Classification criteria and probability risk maps: limitations and perspectives.

PubMed

Saisana, Michaela; Dubois, Gregoire; Chaloulakou, Archontoula; Spyrellis, Nikolas

2004-03-01

Delineation of polluted zones with respect to regulatory standards, accounting at the same time for the uncertainty of the estimated concentrations, relies on classification criteria that can lead to significantly different pollution risk maps, which, in turn, can depend on the regulatory standard itself. This paper reviews four popular classification criteria related to the violation of a probability threshold or a physical threshold, using annual (1996-2000) nitrogen dioxide concentrations from 40 air monitoring stations in Milan. The relative advantages and practical limitations of each criterion are discussed, and it is shown that some of the criteria are more appropriate for the problem at hand and that the choice of the criterion can be supported by the statistical distribution of the data and/or the regulatory standard. Finally, the polluted area is estimated over the different years and concentration thresholds using the appropriate risk maps as an additional source of uncertainty.

CMIP: a software package capable of reconstructing genome-wide regulatory networks using gene expression data.

PubMed

Zheng, Guangyong; Xu, Yaochen; Zhang, Xiujun; Liu, Zhi-Ping; Wang, Zhuo; Chen, Luonan; Zhu, Xin-Guang

2016-12-23

A gene regulatory network (GRN) represents interactions of genes inside a cell or tissue, in which vertexes and edges stand for genes and their regulatory interactions respectively. Reconstruction of gene regulatory networks, in particular, genome-scale networks, is essential for comparative exploration of different species and mechanistic investigation of biological processes. Currently, most of network inference methods are computationally intensive, which are usually effective for small-scale tasks (e.g., networks with a few hundred genes), but are difficult to construct GRNs at genome-scale. Here, we present a software package for gene regulatory network reconstruction at a genomic level, in which gene interaction is measured by the conditional mutual information measurement using a parallel computing framework (so the package is named CMIP). The package is a greatly improved implementation of our previous PCA-CMI algorithm. In CMIP, we provide not only an automatic threshold determination method but also an effective parallel computing framework for network inference. Performance tests on benchmark datasets show that the accuracy of CMIP is comparable to most current network inference methods. Moreover, running tests on synthetic datasets demonstrate that CMIP can handle large datasets especially genome-wide datasets within an acceptable time period. In addition, successful application on a real genomic dataset confirms its practical applicability of the package. This new software package provides a powerful tool for genomic network reconstruction to biological community. The software can be accessed at http://www.picb.ac.cn/CMIP/ .

Modelling the regulatory system for diabetes mellitus with a threshold window

NASA Astrophysics Data System (ADS)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2015-05-01

Piecewise (or non-smooth) glucose-insulin models with threshold windows for type 1 and type 2 diabetes mellitus are proposed and analyzed with a view to improving understanding of the glucose-insulin regulatory system. For glucose-insulin models with a single threshold, the existence and stability of regular, virtual, pseudo-equilibria and tangent points are addressed. Then the relations between regular equilibria and a pseudo-equilibrium are studied. Furthermore, the sufficient and necessary conditions for the global stability of regular equilibria and the pseudo-equilibrium are provided by using qualitative analysis techniques of non-smooth Filippov dynamic systems. Sliding bifurcations related to boundary node bifurcations were investigated with theoretical and numerical techniques, and insulin clinical therapies are discussed. For glucose-insulin models with a threshold window, the effects of glucose thresholds or the widths of threshold windows on the durations of insulin therapy and glucose infusion were addressed. The duration of the effects of an insulin injection is sensitive to the variation of thresholds. Our results indicate that blood glucose level can be maintained within a normal range using piecewise glucose-insulin models with a single threshold or a threshold window. Moreover, our findings suggest that it is critical to individualise insulin therapy for each patient separately, based on initial blood glucose levels.

A novel gene network inference algorithm using predictive minimum description length approach.

PubMed

Chaitankar, Vijender; Ghosh, Preetam; Perkins, Edward J; Gong, Ping; Deng, Youping; Zhang, Chaoyang

2010-05-28

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold which defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we proposed a new inference algorithm which incorporated mutual information (MI), conditional mutual information (CMI) and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm was evaluated using both synthetic time series data sets and a biological time series data set for the yeast Saccharomyces cerevisiae. The benchmark quantities precision and recall were used as performance measures. The results show that the proposed algorithm produced less false edges and significantly improved the precision, as compared to the existing algorithm. For further analysis the performance of the algorithms was observed over different sizes of data. We have proposed a new algorithm that implements the PMDL principle for inferring gene regulatory networks from time series DNA microarray data that eliminates the need of a fine tuning parameter. The evaluation results obtained from both synthetic and actual biological data sets show that the PMDL principle is effective in determining the MI threshold and the developed algorithm improves precision of gene regulatory network inference. Based on the sensitivity analysis of all tested cases, an optimal CMI threshold value has been identified. Finally it was observed that the performance of the algorithms saturates at a certain threshold of data size.

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

10 CFR Appendix E to Part 20 - Nationally Tracked Source Thresholds

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Nationally Tracked Source Thresholds E Appendix E to Part 20 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Pt. 20, App. E Appendix E to Part 20— Nationally Tracked Source Thresholds The Terabecquerel (TBq) values are the...

Rationality, practice variation and person-centred health policy: a threshold hypothesis.

PubMed

Djulbegovic, Benjamin; Hamm, Robert M; Mayrhofer, Thomas; Hozo, Iztok; Van den Ende, Jef

2015-12-01

Variation in practice of medicine is one of the major health policy issues of today. Ultimately, it is related to physicians' decision making. Similar patients with similar likelihood of having disease are often managed by different doctors differently: some doctors may elect to observe the patient, others decide to act based on diagnostic testing and yet others may elect to treat without testing. We explain these differences in practice by differences in disease probability thresholds at which physicians decide to act: contextual social and clinical factors and emotions such as regret affect the threshold by influencing the way doctors integrate objective data related to treatment and testing. However, depending on a theoretical construct each of the physician's behaviour can be considered rational. In fact, we showed that the current regulatory policies lead to predictably low thresholds for most decisions in contemporary practice. As a result, we may expect continuing motivation for overuse of treatment and diagnostic tests. We argue that rationality should take into account both formal principles of rationality and human intuitions about good decisions along the lines of Rawls' 'reflective equilibrium/considered judgment'. In turn, this can help define a threshold model that is empirically testable. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

Our Fat Future: Translating Adipose Stem Cell Therapy.

PubMed

Nordberg, Rachel C; Loboa, Elizabeth G

2015-09-01

Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated closed-system operations, biosensors and real-time monitoring, biomimetics, and rapid manufacturing. In light of recent FDA guidance documents, regulatory concerns about adipose stem cell therapy are discussed. Finally, an update is provided on the current state of clinical trials and the emerging industry that uses human adipose stem cells. This article is expected to stimulate future studies in translational adipose stem cell research. ©AlphaMed Press.

78 FR 75629 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

... Effectiveness of a Proposed Rule Change To Amend the MIAX Fee Schedule December 6, 2013. Pursuant to the... Priority Customer Rebate Program (the ``Program'') to (i) lower the volume thresholds of the four highest... thresholds in a month as described below. The volume thresholds are calculated based on the customer average...

78 FR 38420 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... Proposed Rule Change Amending NYSE Rule 1000 To Increase the Price Threshold for Those Securities... threshold for those securities ineligible for automatic executions from $1,000.00 or more to $10,000.00 or...). Specifically, the Exchange believes that increasing the dollar threshold for high-priced securities would...

Quasi-Experimental Approaches to Evaluating the Impact of Air Pollution on Children’s Health

PubMed Central

Heep, Samantha; Neidell, Matthew

2016-01-01

Many studies have shown a correlation between air pollution and poor children’s health. This paper focuses on recent studies that employ quasi-experimental designs in an effort to minimize the effect of confounding factors. These studies are complementary to studies using other designs and confirm that reducing air pollution reduces infant mortality, low birth weight, prematurity, congenital anomalies, asthma hospitalizations, and school absences. These results suggest that lowering the thresholds for acceptable air pollution levels may be prudent, as research has consistently found that some pollutants have negative impacts even at levels below current regulatory thresholds. Policy makers should also consider providing more information to pregnant women and families about when and where the risk of pollution exposure is highest so that they can employ avoidance behavior. PMID:22147868

Threshold of toxicological concern values for non-genotoxic effects in industrial chemicals: re-evaluation of the Cramer classification.

PubMed

Kalkhof, H; Herzler, M; Stahlmann, R; Gundert-Remy, U

2012-01-01

The TTC concept employs available data from animal testing to derive a distribution of NOAELs. Taking a probabilistic view, the 5th percentile of the distribution is taken as a threshold value for toxicity. In this paper, we use 824 NOAELs from repeated dose toxicity studies of industrial chemicals to re-evaluate the currently employed TTC values, which have been derived for substances grouped according to the Cramer scheme (Cramer et al. in Food Cosm Toxicol 16:255-276, 1978) by Munro et al. (Food Chem Toxicol 34:829-867, 1996) and refined by Kroes and Kozianowski (Toxicol Lett 127:43-46, 2002), Kroes et al. 2000. In our data set, consisting of 756 NOAELs from 28-day repeated dose testing and 57 NOAELs from 90-days repeated dose testing, the experimental NOAEL had to be extrapolated to chronic TTC using regulatory accepted extrapolation factors. The TTC values derived from our data set were higher than the currently used TTC values confirming the safety of the latter. We analysed the prediction of the Cramer classification by comparing the classification by this tool with the guidance values for classification according to the Globally Harmonised System of classification and labelling of the United Nations (GHS). Nearly 90% of the chemicals were in Cramer class 3 and assumed as highly toxic compared to 22% according to the GHS. The Cramer classification does underestimate the toxicity of chemicals only in 4.6% of the cases. Hence, from a regulatory perspective, the Cramer classification scheme might be applied as it overestimates hazard of a chemical.

76 FR 34118 - Self-Regulatory Organizations; The Depository Trust Company; Order Granting Approval of a...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-10

... to be held in its account as a threshold to any intraday redelivery. When the counter for a security... received intraday regardless of any MSEG-related deficit. Recently, DTC was advised by the Regulatory and...

Regulatory forum opinion piece*: supporting the need for international harmonization of safety assessments for food flavoring substances.

PubMed

Konishi, Yoichi; Hayashi, Shim-Mo; Fukushima, Shoji

2014-08-01

The advancement of technology and the growth of international commerce underscore the need for global harmonization of regulatory safety requirements and their assessment pertaining to consumer products such as drugs, medical devices, and food. This need is particularly relevant when safety requirements involve time-intensive and costly animal safety studies. Here we present the current regulatory requirements in Europe, the United States, and Japan for flavoring substances (FSs) used in foods and point out significant differences relevant to the international standardization for safety assessments that in our opinion need to be addressed and overcome. The safety assessments that are carried out for FSs in various countries are influenced by divergent definitions of FS, by the information required and available for regulatory submission, and by different regulatory procedures, including the use of decision tree approaches. The European Food Safety Authority (EFSA), the Expert Panel of the U.S. Flavor and Extract Manufacturers Association (FEMA), and the Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA) are making efforts to improve and harmonize the safety assessment of FSs. The application of in silico methods such as quantitative structure-activity relationships and read-across strategies relying on expert input are useful as a first-step screening of the assessment. Application of the Threshold of Toxicological Concern (TTC) approach permits conclusions that are compatible with the risk assessment approaches currently used by international advisory committees. The Japanese Regulatory Authority, on the other hand, does not yet consider in silico methods but still requires in vivo and in vitro genotoxicity test data as well as repeat-dose 90-day toxicity data in at least one species, to be submitted as the first step in the safety assessment of FSs. With this article, we echo requests that have been made for xenobiotics by the pharmaceutical industry worldwide, extending them to food-related products, especially FSs. We encourage regulatory agencies to adopt globally harmonized safety assessment procedures, regulatory guidelines, and review practices for FSs to foster global trade and to reduce costs and laboratory animal use. © 2013 by The Author(s).

Balancing consumer protection and scientific integrity in the face of uncertainty: the example of gluten-free foods.

PubMed

McCabe, Margaret Sova

2010-01-01

In 2009, gluten-free foods were not only "hot" in the marketplace, several countries, including the United States, continued efforts to define gluten-free and appropriate labeling parameters. The regulatory process illuminates how difficult regulations based on safe scientific thresholds can be for regulators, manufacturers and consumers. This article analyzes the gluten-free regulatory landscape, challenges to defining a safe gluten threshold, and how consumers might need more label information beyond the term "gluten-free." The article includes an overview of international gluten-free regulations, the Food and Drug Administration (FDA) rulemaking process, and issues for consumers.

Bayesian inference and assessment for rare-event bycatch in marine fisheries: a drift gillnet fishery case study.

PubMed

Martin, Summer L; Stohs, Stephen M; Moore, Jeffrey E

2015-03-01

Fisheries bycatch is a global threat to marine megafauna. Environmental laws require bycatch assessment for protected species, but this is difficult when bycatch is rare. Low bycatch rates, combined with low observer coverage, may lead to biased, imprecise estimates when using standard ratio estimators. Bayesian model-based approaches incorporate uncertainty, produce less volatile estimates, and enable probabilistic evaluation of estimates relative to management thresholds. Here, we demonstrate a pragmatic decision-making process that uses Bayesian model-based inferences to estimate the probability of exceeding management thresholds for bycatch in fisheries with < 100% observer coverage. Using the California drift gillnet fishery as a case study, we (1) model rates of rare-event bycatch and mortality using Bayesian Markov chain Monte Carlo estimation methods and 20 years of observer data; (2) predict unobserved counts of bycatch and mortality; (3) infer expected annual mortality; (4) determine probabilities of mortality exceeding regulatory thresholds; and (5) classify the fishery as having low, medium, or high bycatch impact using those probabilities. We focused on leatherback sea turtles (Dermochelys coriacea) and humpback whales (Megaptera novaeangliae). Candidate models included Poisson or zero-inflated Poisson likelihood, fishing effort, and a bycatch rate that varied with area, time, or regulatory regime. Regulatory regime had the strongest effect on leatherback bycatch, with the highest levels occurring prior to a regulatory change. Area had the strongest effect on humpback bycatch. Cumulative bycatch estimates for the 20-year period were 104-242 leatherbacks (52-153 deaths) and 6-50 humpbacks (0-21 deaths). The probability of exceeding a regulatory threshold under the U.S. Marine Mammal Protection Act (Potential Biological Removal, PBR) of 0.113 humpback deaths was 0.58, warranting a "medium bycatch impact" classification of the fishery. No PBR thresholds exist for leatherbacks, but the probability of exceeding an anticipated level of two deaths per year, stated as part of a U.S. Endangered Species Act assessment process, was 0.0007. The approach demonstrated here would allow managers to objectively and probabilistically classify fisheries with respect to bycatch impacts on species that have population-relevant mortality reference points, and declare with a stipulated level of certainty that bycatch did or did not exceed estimated upper bounds.

Event-based cluster synchronization of coupled genetic regulatory networks

NASA Astrophysics Data System (ADS)

Yue, Dandan; Guan, Zhi-Hong; Li, Tao; Liao, Rui-Quan; Liu, Feng; Lai, Qiang

2017-09-01

In this paper, the cluster synchronization of coupled genetic regulatory networks with a directed topology is studied by using the event-based strategy and pinning control. An event-triggered condition with a threshold consisting of the neighbors' discrete states at their own event time instants and a state-independent exponential decay function is proposed. The intra-cluster states information and extra-cluster states information are involved in the threshold in different ways. By using the Lyapunov function approach and the theories of matrices and inequalities, we establish the cluster synchronization criterion. It is shown that both the avoidance of continuous transmission of information and the exclusion of the Zeno behavior are ensured under the presented triggering condition. Explicit conditions on the parameters in the threshold are obtained for synchronization. The stability criterion of a single GRN is also given under the reduced triggering condition. Numerical examples are provided to validate the theoretical results.

78 FR 35082 - Self-Regulatory Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... Organizations; Chicago Stock Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... designated threshold.\\5\\ In addition, the Exchange adopted security-type specific parameter values, such as..., Threshold Away Amount, Minimum Duration and N mult , will be made through proposed fee filings pursuant to...

Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits

PubMed Central

Rodrigo, Guillermo; Poyatos, Juan F.

2016-01-01

Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits. PMID:27741249

Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz

NASA Astrophysics Data System (ADS)

Ebert, S.; Eom, S. J.; Schuderer, J.; Apostel, U.; Tillmann, T.; Dasenbrock, C.; Kuster, N.

2005-11-01

The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR = 0, 2, 5, 7.2, 10, 12.6 and 20 W kg-1) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 ± 2 °C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg-1 and 5 W kg-1, whereas the breakdown of regulation was determined at 10.1 ± 4.0 W kg-1(K = 2) for B6C3F1 mice and 7.7 ± 1.6 W kg-1(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg-1(K = 2) at laboratory conditions.

Two new competing pathways establish the threshold for cyclin-B-Cdk1 activation at the meiotic G2/M transition.

PubMed

Hiraoka, Daisaku; Aono, Ryota; Hanada, Shin-Ichiro; Okumura, Eiichi; Kishimoto, Takeo

2016-08-15

Extracellular ligands control biological phenomena. Cells distinguish physiological stimuli from weak noise stimuli by establishing a ligand-concentration threshold. Hormonal control of the meiotic G2/M transition in oocytes is essential for reproduction. However, the mechanism for threshold establishment is unclear. In starfish oocytes, maturation-inducing hormones activate the PI3K-Akt pathway through the Gβγ complex of heterotrimeric G-proteins. Akt directly phosphorylates both Cdc25 phosphatase and Myt1 kinase, resulting in activation of cyclin-B-Cdk1, which then induces meiotic G2/M transition. Here, we show that cyclin-B-Cdk1 is partially activated after subthreshold hormonal stimuli, but this triggers negative feedback, resulting in dephosphorylation of Akt sites on Cdc25 and Myt1, thereby canceling the signal. We also identified phosphatase activity towards Akt substrates that exists independent of stimuli. In contrast to these negative regulatory activities, an atypical Gβγ-dependent pathway enhances PI3K-Akt-dependent phosphorylation. Based on these findings, we propose a model for threshold establishment in which hormonal dose-dependent competition between these new pathways establishes a threshold; the atypical Gβγ-pathway becomes predominant over Cdk-dependent negative feedback when the stimulus exceeds this threshold. Our findings provide a regulatory connection between cell cycle and signal transduction machineries. © 2016. Published by The Company of Biologists Ltd.

75 FR 52558 - Self-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-26

...-Regulatory Organizations; NASDAQ OMX PHLX, Inc.; Notice of Filing and Immediate Effectiveness of Proposed... costs associated with system issues that are attributable to cancelled AON orders. A Professional order... organization in order for a member organization to be assessed the Cancellation Fee (``500 Threshold''). The...

75 FR 55385 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

...-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... guarantee limits the increase in a Members' execution costs associating with failing to meet the volume thresholds of other exchanges and ECNs while a Member is in the process of migrating volumes from one...

76 FR 65555 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-21

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65583; File No. SR-ISE-2011-68] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend the Volume Threshold for Tier-Based Rebates for Qualified Contingent Cross Orders and Solicitation Orders Executed...

76 FR 77279 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-65898; File No. SR-ISE-2011-78] Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change to Amend the Threshold Levels for Tier-Based Rebates for Qualified Contingent Cross Orders and Solicitation Orders Executed...

Effect of water treatment additives on lime softening residual trace chemical composition--implications for disposal and reuse.

PubMed

Cheng, Weizhi; Roessler, Justin; Blaisi, Nawaf I; Townsend, Timothy G

2014-12-01

Drinking water treatment residues (WTR) offer potential benefits when recycled through land application. The current guidance in Florida, US allows for unrestricted land application of lime softening WTR; alum and ferric WTR require additional evaluation of total and leachable concentrations of select trace metals prior to land application. In some cases a mixed WTR is produced when lime softening is accompanied by the addition of a coagulant or other treatment chemical; applicability of the current guidance is unclear. The objective of this research was to characterize the total and leachable chemical content of WTR from Florida facilities that utilize multiple treatment chemicals. Lime and mixed lime WTR samples were collected from 18 water treatment facilities in Florida. Total and leachable concentrations of the WTR were measured. To assess the potential for disposal of mixed WTR as clean fill below the water table, leaching tests were conducted at multiple liquid to solid ratios and under reducing conditions. The results were compared to risk-based soil and groundwater contamination thresholds. Total metal concentrations of WTR were found to be below Florida soil contaminant thresholds with Fe found in the highest abundance at a concentration of 3600 mg/kg-dry. Aluminum was the only element that exceeded the Florida groundwater contaminant thresholds using SPLP (95% UCL = 0.23 mg/L; risk threshold = 0.2 mg/L). Tests under reducing conditions showed elevated concentrations of Fe and Mn, ranging from 1 to 3 orders of magnitude higher than SPLP leachates. Mixed lime WTR concentrations (total and leachable) were lower than the ferric and alum WTR concentrations, supporting that mixed WTR are appropriately represented as lime WTR. Testing of WTR under reducing conditions demonstrated the potential for release of certain trace metals (Fe, Al, Mn) above applicable regulatory thresholds; additional evaluation is needed to assess management options where reducing conditions may develop. Copyright © 2014 Elsevier Ltd. All rights reserved.

76 FR 41839 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

... Effectiveness of Proposed Rule Change Relating to PAR Official Fees in Volatility Index Options July 7, 2011... threshold tiers for the assessment of PAR Official Fees in Volatility Index Options classes based on the..., 2011 to establish volume threshold tiers for the assessment of PAR Official Fees in Volatility Index...

78 FR 62778 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

...'') to add orders yielding Flag AA to the calculation of the average daily trading (``ADV'') threshold... AA to the calculation of the ADV threshold required to meet the MidPoint Match Volume Tier. Footnote... Match using MidPoint Match order type). The Exchange proposes to add orders yielding Flag AA (MidPoint...

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

PubMed

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

2014-11-01

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

Measuring NMHC and NMOG emissions from motor vehicles via FTIR spectroscopy

NASA Astrophysics Data System (ADS)

Gierczak, Christine A.; Kralik, Lora L.; Mauti, Adolfo; Harwell, Amy L.; Maricq, M. Matti

2017-02-01

The determination of non-methane organic gases (NMOG) emissions according to United States Environmental Protection Agency (EPA) regulations is currently a multi-step process requiring separate measurement of various emissions components by a number of independent on-line and off-line techniques. The Fourier transform infrared spectroscopy (FTIR) method described in this paper records all required components using a single instrument. It gives data consistent with the regulatory method, greatly simplifies the process, and provides second by second time resolution. Non-methane hydrocarbons (NMHCs) are measured by identifying a group of hydrocarbons, including oxygenated species, that serve as a surrogate for this class, the members of which are dynamically included if they are present in the exhaust above predetermined threshold levels. This yields an FTIR equivalent measure of NMHC that correlates within 5% to the regulatory flame ionization detection (FID) method. NMOG is then determined per regulatory calculation solely from FTIR recorded emissions of NMHC, ethanol, acetaldehyde, and formaldehyde, yielding emission rates that also correlate within 5% with the reference method. Examples are presented to show how the resulting time resolved data benefit aftertreatment development for light duty vehicles.

77 FR 15436 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-15

... Effectiveness of a Proposed Rule Change To Amend Its Fees Schedule March 9, 2012. Pursuant to Section 19(b)(1... customer transaction (the threshold for all index options is set at 5,000 contracts other than S&P 500 index options, for which the threshold is 10,000 contracts). The Exchange offers the Discount in order...

78 FR 62903 - Self-Regulatory Organizations; EDGX Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

....0027 per share; (vi) lower the ADV threshold required to meet the MidPoint Match Volume Tier; and (vii...) lower the ADV threshold required to meet the MidPoint Match Volume Tier; and (vii) decrease the rebate... shares in average daily volume (``ADV'') on a daily basis, measured monthly; and (2) add at least 1,000...

77 FR 9288 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-16

... electronic executions and to delete references to Royalty Fees for foreign currency options, which the... posted electronic executions and to delete references to Royalty Fees for foreign currency options, which....... -0.36 Threshold 3 More than 1,200,000.. -0.42 Threshold 4 More than 3,500,000.. -0.43 Royalty Fees...

