 CFR 71 include that the Safety Analysis Report for Packaging (SARP) must identify the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents (10 CFR 71.33(b)(1) and 10 CFR 71.33(b)(2)), and that the application (i.e., SARP submittal or SARP addendum) demonstrates that the external dose rate (due to the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents) on the surface of the packaging (i.e., package and contents) not exceed 200 mrem/hr (10 CFR 71.35(a), 10 CFR 71.47(a)). It has been proposed that a 'Small Gram Quantity' of radioactive material be defined, such that, when loaded in a transportation package, the dose rates at external points of an unshielded packaging not exceed the regulatory limits prescribed by 10 CFR 71 for non-exclusive shipments. The mass of each radioisotope presented in this paper is limited by the radiation dose rate on the external surface of the package, which per the regulatory limit should not exceed 200 mrem/hr. The results presented are a compendium of allowable masses of a variety of different isotopes (with varying impurity levels of beryllium in some of the actinide isotopes) that, when loaded in an unshielded packaging, do not result in an external dose rate on the surface of the package that exceeds 190 mrem/hr (190 mrem/hr was chosen to provide 5% conservatism relative to the regulatory limit). These mass limits define the term 'Small Gram Quantity' (SGQ) contents in the context of radioactive material transportation packages. The term SGQ is isotope-specific and pertains to contents in radioactive material transportation packages that do not require shielding and still satisfy the external dose rate requirements. Since these calculated mass limits are for contents without shielding, they are conservative for packaging materials that provide some limited shielding or if the contents are placed into a shielded package. The isotopes presented in this paper were chosen as the isotopes that Department of Energy (DOE) sites most likely need to ship. Other more rarely shipped isotopes, along with industrial and medical isotopes, are planned to be included in subsequent extensions of this work.« less

The US Food and Drug Administration's tentative approval process and the global fight against HIV.

PubMed

Chahal, Harinder Singh; Murray, Jeffrey S; Shimer, Martin; Capella, Peter; Presto, Ryan; Valdez, Mary Lou; Lurie, Peter G

2017-12-01

In 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource-constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource-constrained settings. Although the tFDA was originally intended to support the United States' President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in-depth review of the relevant legal and regulatory processes. USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use. In this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource-constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Regulatory Actions - Final Mercury and Air Toxics Standards (MATS) for Power Plants

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) has proposed Mercury and Air Toxics Standards (MATS) for power plants to limit mercury, acid gases and other toxic pollution from power plants. This page describes Federal regulatory actions.

77 FR 15447 - Self-Regulatory Organizations; Chicago Mercantile Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66554; File No. SR-CME-2012-04] Self-Regulatory... Change To Amend the Fee Schedule Applicable to Its OTC Interest Rate Swap Clearing Offering March 9, 2012.... Self-Regulatory Organization's Statement of Terms of Substance of the Proposed Rule Change CME is...

78 FR 35646 - Byron Nuclear Station, Units 1 and 2, and Braidwood Nuclear Station, Units 1 and 2

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-13

... NUCLEAR REGULATORY COMMISSION [Docket Nos.: 50-454, 50-455, 50-456, 50-457; NRC-2013-0126] Byron Nuclear Station, Units 1 and 2, and Braidwood Nuclear Station, Units 1 and 2 AGENCY: Nuclear Regulatory.... Nuclear Regulatory Commission (NRC) has received an application, dated May 29, 2013, from Exelon...

78 FR 16341 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

... regulatory regime applicable to the over-the-counter derivatives markets. Title VII provides the SEC and the CFTC with tools to oversee these markets.\\4\\ Under the comprehensive framework established in Title VII... Rule),\\11\\ arising from the daily mark to market of the CDS (``variation margin''). FINRA notes that...

78 FR 5532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... by the Commission. The Commission is publishing this notice to solicit comments on the proposed rule... via an application on FINRA's Firm Gateway. See Regulatory Notice 11-10 (March 2011). Exception for... Depository (CRD[supreg] system) that the data reported on a Form U4 Disclosure Reporting Page (DRP) also be...

47 CFR 1.1157 - Payment of charges for regulatory fees.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regulatory fees applicable to certain wireless radio, mass media, common carrier, cable and international... installment payments may be cancelled. (d) Any Commercial Mobile Radio Service (CMRS) licensee subject to...

47 CFR 1.1157 - Payment of charges for regulatory fees.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regulatory fees applicable to certain wireless radio, mass media, common carrier, cable and international... installment payments may be cancelled. (d) Any Commercial Mobile Radio Service (CMRS) licensee subject to...

47 CFR 1.1157 - Payment of charges for regulatory fees.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regulatory fees applicable to certain wireless radio, mass media, common carrier, cable and international... installment payments may be cancelled. (d) Any Commercial Mobile Radio Service (CMRS) licensee subject to...

Regulatory landscape for cell therapy--EU view.

PubMed

McBlane, James W

2015-09-01

This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial. A regulation is soon to come into force that will address this and introduce a more efficient clinical trial application process. However, at the marketing authorisation stage, the process is pan-national: the Committee for Human Medicinal Products (CHMP) is responsible for giving the final scientific opinion on all EU marketing authorisation applications for cell therapies: favourable scientific opinions are passed to the European Commission (EC) for further consultation and, if successful, grant of a marketing authorisation valid in all 28 EU countries. In its review of applications for marketing authorisations (MAAs) for cell therapies, the CHMP is obliged to consult the Committee for Advanced Therapies (CAT), who conduct detailed scientific assessments of these applications, with assessment by staff from national regulatory authorities and specialist advisors to the regulators. Copyright © 2015.

18 CFR 131.70 - Form 12 of application by State and municipal licensees for exemption from payment of annual...

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Form 12 of application... FORMS, FEDERAL POWER ACT AND PUBLIC UTILITY REGULATORY POLICIES ACT OF 1978 FORMS § 131.70 Form 12 of... form may be obtained upon request from the Federal Energy Regulatory Commission. (See § 11.24 of this...

Five-Year ALARA Review of Dosimetry Results 1 January 2009 through 31 December 2013.

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

Paulus, Luke R

2014-08-01

A review of dosimetry results from 1 January 2009 through 31 December 2013 was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform to the ALARA philosophy. This included a review and evaluation of personnel dosimetry (external and internal) results at Sandia National Laboratories, New Mexico as well as at Sandia National Laboratories, California. Additionally, results of environmental monitoring efforts at Sandia National Laboratories, New Mexico were reviewed. ALARA is a philosophical approach to radiation protection by managing and controlling radiation exposures (individual and collective) to the work force and to the general publicmore » to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limit but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

Five-Year ALARA Review of Dosimetry Results 1 January 2010 through 31 December 2014.

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

Paulus, Luke R.

2015-06-01

A review of dosimetry results from 1 January 2010 through 31 December 2014 was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform to the philosophy to keep exposures to radiation As Low As is Reasonably Achievable (ALARA). This included a review and evaluation of personnel dosimetry (external and internal) results at Sandia National Laboratories, New Mexico as well as at Sandia National Laboratories, California. Additionally, results of environmental monitoring efforts at Sandia National Laboratories, New Mexico were reviewed. ALARA is a philosophical approach to radiation protection by managing and controlling radiation exposures (individualmore » and collective) to the work force and to the general public to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limit but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

SynBioSS-aided design of synthetic biological constructs.

