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

77 FR 71644 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-03

... exercise limits for options on the iShares MSCI Emerging Markets Index Fund (``EEM'') to 500,000 contracts... exercise limits for EEM options to 500,000 contracts.\\3\\ There is precedent for establishing position...\\ \\3\\ By virtue of Rule 1002, which is not being amended by this filing, the exercise limit for EEM...

77 FR 21868 - Safety Zone; Marina Salvage, Bellingham Bay, Bellingham, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-12

.... This rule is not a significant regulatory action due to being limited in size and duration. Small... entities'' comprises small businesses, not-for-profit organizations that are independently owned and... substantial number of small entities because the zone established in this rule is limited in size and short in...

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

10 CFR 34.45 - Operating and emergency procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.45 Operating and... that no person is likely to be exposed to radiation doses in excess of the limits established in 10 CFR...

10 CFR 34.45 - Operating and emergency procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.45 Operating and... that no person is likely to be exposed to radiation doses in excess of the limits established in 10 CFR...

10 CFR 34.45 - Operating and emergency procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.45 Operating and... that no person is likely to be exposed to radiation doses in excess of the limits established in 10 CFR...

10 CFR 34.45 - Operating and emergency procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.45 Operating and... that no person is likely to be exposed to radiation doses in excess of the limits established in 10 CFR...

10 CFR 34.45 - Operating and emergency procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.45 Operating and... that no person is likely to be exposed to radiation doses in excess of the limits established in 10 CFR...

Establishing a Quality Control System for Stem Cell-Based Medicinal Products in China

PubMed Central

2015-01-01

Stem cell-based medicinal products (SCMPs) are emerging as novel therapeutic products. The success of its development depends on the existence of an effective quality control system, which is constituted by quality control technologies, standards, reference materials, guidelines, and the associated management system in accordance with regulatory requirements along product lifespan. However, a worldwide, effective quality control system specific for SCMPs is still far from established partially due to the limited understanding of stem cell sciences and lack of quality control technologies for accurately assessing the safety and biological effectiveness of SCMPs before clinical use. Even though, based on the existing regulations and current stem cell sciences and technologies, initial actions toward the goal of establishing such a system have been taken as exemplified by recent development of new “interim guidelines” for governing quality control along development of SCMPs and new development of the associated quality control technologies in China. In this review, we first briefly introduced the major institutions involved in the regulation of cell substrates and therapeutic cell products in China and the existing regulatory documents and technical guidelines used as critical references for developing the new interim guidelines. With focus only on nonhematopoietic stem cells, we then discussed the principal quality attributes of SCMPs as well as our thinking of proper testing approaches to be established with relevant evaluation technologies to ensure all quality requirements of SCMPs along different manufacturing processes and development stages. At the end, some regulatory and technical challenges were also discussed with the conclusion that combined efforts should be taken to promote stem cell regulatory sciences to establish the effective quality control system for SCMPs. PMID:25471126

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

30 CFR 816.67 - Use of explosives: Control of adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... established in accordance with either the maximum peak-particle-velocity limits of paragraph (d)(2), the... in the blasting plan and approved by the regulatory authority. (2) Maximum peak particle velocity. (i... (D), from the blasting site, in feet Maximum allowable peak particle velocity (V max) for ground...

76 FR 14884 - Atlantic Highly Migratory Species; Modification of the Retention of Incidentally-Caught Highly...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-18

... smoothhound shark complex (which includes smooth dogfish and Florida smoothhound (genus Mustelus) in all... address regulatory discards of incidentally-caught species in the smoothhound shark complex by establishing a retention limit for smoothhound sharks in all Atlantic trawl fisheries. The proposed actions are...

Regulatory ozone modeling: status, directions, and research needs.

PubMed Central

Georgopoulos, P G

1995-01-01

The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAQSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAQSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model's performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. Selected interim results from diagnostic analyses, which are performed as a component of the regulatory ozone modeling process for the Philadelphia-New Jersey region, are also presented to provide some specific examples related to the general issues discussed in this work. Finally, research needs related to a) the evaluation and refinement of regulatory ozone modeling, b) the characterization of uncertainty in photochemical modeling, and c) the improvement of the model-based ozone-attainment demonstration process are presented to identify future directions in this area. Images Figure 7. Figure 7. Figure 7. Figure 8. Figure 9. PMID:7614934

Requirements for authorisation of internal dosimetry services.

PubMed

Melo, D R; Cunha, P G; Torres, M M C; Lourenço, M C

2003-01-01

In order to ensure that a facility is in compliance with the occupational exposure requirements established by regulatory authorities, the measurements and dose assessments specified in the individual monitoring programme need to be reliable. There are two important questions that shall be addressed here: one is how the licensed facilities can demonstrate to their workers and regulatory bodies compliance with the regulatory limits and the reliability of the results of the individual monitoring programmes; the other concerns the mechanisms used to demonstrate to a facility in another country the reliability of the measurement results of an individual monitoring bioassay programme. The accreditation of the bioassay laboratory, according to ISO/IEC 17025, shall be the basic requirement for obtaining the authorisation granted by the national regulatory authority. For the second question, such confidence can be achieved through International Laboratory Accreditation Cooperation (ILAC).

Establishing generic remediation goals for the polycyclic aromatic hydrocarbons: critical issues.

PubMed Central

LaGoy, P K; Quirk, T C

1994-01-01

Polycyclic aromatic hydrocarbons (PAHs) were one of the first classes of compounds identified as carcinogens and are often chemicals of concern at hazardous waste sites. Remediation goals established by regulatory agencies for carcinogenic PAHs in soil are generally either risk based or based on the method detection limits. PAHs are products of incomplete combustion, are components of petroleum, and as such, are prevalent in the environment from both natural and anthropogenic sources. Background concentrations are often above risk- or detection limit-based criteria, and therefore these remediation goals are of limited practical use as target criteria. In addition, the approaches used to establish target criteria do not account for several factors that may produce over- or underestimates of risk associated with the PAHs. Because of the frequency with which these compounds are detected, it is imperative that reasonably achievable and practical remediation goals be established. This paper examines the various factors that contribute to over- and underestimates of risks associated with PAHs and presents an approach for establishing cleanup criteria that takes into account health risks, background concentrations, and achievability. Images p348-a PMID:7925174

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 ...

75 FR 36589 - Financial Crimes Enforcement Network; Amendment to the Bank Secrecy Act Regulations-Definitions...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-28

... regulatory research into the operation of the prepaid industry, we have encountered a number of distinct...: (1) Establish written AML programs that are reasonably designed to prevent the MSB from being used to... limitations of descriptive terms are easily understood. The term ``stored value'' gained a foothold following...

Quantification of patulin in fruit leathers by ultra-high-performance liquid chromatography-photodiode array (UPLC-PDA)

USDA-ARS?s Scientific Manuscript database

Patulin is a mycotoxin commonly found in certain fruit and fruit products. For this reason many countries have established regulatory limits pertaining to, in particular, apple juice and apple products. Fruit leathers are produced by dehydrating fruit puree, leaving a sweet product that has a leathe...

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.

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 aPi'iications of certain materials. Such changes can result in NASA undertaking material replacement efforts. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented several strategies for proactively managing regulatory change to minimize potential adverse impacts to NASA Programs and facilities. This presentation highlights the lessons learned through establishing the RRAC PC, the process by which the RRAC PC monitors and distributes information about emerging regulatory requirements, and the cross-Agency cooperation that is vital to supporting NASA's mission.

A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla.

PubMed

Hauri-Hohl, Mathias; Zuklys, Saulius; Holländer, Georg A; Ziegler, Steven F

2014-06-01

Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-β in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-β signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.

Genetic tools for the investigation of Roseobacter clade bacteria

PubMed Central

2009-01-01

Background The Roseobacter clade represents one of the most abundant, metabolically versatile and ecologically important bacterial groups found in marine habitats. A detailed molecular investigation of the regulatory and metabolic networks of these organisms is currently limited for many strains by missing suitable genetic tools. Results Conjugation and electroporation methods for the efficient and stable genetic transformation of selected Roseobacter clade bacteria including Dinoroseobacter shibae, Oceanibulbus indolifex, Phaeobacter gallaeciensis, Phaeobacter inhibens, Roseobacter denitrificans and Roseobacter litoralis were tested. For this purpose an antibiotic resistance screening was performed and suitable genetic markers were selected. Based on these transformation protocols stably maintained plasmids were identified. A plasmid encoded oxygen-independent fluorescent system was established using the flavin mononucleotide-based fluorescent protein FbFP. Finally, a chromosomal gene knockout strategy was successfully employed for the inactivation of the anaerobic metabolism regulatory gene dnr from D. shibae DFL12T. Conclusion A genetic toolbox for members of the Roseobacter clade was established. This provides a solid methodical basis for the detailed elucidation of gene regulatory and metabolic networks underlying the ecological success of this group of marine bacteria. PMID:20021642

Are occupational exposure limits becoming more alike within the European Union?

PubMed

Schenk, Linda; Hansson, Sven Ove; Rudén, Christina; Gilek, Michael

2008-10-01

The occupational exposure limits (OELs) established by seven different national regulatory agencies of EU member states are compared with those of the European Commission (EC). The comparison concerned: (1) what chemicals have been selected, (2) the average level of exposure limits for all chemicals, and (3) the similarity between the OELs of different EU member states and the OELs recommended by the European Commission. The average level of the exposure limits has declined during the past 10 years in four of the five countries in our study for which historical data were available to us. Poland has not changed its level noticeably and Germany has increased it. Since the first list of indicative OELs was established by the EC, a few of the EU exposure limits have been lowered. The similarity index indicates that the exposure limits of EU member states are converging towards the European Commission's recommended OELs. Still, the average level of OELs differs between organizations--the Estonian OELs are on average 35% higher than the Polish OELs.

78 FR 9966 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... Proposed Rule Change to Establish the Limit Locator Service Offered at No Cost to Subscribing Members... proposed rule change as described in Items I and II below, which Items have been prepared by the Exchange. The Commission is publishing this notice to solicit comments on the proposed rule change from...

78 FR 37870 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... Market Maker Risk Parameters and Complex Orders June 18, 2013. Pursuant to Section 19(b)(1) of the... makers to enter values in the Exchange-provided risk parameters and by limiting the types of complex... complex instruments on the complex order book. Market makers establish a time frame during which the...

Potential environmental impacts of light-emitting diodes (LEDs): metallic resources, toxicity, and hazardous waste classification.

PubMed

Lim, Seong-Rin; Kang, Daniel; Ogunseitan, Oladele A; Schoenung, Julie M

2011-01-01

Light-emitting diodes (LEDs) are advertised as environmentally friendly because they are energy efficient and mercury-free. This study aimed to determine if LEDs engender other forms of environmental and human health impacts, and to characterize variation across different LEDs based on color and intensity. The objectives are as follows: (i) to use standardized leachability tests to examine whether LEDs are to be categorized as hazardous waste under existing United States federal and California state regulations; and (ii) to use material life cycle impact and hazard assessment methods to evaluate resource depletion and toxicity potentials of LEDs based on their metallic constituents. According to federal standards, LEDs are not hazardous except for low-intensity red LEDs, which leached Pb at levels exceeding regulatory limits (186 mg/L; regulatory limit: 5). However, according to California regulations, excessive levels of copper (up to 3892 mg/kg; limit: 2500), Pb (up to 8103 mg/kg; limit: 1000), nickel (up to 4797 mg/kg; limit: 2000), or silver (up to 721 mg/kg; limit: 500) render all except low-intensity yellow LEDs hazardous. The environmental burden associated with resource depletion potentials derives primarily from gold and silver, whereas the burden from toxicity potentials is associated primarily with arsenic, copper, nickel, lead, iron, and silver. Establishing benchmark levels of these substances can help manufacturers implement design for environment through informed materials substitution, can motivate recyclers and waste management teams to recognize resource value and occupational hazards, and can inform policymakers who establish waste management policies for LEDs.

Regulatory risk assessment approaches for synthetic mineral fibres.

PubMed

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

2015-10-01

Exposure to synthetic mineral fibres (SMF) may occur in a number of workplace scenarios. To protect worker health, a number of different organisations worldwide have assessed the health risk of these materials and established workplace exposure limits. This paper outlines the basic principles of risk assessment and the scientific methods used to derive valid (justifiable) occupational exposure limits (OELs) and goes on to show how, for SMF, and particularly for refractory ceramic fibre (otherwise known as aluminosilicate wool, RCF/ASW), the methods used and the associated outcomes differ widely. It is argued that the resulting differences in established OELs prevent consistent and appropriate risk management of SMF worldwide, and that development of a transparent and harmonised approach to fibre risk assessment and limit-setting is required. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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

Metzler, D.; Gibb, J.P.; Glover, W.A.

Compliance with the mandate of the Uranium Mill Tailings Radiation Control Act (UMTRCA) at Uranium Mill Tailings Remedial Action (UMTRA) Project sites requires implementation of a groundwater remedial action plan that meets the requirements of Subpart B of the US Environmental Protection Agency`s proposed groundwater protection standards (40 CFR 192). The UMTRA Groundwater Project will ensure that unacceptable current risk or potential risk to the public health, safety and the environment resulting from the groundwater contamination attributable to the UMTRA sites, is mitigated in a timely and cost-efficient manner. For each UMTRA processing site and vicinity property where contamination exists,more » a groundwater remedial action plan must be developed that identifies hazardous constituents and establishes acceptable concentration limits for the hazardous constituents as either (a) alternate concentration limits (ACL), (b) maximum concentration limits (MCLs), (c) supplemental standards, or (d) background groundwater quality levels. Project optimization is a strategy that will aggressively work within the current regulatory framework using all available options to meet regulatory requirements. This strategy is outlined within.« less

75 FR 2908 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... proposes to adopt in both Rule 8.91 and Rule 8.93 a limited exception for integrated market making in broad... established a new category of market-making participant called e-DPMs, who are member organizations appointed... potential for the sharing of material non-public information between a DPM's market making activities and...

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...

77 FR 68191 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing of Proposed Rule Change Deleting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-15

... same time, on behalf of that account, market or limit orders at the minimum variation on both sides of the market, the broker may liquidate or cover the position established during that trading session... Floor broker can execute any other order for the same account on the same side of the market as that...

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

Exploiting combinatorial cultivation conditions to infer transcriptional regulation

PubMed Central

Knijnenburg, Theo A; de Winde, Johannes H; Daran, Jean-Marc; Daran-Lapujade, Pascale; Pronk, Jack T; Reinders, Marcel JT; Wessels, Lodewyk FA

2007-01-01

Background Regulatory networks often employ the model that attributes changes in gene expression levels, as observed across different cellular conditions, to changes in the activity of transcription factors (TFs). Although the actual conditions that trigger a change in TF activity should form an integral part of the generated regulatory network, they are usually lacking. This is due to the fact that the large heterogeneity in the employed conditions and the continuous changes in environmental parameters in the often used shake-flask cultures, prevent the unambiguous modeling of the cultivation conditions within the computational framework. Results We designed an experimental setup that allows us to explicitly model the cultivation conditions and use these to infer the activity of TFs. The yeast Saccharomyces cerevisiae was cultivated under four different nutrient limitations in both aerobic and anaerobic chemostat cultures. In the chemostats, environmental and growth parameters are accurately controlled. Consequently, the measured transcriptional response can be directly correlated with changes in the limited nutrient or oxygen concentration. We devised a tailor-made computational approach that exploits the systematic setup of the cultivation conditions in order to identify the individual and combined effects of nutrient limitations and oxygen availability on expression behavior and TF activity. Conclusion Incorporating the actual growth conditions when inferring regulatory relationships provides detailed insight in the functionality of the TFs that are triggered by changes in the employed cultivation conditions. For example, our results confirm the established role of TF Hap4 in both aerobic regulation and glucose derepression. Among the numerous inferred condition-specific regulatory associations between gene sets and TFs, also many novel putative regulatory mechanisms, such as the possible role of Tye7 in sulfur metabolism, were identified. PMID:17241460

Exploiting combinatorial cultivation conditions to infer transcriptional regulation.

PubMed

Knijnenburg, Theo A; de Winde, Johannes H; Daran, Jean-Marc; Daran-Lapujade, Pascale; Pronk, Jack T; Reinders, Marcel J T; Wessels, Lodewyk F A

2007-01-22

Regulatory networks often employ the model that attributes changes in gene expression levels, as observed across different cellular conditions, to changes in the activity of transcription factors (TFs). Although the actual conditions that trigger a change in TF activity should form an integral part of the generated regulatory network, they are usually lacking. This is due to the fact that the large heterogeneity in the employed conditions and the continuous changes in environmental parameters in the often used shake-flask cultures, prevent the unambiguous modeling of the cultivation conditions within the computational framework. We designed an experimental setup that allows us to explicitly model the cultivation conditions and use these to infer the activity of TFs. The yeast Saccharomyces cerevisiae was cultivated under four different nutrient limitations in both aerobic and anaerobic chemostat cultures. In the chemostats, environmental and growth parameters are accurately controlled. Consequently, the measured transcriptional response can be directly correlated with changes in the limited nutrient or oxygen concentration. We devised a tailor-made computational approach that exploits the systematic setup of the cultivation conditions in order to identify the individual and combined effects of nutrient limitations and oxygen availability on expression behavior and TF activity. Incorporating the actual growth conditions when inferring regulatory relationships provides detailed insight in the functionality of the TFs that are triggered by changes in the employed cultivation conditions. For example, our results confirm the established role of TF Hap4 in both aerobic regulation and glucose derepression. Among the numerous inferred condition-specific regulatory associations between gene sets and TFs, also many novel putative regulatory mechanisms, such as the possible role of Tye7 in sulfur metabolism, were identified.

[Community antibiotic consumption in Chile, 2000-2008].

PubMed

Bavestrello F, Luis; Cabello M, Angela

2011-04-01

The Chilean Ministry of Health has implemented regulatory rules for the consumption of anti-biotics since September 1999, with sales restriction limited only with medical prescription. To analyze the impact of established regulatory measures from 2000 to 2008. A retrospective analysis of antibiotics sales in pharmacies from 2000 to 2008 was performed. The information was obtained from the International Marketing System (IMS Health), an auditing system of pharmacy sales. The consumption unit used was the Defined Daily Dose per 1000 inhabitants/day (DDD). From 2000 to 2002 the regulatory rules had a great impact, but since 2002 the antibiotic consumption increased, especially amoxicillin, returning to similar levéis observed in 1998. The regulatory measures had an initial impact, but there was not reinforcement in the time and there was no further control. It is necessary to assume a permanent task and support of the authorities of health to edúcate the population about the implications of the inadequate use of antimicrobials and his effect on the microbial ecology.

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.

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

A novel chemometric classification for FTIR spectra of mycotoxin-contaminated maize and peanuts at regulatory limits.

PubMed

Kos, Gregor; Sieger, Markus; McMullin, David; Zahradnik, Celine; Sulyok, Michael; Öner, Tuba; Mizaikoff, Boris; Krska, Rudolf

2016-10-01

The rapid identification of mycotoxins such as deoxynivalenol and aflatoxin B 1 in agricultural commodities is an ongoing concern for food importers and processors. While sophisticated chromatography-based methods are well established for regulatory testing by food safety authorities, few techniques exist to provide a rapid assessment for traders. This study advances the development of a mid-infrared spectroscopic method, recording spectra with little sample preparation. Spectral data were classified using a bootstrap-aggregated (bagged) decision tree method, evaluating the protein and carbohydrate absorption regions of the spectrum. The method was able to classify 79% of 110 maize samples at the European Union regulatory limit for deoxynivalenol of 1750 µg kg -1 and, for the first time, 77% of 92 peanut samples at 8 µg kg -1 of aflatoxin B 1 . A subset model revealed a dependency on variety and type of fungal infection. The employed CRC and SBL maize varieties could be pooled in the model with a reduction of classification accuracy from 90% to 79%. Samples infected with Fusarium verticillioides were removed, leaving samples infected with F. graminearum and F. culmorum in the dataset improving classification accuracy from 73% to 79%. A 500 µg kg -1 classification threshold for deoxynivalenol in maize performed even better with 85% accuracy. This is assumed to be due to a larger number of samples around the threshold increasing representativity. Comparison with established principal component analysis classification, which consistently showed overlapping clusters, confirmed the superior performance of bagged decision tree classification.

Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

PubMed

Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

2010-09-01

Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and interchangeability of conventional monophasic MR products. Additional measures may occasionally be needed to establish the bioequivalence of multiphasic MR products, and development of such measures is an important objective. The metric of partial AUC was proposed for products designed to have a rapid drug action followed by sustained response. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

Animal Health Ireland: providing national leadership and coordination of non-regulatory animal health issues in Ireland.

PubMed

More, S J; Doherty, M L; Downey, L; McKenzie, K; Devitt, C; O'Flaherty, J

2011-12-01

Livestock production plays an important role in the Irish economy. Regulatory animal health issues are the responsibility of government, but until recently there has been no national coordination of non-regulatory animal health issues. This gap has recently been filled with the establishment of Animal Health Ireland (AHI), a not-for-profit, partnership-based organisation providing national leadership and coordination of non-regulatory animal health issues in Ireland. Animal Health Ireland provides benefits to livestock producers and processors by providing the knowledge, education and coordination required to establish effective control strategies, both on-farm and nationally. This paper presents a brief overview of the context for AHI, and of its establishment and initial activities. Non-regulatory animal health issues have been prioritised. A series of work programmes (each focusing on a high-priority issue) have been established. Partnership is critical to success, both for AHI as an organisation and for effective farm-level transfer of knowledge. This model for national leadership and coordination of non-regulatory animal health issues may be of relevance elsewhere.

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

Regionalization as an approach to regulatory systems strengthening: a case study in CARICOM member states.

PubMed

Preston, Charles; Chahal, Harinder S; Porrás, Analia; Cargill, Lucette; Hinds, Maryam; Olowokure, Babatunde; Cummings, Rudolph; Hospedales, James

2016-05-01

Improving basic capacities for regulation of medicines and health technologies through regulatory systems strengthening is particularly challenging in resource-constrained settings. "Regionalization"-an approach in which countries with common histories, cultural values, languages, and economic conditions work together to establish more efficient systems-may be one answer. This report describes the Caribbean Regulatory System (CRS), a regionalization initiative being implemented in the mostly small countries of the Caribbean Community and Common Market (CARICOM). This initiative is an innovative effort to strengthen regulatory systems in the Caribbean, where capacity is limited compared to other subregions of the Americas. The initiative's concept and design includes a number of features and steps intended to enhance sustainability in resource-constrained contexts. The latter include 1) leveraging existing platforms for centralized cooperation, governance, and infrastructure; 2) strengthening regulatory capacities with the largest potential public health impact; 3) incorporating policies that promote reliance on reference authorities; 4) changing the system to encourage industry to market their products in CARICOM (e.g., using a centralized portal of entry to reduce regulatory burdens); and 5) building human resource capacity. If implemented properly, the CRS will be self-sustaining through user fees. The experience and lessons learned thus far in implementing this initiative, described in this report, can serve as a case study for the development of similar regulatory strengthening initiatives in resource-constrained environments.

Ex Ante or Ex Post? Risk, Hedging and Prudence in the Restructured Power Business

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

Makholm, Jeff D.; Meehan, Eugene T.; Sullivan, Julia E.

Inconsistent regulatory decisions continue to frustrate the establishment of a new ex ante regulatory equilibrium that will serve to prevent unfair and inefficient ex post prudence disallowances. Extreme volatility in gas and power markets will continue to tax the uneasy regulatory status quo until a new equilibrium can be established. (author)

Medical and non-medical protection standards for ultrasound and infrasound.

PubMed

Duck, Francis A

2007-01-01

Protection from inappropriate or hazardous exposure to ultrasound is controlled through international standards and national regulations. IEC standard 60601 part 1 establishes requirements for the mechanical, electrical, chemical and thermal safety for all electro-medical equipment. The associated part 2 standard for diagnostic medical ultrasonic equipment sets no upper limits on ultrasonic exposure. Instead, safety indices are defined that are intended to advise users on the degree of thermal and mechanical hazard. At present the display of these safety indices satisfies regulatory requirements in both the USA and Europe. Nevertheless there are reservations about the effectiveness of this approach to protection management. In the USA, there are national regulatory limits on diagnostic exposure, based on acoustic output from clinical equipment in use over 20 years ago. The IEC 60601 part 2 standard for therapeutic equipment sets 3 W cm(-2) as the limit on acoustic intensity. Transducer surface temperature is controlled for both diagnostic and therapy devices. For airborne ultrasound, interim guidelines on limits of human exposure published by the IRPA are now 2 decades old. A limit on sound pressure level of 100 dB for the general population is recommended. The absence of protection standards for infrasound relates to difficulties in measurement at these low frequencies.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

...The Office of the Comptroller of the Currency (OCC), Board of Governors of the Federal Reserve System (Board), and the Federal Deposit Insurance Corporation (FDIC) (collectively, the agencies) are seeking comment on three Notices of Proposed Rulemaking (NPR) that would revise and replace the agencies' current capital rules. In this NPR, the agencies are proposing to revise their risk-based and leverage capital requirements consistent with agreements reached by the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for More Resilient Banks and Banking Systems'' (Basel III). The proposed revisions would include implementation of a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for banking organizations subject to the advanced approaches capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator measure. Additionally, consistent with Basel III, the agencies are proposing to apply limits on a banking organization's capital distributions and certain discretionary bonus payments if the banking organization does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk- based capital requirements. This NPR also would establish more conservative standards for including an instrument in regulatory capital. As discussed in the proposal, the revisions set forth in this NPR are consistent with section 171 of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act), which requires the agencies to establish minimum risk-based and leverage capital requirements. In connection with the proposed changes to the agencies' capital rules in this NPR, the agencies are also seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related NPRs are discussed further in the SUPPLEMENTARY INFORMATION.

Overcoming regulatory challenges in the development of companion diagnostics for monitoring and safety.

PubMed

Shimazawa, Rumiko; Ikeda, Masayuki

2016-03-01

Concurrent development and co-approval of a companion diagnostic (CDx) with a corresponding drug is ideal, but often unfeasible. Because of limited exposure to a drug in clinical trials, crucial information on safety is sometimes revealed only after approval. Therefore, a CDx for monitoring/safety is often developed after approval of a corresponding drug. However, regulatory guidance is insufficient if contemporaneous development is not possible, thereby leaving plenty of opportunities for improvement with respect to pharmacovigilance and retrospective validation of the CDx. Furthermore, global harmonization of guidance on how to incorporate new scientific information from retrospective analyses of biomarkers should lead to the establishment of more evidence for the development of CDx for approved drugs.

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

Not Available

The Low-Level Radioactive Waste Policy Amendments Act of 1985 amends the current act to provide regional facilities established through compacts between two or more states. The Act defines the responsibilities of the federal government and the participating states, and provides for inspection by the Nuclear Regulatory Commission and review by Congress. It also establishes procedures for siting and allocation of facilities during the transition period and the requirements for access to regional facilities, which will have a three-year licensing and construction period. There is a graduated ceiling on surcharges until 1992, when the limit is $40 per cubic foot. Themore » Act lists six compacts which are subject to consent.« less

Portable Infrared Laser Spectroscopy for On-site Mycotoxin Analysis.

PubMed

Sieger, Markus; Kos, Gregor; Sulyok, Michael; Godejohann, Matthias; Krska, Rudolf; Mizaikoff, Boris

2017-03-09

Mycotoxins are toxic secondary metabolites of fungi that spoil food, and severely impact human health (e.g., causing cancer). Therefore, the rapid determination of mycotoxin contamination including deoxynivalenol and aflatoxin B 1 in food and feed samples is of prime interest for commodity importers and processors. While chromatography-based techniques are well established in laboratory environments, only very few (i.e., mostly immunochemical) techniques exist enabling direct on-site analysis for traders and manufacturers. In this study, we present MYCOSPEC - an innovative approach for spectroscopic mycotoxin contamination analysis at EU regulatory limits for the first time utilizing mid-infrared tunable quantum cascade laser (QCL) spectroscopy. This analysis technique facilitates on-site mycotoxin analysis by combining QCL technology with GaAs/AlGaAs thin-film waveguides. Multivariate data mining strategies (i.e., principal component analysis) enabled the classification of deoxynivalenol-contaminated maize and wheat samples, and of aflatoxin B 1 affected peanuts at EU regulatory limits of 1250 μg kg -1 and 8 μg kg -1 , respectively.