Groundwater Quality Data for the Tahoe-Martis Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Fram, Miranda S.; Munday, Cathy; Belitz, Kenneth

2009-01-01

Groundwater quality in the approximately 460-square-mile Tahoe-Martis study unit was investigated in June through September 2007 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw groundwater used for public water supplies within the Tahoe-Martis study unit (Tahoe-Martis) and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 52 wells in El Dorado, Placer, and Nevada Counties. Forty-one of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and 11 were selected to aid in evaluation of specific water-quality issues (understanding wells). The groundwater samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOC], pesticides and pesticide degradates, and pharmaceutical compounds), constituents of special interest (perchlorate and N-nitrosodimethylamine [NDMA]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial indicators. Naturally occurring isotopes (tritium, carbon-14, strontium isotope ratio, and stable isotopes of hydrogen and oxygen of water), and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, 240 constituents and water-quality indicators were investigated. Three types of quality-control samples (blanks, replicates, and samples for matrix spikes) each were collected at 12 percent of the wells, and the results obtained from these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that data for the groundwater samples were not compromised by possible contamination during sample collection, handling or analysis. Differences between replicate samples were within acceptable ranges. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH), and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate of compliance or noncompliance with regulatory thresholds. The concentrations of most constituents detected in groundwater samples from the Tahoe-Martis wells were below drinking-water thresholds. Organic compounds (VOCs and pesticides) were detected in about 40 percent of the samples from grid wells, and most concentrations were less than 1/100th of regulatory and nonregulatory health-based thresholds, although the conentration of perchloroethene in one sample was above the USEPA maximum contaminant level (MCL-US). Concentrations of all trace elements and nutrients in samples from grid wells were below regulatory and nonregulatory health-based thresholds, with five exceptions. Concentra

78 FR 11795 - Minimum Technical Standards for Class II Gaming Systems and Equipment

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

... threshold amount. The Commission increased that amount in the MICS from $1,000,000 to $3,000,000. The... considered to be small entities for the purposes of the Regulatory Flexibility Act. Small Business Regulatory Enforcement Fairness Act The proposed rule is not a major rule under 5 U.S.C. 804(2), the Small Business...

78 FR 26836 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69503; File No. SR-NYSEArca-2013-44] Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Its Schedule of Fees and Charges for Exchange Services To Amend Step Up Tier 2 to Reduce the Volume Threshold Requirements Needed To...

76 FR 77128 - Alternate Tonnage Threshold for Oil Spill Response Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-12

...The Coast Guard is establishing an alternate size threshold based on the measurement system established under the International Convention on Tonnage Measurement of Ships, 1969, for Oil Spill Response Vessels (OSRVs), which are properly certificated under 46 CFR subchapter L. The present size threshold of 500 gross registered tons is based on the U.S. regulatory measurement system. This rule provides an alternative for owners and operators of offshore supply vessels (OSVs) that may result in an increase in oil spill response capacity and capability.

Evaluating links between forest harvest and stream temperature threshold exceedances: the value of spatial and temporal data

Treesearch

Jeremiah D. Groom; Sherri L. Johnson; Joshua D. Seeds; George G. Ice

2017-01-01

We present the results of a replicated before-after-control-impact study on 33 streams to test the effectiveness of riparian rules for private and State forests at meeting temperature criteria in streams in western Oregon. Many states have established regulatory temperature thresholds, referred to as numeric criteria, to protect cold-water fishes such as salmon and...

Predictive minimum description length principle approach to inferring gene regulatory networks.

PubMed

Chaitankar, Vijender; Zhang, Chaoyang; Ghosh, Preetam; Gong, Ping; Perkins, Edward J; Deng, Youping

2011-01-01

Reverse engineering of gene regulatory networks using information theory models has received much attention due to its simplicity, low computational cost, and capability of inferring large networks. One of the major problems with information theory models is to determine the threshold that defines the regulatory relationships between genes. The minimum description length (MDL) principle has been implemented to overcome this problem. The description length of the MDL principle is the sum of model length and data encoding length. A user-specified fine tuning parameter is used as control mechanism between model and data encoding, but it is difficult to find the optimal parameter. In this work, we propose a new inference algorithm that incorporates mutual information (MI), conditional mutual information (CMI), and predictive minimum description length (PMDL) principle to infer gene regulatory networks from DNA microarray data. In this algorithm, the information theoretic quantities MI and CMI determine the regulatory relationships between genes and the PMDL principle method attempts to determine the best MI threshold without the need of a user-specified fine tuning parameter. The performance of the proposed algorithm is evaluated using both synthetic time series data sets and a biological time series data set (Saccharomyces cerevisiae). The results show that the proposed algorithm produced fewer false edges and significantly improved the precision when compared to existing MDL algorithm.

Scientific basis and regulatory aspects for the toxicology of plant protection products in the European Union.

PubMed

Anadón, A; Martínez-Larrañaga, M R; Martínez, M A

2001-10-01

Authorization of plant protection products/agrochemicals/pesticides in the European Union is done on the basis of their toxicological properties. This paper reviews the current legislation for placing an agrochemical on the market (ie a new substance or a existing active substance), and the toxicology studies needed for inclusion of a substance in any of the annexes of the Council Directive of the European Economic Community 91/414/ EEC. Risk analysis and its steps is discussed. The "threshold toxicity" employed to allow risk characterisation of plant protection products is described, such as acceptable daily intake, acceptable operator exposure level, acute reference dose, and maximum admissible concentration in water.

The influence of thresholds on the risk assessment of carcinogens in food.

PubMed

Pratt, Iona; Barlow, Susan; Kleiner, Juliane; Larsen, John Christian

2009-08-01

The risks from exposure to chemical contaminants in food must be scientifically assessed, in order to safeguard the health of consumers. Risk assessment of chemical contaminants that are both genotoxic and carcinogenic presents particular difficulties, since the effects of such substances are normally regarded as being without a threshold. No safe level can therefore be defined, and this has implications for both risk management and risk communication. Risk management of these substances in food has traditionally involved application of the ALARA (As Low as Reasonably Achievable) principle, however ALARA does not enable risk managers to assess the urgency and extent of the risk reduction measures needed. A more refined approach is needed, and several such approaches have been developed. Low-dose linear extrapolation from animal carcinogenicity studies or epidemiological studies to estimate risks for humans at low exposure levels has been applied by a number of regulatory bodies, while more recently the Margin of Exposure (MOE) approach has been applied by both the European Food Safety Authority and the Joint FAO/WHO Expert Committee on Food Additives. A further approach is the Threshold of Toxicological Concern (TTC), which establishes exposure thresholds for chemicals present in food, dependent on structure. Recent experimental evidence that genotoxic responses may be thresholded has significant implications for the risk assessment of chemicals that are both genotoxic and carcinogenic. In relation to existing approaches such as linear extrapolation, MOE and TTC, the existence of a threshold reduces the uncertainties inherent in such methodology and improves confidence in the risk assessment. However, for the foreseeable future, regulatory decisions based on the concept of thresholds for genotoxic carcinogens are likely to be taken case-by-case, based on convincing data on the Mode of Action indicating that the rate limiting variable for the development of cancer lies on a critical pathway that is thresholded.

Australians are not equally protected from industrial air pollution

NASA Astrophysics Data System (ADS)

Dobbie, B.; Green, D.

2015-05-01

Australian air pollution standards are set at national and state levels for a number of chemicals harmful to human health. However, these standards do not need to be met when ad hoc pollution licences are issued by state environment agencies. This situation results in a highly unequal distribution of air pollution between towns and cities, and across the country. This paper examines these pollution regulations through two case studies, specifically considering the ability of the regulatory regime to protect human health from lead and sulphur dioxide pollution in the communities located around smelters. It also considers how the proposed National Clean Air Agreement, once enacted, might serve to reduce this pollution equity problem. Through the case studies we show that there are at least three discrete concerns relating to the current licencing system. They are: non-onerous emission thresholds for polluting industry; temporal averaging thresholds masking emission spikes; and ineffective penalties for breaching licence agreements. In conclusion, we propose a set of new, legally-binding national minimum standards for industrial air pollutants must be developed and enforced, which can only be modified by more (not less) stringent state licence arrangements.

Contributions of adaptation currents to dynamic spike threshold on slow timescales: Biophysical insights from conductance-based models

NASA Astrophysics Data System (ADS)

Yi, Guosheng; Wang, Jiang; Wei, Xile; Deng, Bin; Li, Huiyan; Che, Yanqiu

2017-06-01

Spike-frequency adaptation (SFA) mediated by various adaptation currents, such as voltage-gated K+ current (IM), Ca2+-gated K+ current (IAHP), or Na+-activated K+ current (IKNa), exists in many types of neurons, which has been shown to effectively shape their information transmission properties on slow timescales. Here we use conductance-based models to investigate how the activation of three adaptation currents regulates the threshold voltage for action potential (AP) initiation during the course of SFA. It is observed that the spike threshold gets depolarized and the rate of membrane depolarization (dV/dt) preceding AP is reduced as adaptation currents reduce firing rate. It is indicated that the presence of inhibitory adaptation currents enables the neuron to generate a dynamic threshold inversely correlated with preceding dV/dt on slower timescales than fast dynamics of AP generation. By analyzing the interactions of ionic currents at subthreshold potentials, we find that the activation of adaptation currents increase the outward level of net membrane current prior to AP initiation, which antagonizes inward Na+ to result in a depolarized threshold and lower dV/dt from one AP to the next. Our simulations demonstrate that the threshold dynamics on slow timescales is a secondary effect caused by the activation of adaptation currents. These findings have provided a biophysical interpretation of the relationship between adaptation currents and spike threshold.

AREA RADIATION MONITOR

DOEpatents

Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

1962-06-12

S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

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...

Input-output relation and energy efficiency in the neuron with different spike threshold dynamics.

PubMed

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt) preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC) through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na(+) and K(+) currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism.

Input-output relation and energy efficiency in the neuron with different spike threshold dynamics

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Neuron encodes and transmits information through generating sequences of output spikes, which is a high energy-consuming process. The spike is initiated when membrane depolarization reaches a threshold voltage. In many neurons, threshold is dynamic and depends on the rate of membrane depolarization (dV/dt) preceding a spike. Identifying the metabolic energy involved in neural coding and their relationship to threshold dynamic is critical to understanding neuronal function and evolution. Here, we use a modified Morris-Lecar model to investigate neuronal input-output property and energy efficiency associated with different spike threshold dynamics. We find that the neurons with dynamic threshold sensitive to dV/dt generate discontinuous frequency-current curve and type II phase response curve (PRC) through Hopf bifurcation, and weak noise could prohibit spiking when bifurcation just occurs. The threshold that is insensitive to dV/dt, instead, results in a continuous frequency-current curve, a type I PRC and a saddle-node on invariant circle bifurcation, and simultaneously weak noise cannot inhibit spiking. It is also shown that the bifurcation, frequency-current curve and PRC type associated with different threshold dynamics arise from the distinct subthreshold interactions of membrane currents. Further, we observe that the energy consumption of the neuron is related to its firing characteristics. The depolarization of spike threshold improves neuronal energy efficiency by reducing the overlap of Na+ and K+ currents during an action potential. The high energy efficiency is achieved at more depolarized spike threshold and high stimulus current. These results provide a fundamental biophysical connection that links spike threshold dynamics, input-output relation, energetics and spike initiation, which could contribute to uncover neural encoding mechanism. PMID:26074810

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

Calabrese, Edward J.

This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and 'traditional' medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- andmore » public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment.« less

76 FR 27677 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-12

...] Index and other specified exchange traded products.\\5\\ \\3\\ See ISE Rule 2100(c)(13). \\4\\ See Securities... that this threshold differentiation is appropriate because lower priced securities tend to be more...

77 FR 38729 - Alternate Tonnage Threshold for Oil Spill Response Vessels

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-29

...The Coast Guard is establishing an alternate size threshold based on the measurement system established under the International Convention on Tonnage Measurement of Ships, 1969, for oil spill response vessels, which are properly certificated under 46 CFR chapter I, subchapter L. The present size threshold of 500 gross register tons is based on the U.S. regulatory measurement system. This final rule provides an alternative for owners and operators of offshore supply vessels that may result in an increase in oil spill response capacity and capability. This final rule adopts, without change, the interim rule amending 46 CFR part 126 published in the Federal Register on Monday, December 12, 2011.

Chemical characterization and ecotoxicity of three soil foaming agents used in mechanized tunneling.

PubMed

Baderna, Diego; Lomazzi, Eleonora; Passoni, Alice; Pogliaghi, Alberto; Petoumenou, Maria Ifigeneia; Bagnati, Renzo; Lodi, Marco; Viarengo, Aldo; Sforzini, Susanna; Benfenati, Emilio; Fanelli, Roberto

2015-10-15

The construction of tunnels and rocks with mechanized drills produces several tons of rocky debris that are today recycled as construction material or as soil replacement for covering rocky areas. The lack of accurate information about the environmental impact of these excavated rocks and foaming agents added during the excavation process has aroused increasing concern for ecosystems and human health. The present study proposes an integrated approach to the assessment of the potential environmental impact of three foaming agents containing different anionic surfactants and other polymers currently on the market and used in tunnel boring machines. The strategy includes chemical characterization with high resolution mass spectrometry techniques to identify the components of each product, the use of in silico tools to perform a similarity comparison among these compounds and some pollutants already listed in regulatory frameworks to identify possible threshold concentrations of contamination, and the application of a battery of ecotoxicological assays to investigate the impact of each foaming mixture on model organisms of soil (higher plants and Eisenia andrei) and water communities (Daphnia magna). The study identified eleven compounds not listed on the material safety data sheets for which we have identified possible concentrations of contamination based on existing regulatory references. The bioassays allowed us to determine the no effect concentrations (NOAECs) of the three mixtures, which were subsequently used as threshold concentration for the product in its entirety. The technical mixtures used in this study have a different degree of toxicity and the predicted environmental concentrations based on the conditions of use are lower than the NOAEC for soils but higher than the NOAEC for water, posing a potential risk to the waters due to the levels of foaming agents in the muck. Copyright © 2015 Elsevier B.V. All rights reserved.

Hydrodynamic sensory threshold in harbour seals (Phoca vitulina) for artificial flatfish breathing currents.

PubMed

Niesterok, Benedikt; Dehnhardt, Guido; Hanke, Wolf

2017-07-01

Harbour seals have the ability to detect benthic fish such as flatfish using the water currents these fish emit through their gills (breathing currents). We investigated the sensory threshold in harbour seals for this specific hydrodynamic stimulus under conditions which are realistic for seals hunting in the wild. We used an experimental platform where an artificial breathing current was emitted through one of eight different nozzles. Two seals were trained to search for the active nozzle. Each experimental session consisted of eight test trials of a particular stimulus intensity and 16 supra-threshold trials of high stimulus intensity. Test trials were conducted with the animals blindfolded. To determine the threshold, a series of breathing currents differing in intensity was used. For each intensity, three sessions were run. The threshold in terms of maximum water velocity within the breathing current was 4.2 cm s -1 for one seal and 3.7 cm s -1 for the other. We measured background flow velocities from 1.8 to 3.4 cm s -1 Typical swimming speeds for both animals were around 0.5 m s -1 Swimming speed differed between successful and unsuccessful trials. It appears that swimming speed is restricted for the successful detection of a breathing current close to the threshold. Our study is the first to assess a sensory threshold of the vibrissal system for a moving harbour seal under near-natural conditions. Furthermore, this threshold was defined for a natural type of stimulus differing from classical dipole stimuli which have been widely used in threshold determination so far. © 2017. Published by The Company of Biologists Ltd.

An Approach to Industrial Stormwater Benchmarks: Establishing and Using Site-Specific Threshold Criteria at Lawrence Livermore National Laboratory

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

Campbell, C G; Mathews, S

2006-09-07

Current regulatory schemes use generic or industrial sector specific benchmarks to evaluate the quality of industrial stormwater discharges. While benchmarks can be a useful tool for facility stormwater managers in evaluating the quality stormwater runoff, benchmarks typically do not take into account site-specific conditions, such as: soil chemistry, atmospheric deposition, seasonal changes in water source, and upstream land use. Failing to account for these factors may lead to unnecessary costs to trace a source of natural variation, or potentially missing a significant local water quality problem. Site-specific water quality thresholds, established upon the statistical evaluation of historic data take intomore » account these factors, are a better tool for the direct evaluation of runoff quality, and a more cost-effective trigger to investigate anomalous results. Lawrence Livermore National Laboratory (LLNL), a federal facility, established stormwater monitoring programs to comply with the requirements of the industrial stormwater permit and Department of Energy orders, which require the evaluation of the impact of effluent discharges on the environment. LLNL recognized the need to create a tool to evaluate and manage stormwater quality that would allow analysts to identify trends in stormwater quality and recognize anomalous results so that trace-back and corrective actions could be initiated. LLNL created the site-specific water quality threshold tool to better understand the nature of the stormwater influent and effluent, to establish a technical basis for determining when facility operations might be impacting the quality of stormwater discharges, and to provide ''action levels'' to initiate follow-up to analytical results. The threshold criteria were based on a statistical analysis of the historic stormwater monitoring data and a review of relevant water quality objectives.« less

75 FR 14669 - Regulation of Fuels and Fuel Additives: Changes to Renewable Fuel Standard Program

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

...Under the Clean Air Act Section 211(o), as amended by the Energy Independence and Security Act of 2007 (EISA), the Environmental Protection Agency is required to promulgate regulations implementing changes to the Renewable Fuel Standard program. The revised statutory requirements specify the volumes of cellulosic biofuel, biomass-based diesel, advanced biofuel, and total renewable fuel that must be used in transportation fuel. This action finalizes the regulations that implement the requirements of EISA, including the cellulosic, biomass- based diesel, advanced biofuel, and renewable fuel standards that will apply to all gasoline and diesel produced or imported in 2010. The final regulations make a number of changes to the current Renewable Fuel Standard program while retaining many elements of the compliance and trading system already in place. This final rule also implements the revised statutory definitions and criteria, most notably the new greenhouse gas emission thresholds for renewable fuels and new limits on renewable biomass feedstocks. This rulemaking marks the first time that greenhouse gas emission performance is being applied in a regulatory context for a nationwide program. As mandated by the statute, our greenhouse gas emission assessments consider the full lifecycle emission impacts of fuel production from both direct and indirect emissions, including significant emissions from land use changes. In carrying out our lifecycle analysis we have taken steps to ensure that the lifecycle estimates are based on the latest and most up-to-date science. The lifecycle greenhouse gas assessments reflected in this rulemaking represent significant improvements in analysis based on information and data received since the proposal. However, we also recognize that lifecycle GHG assessment of biofuels is an evolving discipline and will continue to revisit our lifecycle analyses in the future as new information becomes available. EPA plans to ask the National Academy of Sciences for assistance as we move forward. Based on current analyses we have determined that ethanol from corn starch will be able to comply with the required greenhouse gas (GHG) threshold for renewable fuel. Similarly, biodiesel can be produced to comply with the 50% threshold for biomass-based diesel, sugarcane with the 50% threshold for advanced biofuel and multiple cellulosic-based fuels with their 60% threshold. Additional fuel pathways have also been determined to comply with their thresholds. The assessment for this rulemaking also indicates the increased use of renewable fuels will have important environmental, energy and economic impacts for our Nation.

48 CFR 2045.371 - Property accountability procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Property accountability procedures. 2045.371 Section 2045.371 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION... accountability procedures. (a) The threshold for detailed reporting of capitalized equipment by contractors is...

48 CFR 439.101 - Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Specific thresholds at which USDA Office of the Chief Information Officer Information Technology... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 439.101 Policy. (a) In addition to policy and regulatory guidance contained in the FAR and AGAR: (1) The USDA Information Technology Capital Planning and...

48 CFR 439.101 - Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Specific thresholds at which USDA Office of the Chief Information Officer Information Technology... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 439.101 Policy. (a) In addition to policy and regulatory guidance contained in the FAR and AGAR: (1) The USDA Information Technology Capital Planning and...

48 CFR 439.101 - Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Specific thresholds at which USDA Office of the Chief Information Officer Information Technology... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 439.101 Policy. (a) In addition to policy and regulatory guidance contained in the FAR and AGAR: (1) The USDA Information Technology Capital Planning and...

48 CFR 439.101 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Specific thresholds at which USDA Office of the Chief Information Officer Information Technology... CONTRACTING ACQUISITION OF INFORMATION TECHNOLOGY General 439.101 Policy. (a) In addition to policy and regulatory guidance contained in the FAR and AGAR: (1) The USDA Information Technology Capital Planning and...

THE MAQC PROJECT: ESTABLISHING QC METRICS AND THRESHOLDS FOR MICROARRAY QUALITY CONTROL

EPA Science Inventory

Microarrays represent a core technology in pharmacogenomics and toxicogenomics; however, before this technology can successfully and reliably be applied in clinical practice and regulatory decision-making, standards and quality measures need to be developed. The Microarray Qualit...

77 FR 19741 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-02

... will be attractive to all investors and benefit all market participants. The thresholds in the... such rule change if it appears to the Commission that such action is necessary or appropriate in the...

Soil thresholds and a decision tool to manage food safety of crops grown in chlordecone polluted soil in the French West Indies.

PubMed

Clostre, Florence; Letourmy, Philippe; Lesueur-Jannoyer, Magalie

2017-04-01

Due to the persistent pollution of soils by an organochlorine, chlordecone (CLD also known as Kepone © ) in the French West Indies, some crops may be contaminated beyond the European regulatory threshold, the maximum residue limit (MRL). Farmers need to be able to foresee the risk of not complying with the regulatory threshold in each field and for each crop, if not, farmers whose fields are contaminated would have to stop cultivating certain crops in the fields concerned. To help farmers make the right choices, we studied the relationship between contamination of the soil and contamination of crops. We showed that contamination of a crop by CLD depended on the crop concerned, the soil CLD content and the type of soil. We grouped crop products in three categories: (i) non-uptakers and low-uptakers, (ii) medium-uptakers, and (iii) high-uptakers, according to their level of contamination and the resulting risk of exceeding MRL. Using a simulation model, we computed the soil threshold required to ensure the risk of not complying with MRL was sufficiently low for each crop product and soil type. Threshold values ranged from 0.02 μgkg -1 for dasheen grown in nitisol to 1.7 μgkg -1 for yam grown in andosol in the high-uptake category, and from 1 μgkg -1 for lettuce grown in nitisol to 45 μgkg -1 for the leaves of spring onions grown in andosol in the medium-uptake category. Contamination of non-uptakers and low-uptakers did not depend on soil contamination. With these results, we built an easy-to-use decision support tool based on two soil thresholds (0.1 and 1 μgkg -1 ) to enable growers to adapt their cropping system and hence to be able to continue farming. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biophysical mechanism of spike threshold dependence on the rate of rise of the membrane potential by sodium channel inactivation or subthreshold axonal potassium current

PubMed Central

Wester, Jason C.

2013-01-01

Spike threshold filters incoming inputs and thus gates activity flow through neuronal networks. Threshold is variable, and in many types of neurons there is a relationship between the threshold voltage and the rate of rise of the membrane potential (dVm/dt) leading to the spike. In primary sensory cortex this relationship enhances the sensitivity of neurons to a particular stimulus feature. While Na+ channel inactivation may contribute to this relationship, recent evidence indicates that K+ currents located in the spike initiation zone are crucial. Here we used a simple Hodgkin-Huxley biophysical model to systematically investigate the role of K+ and Na+ current parameters (activation voltages and kinetics) in regulating spike threshold as a function of dVm/dt. Threshold was determined empirically and not estimated from the shape of the Vm prior to a spike. This allowed us to investigate intrinsic currents and values of gating variables at the precise voltage threshold. We found that Na+ inactivation is sufficient to produce the relationship provided it occurs at hyperpolarized voltages combined with slow kinetics. Alternatively, hyperpolarization of the K+ current activation voltage, even in the absence of Na+ inactivation, is also sufficient to produce the relationship. This hyperpolarized shift of K+ activation allows an outward current prior to spike initiation to antagonize the Na+ inward current such that it becomes self-sustaining at a more depolarized voltage. Our simulations demonstrate parameter constraints on Na+ inactivation and the biophysical mechanism by which an outward current regulates spike threshold as a function of dVm/dt. PMID:23344915

Prediction Uncertainty and Groundwater Management: Approaches to get the Most out of Probabilistic Outputs

NASA Astrophysics Data System (ADS)

Peeters, L. J.; Mallants, D.; Turnadge, C.