PubMed

Kaznessis, Yiannis N

2011-01-01

We present walkthrough examples of using SynBioSS to design, model, and simulate synthetic gene regulatory networks. SynBioSS stands for Synthetic Biology Software Suite, a platform that is publicly available with Open Licenses at www.synbioss.org. An important aim of computational synthetic biology is the development of a mathematical modeling formalism that is applicable to a wide variety of simple synthetic biological constructs. SynBioSS-based modeling of biomolecular ensembles that interact away from the thermodynamic limit and not necessarily at steady state affords for a theoretical framework that is generally applicable to known synthetic biological systems, such as bistable switches, AND gates, and oscillators. Here, we discuss how SynBioSS creates links between DNA sequences and targeted dynamic phenotypes of these simple systems. Copyright © 2011 Elsevier Inc. All rights reserved.

RCRA/UST, superfund, and EPCRA hotline training module. Introduction to: Generators (40 CFR part 262) updated as of July 1995

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

NONE

1995-11-01

The module presents an overview of regulations applicable to generators of hazardous waste. It defines the terms generator and co-generator. Lists the three classes of generators, outlines the different generation and accumulation limits, and provides specific regulatory and CFR citations. It also defines episodic generation. It explains the use of EPA identification numbers and manifests. It outlines the accumulation standards, defines empty tank and start time for waste accumulation purposes, and identifies regulations pertaining to accumulation in tanks, containers, containment buildings, and on drip pads. It defines satellite accumulation and provides applicable federal register citations. It cites the CFR sectionmore » covering recordkeeping and reporting requirements for generators. It explains how to obtain copies of notification forms and manifests.« less

National Tribal Air Association Operations - Closed Announcement FY 2016

EPA Pesticide Factsheets

OAR is seeking applications from eligible entities to provide comprehensive air quality policy and regulatory analysis including support and national coordination activities to assist tribes participation in policy and regulatory activities.

30 CFR 725.15 - Grant application procedures.

Code of Federal Regulations, 2010 CFR

2010-07-01

... constitutional, statutory and regulatory provisions applicable to the enforcement and administration of the... authorized designee shall process the revised application as an original application. [42 FR 62704, Dec. 13...

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

EPA Science Inventory

In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizatio...

Novel GM animal technologies and their governance.

PubMed

Bruce, Ann; Castle, David; Gibbs, Corrina; Tait, Joyce; Whitelaw, C Bruce A

2013-08-01

Scientific advances in methods of producing genetically modified (GM) animals continue, yet few such animals have reached commercial production. Existing regulations designed for early techniques of genetic modification pose formidable barriers to commercial applications. Radically improved techniques for producing GM animals invite a re-examination of current regulatory regimes. We critically examine current GM animal regulations, with a particular focus on the European Union, through a framework that recognises the importance of interactions among regulatory regimes, innovation outcomes and industry sectors. The current focus on the regulation of risk is necessary but is unable to discriminate among applications and tends to close down broad areas of application rather than facilitate innovation and positive industry interactions. Furthermore, the fields of innovative animal biosciences appear to lack networks of organisations with co-ordinated future oriented actions. Such networks could drive coherent programmes of innovation towards particular visions and contribute actively to the development of regulatory systems for GM animals. The analysis presented makes the case for regulatory consideration of each animal bioscience related innovation on the basis of the nature of the product itself and not the process by which it was developed.

A dynamical systems model for nuclear power plant risk

NASA Astrophysics Data System (ADS)

Hess, Stephen Michael

The recent transition to an open access generation marketplace has forced nuclear plant operators to become much more cost conscious and focused on plant performance. Coincidentally, the regulatory perspective also is in a state of transition from a command and control framework to one that is risk-informed and performance-based. Due to these structural changes in the economics and regulatory system associated with commercial nuclear power plant operation, there is an increased need for plant management to explicitly manage nuclear safety risk. Application of probabilistic risk assessment techniques to model plant hardware has provided a significant contribution to understanding the potential initiating events and equipment failures that can lead to core damage accidents. Application of the lessons learned from these analyses has supported improved plant operation and safety over the previous decade. However, this analytical approach has not been nearly as successful in addressing the impact of plant processes and management effectiveness on the risks of plant operation. Thus, the research described in this dissertation presents a different approach to address this issue. Here we propose a dynamical model that describes the interaction of important plant processes among themselves and their overall impact on nuclear safety risk. We first provide a review of the techniques that are applied in a conventional probabilistic risk assessment of commercially operating nuclear power plants and summarize the typical results obtained. The limitations of the conventional approach and the status of research previously performed to address these limitations also are presented. Next, we present the case for the application of an alternative approach using dynamical systems theory. This includes a discussion of previous applications of dynamical models to study other important socio-economic issues. Next, we review the analytical techniques that are applicable to analysis of these models. Details of the development of the mathematical risk model are presented. This includes discussion of the processes included in the model and the identification of significant interprocess interactions. This is followed by analysis of the model that demonstrates that its dynamical evolution displays characteristics that have been observed at commercially operating plants. The model is analyzed using the previously described techniques from dynamical systems theory. From this analysis, several significant insights are obtained with respect to the effective control of nuclear safety risk. Finally, we present conclusions and recommendations for further research.

Nanoparticle curcumin ameliorates experimental colitis via modulation of gut microbiota and induction of regulatory T cells

PubMed Central

Ohno, Masashi; Sugitani, Yoshihiko; Nishino, Kyohei; Inatomi, Osamu; Sugimoto, Mitsushige; Kawahara, Masahiro; Andoh, Akira

2017-01-01

Background and Aims Curcumin is a hydrophobic polyphenol derived from turmeric, a traditional Indian spice. Curcumin exhibits various biological functions, but its clinical application is limited due to its poor absorbability after oral administration. A newly developed nanoparticle curcumin shows improved absorbability in vivo. In this study, we examined the effects of nanoparticle curcumin (named Theracurmin) on experimental colitis in mice. Methods BALB/c mice were fed with 3% dextran sulfate sodium (DSS) in water. Mucosal cytokine expression and lymphocyte subpopulation were analyzed by real-time PCR and flow cytometry, respectively. The profile of the gut microbiota was analyzed by real-time PCR. Results Treatment with nanoparticle curcumin significantly attenuated body weight loss, disease activity index, histological colitis score and significantly improved mucosal permeability. Immunoblot analysis showed that NF-κB activation in colonic epithelial cells was significantly suppressed by treatment with nanoparticle curcumin. Mucosal mRNA expression of inflammatory mediators was significantly suppressed by treatment with nanoparticle curcumin. Treatment with nanoparticle curcumin increased the abundance of butyrate-producing bacteria and fecal butyrate level. This was accompanied by increased expansion of CD4+ Foxp3+ regulatory T cells and CD103+ CD8α− regulatory dendritic cells in the colonic mucosa. Conclusions Treatment with nanoparticle curcumin suppressed the development of DSS-induced colitis potentially via modulation of gut microbial structure. These responses were associated with induction of mucosal immune cells with regulatory properties. Nanoparticle curcumin is one of the promising candidates as a therapeutic option for the treatment of IBD. PMID:28985227

Regulatory Oversight of Cell and Gene Therapy Products in Canada.