Portable Infrared Laser Spectroscopy for On-site Mycotoxin Analysis

PubMed Central

Sieger, Markus; Kos, Gregor; Sulyok, Michael; Godejohann, Matthias; Krska, Rudolf; Mizaikoff, Boris

2017-01-01

Mycotoxins are toxic secondary metabolites of fungi that spoil food, and severely impact human health (e.g., causing cancer). Therefore, the rapid determination of mycotoxin contamination including deoxynivalenol and aflatoxin B1 in food and feed samples is of prime interest for commodity importers and processors. While chromatography-based techniques are well established in laboratory environments, only very few (i.e., mostly immunochemical) techniques exist enabling direct on-site analysis for traders and manufacturers. In this study, we present MYCOSPEC - an innovative approach for spectroscopic mycotoxin contamination analysis at EU regulatory limits for the first time utilizing mid-infrared tunable quantum cascade laser (QCL) spectroscopy. This analysis technique facilitates on-site mycotoxin analysis by combining QCL technology with GaAs/AlGaAs thin-film waveguides. Multivariate data mining strategies (i.e., principal component analysis) enabled the classification of deoxynivalenol-contaminated maize and wheat samples, and of aflatoxin B1 affected peanuts at EU regulatory limits of 1250 μg kg−1 and 8 μg kg−1, respectively. PMID:28276454

Portable Infrared Laser Spectroscopy for On-site Mycotoxin Analysis

NASA Astrophysics Data System (ADS)

Sieger, Markus; Kos, Gregor; Sulyok, Michael; Godejohann, Matthias; Krska, Rudolf; Mizaikoff, Boris

2017-03-01

Mycotoxins are toxic secondary metabolites of fungi that spoil food, and severely impact human health (e.g., causing cancer). Therefore, the rapid determination of mycotoxin contamination including deoxynivalenol and aflatoxin B1 in food and feed samples is of prime interest for commodity importers and processors. While chromatography-based techniques are well established in laboratory environments, only very few (i.e., mostly immunochemical) techniques exist enabling direct on-site analysis for traders and manufacturers. In this study, we present MYCOSPEC - an innovative approach for spectroscopic mycotoxin contamination analysis at EU regulatory limits for the first time utilizing mid-infrared tunable quantum cascade laser (QCL) spectroscopy. This analysis technique facilitates on-site mycotoxin analysis by combining QCL technology with GaAs/AlGaAs thin-film waveguides. Multivariate data mining strategies (i.e., principal component analysis) enabled the classification of deoxynivalenol-contaminated maize and wheat samples, and of aflatoxin B1 affected peanuts at EU regulatory limits of 1250 μg kg-1 and 8 μg kg-1, respectively.

Decoding the role of regulatory element polymorphisms in complex disease.

PubMed

Vockley, Christopher M; Barrera, Alejandro; Reddy, Timothy E

2017-04-01

Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment. Establishing causality between non-coding genetic variants, gene regulation, and disease has recently become more feasible with advances in genome-editing and epigenome-editing technologies. As establishing causal regulatory mechanisms of diseases becomes routine, functional annotation of target genes is likely to emerge as a major bottleneck for translation into patient benefits. In this review, we discuss the history and recent advances in understanding the regulatory mechanisms of human disease, and new challenges likely to be encountered once establishing those mechanisms becomes rote. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Limits and regulations for mycotoxins in food and feed.

PubMed

Zmudzki, J; Wiśniewska-Dmytrow, H

2004-01-01

Mycotoxins are natural contaminants whose presence in food- and feedstuffs cannot be completely avoided. Since several mycotoxins have been associated with and implicated in human and animal diseases there is a need to establish maximum levels, guidelines or action levels for them in some kinds of commodities. International and government authorities in many countries have been investing in mycotoxins research and initiating administrative actions for elaboration of legislation and implementing regulatory measures for the control of mycotoxins. Codex Alimentarius Commission is established international legislation on food and feed. In European Union specific limits and regulations for mycotoxins and other contaminants are constructed under the general Codex standards and based on proposal from European Commission. The legal basis for European Commission became available with the framework Council Regulation (EEC) No 315/93. In this paper, legislation regarding maximum levels for certain mycotoxins in food- and feedstuffs in European Community and other countries were reviewed and discussed.

The National Shipbuilding Research Program. Analysis of Wash Water Treatment Efficiency for Copper and Zinc

DTIC Science & Technology

2000-12-15

per trillion for tributyltin (“ TBT ”). This regulatory action lead to an intensive research effort to develop a treatment method for ship’s wash water...antifoulant coating systems, including tributyltin , copper and zinc. In 1997 The Commonwealth of Virginia established an effluent discharge limit of 50 parts...waste stream that could consistently remove TBT to levels below this discharge standard. This work is currently being performed by the Center for

Recent Advances in the Measurement of Arsenic, Cadmium, and Mercury in Rice and Other Foods

PubMed Central

Punshon, Tracy

2015-01-01

Trace element analysis of foods is of increasing importance because of raised consumer awareness and the need to evaluate and establish regulatory guidelines for toxic trace metals and metalloids. This paper reviews recent advances in the analysis of trace elements in food, including challenges, state-of-the art methods, and use of spatially resolved techniques for localizing the distribution of As and Hg within rice grains. Total elemental analysis of foods is relatively well-established but the push for ever lower detection limits requires that methods be robust from potential matrix interferences which can be particularly severe for food. Inductively coupled plasma mass spectrometry (ICP-MS) is the method of choice, allowing for multi-element and highly sensitive analyses. For arsenic, speciation analysis is necessary because the inorganic forms are more likely to be subject to regulatory limits. Chromatographic techniques coupled to ICP-MS are most often used for arsenic speciation and a range of methods now exist for a variety of different arsenic species in different food matrices. Speciation and spatial analysis of foods, especially rice, can also be achieved with synchrotron techniques. Sensitive analytical techniques and methodological advances provide robust methods for the assessment of several metals in animal and plant-based foods, in particular for arsenic, cadmium and mercury in rice and arsenic speciation in foodstuffs. PMID:25938012

Influence of Body Weight on Bone Mass, Architecture, and Turnover

PubMed Central

Iwaniec, Urszula T.; Turner, Russell T.

2016-01-01

Weight-dependent loading of the skeleton plays an important role in establishing and maintaining bone mass and strength. This review focuses on mechanical signaling induced by body weight as an essential mechanism for maintaining bone health. In addition, the skeletal effects of deviation from normal weight are discussed. The magnitude of mechanical strain experienced by bone during normal activities is remarkably similar among vertebrates, regardless of size, supporting the existence of a conserved regulatory mechanism, or mechanostat, that senses mechanical strain. The mechanostat functions as an adaptive mechanism to optimize bone mass and architecture based on prevailing mechanical strain. Changes in weight, due to altered mass, weightlessness (spaceflight), and hypergravity (modeled by centrifugation), induce an adaptive skeletal response. However, the precise mechanisms governing the skeletal response are incompletely understood. Furthermore, establishing whether the adaptive response maintains the mechanical competence of the skeleton has proven difficult, necessitating development of surrogate measures of bone quality. The mechanostat is influenced by regulatory inputs to facilitate non-mechanical functions of the skeleton, such as mineral homeostasis, as well as hormones and energy/nutrient availability that support bone metabolism. While the skeleton is very capable of adapting to changes in weight, the mechanostat has limits. At the limits, extreme deviations from normal weight and body composition are associated with impaired optimization of bone strength to prevailing body size. PMID:27352896

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...

Hg0 and HgCl2 Reference Gas Standards: ?NIST Traceability ...

EPA Pesticide Factsheets

EPA and NIST have collaborated to establish the necessary procedures for establishing the required NIST traceability of commercially-provided Hg0 and HgCl2 reference generators. This presentation will discuss the approach of a joint EPA/NIST study to accurately quantify the true concentrations of Hg0 and HgCl2 reference gases produced from high quality, NIST-traceable, commercial Hg0 and HgCl2 generators. This presentation will also discuss the availability of HCl and Hg0 compressed reference gas standards as a result of EPA's recently approved Alternative Methods 114 and 118. Gaseous elemental mercury (Hg0) and oxidized mercury (HgCl2) reference standards are integral to the use of mercury continuous emissions monitoring systems (Hg CEMS) for regulatory compliance emissions monitoring. However, a quantitative disparity of approximately 7-10% has been observed between commercial Hg0 and HgCl2 reference gases which currently limits the use of (HgCl2) reference gas standards. Resolving this disparity would enable the expanded use of (HgCl2) reference gas standards for regulatory compliance purposes.

Rationales for regulatory activity

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

Perhac, R.M.

1997-02-01

The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

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 68873 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of Longer Period for Commission Action on Proceedings to Determine Whether to Approve or Disapprove Proposed Rule Change To Establish... proposed rule change to establish various ``Benchmark Orders'' under NASDAQ Rule 4751(f). The proposed rule...

Intertemporal Regulatory Tasks and Responsibilities for Greenhouse Gas Reductions

ERIC Educational Resources Information Center

Deason, Jeffrey A.; Friedman, Lee S.

2010-01-01

Jurisdictions are in the process of establishing regulatory systems to control greenhouse gas emissions. Short-term and sometimes long-term emissions reduction goals are established, as California does for 2020 and 2050, but little attention has yet been focused on annual emissions targets for the intervening years. We develop recommendations for…

76 FR 12390 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-07

... By-Laws, Article VIII, Section 8.1 (Establishment of Districts) and Section 8.2 (Composition of..., Article VIII, Section 2(c) (District Committees and District Business Conduct Committees), amended...\\ See FINRA Regulation By-Laws, Article VIII, Section 8.1 (Establishment of Districts) and Section 8.2...

Transcriptional and posttranscriptional regulation of cyanobacterial photosynthesis.

PubMed

Wilde, Annegret; Hihara, Yukako

2016-03-01

Cyanobacteria are well established model organisms for the study of oxygenic photosynthesis, nitrogen metabolism, toxin biosynthesis, and salt acclimation. However, in comparison to other model bacteria little is known about regulatory networks, which allow cyanobacteria to acclimate to changing environmental conditions. The current work has begun to illuminate how transcription factors modulate expression of different photosynthetic regulons. During the past few years, the research on other regulatory principles like RNA-based regulation showed the importance of non-protein regulators for bacterial lifestyle. Investigations on modulation of photosynthetic components should elucidate the contributions of all factors within the context of a larger regulatory network. Here, we focus on regulation of photosynthetic processes including transcriptional and posttranscriptional mechanisms, citing examples from a limited number of cyanobacterial species. Though, the general idea holds true for most species, important differences exist between various organisms, illustrating diversity of acclimation strategies in the very heterogeneous cyanobacterial clade. This article is part of a Special Issue entitled Organization and dynamics of bioenergetic systems in bacteria, edited by Prof Conrad Mullineaux. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunomodulatory Effects of Mixed Hematopoietic Chimerism: Immune Tolerance in Canine Model of Lung Transplantation

PubMed Central

Nash;, Richard A.; Yunosov;, Murad; Abrams;, Kraig; Hwang;, Billanna; Castilla-Llorente;, Cristina; Chen;, Peter; Farivar;, Alexander S.; Georges;, George E.; Hackman;, Robert C.; Lamm;, Wayne J.E.; Lesnikova;, Marina; Ochs;, Hans D.; Randolph-Habecker;, Julie; Ziegler;, Stephen F.; Storb;, Rainer; Storer;, Barry; Madtes;, David K.; Glenny;, Robb; Mulligan, Michael S.

2010-01-01

Long-term survival after lung transplantation is limited by acute and chronic graft rejection. Induction of immune tolerance by first establishing mixed hematopoietic chimerism (MC) is a promising strategy to improve outcomes. In a preclinical canine model, stable MC was established in recipients after reduced-intensity conditioning and hematopoietic cell transplantation from a DLA-identical donor. Delayed lung transplantation was performed from the stem cell donor without pharmacological immunosuppression. Lung graft survival without loss of function was prolonged in chimeric (n=5) vs. nonchimeric (n=7) recipients (p≤0.05, Fisher’s test). There were histological changes consistent with low grade rejection in 3/5 of the lung grafts in chimeric recipients at ≥1 year. Chimeric recipients after lung transplantation had a normal immune response to a T-dependent antigen. Compared to normal dogs, there were significant increases of CD4+INFγ+, CD4+IL-4+ and CD8+ INFγ+ T-cell subsets in the blood (p <0.0001 for each of the 3 T-cell subsets). Markers for regulatory T-cell subsets including foxP3, IL10 and TGFβ were also increased in CD3+ T cells from the blood and peripheral tissues of chimeric recipients after lung transplantation. Establishing MC is immunomodulatory and observed changes were consistent with activation of both the effector and regulatory immune response. PMID:19422333

Accounting for metal bioavailability in assessing water quality: A step change?

PubMed

Merrington, Graham; Peters, Adam; Schlekat, Christian E

2016-02-01

Bioavailability of metals to aquatic organisms can be considered to be a combination of the physicochemical factors governing metal behavior and the specific pathophysiological characteristics of the organism's biological receptor. Effectively this means that a measure of bioavailability will reflect the exposures that organisms in the water column actually "experience". This is important because it has long been established that measures of total metal in waters have limited relevance to potential environmental risk. The concept of accounting for bioavailability in regard to deriving and implementing environmental water quality standards is not new, but the regulatory reality has lagged behind the development of scientific evidence supporting the concept. Practical and technical reasons help to explain this situation. For example, concerns remain from regulators and the regulated that the efforts required to change existing systems of metal environmental protection that have been in place for over 35 yr are so great as not to be commensurate with likely benefits. However, more regulatory jurisdictions are now considering accounting for metal bioavailability in assessments of water quality as a means to support evidence-based decision-making. In the past decade, both the US Environmental Protection Agency and the European Commission have established bioavailability-based standards for metals, including Cu and Ni. These actions have shifted the debate toward identifying harmonized approaches for determining when knowledge is adequate to establish bioavailability-based approaches and how to implement them. © 2016 SETAC.

75 FR 13614 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing of Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... to handle the additional traffic associated with the listing and trading of $1 strikes where the...-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing of Proposed Rule Change To Establish Strike... 1012 (Series of Options Open for Trading) to establish strike-price intervals for options on Index...

77 FR 24748 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

... establish a real-time market data set for disseminated Asset-Backed Security transaction information (``ABS Data Set'') and to amend Rule 7730(d) to establish a historic data set for such information (``Historic ABS Data Set'').\\16\\ The provisions of Rule 7730 that currently apply to the two existing real-time...

[Advanced therapy: from European regulatory framework to national regulatory framework].

PubMed

Lucas-Samuel, S

2013-05-01

The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012. Copyright © 2013. Published by Elsevier SAS.

Unmanned Aircraft Hazards and their Implications for Regulation

NASA Technical Reports Server (NTRS)

Hayhurst, Kelly J.; Maddalon, Jeffrey M.; Miner, Paul S.; DeWalt, Michael P.; McCormick, G. Frank

2006-01-01

Use of unmanned aircraft systems (UASs) has been characterized as the next great step forward in the evolution of civil aviation. Indeed, UASs are in limited civil use in the United States today, and many believe that the time is rapidly approaching when they will move into the commercial marketplace, too. To make this a reality, a number of challenges must be overcome to develop the necessary regulatory framework for assuring safe operation of this special class of aircraft. This paper discusses some of what must be done to establish that framework. In particular, we examine hazards specific to the design, operation, and flight crew of UASs, and discuss implications of these hazards for existing policy and guidance. Understanding unique characteristics of UASs that pose new hazards is essential to developing a cogent argument, and the corresponding regulatory framework, for safely integrating these aircraft into civil airspace.

Biosimilars: The US Regulatory Framework.

PubMed

Christl, Leah A; Woodcock, Janet; Kozlowski, Steven

2017-01-14

With the passage of the Biologics Price Competition and Innovation Act of 2009, the US Food and Drug Administration established an abbreviated pathway for developing and licensing biosimilar and interchangeable biological products. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a "totality of the evidence" that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. Although questions and concerns about the biosimilars pathway remain and may slow uptake, a robust scientific program has been put in place. With three biosimilars already licensed and numerous development programs under way, clinicians can expect to see many new biosimilars come onto the US market in the coming decade. [Note added in proof: Since the writing of this article, a fourth biosimilar has been approved.].

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

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...

Feasibility of potable water generators to meet vessel numeric ballast water discharge limits.

PubMed

Albert, Ryan J; Viveiros, Edward; Falatko, Debra S; Tamburri, Mario N

2017-07-15

Ballast water is taken on-board vessels into ballast water tanks to maintain vessel draft, buoyancy, and stability. Unmanaged ballast water contains aquatic organisms that, when transported and discharged to non-native waters, may establish as invasive species. Technologies capable of achieving regulatory limits designed to decrease the likelihood of invasion include onboard ballast water management systems. However, to date, the treatment development and manufacturing marketplace is limited to large vessels with substantial ballast requirements. For smaller vessels or vessels with reduced ballast requirements, we evaluated the feasibility of meeting the discharge limits by generating ballast water using onboard potable water generators. Case studies and parametric analyses demonstrated the architectural feasibility of installing potable water generators onboard actual vessels with minimal impacts for most vessel types evaluated. Furthermore, land-based testing of a potable water generator demonstrated capability to meet current numeric discharge limits for living organisms in all size classes. Published by Elsevier Ltd.

Inferring Regulatory Networks by Combining Perturbation Screens and Steady State Gene Expression Profiles

PubMed Central

Michailidis, George

2014-01-01

Reconstructing transcriptional regulatory networks is an important task in functional genomics. Data obtained from experiments that perturb genes by knockouts or RNA interference contain useful information for addressing this reconstruction problem. However, such data can be limited in size and/or are expensive to acquire. On the other hand, observational data of the organism in steady state (e.g., wild-type) are more readily available, but their informational content is inadequate for the task at hand. We develop a computational approach to appropriately utilize both data sources for estimating a regulatory network. The proposed approach is based on a three-step algorithm to estimate the underlying directed but cyclic network, that uses as input both perturbation screens and steady state gene expression data. In the first step, the algorithm determines causal orderings of the genes that are consistent with the perturbation data, by combining an exhaustive search method with a fast heuristic that in turn couples a Monte Carlo technique with a fast search algorithm. In the second step, for each obtained causal ordering, a regulatory network is estimated using a penalized likelihood based method, while in the third step a consensus network is constructed from the highest scored ones. Extensive computational experiments show that the algorithm performs well in reconstructing the underlying network and clearly outperforms competing approaches that rely only on a single data source. Further, it is established that the algorithm produces a consistent estimate of the regulatory network. PMID:24586224

Ground-water protection, low-level waste, and below regulatory concern: What`s the connection?

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

Gruhlke, J.M.; Galpin, F.L.

1991-12-31

The Environmental Protection Agency (EPA) has a responsibility to protect ground water and drinking water under a wide variety of statutes. Each statute establishes different but specific requirements for EPA and applies to diverse environmental contaminants. Radionuclides are but one of the many contaminants subject to this regulatory matrix. Low-level radioactive waste (LLW) and below regulatory concern (BRC) are but two of many activities falling into this regulatory structure. The nation`s ground water serves as a major source of drinking water, supports sensitive ecosystems, and supplies the needs of agriculture and industry. Ground water can prove enormously expensive to cleanmore » up. EPA policy for protecting ground water has evolved considerably over the last ten years. The overall goal is to prevent adverse effects to human health, both now and in the future, and to protect the integrity of the nation`s ground-water resources. The Agency uses the Maximum Contaminant Levels (MCLs) under the Safe Drinking Water Act as reference points for protection in both prevention and remediation activities. What`s the connection? Both low-level waste management and disposal activities and the implementation of below regulatory concern related to low-level waste disposal have the potential for contaminating ground water. EPA is proposing to use the MCLs as reference points for low-level waste disposal and BRC disposal in order to define limits to the environmental contamination of ground water that is, or may be, used for drinking water.« less

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...

77 FR 14572 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... disseminating information products to purchasers. B. Self-Regulatory Organization's Statement on Burden on...-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of Proposed Rule Change Consisting of Establishment of a Subscription to Historical Information and Documents Submitted to the MSRB's...

78 FR 21522 - Delegation of Authority To Disclose Confidential Information to a Contract Market, Registered...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

... information to self-regulatory organizations newly established in the Wall Street Reform and Consumer... contract market, registered futures association, or certain self-regulatory organizations.\\4\\ With this... Disclose Confidential Information to a Contract Market, Registered Futures Association or Self-Regulatory...

75 FR 79949 - Revision of Delegation of Authority

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-21

... Marketing and Regulatory Programs (MRP) to the Deputy Under Secretary for MRP to establish the order in..., Chief of Staff, Marketing and Regulatory Programs, USDA, 1400 Independence Avenue, SW., Washington, DC... Marketing and Regulatory Programs (MRP) has delegated to the Deputy Under Secretary for MRP the following...

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...

76 FR 60713 - Establishment of Class E Airspace; Bumpass, VA

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

... controlled airspace required to support the new RNA V GPS standard instrument approach procedures developed... regulatory action'' under Executive Order 12866; (2) is not a ``significant rule'' under DOT Regulatory... Regulatory Evaluation as the anticipated impact is so minimal. Since this is a routine matter that will only...

78 FR 21661 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

...-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Establish an Administrative Information Subscriber (AIS) and AIS Port...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change The Exchange is...

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...

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

PubMed

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

2015-01-01

In reaction to breaches of data integrity in the pharmaceutical industry, regulatory authorities have introduced inspection approaches or initiatives with the aim of reducing occurrences of data integrity problems. This review article-based on study of 65 cases of regulatory action from 2002 to 2014-provides an overview of current regulatory thinking and action on breaches of data integrity affecting GxP (health-related regulations) processes supporting non-clinical studies, clinical studies, laboratory controls, and production controls. These case studies largely represent position of the U.S. Food and Drug Administration and the regulatory agencies affiliated with the European Medicines Agency. Also discussed is the role of human factors as a potential source of data integrity problems. The article concludes by recommending some remedial controls that could be established to avoid or reduce occurrences of data integrity problems.Lay Abstract: In fulfilling their mission to protect public health, regulatory agencies (e.g., U.S. Food and Drug Administration, European Medicines Agency) must establish confidence that medical products they approve are fit for their intended use. In so doing they rely on scientific and operational data generated during research, development, manufacturing, sales, marketing, distribution, and post-marketing surveillance activities. The level of confidence they build is directly proportional to the scientific validity and integrity of data presented to them by the sponsors of medical products. In this article we present analysis of 65 case studies that document regulatory action taken by various regulatory agencies on breach of data integrity between 2002 and 2014. The ensuing discussion on current trends largely represents position of the U.S. Food and Drug Administration and European Medicines Agency. The article concludes by proposing some remedial controls that could be established by pharmaceutical companies to avoid or reduce occurrences of data integrity problems. © PDA, Inc. 2015.

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...

Methodological challenges for the evaluation of clinical effectiveness in the context of accelerated regulatory approval: an overview.

PubMed

Woolacott, Nerys; Corbett, Mark; Jones-Diette, Julie; Hodgson, Robert

2017-10-01

Regulatory authorities are approving innovative therapies with limited evidence. Although this level of data is sufficient for the regulator to establish an acceptable risk-benefit balance, it is problematic for downstream health technology assessment, where assessment of cost-effectiveness requires reliable estimates of effectiveness relative to existing clinical practice. Some key issues associated with a limited evidence base include using data, from nonrandomized studies, from small single-arm trials, or from single-center trials; and using surrogate end points. We examined these methodological challenges through a pragmatic review of the available literature. Methods to adjust nonrandomized studies for confounding are imperfect. The relative treatment effect generated from single-arm trials is uncertain and may be optimistic. Single-center trial results may not be generalizable. Surrogate end points, on average, overestimate treatment effects. Current methods for analyzing such data are limited, and effectiveness claims based on these suboptimal forms of evidence are likely to be subject to significant uncertainty. Assessments of cost-effectiveness, based on the modeling of such data, are likely to be subject to considerable uncertainty. This uncertainty must not be underestimated by decision makers: methods for its quantification are required and schemes to protect payers from the cost of uncertainty should be implemented. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

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.

The future of antibiotics

PubMed Central

2014-01-01

Antibiotic resistance continues to spread even as society is experiencing a market failure of new antibiotic research and development (R&D). Scientific, economic, and regulatory barriers all contribute to the antibiotic market failure. Scientific solutions to rekindle R&D include finding new screening strategies to identify novel antibiotic scaffolds and transforming the way we think about treating infections, such that the goal is to disarm the pathogen without killing it or modulate the host response to the organism without targeting the organism for destruction. Future economic strategies are likely to focus on ‘push’ incentives offered by public-private partnerships as well as increasing pricing by focusing development on areas of high unmet need. Such strategies can also help protect new antibiotics from overuse after marketing. Regulatory reform is needed to re-establish feasible and meaningful traditional antibiotic pathways, to create novel limited-use pathways that focus on highly resistant infections, and to harmonize regulatory standards across nations. We need new antibiotics with which to treat our patients. But we also need to protect those new antibiotics from misuse when they become available. If we want to break the cycle of resistance and change the current landscape, disruptive approaches that challenge long-standing dogma will be needed. PMID:25043962

76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

A harmonization effort for acceptable daily exposure application to pharmaceutical manufacturing - Operational considerations.

PubMed

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

2016-08-01

A European Union (EU) regulatory guideline came into effect for all new pharmaceutical products on June 1st, 2015, and for all existing pharmaceutical products on December 1st, 2015. This guideline centers around the use of the Acceptable Daily Exposure (ADE) [synonymous with the Permitted Daily Exposure (PDE)] and operational considerations associated with implementation are outlined here. The EU guidance states that all active pharmaceutical ingredients (API) require an ADE; however, other substances such as starting materials, process intermediates, and cleaning agents may benefit from an ADE. Problems in setting ADEs for these additional substances typically relate to toxicological data limitations precluding the ability to establish a formal ADE. Established methodologies such as occupational exposure limits or bands (OELs or OEBs) and the threshold of toxicological concern (TTC) can be used or adjusted for use as interim ADEs when only limited data are available and until a more formal ADE can be established. Once formal ADEs are derived, it is important that the documents are routinely updated and that these updates are communicated to appropriate stakeholders. Another key operational consideration related to data-poor substances includes the use of maximum daily dose (MDD) in setting cross-contamination limits. The MDD is an important part of the maximum allowable/safe concentration (MAC/MSC) calculation and there are important considerations for its use and definition. Finally, other considerations discussed include operational aspects of setting ADEs for pediatrics, considerations for large molecules, and risk management in shared facilities. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Proteomics of a new esophageal cancer cell line established from Persian patient.

PubMed

Moghanibashi, Mehdi; Jazii, Ferdous Rastgar; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

2012-05-25

Although the highest incidence of esophageal squamous cell carcinoma (ESCC) has repeatedly been reported from Persia (Iran), nevertheless the so far proteomic published reports were limited to one study on tissue specimens. Here we report the proteome of a newly established cell line from Persian ESCC patients and compare it with the normal primary cell proteome. Among polypeptides, whose expression was different in cell line sixteen polypeptides were identified by MALDI/TOF/TOF spectrometry. S100-A8 protein, annexin A1, annexin A2, regulatory subunit of calpain, subunit alpha type-3 of proteasome and glutamate dehydrogenase 1 were proteins down-regulated in cell line while peroxiredoxin-5, non-muscle myosin light polypeptide 6, keratin 1, annexin A4, keratin 8, tropomyosin 3, stress-induced-phosphoprotein 1 and albumin were found to be subject of up-regulation in cell line compared to the primary normal cells. The proteomic results were further verified by western blotting and RT-PCR on annexin A1 and keratin 8. In addition, among the aforementioned proteins, glutamate dehydrogenase 1, regulatory subunit of calpain, subunit alpha of type-3 proteasome and annexin A4 are proteins whose deregulation in ESCC is reported for the first time by this study. Copyright © 2012 Elsevier B.V. All rights reserved.

77 FR 1775 - Self-Regulatory Organizations; Chicago Mercantile Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-11

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66102; File No. SR-CME-2011-22] Self-Regulatory... Change To Establish Certain Fee Programs in Connection With Its OTC Interest Rate Swap Clearing Offering...)(2). I. Self-Regulatory Organization's Statement of Terms of Substance of the Proposed Rule Change...

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression

PubMed Central

Verd, Berta; Crombach, Anton

2017-01-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development. PMID:28158178

Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression.

PubMed

Verd, Berta; Crombach, Anton; Jaeger, Johannes

2017-02-01

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.

17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

Code of Federal Regulations, 2012 CFR

2012-04-01

... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

Code of Federal Regulations, 2010 CFR

2010-04-01

... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

Code of Federal Regulations, 2011 CFR

2011-04-01

... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

Code of Federal Regulations, 2013 CFR

2013-04-01

... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

17 CFR 240.19d-3 - Applications for review of final disciplinary sanctions, denials of membership, participation or...

Code of Federal Regulations, 2014 CFR

2014-04-01

... limitations of access to services imposed by self-regulatory organizations. 240.19d-3 Section 240.19d-3... services imposed by self-regulatory organizations. Applications to the Commission for review of any final... prohibition or limitation with respect to access to services offered by a self-regulatory organization or a...

To what extent could performance-based schemes help increase the effectiveness of prevention of mother-to-child transmission of HIV (PMTCT) programs in resource-limited settings? a summary of the published evidence

PubMed Central

2010-01-01

Background In resource-limited settings, HIV/AIDS remains a serious threat to the social and physical well-being of women of childbearing age, pregnant women, mothers and infants. Discussion In sub-Saharan African countries with high prevalence rates, pediatric HIV/AIDS acquired through mother-to-child transmission (MTCT) can in largely be prevented by using well-established biomedical interventions. Logistical and socio-cultural barriers continue, however, to undermine the successful prevention of MTCT (PMTCT). In this paper, we review reports on maternal, neonatal and child health, as well as HIV care and treatment services that look at program incentives. Summary These studies suggest that comprehensive PMTCT strategies aiming to maximize health-worker motivation in developing countries must involve a mix of both financial and non-financial incentives. The establishment of robust ethical and regulatory standards in public-sector HIV care centers could reduce barriers to PMTCT service provision in sub-Saharan Africa and help them in achieving universal PMTCT targets. PMID:21080926

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...