2017-12-01

Groundwater impact assessments are increasingly being undertaken in a probabilistic framework whereby various sources of uncertainty (model parameters, model structure, boundary conditions, and calibration data) are taken into account. This has resulted in groundwater impact metrics being presented as probability density functions and/or cumulative distribution functions, spatial maps displaying isolines of percentile values for specific metrics, etc. Groundwater management on the other hand typically uses single values (i.e., in a deterministic framework) to evaluate what decisions are required to protect groundwater resources. For instance, in New South Wales, Australia, a nominal drawdown value of two metres is specified by the NSW Aquifer Interference Policy as trigger-level threshold. In many cases, when drawdowns induced by groundwater extraction exceed two metres, "make-good" provisions are enacted (such as the surrendering of extraction licenses). The information obtained from a quantitative uncertainty analysis can be used to guide decision making in several ways. Two examples are discussed here: the first of which would not require modification of existing "deterministic" trigger or guideline values, whereas the second example assumes that the regulatory criteria are also expressed in probabilistic terms. The first example is a straightforward interpretation of calculated percentile values for specific impact metrics. The second examples goes a step further, as the previous deterministic thresholds do not currently allow for a probabilistic interpretation; e.g., there is no statement that "the probability of exceeding the threshold shall not be larger than 50%". It would indeed be sensible to have a set of thresholds with an associated acceptable probability of exceedance (or probability of not exceeding a threshold) that decreases as the impact increases. We here illustrate how both the prediction uncertainty and management rules can be expressed in a probabilistic framework, using groundwater metrics derived for a highly stressed groundwater system.

Very low threshold-current temperature sensitivity in constricted double-heterojunction AlGaAs lasers

NASA Technical Reports Server (NTRS)

Botez, D.; Connolly, J. C.; Gilbert, D. B.; Ettenberg, M.

1981-01-01

The temperature dependence of threshold currents in constricted double-heterojunction diode lasers with strong lateral mode confinement is found to be significantly milder than for other types of lasers. The threshold-current relative variations with ambient temperature are typically two to three times less than for other devices of CW-operation capability. Over the interval 10-70 C the threshold currents fit the empirical exponential law exp/(T2-T1)/T0/ with T0 values in the 240-375 C range in pulsed operation, and in the 200-310 C range in CW operation. The external differential quantum efficiency and the mode far-field pattern near threshold are virtually invariant with temperature. The possible causes of high-T0 behavior are analyzed, and a new phenomenon - temperature-dependent current focusing - is presented to explain the results.

Reverse engineering the gap gene network of Drosophila melanogaster.

PubMed

Perkins, Theodore J; Jaeger, Johannes; Reinitz, John; Glass, Leon

2006-05-01

A fundamental problem in functional genomics is to determine the structure and dynamics of genetic networks based on expression data. We describe a new strategy for solving this problem and apply it to recently published data on early Drosophila melanogaster development. Our method is orders of magnitude faster than current fitting methods and allows us to fit different types of rules for expressing regulatory relationships. Specifically, we use our approach to fit models using a smooth nonlinear formalism for modeling gene regulation (gene circuits) as well as models using logical rules based on activation and repression thresholds for transcription factors. Our technique also allows us to infer regulatory relationships de novo or to test network structures suggested by the literature. We fit a series of models to test several outstanding questions about gap gene regulation, including regulation of and by hunchback and the role of autoactivation. Based on our modeling results and validation against the experimental literature, we propose a revised network structure for the gap gene system. Interestingly, some relationships in standard textbook models of gap gene regulation appear to be unnecessary for or even inconsistent with the details of gap gene expression during wild-type development.

From cradle-to-grave at the nanoscale: gaps in U.S. regulatory oversight along the nanomaterial life cycle.

PubMed

Beaudrie, Christian E H; Kandlikar, Milind; Satterfield, Terre

2013-06-04

Engineered nanomaterials (ENMs) promise great benefits for society, yet our knowledge of potential risks and best practices for regulation are still in their infancy. Toward the end of better practices, this paper analyzes U.S. federal environmental, health, and safety (EHS) regulations using a life cycle framework. It evaluates their adequacy as applied to ENMs to identify gaps through which emerging nanomaterials may escape regulation from initial production to end-of-life. High scientific uncertainty, a lack of EHS and product data, inappropriately designed exemptions and thresholds, and limited agency resources are a challenge to both the applicability and adequacy of current regulations. The result is that some forms of engineered nanomaterials may escape federal oversight and rigorous risk review at one or more stages along their life cycle, with the largest gaps occurring at the postmarket stages, and at points of ENM release to the environment. Oversight can be improved through pending regulatory reforms, increased research and development for the monitoring, control, and analysis of environmental and end-of-life releases, introduction of periodic re-evaluation of ENM risks, and fostering a "bottom-up" stewardship approach to the responsible management of risks from engineered nanomaterials.

Influence of emission threshold of explosive emission cathodes on current waveform in foilless diodes

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

Wu, P.; Liu, G. Z.; Science and Technology on High Power Microwave Laboratory, Northwest Institute of Nuclear Technology, Xi'an 710024

The emission threshold of explosive emission cathodes (EECs) is an important factor for beam quality. It can affect the explosive emission delay time, the plasma expansion process on the cathode surface, and even the current amplitude when the current is not fully space-charge-limited. This paper researches the influence of the emission threshold of an annular EEC on the current waveform in a foilless diode when the current is measured by a Rogowski coil. The particle-in-cell simulation which is performed under some tolerable and necessary simplifications shows that the long explosive emission delay time of high-threshold cathodes may leave an apparentmore » peak of displacement current on the rise edge of the current waveform, and this will occur only when the electron emission starts after this peak. The experimental researches, which are performed under a diode voltage of 1 MV and a repetitive frequency of 20 Hz, demonstrate that the graphite cathode has a lower emission threshold and a longer lifetime than the stainless steel cathode according to the variation of the peak of displacement current on the rise edge of the current waveform.« less

Control of Chrysanthemum flowering through integration with an aging pathway

USDA-ARS?s Scientific Manuscript database

Age, as a threshold of floral competence acquisition, prevents precocious flowering when there is insufficient biomass, and ensures flowering independent of environmental conditions; however, the underlying regulatory mechanisms are largely unknown. In this study, silencing the expression of a nucle...

Ground-Water Quality Data in the Owens and Indian Wells Valleys Study Unit, 2006: Results from the California GAMA Program

USGS Publications Warehouse

Densmore, Jill N.; Fram, Miranda S.; Belitz, Kenneth

2009-01-01

Ground-water quality in the approximately 1,630 square-mile Owens and Indian Wells Valleys study unit (OWENS) was investigated in September-December 2006 as part of the Priority Basin Project of Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in collaboration with the California State Water Resources Control Board (SWRCB). The Owens and Indian Wells Valleys study was designed to provide a spatially unbiased assessment of raw ground-water quality within OWENS study unit, as well as a statistically consistent basis for comparing water quality throughout California. Samples were collected from 74 wells in Inyo, Kern, Mono, and San Bernardino Counties. Fifty-three of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and 21 wells were selected to evaluate changes in water chemistry in areas of interest (understanding wells). The ground-water samples were analyzed for a large number of synthetic organic constituents [volatile organic compounds (VOCs), pesticides and pesticide degradates, pharmaceutical compounds, and potential wastewater- indicator compounds], constituents of special interest [perchlorate, N-nitrosodimethylamine (NDMA), and 1,2,3- trichloropropane (1,2,3-TCP)], naturally occurring inorganic constituents [nutrients, major and minor ions, and trace elements], radioactive constituents, and microbial indicators. Naturally occurring isotopes [tritium, and carbon-14, and stable isotopes of hydrogen and oxygen in water], and dissolved noble gases also were measured to help identify the source and age of the sampled ground water. This study evaluated the quality of raw ground water in the aquifer in the OWENS study unit and did not attempt to evaluate the quality of treated water delivered to consumers. Water supplied to consumers typically is treated after withdrawal from the ground, disinfected, and blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and non-regulatory thresholds established for aesthetic concerns (secondary maximum contamination levels, SMCL-CA) by CDPH. VOCs and pesticides were detected in samples from less than one-third of the grid wells; all detections were below health-based thresholds, and most were less than one-one hundredth of threshold values. All detections of perchlorate and nutrients in samples from OWENS were below health-based thresholds. Most detections of trace elements in ground-water samples from OWENS wells were below health-based thresholds. In samples from the 53 grid wells, three constituents were detected at concentrations above USEPA maximum contaminant levels: arsenic in 5 samples, uranium in 4 samples, and fluoride in 1 sample. Two constituents were detected at concentrations above CDPH notification levels (boron in 9 samples and vanadium in 1 sample), and two were above USEPA lifetime health advisory levels (molybdenum in 3 samples and strontium in 1 sample). Most of the samples from OWENS wells had concentrations of major elements, TDS, and trace elements below the non-enforceable standards set for aesthetic concerns. Samples from nine grid wells had concentrations of manganese, iron, or TDS above the SMCL-CAs.

Temperature dependence of threshold current in GaAs/AlGaAs quantum well lasers

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

Blood, P.; Colak, S.; Kucharska, A.I.

1988-02-22

We have calculated the threshold current and its temperature (T) dependence in the range 200--400 K for AlGaAs quantum well lasers with 25-A-wide GaAs wells using a model which includes lifetime broadening of the transitions and broadening of the density of states function by fluctuations in the well width. The threshold current varies approximately linearly with T and the principal effect of broadening is to increase the threshold current causing a reduction in the fractional change of current with temperature. The apparent value of the parameter T/sub 0/ is increased to approx. =400 K, compared with approx. =320 K withoutmore » broadening. The calculations are compared with experimental data.« less

The influence of stripe width on the threshold current of double-heterojunction lasers

NASA Technical Reports Server (NTRS)

Ladany, I.

1977-01-01

Experimental measurements of the threshold current of oxide-isolated stripe laser as a function of stripe width and p-layer resistivity are presented. A calculation of the influence of carrier outdiffusion has been made, including the effect of current leakage beyond the stripe edges. The calculated threshold increase is in substantial agreement with experiment for stripe widths down to about 10 microns. The data also yield an effective diffusion length of about 7 microns for the lasers studied. Deviations between experimental and calculated thresholds occurring at stripe widths of 4-6 microns are represented by an empirical curve which is compared with previously published calculations of threshold gain.

75 FR 51509 - Self-Regulatory Organizations; Notice of Filing of a Proposed Rule Change by the NASDAQ Stock...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-20

... necessary to have a Professional designation rule as is commonplace in the industry, particularly where NOS... number over a calendar month will prevent gaming of the 390 order threshold.\\25\\ \\23\\ 390 orders is equal...

Thresholds for Chemically Induced Toxicity: Theories and Evidence

EPA Science Inventory

Regulatory agencies define “science policies” as a means of proceeding with risk assessments and management decisions in the absence of all the data these bodies would like. Policies may include the use of default assumptions, values and methodologies. The U.S. EPA 20...

Environmental statistics and optimal regulation

NASA Astrophysics Data System (ADS)

Sivak, David; Thomson, Matt

2015-03-01

The precision with which an organism can detect its environment, and the timescale for and statistics of environmental change, will affect the suitability of different strategies for regulating protein levels in response to environmental inputs. We propose a general framework--here applied to the enzymatic regulation of metabolism in response to changing nutrient concentrations--to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, and the costs associated with enzyme production. We find: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones.

Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode.

PubMed

Jensen, Ralph J; Rizzo, Joseph F; Ziv, Ofer R; Grumet, Andrew; Wyatt, John

2003-08-01

To determine electrical thresholds required for extracellular activation of retinal ganglion cells as part of a project to develop an epiretinal prosthesis. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100- micro s duration were delivered to the inner surface of the retina from a 5- micro m long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one half) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation.

Line length dependence of threshold current density and driving force in eutectic SnPb and SnAgCu solder electromigration

NASA Astrophysics Data System (ADS)

Yoon, Min-Seung; Ko, Min-Ku; Kim, Bit-Na; Kim, Byung-Joon; Park, Yong-Bae; Joo, Young-Chang

2008-04-01

The relationship between the threshold current density and the critical line length in eutectic SnPb and SnAgCu electromigrations were examined using solder lines with the various lengths ranging from 100to1000μm. When the electron wind-force was balanced by the back-stress gradient force, the net flux of electromigration is zero, at which the current density and line length are defined as the threshold current density and the critical length, respectively. It was found that in SnAgCu electromigration, the 1/L dependence on the threshold current density showed good agreement, whereas the threshold current densities of the eutectic SnPb deviated from the 1/L dependence. The balance between the electron wind-force and the back-stress gradient force was the main factor determining the threshold product of SnAgCu electromigration. On the other hand, in the case of eutectic SnPb, the chemical driving force is contributed as a back-flux force in addition to the back-stress gradient force. The existence of the chemical driving force was caused by the nonequilibrium Pb concentration inside the Pb-rich phases between the cathode and anode during the electromigration procedure.

Academic Standards and Regulatory Frameworks: Necessary Compromises?

ERIC Educational Resources Information Center

Stowell, Marie; Falahee, Marie; Woolf, Harvey

2016-01-01

Assessment regulations in higher education, which are important for assuring threshold academic standards, reflect institutional cultures and histories, and are shaped by pragmatic concerns about quality indicators such as retention and progression rates, as well as principles of equity. This paper articulates some of the tensions that confront…

Spontaneous recombination current in InGaAs/GaAs quantum well lasers

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

Blood, P.; Fletcher, E.D.; Woodbridge, K.

1990-10-08

We have studied the intrinsic factors which determine the threshold current and its temperature dependence in 160-A-wide In{sub 0.2}Ga{sub 0.8}As single well quantum lasers with GaAs barriers, grown by molecular beam epitaxy on GaAs substrates. By measuring the relative temperature dependence of the spontaneous emission intensity at threshold we show that radiative transitions between higher order ({ital n}=2,3) electron and heavy hole subbands make a significant contribution to the threshold current and its temperature sensitivity, even in devices where the laser transitions are between {ital n}=1 subbands. These higher transitions will also influence the dependence of threshold current and itsmore » temperature sensitivity on well width.« less

75 FR 1552 - Chemical Facility Anti-Terrorism Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-12

... Protection Agency RMP--Risk Management Program SSP--Site Security Plan STQ--Screening Threshold Quantity SVA... Protection Agency (EPA) under the Clean Air Act's Risk Management Program (RMP) for counting-- or excluding... Safety, Information, Site Security and Fuels Regulatory Relief Act, Public Law 106-40. Cf. 72 FR 65410...

76 FR 82332 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-30

.... Moreover, the competitive pressures from other exchanges in electronic orders and different business model... electronic business and compete with other exchanges for such business. The business models surrounding...). The specific volume thresholds of the Program's tiers were set based upon business determinations and...

76 FR 7762 - Drinking Water: Regulatory Determination on Perchlorate

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-11

... NOEL--no observed effect level NPDWR--National Primary Drinking Water Regulation NRC--National Research... Research Council (NRC) published ``Health Implications of Perchlorate Ingestion,'' a review of the state of... the threshold. For example, if a PWS with 10 entry points serving 200,000 people had a sample from a...

Vitamin D in pregnancy: current perspectives and future directions

PubMed Central

Kiely, Mairead; Hemmingway, Andrea; O’Callaghan, Karen M.

2017-01-01

As neonatal vitamin D status is determined by circulating maternal 25-hydroxyvitamin D [25(OH)D] concentrations, prevention of maternal vitamin D deficiency during pregnancy is essential for the avoidance of neonatal deficiency. However, a high prevalence of vitamin D deficiency has been extensively reported among gravidae and neonates from ethnic minorities and white populations resident at high latitude. Currently, regulatory authorities recommend vitamin D intakes for pregnant women that are similar to non-pregnant adults of the same age, at 10–15 µg/day (400–600 IU), to meet 25(OH)D thresholds of 25–50 nmol/liter. The lack of pregnancy-specific dietary recommendations is due to inadequate data indicating whether nutritional requirements for vitamin D during pregnancy differ from the non-pregnant state. In addition, there are few dose–response studies to determine the maternal 25(OH)D response to vitamin D intake throughout pregnancy at high latitude. These data are also required to determine vitamin D requirements during pregnancy for prevention of neonatal deficiency, an outcome which is likely to require a higher maternal 25(OH)D concentration than prevention of maternal deficiency only. With regard to the impact of vitamin D on perinatal health outcomes, which could guide pregnancy-specific 25(OH)D thresholds, dietary intervention studies to date have been inconsistent and recent systematic reviews have highlighted issues of low quality and a high risk of bias as drawbacks in the trial evidence to date. Many observational studies have been hampered by a reliance on retrospective data, unclear reporting, suboptimal clinical phenotyping and incomplete subject characterization. Current investigations of vitamin D metabolism during pregnancy have potentially exciting implications for clinical research. This paper provides an update of current dietary recommendations for vitamin D in pregnant women and a synopsis of the evidence relating vitamin D status with maternal and infant health. PMID:28620423

The immediate effects of lidocaine iontophoresis using interferential current on pressure sense threshold and tactile sensation.

PubMed

Yoosefinejad, Amin Kordi; Motealleh, Alireza; Abbasnia, Keramatollah

2016-01-01

Iontophoresis is the noninvasive delivery of ions using direct current. The direct current has some disadvantages such as skin burning. Interferential current is a kind of alternating current without limitations of direct current; so the purpose of this study is to investigate and compare the effects of lidocaine, interferential current and lidocaine iontophoresis using interferential current. 30 healthy women aged 20-24 years participated in this randomized clinical trial study. Pressure, tactile and pain thresholds were evaluated before and after the application of treatment methods. Pressure, tactile and pain sensitivity increased significantly after the application of lidocaine alone (p < 0.005) and lidocaine iontophoresis using interferential current (p < 0.0001). Lidocaine iontophoresis using interferential current can increase perception threshold of pain, tactile stimulus and pressure sense more significantly than lidocaine and interferential current alone.

Synthesis of polymer nanostructures with conductance switching properties

DOEpatents

Su, Kai; Nuraje, Nurxat; Zhang, Lingzhi; Matsui, Hiroshi; Yang, Nan Loh

2015-03-03

The present invention is directed to crystalline organic polymer nanoparticles comprising a conductive organic polymer; wherein the crystalline organic polymer nanoparticles have a size of from 10 nm to 200 nm and exhibits two current-voltage states: (1) a high resistance current-voltage state, and (2) a low resistance current-voltage state, wherein when a first positive threshold voltage (V.sub.th1) or higher positive voltage, or a second negative threshold voltage (V.sub.th2) or higher negative voltage is applied to the nanoparticle, the nanoparticle exhibits the low-resistance current-voltage state, and when a voltage less positive than the first positive threshold voltage or a voltage less negative than the second negative threshold voltage is applied to the nanoparticle, the nanoparticle exhibits the high-resistance current-voltage state. The present invention is also directed methods of manufacturing the nanoparticles using novel interfacial oxidative polymerization techniques.

Investigating the effect of freeway congestion thresholds on decision-making inputs.

DOT National Transportation Integrated Search

2010-05-01

Congestion threshold is embedded in the congestion definition. Two basic approaches exist in : current practice for setting the congestion threshold. One common approach uses the free-flow or : unimpeded conditions as the congestion threshold. ...

Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis

PubMed Central

Iwai, Yuta; Shibuya, Kazumoto; Misawa, Sonoko; Sekiguchi, Yukari; Watanabe, Keisuke; Amino, Hiroshi; Kuwabara, Satoshi

2016-01-01

Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS), suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP) amplitude (index of motor neuronal loss) and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44), ALS patients (n = 140) had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p < 0.05), greater threshold changes in depolarizing threshold electrotonus (p < 0.05) and depolarizing current threshold relationship (i.e. less accommodation; (p < 0.05), greater superexcitability (a measure of fast potassium current; p < 0.05) and reduced late subexcitability (a measure of slow potassium current; p < 0.05), suggesting increased persistent sodium currents and decreased potassium currents. The reduced potassium currents were found even in the patient subgroups with normal CMAP (> 5mV). Regression analyses showed that SDTC (R = -0.22) and depolarizing threshold electrotonus (R = -0.22) increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS. PMID:27383069

Estimation of southern resident killer whale exposure to exhaust emissions from whale-watching vessels and potential adverse health effects and toxicity thresholds.

PubMed

Lachmuth, Cara L; Barrett-Lennard, Lance G; Steyn, D Q; Milsom, William K

2011-04-01

Southern resident killer whales in British Columbia and Washington are exposed to heavy vessel traffic. This study investigates their exposure to exhaust gases from whale-watching vessels by using a simple dispersion model incorporating data on whale and vessel behavior, atmospheric conditions, and output of airborne pollutants from the whale-watching fleet based on emissions data from regulatory agencies. Our findings suggest that current whale-watching guidelines are usually effective in limiting pollutant exposure to levels at or just below those at which measurable adverse health effects would be expected in killer whales. However, safe pollutant levels are exceeded under worst-case conditions and certain average-case conditions. To reduce killer whale exposure to exhaust we recommend: vessels position on the downwind side of whales, a maximum of 20 whale-watching vessels should be within 800 m at any given time, viewing periods should be limited, and current whale-watch guidelines and laws should be enforced. Copyright © 2011. Published by Elsevier Ltd.

Dependence of threshold current on the number of wells in AlGaAs-GaAs quantum well lasers

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

Blood, P.; Fletcher, E.D.; Woodbridge, K.

1985-08-01

GaAs-AlGaAs multiple quantum well injection lasers have been grown by molecular beam epitaxy with different numbers (N) of uncoupled GaAs wells 25 A wide symmetrically disposed about the center of a 4000-A-wide waveguide. The devices emit at about 770 nm and for N = 4 the broad area threshold current density is 1.1 kA cm/sup -2/. The threshold current increases with increasing N (2

Groundwater-Quality Data in the Madera-Chowchilla Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Shelton, Jennifer L.; Fram, Miranda S.; Belitz, Kenneth

2009-01-01

Groundwater quality in the approximately 860-square-mile Madera-Chowchilla study unit (MADCHOW) was investigated in April and May 2008 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw groundwater used for public water supplies within MADCHOW, and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 35 wells in Madera, Merced, and Fresno Counties. Thirty of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and five more were selected to provide additional sampling density to aid in understanding processes affecting groundwater quality (flow-path wells). Detection summaries in the text and tables are given for grid wells only, to avoid over-representation of the water quality in areas adjacent to flow-path wells. Groundwater samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOCs], low-level 1,2-dibromo-3-chloropropane [DBCP] and 1,2-dibromoethane [EDB], pesticides and pesticide degradates, polar pesticides and metabolites, and pharmaceutical compounds), constituents of special interest (N-nitrosodimethylamine [NDMA], perchlorate, and low-level 1,2,3-trichloropropane [1,2,3-TCP]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), and radioactive constituents (uranium isotopes, and gross alpha and gross beta particle activities). Naturally occurring isotopes and geochemical tracers (stable isotopes of hydrogen, oxygen, and carbon, and activities of tritium and carbon-14), and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, approximately 300 constituents and field water-quality indicators were investigated. Three types of quality-control samples (blanks, replicates, and samples for matrix spikes) each were collected at approximately 11 percent of the wells sampled for each analysis, and the results obtained from these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that data for the groundwater samples were not compromised by possible contamination during sample collection, handling or analysis. Differences between replicate samples were within acceptable ranges. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH), and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only, and are not indicative of compliance or non-compliance with regulatory thresholds. The concentrations of most constituents detected in groundwater samples from MADCHOW wells were below drinking-water thresholds. Organic compounds (VOCs and pesticides

A gene network simulator to assess reverse engineering algorithms.