PubMed

Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

2015-01-01

Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

Technical guide for applications of gene expression profiling in human health risk assessment of environmental chemicals.

PubMed

Bourdon-Lacombe, Julie A; Moffat, Ivy D; Deveau, Michelle; Husain, Mainul; Auerbach, Scott; Krewski, Daniel; Thomas, Russell S; Bushel, Pierre R; Williams, Andrew; Yauk, Carole L

2015-07-01

Toxicogenomics promises to be an important part of future human health risk assessment of environmental chemicals. The application of gene expression profiles (e.g., for hazard identification, chemical prioritization, chemical grouping, mode of action discovery, and quantitative analysis of response) is growing in the literature, but their use in formal risk assessment by regulatory agencies is relatively infrequent. Although additional validations for specific applications are required, gene expression data can be of immediate use for increasing confidence in chemical evaluations. We believe that a primary reason for the current lack of integration is the limited practical guidance available for risk assessment specialists with limited experience in genomics. The present manuscript provides basic information on gene expression profiling, along with guidance on evaluating the quality of genomic experiments and data, and interpretation of results presented in the form of heat maps, pathway analyses and other common approaches. Moreover, potential ways to integrate information from gene expression experiments into current risk assessment are presented using published studies as examples. The primary objective of this work is to facilitate integration of gene expression data into human health risk assessments of environmental chemicals. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

Code of Federal Regulations, 2014 CFR

2014-10-01

... regulatory body. The Contractor agrees to give written notice of (1) the filing of an application for change...) any changes pending with the regulatory body as of the date of contract award. Such notice shall fully describe the proposed change. If, during the term of this contract, the regulatory body having jurisdiction...

48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... regulatory body. The Contractor agrees to give written notice of (1) the filing of an application for change...) any changes pending with the regulatory body as of the date of contract award. Such notice shall fully describe the proposed change. If, during the term of this contract, the regulatory body having jurisdiction...

48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

Code of Federal Regulations, 2013 CFR

2013-10-01

... regulatory body. The Contractor agrees to give written notice of (1) the filing of an application for change...) any changes pending with the regulatory body as of the date of contract award. Such notice shall fully describe the proposed change. If, during the term of this contract, the regulatory body having jurisdiction...

48 CFR 52.241-7 - Change in Rates or Terms and Conditions of Service for Regulated Services.

Code of Federal Regulations, 2011 CFR

2011-10-01

... regulatory body. The Contractor agrees to give written notice of (1) the filing of an application for change...) any changes pending with the regulatory body as of the date of contract award. Such notice shall fully describe the proposed change. If, during the term of this contract, the regulatory body having jurisdiction...

76 FR 32379 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2011-0114] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of pending...: Applications for licenses are [[Page 32380

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

Functional Evolution of a cis-Regulatory Module

PubMed Central

Palsson, Arnar; Alekseeva, Elena; Bergman, Casey M; Nathan, Janaki; Kreitman, Martin

2005-01-01

Lack of knowledge about how regulatory regions evolve in relation to their structure–function may limit the utility of comparative sequence analysis in deciphering cis-regulatory sequences. To address this we applied reverse genetics to carry out a functional genetic complementation analysis of a eukaryotic cis-regulatory module—the even-skipped stripe 2 enhancer—from four Drosophila species. The evolution of this enhancer is non-clock-like, with important functional differences between closely related species and functional convergence between distantly related species. Functional divergence is attributable to differences in activation levels rather than spatiotemporal control of gene expression. Our findings have implications for understanding enhancer structure–function, mechanisms of speciation and computational identification of regulatory modules. PMID:15757364

Introduction to the fathead minnow genome browser and ...

EPA Pesticide Factsheets

Ab initio gene prediction and evidence alignment were used to produce the first annotations for the fathead minnow SOAPdenovo genome assembly. Additionally, a genome browser hosted at genome.setac.org provides simplified access to the annotation data in context with fathead minnow genomic sequence. This work is meant to extend the utility of fathead minnow genome as a resource and enable the continued development of this species as a model organism. The fathead minnow (Pimephales promelas) is a laboratory model organism widely used in regulatory toxicity testing and ecotoxicology research. Despite, the wealth of toxicological data for this organism, until recently genome scale information was lacking for the species, which limited the utility of the species for pathway-based toxicity testing and research. As part of a EPA Pathfinder Innovation Project, next generation sequencing was applied to generate a draft genome assembly, which was published in 2016. However, application of those genome-scale sequencing resources was still limited by the lack of available gene annotations for fathead minnow. Here we report on development of a first generation genome annotation for fathead minnow and the dissemination of that information through a web-based browser that makes it easy to search for genes of interest, extract the corresponding sequence, identify intron and exon boundaries and regulatory regions, and align the computationally predicted genes with other supporti

The forecast for RAC extrapolation: mostly cloudy.

PubMed

Goldman, Elizabeth; Jacobs, Robert; Scott, Ellen; Scott, Bonnie

2011-09-01

The current statutory and regulatory guidance for recovery audit contractor (RAC) extrapolation leaves providers with minimal protection against the process and a limited ability to challenge overpayment demands. Providers not only should understand the statutory and regulatory basis for extrapolation forecast, but also should be able to assess their extrapolation risk and their recourse through regulatory safeguards against contractor error. Providers also should aggressively appeal all incorrect RAC denials to minimize the potential impact of extrapolation.

Taxi Regulatory Revision in Oakland and Berkeley, California : Two Case Studies

DOT National Transportation Integrated Search

1983-06-01

A case study was performed of regulatory changes pertaining to taxicabs in Oakland and neighboring Berkeley, CA. In Oakland rates were approximately doubled and limits on the number of taxi permits removed. Companies were allowed to levy a per-trip s...

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

PubMed

Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

2013-12-17

Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions.

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea

PubMed Central

2013-01-01

Background Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. Results We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. Conclusions SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bldD, SACE_5599 is involved in morphological development of S. erythraea, suggesting a very close relationship between secondary metabolite biosynthesis and morphological differentiation in this organism. While the mode of action of SACE_5599 remains to be elucidated, the manipulation of this gene clearly shows potential for improvement of erythromycin production in S. erythraea in industrial setting. We have also demonstrated the applicability of the comparative proteomics approach for identifying new regulatory elements involved in biosynthesis of secondary metabolites in industrial conditions. PMID:24341557

Global Summit on Regulatory Science 2013.

PubMed

Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

2014-12-01

Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed. Published by Elsevier Inc.

76 FR 42534 - Mandatory Reliability Standards for Interconnection Reliability Operating Limits; System...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-19

... Reliability Operating Limits; System Restoration Reliability Standards AGENCY: Federal Energy Regulatory... data necessary to analyze and monitor Interconnection Reliability Operating Limits (IROL) within its... Interconnection Reliability Operating Limits, Order No. 748, 134 FERC ] 61,213 (2011). \\2\\ The term ``Wide-Area...