Switching modes in corticogenesis: mechanisms of neuronal subtype transitions and integration in the cerebral cortex

PubMed Central

Toma, Kenichi; Hanashima, Carina

2015-01-01

Information processing in the cerebral cortex requires the activation of diverse neurons across layers and columns, which are established through the coordinated production of distinct neuronal subtypes and their placement along the three-dimensional axis. Over recent years, our knowledge of the regulatory mechanisms of the specification and integration of neuronal subtypes in the cerebral cortex has progressed rapidly. In this review, we address how the unique cytoarchitecture of the neocortex is established from a limited number of progenitors featuring neuronal identity transitions during development. We further illuminate the molecular mechanisms of the subtype-specific integration of these neurons into the cerebral cortex along the radial and tangential axis, and we discuss these key features to exemplify how neocortical circuit formation accomplishes economical connectivity while maintaining plasticity and evolvability to adapt to environmental changes. PMID:26321900

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

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2012-07-25

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2010-04-26

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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...

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices

PubMed Central

Morrison, Tina M.; Dreher, Maureen L.; Nagaraja, Srinidhi; Angelone, Leonardo M.; Kainz, Wolfgang

2018-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making. PMID:29479395

The Role of Computational Modeling and Simulation in the Total Product Life Cycle of Peripheral Vascular Devices.

PubMed

Morrison, Tina M; Dreher, Maureen L; Nagaraja, Srinidhi; Angelone, Leonardo M; Kainz, Wolfgang

2017-01-01

The total product life cycle (TPLC) of medical devices has been defined by four stages: discovery and ideation, regulatory decision, product launch, and postmarket monitoring. Manufacturers of medical devices intended for use in the peripheral vasculature, such as stents, inferior vena cava (IVC) filters, and stent-grafts, mainly use computational modeling and simulation (CM&S) to aid device development and design optimization, supplement bench testing for regulatory decisions, and assess postmarket changes or failures. For example, computational solid mechanics and fluid dynamics enable the investigation of design limitations in the ideation stage. To supplement bench data in regulatory submissions, manufactures can evaluate the effects of anatomical characteristics and expected in vivo loading environment on device performance. Manufacturers might also harness CM&S to aid root-cause analyses that are necessary when failures occur postmarket, when the device is exposed to broad clinical use. Once identified, CM&S tools can then be used for redesign to address the failure mode and re-establish the performance profile with the appropriate models. The Center for Devices and Radiological Health (CDRH) wants to advance the use of CM&S for medical devices and supports the development of virtual physiological patients, clinical trial simulations, and personalized medicine. Thus, the purpose of this paper is to describe specific examples of how CM&S is currently used to support regulatory submissions at different phases of the TPLC and to present some of the stakeholder-led initiatives for advancing CM&S for regulatory decision-making.

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...

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.

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...

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2013-08-20

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

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2013-03-28

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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...

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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...

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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...

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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...

Analysing policy interventions to prohibit over-the-counter antibiotic sales in four Latin American countries.

PubMed

Wirtz, V J; Herrera-Patino, J J; Santa-Ana-Tellez, Y; Dreser, A; Elseviers, M; Vander Stichele, R H

2013-06-01

To describe and evaluate policies implemented in Chile, Colombia, Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore limitations in available data. We searched and analysed legislation, grey literature and peer-reviewed publications on regulatory interventions and implementation strategies to enforce prohibition of OTC antibiotic sales. We also assessed the impact using private sector retail sales data of antibiotics studying changes in level and consumption trends before and after the policy change using segmented time series analysis. Finally, we assessed the completeness and data quality through an established checklist to test the suitability of the data for analysis of the interventions. Whereas Chile implemented a comprehensive package of interventions to accompany regulation changes, Colombia's reform was limited to the capital district and Venezuela's limited to only some antibiotics and without awareness campaigns. In Mexico, no enforcement was enacted. The data showed a differential effect of the intervention among the countries studied with a significant change in level of consumption in Chile (-5.56 DID) and in Colombia (-1.00DID). In Venezuela and Mexico, no significant change in level and slope was found. Changes in population coverage were identified as principal limitations of using sales data for evaluating the reform impact. Retail sales data can be useful when assessing policy impact but should be supplemented by other data sources such as public sector sales and prescription data. Implementing regulatory enforcement has shown some impact, but a sustainable, concerted approach will be needed to address OTC sales in the future. © 2013 John Wiley & Sons Ltd.

Legislative and Regulatory Actions Needed to Deal with a Changing Domestic Telecommunications Industry.

DTIC Science & Technology

1981-09-24

procedures? GAO recommends that the Congress address these questions by amending the Communications Act of 1934 to establish the basic framework to create...concerns with rate of return/rate base regulation 198 VII Basic procedures used in establishing rates of return 201 VIII Problems regarding AT&T’s rate...prompted a critical reexamination of the basic communications policy and regulatory methods con- tained in the Communications Act of 1934 (47 U.S.C

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

The regulatory sciences for stem cell-based medicinal products.

PubMed

Yuan, Bao-Zhu; Wang, Junzhi

2014-06-01

Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.

Challenges of using new and repurposed drugs for the treatment of multidrug-resistant tuberculosis in children.

PubMed

Schaaf, H Simon; Garcia-Prats, Anthony J; McKenna, Lindsay; Seddon, James A

2018-03-01

New and repurposed antituberculosis drugs are urgently needed to more safely and effectively treat multidrug-resistant (MDR) tuberculosis (TB) in children. Multiple challenges limit timely access to new MDR-TB treatments in children. Areas covered: Diagnosis of MDR-TB in children remains a barrier, with few children with MDR-TB diagnosed and treated. Other barriers to timely access to new and repurposed drugs are discussed, and include delayed initiation of paediatric trials, limited funding for paediatric drug development, fragmented regulatory systems and operational challenges. The status of access to current repurposed and novel drugs is presented. Expert commentary: More timely initiation of paediatric trials is needed and paediatric work should happen and be funded in parallel with each phase of adult trials. Better quality data, increased regulator resources and expertise, harmonization of regulatory requirements across borders/organisations and registration fee waivers would improve registration timelines. Improved diagnosis, recording and reporting will establish better demand. Improved systems for procurement and supply chain management would reduce in-country operational barriers to getting medications to children. The challenges must be addressed to ensure timely and equitable access to new drugs and regimens that are urgently needed for effective, safe and shorter treatment of children with MDR-TB.

Regulatory and cost barriers are likely to limit biosimilar development and expected savings in the near future.

PubMed

Grabowski, Henry G; Guha, Rahul; Salgado, Maria

2014-06-01

In March 2010 Congress established an abbreviated Food and Drug Administration approval pathway for biosimilars-drugs that are very similar but not identical to a reference biological product and cost less. Because bringing biosimilars to the market currently requires large investments of money, fewer biosimilars are expected to enter the biologics market than has been the case with generic drugs entering the small-molecule drug market. Additionally, given the high regulatory hurdles to obtaining interchangeability-which would allow pharmacists to substitute a biosimilar for its reference product, subject to evolving state substitution laws-most biosimilars will likely compete as therapeutic alternatives instead of as therapeutic equivalents. In other words, biosimilars will need to compete with their reference product on the basis of quality; price; and manufacturer's reputation with physicians, insurers, and patient groups. Biosimilars also will face dynamic competition from new biologics in the same therapeutic class-including "biobetters," which offer incremental improvements on reference products, such as extended duration of action. The prospects for significant cost savings from the use of biosimilars appear to be limited for the next several years, but their use should increase over time because of both demand- and supply-side factors. Project HOPE—The People-to-People Health Foundation, Inc.

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies.

PubMed

Reichert, Johannes C; Epari, Devakara R; Wullschleger, Martin E; Saifzadeh, Siamak; Steck, Roland; Lienau, Jasmin; Sommerville, Scott; Dickinson, Ian C; Schütz, Michael A; Duda, Georg N; Hutmacher, Dietmar W

2010-02-01

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties; however, they are limited in access and availability and associated with donor-site morbidity, hemorrhage, risk of infection, insufficient transplant integration, graft devitalization, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench-to-bedside translations are still infrequent as the process toward approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence, commercialization, is referred to as the "Valley of Death" and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes and scalable designs and to apply these in preclinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopedic bone engineering from bench to bedside by establishing a preclinical ovine critical-sized tibial segmental bone defect model, and we discuss our preliminary data relating to this decisive step.

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...

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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...

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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...

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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...

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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...

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...

76 FR 40144 - Semiannual Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... the Small Business Administration's regulations establishing the Women-Owned Small Business Program... Government's rulemaking Web site at http://www.regulations.gov . FOR FURTHER INFORMATION CONTACT: Hada Flowers, Division Director, Regulatory Secretariat Director, Room 783E, 1275 First Street, NE., Washington...

DEVELOPMENT OF A FRAMEWORK FOR METALS RISK ASSESSMENT

EPA Science Inventory

Many EPA programs are faced with deciding whether and how to regulate toxic metals. These decisions range from setting regulatory standards for environmental releases, to establishing safe levels in different environmental media, to setting priorities for regulatory or voluntary...

"Nuisance dust": unprotective limits for exposure to coal mine dust in the United States, 1934-1969.

PubMed

Derickson, Alan

2013-02-01

I examine the dismissal of coal mine dust as a mere nuisance, not a potentially serious threat to extractive workers who inhaled it. In the 1930s, the US Public Health Service played a major role in conceptualizing coal mine dust as virtually harmless. Dissent from this position by some federal officials failed to dislodge either that view or the recommendation of minimal limitations on workplace exposure that flowed from it. Privatization of regulatory authority after 1940 ensured that miners would lack protection against respiratory disease. The reform effort that overturned the established misunderstanding in the late 1960s critically depended upon both the production of scientific findings and the emergence of a subaltern movement in the coalfields. This episode illuminates the steep challenges often facing advocates of stronger workplace health standards.

10 CFR 7.4 - Establishment of advisory committees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Establishment of advisory committees. 7.4 Section 7.4 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.4 Establishment of advisory committees. (a) An NRC advisory committee may be established under this part only if its establishment— (1) Is...

10 CFR 7.4 - Establishment of advisory committees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Establishment of advisory committees. 7.4 Section 7.4 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.4 Establishment of advisory committees. (a) An NRC advisory committee may be established under this part only if its establishment— (1) Is...

10 CFR 7.4 - Establishment of advisory committees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Establishment of advisory committees. 7.4 Section 7.4 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.4 Establishment of advisory committees. (a) An NRC advisory committee may be established under this part only if its establishment— (1) Is...

10 CFR 7.4 - Establishment of advisory committees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Establishment of advisory committees. 7.4 Section 7.4 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.4 Establishment of advisory committees. (a) An NRC advisory committee may be established under this part only if its establishment— (1) Is...

10 CFR 7.4 - Establishment of advisory committees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Establishment of advisory committees. 7.4 Section 7.4 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.4 Establishment of advisory committees. (a) An NRC advisory committee may be established under this part only if its establishment— (1) Is...

Factors associated with regulatory action involving investigation of illnesses associated with Shiga toxin-producing Escherichia coli in products regulated by the Food Safety and Inspection Service.

PubMed

Green, Alice L; Seys, Scott; Douris, Aphrodite; Levine, Jeoff; Robertson, Kis

2014-07-01

We described characteristics of the Escherichia coli O157 and Escherichia coli non-O157 illness investigations conducted by the United States Department of Agriculture's Food Safety and Inspection Service (FSIS) during the 5-year period from 2006 through 2010. We created a multivariable logistic regression model to determine characteristics of these investigations that were associated with FSIS regulatory action, which was defined as having occurred if a product recall occurred or if FSIS personnel performed an environmental health assessment (Food Safety Assessment) at the implicated establishment. During this period, FSIS took regulatory action in 38 of 88 (43%) investigations. Illness investigations in which FoodNet states were involved were more likely to result in regulatory action. Illness investigations in which state and local traceback, or FSIS traceback occurred were more likely to result in regulatory action. Reasons for lack of action included evidence of cross-contamination after the product left a regulated establishment, delayed notification, lack of epidemiological information, and insufficient product information.

Portable X-ray Fluorescence Unit for Analyzing Crime Scenes

NASA Astrophysics Data System (ADS)

Visco, A.

2003-12-01

Goddard Space Flight Center and the National Institute of Justice have teamed up to apply NASA technology to the field of forensic science. NASA hardware that is under development for future planetary robotic missions, such as Mars exploration, is being engineered into a rugged, portable, non-destructive X-ray fluorescence system for identifying gunshot residue, blood, and semen at crime scenes. This project establishes the shielding requirements that will ensure that the exposure of a user to ionizing radiation is below the U.S. Nuclear Regulatory Commission's allowable limits, and also develops the benchtop model for testing the system in a controlled environment.

A Regulatory Framework for Nanotechnology

DTIC Science & Technology

informed by a map of the regulatory landscape of nanotechnology and a review of the regulatory frameworks for the aviation and biotechnology industries...aviation and biotechnology and maps the regulatory landscape in the United States by examining stakeholders, regulatory entities, and applicable legislation...state of nanotechnology if the limitations of technical expertise are addressed. This expertise can be provided by advisory committees of technical

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...

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

PubMed

Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

2016-12-30

Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

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...

Decontamination issues for chemical and biological warfare agents: how clean is clean enough?

PubMed

Raber, E; Jin, A; Noonan, K; McGuire, R; Kirvel, R D

2001-06-01

The objective of this assessment is to determine what level of cleanup will be required to meet regulatory and stakeholder needs in the case of a chemical and/or biological incident at a civilian facility. A literature review for selected, potential chemical and biological warfare agents shows that dose information is often lacking or controversial. Environmental regulatory limits or other industrial health guidelines that could be used to help establish cleanup concentration levels for such agents are generally unavailable or not applicable for a public setting. Although dose information, cleanup criteria, and decontamination protocols all present challenges to effective planning, several decontamination approaches are available. Such approaches should be combined with risk-informed decision making to establish reasonable cleanup goals for protecting health, property, and resources. Key issues during a risk assessment are to determine exactly what constitutes a safety hazard and whether decontamination is necessary or not for a particular scenario. An important conclusion is that cleanup criteria are site dependent and stakeholder specific. The results of a modeling exercise for two outdoor scenarios are presented to reinforce this conclusion. Public perception of risk to health, public acceptance of recommendations based on scientific criteria, political support, time constraints, and economic concerns must all be addressed in the context of a specific scenario to yield effective and acceptable decontamination.

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.

Functional and topological characteristics of mammalian regulatory domains

PubMed Central

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

A guide for establishing restoration goals for contaminated ecosystems

USGS Publications Warehouse

Wagner, Anne M.; Larson, Diane L.; DalSoglio, Julie A.; Harris, James A.; Labus, Paul; Rosi-Marshall, Emma J.; Skarbis, Krisin E.

2016-01-01

As natural resources become increasingly limited, the value of restoring contaminated sites, both terrestrial and aquatic, becomes increasingly apparent. Traditionally, goals for remediation have been set before any consideration of goals for ecological restoration. The goals for remediation have focused on removing or limiting contamination whereas restoration goals have targeted the ultimate end use. Here, we present a framework for developing a comprehensive set of achievable goals for ecological restoration of contaminated sites to be used in concert with determining goals for remediation. This framework was developed during a Society of Environmental Toxicology and Chemistry (SETAC) and Society of Ecological Restoration (SER) cosponsored workshop that brought together experts from multiple countries. Although most members were from North America, this framework is designed for use internationally. We discuss the integration of establishing goals for both contaminant remediation and overall restoration, and the need to include both the restoration of ecological and socio-cultural-economic value in the context of contaminated sites. Although recognizing that in some countries there may be regulatory issues associated with contaminants and clean up, landscape setting and social drivers can inform the restoration goals. We provide a decision tree support tool to guide the establishment of restoration goals for contaminated ecosystems. The overall intent of this decision tree is to provide a framework for goal setting and to identify outcomes achievable given the contamination present at a site.

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…

Information Quality in Regulatory Decision Making: Peer Review versus Good Laboratory Practice.

PubMed

McCarty, Lynn S; Borgert, Christopher J; Mihaich, Ellen M

2012-07-01

There is an ongoing discussion on the provenance of toxicity testing data regarding how best to ensure its validity and credibility. A central argument is whether journal peer-review procedures are superior to Good Laboratory Practice (GLP) standards employed for compliance with regulatory mandates. We sought to evaluate the rationale for regulatory decision making based on peer-review procedures versus GLP standards. We examined pertinent published literature regarding how scientific data quality and validity are evaluated for peer review, GLP compliance, and development of regulations. Some contend that peer review is a coherent, consistent evaluative procedure providing quality control for experimental data generation, analysis, and reporting sufficient to reliably establish relative merit, whereas GLP is seen as merely a tracking process designed to thwart investigator corruption. This view is not supported by published analyses pointing to subjectivity and variability in peer-review processes. Although GLP is not designed to establish relative merit, it is an internationally accepted quality assurance, quality control method for documenting experimental conduct and data. Neither process is completely sufficient for establishing relative scientific soundness. However, changes occurring both in peer-review processes and in regulatory guidance resulting in clearer, more transparent communication of scientific information point to an emerging convergence in ensuring information quality. The solution to determining relative merit lies in developing a well-documented, generally accepted weight-of-evidence scheme to evaluate both peer-reviewed and GLP information used in regulatory decision making where both merit and specific relevance inform the process.

75 FR 21689 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Granting Accelerated Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

... To Establish Strike Price Intervals and Trading Hours for Options on Index-Linked Securities April 20... establish strike-price intervals for options on Index-Linked Securities and to establish trading hours for... exchange-traded notes (``ETN'')), Phlx has proposed to establish strike price intervals and trading hours...

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

PubMed

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016. Published by Oxford University Press.

Economic analysis requirements in support of orbital debris regulatory policy

NASA Astrophysics Data System (ADS)

Greenberg, Joel S.

1996-10-01

As the number of Earth orbiting objects increases so does the potential for generating orbital debris with the consequent increase in the likelihood of impacting and damaging operating satellites. Various debris remediation approaches are being considered that encompass both in-orbit and return-to-Earth schema and have varying degrees of operations, cost, international competitiveness, and safety implications. Because of the diversity of issues, concerns and long-term impacts, there is a clear need for the setting of government policies that will lead to an orderly abatement of the potential orbital debris hazards. These policies may require the establishment of a supportive regulatory regime. The Department of Transportation is likely to have regulatory responsibilities relating to orbital debris stemming from its charge to protect the public health and safety, safety of property, and national security interests and foreign policy interests of the United States. This paper describes DOT's potential regulatory role relating to orbital debris remediation, the myriad of issues concerning the need for establishing government policies relating to orbital debris remediation and their regulatory implications, the proposed technological solutions and their economic and safety implications. Particular emphasis is placed upon addressing cost-effectiveness and economic analyses as they relate to economic impact analysis in support of regulatory impact analysis.

IL-35, a hallmark of immune-regulation in cancer progression, chronic infections and inflammatory diseases.

PubMed

Teymouri, Manouchehr; Pirro, Matteo; Fallarino, Francesca; Gargaro, Marco; Sahebkar, Amirhosein

2018-03-25

Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target. © 2018 UICC.

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.

Regulation of epidermal cell fate in Arabidopsis roots: the importance of multiple feedback loops

PubMed Central

Schiefelbein, John; Huang, Ling; Zheng, Xiaohua

2014-01-01

The specification of distinct cell types in multicellular organisms is accomplished via establishment of differential gene expression. A major question is the nature of the mechanisms that establish this differential expression in time and space. In plants, the formation of the hair and non-hair cell types in the root epidermis has been used as a model to understand regulation of cell specification. Recent findings show surprising complexity in the number and the types of regulatory interactions between the multiple transcription factor genes/proteins influencing root epidermis cell fate. Here, we describe this regulatory network and the importance of the multiple feedback loops for its establishment and maintenance. PMID:24596575

Establishing an unusual cell type: How to make a dikaryon

PubMed Central

Kruzel, Emilia K.; Hull, Christina M.

2010-01-01

Summary The dikaryons of basidiomycete fungi represent an unusual cell type required for complete sexual development. Dikaryon formation occurs via the activities of cell type-specific homeodomain transcription factors, which form regulatory complexes to establish the dikaryotic state. Decades of classical genetic and cell biological studies in mushrooms have provided a foundation for more recent molecular studies in the pathogenic species Ustilago maydis and Cryptococcus neoformans. Studies in these systems have revealed novel mechanisms of regulation that function downstream of classic homeodomain complexes to ensure that dikaryons are established and propagated. Comparisons of these dikaryon-specific networks promise to reveal the nature of regulatory network evolution and the adaptations responsible for driving complex eukaryotic development. PMID:21036099

Establishing Total Maximum Daily Load (TMDL) Wasteload Allocations (WLAs) for Storm Water Sources and NPDES Permit Requirements Based on Those WLAs

EPA Pesticide Factsheets

The memoranda clarify existing EPA regulatory requirements for, and provide guidance on, establishing wasteload allocations (WLAs) for storm water discharges in total maximum daily loads (TMDLs) approved or established by EPA.

29 CFR 1630.16 - Specific activities permitted.

Code of Federal Regulations, 2011 CFR

2011-07-01

... regulations (if any) of the Departments of Defense and Transportation and of the Nuclear Regulatory Commission... such regulations comply with the standards established in the regulations (if any) of the Departments of Defense and Transportation, and of the Nuclear Regulatory Commission, regarding alcohol and the...

29 CFR 1630.16 - Specific activities permitted.

Code of Federal Regulations, 2014 CFR

2014-07-01

... regulations (if any) of the Departments of Defense and Transportation and of the Nuclear Regulatory Commission... such regulations comply with the standards established in the regulations (if any) of the Departments of Defense and Transportation, and of the Nuclear Regulatory Commission, regarding alcohol and the...

Regulatory Requirements for Devices for the Handicapped.

ERIC Educational Resources Information Center

Stigi, John, Ed.; Rivera, Richard J., Ed.

This booklet explains in question/answer form the basic regulatory requirements established by the Food and Drug Administration (FDA) of the federal government concerning the manufacture, marketing and distribution of medical devices (including implantable devices and devices previously regulated as drugs) for persons with disabilities. Topics…

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...

Toward the framework and implementation for clearance of materials from regulated facilities.

PubMed

Chen, S Y; Moeller, D W; Dornsife, W P; Meyer, H R; Lamastra, A; Lubenau, J O; Strom, D J; Yusko, J G

2005-08-01

The disposition of solid materials from nuclear facilities has been a subject of public debate for several decades. The primary concern has been the potential health effects resulting from exposure to residual radioactive materials to be released for unrestricted use. These debates have intensified in the last decade as many regulated facilities are seeking viable management decisions on the disposition of the large amounts of materials potentially containing very low levels of residual radioactivity. Such facilities include the nuclear weapons complex sites managed by the U.S. Department of Energy, commercial power plants licensed by the U.S. Nuclear Regulatory Commission (NRC), and other materials licensees regulated by the NRC or the Agreement States. Other facilities that generate radioactive material containing naturally occurring radioactive materials (NORM) or technologically enhanced NORM (TENORM) are also seeking to dispose of similar materials that may be radioactively contaminated. In contrast to the facilities operated by the DOE and the nuclear power plants licensed by the U.S. Nuclear Regulatory Commission, NORM and TENORM facilities are regulated by the individual states. Current federal laws and regulations do not specify criteria for releasing these materials that may contain residual radioactivity of either man-made or natural origin from regulatory controls. In fact, the current regulatory scheme offers no explicit provision to permit materials being released as "non-radioactive," including those that are essentially free of contamination. The only method used to date with limited success has been case-by-case evaluation and approval. In addition, there is a poorly defined and inconsistent regulatory framework for regulating NORM and TENORM. Some years ago, the International Atomic Energy Agency introduced the concept of clearance, that is, controlling releases of any such materials within the regulatory domain. This paper aims to clarify clearance as an important disposition option for solid materials, establish the framework and basis of release, and discuss resolutions regarding the implementation of such a disposition option.

US regulatory system for genetically modified [genetically modified organism (GMO), rDNA or transgenic] crop cultivars.

PubMed

McHughen, Alan; Smyth, Stuart

2008-01-01

This paper reviews the history of the federal regulatory oversight of plant agricultural biotechnology in the USA, focusing on the scientific and political forces moulding the continually evolving regulatory structure in place today. Unlike most other jurisdictions, the USA decided to adapt pre-existing legislation to encompass products of biotechnology. In so doing, it established an overarching committee (Office of Science and Technology Policy) to study and distribute various regulatory responsibilities amongst relevant agencies: the Food and Drug Administration, Environmental Protection Agency and US Department of Agriculture. This paper reviews the history and procedures of each agency in the execution of its regulatory duties and investigates the advantages and disadvantages of the US regulatory strategy.

Modularity and design principles in the sea urchin embryo gene regulatory network

PubMed Central

Peter, Isabelle S.; Davidson, Eric H.

2010-01-01

The gene regulatory network (GRN) established experimentally for the pre-gastrular sea urchin embryo provides causal explanations of the biological functions required for spatial specification of embryonic regulatory states. Here we focus on the structure of the GRN which controls the progressive increase in complexity of territorial regulatory states during embryogenesis; and on the types of modular subcircuits of which the GRN is composed. Each of these subcircuit topologies executes a particular operation of spatial information processing. The GRN architecture reflects the particular mode of embryogenesis represented by sea urchin development. Network structure not only specifies the linkages constituting the genomic regulatory code for development, but also indicates the various regulatory requirements of regional developmental processes. PMID:19932099

The current status of NORM/TENORM industries and establishment of regulatory framework in Korea.

PubMed

Chang, Byung-Uck; Kim, Yongjae; Oh, Jang-Jin

2011-07-01

During the last several years, a nationwide survey on naturally occurring radioactive material (NORM)/technologically enhanced naturally occurring radioactive materials (TENORM) industries has been conducted. Because of the rapid economic growth in Korea, the huge amount of raw materials, including NORM have been consumed in various industrial areas, and some representative TENORM industries exist in Korea. Recently, the Korean government decided to establish a regulatory framework for natural radiation, including NORM/TENORM and is making efforts to introduce relevant publically consent regulations on the basis of international safety standards.

77 FR 4407 - Modernization of Poultry Slaughter Inspection

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-27

...The Food Safety and Inspection Service (FSIS) is proposing a new inspection system for young chicken and turkey slaughter establishments that would replace the current Streamlined Inspection System (SIS), the New Line Speed Inspection System (NELS), and the New Turkey Inspection System (NTIS). The Agency is also proposing several changes that would affect all establishments that slaughter poultry other than ratites, regardless of the inspection system under which they operate. This proposed rule is a result of the Agency's 2011 regulatory review efforts conducted under Executive Order 13563 on Improving Regulation and Regulatory Review.

“Nuisance Dust”: Unprotective Limits for Exposure to Coal Mine Dust in the United States, 1934–1969

PubMed Central

2013-01-01

I examine the dismissal of coal mine dust as a mere nuisance, not a potentially serious threat to extractive workers who inhaled it. In the 1930s, the US Public Health Service played a major role in conceptualizing coal mine dust as virtually harmless. Dissent from this position by some federal officials failed to dislodge either that view or the recommendation of minimal limitations on workplace exposure that flowed from it. Privatization of regulatory authority after 1940 ensured that miners would lack protection against respiratory disease. The reform effort that overturned the established misunderstanding in the late 1960s critically depended upon both the production of scientific findings and the emergence of a subaltern movement in the coalfields. This episode illuminates the steep challenges often facing advocates of stronger workplace health standards. PMID:23237176

Child Sexual Abuse in Zimbabwe.

PubMed

Mantula, Fennie; Saloojee, Haroon

2016-01-01

Although child sexual abuse is a significant public health problem globally, its incidence, prevention, and management is less well described in resource-poor settings. In poorer settings prevention initiatives assume even more importance since resources for managing abused children are severely limited. This article examines the current status of policy and practice related to the prevention of child sexual abuse in Zimbabwe. It identifies implementation challenges and highlights opportunities that could be embraced to reduce CSA in Zimbabwe, based on evidence synthesized from recent work. Although Zimbabwe has a well-established legal and regulatory framework to protect children from child sexual abuse, implementation of existing policies is weak. Financial, human, and material resource constraints are frequently cited to explain limited prevention activity. Effective strategies for the prevention of child sexual abuse should focus on implementing existing legislation, targeting schoolchildren, and getting community involvement. A dedicated budget would help entrench these strategies, but gains can be achieved even in the absence of this.

77 FR 47474 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

... Effectiveness of a Proposed Rule Change To Establish a Rule Regarding Records of Written Complaints for the CBOE... The Exchange proposes to establish a rule regarding records of written complaints that is specific to... Exchange proposes to establish Rule 53.7--CBSX Record of Written Complaints to formally establish a record...