PubMed

Di Camillo, Barbara; Toffolo, Gianna; Cobelli, Claudio

2009-03-01

In the context of reverse engineering of biological networks, simulators are helpful to test and compare the accuracy of different reverse-engineering approaches in a variety of experimental conditions. A novel gene-network simulator is presented that resembles some of the main features of transcriptional regulatory networks related to topology, interaction among regulators of transcription, and expression dynamics. The simulator generates network topology according to the current knowledge of biological network organization, including scale-free distribution of the connectivity and clustering coefficient independent of the number of nodes in the network. It uses fuzzy logic to represent interactions among the regulators of each gene, integrated with differential equations to generate continuous data, comparable to real data for variety and dynamic complexity. Finally, the simulator accounts for saturation in the response to regulation and transcription activation thresholds and shows robustness to perturbations. It therefore provides a reliable and versatile test bed for reverse engineering algorithms applied to microarray data. Since the simulator describes regulatory interactions and expression dynamics as two distinct, although interconnected aspects of regulation, it can also be used to test reverse engineering approaches that use both microarray and protein-protein interaction data in the process of learning. A first software release is available at http://www.dei.unipd.it/~dicamill/software/netsim as an R programming language package.

Assessment of possible allergenicity of hypothetical ORFs in common food crops using current bioinformatic guidelines and its implications for the safety assessment of GM crops.

PubMed

Young, Gregory J; Zhang, Shiping; Mirsky, Henry P; Cressman, Robert F; Cong, Bin; Ladics, Gregory S; Zhong, Cathy X

2012-10-01

Before a genetically modified (GM) crop can be commercialized it must pass through a rigorous regulatory process to verify that it is safe for human and animal consumption, and to the environment. One particular area of focus is the potential introduction of a known or cross-reactive allergen not previously present within the crop. The assessment of possible allergenicity uses the guidelines outlined by the Food and Agriculture Organization (FAO) and World Health Organization's (WHO) Codex Alimentarius Commission (Codex) to evaluate all newly expressed proteins. Some regulatory authorities have broadened the scope of the assessment to include all DNA reading frames between stop codons across the insert and spanning the insert/genomic DNA junctions. To investigate the utility of this bioinformatic assessment, all naturally occurring stop-to-stop frames in the non-transgenic genomes of maize, rice, and soybean, as well as the human genome, were compared against the AllergenOnline (www.allergenonline.org) database using the Codex criteria. We discovered thousands of frames that exceeded the Codex defined threshold for potential cross-reactivity suggesting that evaluating hypothetical ORFs (stop-to-stop frames) has questionable value for making decisions on the safety of GM crops. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effect of laryngotracheal topical anesthesia on recurrent laryngeal nerve monitoring during thyroid Surgery.

PubMed

Pachuski, Justin; Vaida, Sonia; Donahue, Kathleen; Roberts, John; Kunselman, Allen; Oberman, Benjamin; Patel, Hetal; Goldenberg, David

2016-03-01

Intraoperative neuromonitoring of the recurrent laryngeal nerve (RLN) is often used as an adjunct for RLN identification and preservation during thyroidectomies. Laryngotracheal anesthesia (LTA) with topical lidocaine reduces coughing upon emergence from anesthesia and in the immediate postoperative period; however, its use is prohibited with concerns that it could decrease the sensitivity of the intraoperative neuromonitoring. We hypothesize that there is no difference in measurements of nerve conduction made before and after LTA administration. An observational study in which all patients were subjected to LTA administration was conducted. Recurrent laryngeal nerve threshold currents were measured before and after the intervention. Tertiary medical center operating room. Eighteen patients (total of 25 nerves at risk) with American Society of Anesthesiologists classes 1 to 3 undergoing thyroid surgery. After the thyroid was removed and threshold currents at the RLN were obtained, LTA with endotracheal lidocaine was applied on the left and right side of the in situ endotracheal tube (2 cc of 4% lidocaine per side). Threshold currents were reassessed at 5 and 10 minutes after LTA administration. Threshold currents (minimum stimulus current applied to the RLN required to generate a discernible electromyographic response at the vocal cords) were recorded along the RLN for a baseline at 5 and 10 mm from the insertion point of the RLN into the larynx. Threshold currents were reassessed at the same 2 positions on the RLN at 5 and 10 minutes after LTA administration. Differences in mean values, between threshold currents recorded at the 3 different times, at 2 positions on the RLN, were used to compare effects of LTA on nerve conduction. There were no statistically significant differences when comparing threshold currents before and after LTA administration. Laryngotracheal anesthesia had no significant effect on RLN nerve conduction in the period assessed. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulatory and quality considerations for continuous manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.

PubMed

Berghoff, Bork A; Hoekzema, Mirthe; Aulbach, Lena; Wagner, E Gerhart H

2017-03-01

Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity. © 2016 John Wiley & Sons Ltd.

Naming, blaming and shaming?

PubMed

Bismark, M; Paterson, R

2006-03-01

Few doctors at the centre of complaints or disciplinary proceedings wish to be publicly named. Publication of a doctor's name can adversely affect his or her reputation, patients, and family members, even if the allegation is ultimately not upheld. Yet, there is a strong public interest in freedom of speech and transparency of complaints and disciplinary processes. In determining whether to grant name suppression, complaints agencies and disciplinary tribunals are required to balance competing public and private interests. In New Zealand, the Health and Disability Commissioner has responsibility for investigating complaints about the quality of medical care. The Commissioner's current practice is not to publicly name doctors under investigation, or even those who are found to have breached a patient's rights. This approach fits well the non-punitive, rehabilitative focus of New Zealand's medical regulatory system. In the rare cases where a matter reaches the threshold for disciplinary action, the balance tips in favour of disclosure.

75 FR 53169 - Federal Acquisition Regulation; Federal Acquisition Circular 2005-45; Small Entity Compliance Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-30

... Contract Act, and trade agreements thresholds. The Councils have also used the same methodology to adjust... Business Regulatory Enforcement Fairness Act of 1996. It consists of a summary of rules appearing in...-008 Davis. and Reinvestment Act of 2009 (the Recovery Act)-- Buy American Requirements for...

77 FR 60637 - Western Pacific Pelagic Fisheries; Revised Limits on Sea Turtle Interactions in the Hawaii...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... made in 2004, when the fishery was being reopened under an experimental regulatory regime that was... NMFS based the information on Atlantic experimental results. Based on 100 percent observer coverage... quasi-extinction threshold within one generation (25 years) due largely to climate-forcing factors. As...

75 FR 42801 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

... Organizations; International Securities Exchange, LLC; Notice of Filing and Immediate Effectiveness of Proposed... at or under the threshold are charged the constituent's prescribed execution fee. This waiver applies... members to execute large-sized FX options orders on the Exchange in a manner that is cost effective. The...

78 FR 69900 - Self-Regulatory Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-21

... the efficiency and cost-effectiveness of trading on the Exchange. Amended Rebate for Double Play... Organizations; National Stock Exchange, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule... to adjust the volume thresholds that must be met before an ETP Holder can be eligible to pay the...

77 FR 39538 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-03

... Exchange's normal routing strategies would apply, and, to the extent that other market centers have better... the proposed pricing threshold because a User is subject to certain specific obligations when pricing...-Through and Locked and Crossed Market protection. \\17\\ This definition for Crossed Market is consistent...

78 FR 3931 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-17

... thresholds through a single MPID to avoid providing excessive encouragement to members to aggregate the... a particular venue to be excessive, or rebate opportunities available at other venues to be more... standards applicable to exchanges. These competitive forces help to ensure that NASDAQ's fees are reasonable...

78 FR 57669 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-19

... Change Proposing To Modify the Manner in Which It Calculates Volume, Liquidity and Quoting Thresholds... Arca'') filed with the Securities and Exchange Commission (the ``Commission'') the proposed rule change... organization. The Commission is publishing this notice to solicit comments on the proposed rule change from...

77 FR 74719 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-17

... for Electronic Complex Order executions, and (vii) include days when the Exchange closes early in the... combined thresholds in contracts from Customer posted orders in Penny Pilot issues and Electronic Complex Orders.\\5\\ The Exchange proposes not to count Electronic Complex Orders toward the Customer monthly...

12 CFR Appendix A to Part 1310 - Financial Stability Oversight Council Guidance for Nonbank Financial Company Determinations

Code of Federal Regulations, 2013 CFR

2013-01-01

... its review. In the first stage of the process, the Council will apply six uniform quantitative... quantitative thresholds using information available through existing public and regulatory sources, nonbank..., rather than applying a broadly applicable quantitative metric. The Council believes that the threat a...

12 CFR Appendix A to Part 1310 - Financial Stability Oversight Council Guidance for Nonbank Financial Company Determinations

Code of Federal Regulations, 2014 CFR

2014-01-01

... its review. In the first stage of the process, the Council will apply six uniform quantitative... quantitative thresholds using information available through existing public and regulatory sources, nonbank..., rather than applying a broadly applicable quantitative metric. The Council believes that the threat a...

Selective remediation of contaminated sites using a two-level multiphase strategy and geostatistics.

PubMed

Saito, Hirotaka; Goovaerts, Pierre

2003-05-01

Selective soil remediation aims to reduce costs by cleaning only the fraction of an exposure unit (EU) necessary to lower the average concentration below the regulatory threshold. This approach requires a prior stratification of each EU into smaller remediation units (RU) which are then selected according to various criteria. This paper presents a geostatistical framework to account for uncertainties attached to both RU and EU average concentrations in selective remediation. The selection of RUs is based on their impact on the postremediation probability for the EU average concentration to exceed the regulatory threshold, which is assessed using geostatistical stochastic simulation. Application of the technique to a set of 600 dioxin concentrations collected at Piazza Road EPA Superfund site in Missouri shows a substantial decrease in the number of RU remediated compared with single phase remediation. The lower remediation costs achieved by the new strategy are obtained to the detriment of a higher risk of false negatives, yet for this data set this risk remains below the 5% rate set by EPA region 7.

Effects of electrolysis by low-amperage electric current on the chlorophyll fluorescence characteristics of Microcystis aeruginosa.

PubMed

Lin, Li; Feng, Cong; Li, Qingyun; Wu, Min; Zhao, Liangyuan

2015-10-01

Effects of electrolysis by low-amperage electric current on the chlorophyll fluorescence characteristics of Microcystis aeruginosa were investigated in order to reveal the mechanisms of electrolytic inhibition of algae. Threshold of current density was found under a certain initial no. of algae cell. When current density was equal to or higher than the threshold (fixed electrolysis time), growth of algae was inhibited completely and the algae lost the ability to survive. Effect of algal solution volume on algal inhibition was insignificant. Thresholds of current density were 8, 10, 14, 20, and 22 mA cm(-2) at 2.5 × 10(7), 5 × 10(7), 1 × 10(8), 2.5 × 10(8), and 5 × 10(8) cells mL(-1) initial no. of algae cell, respectively. Correlativity between threshold of current and initial no. of algae cells was established for scale-up and determining operating conditions. Changes of chlorophyll fluorescence parameters demonstrated that photosystem (PS) II of algae was damaged by electrolysis but still maintained relatively high activity when algal solution was treated by current densities lower than the threshold. The activity of algae recovered completely after 6 days of cultivation. On the contrary, when current density was higher than the threshold, connection of phycobilisome (PBS) and PS II core complexes was destroyed, PS II system of algae was damaged irreversibly, and algae could not survive thoroughly. The inactivation of M. aeruginosa by electrolysis can be attributed to irreversible separation of PBS from PS II core complexes and the damage of PS II of M. aeruginosa.

Carbon deposition thresholds on nickel-based solid oxide fuel cell anodes II. Steam:carbon ratio and current density

NASA Astrophysics Data System (ADS)

Kuhn, J.; Kesler, O.

2015-03-01

For the second part of a two part publication, coking thresholds with respect to molar steam:carbon ratio (SC) and current density in nickel-based solid oxide fuel cells were determined. Anode-supported button cell samples were exposed to 2-component and 5-component gas mixtures with 1 ≤ SC ≤ 2 and zero fuel utilization for 10 h, followed by measurement of the resulting carbon mass. The effect of current density was explored by measuring carbon mass under conditions known to be prone to coking while increasing the current density until the cell was carbon-free. The SC coking thresholds were measured to be ∼1.04 and ∼1.18 at 600 and 700 °C, respectively. Current density experiments validated the thresholds measured with respect to fuel utilization and steam:carbon ratio. Coking thresholds at 600 °C could be predicted with thermodynamic equilibrium calculations when the Gibbs free energy of carbon was appropriately modified. Here, the Gibbs free energy of carbon on nickel-based anode support cermets was measured to be -6.91 ± 0.08 kJ mol-1. The results of this two part publication show that thermodynamic equilibrium calculations with appropriate modification to the Gibbs free energy of solid-phase carbon can be used to predict coking thresholds on nickel-based anodes at 600-700 °C.

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

PubMed

Tohkin, Masahiro

2017-01-01

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

INTERNATIONAL CONFERENCE ON SEMICONDUCTOR INJECTION LASERS SELCO-87: Injection lasers based on the AlGaAsSb system emitting at 1.6 μm

NASA Astrophysics Data System (ADS)

Virro, A. L.; Eliseev, P. G.; Lyuk, P. A.; Fridental, Ya K.; Khaller, Yu E.

1988-11-01

An experimental dependence of the threshold current density jth on the thickness of the active region was used to find the reduced threshold current density for AlGaAsSb (λ = 1.59μm, T = 295K) lasers: this density was 8 kA·cm-2·μm-1. The minimum threshold current was jth = 1.8 kA/cm2. Wide-contact lasers exhibited cw operation down to 175 K.

Threshold current for fireball generation

NASA Astrophysics Data System (ADS)

Dijkhuis, Geert C.

1982-05-01

Fireball generation from a high-intensity circuit breaker arc is interpreted here as a quantum-mechanical phenomenon caused by severe cooling of electrode material evaporating from contact surfaces. According to the proposed mechanism, quantum effects appear in the arc plasma when the radius of one magnetic flux quantum inside solid electrode material has shrunk to one London penetration length. A formula derived for the threshold discharge current preceding fireball generation is found compatible with data reported by Silberg. This formula predicts linear scaling of the threshold current with the circuit breaker's electrode radius and concentration of conduction electrons.

Regulatory and Quality Considerations for Continuous Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Allison, Gretchen; Cain, Yanxi Tan; Cooney, Charles; Garcia, Tom; Bizjak, Tara Gooen; Holte, Oyvind; Jagota, Nirdosh; Komas, Bekki; Korakianiti, Evdokia; Kourti, Dora; Madurawe, Rapti; Morefield, Elaine; Montgomery, Frank; Nasr, Moheb; Randolph, William; Robert, Jean-Louis; Rudd, Dave; Zezza, Diane

2015-03-01

This paper assesses the current regulatory environment, relevant regulations and guidelines, and their impact on continuous manufacturing. It summarizes current regulatory experience and learning from both review and inspection perspectives. It outlines key regulatory aspects, including continuous manufacturing process description and control strategy in regulatory files, process validation, and key Good Manufacturing Practice (GMP) requirements. In addition, the paper identifies regulatory gaps and challenges and proposes a way forward to facilitate implementation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

High efficiency low threshold current 1.3 μm InAs quantum dot lasers on on-axis (001) GaP/Si

NASA Astrophysics Data System (ADS)

Jung, Daehwan; Norman, Justin; Kennedy, M. J.; Shang, Chen; Shin, Bongki; Wan, Yating; Gossard, Arthur C.; Bowers, John E.

2017-09-01

We demonstrate highly efficient, low threshold InAs quantum dot lasers epitaxially grown on on-axis (001) GaP/Si substrates using molecular beam epitaxy. Electron channeling contrast imaging measurements show a threading dislocation density of 7.3 × 106 cm-2 from an optimized GaAs template grown on GaP/Si. The high-quality GaAs templates enable as-cleaved quantum dot lasers to achieve a room-temperature continuous-wave (CW) threshold current of 9.5 mA, a threshold current density as low as 132 A/cm2, a single-side output power of 175 mW, and a wall-plug-efficiency of 38.4% at room temperature. As-cleaved QD lasers show ground-state CW lasing up to 80 °C. The application of a 95% high-reflectivity coating on one laser facet results in a CW threshold current of 6.7 mA, which is a record-low value for any kind of Fabry-Perot laser grown on Si.

InAs-based interband-cascade-lasers emitting around 7 μm with threshold current densities below 1 kA/cm{sup 2} at room temperature

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

Dallner, Matthias; Hau, Florian; Kamp, Martin

2015-01-26

Interband cascade lasers (ICLs) grown on InAs substrates with threshold current densities below 1 kA/cm{sup 2} are presented. Two cascade designs with different lengths of the electron injector were investigated. Using a cascade design with 3 InAs quantum wells (QWs) in the electron injector, a device incorporating 22 stages in the active region exhibited a threshold current density of 940 A/cm{sup 2} at a record wavelength of 7 μm for ICLs operating in pulsed mode at room temperature. By investigating the influence of the number of stages on the device performance for a cascade design with 2 QWs in the electron injector, amore » further reduction of the threshold current density to 800 A/cm{sup 2} was achieved for a 30 stage device.« less

Ultralow threshold graded-index separate-confinement heterostructure single quantum well (Al, Ga) As lasers

NASA Technical Reports Server (NTRS)

Derry, P. L.; Chen, H. Z.; Morkoc, H.; Yariv, A.; Lau, K. Y.

1988-01-01

Broad area graded-index separate-confinement heterostructure single quantum well lasers grown by molecular-beam epitaxy (MBE) with threshold current density as low as 93 A/sq cm (520 microns long) have been fabricated. Buried lasers formed from similarly structured MBE material with liquid phase epitaxy regrowth had threshold currents at submilliampere levels when high reflectivity coatings were applied to the end facets. A CW threshold current of 0.55 mA was obtained for a laser with facet reflectivities of about 80 percent, a cavity length of 120 micron, and an active region stripe width of 1 micron. These devices driven directly with logic level signals have switch-on delays less than 50 ps without any current prebias. Such lasers permit fully on-off switching while at the same time obviating the need for bias monitoring and feedback control.

Limitations of on-site dairy farm regulatory debits as milk quality predictors.

PubMed

Borneman, Darand L; Stiegert, Kyle; Ingham, Steve

2015-03-01

In the United States, compliance with grade A raw fluid milk regulatory standards is assessed via laboratory milk quality testing and by on-site inspection of producers (farms). This study evaluated the correlation between on-site survey debits being marked and somatic cell count (SCC) or standard plate count (SPC) laboratory results for 1,301 Wisconsin grade A dairy farms in 2012. Debits recorded on the survey form were tested as predictors of laboratory results utilizing ordinary least squares regression to determine if results of the current method for on-site evaluation of grade A dairy farms accurately predict SCC and SPC test results. Such a correlation may indicate that current methods of on-site inspection serve the primary intended purpose of assuring availability of high-quality milk. A model for predicting SCC was estimated using ordinary least squares regression methods. Step-wise selected regressors of grouped debit items were able to predict SCC levels with some degree of accuracy (adjusted R2=0.1432). Specific debit items, seasonality, and farm size were the best predictors of SCC levels. The SPC data presented an analytical challenge because over 75% of the SPC observations were at or below a 25,000 cfu/mL threshold but were recorded by testing laboratories as at the threshold value. This classic censoring problem necessitated the use of a Tobit regression approach. Even with this approach, prediction of SPC values based on on-site survey criteria was much less successful (adjusted R2=0.034) and provided little support for the on-site survey system as a way to inform farmers about making improvements that would improve SPC. The lower level of correlation with SPC may indicate that factors affecting SPC are more varied and differ from those affecting SCC. Further, unobserved deficiencies in postmilking handling and storage sanitation could enhance bacterial growth and increase SPC, whereas postmilking sanitation will have no effect on SCC because somatic cells do not reproduce in stored milk. Results suggest that close examination, and perhaps redefinition, of survey debits, along with making the survey coincident with SCC and SPC sampling, could make the on-site survey a better tool for ensuring availability of high-quality milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Active-Matrix Organic Light Emission Diode Pixel Circuit for Suppressing and Compensating for the Threshold Voltage Degradation of Hydrogenated Amorphous Silicon Thin Film Transistors

NASA Astrophysics Data System (ADS)

Shin, Hee-Sun; Lee, Won-Kyu; Park, Sang-Guen; Kuk, Seung-Hee; Han, Min-Koo

2009-03-01

A new hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) pixel circuit for active-matrix organic light emission diodes (AM-OLEDs), which significantly compensates the OLED current degradation by memorizing the threshold voltage of driving TFT and suppresses the threshold voltage shift of a-Si:H TFTs by negative bias annealing, is proposed and fabricated. During the first half of each frame, the driving TFT of the proposed pixel circuit supplies current to the OLED, which is determined by modified data voltage in the compensation scheme. The proposed pixel circuit was able to compensate the threshold voltage shift of the driving TFT as well as the OLED. During the remaining half of each frame, the proposed pixel circuit induces the recovery of the threshold voltage degradation of a-Si:H TFTs owing to the negative bias annealing. The experimental results show that the proposed pixel circuit was able to successfully compensate for the OLED current degradation and suppress the threshold voltage degradation of the driving TFT.

Regulatory system reform of occupational health and safety in China.

PubMed

Wu, Fenghong; Chi, Yan

2015-01-01

With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

Regulatory system reform of occupational health and safety in China

PubMed Central

WU, Fenghong; CHI, Yan

2015-01-01

With the explosive economic growth and social development, China’s regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined. PMID:25843565

Evaluation and comparison of 50 Hz current threshold of electrocutaneous sensations using different methods

PubMed Central

Lindenblatt, G.; Silny, J.

2006-01-01

Leakage currents, tiny currents flowing from an everyday-life appliance through the body to the ground, can cause a non-adequate perception (called electrocutaneous sensation, ECS) or even pain and should be avoided. Safety standards for low-frequency range are based on experimental results of current thresholds of electrocutaneous sensations, which however show a wide range between about 50 μA (rms) and 1000 μA (rms). In order to be able to explain these differences, the perception threshold was measured repeatedly in experiments with test persons under identical experimental setup, but by means of different methods (measuring strategies), namely: direct adjustment, classical threshold as amperage of 50% perception probability, and confidence rating procedure of signal detection theory. The current is injected using a 1 cm2 electrode at the highly touch sensitive part of the index fingertip. These investigations show for the first time that the threshold of electrocutaneous sensations is influenced both by adaptation to the non-adequate stimulus and individual, emotional factors. Therefore, classical methods, on which the majority of the safety investigations are based, cannot be used to determine a leakage current threshold. The confidence rating procedure of the modern signal detection theory yields a value of 179.5 μA (rms) at 50 Hz power supply net frequency as the lower end of the 95% confidence range considering the variance in the investigated group. This value is expected to be free of adaptation influences, and is distinctly lower than the European limits and supports the stricter regulations of Canada and USA. PMID:17111461

Mouse current vocalization threshold measured with a neurospecific nociception assay: The effect of sex, morphine, and isoflurane

PubMed Central

Spornick, Nicholas; Guptill, Virginia; Koziol, Deloris; Wesley, Robert; Finkel, Julia; Quezado, Zenaide M.N.

2012-01-01

Sine-wave electrical stimulation at frequencies 2000, 250, and 5 Hz to respectively evaluate Aβ, Aδ, and C sensory neurons has recently been added to the armamentarium used to evaluate sensory neurons. We developed an automated nociception assay using sine-wave stimulation methodology to determine current vocalization threshold in response to 2000, 250, and 5 Hz and examine the effects of sex, analgesics, and anesthetics in mice. At baseline, males had significantly higher mean current vocalization thresholds compared with female mice at 2000, 250, and 5 Hz (p ≤ 0.019). By 1 h after intrathecal injections of morphine there were significant increases in current vocalization threshold percent changes from baseline that varied with doses (p = 0.0001) and frequency used (p < 0.0001). Specifically, with increasing doses of morphine, there were significantly greater increases in current vocalization threshold percent changes from baseline in response to 5 Hz compared with 250 and 2000 Hz stimulation in a significantly ordered pattern: 5 Hz > 250 Hz (p < 0.0001) and 250 Hz > 2000 Hz (p = 0.0002). Forty-five minutes after exposure, there were no effects of isoflurane on current vocalization thresholds at any frequency. Therefore, our findings suggest that this automated nociception assay using sine-wave stimulation in mice, can be valuable for measurements of the effects of sex, opioids, and anesthetics on the response to electrical stimuli that preferentially stimulate Aβ, Aδ, and C-sensory fibers in vivo. This investigation suggests the validation of this assay and supports its use to examine mechanisms of nociception in mice. PMID:21864576

Environmental statistics and optimal regulation.