Regulatory Promotion of Emergent CCS Technology

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

Davies, Lincoln; Uchitel, Kirsten; Johnson, David

2014-01-01

Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensivemore » regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.« less

Regulatory Flexibility: An Individual Differences Perspective on Coping and Emotion Regulation.

PubMed

Bonanno, George A; Burton, Charles L

2013-11-01

People respond to stressful events in different ways, depending on the event and on the regulatory strategies they choose. Coping and emotion regulation theorists have proposed dynamic models in which these two factors, the person and the situation, interact over time to inform adaptation. In practice, however, researchers have tended to assume that particular regulatory strategies are consistently beneficial or maladaptive. We label this assumption the fallacy of uniform efficacy and contrast it with findings from a number of related literatures that have suggested the emergence of a broader but as yet poorly defined construct that we refer to as regulatory flexibility. In this review, we articulate this broader construct and define both its features and limitations. Specifically, we propose a heuristic individual differences framework and review research on three sequential components of flexibility for which propensities and abilities vary: sensitivity to context, availability of a diverse repertoire of regulatory strategies, and responsiveness to feedback. We consider the methodological limitations of research on each component, review questions that future research on flexibility might address, and consider how the components might relate to each other and to broader conceptualizations about stability and change across persons and situations. © The Author(s) 2013.

Overview of Sensors and Needs for Environmental Monitoring

PubMed Central

Ho, Clifford K.; Robinson, Alex; Miller, David R.; Davis, Mary J.

2005-01-01

This paper surveys the needs associated with environmental monitoring and long-term environmental stewardship. Emerging sensor technologies are reviewed to identify compatible technologies for various environmental monitoring applications. The contaminants that are considered in this report are grouped into the following categories: (1) metals, (2) radioisotopes, (3) volatile organic compounds, and (4) biological contaminants. United States regulatory drivers are evaluated for different applications (e.g., drinking water, storm water, pretreatment, and air emissions), and sensor requirements are derived from these regulatory metrics. Sensor capabilities are then summarized according to contaminant type, and the applicability of the different sensors to various environmental monitoring applications is discussed.

Radiation Protection, Safety and Security Issues in Ghana.

PubMed

Boadu, Mary; Emi-Reynolds, Geoffrey; Amoako, Joseph Kwabena; Akrobortu, Emmanuel; Hasford, Francis

2016-11-01

Although the use of radioisotopes in Ghana began in 1952, the Radiation Protection Board of Ghana was established in 1993 and served as the national competent authority for authorization and inspection of practices and activities involving radiation sources until 2015. The law has been superseded by an Act of Parliament, Act 895 of 2015, mandating the Nuclear Regulatory Authority of Ghana to take charge of the regulation of radiation sources and their applications. The Radiation Protection Institute in Ghana provided technical support to the regulatory authority. Regulatory and service activities that were undertaken by the Institute include issuance of permits for handling of a radiation sources, authorization and inspection of radiation sources, radiation safety assessment, safety assessment of cellular signal towers, and calibration of radiation-emitting equipment. Practices and activities involving application of radiation are brought under regulatory control in the country through supervision by the national competent authority.

21 CFR 60.32 - Applicant response to petition.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PATENT TERM RESTORATION Due Diligence Petitions § 60.32 Applicant response to petition. (a) The applicant... applicant acted with due diligence during the regulatory review period. The applicant's response may include... term restoration application, due diligence petition, and FDA records. ...

Evolution of chemical-specific adjustment factors (CSAF) based on recent international experience; increasing utility and facilitating regulatory acceptance.

PubMed

Bhat, Virunya S; Meek, M E Bette; Valcke, Mathieu; English, Caroline; Boobis, Alan; Brown, Richard

2017-10-01

The application of chemical-specific toxicokinetic or toxicodynamic data to address interspecies differences and human variability in the quantification of hazard has potential to reduce uncertainty and better characterize variability compared with the use of traditional default or categorically-based uncertainty factors. The present review summarizes the state-of-the-science since the introduction of the World Health Organization/International Programme on Chemical Safety (WHO/IPCS) guidance on chemical-specific adjustment factors (CSAF) in 2005 and the availability of recent applicable guidance including the WHO/IPCS guidance on physiologically-based pharmacokinetic (PBPK) modeling in 2010 as well as the U.S. EPA guidance on data-derived extrapolation factors in 2014. A summary of lessons learned from an analysis of more than 100 case studies from global regulators or published literature illustrates the utility and evolution of CSAF in regulatory decisions. Challenges in CSAF development related to the adequacy of, or confidence in, the supporting data, including verification or validation of PBPK models. The analysis also identified issues related to adequacy of CSAF documentation, such as inconsistent terminology and often limited and/or inconsistent reporting, of both supporting data and/or risk assessment context. Based on this analysis, recommendations for standardized terminology, documentation and relevant interdisciplinary research and engagement are included to facilitate the continuing evolution of CSAF development and guidance.

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

Faidy, C.; Gilles, P.

The objective of the seminar was to present the current state of the art in Leak-Before-Break (LBB) methodology development, validation, and application in an international forum. With particular emphasis on industrial applications and regulatory policies, the seminar provided an opportunity to compare approaches, experiences, and codifications developed by different countries. The seminar was organized into four topic areas: status of LBB applications; technical issues in LBB methodology; complementary requirements (leak detection and inspection); LBB assessment and margins. As a result of this seminar, an improved understanding of LBB gained through sharing of different viewpoints from different countries, permits consideration of:more » simplified pipe support design and possible elimination of loss-of-coolant-accident (LOCA) mechanical consequences for specific cases; defense-in-depth type of applications without support modifications; support of safety cases for plants designed without the LOCA hypothesis. In support of these activities, better estimates of the limits to the LBB approach should follow, as well as an improvement in codifying methodologies. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.« less

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

Roussel, G.

Leak-Before-Break (LBB) technology has not been applied in the first design of the seven Pressurized Water Reactors the Belgian utility is currently operating. The design basis of these plants required to consider the dynamic effects associated with the ruptures to be postulated in the high energy piping. The application of the LBB technology to the existing plants has been recently approved by the Belgian Safety Authorities but with a limitation to the primary coolant loop. LBB analysis has been initiated for the Doel 3 and Tihange 2 plants to allow the withdrawal of some of the reactor coolant pump snubbersmore » at both plants and not reinstall some of the restraints after steam generator replacement at Doel 3. LBB analysis was also found beneficial to demonstrate the acceptability of the primary components and piping to the new conditions resulting from power uprating and stretch-out operation. LBB analysis has been subsequently performed on the primary coolant loop of the Tihange I plant and is currently being performed for the Doel 4 plant. Application of the LBB to the primary coolant loop is based in Belgium on the U.S. Nuclear Regulatory Commission requirements. However the Belgian Safety Authorities required some additional analyses and put some restrictions on the benefits of the LBB analysis to maintain the global safety of the plant at a sufficient level. This paper develops the main steps of the safety evaluation performed by the Belgian Safety Authorities for accepting the application of the LBB technology to existing plants and summarizes the requirements asked for in addition to the U.S. Nuclear Regulatory Commission rules.« less

Selecting "saviour siblings": reconsidering the regulation in Australia of pre-implantation genetic diagnosis in conjunction with tissue typing.