Sharing regulatory data as tools for strengthening health systems in the Region of the Americas.

PubMed

Sousa, Varley Dias; Ramalho, Pedro I; Silveira, Dâmaris

2016-05-01

Regulatory transparency is an imperative characteristic of a reliable National Regulatory Authority. In the region of the Americas, the process of building an open government is still fragile and fragmented across various Health Regulatory Agencies (HRAs) and Regional Reference Authorities (RRAs). This study assessed the transparency status of RRAs, focusing on various medicine life-cycle documents (the Medicine Dossier, Clinical Trial Report, and Inspection Report) as tools for strengthening health systems. Based on a narrative (nonsystematic) review of RRA regulatory transparency, transparency status was classified as one of two types: public disclosure of information (intra-agency data) and data- and work-sharing (inter-agency data). The risks/benefits of public disclosure of medicine-related information were assessed, taking into account 1) the involvement and roles of multiple stakeholders (health care professionals, regulators, industry, community, and academics) and 2) the protection of commercial and personal confidential data. Inter-agency data- and work-sharing was evaluated in the context of harmonization and cooperation projects that focus on regulatory convergence. Technical and practical steps for establishing an openness directive for the pharmaceutical regulatory environment are proposed to improve and strengthen health systems in the Americas. Addressing these challenges requires leadership from entities such as the Pan American Health Organization to steer and support collaborative regional alliances that advance the development and establishment of a trustworthy regulatory environment and a sustainable public health system in the Americas, using international successful initiatives as reference and taking into account the domestic characteristics and experiences of each individual country.

77 FR 26061 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-02

...-Regulatory Organizations; Municipal Securities Rulemaking Board; Order Granting Approval of Proposed Rule Change Consisting of Establishment of a Subscription to Historical Information and Documents Submitted to... historical information and documents submitted to the MSRB's Short-Term Obligation Rate Transparency System...

78 FR 76751 - Safety Zone; Vessel Launch; Menominee River; Marinette, WI

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... Agriculture Regulatory Enforcement Ombudsman and the Regional Small Business Regulatory Fairness Boards. The... consensus standards. 14. Environment We have analyzed this rule under Department of Homeland Security... significant effect on the human environment. This rule involves the establishment of a safety zone and...

78 FR 909 - Further Proposed Guidance Regarding Compliance With Certain Swap Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-07

... establish a new regulatory framework for swaps. The legislation was enacted to reduce systemic risk... increase understanding of each other's regulatory approaches and to harmonize the cross-border approaches... may lead to divergent approaches to cross-border activities. The Commission also recognizes the...

10 CFR 7.1 - Policy.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Policy. 7.1 Section 7.1 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.1 Policy. The regulations in this part define the policies and procedures to be followed by the Nuclear Regulatory Commission in the establishment, utilization, and...

10 CFR 7.1 - Policy.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Policy. 7.1 Section 7.1 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.1 Policy. The regulations in this part define the policies and procedures to be followed by the Nuclear Regulatory Commission in the establishment, utilization, and...

10 CFR 7.1 - Policy.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Policy. 7.1 Section 7.1 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.1 Policy. The regulations in this part define the policies and procedures to be followed by the Nuclear Regulatory Commission in the establishment, utilization, and...

75 FR 13174 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-18

...-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Approving Proposed Rule Change To Establish Strike Price Intervals and Trading Hours for Options on Index-Linked Securities March 12, 2010. I. Introduction On January 27, 2010, the Chicago Board Options Exchange, Incorporated (``CBOE...

10 CFR 7.1 - Policy.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Policy. 7.1 Section 7.1 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.1 Policy. The regulations in this part define the policies and procedures to be followed by the Nuclear Regulatory Commission in the establishment, utilization, and...

10 CFR 7.1 - Policy.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Policy. 7.1 Section 7.1 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.1 Policy. The regulations in this part define the policies and procedures to be followed by the Nuclear Regulatory Commission in the establishment, utilization, and...

Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand.

PubMed

Rychert, Marta; Wilkins, Chris; Witten, Karen

2017-09-01

New Zealand's Psychoactive Substances Act (2013) established the world's first regulated market for 'low risk' psychoactive products ('legal highs'). Under an interim PSA regime, 47 existing products were permitted to be continued to be sold. To explore issues with the implementation of regulatory systems to monitor the safety of products on the legal market under the interim Psychoactive Substances Act regime. Semi-structured interviews with 30 key stakeholders, including industry, government agency, health and drug service professionals were conducted, transcribed and analysed thematically. In retrospect stakeholders questioned the decision to approve strong synthetic cannabinoid smoking products, noting their health risks because of product formulation, inconsistent manufacturing practices and smoking as the means of administration. Industry actors claimed the decision to approve synthetic cannabinoid smokeable products prevented potentially safer products from gaining market share. The system for withdrawing approved products which were subsequently found to be harmful was criticised for the poor quality of data available, limited engagement with health professionals and the slowness of product withdrawal. Many of the problems with the regime were attributed to the urgency under which the legal market under the interim Psychoactive Substances Act was established and implemented. The selection of 'safer' products, implementation of the product monitoring system, and engagement with health professionals may have benefited from more time and resources. An incremental approach to establishing the new market may have made the regulatory management of the new regime more workable. [Rychert M, Wilkins C, Witten K. Issues with monitoring the safety of psychoactive products under a legal regulated market for new psychoactive substances ('legal highs') in New Zealand. Drug Alcohol Rev 2017;00:000-000]. © 2017 Australasian Professional Society on Alcohol and other Drugs.

Per capita invasion probabilities: an empirical model to predict rates of invasion via ballast water

USGS Publications Warehouse

Reusser, Deborah A.; Lee, Henry; Frazier, Melanie; Ruiz, Gregory M.; Fofonoff, Paul W.; Minton, Mark S.; Miller, A. Whitman

2013-01-01

Ballast water discharges are a major source of species introductions into marine and estuarine ecosystems. To mitigate the introduction of new invaders into these ecosystems, many agencies are proposing standards that establish upper concentration limits for organisms in ballast discharge. Ideally, ballast discharge standards will be biologically defensible and adequately protective of the marine environment. We propose a new technique, the per capita invasion probability (PCIP), for managers to quantitatively evaluate the relative risk of different concentration-based ballast water discharge standards. PCIP represents the likelihood that a single discharged organism will become established as a new nonindigenous species. This value is calculated by dividing the total number of ballast water invaders per year by the total number of organisms discharged from ballast. Analysis was done at the coast-wide scale for the Atlantic, Gulf, and Pacific coasts, as well as the Great Lakes, to reduce uncertainty due to secondary invasions between estuaries on a single coast. The PCIP metric is then used to predict the rate of new ballast-associated invasions given various regulatory scenarios. Depending upon the assumptions used in the risk analysis, this approach predicts that approximately one new species will invade every 10–100 years with the International Maritime Organization (IMO) discharge standard of 50 μm per m3 of ballast. This approach resolves many of the limitations associated with other methods of establishing ecologically sound discharge standards, and it allows policy makers to use risk-based methodologies to establish biologically defensible discharge standards.

Strategic establishment of an International Pharmacology Specialty Laboratory in a resource-limited setting.

PubMed

Mtisi, Takudzwa J; Maponga, Charles; Monera-Penduka, Tsitsi G; Mudzviti, Tinashe; Chagwena, Dexter; Makita-Chingombe, Faithful; DiFranchesco, Robin; Morse, Gene D

2018-01-01

A growing number of drug development studies that include pharmacokinetic evaluations are conducted in regions lacking a specialised pharmacology laboratory. This necessitated the development of an International Pharmacology Specialty Laboratory (IPSL) in Zimbabwe. The aim of this article is to describe the development of an IPSL in Zimbabwe. The IPSL was developed collaboratively by the University of Zimbabwe and the University at Buffalo Center for Integrated Global Biomedical Sciences. Key stages included infrastructure development, establishment of quality management systems and collaborative mentorship in clinical pharmacology study design and chromatographic assay development and validation. Two high performance liquid chromatography instruments were donated by an instrument manufacturer and a contract research organisation. Laboratory space was acquired through association with the Zimbabwe national drug regulatory authority. Operational policies, standard operating procedures and a document control system were established. Scientists and technicians were trained in aspects relevant to IPSL operations. A high-performance liquid chromatography method for nevirapine was developed with the guidance of the Clinical Pharmacology Quality Assurance programme and approved by the assay method review programme. The University of Zimbabwe IPSL is engaged with the United States National Institute of Allergy and Infectious Diseases Division of AIDS research networks and is poised to begin drug assays and pharmacokinetic analyses. An IPSL has been successfully established in a resource-limited setting through the efforts of an external partnership providing technical guidance and motivated internal faculty and staff. Strategic partnerships were beneficial in navigating challenges leading to laboratory development and training new investigators. The IPSL is now engaged in clinical pharmacology research.

The use of Minilabs to improve the testing capacity of regulatory authorities in resource limited settings: Tanzanian experience.

PubMed

Risha, Peter Gasper; Msuya, Zera; Clark, Malcolm; Johnson, Keith; Ndomondo-Sigonda, Margareth; Layloff, Thomas

2008-08-01

The Tanzania Food and Drugs Authority piloted the use of Minilab kits, a thin-layer-chromatographic based drug quality testing technique, in a two-tier quality assurance program. The program is intended to improve testing capacity with timely screening of the quality of medicines as they enter the market. After 1 week training of inspectors on Minilab screening techniques, they were stationed at key Ports-of-Entry (POE) to screen the quality of imported medicines. In addition, three non-Ports-of-Entry centres were established to screen samples collected during Post-Marketing-Surveillance. Standard operating procedures (SOPs) were developed to structure and standardize the implementation process. Over 1200 samples were tested using the Minilab outside the central quality control laboratory (QCL), almost doubling the previous testing capacity. The program contributed to increased regulatory reach and visibility of the Authority throughout the country, serving as a deterrent against entry of substandard medicines into market. The use of Minilab for quality screening was inexpensive and provided a high sample throughput. However, it suffers from the limitation that it can reliably detect only grossly substandard or wrong drug samples and therefore, it should not be used as an independent testing resource but in conjunction with a full-service quality control laboratory capable of auditing reported substandard results.

10 CFR 7.5 - Consultation with Committee Management Secretariat on establishment of advisory committees...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Consultation with Committee Management Secretariat on establishment of advisory committees; advisory committee charters. 7.5 Section 7.5 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.5 Consultation with Committee Management Secretariat on establishment of...

10 CFR 7.5 - Consultation with Committee Management Secretariat on establishment of advisory committees...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Consultation with Committee Management Secretariat on establishment of advisory committees; advisory committee charters. 7.5 Section 7.5 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.5 Consultation with Committee Management Secretariat on establishment of...

10 CFR 7.5 - Consultation with Committee Management Secretariat on establishment of advisory committees...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Consultation with Committee Management Secretariat on establishment of advisory committees; advisory committee charters. 7.5 Section 7.5 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.5 Consultation with Committee Management Secretariat on establishment of...

10 CFR 7.5 - Consultation with Committee Management Secretariat on establishment of advisory committees...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Consultation with Committee Management Secretariat on establishment of advisory committees; advisory committee charters. 7.5 Section 7.5 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.5 Consultation with Committee Management Secretariat on establishment of...

10 CFR 7.5 - Consultation with Committee Management Secretariat on establishment of advisory committees...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Consultation with Committee Management Secretariat on establishment of advisory committees; advisory committee charters. 7.5 Section 7.5 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.5 Consultation with Committee Management Secretariat on establishment of...

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...

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...

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.

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.).

10 CFR 1.1 - Creation and authority.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Creation and authority. 1.1 Section 1.1 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.1 Creation and authority. (a) The Nuclear Regulatory Commission was established by the Energy Reorganization Act of 1974...

10 CFR 1.1 - Creation and authority.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Creation and authority. 1.1 Section 1.1 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.1 Creation and authority. (a) The Nuclear Regulatory Commission was established by the Energy Reorganization Act of 1974...

76 FR 12141 - New Postal Product and New Price Category

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-23 and CP2011-62; Order No. 683] New Postal Product and New Price Category AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The... competitive product list. The Postal Service also states that it has established a new price category under...

77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-10

... initiating and adjudicating various types of actions, including disciplinary, eligibility, expedited, and... also may review the decision. Oral Argument in Review of Proceedings FINRA Rule 9341(a) establishes the procedure for a party requesting an oral argument before the Subcommittee or, if applicable, the Extended...

10 CFR 1.1 - Creation and authority.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Creation and authority. 1.1 Section 1.1 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.1 Creation and authority. (a) The Nuclear Regulatory Commission was established by the Energy Reorganization Act of 1974...

10 CFR 1.1 - Creation and authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Creation and authority. 1.1 Section 1.1 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.1 Creation and authority. (a) The Nuclear Regulatory Commission was established by the Energy Reorganization Act of 1974...

10 CFR 1.1 - Creation and authority.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Creation and authority. 1.1 Section 1.1 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.1 Creation and authority. (a) The Nuclear Regulatory Commission was established by the Energy Reorganization Act of 1974...

76 FR 40738 - Agency Information Collection Activities: Proposed Collection; Comment Request; Standard Flood...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... Community Development and Regulatory Improvement Act of 1994 was signed into law. Section 303 (a) of this... requirement for federally regulated lending institutions to determine whether a building or mobile home... Regulatory Improvement Act of 1994. The establishment of the Standard Flood Hazard Determination form has...

Regulations: Can They Control Staff Compliance in Human Services Systems?

ERIC Educational Resources Information Center

Jacobson, John W.

1990-01-01

This article discusses results of regulations for Intermediate Care Facilities for the Mentally Retarded, arguing that, by establishing minimum standards for funding, these policies promote mediocrity. Strategies for promoting compliance behaviors are offered, as are observations on regulatory reform and the process of regulatory impact. (PB)

10 CFR 9.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Definitions. 9.3 Section 9.3 Energy NUCLEAR REGULATORY... the Nuclear Regulatory Commission, established by the Energy Reorganization Act of 1974. NRC personnel... members or a quorum thereof sitting as a body, as provided by section 201 of the Energy Reorganization Act...

10 CFR 9.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Definitions. 9.3 Section 9.3 Energy NUCLEAR REGULATORY... the Nuclear Regulatory Commission, established by the Energy Reorganization Act of 1974. NRC personnel... members or a quorum thereof sitting as a body, as provided by section 201 of the Energy Reorganization Act...

10 CFR 9.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Definitions. 9.3 Section 9.3 Energy NUCLEAR REGULATORY... the Nuclear Regulatory Commission, established by the Energy Reorganization Act of 1974. NRC personnel... members or a quorum thereof sitting as a body, as provided by section 201 of the Energy Reorganization Act...

47 CFR 1.1166 - Waivers, reductions and deferrals of regulatory fees.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fees. 1.1166 Section 1.1166 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND... deferrals of regulatory fees. The fees established by sections 1.1152 through 1.1156 may be waived, reduced... waiver, reduction or deferral of the fee would promote the public interest. Requests for waivers...

10 CFR 9.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Definitions. 9.3 Section 9.3 Energy NUCLEAR REGULATORY... the Nuclear Regulatory Commission, established by the Energy Reorganization Act of 1974. NRC personnel... members or a quorum thereof sitting as a body, as provided by section 201 of the Energy Reorganization Act...

10 CFR 9.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Definitions. 9.3 Section 9.3 Energy NUCLEAR REGULATORY... the Nuclear Regulatory Commission, established by the Energy Reorganization Act of 1974. NRC personnel... members or a quorum thereof sitting as a body, as provided by section 201 of the Energy Reorganization Act...

Development of a Course of Study in FDA Drug Regulatory Procedures

ERIC Educational Resources Information Center

Jacobs, Robin Wills; King, James C.

1977-01-01

It is evident that more colleges of pharmacy should establish some major course of study in the area of governmental drug regulatory procedures. This study is aimed at expanding cooperative educational programs through an FDA residency for pharmacy students and preparing a didactic course in FDA procedures. (LBH)

75 FR 60843 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-01

... Effectiveness of a Proposed Rule Change Relating to FINRA Trade Reporting Notice on Price Validation and Price... (``Notice'') that explains the price validation protocol of the FINRA trade reporting facilities and sets... trades by comparing the submitted price against price validation parameters established by FINRA...

The Deadly Dance of B Cells with Trypanosomatids.

PubMed

Silva-Barrios, Sasha; Charpentier, Tania; Stäger, Simona

2018-02-01

B cells are notorious actors for the host's protection against several infectious diseases. So much so that early vaccinology seated its principles upon their long-term protective antibody secretion capabilities. Indeed, there are many examples of acute infectious diseases that are combated by functional humoral responses. However, some chronic infectious diseases actively induce immune deregulations that often lead to defective, if not deleterious, humoral immune responses. In this review we summarize how Leishmania and Trypanosoma spp. directly manipulate B cell responses to induce polyclonal B cell activation, hypergammaglobulinemia, low-specificity antibodies, limited B cell survival, and regulatory B cells, contributing therefore to immunopathology and the establishment of persistent infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration of human pancreatic islet genomic data refines regulatory mechanisms at Type 2 Diabetes susceptibility loci

PubMed Central

Thurner, Matthias; van de Bunt, Martijn; Torres, Jason M; Mahajan, Anubha; Nylander, Vibe; Bennett, Amanda J; Gaulton, Kyle J; Barrett, Amy; Burrows, Carla; Bell, Christopher G; Lowe, Robert; Beck, Stephan; Rakyan, Vardhman K; Gloyn, Anna L

2018-01-01

Human genetic studies have emphasised the dominant contribution of pancreatic islet dysfunction to development of Type 2 Diabetes (T2D). However, limited annotation of the islet epigenome has constrained efforts to define the molecular mechanisms mediating the, largely regulatory, signals revealed by Genome-Wide Association Studies (GWAS). We characterised patterns of chromatin accessibility (ATAC-seq, n = 17) and DNA methylation (whole-genome bisulphite sequencing, n = 10) in human islets, generating high-resolution chromatin state maps through integration with established ChIP-seq marks. We found enrichment of GWAS signals for T2D and fasting glucose was concentrated in subsets of islet enhancers characterised by open chromatin and hypomethylation, with the former annotation predominant. At several loci (including CDC123, ADCY5, KLHDC5) the combination of fine-mapping genetic data and chromatin state enrichment maps, supplemented by allelic imbalance in chromatin accessibility pinpointed likely causal variants. The combination of increasingly-precise genetic and islet epigenomic information accelerates definition of causal mechanisms implicated in T2D pathogenesis. PMID:29412141

Biomarkers as drug development tools: discovery, validation, qualification and use.

PubMed

Kraus, Virginia B

2018-06-01

The 21st Century Cures Act, approved in the USA in December 2016, has encouraged the establishment of the national Precision Medicine Initiative and the augmentation of efforts to address disease prevention, diagnosis and treatment on the basis of a molecular understanding of disease. The Act adopts into law the formal process, developed by the FDA, of qualification of drug development tools, including biomarkers and clinical outcome assessments, to increase the efficiency of clinical trials and encourage an era of molecular medicine. The FDA and European Medicines Agency (EMA) have developed similar processes for the qualification of biomarkers intended for use as companion diagnostics or for development and regulatory approval of a drug or therapeutic. Biomarkers that are used exclusively for the diagnosis, monitoring or stratification of patients in clinical trials are not subject to regulatory approval, although their qualification can facilitate the conduct of a trial. In this Review, the salient features of biomarker discovery, analytical validation, clinical qualification and utilization are described in order to provide an understanding of the process of biomarker development and, through this understanding, convey an appreciation of their potential advantages and limitations.

Voluntary coordination as a strategy of plan implementation for health systems agencies.

PubMed

Berry, D E; Candia, G R

1979-10-01

Health planning agencies are faced with the difficult mission of guiding change within a large complex social system whose power is dispersed. Initial short- and long-range plans have been established as frameworks, and now the major focus is implementation. Regulation (non-voluntary coordination) and voluntary coordination are the major means of implementation. Voluntary coordination is a significant strategy for consideration by Health Systems Agencies (HSAs). It may interact with regulation as a competitor, substitute, or complement. Because of limited regulatory powers, HSAs are dependent upon voluntary coordination as a major means of influencing behavior. Conflict, a major feature of voluntary coordination, has the potential of being used as a constructive means for dialogue; negotiation and bargaining may become positive approaches to arriving at decisions. Legitimized community authority is the primary source of authority in a strategy dominated by voluntary coordination as contrasted to state or federal mandates in a regulatory strategy. Knowledge of the environment within which the HSA operates will assist HSA staff and board to arrive at rational and realistic decisions.

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.

[CD4 + CD25 + regulatory T cells and their importance to human illnesses].

PubMed

Kelsen, Jens; Hvas, Christian Lodberg; Agnholt, Jørgen; Dahlerup, Jens F

2006-01-03

Regulatory T cells ensure a balanced immune response that is competent both to fight pathogens, at the same time, to recognize self-antigens and commensals as harmless. Regulatory mechanisms are essential in preventing autoimmune disorders but may also facilitate the progression of malignant diseases and the establishment of latent infections via suppression of the host immune response. Regulatory T cells arise in the thymus, and regulatory T cell function can be induced in the periphery, so-called infectious tolerance. An absolute or relative defect in regulatory T cell function may contribute to the development of autoimmune disorders such as rheumatoid arthritis, type 1 diabetes mellitus, multiple sclerosis and chronic inflammatory bowel disease. Regulatory T cell therapy is a tempting strategy for reestablishing the immune balance and thus preventing or reversing these disorders. Reestablishment of the immune balance may be accomplished by adoptive transfer of ex vivo-propagated regulatory T cells or by induction of regulatory functions locally in the organs, although such strategies are in their infancy in human research.

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

RCRA, superfund and EPCRA hotline training module. Introduction to: RCRA corrective action updated July 1996

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

NONE

1996-07-01

The module discusses the regulatory and statutory requirements and authorities governing the Resource Conservation and Recovery Act (RCRA) corrective action process. There are minimal regulatory requirements at present, but the Agency has issued a proposed rule (55 FR 30798; July 27, 1990) that would establish a comprehensive regulatory framework for implementing the corrective action program. This proposed rule and other guidance developed pursuant to statutory authorities are used to structure corrective action requirements in facility permits and orders. This module describes the current statutory and regulatory structure and discusses the future of the proposed rule.

Establishing Policy Foundations and Regulatory Systems to Enhance Nursing Practice in the United Arab Emirates.

PubMed

Brownie, Sharon M; Hunter, Lyndal H; Aqtash, Salah; Day, Gary E

2015-01-01

In 2009, the United Arab Emirates (UAE) established a Nursing and Midwifery Council with a mandate to develop standards for the registration and regulation of nursing and midwifery and to strengthen the nursing and midwifery workforce. Priorities included workforce Emiratization and the development of regulatory standards to support advanced and speciality nursing practice and new models of care-particularly for the management of noncommunicable diseases. This article provides background, context for, and best practice inputs to the effort to provide one unified framework of nursing regulation and licensure across the whole of the UAE. This article is intended for nurse leaders, policy makers, and regulators who are reviewing or developing nursing regulatory processes and advancing nursing workforce capacity building activities; and nurse educators and nurses wishing to work in the UAE. © The Author(s) 2015.

Establishing Policy Foundations and Regulatory Systems to Enhance Nursing Practice in the United Arab Emirates

PubMed Central

Hunter, Lyndal H.; Aqtash, Salah; Day, Gary E.

2015-01-01

In 2009, the United Arab Emirates (UAE) established a Nursing and Midwifery Council with a mandate to develop standards for the registration and regulation of nursing and midwifery and to strengthen the nursing and midwifery workforce. Priorities included workforce Emiratization and the development of regulatory standards to support advanced and speciality nursing practice and new models of care—particularly for the management of noncommunicable diseases. This article provides background, context for, and best practice inputs to the effort to provide one unified framework of nursing regulation and licensure across the whole of the UAE. This article is intended for nurse leaders, policy makers, and regulators who are reviewing or developing nursing regulatory processes and advancing nursing workforce capacity building activities; and nurse educators and nurses wishing to work in the UAE. PMID:25944674

FoxP3 Expression in Macrophages, Cancer, and B Cells-Is It Real?

PubMed

Vadasz, Zahava; Toubi, Elias

2017-06-01

During the last decade, B regulatory cells are appreciated to have a central role in preventing autoimmunity and maintaining self-tolerance. They are characterized by expressing different phenotypic markers and the production of either IL-10 or TGF-β or both. The recent recognition of Fas ligand expressing B regulatory cells as "killer" cells established their role in maintaining viral persistence by preventing effective antiviral immune responses. The forkhead lineage-transcription factor (FoxP3) was considered for many years to be a highly specific intracellular regulatory marker of CD4+CD25+ T regulatory cells. The possibility of FoxP3 being expressed in B regulatory cells was suggested in many studies. Though controversial, FoxP3 expression was also reported in macrophages and cancer cells. Aiming to avoid artifact staining, many researchers required the usage of FoxP3 messenger RNA (mRNA) and PCR in order to prove a true expression of FoxP3 in these different cells. In addition, most studies' report on that FoxP3 expression in all abovementioned cells is related to their status of activation since naïve (non-activated cells) were found poorly FoxP3 expressing. In this review, we present the existing data on FoxP3 expression in non-T-regulatory cells, but we suggest that further studies are needed to better establish this concept.

75 FR 76729 - Market Access Agreement

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-09

... falls below pre-established financial performance thresholds. The draft amendment (MAA Amendment) is... System banks and the Funding Corporation that establishes certain financial performance criteria. Under... Agreement). FOR FURTHER INFORMATION CONTACT: Chris Wilson, Financial Analyst, Office of Regulatory Policy...

Risk Analysis as Regulatory Science: Toward The Establishment of Standards

PubMed Central

Murakami, Michio

2016-01-01

Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional ‘Standard I’, which has a paternalistic orientation, and ‘Standard II’, established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being. PMID:27475751

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

PubMed

Murakami, Michio

2016-09-01

Understanding how to establish standards is essential for risk communication and also provides perspectives for further study. In this paper, the concept of risk analysis as regulatory science for the establishment of standards is demonstrated through examples of standards for evacuation and provisional regulation values in foods and drinking water. Moreover, academic needs for further studies related to standards are extracted. The concepts of the traditional 'Standard I', which has a paternalistic orientation, and 'Standard II', established through stakeholder consensus, are then systemized by introducing the current status of the new standards-related movement that developed after the Fukushima nuclear power plant accident, and the perspectives of the standards are discussed. Preparation of standards on the basis of stakeholder consensus through intensive risk dialogue before a potential nuclear power plant accident is suggested to be a promising approach to ensure a safe society and enhance subjective well-being. © The Author 2016. Published by Oxford University Press.

Gene network analysis: from heart development to cardiac therapy.

PubMed

Ferrazzi, Fulvia; Bellazzi, Riccardo; Engel, Felix B

2015-03-01

Networks offer a flexible framework to represent and analyse the complex interactions between components of cellular systems. In particular gene networks inferred from expression data can support the identification of novel hypotheses on regulatory processes. In this review we focus on the use of gene network analysis in the study of heart development. Understanding heart development will promote the elucidation of the aetiology of congenital heart disease and thus possibly improve diagnostics. Moreover, it will help to establish cardiac therapies. For example, understanding cardiac differentiation during development will help to guide stem cell differentiation required for cardiac tissue engineering or to enhance endogenous repair mechanisms. We introduce different methodological frameworks to infer networks from expression data such as Boolean and Bayesian networks. Then we present currently available temporal expression data in heart development and discuss the use of network-based approaches in published studies. Collectively, our literature-based analysis indicates that gene network analysis constitutes a promising opportunity to infer therapy-relevant regulatory processes in heart development. However, the use of network-based approaches has so far been limited by the small amount of samples in available datasets. Thus, we propose to acquire high-resolution temporal expression data to improve the mathematical descriptions of regulatory processes obtained with gene network inference methodologies. Especially probabilistic methods that accommodate the intrinsic variability of biological systems have the potential to contribute to a deeper understanding of heart development.

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

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

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... 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...

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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...

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... 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...

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

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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.

A proximity-based graph clustering method for the identification and application of transcription factor clusters.

PubMed

Spadafore, Maxwell; Najarian, Kayvan; Boyle, Alan P

2017-11-29

Transcription factors (TFs) form a complex regulatory network within the cell that is crucial to cell functioning and human health. While methods to establish where a TF binds to DNA are well established, these methods provide no information describing how TFs interact with one another when they do bind. TFs tend to bind the genome in clusters, and current methods to identify these clusters are either limited in scope, unable to detect relationships beyond motif similarity, or not applied to TF-TF interactions. Here, we present a proximity-based graph clustering approach to identify TF clusters using either ChIP-seq or motif search data. We use TF co-occurrence to construct a filtered, normalized adjacency matrix and use the Markov Clustering Algorithm to partition the graph while maintaining TF-cluster and cluster-cluster interactions. We then apply our graph structure beyond clustering, using it to increase the accuracy of motif-based TFBS searching for an example TF. We show that our method produces small, manageable clusters that encapsulate many known, experimentally validated transcription factor interactions and that our method is capable of capturing interactions that motif similarity methods might miss. Our graph structure is able to significantly increase the accuracy of motif TFBS searching, demonstrating that the TF-TF connections within the graph correlate with biological TF-TF interactions. The interactions identified by our method correspond to biological reality and allow for fast exploration of TF clustering and regulatory dynamics.