PubMed

Sivak, David A; Thomson, Matt

2014-09-01

Any organism is embedded in an environment that changes over time. The timescale for and statistics of environmental change, the precision with which the organism can detect its environment, and the costs and benefits of particular protein expression levels all will affect the suitability of different strategies--such as constitutive expression or graded response--for regulating protein levels in response to environmental inputs. We propose a general framework-here specifically applied to the enzymatic regulation of metabolism in response to changing concentrations of a basic nutrient-to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, respectively, and the costs associated with enzyme production. We use this framework to address three fundamental questions: (i) when a cell should prefer thresholding to a graded response; (ii) when there is a fitness advantage to implementing a Bayesian decision rule; and (iii) when retaining memory of the past provides a selective advantage. We specifically find that: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones.

78 FR 79053 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... discretion to the member organizations to define pre-set risk thresholds. The tools are designed to act as a... comments more efficiently, please use only one method. The Commission will post all comments on the... To Offer Risk Management Tools Designed To Allow Member Organizations To Monitor and Address Exposure...

78 FR 75644 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-12

... Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate Effectiveness of a Proposed Rule Change... thresholds required to achieve each volume tier and will issue an information circular to inform Participants... calculation is pro- competitive and will result in lower total costs to Participants, a positive [[Page 75645...

78 FR 28692 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

... standard SPY options, (2) codify the minimum contract threshold requirement for the execution of Jumbo SPY... Fund (``IWM''). QQQQ, SPY and IWM are quoted in $0.01 increments for all options series. This proposed... Exchange believes that by reducing the minimum trading increments for Jumbo SPY Options to $0.01, the...

78 FR 28669 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

... ``Options Pricing'' section of its fee schedule effective immediately, in order to (i) increase fees for any...'') thresholds. The Exchange offers a bulk-quoting interface which allows Users \\6\\ of BATS Options to submit and... receipt. The bulk-quoting application for BATS Options is a particularly useful feature for Users that...

A THRESHOLD ANALYSIS OF THE TUNNEL INJECTION LASER.

DTIC Science & Technology

A new threshold analysis of the tunnel injection laser is given that differs from previous treatments in that an additional loss mechanism is...a slight increase in the threshold current density of the tunnel laser. For a device one millimeter long composed of GaAs at 77K, the threshold

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

EPA Science Inventory

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

High power single mode 980 nm AlGaInAs/AlGaAs quantum well lasers with a very low threshold current

NASA Astrophysics Data System (ADS)

Zhen, Dong; Cuiluan, Wang; Hongqi, Jing; Suping, Liu; Xiaoyu, Ma

2013-11-01

To achieve low threshold current as well as high single mode output power, a graded index separate confinement heterostructure (GRIN-SCH) AlGaInAs/AlGaAs quantum well laser with an optimized ridge waveguide was fabricated. The threshold current was reduced to 8 mA. An output power of 76 mW was achieved at 100 mA current at room temperature, with a slope efficiency of 0.83 W/A and a horizon divergent angle of 6.3°. The maximum single mode output power of the device reached as high as 450 mW.

Constant-current regulator improves tunnel diode threshold-detector performance

NASA Technical Reports Server (NTRS)

Cancro, C. A.

1965-01-01

Grounded-base transistor is placed in a tunnel diode threshold detector circuit, and a bias voltage is applied to the tunnel diode. This provides the threshold detector with maximum voltage output and overload protection.

Regulatory cross-cutting topics for fuel cycle facilities.

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

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

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

Dynamical predictors of an imminent phenotypic switch in bacteria

NASA Astrophysics Data System (ADS)

Wang, Huijing; Ray, J. Christian J.

2017-08-01

Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is ‘flickering’ of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite and protein fluctuations in bacteria, we hypothesized that metabolic early warning indicators predict imminent transitions across a network threshold caused by enzyme saturation. We used stochastic simulations to determine if flickering predicts phenotypic transitions, accounting for a variety of molecular physiological parameters, including enzyme affinity, burstiness of enzyme gene expression, homeostatic feedback, and rates of metabolic precursor influx. In most cases, we found that metabolic flickering rates are robustly peaked near the enzyme saturation threshold. The degree of fluctuation was amplified by product inhibition of the enzyme. We conclude that sensitivity to flickering in fast variables may be a possible natural or synthetic strategy to prepare physiological states for an imminent transition.

Income (In-) Adequacy? The Official Poverty Line, Possible Changes, and Some Historical Lessons.

ERIC Educational Resources Information Center

Fisher, Gordon

1999-01-01

Examines the current official poverty thresholds (including Orshansky's thresholds) and the possibility that a new poverty measure may be adopted soon, discussing the thresholds from a historical perspective. Lessons drawn from the history of poverty thresholds and of early unofficial poverty lines in the United States are included. Recent…

Effect of transcranial direct current stimulation on vestibular-ocular and vestibulo-perceptual thresholds.

PubMed

Kyriakareli, Artemis; Cousins, Sian; Pettorossi, Vito E; Bronstein, Adolfo M

2013-10-02

Transcranial direct current stimulation (tDCS) was used in 17 normal individuals to modulate vestibulo-ocular reflex (VOR) and self-motion perception rotational thresholds. The electrodes were applied over the temporoparietal junction bilaterally. Both vestibular nystagmic and perceptual thresholds were increased during as well as after tDCS stimulation. Body rotation was labeled as ipsilateral or contralateral to the anode side, but no difference was observed depending on the direction of rotation or hemisphere polarity. Threshold increase during tDCS was greater for VOR than for motion perception. 'Sham' stimulation had no effect on thresholds. We conclude that tDCS produces an immediate and sustained depression of cortical regions controlling VOR and movement perception. Temporoparietal areas appear to be involved in vestibular threshold modulation but the differential effects observed between VOR and perception suggest a partial dissociation between cortical processing of reflexive and perceptual responses.

Effectiveness of the hearing conservation program: Change in hearing threshold shift incidence among industrial workers, 1978 to 2003

NASA Astrophysics Data System (ADS)

Davies, Hugh

2005-04-01

Hearing conservation programs (HCP) are widely employed in preventing noise-induced hearing loss, but studies of their effectiveness have been rare. The impact of the implementation of hearing conservation programs was assessed in a large group of highly noise-exposed blue-collar workers by investigating time-trends in hearing-threshold shift incidence. Serial annual audiograms for employees of 14 British Columbia lumber mills for the period 1978 to 2003 were obtained from local regulatory-agency archives. Audiograms and concomitant otological medical histories were linked to subjects' work histories and noise exposure data. Multivariable Cox proportional hazard models were used to model the incidence of hearing threshold shift while controlling for age, baseline level of hearing loss, and other potential confounders. A total of 109257 audiograms were associated with 10590 subjects. Mean noise exposure in this group was 91.4 dBA(A). Mean interval between hearing tests was 566 days and mean age at first threshold shift was 44. Forty-six percent of subjects had at least one OSHA significant threshold shift during follow up. Preliminary analyses indicated a trend toward lower incidence of threshold shifts over the study period, with incidence in 5 approximately equal 5-year periods from 1978 to 2003 being 3.2%, 6.6%, 4.9%, 4.3% and 2.4%, respectively.

Transverse tripolar stimulation of peripheral nerve: a modelling study of spatial selectivity.

PubMed

Deurloo, K E; Holsheimer, J; Boom, H B

1998-01-01

Various anode-cathode configurations in a nerve cuff are modelled to predict their spatial selectivity characteristics for functional nerve stimulation. A 3D volume conductor model of a monofascicular nerve is used for the computation of stimulation-induced field potentials, whereas a cable model of myelinated nerve fibre is used for the calculation of the excitation thresholds of fibres. As well as the usual configurations (monopole, bipole, longitudinal tripole, 'steering' anode), a transverse tripolar configuration (central cathode) is examined. It is found that the transverse tripole is the only configuration giving convex recruitment contours and therefore maximises activation selectivity for a small (cylindrical) bundle of fibres in the periphery of a monofascicular nerve trunk. As the electrode configuration is changed to achieve greater selectivity, the threshold current increases. Therefore threshold currents for fibre excitation with a transverse tripole are relatively high. Inverse recruitment is less extreme than for the other configurations. The influences of several geometrical parameters and model conductivities of the transverse tripole on selectivity and threshold current are analysed. In chronic implantation, when electrodes are encapsulated by a layer of fibrous tissue, threshold currents are low, whereas the shape of the recruitment contours in transverse tripolar stimulation does not change.

Low-threshold high-T/0/ constricted double heterojunction AlGaAs diode lasers

NASA Technical Reports Server (NTRS)

Botez, D.; Connolly, J. C.

1980-01-01

Constricted double heterojunction diode lasers of relatively low CW thresholds (28-40 mA) are obtained by growing structures that maximize the amount of current flow into the lasing spot. These values are obtained while still using standard 10 microns wide oxide-defined stripe contacts. Over the 20-70 C temperature interval, threshold current temperature coefficients as high as 320 C and a virtually constant external differential quantum efficiency, are found.

Implementation of a WRF-CMAQ Air Quality Modeling System in Bogotá, Colombia

NASA Astrophysics Data System (ADS)

Nedbor-Gross, R.; Henderson, B. H.; Pachon, J. E.; Davis, J. R.; Baublitz, C. B.; Rincón, A.

2014-12-01

Due to a continuous economic growth Bogotá, Colombia has experienced air pollution issues in recent years. The local environmental authority has implemented several strategies to curb air pollution that have resulted in the decrease of PM10 concentrations since 2010. However, more activities are necessary in order to meet international air quality standards in the city. The University of Florida Air Quality and Climate group is collaborating with the Universidad de La Salle to prioritize regulatory strategies for Bogotá using air pollution simulations. To simulate pollution, we developed a modeling platform that combines the Weather Research and Forecasting Model (WRF), local emissions, and the Community Multi-scale Air Quality model (CMAQ). This platform is the first of its kind to be implemented in the megacity of Bogota, Colombia. The presentation will discuss development and evaluation of the air quality modeling system, highlight initial results characterizing photochemical conditions in Bogotá, and characterize air pollution under proposed regulatory strategies. The WRF model has been configured and applied to Bogotá, which resides in a tropical climate with complex mountainous topography. Developing the configuration included incorporation of local topography and land-use data, a physics sensitivity analysis, review, and systematic evaluation. The threshold, however, was set based on synthesis of model performance under less mountainous conditions. We will evaluate the impact that differences in autocorrelation contribute to the non-ideal performance. Air pollution predictions are currently under way. CMAQ has been configured with WRF meteorology, global boundary conditions from GEOS-Chem, and a locally produced emission inventory. Preliminary results from simulations show promising performance of CMAQ in Bogota. Anticipated results include a systematic performance evaluation of ozone and PM10, characterization of photochemical sensitivity, and air quality predictions under proposed regulatory scenarios.

Drug-induced QT interval prolongation: does ethnicity of the thorough QT study population matter?

PubMed Central

Shah, Rashmi R

2013-01-01

Inter-ethnic differences in drug responses have been well documented. Drug-induced QT interval prolongation is a major safety concern and therefore, regulatory authorities recommend a clinical thorough QT study (TQT) to investigate new drugs for their QT-prolonging potential. A positive study, determined by breach of a preset regulatory threshold, significantly influences late phase clinical trials by requiring intense ECG monitoring. A few studies that are currently available, although not statistically conclusive at present, question the assumption that ethnicity of the study population may not influence the outcome of a TQT study. Collective consideration of available pharmacogenetic and clinical information suggests that there may be inter-ethnic differences in QT-prolonging effects of drugs and that Caucasians may be more sensitive than other populations. The information also suggest s that (a) these differences may depend on the QT-prolonging potency of the drug and (b) exposure–response (E–R) analysis may be more sensitive than simple changes in QTc interval in unmasking this difference. If the QT response in Caucasians is generally found to be more intense than in non-Caucasians, there may be significant regulatory implications for domestic acceptance of data from a TQT study conducted in foreign populations. However, each drug will warrant an individual consideration when extrapolating the results of a TQT studyfrom one ethnic population to another and the ultimate clinical relevance of any difference. Further adequately designed and powered studies, investigating the pharmacologic properties and E–R relationships of additional drugs with different potencies, are needed in Caucasians, Oriental/Asian and African populations before firm conclusions can be drawn. PMID:22882246

Bioavailability and Environmental Regulation - Integrating a Fate & Effects Model with a Biotic Ligand Model for Copper in Seawater

NASA Astrophysics Data System (ADS)

Rivera, I.; Chadwick, B.; Rosen, G.; Wang, P. F.; Paquin, P.; Santore, R.; Ryan, A.

2015-12-01

Understanding the bioavailability of metals in the aquatic environment is important for defining appropriate regulatory constraints. A failure to recognize the importance of bioavailability factors on metal toxicity can result in criteria that are over- or under-protective. USEPA addresses the tendency of the national Water Quality Criterion (WQC) for regulation of copper in marine waters to underestimate the natural attenuation of copper toxicity in harbors by the application of site-specific Water Quality Standards (WQS). Which provides the level of protection intended by the WQC, and establishes realistic regulatory objectives. However, development of site-specific WQS involves a long-term effort, and does not account for temporal variation. The toxicity model seawater-Biotic Ligand Model (BLM) was developed and integrated with the existing Curvilinear Hydrodynamics in 3 Dimensions (CH3D) transport & fate model to create an efficient tool for development of site-specific WQS in harbors. The integrated model was demonstrated at a harbor-wide scale in San Diego Bay and Pearl Harbor, and accounted for the natural physical, chemical, biological and toxicological characteristics of the harbor to achieve more scientifically based compliance. In both harbors the spatial and temporal distributions of copper species, toxic effects, and Water Effect Ratio predicted by the integrated model are comparable to previous data. The model was further demonstrated in Shelter Island Yacht Basin (SIYB) marina in San Diego Bay. The integrated model agreed with toxicological and chemical approaches by indicating negligible bioavailability as well as no toxicity; but for a single event, even though an increasing gradient in Cu was observed both horizontally and vertically, with concentrations that reached levels well above current regulatory thresholds. These results support the incorporation by USEPA of the seawater-BLM in a full-strength seawater criterion.

SONOS Nonvolatile Memory Cell Programming Characteristics

NASA Technical Reports Server (NTRS)

MacLeod, Todd C.; Phillips, Thomas A.; Ho, Fat D.

2010-01-01

Silicon-oxide-nitride-oxide-silicon (SONOS) nonvolatile memory is gaining favor over conventional EEPROM FLASH memory technology. This paper characterizes the SONOS write operation using a nonquasi-static MOSFET model. This includes floating gate charge and voltage characteristics as well as tunneling current, voltage threshold and drain current characterization. The characterization of the SONOS memory cell predicted by the model closely agrees with experimental data obtained from actual SONOS memory cells. The tunnel current, drain current, threshold voltage and read drain current all closely agreed with empirical data.

78 FR 79046 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-27

... ETP Holder to define pre-set risk thresholds. The tools are designed to act as a backstop for ETP... one method. The Commission will post all comments on the Commission's Internet Web site ( http://www... Change To Offer Risk Management Tools Designed To Allow ETP Holders To Monitor and Address Exposure to...

75 FR 22884 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... uniform time frame for the introduction of new LEAPS on equity option classes, options on exchange traded... minimum volume threshold per underlying class to qualify for the introduction of a new expiration year of... 30 days from the date on which it was filed, or such shorter time as the Commission may designate if...

75 FR 51126 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-18

... accordance with Rule 6.24. \\6\\ The term OTP refers to an Options Trading Permit issued by the Exchange for... Ex-by-Ex threshold, coupled with the dramatic increase in option trading volume from 2003 to 2009... and the increase in trading, the existing deadline for submitting CEAs to the Exchange is problematic...

76 FR 20793 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

..., approximately 40% of CBOE Floor Broker Trading Permit Holders would fall under Tier 1 and would no longer be... Holders fall under Tier 4, having a PAR Official execute more than 75% of the Trading Permit Holder's... ``Exchange'') proposes to amend its Fees Schedule to establish volume threshold tiers for the assessment of...

The twilight zone of cis element alignments.

PubMed

Sebastian, Alvaro; Contreras-Moreira, Bruno

2013-02-01

Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare (http://floresta.eead.csic.es/tfcompare), a structural alignment method for protein-DNA complexes; (ii) to benchmark the pairwise alignment of regulatory elements; (iii) to define the confidence limits and the twilight zone of such alignments and (iv) to evaluate the relevance of these thresholds with elements obtained experimentally. We find that the structure of cis elements and protein-DNA interfaces is significantly more conserved than their sequence and measures how this correlates with alignment errors when only sequence information is considered. Our results confirm that DNA motifs in the form of matrices produce better alignments than individual sequences. Finally, we report that empirical and theoretically derived twilight thresholds are useful for estimating the natural plasticity of regulatory sequences, and hence for filtering out unreliable alignments.

The twilight zone of cis element alignments

PubMed Central

Sebastian, Alvaro; Contreras-Moreira, Bruno

2013-01-01

Sequence alignment of proteins and nucleic acids is a routine task in bioinformatics. Although the comparison of complete peptides, genes or genomes can be undertaken with a great variety of tools, the alignment of short DNA sequences and motifs entails pitfalls that have not been fully addressed yet. Here we confront the structural superposition of transcription factors with the sequence alignment of their recognized cis elements. Our goals are (i) to test TFcompare (http://floresta.eead.csic.es/tfcompare), a structural alignment method for protein–DNA complexes; (ii) to benchmark the pairwise alignment of regulatory elements; (iii) to define the confidence limits and the twilight zone of such alignments and (iv) to evaluate the relevance of these thresholds with elements obtained experimentally. We find that the structure of cis elements and protein–DNA interfaces is significantly more conserved than their sequence and measures how this correlates with alignment errors when only sequence information is considered. Our results confirm that DNA motifs in the form of matrices produce better alignments than individual sequences. Finally, we report that empirical and theoretically derived twilight thresholds are useful for estimating the natural plasticity of regulatory sequences, and hence for filtering out unreliable alignments. PMID:23268451

End-of-life management of corrosive drywall.

PubMed

Kim, Hwidong; Krause, Max J; Townsend, Timothy

2016-11-01

Recently, gypsum drywall products imported to the United States (US) were found to cause metal corrosion and tarnishing in some homes, often necessitating that this drywall be discarded. Research assessed the potential implications of recycling and landfilling corrosive/imported drywall. Samples of corrosive drywall were collected from homes in Florida, US and these characteristics were assessed relative to domestically-produced drywall purchased from retail outlets. The total and synthetic precipitation leaching procedure (SPLP) leachable heavy metal concentrations were measured and compared to risk-based regulatory thresholds to assess the possible land application risk. In a majority of samples, concentrations were below levels of regulatory concern. The mean concentration of several elements exceeded the thresholds in a few samples for the direct exposure assessment (As) and the groundwater leaching assessment (Al, B, Hg, Mn, Sr and V); but the results did not suggest that corrosive drywall would present a greater risk than domestic drywall. To assess landfilling concerns, the potential for sulfur gases emissions upon disposal was evaluated. Experiments indicated that corrosive drywall would not pose a greater risk of long-term H2S emissions compared to domestic drywall. Copyright © 2016 Elsevier Ltd. All rights reserved.

Practical aspects of mutagenicity testing strategy: an industrial perspective.

PubMed

Gollapudi, B B; Krishna, G

2000-11-20

Genetic toxicology studies play a central role in the development and marketing of new chemicals for pharmaceutical, agricultural, industrial, and consumer use. During the discovery phase of product development, rapid screening tests that require minimal amounts of test materials are used to assist in the design and prioritization of new molecules. At this stage, a modified Salmonella reverse mutation assay and an in vitro micronucleus test with mammalian cell culture are frequently used for screening. Regulatory genetic toxicology studies are conducted with a short list of compounds using protocols that conform to various international guidelines. A set of four assays usually constitutes the minimum test battery that satisfies global requirements. This set includes a bacterial reverse mutation assay, an in vitro cytogenetic test with mammalian cell culture, an in vitro gene mutation assay in mammalian cell cultures, and an in vivo rodent bone marrow micronucleus test. Supplementary studies are conducted in certain instances either as a follow-up to the findings from this initial testing battery and/or to satisfy a regulatory requirement. Currently available genetic toxicology assays have helped the scientific and industrial community over the past several decades in evaluating the mutagenic potential of chemical agents. The emerging field of toxicogenomics has the potential to redefine our ability to study the response of cells to genetic damage and hence our ability to study threshold phenomenon.

Reducing abrupt climate change risk using the Montreal Protocol and other regulatory actions to complement cuts in CO2 emissions.

PubMed

Molina, Mario; Zaelke, Durwood; Sarma, K Madhava; Andersen, Stephen O; Ramanathan, Veerabhadran; Kaniaru, Donald

2009-12-08

Current emissions of anthropogenic greenhouse gases (GHGs) have already committed the planet to an increase in average surface temperature by the end of the century that may be above the critical threshold for tipping elements of the climate system into abrupt change with potentially irreversible and unmanageable consequences. This would mean that the climate system is close to entering if not already within the zone of "dangerous anthropogenic interference" (DAI). Scientific and policy literature refers to the need for "early," "urgent," "rapid," and "fast-action" mitigation to help avoid DAI and abrupt climate changes. We define "fast-action" to include regulatory measures that can begin within 2-3 years, be substantially implemented in 5-10 years, and produce a climate response within decades. We discuss strategies for short-lived non-CO(2) GHGs and particles, where existing agreements can be used to accomplish mitigation objectives. Policy makers can amend the Montreal Protocol to phase down the production and consumption of hydrofluorocarbons (HFCs) with high global warming potential. Other fast-action strategies can reduce emissions of black carbon particles and precursor gases that lead to ozone formation in the lower atmosphere, and increase biosequestration, including through biochar. These and other fast-action strategies may reduce the risk of abrupt climate change in the next few decades by complementing cuts in CO(2) emissions.

Disposition of the anti-ulcer medications ranitidine, cimetidine, and omeprazole following administration of multiple doses to exercised Thoroughbred horses.

PubMed

Knych, H K; Stanley, S D; Arthur, R M; McKemie, D S

2017-01-01

The use of anti-ulcer medications, such as cimetidine, ranitidine, and omeprazole, is common in performance horses. The use of these drugs is regulated in performance horses, and as such a withdrawal time is necessary prior to competition to avoid a medication violation. To the authors' knowledge, there are no reports in the literature describing repeated oral administrations of these drugs in the horse to determine a regulatory threshold and related withdrawal time recommendations. Therefore, the objective of the current study was to describe the disposition and elimination pharmacokinetics of these anti-ulcer medications following oral administration to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 20 mg/kg BID of cimetidine or 8 mg/kg BID of ranitidine, both for seven doses or 2.28 g of omeprazole SID for four doses. Blood samples were collected, serum drug concentrations were determined, and elimination pharmacokinetic parameters were calculated. The serum elimination half-life was 7.05 ± 1.02, 7.43 ± 0.851 and 3.94 ± 1.04 h for cimetidine, ranitidine, and omeprazole, respectively. Serum cimetidine and ranitidine concentrations were above the LOQ and omeprazole and omeprazole sulfide below the LOQ in all horses studied upon termination of sample collection. © 2016 John Wiley & Sons Ltd.