PubMed

Taylor-Sands, Michelle

2007-05-01

In recent years, pre-implantation genetic diagnosis (PGD) has been developed to enable the selection of a tissue type matched "saviour sibling" for a sick child. This article examines the current regulatory framework governing PGD in Australia. The availability of PGD in Australia to create a saviour sibling depends on the regulation of ART services by each State and Territory. The limitations on the use of PGD vary throughout Australia, according to the level of regulation of ART in each jurisdiction. This article considers the limitations on the use of PGD for tissue typing in Australia and argues that some of these should be removed for a more consistent national approach. In particular, the focus in ART legislation on the "paramount interests" of the child to be born is inappropriate for the application of tissue typing, which necessarily involves the interests of other family members.

Good modeling practice guidelines for applying multimedia models in chemical assessments.

PubMed

Buser, Andreas M; MacLeod, Matthew; Scheringer, Martin; Mackay, Don; Bonnell, Mark; Russell, Mark H; DePinto, Joseph V; Hungerbühler, Konrad

2012-10-01

Multimedia mass balance models of chemical fate in the environment have been used for over 3 decades in a regulatory context to assist decision making. As these models become more comprehensive, reliable, and accepted, there is a need to recognize and adopt principles of Good Modeling Practice (GMP) to ensure that multimedia models are applied with transparency and adherence to accepted scientific principles. We propose and discuss 6 principles of GMP for applying existing multimedia models in a decision-making context, namely 1) specification of the goals of the model assessment, 2) specification of the model used, 3) specification of the input data, 4) specification of the output data, 5) conduct of a sensitivity and possibly also uncertainty analysis, and finally 6) specification of the limitations and limits of applicability of the analysis. These principles are justified and discussed with a view to enhancing the transparency and quality of model-based assessments. Copyright © 2012 SETAC.

Advancing a Vision for Regulatory Science Training

PubMed Central

Adamo, Joan E.; Wilhelm, Erin E.

2015-01-01

Abstract Regulatory science, a complex field which draws on science, law, and policy, is a growing discipline in medical‐related applications. Competencies help define both a discipline and the criteria to measure high‐quality learning experiences. This paper identifies competencies for regulatory science, how they were developed, and broader recommendations to enhance education and training in this burgeoning field, including a multifaceted training approach. PMID:26083660

CsrB, a noncoding regulatory RNA, is required for BarA-dependent expression of biocontrol traits in Rahnella aquatilis HX2.

PubMed

Mei, Li; Xu, Sanger; Lu, Peng; Lin, Haiping; Guo, Yanbin; Wang, Yongjun

2017-01-01

Rahnella aquatilis is ubiquitous and its certain strains have the applicative potent as a plant growth-promoting rhizobacteria. R. aquatilis HX2 is a biocontrol agent to produce antibacterial substance (ABS) and showed efficient biocontrol against crown gall caused by Agrobacterium vitis on sunflower and grapevine plants. The regulatory network of the ABS production and biocontrol activity is still limited known. In this study, a transposon-mediated mutagenesis strategy was used to investigate the regulators that involved in the biocontrol activity of R. aquatilis HX2. A 366-nt noncoding RNA CsrB was identified in vitro and in vivo, which regulated ABS production and biocontrol activity against crown gall on sunflower plants, respectively. The predicted product of noncoding RNA CsrB contains 14 stem-loop structures and an additional ρ-independent terminator harpin, with 23 characteristic GGA motifs in the loops and other unpaired regions. CsrB is required for ABS production and biocontrol activity in the biocontrol regulation by a two-component regulatory system BarA/UvrY in R. aquatilis HX2. The noncoding RNA CsrB regulates BarA-dependent ABS production and biocontrol activity in R. aquatilis HX2. To the best of our knowledge, this is the first report of noncoding RNA as a regulator for biocontrol function in R. aquatilis.

CsrB, a noncoding regulatory RNA, is required for BarA-dependent expression of biocontrol traits in Rahnella aquatilis HX2

PubMed Central

Lu, Peng; Lin, Haiping; Guo, Yanbin

2017-01-01

Background Rahnella aquatilis is ubiquitous and its certain strains have the applicative potent as a plant growth-promoting rhizobacteria. R. aquatilis HX2 is a biocontrol agent to produce antibacterial substance (ABS) and showed efficient biocontrol against crown gall caused by Agrobacterium vitis on sunflower and grapevine plants. The regulatory network of the ABS production and biocontrol activity is still limited known. Methodology/Principal findings In this study, a transposon-mediated mutagenesis strategy was used to investigate the regulators that involved in the biocontrol activity of R. aquatilis HX2. A 366-nt noncoding RNA CsrB was identified in vitro and in vivo, which regulated ABS production and biocontrol activity against crown gall on sunflower plants, respectively. The predicted product of noncoding RNA CsrB contains 14 stem-loop structures and an additional ρ-independent terminator harpin, with 23 characteristic GGA motifs in the loops and other unpaired regions. CsrB is required for ABS production and biocontrol activity in the biocontrol regulation by a two-component regulatory system BarA/UvrY in R. aquatilis HX2. Conclusion/Significance The noncoding RNA CsrB regulates BarA-dependent ABS production and biocontrol activity in R. aquatilis HX2. To the best of our knowledge, this is the first report of noncoding RNA as a regulator for biocontrol function in R. aquatilis. PMID:29091941

78 FR 60977 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... Volatility \\6\\ (the ``Limit Up-Limit Down Plan''). The Exchange believes the benefits to market participants... April 8, 2014, which is one year following commencement of operations of the Limit Up-Limit Down Plan... should continue while the industry gains further experience operating the Limit Up-Limit Down Plan. \\3...

78 FR 61431 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

... National Market System Plan to Address Extraordinary Market Volatility \\7\\ (the ``Limit Up-Limit Down Plan... commencement of operations of the Limit Up- Limit Down Plan. The Exchange believes that continuing the pilot... further experience operating the Limit Up-Limit Down Plan. \\3\\ Securities Exchange Act Release No. 62886...

78 FR 60991 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-02

... of Regulation NMS under the Act (the ``Limit Up- Limit Down Plan'' or the ``Plan'').\\6\\ The Exchange... Erroneous Rule should continue while the industry gains further experience operating the Limit Up-Limit Down... (June 6, 2012) (the ``Limit Up-Limit Down Release''); see also ISE Rule 2128(i). The Exchange also...

78 FR 61427 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-03

...\\ (the ``Limit Up-Limit Down Plan''). The Exchange believes the benefits to market participants from the..., which is one year following commencement of operations of the Limit Up-Limit Down Plan. The Exchange... the industry gains further experience operating the Limit Up-Limit Down Plan. \\3\\ Securities Exchange...