Quantification of patulin in fruit leathers by ultra-high-performance liquid chromatography-photodiode array (UPLC-PDA).

PubMed

Maragos, Chris M; Busman, Mark; Ma, Liang; Bobell, John

2015-01-01

Patulin is a mycotoxin commonly found in certain fruit and fruit products. For this reason many countries have established regulatory limits pertaining to, in particular, apple juice and apple products. Fruit leathers are produced by dehydrating fruit puree, leaving a sweet product that has a leathery texture. A recent report in the literature described the detection of patulin at substantial levels in fruit leathers. To investigate this further, an ultra-high-performance liquid chromatography-photodiode array (UPLC-PDA) method was developed for the sensitive detection of patulin in fruit leathers. Investigations were also made of the suitability of direct analysis in real time-mass spectrometry (DART-MS) for detection of patulin from the surface of fruit leathers. Results indicated DART-MS was insufficiently sensitive for quantification from the surface of home-style apple leathers, although patulin spiked onto the surface of leather or peel could be detected. The UPLC-PDA method was used to determine the fate of patulin during the preparation of home-made fruit leathers. Interestingly, when a home-style process was used, the patulin was not destroyed, but rather increased in concentration as the puree was dehydrated. The UPLC-PDA method was also used to screen for patulin in commercial fruit leathers. Of the 36 products tested, 14 were above the limit of detection (3.5 μg kg(-1)) and nine were above the limit of quantification (12 μg kg(-1)). Positive samples were confirmed by UPLC-MS/MS. Only one sample was found above the US regulatory limit for single-strength apple juice products (50 μg kg(-1)). These results suggest patulin can be concentrated during preparation and can be found in fruit leathers. The limited survey suggests that patulin is fairly prevalent in such commercial products, but that the levels are usually low.

75 FR 16869 - Areva Enrichment Services, LLC; Establishment of Atomic Safety and Licensing Board

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76 FR 79229 - Exelon Generation Company, LLC; Establishment of Atomic Safety and Licensing Board

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48 CFR 8.404 - Use of Federal Supply Schedules.

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... considered to be issued using full and open competition (see 6.102(d)(3)). Therefore, when establishing a BPA..., when placing an order or establishing a BPA, is responsible for applying the regulatory and statutory requirements applicable to the agency for which the order is placed or the BPA is established. The requiring...

48 CFR 8.404 - Use of Federal Supply Schedules.

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48 CFR 8.404 - Use of Federal Supply Schedules.

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48 CFR 8.404 - Use of Federal Supply Schedules.

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... 10 Energy 1 2013-01-01 2013-01-01 false Public notice of advisory committee establishment, reestablishment, or renewal. 7.9 Section 7.9 Energy NUCLEAR REGULATORY COMMISSION ADVISORY COMMITTEES § 7.9 Public notice of advisory committee establishment, reestablishment, or renewal. (a) After the Commission has...

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2011-01-01

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76 FR 2182 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Granting Approval of Proposed Rule...

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75 FR 39721 - Self-Regulatory Organizations; National Securities Clearing Corporation; Notice of Filing and...

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18 CFR 367.2540 - Account 254, Other regulatory liabilities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... accounts, imposed on the service company by the ratemaking actions of regulatory agencies. (See Definitions § 367.1(a)(38).) (b) The amounts included in this account are to be established by those credits which... authorized to charge for its services; or refunds to customers, not provided for in other accounts, will be...

18 CFR 367.1823 - Account 182.3, Other regulatory assets.

Code of Federal Regulations, 2010 CFR

2010-04-01

...).) (b) The amounts included in this account are to be established by those charges which would have been... account are generally to be charged, concurrently with the recovery of the amounts in rates, to the same account that would have been charged if included in income when incurred, except all regulatory assets...

75 FR 74117 - Self-Regulatory Organizations; National Securities Clearing Corporation; Notice of Filing of...

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2011-11-23

... Officer copies of documentary exhibits the parties intend to introduce and the names of the witnesses each party intends to present at a hearing. Currently, pre-hearing, proposed documentary evidence submitted... change amends FINRA Rule 9261(a) to establish that documentary evidence submitted prior to a hearing...

78 FR 68840 - Public Workshop: Follow-On Biologics: Impact of Recent Legislative and Regulatory Naming...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... Accountability Office, Food and Drug Administration: Response to Heparin Contamination Helped Protect Public... obtain approval from the Food & Drug Administration (``FDA'') pursuant to an abbreviated regulatory pathway established by the Hatch-Waxman Act.\\1\\ \\1\\ See The Federal Food, Drug, and Cosmetic Act, 21 U.S.C...

78 FR 20325 - 2013 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

... Quality and Compliance Throughout the Product Life Cycle in a Global Regulatory Environment AGENCY: Food... Environment.'' The conference will cover current issues affecting the industry as well as explore strategies... improvement of safe and effective medical products. The conference establishes a unique forum to discuss the...

78 FR 4917 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-23

... establish two new optional TRACE data delivery services, TRACE Data Delivery Plus and TRACE Data Delivery... Data Delivery Plus would provide greater access to TRACE trade journal files by allowing an MPID... the free FINRA ADDS service, firms interested in TRACE Data Delivery Plus must subscribe per MPID. To...

76 FR 5412 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-31

...); ISE Semiconductors (BYT); ISE Electronic Trading (DMA); ISE-Revere Natural Gas (FUM); ISE Water (HHO... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63761; File No. SR-ISE-2011-04] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of Proposed Rule Change To Establish a...

Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells

PubMed Central

Leddin, Mathias; Perrod, Chiara; Hoogenkamp, Maarten; Ghani, Saeed; Assi, Salam; Heinz, Sven; Wilson, Nicola K.; Follows, George; Schönheit, Jörg; Vockentanz, Lena; Mosammam, Ali M.; Chen, Wei; Tenen, Daniel G.; Westhead, David R.; Göttgens, Berthold

2011-01-01

The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type–specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. PMID:21239694

Complex mixtures in industrial workspaces: lessons for indoor air quality evaluations.

PubMed

Lippy, B E; Turner, R W

1991-11-01

Acceptable occupational exposure levels for hundreds of airborne concentrations of dusts, vapors, fumes, and gases have been set by consensus organizations and regulatory bodies for decades. These levels have established tremendous precedent and are tempting reference values in the relatively new field of indoor air quality evaluations where validated criteria are greatly needed. The American Conference of Government Industrial Hygienists (ACGIH) has been the most visible and productive group setting these guidelines for industrial exposure. The ACGIH Chemical Substances Committee has published an annual list of threshold limit values (TLVs) for more than 40 years. Currently the list covers more than 400 substances. In 1989, the Occupational Safety and Health Administration (OSHA) published updated permissible exposure limits (PELs) for approximately 600 substances. Most PELs before this update were adopted from the 1968 ACGIH list of TLVs and consensus standards of the American Standards Association. This OSHA update has resulted in reductions of 212 PELs and the addition of 164 new levels. The magnitude of the problem of protecting workers can be seen by the small fraction that the OSHA PELs represent of the more than 60,000 entries in the National Institute for Occupational Safety and Health's Registry of Toxic Effects of Chemical Substances. None of these levels, whether guidelines or regulatory requirements, are established based on any possible synergistic effect with other chemicals. The only guidance given by the ACGIH for synergistic effects is that such cases must be determined individually. Clearly, there are major drawbacks in using occupational standards and guidelines for evaluating the health effects of chemical agents that can be found in office settings, often in concentrations orders of magnitude less than what is routinely measured in the workplace. These guidelines are even less valuable when the concern is the complex mixing of chemicals in nonoccupational environments.

[European Marketing Authorisation: a long process. Experiences of small biotech companies with the ATMP regulation].

PubMed

Buljovčić, Z

2011-07-01

On 30 December 2008, the Regulation (EC) 1394/2007 on advanced therapy medicinal products (ATMPs) entered into force. Herewith the first EU-wide regulatory framework for ATMPs was established. It requires a central marketing authorisation application to the EMA (European Medicinal Agency). This new framework especially changes the code of regulatory practice for tissue engineered products (TEPs), as no registration procedure had been previously required for autologous TEPs. This also meant that no clinical proof of efficacy achieved by a pivotal clinical trial was necessary. Difficulties and their background as well as the vast requirements for product development that have to be addressed by small companies within a very short time frame are presented. Hereby, it is obvious that regulatory experience which is required to identify and implement the resulting implications was not in place yet and still had to be established. The lack of regulatory experience also resulted in difficulties with scientific advice preparation, expectations toward regulatory agencies, consultants, and transformation of regulatory requirements. Addressing the regulatory requirements within the transition period is even more difficult for entrepreneurs with products which are assigned for indications resulting in complex challenges to the trial design. Due to the enormous time pressure to generate data and due to the implied financial pressure, different adaptation strategies are evolving. In Germany the "hospital exemption" according to §4b AMG (German Medicinal Products Law) is of major importance. A reorientation toward acellular products and a slow down in development of new ATMP products is expected.

[Better medical devices regulations for better health care: enlightenment for medical devices regulatory reform in China, from experiences of the E.U. and the U.S.A].

PubMed

Sun, Qin; Yan, Liang

2006-01-01

The expansion of applications of medical devices has attracted the increased attention of government regulatory bodies around the world to the safety and effectiveness of these products. Most developed countries, such as the United States and European Union, have developed well-established regulatory systems for medical devices, which have also consistently been amended to accommodate the changing requirements of safety and the trend of globalization.The current "Regulations for the Supervision and Administration of Medical Device (China)", established in 2000, has brought about great improvements for the safety and effectiveness of products, safeguarding public health. But there are still, at present, a lot of counterfeit and poor quality devices and device-related adverse events for lack of powerful post -market and in-use regulatory controls for products. It is therefore very urgent for the Chinese government to reform its medical device administration and management. This research paper analyses and compares the different requirements and executions of medical devices regulations in the EU, the US and China, to draw some experiences of the EU and US regimes that are very useful to China's regulatory reform. It is suggested that when developing a new scheme of medical devices regulatory reform in China, two prominent aspects have to be considered by policy makers and regulators. Firstly, the global trend of medical devices regulations has to be taken into account. Secondly, the experiences learned from the EU and US systems should be applied to the Chinese regulatory reform in combination with the concrete practice of China.

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

Evaluating confidence in the impact of regulatory nutrient reduction and assessing the competing impact of climate change

NASA Astrophysics Data System (ADS)

Irby, I.; Friedrichs, M. A. M.

2017-12-01

Human impacts on the Chesapeake Bay through increased nutrient run-off as a result of land-use change, urbanization, and industrialization, have resulted in a degradation of water quality over the last half-century. These direct impacts, compounded with human-induced climate changes such as warming, rising sea level, and changes in precipitation, have elevated the conversation surrounding the future of the Bay's water quality. As a result, in 2010, a Total Maximum Daily Load (TMDL) was established for the Chesapeake Bay that limited nutrient and sediment input in an effort to increase dissolved oxygen. This research utilizes a multiple model approach to evaluate confidence in the estuarine water quality modeling portion of the TMDL. One of the models is then used to assess the potential impact climate change may have on the success of currently mandated nutrient reduction levels in 2050. Results demonstrate that although the models examined differ structurally and in biogeochemical complexity, they project a similar attainment of regulatory water quality standards after nutrient reduction, while also establishing that meeting water quality standards is relatively independent of hydrologic conditions. By developing a Confidence Index, this research identifies the locations and causes of greatest uncertainty in modeled projections of water quality. Although there are specific locations and times where the models disagree, this research lends an increased degree of confidence in the appropriateness of the TMDL levels and in the general impact nutrient reductions will have on Chesapeake Bay water quality under current environmental conditions. However, when examining the potential impacts of climate change, this research shows that the combined impacts of increasing temperature, sea level, and river flow negatively affect dissolved oxygen throughout the Chesapeake Bay and impact progress towards meeting the water quality standards associated with the TMDL with increased temperature as the primary culprit. These results, having been continually shared with the regulatory TMDL modelers, will aid in the decision making for the 2017 TMDL Mid-Point Assessment.

Comparative assessment of status and opportunities for carbon Dioxide Capture and storage and Radioactive Waste Disposal In North America

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

Oldenburg, C.; Birkholzer, J.T.

Aside from the target storage regions being underground, geologic carbon sequestration (GCS) and radioactive waste disposal (RWD) share little in common in North America. The large volume of carbon dioxide (CO{sub 2}) needed to be sequestered along with its relatively benign health effects present a sharp contrast to the limited volumes and hazardous nature of high-level radioactive waste (RW). There is well-documented capacity in North America for 100 years or more of sequestration of CO{sub 2} from coal-fired power plants. Aside from economics, the challenges of GCS include lack of fully established legal and regulatory framework for ownership of injectedmore » CO{sub 2}, the need for an expanded pipeline infrastructure, and public acceptance of the technology. As for RW, the USA had proposed the unsaturated tuffs of Yucca Mountain, Nevada, as the region's first high-level RWD site before removing it from consideration in early 2009. The Canadian RW program is currently evolving with options that range from geologic disposal to both decentralized and centralized permanent storage in surface facilities. Both the USA and Canada have established legal and regulatory frameworks for RWD. The most challenging technical issue for RWD is the need to predict repository performance on extremely long time scales (10{sup 4}-10{sup 6} years). While attitudes toward nuclear power are rapidly changing as fossil-fuel costs soar and changes in climate occur, public perception remains the most serious challenge to opening RW repositories. Because of the many significant differences between RWD and GCS, there is little that can be shared between them from regulatory, legal, transportation, or economic perspectives. As for public perception, there is currently an opportunity to engage the public on the benefits and risks of both GCS and RWD as they learn more about the urgent energy-climate crisis created by greenhouse gas emissions from current fossil-fuel combustion practices.« less

A Hox regulatory network establishes motor neuron pool identity and target-muscle connectivity.

PubMed

Dasen, Jeremy S; Tice, Bonnie C; Brenner-Morton, Susan; Jessell, Thomas M

2005-11-04

Spinal motor neurons acquire specialized "pool" identities that determine their ability to form selective connections with target muscles in the limb, but the molecular basis of this striking example of neuronal specificity has remained unclear. We show here that a Hox transcriptional regulatory network specifies motor neuron pool identity and connectivity. Two interdependent sets of Hox regulatory interactions operate within motor neurons, one assigning rostrocaudal motor pool position and a second directing motor pool diversity at a single segmental level. This Hox regulatory network directs the downstream transcriptional identity of motor neuron pools and defines the pattern of target-muscle connectivity.

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

Identification and assessment of endocrine disruptors: limitations of in vivo and in vitro assays.

PubMed Central

Zacharewski, T

1998-01-01

It has been suggested that chemicals and complex mixtures capable of modulating the endocrine system may contribute to adverse health, reproduction, and developmental effects in humans and wildlife. These effects include increased incidence of hormone-dependent cancers, compromised reproductive fitness, and abnormal reproductive system development. In response to public concern, regulatory agencies in North America and Europe are formulating potential strategies to systematically test chemicals and complex mixtures for their endocrine-disrupting activities. Because of the complexity of the endocrine system and the number of potential endocrine disruptor targets, a tiered approach involving a complementary battery of short- and long-term in vivo and in vitro assays that assesses both receptor and nonreceptor-mediated mechanisms of action is being considered. However, the available established assays use a limited number of end points, and significant information gaps exist for other potential targets in the endocrine system. In addition to discussing the merits and limitations of the assays that may be adopted, this paper also highlights potential problems associated with the use of a tiered testing strategy. PMID:9599705

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...

78 FR 28917 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... Change Establishing Non- Display Usage Fees and Amending the Professional End-User Fees for NYSE Arca... Proposed Rule Change The Exchange proposes to establish non-display usage fees and to amend the... Proposed Rule Change 1. Purpose The Exchange proposes to establish non-display usage fees and to amend the...

76 FR 65765 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... Proposed Rule Change Relating to the Establishment of a Direct Market Data Product, NASDAQ Options Trade... establish a direct market data product, NASDAQ Options Trade Outline (``NOTO''). The text of the proposed.... Purpose The purpose of the proposed rule change is to establish the NOTO market data product. NOTO is a...

75 FR 27608 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-17

... Change To Establish Strike Price Intervals and Trading Hours for Options on Index Linked Securities May....4 Commentary .05 to establish strike price intervals for options on Index Linked Securities,\\3\\ and... Rule 7.1 Commentary .02 to establish strike price intervals and trading hours for options on Index...

75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-01

... closely the governance structure of the FINRA Board. Section 4.3--Qualifications The proposed rule change would amend Article IV, section 4.3(a) to reflect FINRA's current governance structure by establishing... to Article IV, section 4.3 as follows: Re-structure the Board to remove the President of NASD Dispute...

75 FR 24786 - List of Approved Spent Fuel Storage Casks: NUHOMS® HD System Revision 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-06

... of establishing one or more technologies that the [Nuclear Regulatory] Commission may, by rule... technology approved by the Commission under Section 218(a) for use at the site of any civilian nuclear power... NUCLEAR REGULATORY COMMISSION 10 CFR Part 72 RIN 3150-AI75 [NRC-2009-0538] List of Approved Spent...

75 FR 33678 - List of Approved Spent Fuel Storage Casks: MAGNASTOR System, Revision 1

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-15

... of establishing one or more technologies that the [Nuclear Regulatory] Commission may, by rule... technology approved by the Commission under Section 218(a) for use at the site of any civilian nuclear power... NUCLEAR REGULATORY COMMISSION 10 CFR Part 72 [NRC-2010-0140] RIN 3150-AI86 List of Approved Spent...

78 FR 15394 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-11

...-Regulatory Organizations; New York Stock Exchange LLC; Order Approving Proposed Rule Change Adopting... paragraph (d) it contains a provision establishing how the transition period from NYSE Rule 477 will work... to announce the effective date of the new rules at least 30 days in advance in an Information...

77 FR 31050 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... from NASDAQ Rule 2460 (Payment for Market Making). Accordingly, the Commission, pursuant to Section 19...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change, as Modified by Amendment No. 1 Thereto, To Establish the Market...

75 FR 48391 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62639; File No. SR-Phlx-2010-89] Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Order Approving a Proposed Rule Change Relating to Pricing... proposed rule change to establish pricing for 10Gb direct circuit connections and codify pricing for 10Gb...

75 FR 48390 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62638; File No. SR-BX-2010-043] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change Relating to Pricing for Direct... establish pricing for 10Gb direct circuit connections and codify pricing for 1Gb direct circuit connections...

77 FR 12340 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... change to adopt Section 14 to Schedule A of the FINRA By- Laws to establish an accounting support fee to adequately fund the annual budget of the Governmental Accounting Standards Board (``GASB''). The proposed... fee to adequately fund the annual budget of the GASB (``GASB Accounting Support Fee''), and rules and...

78 FR 62788 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... fees for real- time and historic data sets of transactions in TRACE-Eligible Securities \\5\\ that are... data sets; and (3) make other technical amendments. \\5\\ The term TRACE-Eligible Security is defined in... transactions and to establish real-time and historic data sets for Rule 144A transactions. The effective date...

75 FR 37864 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-30

... and Rules To Establish a Clearing Fund Amount Intended To Support Losses Under a Defined Set of... intended to support losses under a defined set of default scenarios. II. Self-Regulatory Organization's... discussed any comments it received on the proposed rule change. The text of these statements may be examined...

77 FR 39314 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-02

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change To Establish ``Benchmark Orders'' Under NASDAQ Rule 4751(f) June 26, 2012. On May 1, 2012, The NASDAQ Stock Market LLC (``NASDAQ'' or ``Exchange'') filed with the...

39 CFR 3002.10 - The Commission and its offices.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false The Commission and its offices. 3002.10 Section 3002.10 Postal Service POSTAL REGULATORY COMMISSION PERSONNEL ORGANIZATION § 3002.10 The Commission and its offices. (a) The Commissioners. The Postal Regulatory Commission is an independent establishment of the executive branch of the U.S. Government...

MicroRNA regulation of immune events at conception.

PubMed

Robertson, Sarah A; Zhang, Bihong; Chan, Honyueng; Sharkey, David J; Barry, Simon C; Fullston, Tod; Schjenken, John E

2017-09-01

The reproductive tract environment at conception programs the developmental trajectory of the embryo, sets the course of pregnancy, and impacts offspring phenotype and health. Despite the fundamental importance of this stage of reproduction, the rate-limiting regulatory mechanisms operating locally to control fertility and fecundity are incompletely understood. Emerging studies highlight roles for microRNAs (miRNAs) in regulating reproductive and developmental processes and in modulating the quality and strength of the female immune response. Since endometrial receptivity and robust placentation require specific adaptation of the immune response, we hypothesize that miRNAs participate in establishing pregnancy through effects on key gene networks in immune cells. Our recent studies investigated miRNAs that are induced in the peri-conception environment, focusing on miRNAs that have immune-regulatory roles-particularly miR-223, miR-155, and miR-146a. Genetic mouse models deficient in individual miRNAs are proving informative in defining roles for these miRNAs in the generation and stabilization of regulatory T cells (Treg cells) that confer adaptive immune tolerance. Overlapping and redundant functions between miRNAs that target multiple genes, combined with multiple miRNAs targeting individual genes, indicate complex and sensitive regulatory networks. Although to date most data on miRNA regulation of reproductive events are from mice, conserved functions of miRNAs across species imply similar biological pathways operate in all mammals. Understanding the regulation and roles of miRNAs in the peri-conception immune response will advance our knowledge of how environmental determinants act at conception, and could have practical applications for animal breeding as well as human fertility. © 2017 Wiley Periodicals, Inc.

10 CFR 1.55 - Establishment of official NRC flag.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Establishment of official NRC flag. 1.55 Section 1.55 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION NRC Seal and Flag... dark blue field with a gold fringe. ...

78 FR 51780 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Designation of Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... and To Establish a Five-Year Fee for the Development of an Enhanced Brokers Internet Platform August... and to establish a five-year fee for the development of an enhanced brokers internet platform. The...

Health Effects of Environmental Exposures, Occupational Hazards and Climate Change in Ethiopia: Synthesis of Situational Analysis, Needs Assessment and the Way Forward.

PubMed

Berhane, Kiros; Kumie, Abera; Samet, Jonathan

2016-01-01

The burden of diseases caused by environmental and occupational health hazards and the effects of global climate change are of growing concerns in Ethiopia. However, no adequate information seems to be available on the current situation. This means there is a critical gap in research, policy framework and implementation in the country. The purpose of this paper was to synthesize evidence from a systematic situational analysis and needs assessment to help establish a hub for research and training on three major themes and their related policy frameworks: air pollution and health, occupational health and safety and climate change and health. The methods used in this work include a systematic review of secondary data from peer-reviewed literature, thesis reports from academia, government and national statistical reports. Limited primary data based on key informant interviews held with major stakeholders were also used as sources of data. Exposures to high levels of indoor and outdoor air pollutants were found to be major sources of public health challenges. Lack of occupational safety and health due to agricultural activities and exposure to industries was found to be substantial. Worse is the growing fear that climate change will pose increasingly significant multidimensional challenges to the environment and public health. Across all three areas of focus, there was a paucity of information on local scientific evidence. There is also very limited trained skilled manpower and physical infrastructure to monitor the environment and enforce regulatory guidelines. Research, policy frameworks and regulatory mechanisms were among the cross-cutting issues that needed urgent attention. Critical gaps were observed in research and training across the three themes. Also, there is a limitation in implementing the link between policy and related regulations in the environment and health.

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...

A comprehensive study on regulatory requirements for development and filing of generic drugs globally

PubMed Central

Handoo, Shweta; Arora, Vandana; Khera, Deepak; Nandi, Prafulla Kumar; Sahu, Susanta Kumar

2012-01-01

The regulatory requirements of various countries of the world vary from each other. Therefore, it is challenging for the companies to develop a single drug which can be simultaneously submitted in all the countries for approval. The regulatory strategy for product development is essentially to be established before commencement of developmental work in order to avoid major surprises after submission of the application. The role of the regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. It not only includes the process of regulating and monitoring the drugs but also the process of manufacturing, distribution, and promotion of it. One of the primary challenges for regulatory authority is to ensure that the pharmaceutical products are developed as per the regulatory requirement of that country. This process involves the assessment of critical parameters during product development. PMID:23373001

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.

78 FR 62017 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-11

...The Office of the Comptroller of the Currency (OCC) and Board of Governors of the Federal Reserve System (Board), are adopting a final rule that revises their risk-based and leverage capital requirements for banking organizations. The final rule consolidates three separate notices of proposed rulemaking that the OCC, Board, and FDIC published in the Federal Register on August 30, 2012, with selected changes. The final rule implements a revised definition of regulatory capital, a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for banking organizations subject to the advanced approaches risk-based capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator. The final rule incorporates these new requirements into the agencies' prompt corrective action (PCA) framework. In addition, the final rule establishes limits on a banking organization's capital distributions and certain discretionary bonus payments if the banking organization does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk-based capital requirements. Further, the final rule amends the methodologies for determining risk-weighted assets for all banking organizations, and introduces disclosure requirements that would apply to top-tier banking organizations domiciled in the United States with $50 billion or more in total assets. The final rule also adopts changes to the agencies' regulatory capital requirements that meet the requirements of section 171 and section 939A of the Dodd-Frank Wall Street Reform and Consumer Protection Act. The final rule also codifies the agencies' regulatory capital rules, which have previously resided in various appendices to their respective regulations, into a harmonized integrated regulatory framework. In addition, the OCC is amending the market risk capital rule (market risk rule) to apply to Federal savings associations, and the Board is amending the advanced approaches and market risk rules to apply to top-tier savings and loan holding companies domiciled in the United States, except for certain savings and loan holding companies that are substantially engaged in insurance underwriting or commercial activities, as described in this preamble.

78 FR 28926 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-16

... Establishing Non- Display Usage Fees and Amending the Professional End-User Fees for NYSE Amex Options Market... proposes to establish non-display usage fees and to amend the Professional End-User fees for NYSE Amex... The Exchange proposes to establish non-display usage fees and to amend the Professional End-User fees...

Regulatory perspective on remaining challenges for utilization of pharmacogenomics-guided drug developments.

PubMed

Otsubo, Yasuto; Ishiguro, Akihiro; Uyama, Yoshiaki

2013-01-01

Pharmacogenomics-guided drug development has been implemented in practice in the last decade, resulting in increased labeling of drugs with pharmacogenomic information. However, there are still many challenges remaining in utilizing this process. Here, we describe such remaining challenges from the regulatory perspective, specifically focusing on sample collection, biomarker qualification, ethnic factors, codevelopment of companion diagnostics and means to provide drugs for off-target patients. To improve the situation, it is important to strengthen international harmonization and collaboration among academia, industries and regulatory agencies, followed by the establishment of an international guideline on this topic. Communication with a regulatory agency from an early stage of drug development is also a key to success.

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.

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

75 FR 43217 - Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62524; File No. SR-BATS-2010-008] Self-Regulatory Organizations; BATS Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Amendment No. 1 Thereto, To Amend BATS Rules 2.5 and 17.2 To Establish a Registration Requirement for Principals July 16, 2010. I. Introduction On April 9,...

75 FR 16221 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-31

...-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing of Proposed Rule Change To Establish Strike Price Intervals and Trading Hours for Options on Index-Linked Securities March 23, 2010. Pursuant... 19b-4 thereunder,\\2\\ notice is hereby given that on March 11, 2010, The NASDAQ Stock Market LLC...

The VTAC Committee: developing guidance for an alternative regulatory pathway to the anadromous salmonid protection rules

Treesearch

Michael Liquori; Peter Cafferata; Kevin Boston; Richard Gienger; David Hope

2012-01-01

In recent decades, riparian protection standards have been guided by generalized prescriptive rules. With the passage of the Anadromous Salmonid Protection rules in 2009, the Board of Forestry and Fire Protection (Board) established a regulatory pathway that provides an alternative approach for riparian protection based on site-specific criteria (14 CCR § 916....

77 FR 15826 - Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-16

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66576; File No. SR-NYSE-2012-01] Self-Regulatory Organizations; New York Stock Exchange LLC; Order Approving a Proposed Rule Change To Establish an NYBX Immediate-or- Cancel Order March 12, 2012. I. Introduction On January 11, 2012, the New York Stock Exchange LLC (``NYSE'' or ``Exchange'') file...

75 FR 47651 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-62605; File No. SR-NASDAQ-2010-068] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change to Establish a Revenue Sharing Program With Correlix, Inc. July 30, 2010. On June 8, 2010, The NASDAQ Stock Market LLC (``NASDAQ'' or the ``Exchange'') filed wit...

78 FR 9979 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... the Month). x (Number of Trading Days During the Month) Standard Fees: Clearing report to transfer a... Business Member establishes pricing for use of the FINRA/Nasdaq TRF, and such pricing is implemented.../Nasdaq TRF and the FINRA/NYSE TRF), FINRA does not take a position on whether the pricing for one TRF is...

Pluripotency and lineages in the mammalian blastocyst: an evolutionary view.