Groundwater-Quality Data in the Antelope Valley Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Schmitt, Stephen J.; Milby Dawson, Barbara J.; Belitz, Kenneth

2009-01-01

Groundwater quality in the approximately 1,600 square-mile Antelope Valley study unit (ANT) was investigated from January to April 2008 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001, and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw groundwater used for public water supplies within ANT, and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 57 wells in Kern, Los Angeles, and San Bernardino Counties. Fifty-six of the wells were selected using a spatially distributed, randomized, grid-based method to provide statistical representation of the study area (grid wells), and one additional well was selected to aid in evaluation of specific water-quality issues (understanding well). The groundwater samples were analyzed for a large number of organic constituents (volatile organic compounds [VOCs], gasoline additives and degradates, pesticides and pesticide degradates, fumigants, and pharmaceutical compounds), constituents of special interest (perchlorate, N-nitrosodimethylamine [NDMA], and 1,2,3-trichloropropane [1,2,3-TCP]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), and radioactive constituents (gross alpha and gross beta radioactivity, radium isotopes, and radon-222). Naturally occurring isotopes (strontium, tritium, and carbon-14, and stable isotopes of hydrogen and oxygen in water), and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, 239 constituents and water-quality indicators (field parameters) were investigated. Quality-control samples (blanks, replicates, and samples for matrix spikes) were collected at 12 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the groundwater samples. Differences between replicate samples generally were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most compoundsThis study did not evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only, and are not indicative of compliance or non-compliance with drinking water standards. Most constituents that were detected in groundwater samples were found at concentrations below drinking-water thresholds. Volatile organic compounds (VOCs) were detected in about one-half of the samples and pesticides detected in about one-third of the samples; all detections of these constituents were below health-based thresholds. Most detections of trace elements and nutrients in samples from ANT wells were below health-based thresholds. Exceptions include: one detection of nitrite plus nitr

Definition of temperature thresholds: the example of the French heat wave warning system.

PubMed

Pascal, Mathilde; Wagner, Vérène; Le Tertre, Alain; Laaidi, Karine; Honoré, Cyrille; Bénichou, Françoise; Beaudeau, Pascal

2013-01-01

Heat-related deaths should be somewhat preventable. In France, some prevention measures are activated when minimum and maximum temperatures averaged over three days reach city-specific thresholds. The current thresholds were computed based on a descriptive analysis of past heat waves and on local expert judgement. We tested whether a different method would confirm these thresholds. The study was set in the six cities of Paris, Lyon, Marseille, Nantes, Strasbourg and Limoges between 1973 and 2003. For each city, we estimated the excess in mortality associated with different temperature thresholds, using a generalised additive model, controlling for long-time trends, seasons and days of the week. These models were used to compute the mortality predicted by different percentiles of temperatures. The thresholds were chosen as the percentiles associated with a significant excess mortality. In all cities, there was a good correlation between current thresholds and the thresholds derived from the models, with 0°C to 3°C differences for averaged maximum temperatures. Both set of thresholds were able to anticipate the main periods of excess mortality during the summers of 1973 to 2003. A simple method relying on descriptive analysis and expert judgement is sufficient to define protective temperature thresholds and to prevent heat wave mortality. As temperatures are increasing along with the climate change and adaptation is ongoing, more research is required to understand if and when thresholds should be modified.

Use of the dog as non-rodent test species in the safety testing schedule associated with the registration of crop and plant protection products (pesticides): present status.

PubMed

Box, Rainer J; Spielmann, Horst

2005-11-01

The results from a survey of the expert information that is publicly accessible on the use of the dog as test species during the regulatory evaluation of agricultural chemicals and pesticides are reported. Methods that are being used or considered in order to reduce the number of dogs used for this purpose are described. Regulatory evaluation aims at establishing threshold values for safe human exposure; it is based on no-observed-adverse-effect levels (NOELs) determined in animal studies. Current regulations require testing in two species, a rodent species (usually rat or mouse), and a non-rodent species (usually the dog). Subchronic (90-day) and chronic (12-month) repeated-dose feeding studies must be routinely conducted in dogs. This report first focuses on the results from a retrospective study analysing data on 216 pesticides kept on record by the Bundesinstitut für Risikobewertung, BfR (German Federal Institute for Risk Assessment), the competent regulatory authority in Germany. The study was sponsored and coordinated by SET, the German Foundation for the Promotion of Research on Replacement and Complementary Methods to Reduce Animal Testing (Stiftung zur Förderung der Erforschung von Ersatz-und Ergänzungsmethoden zur Einschränkung von Tierversuchen, Mainz) and conducted by the BfR. Since the data submitted for registration of a product is the property of the manufacturer, the study could only proceed with the collaboration of the German Association of Manufacturers of Agricultural Chemicals (Industrieverband Agrar, IVA). To ensure confidentiality, designated codes were used instead of the compounds' proper names when the study was published. The results support two major conclusions. The use of the dog for the testing of pesticides is indeed necessary because the dog has proved to be the most sensitive species for about 15% of the compounds examined. However, chronic studies are only of limited value since they only provide essential information that cannot be obtained in sub-chronic studies in about 5% of cases. These conclusions are supported by several retrospective analyses using data on pharmaceutical drugs carried out in the context of the International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (ICH). Over 90% of drugs elicited no toxic symptoms in 12-month studies in dogs in addition to those that had been recorded previously in studies conducted for 90 or 180 days in dogs and rats. Another approach comparing the results from pre-clinical animal studies with clinical studies noted that animal studies predicted about 70% of the effects observed in volunteers, and in about 94% of cases the effects occurred in animal studies lasting not more than one month. Furthermore, the report summarises the current methods under consideration that could refine or reduce the use of dogs in toxicity testing: industrial data sharing and harmonisation of guidelines, in vitro methods, human studies, computational prediction models, and integrated testing approaches. The integrated Agricultural Chemicals Safety Assessment (ACSA) testing scheme, which is currently being developed in an international project initiated by the International Life Sciences Institute (ILSI, USA), is of particular relevance, since an ambitious attempt is being made to design a new comprehensive test framework incorporating modern scientific approaches and covering most aspects of current regulatory testing requirements. The ACSA project has access to the pesticide database of the US EPA's Office of Pesticide Programs (OPP). Preliminary results have confirmed the two major conclusions from the joint SET/BfR study conducted in Germany. Taking these results into account, it is recommended that the regulatory requirement for 12-month studies to be routinely carried out in dogs should be abandoned. While 90-day studies should be conducted in both rats and dogs, chronic studies should only take place in rats. If the dog is more sensitive than the rat in the 90-day study, an additional safety factor to the NOEL value obtained in the chronic rat study should be applied in order to set the threshold for safe human exposure, instead of conducting a 12-month study in dogs. This safety factor may be calculated from chronic NOEL data available in several pesticide databases. Chronic tests using dogs would then only be required if the test compound belongs to a new class of chemicals that has never been tested before. Thus, the report concludes that, according to current scientific knowledge, the routine 12-month studies in dogs are no longer required for agricultural chemicals and pesticides, and international regulations should be changed accordingly. Active international support of such measures is welcomed, from both an economical and an animal welfare perspective.

78 FR 803 - Revisions to Electric Reliability Organization Definition of Bulk Electric System and Rules of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

...In this Final Rule, pursuant to section 215 of the Federal Power Act, the Federal Energy Regulatory Commission (Commission) approves modifications to the currently-effective definition of ``bulk electric system'' developed by the North American Electric Reliability Corporation (NERC), the Commission-certified Electric Reliability Organization. The Commission finds that the modified definition of ``bulk electric system'' removes language allowing for regional discretion in the currently-effective bulk electric system definition and establishes a bright-line threshold that includes all facilities operated at or above 100 kV. The modified definition also identifies specific categories of facilities and configurations as inclusions and exclusions to provide clarity in the definition of ``bulk electric system.'' In this Final Rule, the Commission also approves: NERC's revisions to its Rules of Procedure, which create an exception process to add elements to, or remove elements from, the definition of ``bulk electric system'' on a case-by-case basis; NERC's form entitled ``Detailed Information To Support an Exception Request'' that entities will use to support requests for exception from the ``bulk electric system'' definition; and NERC's implementation plan for the revised ``bulk electric system'' definition.

Hazardous Compounds in Tobacco Smoke

PubMed Central

Talhout, Reinskje; Schulz, Thomas; Florek, Ewa; van Benthem, Jan; Wester, Piet; Opperhuizen, Antoon

2011-01-01

Tobacco smoke is a toxic and carcinogenic mixture of more than 5,000 chemicals. The present article provides a list of 98 hazardous smoke components, based on an extensive literature search for known smoke components and their human health inhalation risks. An electronic database of smoke components containing more than 2,200 entries was generated. Emission levels in mainstream smoke have been found for 542 of the components and a human inhalation risk value for 98 components. As components with potential carcinogenic, cardiovascular and respiratory effects have been included, the three major smoke-related causes of death are all covered by the list. Given that the currently used Hoffmann list of hazardous smoke components is based on data from the 1990s and only includes carcinogens, it is recommended that the current list of 98 hazardous components is used for regulatory purposes instead. To enable risk assessment of components not covered by this list, thresholds of toxicological concern (TTC) have been established from the inhalation risk values found: 0.0018 μg day−1 for all risks, and 1.2 μg day−1 for all risks excluding carcinogenicity, the latter being similar to previously reported inhalation TTCs. PMID:21556207

Device for monitoring cell voltage

DOEpatents

Doepke, Matthias [Garbsen, DE; Eisermann, Henning [Edermissen, DE

2012-08-21

A device for monitoring a rechargeable battery having a number of electrically connected cells includes at least one current interruption switch for interrupting current flowing through at least one associated cell and a plurality of monitoring units for detecting cell voltage. Each monitoring unit is associated with a single cell and includes a reference voltage unit for producing a defined reference threshold voltage and a voltage comparison unit for comparing the reference threshold voltage with a partial cell voltage of the associated cell. The reference voltage unit is electrically supplied from the cell voltage of the associated cell. The voltage comparison unit is coupled to the at least one current interruption switch for interrupting the current of at least the current flowing through the associated cell, with a defined minimum difference between the reference threshold voltage and the partial cell voltage.

Value of information and pricing new healthcare interventions.

PubMed

Willan, Andrew R; Eckermann, Simon

2012-06-01

Previous application of value-of-information methods to optimal clinical trial design have predominantly taken a societal decision-making perspective, implicitly assuming that healthcare costs are covered through public expenditure and trial research is funded by government or donation-based philanthropic agencies. In this paper, we consider the interaction between interrelated perspectives of a societal decision maker (e.g. the National Institute for Health and Clinical Excellence [NICE] in the UK) charged with the responsibility for approving new health interventions for reimbursement and the company that holds the patent for a new intervention. We establish optimal decision making from societal and company perspectives, allowing for trade-offs between the value and cost of research and the price of the new intervention. Given the current level of evidence, there exists a maximum (threshold) price acceptable to the decision maker. Submission for approval with prices above this threshold will be refused. Given the current level of evidence and the decision maker's threshold price, there exists a minimum (threshold) price acceptable to the company. If the decision maker's threshold price exceeds the company's, then current evidence is sufficient since any price between the thresholds is acceptable to both. On the other hand, if the decision maker's threshold price is lower than the company's, then no price is acceptable to both and the company's optimal strategy is to commission additional research. The methods are illustrated using a recent example from the literature.

Comparisons between detection threshold and loudness perception for individual cochlear implant channels

PubMed Central

Bierer, Julie Arenberg; Nye, Amberly D

2014-01-01

Objective The objective of the present study, performed in cochlear implant listeners, was to examine how the level of current required to detect single-channel electrical pulse trains relates to loudness perception on the same channel. The working hypothesis was that channels with relatively high thresholds, when measured with a focused current pattern, interface poorly to the auditory nerve. For such channels a smaller dynamic range between perceptual threshold and the most comfortable loudness would result, in part, from a greater sensitivity to changes in electrical field spread compared to low-threshold channels. The narrower range of comfortable listening levels may have important implications for speech perception. Design Data were collected from eight, adult cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp.). The partial tripolar (pTP) electrode configuration, consisting of one intracochlear active electrode, two flanking electrodes carrying a fraction (σ) of the return current, and an extracochlear ground, was used for stimulation. Single-channel detection thresholds and most comfortable listening levels were acquired using the most focused pTP configuration possible (σ ≥ 0.8) to identify three channels for further testing – those with the highest, median, and lowest thresholds – for each subject. Threshold, equal-loudness contours (at 50% of the monopolar dynamic range), and loudness growth functions were measured for each of these three test channels using various partial tripolar fractions. Results For all test channels, thresholds increased as the electrode configuration became more focused. The rate of increase with the focusing parameter σ was greatest for the high-threshold channel compared to the median- and low-threshold channels. The 50% equal-loudness contours exhibited similar rates of increase in level across test channels and subjects. Additionally, test channels with the highest thresholds had the narrowest dynamic ranges (for σ ≥ 0.5) and steepest growth of loudness functions for all electrode configurations. Conclusions Together with previous studies using focused stimulation, the results suggest that auditory responses to electrical stimuli at both threshold and suprathreshold current levels are not uniform across the electrode array of individual cochlear implant listeners. Specifically, the steeper growth of loudness and thus smaller dynamic ranges observed for high-threshold channels are consistent with a degraded electrode-neuron interface, which could stem from lower numbers of functioning auditory neurons or a relatively large distance between the neurons and electrodes. These findings may have potential implications for how stimulation levels are set during the clinical mapping procedure, particularly for speech-processing strategies that use focused electrical fields. PMID:25036146

Environmental Statistics and Optimal Regulation

PubMed Central

2014-01-01

Any organism is embedded in an environment that changes over time. The timescale for and statistics of environmental change, the precision with which the organism can detect its environment, and the costs and benefits of particular protein expression levels all will affect the suitability of different strategies–such as constitutive expression or graded response–for regulating protein levels in response to environmental inputs. We propose a general framework–here specifically applied to the enzymatic regulation of metabolism in response to changing concentrations of a basic nutrient–to predict the optimal regulatory strategy given the statistics of fluctuations in the environment and measurement apparatus, respectively, and the costs associated with enzyme production. We use this framework to address three fundamental questions: (i) when a cell should prefer thresholding to a graded response; (ii) when there is a fitness advantage to implementing a Bayesian decision rule; and (iii) when retaining memory of the past provides a selective advantage. We specifically find that: (i) relative convexity of enzyme expression cost and benefit influences the fitness of thresholding or graded responses; (ii) intermediate levels of measurement uncertainty call for a sophisticated Bayesian decision rule; and (iii) in dynamic contexts, intermediate levels of uncertainty call for retaining memory of the past. Statistical properties of the environment, such as variability and correlation times, set optimal biochemical parameters, such as thresholds and decay rates in signaling pathways. Our framework provides a theoretical basis for interpreting molecular signal processing algorithms and a classification scheme that organizes known regulatory strategies and may help conceptualize heretofore unknown ones. PMID:25254493

High-wafer-yield, high-performance vertical cavity surface-emitting lasers

NASA Astrophysics Data System (ADS)

Li, Gabriel S.; Yuen, Wupen; Lim, Sui F.; Chang-Hasnain, Constance J.

1996-04-01

Vertical cavity surface emitting lasers (VCSELs) with very low threshold current and voltage of 340 (mu) A and 1.5 V is achieved. The molecular beam epitaxially grown wafers are grown with a highly accurate, low cost and versatile pre-growth calibration technique. One- hundred percent VCSEL wafer yield is obtained. Low threshold current is achieved with a native oxide confined structure with excellent current confinement. Single transverse mode with stable, predetermined polarization direction up to 18 times threshold is also achieved, due to stable index guiding provided by the structure. This is the highest value reported to data for VCSELs. We have established that p-contact annealing in these devices is crucial for low voltage operation, contrary to the general belief. Uniform doping in the mirrors also appears not to be inferior to complicated doping engineering. With these design rules, very low threshold voltage VCSELs are achieved with very simple growth and fabrication steps.

Unidirectional threshold switching in Ag/Si-based electrochemical metallization cells for high-density bipolar RRAM applications

NASA Astrophysics Data System (ADS)

Wang, Chao; Song, Bing; Li, Qingjiang; Zeng, Zhongming

2018-03-01

We herein present a novel unidirectional threshold selector for cross-point bipolar RRAM array. The proposed Ag/amorphous Si based threshold selector showed excellent threshold characteristics in positive field, such as high selectivity ( 105), steep slope (< 5 mV/decade) and low off-state current (< 300 pA). Meanwhile, the selector exhibited rectifying characteristics in the high resistance state as well and the rectification ratio was as high as 103 at ± 1.5 V. Nevertheless, due to the high reverse current about 9 mA at - 3 V, this unidirectional threshold selector can be used as a selection element for bipolar-type RRAM. By integrating a bipolar RRAM device with the selector, experiments showed that the undesired sneak was significantly suppressed, indicating its potentiality for high-density integrated nonvolatile memory applications.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

NASA Astrophysics Data System (ADS)

Le Gallo, Manuel; Athmanathan, Aravinthan; Krebs, Daniel; Sebastian, Abu

2016-01-01

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current in doped Ge2Sb2Te5 nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.

Method and system for controlling a rotational speed of a rotor of a turbogenerator

DOEpatents

Stahlhut, Ronnie Dean; Vuk, Carl Thomas

2008-12-30

A system and method controls a rotational speed of a rotor or shaft of a turbogenerator in accordance with a present voltage level on a direct current bus. A lower threshold and a higher threshold are established for a speed of a rotor or shaft of a turbogenerator. A speed sensor determines speed data or a speed signal for the rotor or shaft associated with a turbogenerator. A voltage regulator adjusts a voltage level associated with a direct current bus within a target voltage range if the speed data or speed signal indicates that the speed is above the higher threshold or below the lower threshold.

Electric field characteristics of electroconvulsive therapy with individualized current amplitude: a preclinical study.

PubMed

Lee, Won Hee; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2013-01-01

This study examines the characteristics of the electric field induced in the brain by electroconvulsive therapy (ECT) with individualized current amplitude. The electric field induced by bilateral (BL), bifrontal (BF), right unilateral (RUL), and frontomedial (FM) ECT electrode configurations was computed in anatomically realistic finite element models of four nonhuman primates (NHPs). We generated maps of the electric field strength relative to an empirical neural activation threshold, and determined the stimulation strength and focality at fixed current amplitude and at individualized current amplitudes corresponding to seizure threshold (ST) measured in the anesthetized NHPs. The results show less variation in brain volume stimulated above threshold with individualized current amplitudes (16-36%) compared to fixed current amplitude (30-62%). Further, the stimulated brain volume at amplitude-titrated ST is substantially lower than that for ECT with conventional fixed current amplitudes. Thus individualizing the ECT stimulus current could compensate for individual anatomical variability and result in more focal and uniform electric field exposure across different subjects compared to the standard clinical practice of using high, fixed current for all patients.

Future needs and recommendations in the development of species sensitivity distributions: Estimating toxicity thresholds for aquatic ecological communities and assessing impacts of chemical exposures.

PubMed

Belanger, Scott; Barron, Mace; Craig, Peter; Dyer, Scott; Galay-Burgos, Malyka; Hamer, Mick; Marshall, Stuart; Posthuma, Leo; Raimondo, Sandy; Whitehouse, Paul

2017-07-01

A species sensitivity distribution (SSD) is a probability model of the variation of species sensitivities to a stressor, in particular chemical exposure. The SSD approach has been used as a decision support tool in environmental protection and management since the 1980s, and the ecotoxicological, statistical, and regulatory basis and applications continue to evolve. This article summarizes the findings of a 2014 workshop held by the European Centre for Toxicology and Ecotoxicology of Chemicals and the UK Environment Agency in Amsterdam, The Netherlands, on the ecological relevance, statistical basis, and regulatory applications of SSDs. An array of research recommendations categorized under the topical areas of use of SSDs, ecological considerations, guideline considerations, method development and validation, toxicity data, mechanistic understanding, and uncertainty were identified and prioritized. A rationale for the most critical research needs identified in the workshop is provided. The workshop reviewed the technical basis and historical development and application of SSDs, described approaches to estimating generic and scenario-specific SSD-based thresholds, evaluated utility and application of SSDs as diagnostic tools, and presented new statistical approaches to formulate SSDs. Collectively, these address many of the research needs to expand and improve their application. The highest priority work, from a pragmatic regulatory point of view, is to develop a guidance of best practices that could act as a basis for global harmonization and discussions regarding the SSD methodology and tools. Integr Environ Assess Manag 2017;13:664-674. © 2016 SETAC. © 2016 SETAC.

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.

75 FR 45685 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... list (see current List 7 titled Misrepresentation/Omissions, List 9 titled Negligence/Breach of... claims alleging misrepresentation/ omissions (see current List 8, Item 1), negligence/breach of fiduciary... claims alleging misrepresentation/ omission (see current List 8, Item 2), negligence/breach of fiduciary...

Ground-Water Quality Data in the Monterey Bay and Salinas Valley Basins, California, 2005 - Results from the California GAMA Program

USGS Publications Warehouse

Kulongoski, Justin T.; Belitz, Kenneth

2007-01-01

Ground-water quality in the approximately 1,000-square-mile Monterey Bay and Salinas Valley study unit was investigated from July through October 2005 as part of the California Ground-Water Ambient Monitoring and Assessment (GAMA) program. The study was designed to provide a spatially unbiased assessment of raw ground-water quality, as well as a statistically consistent basis for comparing water quality throughout California. Samples were collected from 94 public-supply wells and 3 monitoring wells in Monterey, Santa Cruz, and San Luis Obispo Counties. Ninety-one of the public-supply wells sampled were selected to provide a spatially distributed, randomized monitoring network for statistical representation of the study area. Six wells were sampled to evaluate changes in water chemistry: three wells along a ground-water flow path were sampled to evaluate lateral changes, and three wells at discrete depths from land surface were sampled to evaluate changes in water chemistry with depth from land surface. The ground-water samples were analyzed for volatile organic compounds (VOCs), pesticides, pesticide degradates, nutrients, major and minor ions, trace elements, radioactivity, microbial indicators, and dissolved noble gases (the last in collaboration with Lawrence Livermore National Laboratory). Naturally occurring isotopes (tritium, carbon-14, helium-4, and the isotopic composition of oxygen and hydrogen) also were measured to help identify the source and age of the sampled ground water. In total, 270 constituents and water-quality indicators were investigated for this study. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain water quality. In addition, regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. In this study, only six constituents, alpha radioactivity, N-nitrosodimethylamine, 1,2,3-trichloropropane, nitrate, radon-222, and coliform bacteria were detected at concentrations higher than health-based regulatory thresholds. Six constituents, including total dissolved solids, hexavalent chromium, iron, manganese, molybdenum, and sulfate were detected at concentrations above levels set for aesthetic concerns. One-third of the randomized wells sampled for the Monterey Bay and Salinas Valley GAMA study had at least a single detection of a VOC or gasoline additive. Twenty-eight of the 88 VOCs and gasoline additives investigated were found in ground-water samples; however, detected concentrations were one-third to one-sixty-thousandth of their respective regulatory thresholds. Compounds detected in 10 percent or more of the wells sampled include chloroform, a compound resulting from the chlorination of water, and tetrachloroethylene (PCE), a common solvent. Pesticides and pesticide degradates also were detected in one-third of the ground-water samples collected; however, detected concentrations were one-thirtieth to one-fourteen-thousandth of their respective regulatory thresholds. Ten of the 122 pesticides and pesticide degradates investigated were found in ground-water samples. Compounds detected in 10 percent or more of the wells sampled include the herbicide simazine, and the pesticide degradate deethylatrazine. Ground-water samples had a median total dissolved solids (TDS) concentration of 467 milligrams per liter (mg/L), and 16 of the 34 samples had TDS concentrations above the recommended secondary maximum contaminant level (SMCL-a threshold established for aesthetic qualities: taste, odor, and color) of 500 mg/L, while four samples had concentrations above the upper SMCL of 1,000 mg/L. Concentrations of nitrate plus nitrite ranged from 0.04 to 37.8 mg/L (as nitrogen), and two samples had concentrations above the health-based threshold for nitrate of 10 mg/L (as nitrogen). The median sulfate concentration

Pixel structures to compensate nonuniform threshold voltage and mobility of polycrystalline silicon thin-film transistors using subthreshold current for large-size active matrix organic light-emitting diode displays

NASA Astrophysics Data System (ADS)

Na, Jun-Seok; Kwon, Oh-Kyong

2014-01-01

We propose pixel structures for large-size and high-resolution active matrix organic light-emitting diode (AMOLED) displays using a polycrystalline silicon (poly-Si) thin-film transistor (TFT) backplane. The proposed pixel structures compensate the variations of the threshold voltage and mobility of the driving TFT using the subthreshold current. The simulated results show that the emission current error of the proposed pixel structure B ranges from -2.25 to 2.02 least significant bit (LSB) when the variations of the threshold voltage and mobility of the driving TFT are ±0.5 V and ±10%, respectively.

On the threshold conditions for electron beam damage of asbestos amosite fibers in the transmission electron microscope (TEM).