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

PubMed

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

2018-03-28

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

Absence of Foxp3+ Regulatory T Cells during Allergen Provocation Does Not Exacerbate Murine Allergic Airway Inflammation

PubMed Central

Baru, Abdul Mannan; Ganesh, Venkateswaran; Krishnaswamy, Jayendra Kumar; Hesse, Christina; Untucht, Christopher; Glage, Silke; Behrens, Georg; Mayer, Christian Thomas; Puttur, Franz; Sparwasser, Tim

2012-01-01

Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naïve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence of Foxp3+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics. PMID:23071726

Polyamines in plant physiology

NASA Technical Reports Server (NTRS)

Galston, A. W.; Sawhney, R. K.

1990-01-01

The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.

Avoiding the Enumeration of Infeasible Elementary Flux Modes by Including Transcriptional Regulatory Rules in the Enumeration Process Saves Computational Costs

PubMed Central

Jungreuthmayer, Christian; Ruckerbauer, David E.; Gerstl, Matthias P.; Hanscho, Michael; Zanghellini, Jürgen

2015-01-01

Despite the significant progress made in recent years, the computation of the complete set of elementary flux modes of large or even genome-scale metabolic networks is still impossible. We introduce a novel approach to speed up the calculation of elementary flux modes by including transcriptional regulatory information into the analysis of metabolic networks. Taking into account gene regulation dramatically reduces the solution space and allows the presented algorithm to constantly eliminate biologically infeasible modes at an early stage of the computation procedure. Thereby, computational costs, such as runtime, memory usage, and disk space, are extremely reduced. Moreover, we show that the application of transcriptional rules identifies non-trivial system-wide effects on metabolism. Using the presented algorithm pushes the size of metabolic networks that can be studied by elementary flux modes to new and much higher limits without the loss of predictive quality. This makes unbiased, system-wide predictions in large scale metabolic networks possible without resorting to any optimization principle. PMID:26091045

Functional characterization of the vitellogenin promoter in the silkworm, Bombyx mori.

PubMed

Xu, J; Wang, Y Q; Li, Z Q; Ling, L; Zeng, B S; You, L; Chen, Y Z; Aslam, A F M; Huang, Y P; Tan, A J

2014-10-01

Genetic transformation and genome editing technologies have been successfully established in the lepidopteran insect model, the domesticated silkworm, Bombyx mori, providing great potential for functional genomics and practical applications. However, the current lack of cis-regulatory elements in B. mori gene manipulation research limits further exploitation in functional gene analysis. In the present study, we characterized a B. mori endogenous promoter, Bmvgp, which is a 798-bp DNA sequence adjacent to the 5'-end of the vitellogenin gene (Bmvg). PiggyBac-based transgenic analysis shows that Bmvgp precisely directs expression of a reporter gene, enhanced green fluorescent protein (EGFP), in a sex-, tissue- and stage-specific manner. In transgenic animals, EGFP expression can be detected in the female fat body from larval-pupal ecdysis to the following pupal and adult stage. Furthermore, in vitro and in vivo experiments revealed that EGFP expression can be activated by 20-hydroxyecdysone, which is consistent with endogenous Bmvg expression. These data indicate that Bmvgp is an effective endogenous cis-regulatory element in B. mori. © 2014 The Royal Entomological Society.

Insertion loss of noise barriers on an aboveground, full-scale model longwall coal mining shearer.

PubMed

Sweeney, Daniel D; Slagley, Jeremy M; Smith, David A

2010-05-01

The U.S. mining industry struggles with hazardous noise and dust exposures in underground mining. Specifically, longwall coal mine shearer operators are routinely exposed to noise levels at 151% of the allowable daily dose, and approximately 20% exceed regulatory dust levels. In the current study, a partial barrier was mounted on the full-scale mock shearer at the National Institute for Occupational Safety and Health Pittsburgh Research Laboratory. A simulated, full-scale, coal mine longwall shearer operation was employed to test the feasibility of utilizing a barrier to separate the shearer operator from the direct path of the noise and dust source during mining operations. In this model, noise levels at the operators' positions were reduced by 2.6 to 8.2 A-weighted decibels (dBA) from the application of the test barriers. Estimated insertion loss underground was 1.7 to 7.3 dBA. The barrier should be tested in an underground mining operation to determine if it can reduce shearer operators' noise exposure to below regulatory limits.

78 FR 73897 - SHINE Medical Technologies, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-09

... NUCLEAR REGULATORY COMMISSION [Docket No. 50-608; NRC-2013-0053] SHINE Medical Technologies, Inc. AGENCY: Nuclear Regulatory Commission. ACTION: License application; docketing. SUMMARY: The U.S. Nuclear... construction permit, submitted by SHINE Medical Technologies, Inc. (SHINE) is acceptable for docketing...

Fallen Angels or Risen Apes? A Tale of the Intricate Complexities of Imbalanced Immune Responses in the Pathogenesis and Progression of Immune-Mediated and Viral Cancers

PubMed Central

Ondondo, Beatrice Omusiro

2014-01-01

Excessive immune responses directed against foreign pathogens, self-antigens, or commensal microflora can cause cancer establishment and progression if the execution of tight immuno-regulatory mechanisms fails. On the other hand, induction of potent tumor antigen-specific immune responses together with stimulation of the innate immune system is a pre-requisite for effective anti-tumor immunity, and if suppressed by the strong immuno-regulatory mechanisms can lead to cancer progression. Therefore, it is crucial that the inevitable co-existence of these fundamental, yet conflicting roles of immune-regulatory cells is carefully streamlined as imbalances can be detrimental to the host. Infection with chronic persistent viruses is characterized by severe immune dysfunction resulting in T cell exhaustion and sometimes deletion of antigen-specific T cells. More often, this is due to increased immuno-regulatory processes, which are triggered to down-regulate immune responses and limit immunopathology. However, such heightened levels of immune disruption cause a concomitant loss of tumor immune-surveillance and create a permissive microenvironment for cancer establishment and progression, as demonstrated by increased incidences of cancer in immunosuppressed hosts. Paradoxically, while some cancers arise as a consequence of increased immuno-regulatory mechanisms that inhibit protective immune responses and impinge on tumor surveillance, other cancers arise due to impaired immuno-regulatory mechanisms and failure to limit pathogenic inflammatory responses. This intricate complexity, where immuno-regulatory cells can be beneficial in certain immune settings but detrimental in other settings underscores the need for carefully formulated interventions to equilibrate the balance between immuno-stimulatory and immuno-regulatory processes. PMID:24639678

78 FR 1536 - Fall 2012 Semiannual Agenda of Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-08

... of Regulatory Priorities are included in the Regulatory Plan, which appears in both the online... Unified Agenda. The complete Unified Agenda is available online at www.reginfo.gov , in a format that... dogfish quota and/or possession limits by sex; adding a recreational fishery to the FMP; identifying...

76 FR 76115 - Revisions to the California State Implementation Plan, Feather River Air Quality Management District

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-06

... the California State Implementation Plan, Feather River Air Quality Management District AGENCY... limited disapproval of revisions to the Feather River Air Quality Management District (FRAQMD) portion of..., Regulatory Planning and Review The Office of Management and Budget (OMB) has exempted this regulatory action...