PubMed

Cañon, Susana; Fernandez-Tresguerres, Beatriz; Manzanares, Miguel

2011-06-01

Early mammalian development is characterized by a highly specific stage, the blastocyst, by which embryonic and extraembryonic lineages have been determined, but pattern formation has not yet begun. The blastocyst is also of interest because cell precursors of the embryo proper retain for a certain time the capability to generate all the cell types of the adult animal. This embryonic pluripotency is established and maintained by a regulatory network under the control of a small set of transcription factors, comprising Oct4, Sox2 and Nanog. This network is largely conserved in eutherian mammals, but there is scarce information about how it arose in vertebrates. We have analysed the conservation of gene regulatory networks controlling blastocyst lineages and pluripotency in the mouse by comparison with the chick. We found that few of elements of the network are novel to mammals; rather, most of them were present before the separation of the mammalian lineage from other amniotes, but acquired novel expression domains during early mammalian development. Our results strongly support the hypothesis that mammalian blastocyst regulatory networks evolved through rewiring of pre-existing components, involving the co-option and duplication of existing genes and the establishment of new regulatory interactions among them.

Technical and economic evaluation of controlled disposal options for very low level radioactive wastes

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

Robinson, P.J.; Vance, J.N.

1990-08-01

Over the past several years, there has been considerable interest by the nuclear industry in the Nuclear Regulatory Commission (NRC) explicitly defined an activity level in plant waste materials at which the radiological impacts would be so low as to be considered Below Regulatory Concern (BRC). In January 1989, Electric Power Research Institute (EPRI) completed an extensive industry research effort to develop the technical bases for establishing criteria for the disposal of very low activity wastes in ordinary disposal facilities. The Nuclear Management and Resources Council (NUMARC), with assistance from the Edison Electric Institute (EEI) and the Electric Power Researchmore » Institute (EPRI), drafted a petition titled: Petition for Rulemaking Regarding Disposal of Below Regulatory Concern Radioactive Wastes from Commercial Nuclear Power Plants.'' Subsequent to the industry making a final decision for submittal of the drafted BRC petition, EPRI was requested to evaluate the technical and economic impact of six BRC options. These options are: take no action in pursuing a BRC waste exemption, petition the NRC for authorization to disposal of any BRC waste in any ordinary disposal facility, limit disposal of BRC waste to the nuclear power plant site, limit disposal of BRC waste to the nuclear power plant site and other utility owned property, petition for a mixed waste exemption, and petition for single waste stream exemptions in sequence (i.e. soil, followed by sewage sludge, etc.). The petition and technical bases were written to support the disposal of any BRC waste type in any ordinary disposal facility. These documents do not provide all of the technical and economic information needed to completely assessment the BRC options. This report provides the technical and economic basis for a range of options concerning disposal of very low activity wastes. 3 figs., 20 tabs.« less

76 FR 44155 - Pacific Halibut Fisheries; Catch Sharing Plan for Guided Sport and Commercial Fisheries in Alaska

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-22

...NMFS proposes regulations that would implement a catch sharing plan for the guided sport and commercial fisheries for Pacific halibut in waters of International Pacific Halibut Commission (IPHC) Regulatory Areas 2C (Southeast Alaska) and 3A (Central Gulf of Alaska). If approved, this catch sharing plan will change the annual process of allocating halibut between the guided sport and commercial fisheries in Area 2C and Area 3A, establish allocations for each sector, and specify harvest restrictions for guided sport anglers that are intended to limit harvest to the annual guided sport fishery catch limit. In order to provide flexibility for individual commercial and guided sport fishery participants, the proposed catch sharing plan also will authorize annual transfers of commercial halibut quota to charter halibut permit holders for harvest in the guided sport fishery. This action is necessary to achieve the halibut fishery management goals of the North Pacific Fishery Management Council.

Mapping the Shh long-range regulatory domain

PubMed Central

Anderson, Eve; Devenney, Paul S.; Hill, Robert E.; Lettice, Laura A.

2014-01-01

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains. PMID:25252942

Immunization in pregnancy clinical research in low- and middle-income countries - Study design, regulatory and safety considerations.

PubMed

Kochhar, Sonali; Bonhoeffer, Jan; Jones, Christine E; Muñoz, Flor M; Honrado, Angel; Bauwens, Jorgen; Sobanjo-Ter Meulen, Ajoke; Hirschfeld, Steven

2017-12-04

Immunization of pregnant women is a promising public health strategy to reduce morbidity and mortality among both the mothers and their infants. Establishing safety and efficacy of vaccines generally uses a hybrid design between a conventional interventional study and an observational study that requires enrolling thousands of study participants to detect an unknown number of uncommon events. Historically, enrollment of pregnant women in clinical research studies encountered many barriers based on risk aversion, lack of knowledge, and regulatory ambiguity. Conducting research enrolling pregnant women in low- and middle-income countries can have additional factors to address such as limited availability of baseline epidemiologic data on disease burden and maternal and neonatal outcomes during and after pregnancy; challenges in recruiting and retaining pregnant women in research studies, variability in applying and interpreting assessment methods, and variability in locally acceptable and available infrastructure. Some measures to address these challenges include adjustment of study design, tailoring recruitment, consent process, retention strategies, operational and logistical processes, and the use of definitions and data collection methods that will align with efforts globally. Copyright © 2017. Published by Elsevier Ltd.

76 FR 6688 - Land Border Carrier Initiative Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-08

... [Docket No. USCBP-2006-0132; CBP Dec. No. 11-04] RIN 1651-AA68 Land Border Carrier Initiative Program... Carrier Initiative Program (LBCIP). The LBCIP was established as a voluntary industry partnership program... Initiative Program (LBCIP) was established as a CBP-industry partnership regulatory program enlisting the...

78 FR 24273 - Self-Regulatory Organizations; International Securities Exchange, LLC; Order Granting Approval of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-24

... Exchange shall establish and maintain procedures and internal controls reasonably designed to adequately... controls designed to protect confidential and proprietary information, which should help ensure that the... that are reasonably designed to prevent trade-throughs and establish, maintain and enforce written...

75 FR 11964 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-12

... Rule Change To Establish Procedures To Prevent Informational Advantages Resulting From the Affiliation... proposes a rule change to establish procedures designed to manage potential informational advantages... concerns about potential informational advantages and conflicts of interest between an exchange's self...

18 CFR 154.501 - Refunds.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Refunds. 154.501 Section 154.501 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... other time period established by the Commission or as established in the pipeline's tariff. (b) Costs of...

18 CFR 154.501 - Refunds.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Refunds. 154.501 Section 154.501 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... other time period established by the Commission or as established in the pipeline's tariff. (b) Costs of...

18 CFR 154.501 - Refunds.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Refunds. 154.501 Section 154.501 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT... other time period established by the Commission or as established in the pipeline's tariff. (b) Costs of...

Pharmaceutical Regulatory Framework in Ethiopia: A Critical Evaluation of Its Legal Basis and Implementation.

PubMed

Suleman, Sultan; Woliyi, Abdulkadir; Woldemichael, Kifle; Tushune, Kora; Duchateau, Luc; Degroote, Agnes; Vancauwenberghe, Roy; Bracke, Nathalie; De Spiegeleer, Bart

2016-05-01

Effective and enforceable national regulations describing the manufacture and (re)packaging, export and import, distribution and storage, supply and sale, information and pharmaco-vigilance of medicines are required to consistently ensure optimal patient benefit. Expansion of pharmaceutical industries in many countries with advancement in transport technologies facilitated not only trade of genuine pharmaceutical products but also the circulation of poor quality medicines across the globe. In Ethiopia, even though "The Pharmacists and Druggists Proclamation No 43/1942" was used to regulate both the professions and the facilities where they were practiced, comprehensive regulation of the pharmaceutical market was introduced in 1964 by a regulation called "Pharmacy Regulation No. 288/ 1964". This legislation formed the legal basis for official establishment of drug regulation in the history of Ethiopia, enabling the regulation of the practice of pharmacists, druggists and pharmacy technicians; manufacturing, distribution, and sale of medicines. In June 1999, a new regulation called the "Drug Administration and Control Proclamation No. 176/1999" repealed most parts of the regulation 288/1964. The law established an independent Drug Administration and Control Authority (DACA) with further mandate of setting standards of competence for licensing institutions/facilities. DACA was re-structured as Food, Medicine and Health Care Administration and Control Authority (EFMHACA) of Ethiopia by the "Proclamation No. 661/2009" in 2010 bearing additional responsibilities like regulation of food, health care personnel and settings. The mere existence of this legal framework does not guarantee complete absence of illegal, substandard and falsified products as well as illegal establishments in the pharmaceutical chain. Therefore, the objective of the research is to assess the pharmaceutical regulatory system in Ethiopia and to reveal possible reasons for deficiencies in the pharmaceutical chain. An archival review, an in-depth interview of key informants and an institutions-based cross-sectional survey study were conducted during March to April 2013. The comprehensiveness of the pharmaceutical law to protect public health relative to three selected African countries (South Africa, Tanzania and Uganda) and European Union, and implementation was assessed. The study revealed that Ethiopia does have a written national drug policy upon which the Medicines Regulatory Proclamation 661/2009 is based. According to this proclamation, the Ethiopian The Food, Medicines and Healthcare Administration and Control Authority is mandated to execute the regulatory activities as per the council of ministers regulation 189/2010. The legal framework for pharmaceutical regulation of Ethiopia was founded to fulfill all the medicines regulatory functions potentially enabling to combat illegal, substandard and falsified medicines and illegal establishments. Moreover, all the key informants witnessed that the government is commited and proclamation 661/2009 is comprehensive, but they stressed the compelling need of regulatory tools for effective implementation. From the institution-based cross-sectional study, it was revealed that there exist illegal sources formedicine in the pharmaceutical market. The main reasons for their existence were regulatory factors including weak regulatory enforcement (64.5%), lack of informal market control (60.8%), weak port control (50.0%), and poor cooperation between executive bodies (39.6%); and resource constraint (27.8%), which is an institutional factor. From legislative point of view, the medicines regulatory framework in Ethiopia fulfils all regulatory functions required for effective medicines regulation. However, the existence of the legislation by its own is not a guarantee to prevent the existence of unauthorized/illegal medicine sources since this requires effective implementation of the legislation, which is in fact affected by the governments political commitment, resource and intergovernmental cooperation.

MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic

PubMed Central

Stanton, Bruce A.

2015-01-01

This report is the outcome of the meeting: “Environmental and Human Health Consequences of Arsenic”, held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13–15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the U.S. Environmental Protection Agency (EPA) has set a limit of 10 micrograms per liter (10 μg/L) in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry and educators at the local, state, national and international levels to: (1) Establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) Work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry and others; (3) Develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) Develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods, and (5) Develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies. PMID:26231509

MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

PubMed

Stanton, Bruce A; Caldwell, Kathleen; Congdon, Clare Bates; Disney, Jane; Donahue, Maria; Ferguson, Elizabeth; Flemings, Elsie; Golden, Meredith; Guerinot, Mary Lou; Highman, Jay; James, Karen; Kim, Carol; Lantz, R Clark; Marvinney, Robert G; Mayer, Greg; Miller, David; Navas-Acien, Ana; Nordstrom, D Kirk; Postema, Sonia; Rardin, Laurie; Rosen, Barry; SenGupta, Arup; Shaw, Joseph; Stanton, Elizabeth; Susca, Paul

2015-09-01

This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 μg/L in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies.

78 FR 20973 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-08

... Proposed Rule Change To Establish Non-Display Usage Fees for NYSE OpenBook, NYSE Trades, and NYSE BBO and a... Terms of Substance of the Proposed Rule Change The Exchange proposes to establish non-display usage fees... establish non-display usage fees for NYSE OpenBook, NYSE Trades, and NYSE BBO and a redistribution fee for...

RNA splicing and its connection with other regulatory layers in somatic cell reprogramming.

PubMed

Zavolan, Mihaela; Kanitz, Alexander

2018-06-01

Understanding how cell identity is established and maintained is one of the most exciting challenges of molecular biology today. Recent work has added a conserved layer of RNA splicing and other post-transcriptional regulatory processes to the transcriptional and epigenetic networks already known to cooperate in the establishment and maintenance of cell identity. Here we summarize these findings, highlighting specifically the multitude of splicing factors that can modulate the efficiency of somatic cell reprogramming. Distinct patterns of gene expression dynamics of these factors during reprogramming suggest that further improvements in efficiency could be obtained through optimal timing of overexpression or knockdown of individual regulators. Copyright © 2017 Elsevier Ltd. All rights reserved.

[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.

Resilience as Regulation of Developmental and Family Processes

PubMed Central

MacPhee, David; Lunkenheimer, Erika; Riggs, Nathaniel

2015-01-01

Resilience can be defined as establishing equilibrium subsequent to disturbances to a system caused by significant adversity. When families experience adversity or transitions, multiple regulatory processes may be involved in establishing equilibrium, including adaptability, regulation of negative affect, and effective problem-solving skills. The authors’ resilience-as-regulation perspective integrates insights about the regulation of individual development with processes that regulate family systems. This middle-range theory of family resilience focuses on regulatory processes across levels that are involved in adaptation: whole-family systems such as routines and sense of coherence; coregulation of dyads involving emotion regulation, structuring, and reciprocal influences between social partners; and individual self-regulation. Insights about resilience-as-regulation are then applied to family-strengthening interventions that are designed to promote adaptation to adversity. Unresolved issues are discussed in relation to resilience-as-regulation in families, in particular how risk exposure is assessed, interrelations among family regulatory mechanisms, and how families scaffold the development of children’s resilience. PMID:26568647

76 FR 77856 - International Mail Price Change for Inbound Air Parcel Post

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... POSTAL REGULATORY COMMISSION [Docket No. CP2012-3; Order No. 1033] International Mail Price Change..., Notice of Establishment of Prices and Classifications Not of General Applicability for Inbound Air Parcel... Governors' Decision No. 09-15 which establishes prices and classifications for Inbound Air Parcel Post at...

76 FR 80992 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

... 7034 Regarding Low Latency Network Connections December 20, 2011. I. Introduction On October 31, 2011...- Location Services'' to establish a program for offering low latency network connections and to establish the initial fees for such connections. The Exchange also proposed administrative modifications to...

77 FR 16951 - Livestock Mandatory Reporting Program; Establishment of the Reporting Regulation for Wholesale Pork

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

... the Reporting Regulation for Wholesale Pork AGENCY: Agricultural Marketing Service, USDA. ACTION... wholesale pork cuts. The 2010 Reauthorization Act directed the Secretary to engage in negotiated rulemaking to make required regulatory changes for mandatory wholesale pork reporting and establish a negotiated...

77 FR 24730 - Submission of Information Collection Under the Paperwork Reduction Act; Reinstatement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-25

... regulatory authorities to establish and implement tribal internal control standards that provide a level of... system that, at a minimum, complies with the tribal internal control standards established by the tribal... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission Submission of Information Collection...

77 FR 9261 - Submission of Information Collection Under the Paperwork Reduction Act; Reinstatement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... regulatory authorities to establish and implement tribal internal control standards that provide a level of... system that, at a minimum, complies with the tribal internal control standards established by the tribal... DEPARTMENT OF THE INTERIOR National Indian Gaming Commission Submission of Information Collection...

75 FR 31430 - Frequency Regulation Compensation in the Organized Wholesale Power Markets; Notice Establishing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-03

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD10-11-000] Frequency Regulation Compensation in the Organized Wholesale Power Markets; Notice Establishing Date for Comments May 27, 2010. On May 26, 2010, Commission staff convened a technical conference regarding frequency...

10 CFR 95.29 - Establishment of Restricted or Closed areas.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Establishment of Restricted or Closed areas. 95.29 Section 95.29 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING...) The Closed Area must be accorded supplemental protection during non-working hours. During these hours...

10 CFR 95.29 - Establishment of Restricted or Closed areas.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Establishment of Restricted or Closed areas. 95.29 Section 95.29 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING...) The Closed Area must be accorded supplemental protection during non-working hours. During these hours...

10 CFR 95.29 - Establishment of Restricted or Closed areas.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Establishment of Restricted or Closed areas. 95.29 Section 95.29 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING...) The Closed Area must be accorded supplemental protection during non-working hours. During these hours...

10 CFR 95.29 - Establishment of Restricted or Closed areas.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Establishment of Restricted or Closed areas. 95.29 Section 95.29 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING...) The Closed Area must be accorded supplemental protection during non-working hours. During these hours...

10 CFR 95.29 - Establishment of Restricted or Closed areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Establishment of Restricted or Closed areas. 95.29 Section 95.29 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) FACILITY SECURITY CLEARANCE AND SAFEGUARDING...) The Closed Area must be accorded supplemental protection during non-working hours. During these hours...

77 FR 54908 - TC Offshore, LLC; Notice Establishing Deadline for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. RP12-908-000] TC Offshore, LLC; Notice Establishing Deadline for Comments On August 29, 2012, TC Offshore, LLC (TC Offshore... is hereby given that participants in the captioned proceedings may file comments to TC Offshsore's...

75 FR 17820 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-07

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-61812; File No. SR-Phlx-2010-49] Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change by NASDAQ OMX PHLX, Inc. To Establish $2.50 Strike Price Intervals for Options on the NASDAQ Internet Index \\SM\\ March 31, 2010. Pursuant to Section 19(b)(1) of...

77 FR 20863 - Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66714; File No. SR-EDGA-2012-09] Self-Regulatory Organizations; EDGA Exchange, Inc.; Notice of Filing of Proposed Rule Change Relating to Amendments to Rule 2.11 That Establish the Authority To Cancel Orders and Describe the Operation of an Error Account April 2, 2012. Pursuant to Section 19(b)(...

77 FR 20854 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing of Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66713; File No. SR-EDGX-2012-08] Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing of Proposed Rule Change Relating to Amendments to Rule 2.11 That Establish the Authority To Cancel Orders and Describe the Operation of an Error Account April 2, 2012. Pursuant to Section 19(b)(...

78 FR 18655 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-27

... from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization... simple, non-complex orders only. The Exchange now proposes to establish the Complex Order Router Subsidy... simple, non-complex orders under the ORS Program. The Participants would have to agree that they are not...

76 FR 9620 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63906; File No. SR-NASDAQ-2011-024] Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Establish and Adopt Fees for the New Short Sale Monitor Service and Nasdaq Data Add-On February 14, 2011. Pursuant to Section...

Lessons learned in acquiring new regulations for shipping advanced electric vehicle batteries

NASA Astrophysics Data System (ADS)

Henriksen, Gary; Hammel, Carol; Altemos, Edward A.

1994-12-01

In 1990, the Electric and Hybrid Propulsion Division of the US Department of Energy established its ad hoc EV Battery Readiness Working Group to identify regulatory barriers to the commercialization of advanced EV battery technologies and facilitate the removal of these barriers. A Shipping Sub-Working Group (SSWG) was formed to address the regulatory issues associated with the domestic and international shipment of these new battery technologies. The SSWG invites major industrial developers of advanced battery technologies to join as members and work closely with appropriate domestic and international regulatory authorities to develop suitable regulations and procedures for the safe transport of these new battery technologies. This paper describes the domestic and international regulatory processes for the transport of dangerous goods; reviews the status of shipping regulations for sodium-beta and lithium batteries; and delineates the lessons learned to date in this process. The sodium-beta battery family was the first category of advanced EV batteries to be addressed by the SSWG. It includes both sodium/sulfur and sodium/metal chloride batteries. Their efforts led to the establishment of a UN number (UN 3292) in the UN Recommendations, for cold cells and batteries, and establishment of a US Department of Transportation general exemption (DOT-E-10917) covering cold and hot batteries, as well as cold cells. The lessons learned for sodium-beta batteries, over the period of 1990--94, are now being applied to the development of regulations for shipping a new generation of lithium battery technologies (lithium-polymer and lithium-aluminum/iron sulfide batteries).

Modelling and analysis of gene regulatory network using feedback control theory

NASA Astrophysics Data System (ADS)

El-Samad, H.; Khammash, M.

2010-01-01

Molecular pathways are a part of a remarkable hierarchy of regulatory networks that operate at all levels of organisation. These regulatory networks are responsible for much of the biological complexity within the cell. The dynamic character of these pathways and the prevalence of feedback regulation strategies in their operation make them amenable to systematic mathematical analysis using the same tools that have been used with success in analysing and designing engineering control systems. In this article, we aim at establishing this strong connection through various examples where the behaviour exhibited by gene networks is explained in terms of their underlying control strategies. We complement our analysis by a survey of mathematical techniques commonly used to model gene regulatory networks and analyse their dynamic behaviour.

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...

Tregs: Where We Are and What Comes Next?

PubMed

Zhao, Hai; Liao, Xuelian; Kang, Yan

2017-01-01

Regulatory T cells are usually recognized as a specialized subset of CD4 + T cells functioning in establishment and maintenance of immune tolerance. Meanwhile, there is emerging evidence that regulatory T cells (Tregs) are also present in various non-lymphoid tissues, and that they have unique phenotypes credited with activities distinct from regulatory function. Their development and function have been described in plenty of manuscripts in the past two decades. However, with the deepening of research in recent years, emerging evidence revealed some novel mechanisms about how Tregs exert their activities. First, we discuss the expanding family of regulatory lymphocytes briefly and then, try to interpret how fork-head box P3 (Foxp3), a master regulator of the regulatory pathway in the development and function of regulatory T cells, functions. Subsequently, another part of our focus is varieties of tissue Tregs. Next, we primarily discuss recent research on how Tregs work and their faceted functions in terms of soluble mediators, functional proteins, and inhibitory receptors. In particular, unless otherwise noted, the term "Treg" is used here to refer specially to the "CD4 + CD25 + Foxp3 +" regulatory cells.

Sparse Additive Ordinary Differential Equations for Dynamic Gene Regulatory Network Modeling.

PubMed

Wu, Hulin; Lu, Tao; Xue, Hongqi; Liang, Hua

2014-04-02

The gene regulation network (GRN) is a high-dimensional complex system, which can be represented by various mathematical or statistical models. The ordinary differential equation (ODE) model is one of the popular dynamic GRN models. High-dimensional linear ODE models have been proposed to identify GRNs, but with a limitation of the linear regulation effect assumption. In this article, we propose a sparse additive ODE (SA-ODE) model, coupled with ODE estimation methods and adaptive group LASSO techniques, to model dynamic GRNs that could flexibly deal with nonlinear regulation effects. The asymptotic properties of the proposed method are established and simulation studies are performed to validate the proposed approach. An application example for identifying the nonlinear dynamic GRN of T-cell activation is used to illustrate the usefulness of the proposed method.

Current status of radiological protection at nuclear power stations in Japan.

PubMed

Suzuki, Akira; Hori, Shunsuke

2011-07-01

The radiation dose to workers at nuclear power stations (NPSs) in Japan was drastically reduced between the late-1970s and the early-1990s by continuous dose-reduction programmes. The total collective dose of radiation workers in FY 2008 was 84.04 person Sv, while the average collective dose was 1.5 person Sv per reactor. The average annual individual dose was 1.1 mSv and the maximum annual individual dose was 19.5 mSv. These values are sufficiently lower than the regulatory dose limits. Radioactive effluent released from NPSs is already so trivial that additional protective measures will not be necessary. Experience in radiation protection at NPSs has been accumulated over 40 y and will be very useful in establishing a rational radiation control system in the future.

Identification of polycomb and trithorax group responsive elements in the regulatory region of the Drosophila homeotic gene Sex combs reduced

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

Gindhart, J.G. Jr.; Kaufman, T.C.

1995-02-01

The Drosophilia homeotic gene Sex combs reduced (Scr) is necessary for the establishment and maintenance of the morphological identity of the labial and prothoracic segments. In the early embryo, its expression pattern is established through the activity of several gap and segmentation gene products, as well as other transcription factors. Once established, the Polycomb group (Pc-G) and trithorax group (trx-G) gene products maintain the spatial pattern of Scr expression for the remainder of development. We report the identification of DNA fragments in the Scr regulatory region that may be important for its regulation by Polycomb and trithorax group gene products.more » When DNA fragments containing these regulatory sequences are subcloned into P-element vectors containing a white minigene, transformants containing these constructs exhibit mosaic patterns of pigmentation in the adult eye, indicating that white minigene expression is repressed in a clonally heritable manner. The size of pigmented and nonpigmented clones in the adult eye suggests that the event determining whether a cell in the eye anlagen will express white occurs at least as early as the first larval instar. The amount of white minigene repression is reduced in some Polycomb group mutants, whereas repression is enhanced in flies mutant for a subset of trithorax group loci. The repressor activity of one fragment, normally located in Scr Intron 2, is increased when it is able to homologously pair, a property consistent with genetic data suggesting that Scr exhibits transvection. Another Scr regulatory fragment, normally located 40 kb upstream of the Scr promoter, silences ectopic expression of an Scr-lacZ fusion gene in the embryo and does so in a Polycomb-dependent manner. We propose that the regulatory sequences located within these DNA fragments may normally mediate the regulation of Scr by proteins encoded by members of Polycomb and trithorax group loci. 98 refs., 6 figs., 4 tabs.« less

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.

A combined park management framework based on regulatory and behavioral strategies: use of visitors' knowledge to assess effectiveness.

PubMed

Papageorgiou, K

2001-07-01

In light of the increasing mandate for greater efficiency in conservation of natural reserves such as national parks, the present study suggests educational approaches as a tool to achieve conservation purposes. Currently, the management of human-wildlife interactions is dominated by regulatory strategies, but considerable potential exists for environmental education to enhance knowledge in the short run and to prompt attitude change in the long run. A framework for conservation based on both traditional regulatory- and behavior-oriented strategies was proposed whereby the level of knowledge that park visitors have acquired comprises an obvious outcome and establishes a basis upon which the effectiveness of regulatory- and behavior-based regimes could be assessed. The perceptions regarding park-related issues of two distinct visitor groups (locals and nonlocals) are summarized from a survey undertaken in Vikos-Aoos national park. The findings suggest a superficial knowledge for certain concepts but little profound understanding of the content of such concepts, indicating that knowledge-raising efforts should go a long way towards establishing a positive attitude for the resource. Visitors' poor knowledge of the park's operation regulation contest the efficiency of the presently dominant regulatory management regime. While geographical distances did not appear to significantly differentiate knowledge between the two groups, wilderness experience (as certified by visits to other parks) was proved to be an impetus for generating substantial learner interest in critical park issues among nonlocal visitors. School education and media were found to be significant knowledge providers.

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.

76 FR 13112 - Maryland Regulatory Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-10

... generation, storage, handling, processing, disposal, recycling, beneficial use, or other use of CCBs within... establish requirements pertaining to the generation, storage, handling, processing, disposal, recycling...

77 FR 7663 - Introduction to the Unified Agenda of Federal Regulatory and Deregulatory Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

...The Regulatory Flexibility Act requires that agencies publish semiannual regulatory agendas in the Federal Register describing regulatory actions they are developing that may have a significant economic impact on a substantial number of small entities (5 U.S.C. 602). Executive Order 12866 ``Regulatory Planning and Review,'' signed September 30, 1993 (58 FR 51735), and Office of Management and Budget memoranda implementing section 4 of that Order establish minimum standards for agencies' agendas, including specific types of information for each entry. The Unified Agenda of Federal Regulatory and Deregulatory Actions (Unified Agenda) helps agencies fulfill these requirements. All Federal regulatory agencies have chosen to publish their regulatory agendas as part of the Unified Agenda. Editions of the Unified Agenda prior to fall 2007 were printed in their entirety in the Federal Register. Beginning with the fall 2007 edition, the Internet is the basic means for conveying regulatory agenda information to the maximum extent legally permissible. The complete Unified Agenda for fall 2011, which contains the regulatory agendas for 59 Federal agencies, is available to the public at http:// reginfo.gov. The fall 2011 Unified Agenda publication appearing in the Federal Register consists of agency regulatory flexibility agendas, in accordance with the publication requirements of the Regulatory Flexibility Act. Agency regulatory flexibility agendas contain only those Agenda entries for rules that are likely to have a significant economic impact on a substantial number of small entities and entries that have been selected for periodic review under section 610 of the Regulatory Flexibility Act.

77 FR 4604 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-30

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66218; File No. SR-NYSE-2012-01] Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule Change To Establish an NYBX Immediate-or-Cancel Order January 24, 2012. Pursuant to Section 19(b)(1) of the Securities Exchange Act of 1934 (``Act'') \\1\\ and Rule 19b-4...

Licensing of future mobile satellite systems

NASA Technical Reports Server (NTRS)

Lepkowski, Ronald J.

1990-01-01

The regulatory process for licensing mobile satellite systems is complex and can require many years to complete. This process involves frequency allocations, national licensing, and frequency coordination. The regulatory process that resulted in the establishment of the radiodetermination satellite service (RDSS) between 1983 and 1987 is described. In contrast, each of these steps in the licensing of the mobile satellite service (MSS) is taking a significantly longer period of time to complete.

76 FR 9618 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63905; File No. SR-Phlx-2011-17] Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Establish and Adopt Fees for the New Short Sale Monitor Service and PSX Data Add-On February 14, 2011. Pursuant to Section 19(b)(1) of th...