PubMed

Martin, Joannie; Beauparlant, Martin; Sauvé, Sébastien; L'Espérance, Gilles

2016-12-01

Asbestos amosite fibers were investigated to evaluate the damage caused by a transmission electron microscope (TEM) electron beam. Since elemental x-ray intensity ratios obtained by energy dispersive x-ray spectroscopy (EDS) are commonly used for asbestos identification, the impact of beam damage on these ratios was evaluated. It was determined that the magnesium/silicon ratio best represented the damage caused to the fiber. Various tests showed that most fibers have a current density threshold above which the chemical composition of the fiber is modified. The value of this threshold current density varied depending on the fiber, regardless of fiber diameter, and in some cases could not be determined. The existence of a threshold electron dose was also demonstrated. This value was dependent on the current density used and can be increased by providing a recovery period between exposures to the electron beam. This study also established that the electron beam current is directly related to the damage rate above a current density of 165 A/cm 2 . The large number of different results obtained suggest, that in order to ensure that the amosite fibers are not damaged, analysis should be conducted below a current density of 100 A/cm 2 .

First direct measurements of behavioural responses by Cuvier's beaked whales to mid-frequency active sonar.

PubMed

DeRuiter, Stacy L; Southall, Brandon L; Calambokidis, John; Zimmer, Walter M X; Sadykova, Dinara; Falcone, Erin A; Friedlaender, Ari S; Joseph, John E; Moretti, David; Schorr, Gregory S; Thomas, Len; Tyack, Peter L

2013-08-23

Most marine mammal- strandings coincident with naval sonar exercises have involved Cuvier's beaked whales (Ziphius cavirostris). We recorded animal movement and acoustic data on two tagged Ziphius and obtained the first direct measurements of behavioural responses of this species to mid-frequency active (MFA) sonar signals. Each recording included a 30-min playback (one 1.6-s simulated MFA sonar signal repeated every 25 s); one whale was also incidentally exposed to MFA sonar from distant naval exercises. Whales responded strongly to playbacks at low received levels (RLs; 89-127 dB re 1 µPa): after ceasing normal fluking and echolocation, they swam rapidly, silently away, extending both dive duration and subsequent non-foraging interval. Distant sonar exercises (78-106 dB re 1 µPa) did not elicit such responses, suggesting that context may moderate reactions. The observed responses to playback occurred at RLs well below current regulatory thresholds; equivalent responses to operational sonars could elevate stranding risk and reduce foraging efficiency.

Clinical imaging in regenerative medicine

PubMed Central

Naumova, Anna V; Modo, Michel; Moore, Anna; Murry, Charles E; Frank, Joseph A

2014-01-01

In regenerative medicine, clinical imaging is indispensable for characterizing damaged tissue and for measuring the safety and efficacy of therapy. However, the ability to track the fate and function of transplanted cells with current technologies is limited. Exogenous contrast labels such as nanoparticles give a strong signal in the short term but are unreliable long term. Genetically encoded labels are good both short- and long-term in animals, but in the human setting they raise regulatory issues related to the safety of genomic integration and potential immunogenicity of reporter proteins. Imaging studies in brain, heart and islets share a common set of challenges, including developing novel labeling approaches to improve detection thresholds and early delineation of toxicity and function. Key areas for future research include addressing safety concerns associated with genetic labels and developing methods to follow cell survival, differentiation and integration with host tissue. Imaging may bridge the gap between cell therapies and health outcomes by elucidating mechanisms of action through longitudinal monitoring. PMID:25093889

Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

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

Murphy, E.L.; Sullivan, E.J.

1997-02-01

In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule asmore » a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with.« less

Defining indoor heat thresholds for health in the UK.

PubMed

Anderson, Mindy; Carmichael, Catriona; Murray, Virginia; Dengel, Andy; Swainson, Michael

2013-05-01

It has been recognised that as outdoor ambient temperatures increase past a particular threshold, so do mortality/morbidity rates. However, similar thresholds for indoor temperatures have not yet been identified. Due to a warming climate, the non-sustainability of air conditioning as a solution, and the desire for more energy-efficient airtight homes, thresholds for indoor temperature should be defined as a public health issue. The aim of this paper is to outline the need for indoor heat thresholds and to establish if they can be identified. Our objectives include: describing how indoor temperature is measured; highlighting threshold measurements and indices; describing adaptation to heat; summary of the risk of susceptible groups to heat; reviewing the current evidence on the link between sleep, heat and health; exploring current heat and health warning systems and thresholds; exploring the built environment and the risk of overheating; and identifying the gaps in current knowledge and research. A global literature search of key databases was conducted using a pre-defined set of keywords to retrieve peer-reviewed and grey literature. The paper will apply the findings to the context of the UK. A summary of 96 articles, reports, government documents and textbooks were analysed and a gap analysis was conducted. Evidence on the effects of indoor heat on health implies that buildings are modifiers of the effect of climate on health outcomes. Personal exposure and place-based heat studies showed the most significant correlations between indoor heat and health outcomes. However, the data are sparse and inconclusive in terms of identifying evidence-based definitions for thresholds. Further research needs to be conducted in order to provide an evidence base for threshold determination. Indoor and outdoor heat are related but are different in terms of language and measurement. Future collaboration between the health and building sectors is needed to develop a common language and an index for indoor heat and health thresholds in a changing climate.

Ground-Water Quality Data in the Upper Santa Ana Watershed Study Unit, November 2006-March 2007: Results from the California GAMA Program

USGS Publications Warehouse

Kent, Robert; Belitz, Kenneth

2009-01-01

Ground-water quality in the approximately 1,000-square-mile Upper Santa Ana Watershed study unit (USAW) was investigated from November 2006 through March 2007 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin project was developed in response to the Groundwater Quality Monitoring Act of 2001, and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The Upper Santa Ana Watershed study was designed to provide a spatially unbiased assessment of raw ground-water quality within USAW, as well as a statistically consistent basis for comparing water quality throughout California. Samples were collected from 99 wells in Riverside and San Bernardino Counties. Ninety of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study unit (grid wells). Nine wells were selected to provide additional understanding of specific water-quality issues identified within the basin (understanding wells). The ground-water samples were analyzed for a large number of organic constituents (volatile organic compounds [VOCs], pesticides and pesticide degradates, pharmaceutical compounds, and potential wastewater-indicator compounds), constituents of special interest (perchlorate, N-nitrosodimethylamine [NDMA], 1,4-dioxane, and 1,2,3-trichloropropane [1,2,3-TCP]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial indicators. Naturally occurring isotopes (tritium, carbon-14, and stable isotopes of hydrogen and oxygen in water) and dissolved noble gases also were measured to help identify sources and ages of the sampled ground water. Dissolved gases, and isotopes of nitrogen gas and of dissolved nitrate also were measured in order to investigate the sources and occurrence of nitrate in the study unit. In total, nearly 400 constituents and water-quality indicators were investigated for this study. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Volatile organic compounds (VOCs) were detected in more than 80 percent of USAW grid wells. Most VOCs detected were at concentrations far less than thresholds established for drinking water to protect human health; however, six wells had VOC concentrations above health-based thresholds. Twenty-four of the 85 VOCs investigated were detected in the study unit;11 were detected in more than 10 percent of the wells. The VOCs detected above health-based thresholds in at least one well were dibromochloropropane (DBCP), tetrachloroethene (PCE), trichloroethene (TCE), carbon tetrachloride, and 1,1-dichoroethene. Pesticide compounds were detected in more than 75 percent of the grid wells. However, of the 134 different pesticide compounds investigated, 13 were detected at concentrations greater than their respective long-term method detection limits, and only 7 compounds (all herbicides or herbicide degradates) were detected in more than 10 percent of the wells. No pesticide compound was detected above its health-based threshold, although thresholds exist for fewer than half of the pesticide compounds investigat

The influence of current direction on phosphene thresholds evoked by transcranial magnetic stimulation.

PubMed

Kammer, T; Beck, S; Erb, M; Grodd, W

2001-11-01

To quantify phosphene thresholds evoked by transcranial magnetic stimulation (TMS) in the occipital cortex as a function of induced current direction. Phosphene thresholds were determined in 6 subjects. We compared two stimulator types (Medtronic-Dantec and Magstim) with monophasic pulses using the standard figure-of-eight coils and systematically varied hemisphere (left and right) and induced current direction (latero-medial and medio-lateral). Each measurement was made 3 times, with a new stimulation site chosen for each repetition. Only those stimulation sites were investigated where phosphenes were restricted to one visual hemifield. Coil positions were stereotactically registered. Functional magnetic resonance imaging (fMRI) of retinotopic areas was performed in 5 subjects to individually characterize the borders of visual areas; TMS stimulation sites were coregistered with respect to visual areas. Despite large interindividual variance we found a consistent pattern of phosphene thresholds. They were significantly lower if the direction of the induced current was oriented from lateral to medial in the occipital lobe rather than vice versa. No difference with respect to the hemisphere was found. Threshold values normalized to the square root of the stored energy in the stimulators were lower with the Medtronic-Dantec device than with the Magstim device. fMRI revealed that stimulation sites generating unilateral phosphenes were situated at V2 and V3. Variability of phosphene thresholds was low within a cortical patch of 2x2cm(2). Stimulation over V1 yields phosphenes in both visual fields. The excitability of visual cortical areas depends on the direction of the induced current with a preference for latero-medial currents. Although the coil positions used in this study were centered over visual areas V2 and V3, we cannot rule out the possibility that subcortical structures or V1 could actually be the main generator for phosphenes.

Evidence for thermally assisted threshold switching behavior in nanoscale phase-change memory cells

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

Le Gallo, Manuel; Athmanathan, Aravinthan; Krebs, Daniel

2016-01-14

In spite of decades of research, the details of electrical transport in phase-change materials are still debated. In particular, the so-called threshold switching phenomenon that allows the current density to increase steeply when a sufficiently high voltage is applied is still not well understood, even though there is wide consensus that threshold switching is solely of electronic origin. However, the high thermal efficiency and fast thermal dynamics associated with nanoscale phase-change memory (PCM) devices motivate us to reassess a thermally assisted threshold switching mechanism, at least in these devices. The time/temperature dependence of the threshold switching voltage and current inmore » doped Ge{sub 2}Sb{sub 2}Te{sub 5} nanoscale PCM cells was measured over 6 decades in time at temperatures ranging from 40 °C to 160 °C. We observe a nearly constant threshold switching power across this wide range of operating conditions. We also measured the transient dynamics associated with threshold switching as a function of the applied voltage. By using a field- and temperature-dependent description of the electrical transport combined with a thermal feedback, quantitative agreement with experimental data of the threshold switching dynamics was obtained using realistic physical parameters.« less

Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.

PubMed

Guo, Yu; Su, Zi-Jun; Chen, Yi-Kun; Chai, Zhen

2017-07-01

Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology. © 2017 International Society for Neurochemistry.

Excitable Neurons, Firing Threshold Manifolds and Canards

PubMed Central

2013-01-01

We investigate firing threshold manifolds in a mathematical model of an excitable neuron. The model analyzed investigates the phenomenon of post-inhibitory rebound spiking due to propofol anesthesia and is adapted from McCarthy et al. (SIAM J. Appl. Dyn. Syst. 11(4):1674–1697, [2012]). Propofol modulates the decay time-scale of an inhibitory GABAa synaptic current. Interestingly, this system gives rise to rebound spiking within a specific range of propofol doses. Using techniques from geometric singular perturbation theory, we identify geometric structures, known as canards of folded saddle-type, which form the firing threshold manifolds. We find that the position and orientation of the canard separatrix is propofol dependent. Thus, the speeds of relevant slow synaptic processes are encoded within this geometric structure. We show that this behavior cannot be understood using a static, inhibitory current step protocol, which can provide a single threshold for rebound spiking but cannot explain the observed cessation of spiking for higher propofol doses. We then compare the analyses of dynamic and static synaptic inhibition, showing how the firing threshold manifolds of each relate, and why a current step approach is unable to fully capture the behavior of this model. PMID:23945278

Redefining the Speed Limit of Phase Change Memory Revealed by Time-resolved Steep Threshold-Switching Dynamics of AgInSbTe Devices

NASA Astrophysics Data System (ADS)

Shukla, Krishna Dayal; Saxena, Nishant; Durai, Suresh; Manivannan, Anbarasu

2016-11-01

Although phase-change memory (PCM) offers promising features for a ‘universal memory’ owing to high-speed and non-volatility, achieving fast electrical switching remains a key challenge. In this work, a correlation between the rate of applied voltage and the dynamics of threshold-switching is investigated at picosecond-timescale. A distinct characteristic feature of enabling a rapid threshold-switching at a critical voltage known as the threshold voltage as validated by an instantaneous response of steep current rise from an amorphous off to on state is achieved within 250 picoseconds and this is followed by a slower current rise leading to crystallization. Also, we demonstrate that the extraordinary nature of threshold-switching dynamics in AgInSbTe cells is independent to the rate of applied voltage unlike other chalcogenide-based phase change materials exhibiting the voltage dependent transient switching characteristics. Furthermore, numerical solutions of time-dependent conduction process validate the experimental results, which reveal the electronic nature of threshold-switching. These findings of steep threshold-switching of ‘sub-50 ps delay time’, opens up a new way for achieving high-speed non-volatile memory for mainstream computing.

Is the diagnostic threshold for bulimia nervosa clinically meaningful?

PubMed

Chapa, Danielle A N; Bohrer, Brittany K; Forbush, Kelsie T

2018-01-01

The DSM-5 differentiates full- and sub-threshold bulimia nervosa (BN) according to average weekly frequencies of binge eating and inappropriate compensatory behaviors. This study was the first to evaluate the modified frequency criterion for BN published in the DSM-5. The purpose of this study was to test whether community-recruited adults (N=125; 83.2% women) with current full-threshold (n=77) or sub-threshold BN (n=48) differed in comorbid psychopathology and eating disorder (ED) illness duration, symptom severity, and clinical impairment. Participants completed the Clinical Impairment Assessment and participated in semi-structured clinical interviews of ED- and non-ED psychopathology. Differences between the sub- and full-threshold BN groups were assessed using MANOVA and Chi-square analyses. ED illness duration, age-of-onset, body mass index (BMI), alcohol and drug misuse, and the presence of current and lifetime mood or anxiety disorders did not differ between participants with sub- and full-threshold BN. Participants with full-threshold BN had higher levels of clinical impairment and weight concern than those with sub-threshold BN. However, minimal clinically important difference analyses suggested that statistically significant differences between participants with sub- and full-threshold BN on clinical impairment and weight concern were not clinically significant. In conclusion, sub-threshold BN did not differ from full-threshold BN in clinically meaningful ways. Future studies are needed to identify an improved frequency criterion for BN that better distinguishes individuals in ways that will more validly inform prognosis and effective treatment planning for BN. Copyright © 2017 Elsevier Ltd. All rights reserved.

Building Synergy between Regulatory and HTA Agencies beyond Processes and Procedures-Can We Effectively Align the Evidentiary Requirements? A Survey of Stakeholder Perceptions.

PubMed

Wang, Ting; McAuslane, Neil; Liberti, Lawrence; Leufkens, Hubert; Hövels, Anke

2018-06-01

To evaluate the current practice of companies and agencies to assess the changes made in aligning regulatory and health technology assessment (HTA) stakeholders; to identify areas of commonality of evidentiary requirements that could occur; and to identify strategic issues and trends of regulatory and HTA synergy. Two separate questionnaires were developed to assess stakeholders' perceptions on regulatory and HTA alignment, one for pharmaceutical companies and the other for regulatory and HTA agencies. The responses were analyzed using descriptive statistics. Seven regulatory and 8 HTA agencies from Australia, Canada, and Europe and 19 international companies developing innovative medicine responded to the survey. This study provided a snapshot of the current regulatory and HTA landscape. Changes made over the past 5 years were reflected in three main areas: there is an increasing interaction between regulatory and HTA agencies; current conditional regulatory approvals are not always linked with flexible HTA approaches; and companies are more supportive of joint scientific advice. Four types of evidentiary requirements were identified as building blocks for better alignment: acceptable primary end points, inclusion of an active comparator, use of patient-reported outcomes, and choice and use of surrogate end point. The study showed that the gap between regulatory and HTA requirements has narrowed over the past 5 years. All respondents supported synergy between regulatory and HTA stakeholders, and the study provided several recommendations on how to further improve evidentiary alignment including the provision of joint scientific advice, which was rated as a key strategy by both agencies and companies. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Breaking the current density threshold in spin-orbit-torque magnetic random access memory

NASA Astrophysics Data System (ADS)

Zhang, Yin; Yuan, H. Y.; Wang, X. S.; Wang, X. R.

2018-04-01

Spin-orbit-torque magnetic random access memory (SOT-MRAM) is a promising technology for the next generation of data storage devices. The main bottleneck of this technology is the high reversal current density threshold. This outstanding problem is now solved by a new strategy in which the magnitude of the driven current density is fixed while the current direction varies with time. The theoretical limit of minimal reversal current density is only a fraction (the Gilbert damping coefficient) of the threshold current density of the conventional strategy. The Euler-Lagrange equation for the fastest magnetization reversal path and the optimal current pulse is derived for an arbitrary magnetic cell and arbitrary spin-orbit torque. The theoretical limit of minimal reversal current density and current density for a GHz switching rate of the new reversal strategy for CoFeB/Ta SOT-MRAMs are, respectively, of the order of 105 A/cm 2 and 106 A/cm 2 far below 107 A/cm 2 and 108 A/cm 2 in the conventional strategy. Furthermore, no external magnetic field is needed for a deterministic reversal in the new strategy.

77 FR 74034 - Self-Regulatory Organizations; New York Stock Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-12

... (``NYSE CADV'') or of September 2012 Adding ADV (``SLP Baseline ADV''). If the Exchange did not exclude...% of NYSE CADV that relates to the SLP credit of $0.0023 (or $0.0018 if a Non-Displayed Reserve Order) per share; The thresholds of ADV of 0.22% of NYSE CADV and 0.18% of SLP Baseline ADV, as well as the...

OEM Emergency Prevention and Mitigation Information

EPA Pesticide Factsheets

The Office of Emergency Management maintains information relevant to preventing emergencies before they occur, and/or mitigating the effects of emergency when they do occur. A principal element of this data asset is the information managed by the System for Risk Management Plans (SRMP), which compiles risk management plans submitted by facilities in accordance with the Clean Air Act, Section 112(r). Affected facilities are to develop risk management programs which will prevent and minimize consequences of accidental releases of certain hazardous chemicals that could harm public health and the environment.Another component of this data asset are the results generated by the Priority Assessment Model (PAM), which analyzes information concerning low-level chronic emissions from facilities and sets priorities (low, medium, high) for proactive controls on releases that do not necessarily pose imminent threats, but which may under adverse circumstances create unacceptable health or ecological risks.Also included are inspection records compiled by the Oil Inspection Program. Under the Clean Water Act Section 311, EPA regulates oil storage that meets a specific regulatory threshold. Facilities that store oil and meet the regulatory threshold need to prepare and implement a Spill Prevention, Control, and Countermeasures (SPCC) Plan which needs to be reviewed and approved by a professional engineer. Additionally, facilities with larger oil storage capacity may have to pre

Negative regulators in homeostasis of naïve peripheral T cells.

PubMed

Modiano, Jaime F; Johnson, Lisa D S; Bellgrau, Donald

2008-01-01

It is now apparent that naïve peripheral T cells are a dynamic population where active processes prevent inappropriate activation while supporting survival. The process of thymic education makes naïve peripheral T cells dependent on interactions with self-MHC for survival. However, as these signals can potentially result in inappropriate activation, various non-redundant, intrinsic negative regulatory molecules including Tob, Nfatc2, and Smad3 actively enforce T cell quiescence. Interactions among these pathways are only now coming to light and may include positive or negative crosstalk. In the case of positive crosstalk, self-MHC initiated signals and intrinsic negative regulatory factors may cooperate to dampen T cell activation and sustain peripheral tolerance in a binary fashion (on-off). In the case of negative crosstalk, self-MHC signals may promote survival through partial activation while intrinsic negative regulatory factors act as rheostats to restrain cell cycle entry and prevent T cells from crossing a threshold that would break tolerance.

Sub-cellular mRNA localization modulates the regulation of gene expression by small RNAs in bacteria

NASA Astrophysics Data System (ADS)

Teimouri, Hamid; Korkmazhan, Elgin; Stavans, Joel; Levine, Erel

2017-10-01

Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA. We also identify conditions where the sub-cellular organization of cofactors in the sRNA pathway can induce spatial heterogeneity on sRNA targets. Our results suggest that under certain conditions, interpretation and modeling of natural and synthetic gene regulatory circuits need to take into account the spatial organization of the transcripts of participating genes.

Setting limits: Using air pollution thresholds to protect and restore U.S. ecosystems

USGS Publications Warehouse

Fenn, M.E.; Lambert, K.F.; Blett, T.F.; Burns, Douglas A.; Pardo, L.H.; Lovett, Gary M.; Haeuber, R. A.; Evers, D.C.; Driscoll, C.T.; Jeffries, D.S.

2011-01-01

More than four decades of research provide unequivocal evidence that sulfur, nitrogen, and mercury pollution have altered, and will continue to alter, our nation's lands and waters. The emission and deposition of air pollutants harm native plants and animals, degrade water quality, affect forest productivity, and are damaging to human health. Many air quality policies limit emissions at the source but these control measures do not always consider ecosystem impacts. Air pollution thresholds at which ecological effects are observed, such as critical loads, are effective tools for assessing the impacts of air pollution on essential ecosystem services and for informing public policy. U.S. ecosystems can be more effectively protected and restored by using a combination of emissions-based approaches and science-based thresholds of ecosystem damage. Based on the results of a comprehensive review of air pollution thresholds, we conclude: ??? Ecosystem services such as air and water purification, decomposition and detoxification of waste materials, climate regulation, regeneration of soil fertility, production and biodiversity maintenance, as well as crop, timber and fish supplies are impacted by deposition of nitrogen, sulfur, mercury and other pollutants. The consequences of these changes may be difficult or impossible to reverse as impacts cascade throughout affected ecosystems. ??? The effects of too much nitrogen are common across the U.S. and include altered plant and lichen communities, enhanced growth of invasive species, eutrophication and acidification of lands and waters, and habitat deterioration for native species, including endangered species. ??? Lake, stream and soil acidification is widespread across the eastern United States. Up to 65% of lakes within sensitive areas receive acid deposition that exceeds critical loads. ??? Mercury contamination adversely affects fish in many inland and coastal waters. Fish consumption advisories for mercury exist in all 50 states and on many tribal lands. High concentrations of mercury in wildlife are also widespread and have multiple adverse effects. ??? Air quality programs, such as those stemming from the 1990 Clean Air Act Amendments, have helped decrease air pollution even as population and energy demand have increased. Yet, they do not adequately protect ecosystems from long-term damage. Moreover they do not address ammonia emissions. ??? A stronger ecosystem basis for air pollutant policies could be established through adoption of science-based thresholds. Existing monitoring programs track vital information needed to measure the response to policies, and could be expanded to include appropriate chemical and biological indicators for terrestrial and aquatic ecosystems and establishment of a national ecosystem monitoring network for mercury. The development and use of air pollution thresholds for ecosystem protection and management is increasing in the United States, yet threshold approaches remain underutilized. Ecological thresholds for air pollution, such as critical loads for nitrogen and sulfur deposition, are not currently included in the formal regulatory process for emissions controls in the United States, although they are now considered in local management decisions by the National Park Service and U.S. Forest Service. Ecological thresholds offer a scientifically sound approach to protecting and restoring U.S. ecosystems and an important tool for natural resource management and policy. ?? The Ecological Society of America.

The effects of HIV-1 regulatory TAT protein expression on brain reward function, response to psychostimulants and delay-dependent memory in mice.