30 CFR 800.70 - Bonding for anthracite operations in Pennsylvania.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Pennsylvania. 800.70 Section 800.70 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT... REGULATORY PROGRAMS § 800.70 Bonding for anthracite operations in Pennsylvania. (a) All of the provisions of... operations in Pennsylvania except that— (1) Specified bond limits shall be determined by the regulatory...

Structure of soybean serine acetyltransferase and formation of the cysteine regulatory complex as a molecular chaperone

USDA-ARS?s Scientific Manuscript database

Serine acetyltransferase (SAT) catalyzes the limiting reaction in plant and microbial biosynthesis of cysteine. In addition to its enzymatic function, SAT forms a macromolecular complex with O-acetylserine sulfhydrylase (OASS). Formation of the cysteine regulatory complex (CRC) is a critical biochem...

78 FR 69737 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-70878; File No. SR-CBOE-2013-106] Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and Immediate... Position and Exercise Limits for Physically-Settled SPDR S&P 500 ETF Trust (``SPY'') Options November 14...

75 FR 16516 - Draft Regulatory Guide: Issuance, Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

...: R.A. Jervey, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: (301) 251...'' series. This series was developed to describe and make available to the public such information as.... Although a time limit is given, comments and suggestions in connection with items for inclusion in guides...

Universal Service Brings Fiber to Their Doorsteps.

ERIC Educational Resources Information Center

Vedro, Steven

1996-01-01

In a time of fiscal belt tightening, many states will hesitate to launch new multimillion-dollar distance education network projects. Instead they will concentrate on regulatory initiatives to stimulate the development of affordable advanced universal service by the private sector. Discusses the limitations of state regulatory strategies in the…

Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum

USDA-ARS?s Scientific Manuscript database

Head blight caused by Fusarium graminearum (Fg) is a major limiting factor of wheat production with both yield loss and mycotoxin contamination. Here we report a model for global Fg gene regulatory networks (GRNs) inferred from a large collection of transcriptomic data using a machine-learning appro...

USE OF METHOD DETECTION LIMITS IN ENVIRONMENTAL MEASUREMENTS

EPA Science Inventory

Environmental measurements often produce values below the method detection limit (MDL). Because low or zero values may be used in determining compliance with regulatory limits, in determining emission factors (typical concentrations emitted by a given type of source), or in model...

[Effects of combined application of nitrogen and phosphorus on diurnal variation of photosynthesis at grain-filling stage and grain yield of super high-yielding wheat].

PubMed

Zhao, Hai-bo; Lin, Qi; Liu, Yi-guo; Jiang, Wen; Liu, Jian-jun; Zhai, Yan-ju

2010-10-01

Taking super high-yielding wheat cultivar Jimai 22 as test material, a field experiment was conducted to study the effects of combined application of nitrogen (N) and phosphorus (P) on the diurnal variation of photosynthesis at grain-filling stage and the grain yield of the cultivar. In treatments CK (without N and P application) and low N/P application (225 kg N x hm(-2) and 75 kg P x hm(-2)), the diurnal variation of net photosynthetic rate (Pn) was presented as double-peak curve, and there existed obvious midday depression of photosynthesis. Under reasonable application of N/P (300 kg N x hm(-2) and 150 kg P x hm(-2), treatment N2P2), the midday depression of photosynthesis weakened or even disappeared. Stomatal and non-stomatal limitations could be the causes of the midday depression. Increasing N and P supply increased the Pn, stomatal conductance (Gs), stomatal limitation value (Ls), and transpiration rate (Tr). Fertilizer P had less effects on the photosynthesis, compared with fertilizer N. When the P supply was over 150 kg x hm(-2), the increment of Pn was alleviated and even decreased. Among the fertilization treatments, treatment N2P2 had the highest Pn, Gs, and water use efficiency, being significantly different from CK. It appeared that fertilizer N had greater regulatory effect on the diurnal variation of photosynthesis, compared with fertilizer P, while the combined application of N and P had significant co-effect on the Pn, Gs, and Tr. A combined application of 300 kg N x hm(-2) and 150 kg P x hm(-2) benefited the enhancement of Pn and grain yield.

How regulatory T cells work

PubMed Central

Vignali, Dario A. A.; Collison, Lauren W.; Workman, Creg J.

2009-01-01

Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting anti-tumour immunity. Given that Treg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we discuss the basic mechanisms used by Treg cells to mediate suppression, and discuss whether one or many of these mechanisms are likely to be crucial for Treg-cell function. In addition, we present the hypothesis that effector T cells may not be ‘innocent’ parties in this suppressive process and might in fact potentiate Treg-cell function. PMID:18566595

QSAR modeling: where have you been? Where are you going to?

PubMed

Cherkasov, Artem; Muratov, Eugene N; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-06-26

Quantitative structure-activity relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists toward collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making.

QSAR Modeling: Where have you been? Where are you going to?

PubMed Central

Cherkasov, Artem; Muratov, Eugene N.; Fourches, Denis; Varnek, Alexandre; Baskin, Igor I.; Cronin, Mark; Dearden, John; Gramatica, Paola; Martin, Yvonne C.; Todeschini, Roberto; Consonni, Viviana; Kuz'min, Victor E.; Cramer, Richard; Benigni, Romualdo; Yang, Chihae; Rathman, James; Terfloth, Lothar; Gasteiger, Johann; Richard, Ann; Tropsha, Alexander

2014-01-01

Quantitative Structure-Activity Relationship modeling is one of the major computational tools employed in medicinal chemistry. However, throughout its entire history it has drawn both praise and criticism concerning its reliability, limitations, successes, and failures. In this paper, we discuss: (i) the development and evolution of QSAR; (ii) the current trends, unsolved problems, and pressing challenges; and (iii) several novel and emerging applications of QSAR modeling. Throughout this discussion, we provide guidelines for QSAR development, validation, and application, which are summarized in best practices for building rigorously validated and externally predictive QSAR models. We hope that this Perspective will help communications between computational and experimental chemists towards collaborative development and use of QSAR models. We also believe that the guidelines presented here will help journal editors and reviewers apply more stringent scientific standards to manuscripts reporting new QSAR studies, as well as encourage the use of high quality, validated QSARs for regulatory decision making. PMID:24351051

Deep learning for computational biology.

PubMed

Angermueller, Christof; Pärnamaa, Tanel; Parts, Leopold; Stegle, Oliver

2016-07-29

Technological advances in genomics and imaging have led to an explosion of molecular and cellular profiling data from large numbers of samples. This rapid increase in biological data dimension and acquisition rate is challenging conventional analysis strategies. Modern machine learning methods, such as deep learning, promise to leverage very large data sets for finding hidden structure within them, and for making accurate predictions. In this review, we discuss applications of this new breed of analysis approaches in regulatory genomics and cellular imaging. We provide background of what deep learning is, and the settings in which it can be successfully applied to derive biological insights. In addition to presenting specific applications and providing tips for practical use, we also highlight possible pitfalls and limitations to guide computational biologists when and how to make the most use of this new technology. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Ribo-attenuators: novel elements for reliable and modular riboswitch engineering.