76 FR 9623 - Self-Regulatory Organizations; NASDAQ OMX BX; Notice of Filing and Immediate Effectiveness of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-18

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-63907; File No. SR-BX-2011-008] Self-Regulatory Organizations; NASDAQ OMX BX; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change To Establish and Adopt Fees for the New Short Sale Monitor Service and BX Data Add-On February 14, 2011. Pursuant to Section 19(b)(1) of the...

Widespread arsenic contamination of soils in residential areas and public spaces: an emerging regulatory or medical crisis?

PubMed

Belluck, D A; Benjamin, S L; Baveye, P; Sampson, J; Johnson, B

2003-01-01

A critical review finds government agencies allow, permit, license, or ignore arsenic releases to surface soils. Release rates are controlled or evaluated using risk-based soil contaminant numerical limits employing standardized risk algorithms, chemical-specific and default input values. United States arsenic residential soil limits, approximately 0.4- approximately 40 ppm, generally correspond to a one-in-one-million to a one-in-ten-thousand incremental cancer risk range via ingestion of or direct contact with contaminated residential soils. Background arsenic surface soil levels often exceed applicable limits. Arsenic releases to surface soils (via, e.g., air emissions, waste recycling, soil amendments, direct pesticide application, and chromated copper arsenic (CCA)-treated wood) can result in greatly elevated arsenic levels, sometimes one to two orders of magnitude greater than applicable numerical limits. CCA-treated wood, a heavily used infrastructure material at residences and public spaces, can release sufficient arsenic to result in surface soil concentrations that exceed numerical limits by one or two orders of magnitude. Although significant exceedence of arsenic surface soil numerical limits would normally result in regulatory actions at industrial or hazardous waste sites, no such pattern is seen at residential and public spaces. Given the current risk assessment paradigm, measured or expected elevated surface soil arsenic levels at residential and public spaces suggest that a regulatory health crisis of sizeable magnitude is imminent. In contrast, available literature and a survey of government agencies conducted for this paper finds no verified cases of human morbidity or mortality resulting from exposure to elevated levels of arsenic in surface soils. This concomitance of an emerging regulatory health crisis in the absence of a medical crisis is arguably partly attributable to inadequate government and private party attention to the issue.

Comparative genomics of metabolic capacities of regulons controlled by cis-regulatory RNA motifs in bacteria.

PubMed

Sun, Eric I; Leyn, Semen A; Kazanov, Marat D; Saier, Milton H; Novichkov, Pavel S; Rodionov, Dmitry A

2013-09-02

In silico comparative genomics approaches have been efficiently used for functional prediction and reconstruction of metabolic and regulatory networks. Riboswitches are metabolite-sensing structures often found in bacterial mRNA leaders controlling gene expression on transcriptional or translational levels.An increasing number of riboswitches and other cis-regulatory RNAs have been recently classified into numerous RNA families in the Rfam database. High conservation of these RNA motifs provides a unique advantage for their genomic identification and comparative analysis. A comparative genomics approach implemented in the RegPredict tool was used for reconstruction and functional annotation of regulons controlled by RNAs from 43 Rfam families in diverse taxonomic groups of Bacteria. The inferred regulons include ~5200 cis-regulatory RNAs and more than 12000 target genes in 255 microbial genomes. All predicted RNA-regulated genes were classified into specific and overall functional categories. Analysis of taxonomic distribution of these categories allowed us to establish major functional preferences for each analyzed cis-regulatory RNA motif family. Overall, most RNA motif regulons showed predictable functional content in accordance with their experimentally established effector ligands. Our results suggest that some RNA motifs (including thiamin pyrophosphate and cobalamin riboswitches that control the cofactor metabolism) are widespread and likely originated from the last common ancestor of all bacteria. However, many more analyzed RNA motifs are restricted to a narrow taxonomic group of bacteria and likely represent more recent evolutionary innovations. The reconstructed regulatory networks for major known RNA motifs substantially expand the existing knowledge of transcriptional regulation in bacteria. The inferred regulons can be used for genetic experiments, functional annotations of genes, metabolic reconstruction and evolutionary analysis. The obtained genome-wide collection of reference RNA motif regulons is available in the RegPrecise database (http://regprecise.lbl.gov/).

[Regulatory Framework for Approval of PET Drug in Korea: A Survey Report].

PubMed

Kurihara, Chieko; Inoue, Tomio

2015-11-01

To identify regulatory framework for approval of PET drugs in Korea. Interview and literature survey. In Korea Good Manufacturing Practice (GMP) regulation specific to radiopharmaceuticals, including PET (Positron Emission Tomography) drugs, under the Pharmaceutical Affairs Act was issued in August 2014, to be enforced on July 1, 2015, and its guidance was issued in December 2014. The new facilities to be established after July 1 of 2015 have to be compatible with this new regulation and already established facilities have two years grace period until June 30 of 2017. During this period, the regulatory authority will inspect all of the production sites which hold or submit approvals of radiopharmaceuticals. As of September 2015 in Korea, there are 7 commercial companies and 15 hospitals and institutes, which have approvals of PET drugs mainly FDG, and these companies and/or hospitals can supply PET drugs outside institutions. In this article we introduce the Korean regulations of development and approval of radiopharmaceuticals. The Korean regulatory authorization policy for radiopharmaceuticals are to some extent similar to the policy which the U.S. regulators set as the new regulations of PET drug. It is expected that the situations of production sites in Korea are to be improved through actual discussions among regulators and PET community through the process of actual inspection.

76 FR 17460 - South Texas Project Nuclear Operating Company; Establishment of Atomic Safety and Licensing Board

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-29

...] South Texas Project Nuclear Operating Company; Establishment of Atomic Safety and Licensing Board..., 2.318, and 2.321, notice is hereby given that an Atomic Safety and Licensing Board (Board) is being...: Ronald M. Spritzer, Chair, Atomic Safety and Licensing Board Panel, U.S. Nuclear Regulatory Commission...

75 FR 71397 - Regulations Establishing and Governing the Duties of Swap Dealers and Major Swap Participants

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-23

... risks associated with the use of models to derive market valuations or otherwise calculate or evaluate... swap dealers and major swap participants registered with the Commission with regard to: Risk management...) \\3\\ to establish a comprehensive regulatory framework to reduce risk, increase transparency, and...

76 FR 80999 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Order Approving a Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

...-Location Fee Schedule Regarding Low Latency Network Connections December 20, 2011. I. Introduction On... connections and to establish the initial fees for such connections. The Exchange also proposed administrative... connections and to establish the fees for such connections. As its initial offering, the Exchange proposed to...

78 FR 68441 - Information Collection Being Submitted for Review and Approval to the Office of Management and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-14

... disclosure requirement. Obligation to Respond: Required to obtain or retain benefits. Statutory authority for...-222 MHz and (220 MHz service). In establishing this licensing plan, FCC's goal is to establish a flexible regulatory framework that allows for efficient licensing of the 220 MHz service, eliminates...

75 FR 51306 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-19

... systems capacity to handle the additional traffic associated with the listing and trading of $1 strikes... Relating to Establishing Strike Price Intervals for Options on Trust Issued Receipts, Including Holding... Rules of the Boston Options Exchange Group, LLC (``BOX'') to establish strike price intervals for...

75 FR 6243 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... capacity to handle the additional traffic associated with the listing and trading of $1 strikes (where the... Change, and Amendment No. 1 Thereto, To Establish Strike Price Intervals and Trading Hours for Options on... the commencement of trading options on Index-Linked Securities, CBOE proposes to establish strike...

78 FR 17958 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

..., market making activity on the Exchange, by establishing quoting compliance standards that are reasonable..., market making activity on the Exchange, by establishing quoting compliance standards that are reasonable... Exchange believes that the proposal will not diminish and in fact may increase, market making activity on...

76 FR 68236 - Self-Regulatory Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-03

... Organizations; Options Clearing Corporation; Order Approving Proposed Rule Change To Adopt Fitness Standards for... amended by the Dodd-Frank Act. In particular, new DCO Core Principle O requires DCOs to establish fitness...) establish and enforce appropriate fitness standards for (I) directors, (II) members of any disciplinary...

76 FR 58061 - Self-Regulatory Organizations; Options Clearing Corporation; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

... Organizations; Options Clearing Corporation; Notice of Filing of Proposed Rule Change To Adopt Fitness Standards... purpose of the proposed rule change is to establish fitness standards for directors, clearing members, and... Core Principle O requires DCOs to establish fitness standards for directors, clearing members and...

78 FR 2295 - Charlissa C. Smith; Establishment of Atomic Safety and Licensing Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-10

... NUCLEAR REGULATORY COMMISSION [Docket No. 55-23694-SP; ASLBP No. 13-925-01-SP-BD01] Charlissa C... (Board) is being established to preside over the following proceeding: Charlissa C. Smith, (Denial of Senior Reactor Operator License). This proceeding concerns a hearing request from Charlissa C. Smith...

Do hedonic motives moderate regulatory focus motives? Evidence from the framing of persuasive messages.

PubMed

Malaviya, Prashant; Brendl, C Miguel

2014-01-01

Research on regulatory focus has established a regulatory matching effect: The persuasiveness of a message is enhanced when regulatory orientations of message and perceiver match (i.e., both are promotion or both are prevention). We report evidence that varying the hedonic outcome reverses this effect. We manipulated hedonic outcome by explicitly stating pleasurable versus painful outcomes as part of the message frame as well as by priming perceivers to focus on either pleasurable or painful outcomes. When both message and perceiver were focused on pleasurable outcomes, we replicated the regulatory matching effect. However, the matching effect reversed when the hedonic outcome of the message was opposed to that of the perceiver (i.e., one was pleasurable and the other painful). Under these conditions, messages that mismatched the perceivers' regulatory orientation were more persuasive (i.e., promotion message for a prevention oriented perceiver or vice versa). We also examined the persuasion effects when both message and perceiver were focused on painful outcomes and found that the regulatory matching effect re-emerged. The reversal of the regulatory matching effect by hedonic outcome strongly suggests that hedonic motives (approach of pleasure vs. avoidance of pain) and regulatory focus motives are distinct constructs. This is important because contrary to theoretical statements these constructs have often been confounded.

Current and anticipated uses of thermal-hydraulic codes in Spain

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

Pelayo, F.; Reventos, F.

1997-07-01

Spanish activities in the field of Applied Thermal-Hydraulics are steadily increasing as the codes are becoming practicable enough to efficiently sustain engineering decision in the Nuclear Power industry. Before reaching this point, a lot of effort has been devoted to achieve this goal. This paper briefly describes this process, points at the current applications and draws conclusions on the limitations. Finally it establishes the applications where the use of T-H codes would be worth in the future, this in turn implies further development of the codes to widen the scope of application and improve the general performance. Due to themore » different uses of the codes, the applications mainly come from the authority, industry, universities and research institutions. The main conclusion derived from this paper establishes that further code development is justified if the following requisites are considered: (1) Safety relevance of scenarios not presently covered is established. (2) A substantial gain in margins or the capability to use realistic assumptions is obtained. (3) A general consensus on the licensability and methodology for application is reached. The role of Regulatory Body is stressed, as the most relevant outcome of the project may be related to the evolution of the licensing frame.« less

Electronic cigarettes in North America: history, use, and implications for smoking cessation.

PubMed

Franck, Caroline; Budlovsky, Talia; Windle, Sarah B; Filion, Kristian B; Eisenberg, Mark J

2014-05-13

Designed to mimic the look and feel of tobacco cigarettes, electronic cigarettes (e-cigarettes) may facilitate smoking cessation. However, the efficacy and safety of e-cigarette use for this purpose remain poorly understood. Our objectives were to review the available data on the efficacy and safety of e-cigarettes for smoking cessation and to consider issues relevant to the context in which they are used, including product awareness and regulatory and ethical concerns. We systematically searched PubMed for randomized controlled trials and uncontrolled, experimental studies involving e-cigarettes. Included studies were limited to English or French language reports. Quality assessment was performed according to the Cochrane Risk of Bias tool. We identified 169 publications, of which 7 studies were included. Studies have concluded that e-cigarettes can help reduce the number of cigarettes smoked and may be as effective for smoking cessation as the nicotine patch. Although there is a lack of data concerning the safety and efficacy of e-cigarettes as a smoking cessation therapy, available evidence showed no significant difference in adverse event rates between e-cigarettes and the nicotine patch. E-cigarettes are widely used among smokers attempting to quit. However, significant international variation remains in the regulatory mechanisms governing the sale and distribution of e-cigarettes. Ethical concerns surround the use of e-cigarettes among minors and their potential to undermine efforts to reduce cigarette smoking. Given the limited available evidence on the risks and benefits of e-cigarette use, large, randomized, controlled trials are urgently needed to definitively establish their potential for smoking cessation.

Autocrine IL-10 functions as a rheostat for M1 macrophage glycolytic commitment by tuning nitric oxide production.

PubMed

Baseler, Walter A; Davies, Luke C; Quigley, Laura; Ridnour, Lisa A; Weiss, Jonathan M; Hussain, S Perwez; Wink, David A; McVicar, Daniel W

2016-12-01

Inflammatory maturation of M1 macrophages by proinflammatory stimuli such as toll like receptor ligands results in profound metabolic reprogramming resulting in commitment to aerobic glycolysis as evidenced by repression of mitochondrial oxidative phosphorylation (OXPHOS) and enhanced glucose utilization. In contrast, "alternatively activated" macrophages adopt a metabolic program dominated by fatty acid-fueled OXPHOS. Despite the known importance of these developmental stages on the qualitative aspects of an inflammatory response, relatively little is know regarding the regulation of these metabolic adjustments. Here we provide evidence that the immunosuppressive cytokine IL-10 defines a metabolic regulatory loop. Our data show for the first time that lipopolysaccharide (LPS)-induced glycolytic flux controls IL-10-production via regulation of mammalian target of rapamycin (mTOR) and that autocrine IL-10 in turn regulates macrophage nitric oxide (NO) production. Genetic and pharmacological manipulation of IL-10 and nitric oxide (NO) establish that metabolically regulated autocrine IL-10 controls glycolytic commitment by limiting NO-mediated suppression of OXPHOS. Together these data support a model where autocine IL-10 production is controlled by glycolytic flux in turn regulating glycolytic commitment by preserving OXPHOS via suppression of NO. We propose that this IL-10-driven metabolic rheostat maintains metabolic equilibrium during M1 macrophage differentiation and that perturbation of this regulatory loop, either directly by exogenous cellular sources of IL-10 or indirectly via limitations in glucose availability, skews the cellular metabolic program altering the balance between inflammatory and immunosuppressive phenotypes. Copyright © 2016. Published by Elsevier B.V.

Development and validation of a liquid chromatography-UV detection method for the determination of sulfonamides in fish muscle and shrimp according to European Union Decision 2002/657/EC.

PubMed

Granja, Rodrigo H M M; De Lima, Andreia C; Salerno, Alessandro G; Wanschel, Amarylis C B A

2013-01-01

Sulfonamides are one class of antimicrobial agents used in aquaculture production. Sulfonamides are often overused because they are inexpensive and readily available. Their presence at a concentration above the legal limits is a potential hazard to human health. Brazilian authorities have included in the National Regulatory Monitoring Program the control of the three most widely used sulfonamides in aquaculture production, i.e., sulfathiazole, sulfamethazine, and sulfadimethoxine. An LC method with UV detection for the determination of residual sulfonamides in fish muscle, using sulfapyridine as an internal standard has been developed and validated. The validation was performed according to the Brazilian Regulation 24/2009 (equivalent to European Union Decision 2002/657/EC). The method meets the Brazilian regulatory requirement that establishes criteria and procedures for determination of parameters such as decision limit (CCalpha), detection capability (CCbeta), precision, and recovery. For fish muscle, CCalpha was determined at 3.63, 2.91, and 7.46 microg/kg for sulfathiazole, sulfamethazine, and sulfadimethoxine, respectively. CCbeta was 9.39, 14.54, and 9.39 microg/kg for sulfathiazole, sulfamethazine, and sulfadimethoxine, respectively. For shrimp, CCalpha was 11.5, 8.67, and 4.46 microg/kg for sulfathiazole, sulfamethazine, and sulfadimethoxine, respectively. CCbeta was 18, 11.93, and 5.24 microg/kg for sulfathiazole, sulfamethazine, and sulfadimethoxine, respectively. A complete statistical analysis was performed on the results obtained. The results indicate that the method is robust when subjected to day-to-day analytical variations.

A Personal Perspective on the Initial Federal Health-Based Regulation to Remove Lead from Gasoline

PubMed Central

Bridbord, Kenneth; Hanson, David

2009-01-01

Objective This article describes the personal experience and perspective of the authors, who had primary responsibility for drafting the initial health-based regulation limiting lead content of gasoline during the early 1970s while employed by the U.S. Environmental Protection Agency (EPA). Data source Information used by the U.S. EPA in developing the initial health-based regulation limiting lead content of gasoline in December 1973 and studies documenting the impact of that and subsequent actions. Data extraction Among the lessons learned from this experience is the importance of having input from independent scientists to the regulatory decision-making process. This also demonstrates the critical role of independent peer-reviewed research, such as that supported by the National Institutes of Health, as well as research conducted by scientists from the Centers for Disease Control and Prevention, in delineating the consequences of lead exposure in the population. Data synthesis Removal of lead from gasoline in the United States has been described as one of the great public health achievements of the 20th century, but it almost did not happen. The experience of the authors in developing this regulation may be helpful to others involved in developing health-based regulatory policy in the future. Conclusion The initial U.S. EPA health-based regulation to remove lead from gasoline is clearly an example where science successfully affected public policy. The leadership of the U.S. EPA at that time deserves much credit for establishing an atmosphere in which this was possible. PMID:19672397

Effect of land-applied biosolids on surface-water nutrient yields and groundwater quality in Orange County, North Carolina

USGS Publications Warehouse

Wagner, Chad R.; Fitzgerald, Sharon A.; McSwain, Kristen Bukowski; Harden, Stephen L.; Gurley, Laura N.; Rogers, Shane W.

2015-01-01

The data, analysis, and conclusions associated with this study can be used by regulatory agencies, resource managers, and wastewater-treatment operators to (1) better understand the quantity and characteristics of nutrients, bacteria, metals, and contaminants of emerging concern that are transported away from biosolids land-application fields to surface water and groundwater under current regulations for the purposes of establishing effective total maximum daily loads (TMDLs) and restoring impaired water resources, (2) assess how well existing regulations protect waters of the State and potentially recommend effective changes to regulations or land-application procedures, and (3) establish a framework for developing guidance on effective techniques for monitoring and regulatory enforcement of permitted biosolids land-application fields.

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...

Viral microRNA effects on persistent infection of human lymphoid cells by polyomavirus SV40

PubMed Central

McNees, Adrienne L.; Harrigal, Lindsay J.; Kelly, Aoife; Minard, Charles G.; Wong, Connie

2018-01-01

Background Polyomaviruses, including simian virus 40 (SV40), display evidence of lymphotropic properties. This study analyzed the nature of SV40–human lymphocyte interactions in established cell lines and in primary lymphocytes. The effects of viral microRNA and the structure of the viral regulatory region on SV40 persistence were examined. Results SV40 DNA was maintained in infected B cell and myeloid cell lines during cell growth for at least 28 days. Limiting dilution analysis showed that low amounts of SV40 DNA (~2 copies per cell) were retained over time. Infected B cells remained viable and able to proliferate. Genome copies of the SV40 microRNA-null mutant persisted at higher levels than the DNA of wild-type viruses. Complex viral regulatory regions produced modestly higher DNA levels than simple regulatory regions. Viral large T-antigen protein was detected at low frequency and at low levels in infected B cells. Following infection of primary lymphocytes, SV40 DNA was detected in CD19+ B cells and CD14+ monocytes, but not in CD3+ T cells. Rescue attempts using either lysates of SV40-infected B lymphocytes, coculture of live cells, or infectious center assays all showed that replication-competent SV40 could be recovered on rare occasions. SV40 infections altered the expression of several B cell surface markers, with more pronounced changes following infections with the microRNA-null mutant. Conclusion These findings indicate that SV40 can establish persistent infections in human B lymphocytes. The cells retain low copy numbers of viral DNA; the infections are nonproductive and noncytolytic but can occasionally produce infectious virus. SV40 microRNA negatively regulates the degree of viral effects on B cells. Significance Lymphocytes may serve as viral reservoirs and may function to disseminate polyomaviruses to different tissues in a host. To our knowledge, this report is the first extensive analysis of viral microRNA effects on SV40 infection of human lymphocytes. PMID:29432481

On the regulator-insurer interaction in a structural model

NASA Astrophysics Data System (ADS)

Bernard, Carole; Chen, An

2009-11-01

In this paper, we provide a new insight to the previous work of Briys and de Varenne [E. Briys, F. de Varenne, Life insurance in a contingent claim framework: Pricing and regulatory implications, Geneva Papers on Risk and Insurance Theory 19 (1) (1994) 53-72], Grosen and Jørgensen [A. Grosen, P.L. Jørgensen, Life insurance liabilities at market value: An analysis of insolvency risk, bonus policy, and regulatory intervention rules in a barrier option framework, Journal of Risk and Insurance 69 (1) (2002) 63-91] and Chen and Suchanecki [A. Chen, M. Suchanecki, Default risk, bankruptcy procedures and the market value of life insurance liabilities, Insurance: Mathematics and Economics 40 (2007) 231-255]. We show that the particular risk management strategy followed by the insurance company can significantly change the risk exposure of the company, and that it should thus be taken into account by regulators. We first study how the regulator establishes regulation intervention levels in order to control for instance the default probability of the insurance company. This part of the analysis is based on a constant volatility. Given that the insurance company is informed of regulatory rules, we study how results can be significantly different when the insurance company follows a risk management strategy with non-constant volatilities. We thus highlight some limits of the prior literature and believe that the risk management strategy of the company should be taken into account in the estimation of the risk exposure as well as in that of the market value of liabilities.

Aromatic inhibitors derived from ammonia-pretreated lignocellulose hinder bacterial ethanologenesis by activating regulatory circuits controlling inhibitor efflux and detoxification

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

Keating, David H.; Zhang, Yaoping; Ong, Irene M.

2014-08-13

Efficient microbial conversion of lignocellulosic hydrolysates to biofuels is a key barrier to the economically viable deployment of lignocellulosic biofuels. A chief contributor to this barrier is the impact on microbial processes and energy metabolism of lignocellulose-derived inhibitors, including phenolic carboxylates, phenolic amides (for ammonia-pretreated biomass), phenolic aldehydes, and furfurals. To understand the bacterial pathways induced by inhibitors present in ammonia-pretreated biomass hydrolysates, which are less well studied than acid-pretreated biomass hydrolysates, we developed and exploited synthetic mimics of ammonia-pretreated corn stover hydrolysate (ACSH). To determine regulatory responses to the inhibitors normally present in ACSH, we measured transcript and proteinmore » levels in an Escherichia coli ethanologen using RNA-seq and quantitative proteomics during fermentation to ethanol of synthetic hydrolysates containing or lacking the inhibitors. Our study identified four major regulators mediating these responses, the MarA/SoxS/Rob network, AaeR, FrmR, and YqhC. Induction of these regulons was correlated with a reduced rate of ethanol production, buildup of pyruvate, depletion of ATP and NAD(P)H, and an inhibition of xylose conversion. The aromatic aldehyde inhibitor 5-hydroxymethylfurfural appeared to be reduced to its alcohol form by the ethanologen during fermentation, whereas phenolic acid and amide inhibitors were not metabolized. Together, our findings establish that the major regulatory responses to lignocellulose-derived inhibitors are mediated by transcriptional rather than translational regulators, suggest that energy consumed for inhibitor efflux and detoxification may limit biofuel production, and identify a network of regulators for future synthetic biology efforts.« less

Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science.

PubMed

Siddiqui, Mohammad Shadab; Harrison, Stephen A; Abdelmalek, Manal F; Anstee, Quentin M; Bedossa, Pierre; Castera, Laurent; Dimick-Santos, Lara; Friedman, Scott L; Greene, Katherine; Kleiner, David E; Megnien, Sophie; Neuschwander-Tetri, Brent A; Ratziu, Vlad; Schabel, Elmer; Miller, Veronica; Sanyal, Arun J

2018-05-01

Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001-2012). © 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases.

AtmiRNET: a web-based resource for reconstructing regulatory networks of Arabidopsis microRNAs.

PubMed

Chien, Chia-Hung; Chiang-Hsieh, Yi-Fan; Chen, Yi-An; Chow, Chi-Nga; Wu, Nai-Yun; Hou, Ping-Fu; Chang, Wen-Chi

2015-01-01

Compared with animal microRNAs (miRNAs), our limited knowledge of how miRNAs involve in significant biological processes in plants is still unclear. AtmiRNET is a novel resource geared toward plant scientists for reconstructing regulatory networks of Arabidopsis miRNAs. By means of highlighted miRNA studies in target recognition, functional enrichment of target genes, promoter identification and detection of cis- and trans-elements, AtmiRNET allows users to explore mechanisms of transcriptional regulation and miRNA functions in Arabidopsis thaliana, which are rarely investigated so far. High-throughput next-generation sequencing datasets from transcriptional start sites (TSSs)-relevant experiments as well as five core promoter elements were collected to establish the support vector machine-based prediction model for Arabidopsis miRNA TSSs. Then, high-confidence transcription factors participate in transcriptional regulation of Arabidopsis miRNAs are provided based on statistical approach. Furthermore, both experimentally verified and putative miRNA-target interactions, whose validity was supported by the correlations between the expression levels of miRNAs and their targets, are elucidated for functional enrichment analysis. The inferred regulatory networks give users an intuitive insight into the pivotal roles of Arabidopsis miRNAs through the crosstalk between miRNA transcriptional regulation (upstream) and miRNA-mediate (downstream) gene circuits. The valuable information that is visually oriented in AtmiRNET recruits the scant understanding of plant miRNAs and will be useful (e.g. ABA-miR167c-auxin signaling pathway) for further research. Database URL: http://AtmiRNET.itps.ncku.edu.tw/ © The Author(s) 2015. Published by Oxford University Press.

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...

Piecing together cis-regulatory networks: insights from epigenomics studies in plants.

PubMed

Huang, Shao-Shan C; Ecker, Joseph R

2018-05-01

5-Methylcytosine, a chemical modification of DNA, is a covalent modification found in the genomes of both plants and animals. Epigenetic inheritance of phenotypes mediated by DNA methylation is well established in plants. Most of the known mechanisms of establishing, maintaining and modifying DNA methylation have been worked out in the reference plant Arabidopsis thaliana. Major functions of DNA methylation in plants include regulation of gene expression and silencing of transposable elements (TEs) and repetitive sequences, both of which have parallels in mammalian biology, involve interaction with the transcriptional machinery, and may have profound effects on the regulatory networks in the cell. Methylome and transcriptome dynamics have been investigated in development and environmental responses in Arabidopsis and agriculturally and ecologically important plants, revealing the interdependent relationship among genomic context, methylation patterns, and expression of TE and protein coding genes. Analyses of methylome variation among plant natural populations and species have begun to quantify the extent of genetic control of methylome variation vs. true epimutation, and model the evolutionary forces driving methylome evolution in both short and long time scales. The ability of DNA methylation to positively or negatively modulate binding affinity of transcription factors (TFs) provides a natural link from genome sequence and methylation changes to transcription. Technologies that allow systematic determination of methylation sensitivities of TFs, in native genomic and methylation context without confounding factors such as histone modifications, will provide baseline datasets for building cell-type- and individual-specific regulatory networks that underlie the establishment and inheritance of complex traits. This article is categorized under: Laboratory Methods and Technologies > Genetic/Genomic Methods Biological Mechanisms > Regulatory Biology. © 2017 Wiley Periodicals, Inc.

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

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.

40 CFR 192.32 - Standards.

Code of Federal Regulations, 2011 CFR

2011-07-01

... § 192.32 Standards. (a) Standards for application during processing operations and prior to the end of... nonoperational and subject to a license by the Nuclear Regulatory Commission or an Agreement State shall limit... the Nuclear Regulatory Commission or Agreement State into individual site licenses. (ii) The Nuclear...

40 CFR 192.32 - Standards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... § 192.32 Standards. (a) Standards for application during processing operations and prior to the end of... nonoperational and subject to a license by the Nuclear Regulatory Commission or an Agreement State shall limit... the Nuclear Regulatory Commission or Agreement State into individual site licenses. (ii) The Nuclear...

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...

SND1 Transcription Factor–Directed Quantitative Functional Hierarchical Genetic Regulatory Network in Wood Formation in Populus trichocarpa[C][W

PubMed Central

Lin, Ying-Chung; Li, Wei; Sun, Ying-Hsuan; Kumari, Sapna; Wei, Hairong; Li, Quanzi; Tunlaya-Anukit, Sermsawat; Sederoff, Ronald R.; Chiang, Vincent L.

2013-01-01

Wood is an essential renewable raw material for industrial products and energy. However, knowledge of the genetic regulation of wood formation is limited. We developed a genome-wide high-throughput system for the discovery and validation of specific transcription factor (TF)–directed hierarchical gene regulatory networks (hGRNs) in wood formation. This system depends on a new robust procedure for isolation and transfection of Populus trichocarpa stem differentiating xylem protoplasts. We overexpressed Secondary Wall-Associated NAC Domain 1s (Ptr-SND1-B1), a TF gene affecting wood formation, in these protoplasts and identified differentially expressed genes by RNA sequencing. Direct Ptr-SND1-B1–DNA interactions were then inferred by integration of time-course RNA sequencing data and top-down Graphical Gaussian Modeling–based algorithms. These Ptr-SND1-B1-DNA interactions were verified to function in differentiating xylem by anti-PtrSND1-B1 antibody-based chromatin immunoprecipitation (97% accuracy) and in stable transgenic P. trichocarpa (90% accuracy). In this way, we established a Ptr-SND1-B1–directed quantitative hGRN involving 76 direct targets, including eight TF and 61 enzyme-coding genes previously unidentified as targets. The network can be extended to the third layer from the second-layer TFs by computation or by overexpression of a second-layer TF to identify a new group of direct targets (third layer). This approach would allow the sequential establishment, one two-layered hGRN at a time, of all layers involved in a more comprehensive hGRN. Our approach may be particularly useful to study hGRNs in complex processes in plant species resistant to stable genetic transformation and where mutants are unavailable. PMID:24280390

Hypoactive sexual desire disorder: inventing a disease to sell low libido.

PubMed

Meixel, Antonie; Yanchar, Elena; Fugh-Berman, Adriane

2015-10-01

Condition branding is a marketing technique in which companies develop conditions concurrently with developing drugs; examples include gastro-oesophageal reflux disease, premenstrual dysphoric disorder, social anxiety disorder, erectile dysfunction and hypoactive sexual desire disorder. Although it is illegal for pharmaceutical companies to market drugs prior to regulatory approval, there are no restrictions on marketing diseases, and industry seeks to establish a disease state in the minds of clinicians years before an expected drug launch. Continuing medical education (CME) courses are an important part of promotion prior to drug approval and have become a key marketing tool for increasing clinician receptivity to new products. We systematically identified 14 free, internet-based, industry-funded, accredited CME modules on hypoactive sexual desire disorder in women which came out before a new drug, flibanserin, was being considered for regulatory approval in the USA. Common themes in these modules included the following: (1) Hypoactive sexual desire disorder is common, underdiagnosed and can have a profound effect on quality of life. (2) Women may not be aware that they are sick or distressed. (3) Simple questionnaires can assist clinicians in diagnosing the disorder. (4) It is problematic that there are medicines available to treat sexual problems for men but not women. In fact, there is no scientifically established norm for sexual activity, feelings or desire, and there is no evidence that hypoactive sexual desire disorder is a medical condition. Hypoactive sexual desire disorder is a typical example of a condition that was sponsored by industry to prepare the market for a specific treatment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

76 FR 82005 - Self-Regulatory Organizations; Chicago Mercantile Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-66029; File No. SR-CME-2011-20] Self-Regulatory... Change To Establish a Fee Schedule Applicable to Its OTC Interest Rate Swap Clearing Offering December 22.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. \\3\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240.19b-4(f)(2). I. Self...

78 FR 23960 - Annual Public Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-23

... Medical Evidence Development and Surveillance (IMEDS) Program, methods for using observational electronic... research projects to advance regulatory science. The Foundation acts as a neutral third party to establish...

Septic Systems Guidance, Policy, and Regulations

EPA Pesticide Factsheets

EPA has developed several documents outlining its mission, priorities and regulatory authorities as well as guidance and technical information to help communities establish comprehensive septic (onsite) management programs.

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.

75 FR 18560 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-12

... proposes to extend the operation of its Supplemental Liquidity Providers Pilot (``SLP Pilot'' or ``Pilot...) (SR-NYSEAmex-2009-98) (establishing the NYSE Amex Equities SLP Pilot). See also Securities Exchange...) (establishing the SLP Pilot). See also Securities Exchange Act Release No. 59869 (May 6, 2009), 74 FR 22796 (May...

76 FR 80998 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Order Approving a Proposed Rule Change To...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-27

... Latency Network Connections December 20, 2011. I. Introduction On October 31, 2011, NASDAQ OMX BX, Inc... establish a program for offering low latency network connections and to establish the initial fees for such connections. The Exchange also proposed administrative modifications to Exchange Rule 7034. The proposed rule...

77 FR 24538 - Fukushima-Related Orders Modifying Licenses; Establishment of Atomic Safety and Licensing Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-24

... NUCLEAR REGULATORY COMMISSION [Docket Nos. EA-12-050, EA-12-051; ASLBP No. 12-918-01-EA-BD01] Fukushima-Related Orders Modifying Licenses; Establishment of Atomic Safety and Licensing Board Pursuant to delegation by the Commission dated December 29, 1972, published in the Federal Register, 37 FR 28,710 (1972...

78 FR 76350 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... switch port in the test environment. The test environment is designed to closely mirror the live equity... Change To Establish Fees Under the PHLX Pricing Schedule for Use of the Carteret Testing Facility Test... establish fees under the Pricing Schedule for use of the Testing Facility (``NTF'') test environment located...

76 FR 3184 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-19

...); (ii) establish a VIX Tier Appointment; (iii) amend the monthly fee for Floor Broker Trading Permits... demutualization, CBOE amended its Fees Schedule to establish Trading Permit, tier appointment and bandwidth packet... permit ($) 1 permit 10 permits 6,000 Tier 1 11 permits 20 permits 4,800 Tier 2 21 or more permits...

75 FR 3946 - Tennessee Valley Authority; Establishment of Atomic Safety and Licensing Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-25

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-438-CP, 50-439-CP; ASLBP No. 10-896-01-CP-BD01] Tennessee Valley Authority; Establishment of Atomic Safety and Licensing Board Pursuant to delegation by the Commission dated December 29, 1972, published in the Federal Register, 37 FR 28,710 (1972), and the...

75 FR 77024 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-10

... Bond Trading License for Member Organizations and Establish Bonds Liquidity Providers as a New Market... securities on the Exchange; and (2) establish a new class of NYSE market participants, ``Bonds Liquidity... financial incentives for bringing liquidity to the Exchange's bond market. The purpose of the proposed rule...

78 FR 5529 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Designation of a Longer...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68694; File No. SR-NASDAQ-2012-129] Self... Commission Action on Proposed Rule Change To Establish the Retail Price Improvement Program on a Pilot Basis...,\\2\\ a proposed rule change to establish a Retail Price Improvement Program to attract additional...

78 FR 40782 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

... the release for trading of the IPO until the end of the order imbalance and satisfaction of the other...) shall be established when (i) the Current Reference Prices, as defined in Rule 4753(a)(2)(A.... Order imbalances under subparagraph (B) shall be established when (i) the Current Reference Prices, as...

Establishing glucose- and ABA-regulated transcription networks in Arabidopsis by microarray analysis and promoter classification using a Relevance Vector Machine.

PubMed

Li, Yunhai; Lee, Kee Khoon; Walsh, Sean; Smith, Caroline; Hadingham, Sophie; Sorefan, Karim; Cawley, Gavin; Bevan, Michael W

2006-03-01

Establishing transcriptional regulatory networks by analysis of gene expression data and promoter sequences shows great promise. We developed a novel promoter classification method using a Relevance Vector Machine (RVM) and Bayesian statistical principles to identify discriminatory features in the promoter sequences of genes that can correctly classify transcriptional responses. The method was applied to microarray data obtained from Arabidopsis seedlings treated with glucose or abscisic acid (ABA). Of those genes showing >2.5-fold changes in expression level, approximately 70% were correctly predicted as being up- or down-regulated (under 10-fold cross-validation), based on the presence or absence of a small set of discriminative promoter motifs. Many of these motifs have known regulatory functions in sugar- and ABA-mediated gene expression. One promoter motif that was not known to be involved in glucose-responsive gene expression was identified as the strongest classifier of glucose-up-regulated gene expression. We show it confers glucose-responsive gene expression in conjunction with another promoter motif, thus validating the classification method. We were able to establish a detailed model of glucose and ABA transcriptional regulatory networks and their interactions, which will help us to understand the mechanisms linking metabolism with growth in Arabidopsis. This study shows that machine learning strategies coupled to Bayesian statistical methods hold significant promise for identifying functionally significant promoter sequences.

Tregs: Where We Are and What Comes Next?

PubMed Central

Zhao, Hai; Liao, Xuelian; Kang, Yan

2017-01-01

Regulatory T cells are usually recognized as a specialized subset of CD4+ T cells functioning in establishment and maintenance of immune tolerance. Meanwhile, there is emerging evidence that regulatory T cells (Tregs) are also present in various non-lymphoid tissues, and that they have unique phenotypes credited with activities distinct from regulatory function. Their development and function have been described in plenty of manuscripts in the past two decades. However, with the deepening of research in recent years, emerging evidence revealed some novel mechanisms about how Tregs exert their activities. First, we discuss the expanding family of regulatory lymphocytes briefly and then, try to interpret how fork-head box P3 (Foxp3), a master regulator of the regulatory pathway in the development and function of regulatory T cells, functions. Subsequently, another part of our focus is varieties of tissue Tregs. Next, we primarily discuss recent research on how Tregs work and their faceted functions in terms of soluble mediators, functional proteins, and inhibitory receptors. In particular, unless otherwise noted, the term “Treg” is used here to refer specially to the “CD4+CD25+Foxp3+” regulatory cells. PMID:29225597

Which bank? A guardian model for regulation of embryonic stem cell research in Australia.

PubMed

McLennan, A

2007-08-01

In late 2005 the Legislation Review: Prohibition of Human Cloning Act 2002 (Cth) and the Research Involving Human Embryos Act 2002 (Cth) recommended the establishment of an Australian stem cell bank. This article aims to address a lack of discussion of issues surrounding stem cell banking by suggesting possible answers to the questions of whether Australia should establish a stem cell bank and what its underlying philosophy and functions should be. Answers are developed through an analysis of regulatory, scientific and intellectual property issues relating to embryonic stem cell research in the United Kingdom, United States and Australia. This includes a detailed analysis of the United Kingdom Stem Cell Bank. It is argued that a "guardian" model stem cell bank should be established in Australia. This bank would aim to promote the maximum public benefit from human embryonic stem cell research by providing careful regulatory oversight and addressing ethical issues, while also facilitating research by addressing practical scientific concerns and intellectual property issues.

Confronting Ethical and Regulatory Challenges of Emergency Care Research With Conscious Patients.

PubMed

Dickert, Neal W; Brown, Jeremy; Cairns, Charles B; Eaves-Leanos, Aaliyah; Goldkind, Sara F; Kim, Scott Y H; Nichol, Graham; O'Conor, Katie J; Scott, Jane D; Sinert, Richard; Wendler, David; Wright, David W; Silbergleit, Robert

2016-04-01

Barriers to informed consent are ubiquitous in the conduct of emergency care research across a wide range of conditions and clinical contexts. They are largely unavoidable; can be related to time constraints, physical symptoms, emotional stress, and cognitive impairment; and affect patients and surrogates. US regulations permit an exception from informed consent for certain clinical trials in emergency settings, but these regulations have generally been used to facilitate trials in which patients are unconscious and no surrogate is available. Most emergency care research, however, involves conscious patients, and surrogates are often available. Unfortunately, there is neither clear regulatory guidance nor established ethical standards in regard to consent in these settings. In this report-the result of a workshop convened by the National Institutes of Health Office of Emergency Care Research and Department of Bioethics to address ethical challenges in emergency care research-we clarify potential gaps in ethical understanding and federal regulations about research in emergency care in which limited involvement of patients or surrogates in enrollment decisions is possible. We propose a spectrum of approaches directed toward realistic ethical goals and a research and policy agenda for addressing these issues to facilitate clinical research necessary to improve emergency care. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

[Why are some drugs so expensive? The price policy of pharmaceutical companies--"digging the grave of our health insurance-system"?].

PubMed

Glaeske, Gerd

2008-01-01

A decisive influence on the attractiveness of the German drug market is exerted by the institutions responsible for the prescribability of a drug in the framework of the Statutory Health Insurance (SHI). In this most lucrative segment of the German market, a host of reforms in recent years has led to declining transparency, where the short-lived regulatory interventions aimed - with limited success - at containing the increase in expenditure on drugs. From 1997 to 2003, however, new and patented drugs were largely protected against regulatory measures, such as fixed reimbursement rates (reference prices). However, only little use was made of this additional promotion of research activities. The majority of the new drugs in this period were me-too products, which only rarely had therapeutic advantages or advantages in the price competition with established medicines. In addition, the pharmaceutical companies widely use the privilege to set a price for drugs being prescribed in the SHI without undertaking any negotiations or presenting cost-effectiveness studies, which is unique in the European comparison. In future, the decision regarding the reimbursability of, or the reimbursable amount for, a preparation should thus be geared to lasting, transparent and unequivocal criteria guided by efficiency optimization and therapeutic progress.

International Harmonization and Cooperation in the Validation of Alternative Methods.

PubMed

Barroso, João; Ahn, Il Young; Caldeira, Cristiane; Carmichael, Paul L; Casey, Warren; Coecke, Sandra; Curren, Rodger; Desprez, Bertrand; Eskes, Chantra; Griesinger, Claudius; Guo, Jiabin; Hill, Erin; Roi, Annett Janusch; Kojima, Hajime; Li, Jin; Lim, Chae Hyung; Moura, Wlamir; Nishikawa, Akiyoshi; Park, HyeKyung; Peng, Shuangqing; Presgrave, Octavio; Singer, Tim; Sohn, Soo Jung; Westmoreland, Carl; Whelan, Maurice; Yang, Xingfen; Yang, Ying; Zuang, Valérie

The development and validation of scientific alternatives to animal testing is important not only from an ethical perspective (implementation of 3Rs), but also to improve safety assessment decision making with the use of mechanistic information of higher relevance to humans. To be effective in these efforts, it is however imperative that validation centres, industry, regulatory bodies, academia and other interested parties ensure a strong international cooperation, cross-sector collaboration and intense communication in the design, execution, and peer review of validation studies. Such an approach is critical to achieve harmonized and more transparent approaches to method validation, peer-review and recommendation, which will ultimately expedite the international acceptance of valid alternative methods or strategies by regulatory authorities and their implementation and use by stakeholders. It also allows achieving greater efficiency and effectiveness by avoiding duplication of effort and leveraging limited resources. In view of achieving these goals, the International Cooperation on Alternative Test Methods (ICATM) was established in 2009 by validation centres from Europe, USA, Canada and Japan. ICATM was later joined by Korea in 2011 and currently also counts with Brazil and China as observers. This chapter describes the existing differences across world regions and major efforts carried out for achieving consistent international cooperation and harmonization in the validation and adoption of alternative approaches to animal testing.

Will the Occupational Safety and Health Administration's Proposed Standards for Occupational Exposure to Respirable Crystalline Silica Reduce Workplace Risk?

PubMed

Dudley, Susan E; Morriss, Andrew P

2015-07-01

The Occupational Safety and Health Administration (OSHA) is developing regulations to amend existing standards for occupational exposure to respirable crystalline silica by establishing a new permissible exposure limit as well as a series of ancillary provisions for controlling exposure. This article briefly reviews OSHA's proposed regulatory approach and the statutory authority on which it is based. It then evaluates OSHA's preliminary determination of significant risk and its analysis of the risk reduction achievable by its proposed controls. It recognizes that OSHA faces multiple challenges in devising a regulatory approach that reduces exposures and health risks and meets its statutory goal. However, the greatest challenge to reducing risks associated with silica exposure is not the lack of incentives (for either employers or employees) but rather lack of information, particularly information on the relative toxicity of different forms of silica. The article finds that OSHA's proposed rule would contribute little in the way of new information, particularly since it is largely based on information that is at least a decade old--a significant deficiency, given the rapidly changing conditions observed over the last 45 years. The article concludes with recommendations for alternative approaches that would be more likely to generate information needed to improve worker health outcomes. © 2015 Society for Risk Analysis.

Overview of the Regulatory Oversight Implemented by the French Regulatory Authorities for the Clinical Investigation of Gene Therapy and Cell Therapy Products.

PubMed

Lucas-Samuel, Sophie; Ferry, Nicolas; Trouvin, Jean-Hugues

2015-01-01

Advanced therapy medicinal products, a new class of products with promising therapeutic effects, have been classified as medicinal products and as such should be developed according to a well-structured development plan, to establish their quality, safety and efficacy profile and conclude, at the time of the marketing authorisation evaluation, on a positive risk/benefit balance for patients. An important part of this development plan is achieved through clinical trials, which have also to be approved according to a well-established regulatory process, prior any initiation. This chapter is dedicated to describe the regulatory pathway to be followed in France, before initiating any clinical trial with those investigational advanced therapy medicinal products. In France, to get the final authorisation to initiate a clinical trial, the legislation imposes to run in parallel two independent but complementary authorisation procedures. The first procedure is aimed at assessing the ethical aspect of the biomedical research, while the second has to review the safety and regulatory aspects. A third procedure has to be envisaged where in case the investigational product consists or contains a genetically modified organism. The French system herein described is in line with the EU regulation on clinical trial and follows the respective deadlines for granting the final approval. The complexity of the procedure is in fact more due to the complexity of the products and protocols to be assessed than to the procedure itself which is now very close to the well-known procedure applied routinely for more conventional chemical or biological candidate medicinal products.

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...

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.

Regulatory protein BBD18 of the lyme disease spirochete: essential role during tick acquisition?

PubMed

Hayes, Beth M; Dulebohn, Daniel P; Sarkar, Amit; Tilly, Kit; Bestor, Aaron; Ambroggio, Xavier; Rosa, Patricia A

2014-04-01

The Lyme disease spirochete Borrelia burgdorferi senses and responds to environmental cues as it transits between the tick vector and vertebrate host. Failure to properly adapt can block transmission of the spirochete and persistence in either vector or host. We previously identified BBD18, a novel plasmid-encoded protein of B. burgdorferi, as a putative repressor of the host-essential factor OspC. In this study, we investigate the in vivo role of BBD18 as a regulatory protein, using an experimental mouse-tick model system that closely resembles the natural infectious cycle of B. burgdorferi. We show that spirochetes that have been engineered to constitutively produce BBD18 can colonize and persist in ticks but do not infect mice when introduced by either tick bite or needle inoculation. Conversely, spirochetes lacking BBD18 can persistently infect mice but are not acquired by feeding ticks. Through site-directed mutagenesis, we have demonstrated that abrogation of spirochete infection in mice by overexpression of BBD18 occurs only with bbd18 alleles that can suppress OspC synthesis. Finally, we demonstrate that BBD18-mediated regulation does not utilize a previously described ospC operator sequence required by B. burgdorferi for persistence in immunocompetent mice. These data lead us to conclude that BBD18 does not represent the putative repressor utilized by B. burgdorferi for the specific downregulation of OspC in the mammalian host. Rather, we suggest that BBD18 exhibits features more consistent with those of a global regulatory protein whose critical role occurs during spirochete acquisition by feeding ticks. IMPORTANCE Lyme disease, caused by Borrelia burgdorferi, is the most common arthropod-borne disease in North America. B. burgdorferi is transmitted to humans and other vertebrate hosts by ticks as they take a blood meal. Transmission between vectors and hosts requires the bacterium to sense changes in the environment and adapt. However, the mechanisms involved in this process are not well understood. By determining how B. burgdorferi cycles between two very different environments, we can potentially establish novel ways to interfere with transmission and limit infection of this vector-borne pathogen. We are studying a regulatory protein called BBD18 that we recently described. We found that too much BBD18 interferes with the spirochete's ability to establish infection in mice, whereas too little BBD18 appears to prevent colonization in ticks. Our study provides new insight into key elements of the infectious cycle of the Lyme disease spirochete.

Azaspiracid Shellfish Poisoning: A Review on the Chemistry, Ecology, and Toxicology with an Emphasis on Human Health Impacts

PubMed Central

Twiner, Michael J.; Rehmann, Nils; Hess, Philipp; Doucette, Gregory J.

2008-01-01

Azaspiracids (AZA) are polyether marine toxins that accumulate in various shellfish species and have been associated with severe gastrointestinal human intoxications since 1995. This toxin class has since been reported from several countries, including Morocco and much of western Europe. A regulatory limit of 160 μg AZA/kg whole shellfish flesh was established by the EU in order to protect human health; however, in some cases, AZA concentrations far exceed the action level. Herein we discuss recent advances on the chemistry of various AZA analogs, review the ecology of AZAs, including the putative progenitor algal species, collectively interpret the in vitro and in vivo data on the toxicology of AZAs relating to human health issues, and outline the European legislature associated with AZAs. PMID:18728760

Evaluation of Unbound Engineered Nanoparticles from a Worker Exposure and Environmental Release Perspective

NASA Astrophysics Data System (ADS)

Bunker, K.; Casuccio, G.; Lersch, T.; Ogle, R.; Wahl, L.

2009-12-01

Nanotechnology and the use of unbound engineered nanoparticles (UNP) is a rapidly developing area of materials science. UNP are defined as engineered nanoparticles that are not contained within a matrix that would prevent the nanoparticles from being mobile and a potential source of exposure. At this time there are no regulatory environmental release limits or worker exposure limits for UNP. The Lawrence Berkeley National Laboratory (LBNL) has initiated a study to evaluate worker exposure and potential environmental release of UNP related to various research activities at LBNL. The study is being performed to help identify and manage potential health and safety hazards as well as environmental impacts related to UNP. A key component of the study is the characterization of starting (source) UNP materials to assist in the determination of worker exposure and environmental release. Analysis of the starting materials is being used to establish source signatures. The source signatures will then be used in the evaluation of worker exposure and environmental release. This presentation will provide an overview of the LBNL study with a focus on the methodologies being used to analyze the samples.

Species-specific accumulation of methyl and total mercury in sharks from offshore and coastal waters of Korea.

PubMed

Kim, Sang-Jo; Lee, Hyun-Kyung; Badejo, Abimbola C; Lee, Won-Chan; Moon, Hyo-Bang

2016-01-15

Limited information is available on mercury (Hg) levels in various shark species consumed in Korea. The methyl-Hg (Me-Hg) and total Hg concentrations in all shark species ranged from 0.08 to 4.5 (mean: 1.2) mg/kg wet weight and from 0.1 to 7.0 (mean: 1.4) mg/kg wet weight, respectively. Inter-species differences in Hg accumulation were found among the species; however, Hg accumulation was homogenous between dorsal and pectoral fins within species. The highest Hg levels were found in aggressive carnivore shark species. Trophic position was important in determining Hg accumulation for aggressive carnivore sharks. Approximately 80% of shark species exceeded the safety limits for Me-Hg established by domestic and international authorities. The mean estimated daily intake of Me-Hg (1.3 μg/kg body weight/day) for Korean populations consuming various sharks was higher than the guidelines proposed by international regulatory authorities, suggesting that excessive shark fin consumption may pose potential health risks for Koreans. Copyright © 2015 Elsevier Ltd. All rights reserved.

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

PubMed

González-García, I; García-Arieta, A; Merino-Sanjuan, M; Mangas-Sanjuan, V; Bermejo, M

2018-07-01

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and C max between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. C max ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or C max ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed. Copyright © 2018 Elsevier B.V. All rights reserved.

Automotive Sectors (NAICS 336, 4231, 8111)

EPA Pesticide Factsheets

Find regulatory, compliance, and enforcement information for environmental laws and regulations for the automotive sectors, which includes transportation equipment manufacturing, and establishments involved in repair and maintenance services for vehicles

Dry Cleaning Sector (NAICS 8123)

EPA Pesticide Factsheets

The dry cleaning sector includes establishments engaged in providing laundry services and industrial launderers. Find environmental regulatory information for perchloroethylene (PERC) cleaners as well as hazardous waste regulations for dry cleaners.

Institutional and Regulatory Economics of Electricity Market Reforms: the Evidence from India, Pakistan, Bangladesh, Nepal, and Sri Lanka

NASA Astrophysics Data System (ADS)

Singh, Bipulendu

Five South Asian countries-- India, Pakistan, Bangladesh, Nepal and Sri Lanka -- embarked on electricity market reforms in the 1990's. The dissertation uses the framework of New Institutional Economics to assess the effects on electricity sector performance of both observables elements of reform (i.e. privatization, unbundling, establishment of independent regulatory agencies etc.) as well as the unobservable elements (informal beliefs, habit, norms and culture of the actors involved in reforms). The first part of the dissertation -- econometric analysis of the relationship between observable electricity market reform measures and performance indicators -- finds that for the most part electricity market reforms in South Asia are having a positive impact on the performance of the sector. This is particularly the case for reforms that have increased private sector participation in generation and distribution and have vertically unbundled utilities into generation, transmission and distribution entities. Many of the reforms are positively correlated with higher tariffs, indicating a cost to the consumers from the reforms. The relationship between independent regulation and performance indicators , however, is not established. The second part of the dissertation - analytical narrative of the reform experiences of Gujarat and Nepal -- examines the informal elements (such as beliefs, norms, culture) that motivate behavior and explains how and why reform outcomes differed in these two places. The dissertation finds that the strength of formal institutions rules and the nature of social norms and customs have a significant influence on the outcome of reforms. Aided by the strength of its formal institutional framework and more evolved social norms and customs that encouraged people to follow formal rules, reforms in the Indian state of Gujarat were a success. The weakness of the formal institutional framework and the predominance of relation-based norms and customs in Nepal that led to limited compliance with formal rules, by contrast, limited the success of power sector reforms there. Efforts to reform the electricity sector in South Asia undertaken by governments with the assistance of development agencies such as the World Bank and the Asian Development Bank have focused to a large extent on getting the content of electricity market reform measures such as unbundling, privatization, and establishment of a power market right. The analysis in this dissertation suggests that such measures will be more successful in places with relatively robust formal rule based systems. Countries that are planning to carry out significant reforms in the electricity sector will benefit from the explicit consideration of the informal norms, habits and customs of the actors that will be affected by the reforms.

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

PubMed

Bosone, Lucia; Martinez, Frédéric; Kalampalikis, Nikos

2015-04-01

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

Pharma Opportunities and Risks Multiply as Regulatory Reform Remakes APAC: Expanded Accelerated Pathways Challenge Developer Value Story, Evidence Collection, and Market Access Strategies.

PubMed

Grignolo, Alberto; Mingping, Zhang

2018-01-01

Sweeping reforms in the largest markets of the Asia-Pacific region are transforming the regulatory and commercial landscape for foreign pharmaceutical companies. Japan, South Korea, and China are leading the charge, establishing mechanisms and infrastructure that both reflect and help drive international regulatory convergence and accelerate delivery of needed, innovative products to patients. In this rapidly evolving regulatory and commercial environment, drug developers can benefit from reforms and proliferating accelerated pathway (AP) frameworks, but only with regulatory and evidence-generation strategies tailored to the region. Otherwise, they will confront significant pricing and reimbursement headwinds. Although APAC economies are at different stages of development, they share a common imperative: to balance pharmaceutical innovation with affordability. Despite the complexity of meeting these sometimes conflicting demands, companies that focus on demonstrating and delivering value for money, and that price new treatments reasonably and sustainably, can succeed both for their shareholders and the region's patient population.

Regulatory networks and connected components of the neutral space. A look at functional islands

NASA Astrophysics Data System (ADS)

Boldhaus, G.; Klemm, K.

2010-09-01

The functioning of a living cell is largely determined by the structure of its regulatory network, comprising non-linear interactions between regulatory genes. An important factor for the stability and evolvability of such regulatory systems is neutrality - typically a large number of alternative network structures give rise to the necessary dynamics. Here we study the discretized regulatory dynamics of the yeast cell cycle [Li et al., PNAS, 2004] and the set of networks capable of reproducing it, which we call functional. Among these, the empirical yeast wildtype network is close to optimal with respect to sparse wiring. Under point mutations, which establish or delete single interactions, the neutral space of functional networks is fragmented into ≈ 4.7 × 108 components. One of the smaller ones contains the wildtype network. On average, functional networks reachable from the wildtype by mutations are sparser, have higher noise resilience and fewer fixed point attractors as compared with networks outside of this wildtype component.

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...

Cyclin-dependent kinases: engines, clocks, and microprocessors.

PubMed

Morgan, D O

1997-01-01

Cyclin-dependent kinases (Cdks) play a well-established role in the regulation of the eukaryotic cell division cycle and have also been implicated in the control of gene transcription and other processes. Cdk activity is governed by a complex network of regulatory subunits and phosphorylation events whose precise effects on Cdk conformation have been revealed by recent crystallographic studies. In the cell, these regulatory mechanisms generate an interlinked series of Cdk oscillators that trigger the events of cell division.

Biotechnology; Managing the Risks of Field Testing Genetically Engineered Organisms

DTIC Science & Technology

1988-06-01

jurisdictional lines. The agencies’ principal regulatory tool for managing the risks of field testing genetically engineered organisms is the authority to...Regulatory authority has been established in numerous federal statutes designed to prevent the occurrence of harm to the environment and public health...would not be reviewed or regulated at all. According to the Insti- tute, "there are numerous organisms outside the confines of t he plant ST~( Iflt l l l