PubMed

Folliard, Thomas; Mertins, Barbara; Steel, Harrison; Prescott, Thomas P; Newport, Thomas; Jones, Christopher W; Wadhams, George; Bayer, Travis; Armitage, Judith P; Papachristodoulou, Antonis; Rothschild, Lynn J

2017-07-04

Riboswitches are structural genetic regulatory elements that directly couple the sensing of small molecules to gene expression. They have considerable potential for applications throughout synthetic biology and bio-manufacturing as they are able to sense a wide range of small molecules and regulate gene expression in response. Despite over a decade of research they have yet to reach this considerable potential as they cannot yet be treated as modular components. This is due to several limitations including sensitivity to changes in genetic context, low tunability, and variability in performance. To overcome the associated difficulties with riboswitches, we have designed and introduced a novel genetic element called a ribo-attenuator in Bacteria. This genetic element allows for predictable tuning, insulation from contextual changes, and a reduction in expression variation. Ribo-attenuators allow riboswitches to be treated as truly modular and tunable components, thus increasing their reliability for a wide range of applications.

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

McKenzie-Carter, M.A.; Lyon, R.E.

This report contains information to support the Environmental Assessment for the Compact Ignition Tokamak Project (CIT) proposed for Princeton Plasma Physics Laboratory (PPPL). The assumptions and methodology used to assess the impact to members of the public from operational and accidental releases of radioactive material from the proposed CIT during the operational period of the project are described. A description of the tracer release tests conducted at PPPL by NOAA is included; dispersion values from these tests are used in the dose calculation. Radiological releases, doses, and resulting health risks are calculated. The computer code AIRDOS-EPA is used to calculatemore » the individual and population doses for routine releases; FUSCRAC3 is used to calculate doses resulting from off-normal releases where direct application of the NOAA tracer test data is not practical. Where applicable, doses are compared to regulatory limits and guidelines values. 44 refs., 5 figs., 18 tabs.« less

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

McKenzie-Carter, M.A.; Lyon, R.E.; Rope, S.K.

This report contains information to support the Environmental Assessment for the Burning Plasma Experiment (BPX) Project proposed for the Princeton Plasma Physics Laboratory (PPPL). The assumptions and methodology used to assess the impact to members of the public from operational and accidental releases of radioactive material from the proposed BPX during the operational period of the project are described. A description of the tracer release tests conducted at PPPL by NOAA is included; dispersion values from these tests are used in the dose calculations. Radiological releases, doses, and resulting health risks are calculated and summarized. The computer code AIRDOS- EPA,more » which is part of the computer code system CAP-88, is used to calculate the individual and population doses for routine releases; FUSCRAC3 is used to calculate doses resulting from off-normal releases where direct application of the NOAA tracer test data is not practical. Where applicable, doses are compared to regulatory limits and guideline values. 48 refs., 16 tabs.« less

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

PubMed

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

2015-08-01

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

Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective.

PubMed

McBlane, James W; Phul, Parvinder; Sharpe, Michaela

2018-06-25

This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical. After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined. This includes understanding biodistribution, persistence and toxicity, including potential for malignant transformation. These elements need to be considered in the context of the intended clinical development. This article describes regulatory mechanisms available to developers to support product development that aim to resolve scientific issues prior to marketing authorization application, to enable patients to have faster access to the product than would otherwise be the case. Developers are encouraged to be aware of both the scientific issues and regulatory mechanisms to ensure patients can be supplied with these products.

Developing a strategy and closure criteria for radioactive and mixed waste sites in the ORNL remedial action program: Regulatory interface

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

Trabalka, J.R.

1987-09-01

Some options for stabilization and treatment of contaminated sites can theoretically provide a once-and-for-all solution (e.g., removal or destruction of contaminants). Most realizable options, however, leave contaminants in place (in situ), potentially isolated by physical or chemical, but more typically, by hydrologic measures. As a result of the dynamic nature of the interactions between contaminants, remedial measures, and the environment, in situ stablization measures are likely to have limited life spans, and maintenance and monitoring of performance become an essential part of the scheme. The length of formal institutional control over the site and related questions about future uses ofmore » the land and waters are of paramount importance. Unique features of the ORNL site and environs appear to be key ingredients in achieving the very long term institutional control necessary for successful financing and implementation of in situ stabilization. Some formal regulatory interface is necessary to ensure that regulatory limitations and new guidance which can affect planning and implementation of the ORNL Remedial Action Program are communicated to ORNL staff and potential technical and financial limitations which can affect schedules or alternatives for achievement of long-term site stabilization and the capability to meet environmental regulations are provided to regulatory bodies as early as possible. Such an interface should allow decisions on closure criteria to be based primarily on technical merit and protection of human health and the environment. A plan for interfacing with federal and state regulatory authorities is described. 93 refs., 1 fig., 4 tabs.« less

A Liquid Chromatography – Tandem Mass Spectrometry Approach for the Identification of Mebendazole Residue in Pork, Chicken, and Horse

PubMed Central

Lee, Ji Sun; Cho, Soo Hee; Lim, Chae Mi; Chang, Moon Ik; Joo, Hyun Jin; Park, Hyun Jin

2017-01-01

A confirmatory and quantitative method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of mebendazole and its hydrolyzed and reduced metabolites in pork, chicken, and horse muscles was developed and validated in this study. Anthelmintic compounds were extracted with ethyl acetate after sample mixture was made alkaline followed by liquid chromatographic separation using a reversed phase C18 column. Gradient elution was performed with a mobile phase consisting of water containing 10 mM ammonium formate and methanol. This confirmatory method was validated according to EU requirements. Evaluated validation parameters included specificity, accuracy, precision (repeatability and within-laboratory reproducibility), analytical limits (decision limit and detection limit), and applicability. Most parameters were proved to be conforming to the EU requirements. The decision limit (CCα) and detection capability (CCβ) for all analytes ranged from 15.84 to 17.96 μgkg-1. The limit of detection (LOD) and the limit of quantification (LOQ) for all analytes were 0.07 μgkg-1 and 0.2 μgkg-1, respectively. The developed method was successfully applied to monitoring samples collected from the markets in major cities and proven great potential to be used as a regulatory tool to determine mebendazole residues in animal based foods. PMID:28085912

30 CFR 701.1 - Scope.

Code of Federal Regulations, 2014 CFR

2014-07-01

... regulatory program required by the Act. (b) The following regulations apply to the permanent regulatory program: (1) Subchapter C on State program application, approval, withdrawal, and grants, and Federal program implementation; (2) Subchapter D on surface coal mining and reclamation operations on Federal...

30 CFR 701.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-07-01

... regulatory program required by the Act. (b) The following regulations apply to the permanent regulatory program: (1) Subchapter C on State program application, approval, withdrawal, and grants, and Federal program implementation; (2) Subchapter D on surface coal mining and reclamation operations on Federal...

30 CFR 701.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-07-01

... regulatory program required by the Act. (b) The following regulations apply to the permanent regulatory program: (1) Subchapter C on State program application, approval, withdrawal, and grants, and Federal program implementation; (2) Subchapter D on surface coal mining and reclamation operations on Federal...