PubMed

Kesby, James P; Markou, Athina; Semenova, Svetlana

2016-10-01

Depression and psychostimulant abuse are common comorbidities among humans with immunodeficiency virus (HIV) disease. The HIV regulatory protein TAT is one of multiple HIV-related proteins associated with HIV-induced neurotoxicity. TAT-induced dysfunction of dopamine and serotonin systems in corticolimbic brain areas may result in impaired reward function, thus, contributing to depressive symptoms and psychostimulant abuse. Transgenic mice with doxycycline-induced TAT protein expression in the brain (TAT+, TAT- control) show neuropathology resembling brain abnormalities in HIV+ humans. We evaluated brain reward function in response to TAT expression, nicotine and methamphetamine administration in TAT+ and TAT- mice using the intracranial self-stimulation procedure. We evaluated the brain dopamine and serotonin systems with high-performance liquid chromatography. The effects of TAT expression on delay-dependent working memory in TAT+ and TAT- mice using the operant delayed nonmatch-to-position task were also assessed. During doxycycline administration, reward thresholds were elevated by 20% in TAT+ mice compared with TAT- mice. After the termination of doxycycline treatment, thresholds of TAT+ mice remained significantly higher than those of TAT- mice and this was associated with changes in mesolimbic serotonin and dopamine levels. TAT+ mice showed a greater methamphetamine-induced threshold lowering compared with TAT- mice. TAT expression did not alter delay-dependent working memory. These results indicate that TAT expression in mice leads to reward deficits, a core symptom of depression, and a greater sensitivity to methamphetamine-induced reward enhancement. Our findings suggest that the TAT protein may contribute to increased depressive-like symptoms and continued methamphetamine use in HIV-positive individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

PubMed

Del Paggio, J C; Azariah, B; Sullivan, R; Hopman, W M; James, F V; Roshni, S; Tannock, I F; Booth, C M

2017-01-01

The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Signal processing system for electrotherapy applications

NASA Astrophysics Data System (ADS)

Płaza, Mirosław; Szcześniak, Zbigniew

2017-08-01

The system of signal processing for electrotherapeutic applications is proposed in the paper. The system makes it possible to model the curve of threshold human sensitivity to current (Dalziel's curve) in full medium frequency range (1kHz-100kHz). The tests based on the proposed solution were conducted and their results were compared with those obtained according to the assumptions of High Tone Power Therapy method and referred to optimum values. Proposed system has high dynamics and precision of mapping the curve of threshold human sensitivity to current and can be used in all methods where threshold curves are modelled.

Groundwater-Quality Data in the Colorado River Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Goldrath, Dara A.; Wright, Michael T.; Belitz, Kenneth

2010-01-01

Groundwater quality in the 188-square-mile Colorado River Study unit (COLOR) was investigated October through December 2007 as part of the Priority Basin Project of the California State Water Resources Control Board (SWRCB) Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001, and the U.S. Geological Survey (USGS) is the technical project lead. The Colorado River study was designed to provide a spatially unbiased assessment of the quality of raw groundwater used for public water supplies within COLOR, and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 28 wells in three study areas in San Bernardino, Riverside, and Imperial Counties. Twenty wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the Study unit; these wells are termed 'grid wells'. Eight additional wells were selected to evaluate specific water-quality issues in the study area; these wells are termed `understanding wells.' The groundwater samples were analyzed for organic constituents (volatile organic compounds [VOC], gasoline oxygenates and degradates, pesticides and pesticide degradates, pharmaceutical compounds), constituents of special interest (perchlorate, 1,4-dioxane, and 1,2,3-trichlorpropane [1,2,3-TCP]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), and radioactive constituents. Concentrations of naturally occurring isotopes (tritium, carbon-14, and stable isotopes of hydrogen and oxygen in water), and dissolved noble gases also were measured to help identify the sources and ages of the sampled groundwater. In total, approximately 220 constituents and water-quality indicators were investigated. Quality-control samples (blanks, replicates, and matrix spikes) were collected at approximately 30 percent of the wells, and the results were used to evaluate the quality of the data obtained from the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias in the data. Differences between replicate samples were within acceptable ranges and matrix-spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw groundwater. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared to regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and to thresholds established for aesthetic concerns by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate compliance or noncompliance with those thresholds. The concentrations of most constituents detected in groundwater samples were below drinking-water thresholds. Volatile organic compounds (VOC) were detected in approximately 35 percent of grid well samples; all concentrations were below health-based thresholds. Pesticides and pesticide degradates were detected in about 20 percent of all samples; detections were below health-based thresholds. No concentrations of constituents of special interest or nutrients were detected above health-based thresholds. Most of the major and minor ion constituents sampled do not have health-based thresholds; the exception is chloride. Concentrations of chloride, sulfate, and total dis

Toxicogenomics and the Regulatory Framework

EPA Science Inventory

Toxicogenomics presents regulatory agencies with the opportunity to revolutionize their analyses by enabling the collection of information on a broader range of responses than currently considered in traditional regulatory decision making. Analyses of genomic responses are expec...

75 FR 22868 - Withdrawal of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Characterization of Seismic Sources and Determination of Safe Shutdown Earthquake Ground Motion.'' FOR FURTHER.... Nuclear Regulatory Commission (NRC) is withdrawing RG 1.165, ``Identification and Characterization of... alter the licensing basis of any currently operating reactor or any of the currently issued early site...

[Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

PubMed

Furong, Liu; Shengtian, L I

2016-05-25

To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

Reducing abrupt climate change risk using the Montreal Protocol and other regulatory actions to complement cuts in CO2 emissions

PubMed Central

Molina, Mario; Zaelke, Durwood; Sarma, K. Madhava; Andersen, Stephen O.; Ramanathan, Veerabhadran; Kaniaru, Donald

2009-01-01

Current emissions of anthropogenic greenhouse gases (GHGs) have already committed the planet to an increase in average surface temperature by the end of the century that may be above the critical threshold for tipping elements of the climate system into abrupt change with potentially irreversible and unmanageable consequences. This would mean that the climate system is close to entering if not already within the zone of “dangerous anthropogenic interference” (DAI). Scientific and policy literature refers to the need for “early,” “urgent,” “rapid,” and “fast-action” mitigation to help avoid DAI and abrupt climate changes. We define “fast-action” to include regulatory measures that can begin within 2–3 years, be substantially implemented in 5–10 years, and produce a climate response within decades. We discuss strategies for short-lived non-CO2 GHGs and particles, where existing agreements can be used to accomplish mitigation objectives. Policy makers can amend the Montreal Protocol to phase down the production and consumption of hydrofluorocarbons (HFCs) with high global warming potential. Other fast-action strategies can reduce emissions of black carbon particles and precursor gases that lead to ozone formation in the lower atmosphere, and increase biosequestration, including through biochar. These and other fast-action strategies may reduce the risk of abrupt climate change in the next few decades by complementing cuts in CO2 emissions. PMID:19822751

Pharmacokinetics of guaifenesin following administration of multiple doses to exercised Thoroughbred horses.

PubMed

Knych, H K; Stanley, S D; Benson, D; Arthur, R M

2016-08-01

Guaifenesin is an expectorant commonly used in performance horses to aid in the clearance of mucus from the airways. Guaifenesin is also a centrally acting skeletal muscle relaxant and as such is a prohibited drug with withdrawal necessary prior to competition. To the authors' knowledge, there are no reports in the literature describing single or multiple oral administrations of guaifenesin in the horse to determine a regulatory threshold and related withdrawal time. Therefore, the objective of the current study was to describe the pharmacokinetics of guaifenesin following oral administration in order to provide data upon which appropriate regulatory recommendations can be established. Nine exercised Thoroughbred horses were administered 2 g of guaifenesin orally BID for a total of five doses. Blood samples were collected immediately prior to drug administration and at various times postadministration. Serum guaifenesin concentrations were determined and pharmacokinetic parameters calculated. Guaifenesin was rapidly absorbed (Tmax of 15 min) following oral administration. The Cmax was 681.3 ± 323.8 ng/mL and 1080 ± 732.8 following the first and last dose, respectively. The serum elimination half-life was 2.62 ± 1.24 h. Average serum guaifenesin concentrations remained above the LOQ of the assay (0.5 ng/mL) by 48 h postadministration of the final dose in 3 of 9 horses. © 2016 John Wiley & Sons Ltd.

GALVANOTAXIS OF SLIME MOLD

PubMed Central

Anderson, John D.

1951-01-01

The plasmodium of Physarum polycephalum reacts to direct current by migration toward the cathode. Cathodal migration was obtained upon a variety of substrata such as baked clay, paper, cellophane, and agar with a current density in the substratum of 1.0 µa./mm.2 Injury was produced by current densities of 8.0 to 12.0 µa./mm.2 The negative galvanotactic response was not due to electrode products. Attempts to demonstrate that the response was due to gradients or orientation in the substratum, pH changes in the mold, cataphoresis, electroosmosis, or endosmosis were not successful. The addition of salts (CaCl2, LiCl, NaCl, Na2SO4, NaHCO3, KCl, MgSO4, sodium citrate, and sea water) to agar indicated that change of cations had more effect than anions upon galvanotaxis and that the effect was upon threshold values. K ion (0.01 M KCl) increased the lower threshold value to 8.0 µa./mm.2 and the upper threshold value to 32.0 µa./mm.2, whereas the Li ion (0.01 M LiCl) increased the lower threshold to only 4.0 µa./mm.2 and the upper threshold to only 16.0 µa./mm.2 The passage of electric current produced no increase in the rate of cathodal migration; neither was there a decrease until injurious current densities were reached. With increase of subthreshold current densities there was a progressive decrease in rate of migration toward the anode until complete anodal inhibition occurred. There was orientation at right angles to the electrodes in alternating current (60 cycle) with current density of 4.0 µa./mm.2 and in direct current of 5.0 µa./mm.2 when polarity of current was reversed every minute. It is concluded that the negative galvanotactic response of P. polycephalum is due to inhibition of migration on the anodal side of the plasmodium and that this inhibition results in the limitation of the normal migration of the mold to a cathodal direction. The mechanism of the anodal inhibition has not been elucidated. PMID:14873916

Groundwater Quality Data in the Mojave Study Unit, 2008: Results from the California GAMA Program

USGS Publications Warehouse

Mathany, Timothy M.; Belitz, Kenneth

2009-01-01

Groundwater quality in the approximately 1,500 square-mile Mojave (MOJO) study unit was investigated from February to April 2008, as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). MOJO was the 23rd of 37 study units to be sampled as part of the GAMA Priority Basin Project. The MOJO study was designed to provide a spatially unbiased assessment of the quality of untreated ground water used for public water supplies within MOJO, and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 59 wells in San Bernardino and Los Angeles Counties. Fifty-two of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and seven were selected to aid in evaluation of specific water-quality issues (understanding wells). The groundwater samples were analyzed for a large number of organic constituents [volatile organic compounds (VOCs), pesticides and pesticide degradates, and pharmaceutical compounds], constituents of special interest (perchlorate and N-nitrosodimethylamine [NDMA]) naturally occurring inorganic constituents (nutrients, dissolved organic carbon [DOC], major and minor ions, silica, total dissolved solids [TDS], and trace elements), and radioactive constituents (gross alpha and gross beta radioactivity, radium isotopes, and radon-222). Naturally occurring isotopes (stable isotopes of hydrogen, oxygen, and carbon, stable isotopes of nitrogen and oxygen in nitrate, and activities of tritium and carbon-14), and dissolved noble gases also were measured to help identify the sources and ages of the sampled ground water. In total, over 230 constituents and water-quality indicators (field parameters) were investigated. Three types of quality-control samples (blanks, replicates, and matrix spikes) each were collected at approximately 5-8 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a significant source of bias in the data for the groundwater samples. Differences between replicate samples generally were within acceptable ranges, indicating acceptable analytical reproducibility. Matrix spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, untreated groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to untreated ground water. However, to provide some context for the results, concentrations of constituents measured in the untreated ground water were compared with regulatory and non-regulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic and technical concerns by CDPH. Comparisons between data collected for this study and thresholds for drinking-water are for illustrative purposes only, and are not indicative of compliance or non-compliance with those thresholds. Most constituents that were detected in groundwater samples in the 59 wells in MOJO were found at concentrations below drinking-water thresholds. In MOJO's 52 grid wells, volatile organic compounds (VOCs) were detected in 40 percent of the wells, and pesticides and pesticide degradates were detected in 23 percent of the grid wel

Searching for statistically significant regulatory modules.

PubMed

Bailey, Timothy L; Noble, William Stafford

2003-10-01

The regulatory machinery controlling gene expression is complex, frequently requiring multiple, simultaneous DNA-protein interactions. The rate at which a gene is transcribed may depend upon the presence or absence of a collection of transcription factors bound to the DNA near the gene. Locating transcription factor binding sites in genomic DNA is difficult because the individual sites are small and tend to occur frequently by chance. True binding sites may be identified by their tendency to occur in clusters, sometimes known as regulatory modules. We describe an algorithm for detecting occurrences of regulatory modules in genomic DNA. The algorithm, called mcast, takes as input a DNA database and a collection of binding site motifs that are known to operate in concert. mcast uses a motif-based hidden Markov model with several novel features. The model incorporates motif-specific p-values, thereby allowing scores from motifs of different widths and specificities to be compared directly. The p-value scoring also allows mcast to only accept motif occurrences with significance below a user-specified threshold, while still assigning better scores to motif occurrences with lower p-values. mcast can search long DNA sequences, modeling length distributions between motifs within a regulatory module, but ignoring length distributions between modules. The algorithm produces a list of predicted regulatory modules, ranked by E-value. We validate the algorithm using simulated data as well as real data sets from fruitfly and human. http://meme.sdsc.edu/MCAST/paper

Unified planar process for fabricating heterojunction bipolar transistors and buried-heterostructure lasers utilizing impurity-induced disordering

NASA Astrophysics Data System (ADS)

Thornton, R. L.; Mosby, W. J.; Chung, H. F.

1988-12-01

We describe results on a novel geometry of heterojunction bipolar transistor that has been realized by impurity-induced disordering. This structure is fabricated by a method that is compatible with techniques for the fabrication of low threshold current buried-heterostructure lasers. We have demonstrated this compatibility by fabricating a hybrid laser/transistor structure that operates as a laser with a threshold current of 6 mA at room temperature, and as a transistor with a current gain of 5.

High-temperature performance of MoS2 thin-film transistors: Direct current and pulse current-voltage characteristics

NASA Astrophysics Data System (ADS)

Jiang, C.; Rumyantsev, S. L.; Samnakay, R.; Shur, M. S.; Balandin, A. A.

2015-02-01

We report on fabrication of MoS2 thin-film transistors (TFTs) and experimental investigations of their high-temperature current-voltage characteristics. The measurements show that MoS2 devices remain functional to temperatures of at least as high as 500 K. The temperature increase results in decreased threshold voltage and mobility. The comparison of the direct current (DC) and pulse measurements shows that the direct current sub-linear and super-linear output characteristics of MoS2 thin-films devices result from the Joule heating and the interplay of the threshold voltage and mobility temperature dependences. At temperatures above 450 K, a kink in the drain current occurs at zero gate voltage irrespective of the threshold voltage value. This intriguing phenomenon, referred to as a "memory step," was attributed to the slow relaxation processes in thin films similar to those in graphene and electron glasses. The fabricated MoS2 thin-film transistors demonstrated stable operation after two months of aging. The obtained results suggest new applications for MoS2 thin-film transistors in extreme-temperature electronics and sensors.

Inhibition of Cav3.2 T-type Calcium Channels by Its Intracellular I-II Loop*

PubMed Central

Monteil, Arnaud; Chausson, Patrick; Boutourlinsky, Katia; Mezghrani, Alexandre; Huc-Brandt, Sylvaine; Blesneac, Iulia; Bidaud, Isabelle; Lemmers, Céline; Leresche, Nathalie; Lambert, Régis C.; Lory, Philippe

2015-01-01

Voltage-dependent calcium channels (Cav) of the T-type family (Cav3.1, Cav3.2, and Cav3.3) are activated by low threshold membrane depolarization and contribute greatly to neuronal network excitability. Enhanced T-type channel activity, especially Cav3.2, contributes to disease states, including absence epilepsy. Interestingly, the intracellular loop connecting domains I and II (I-II loop) of Cav3.2 channels is implicated in the control of both surface expression and channel gating, indicating that this I-II loop plays an important regulatory role in T-type current. Here we describe that co-expression of this I-II loop or its proximal region (Δ1-Cav3.2; Ser423–Pro542) together with recombinant full-length Cav3.2 channel inhibited T-type current without affecting channel expression and membrane incorporation. Similar T-type current inhibition was obtained in NG 108-15 neuroblastoma cells that constitutively express Cav3.2 channels. Of interest, Δ1-Cav3.2 inhibited both Cav3.2 and Cav3.1 but not Cav3.3 currents. Efficacy of Δ1-Cav3.2 to inhibit native T-type channels was assessed in thalamic neurons using viral transduction. We describe that T-type current was significantly inhibited in the ventrobasal neurons that express Cav3.1, whereas in nucleus reticularis thalami neurons that express Cav3.2 and Cav3.3 channels, only the fast inactivating T-type current (Cav3.2 component) was significantly inhibited. Altogether, these data describe a new strategy to differentially inhibit Cav3 isoforms of the T-type calcium channels. PMID:25931121

Assessing safety of extractables from materials and leachables in pharmaceuticals and biologics - Current challenges and approaches.

PubMed

Broschard, Thomas H; Glowienke, Susanne; Bruen, Uma S; Nagao, Lee M; Teasdale, Andrew; Stults, Cheryl L M; Li, Kim L; Iciek, Laurie A; Erexson, Greg; Martin, Elizabeth A; Ball, Douglas J

2016-11-01

Leachables from pharmaceutical container closure systems can present potential safety risks to patients. Extractables studies may be performed as a risk mitigation activity to identify potential leachables for dosage forms with a high degree of concern associated with the route of administration. To address safety concerns, approaches to toxicological safety evaluation of extractables and leachables have been developed and applied by pharmaceutical and biologics manufacturers. Details of these approaches may differ depending on the nature of the final drug product. These may include application, the formulation, route of administration and length of use. Current regulatory guidelines and industry standards provide general guidance on compound specific safety assessments but do not provide a comprehensive approach to safety evaluations of leachables and/or extractables. This paper provides a perspective on approaches to safety evaluations by reviewing and applying general concepts and integrating key steps in the toxicological evaluation of individual extractables or leachables. These include application of structure activity relationship studies, development of permitted daily exposure (PDE) values, and use of safety threshold concepts. Case studies are provided. The concepts presented seek to encourage discussion in the scientific community, and are not intended to represent a final opinion or "guidelines." Copyright © 2016 Elsevier Inc. All rights reserved.

Recent regulatory experience of low-Btu coal gasification. Volume III. Supporting case studies

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

Ackerman, E.; Hart, D.; Lethi, M.

The MITRE Corporation conducted a five-month study for the Office of Resource Applications in the Department of Energy on the regulatory requirements of low-Btu coal gasification. During this study, MITRE interviewed representatives of five current low-Btu coal gasification projects and regulatory agencies in five states. From these interviews, MITRE has sought the experience of current low-Btu coal gasification users in order to recommend actions to improve the regulatory process. This report is the third of three volumes. It contains the results of interviews conducted for each of the case studies. Volume 1 of the report contains the analysis of themore » case studies and recommendations to potential industrial users of low-Btu coal gasification. Volume 2 contains recommendations to regulatory agencies.« less

Anatomy of filamentary threshold switching in amorphous niobium oxide.

PubMed

Li, Shuai; Liu, Xinjun; Nandi, Sanjoy Kumar; Elliman, Robert Glen

2018-06-25

The threshold switching behaviour of Pt/NbOx/TiN devices is investigated as a function device area and NbOx film thickness and shown to reveal important insight into the structure of the self-assembled switching region. The devices exhibit combined selector-memory (1S1R) behavior after an initial voltage-controlled forming process, but exhibit symmetric threshold switching when the RESET and SET currents are kept below a critical value. In this mode, the threshold and hold voltages are independent of the device area and film thickness but the threshold current (power), while independent of device area, decreases with increasing film thickness. These results are shown to be consistent with a structure in which the threshold switching volume is confined, both laterally and vertically, to the region between the residual memory filament and the TiN electrode, and where the memory filament has a core-shell structure comprising a metallic core and a semiconducting shell. The veracity of this structure is demonstrated by comparing experimental results with the predictions of a simple circuit model, and more detailed finite element simulations. These results provide further insight into the structure and operation of NbOx threshold switching devices that have application in emerging memory and neuromorphic computing fields. © 2018 IOP Publishing Ltd.

Effect of Unmodulated 5-kHz Alternating Currents Versus Transcutaneous Electrical Nerve Stimulation on Mechanical and Thermal Pain, Tactile Threshold, and Peripheral Nerve Conduction: A Double-Blind, Placebo-Controlled Crossover Trial.

PubMed

Avendaño-Coy, Juan; Gómez-Soriano, Julio; Goicoechea-García, Carlos; Basco-López, Julian Angel; Taylor, Julian

2017-05-01

To investigate the effect of unmodulated 5-kHz alternating current on mechanical pain threshold (MPT), heat pain threshold (HPT), tactile threshold (TT), and peripheral nerve conduction (PNC) compared with transcutaneous electrical nerve stimulation (TENS) and sham stimulation. National referral center. Randomized, double-blind, placebo-controlled crossover trial. Healthy volunteers (N=38). No dropouts or adverse events were reported. TENS, unmodulated 5-kHz currents, and sham stimulation were applied on the radial nerve for 20 minutes with a 24-hour washout period between them and concealed intervention allocation. Four measures were taken: before, during, and 2 after the interventions. Algometry was used to assess MPT, a Peltier thermode for HPT using the method of limits, Von Frey filaments for TT, and radial nerve compound action potential. No differences were observed on MPT, HPT, and PNC when 5-kHz current and TENS were compared. However, TT increased 56.2mN (95% confidence interval [CI], 28.8-83.6) in the TENS group compared with the 5-kHz current group during intervention. Compared with sham stimulation during intervention, MPT increased 4.7N (95% CI, 0.3-9.2) using 5-kHz current and 10.4N (95% CI, 3.5-17.3) with TENS. TT increased 17.2mN (95% CI, 4.7-29.7) with 5-kHz current and 73.4mN (95% CI, 47.5-99.2) with TENS. However, HPT increased 1.0°C (95% CI, 0.2-2.0) only with TENS. For the PNC, no differences were found among the 3 groups. Unmodulated 5-kHz current produced an increase in somatosensory thresholds that was greater than placebo but not when compared with TENS; however, participants perceived 5-kHz currents to be more comfortable and showed more habituation to them. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Randomness fault detection system

NASA Technical Reports Server (NTRS)

Russell, B. Don (Inventor); Aucoin, B. Michael (Inventor); Benner, Carl L. (Inventor)

1996-01-01

A method and apparatus are provided for detecting a fault on a power line carrying a line parameter such as a load current. The apparatus monitors and analyzes the load current to obtain an energy value. The energy value is compared to a threshold value stored in a buffer. If the energy value is greater than the threshold value a counter is incremented. If the energy value is greater than a high value threshold or less than a low value threshold then a second counter is incremented. If the difference between two subsequent energy values is greater than a constant then a third counter is incremented. A fault signal is issued if the counter is greater than a counter limit value and either the second counter is greater than a second limit value or the third counter is greater than a third limit value.

Quantitative Sensory Testing and Current Perception Threshold Testing in Patients With Chronic Pain Following Lower Extremity Fracture.

PubMed

Griffioen, Mari A; Greenspan, Joel D; Johantgen, Meg; Von Rueden, Kathryn; O'Toole, Robert V; Dorsey, Susan G; Renn, Cynthia L

2018-01-01

Chronic pain is a significant problem for patients with lower extremity injuries. While pain hypersensitivity has been identified in many chronic pain conditions, it is not known whether patients with chronic pain following lower extremity fracture report pain hypersensitivity in the injured leg. To quantify and compare peripheral somatosensory function and sensory nerve activation thresholds in persons with chronic pain following lower extremity fractures with a cohort of persons with no history of lower extremity fractures. This was a cross-sectional study where quantitative sensory testing and current perception threshold testing were conducted on the injured and noninjured legs of cases and both legs of controls. A total of 14 cases and 28 controls participated in the study. Mean time since injury at the time of testing for cases was 22.3 (standard deviation = 12.1) months. The warmth detection threshold ( p = .024) and nerve activation thresholds at 2,000 Hz ( p < .001) and 250 Hz ( p = .002), respectively, were significantly higher in cases compared to controls. This study suggests that patients with chronic pain following lower extremity fractures may experience hypoesthesia in the injured leg, which contrasts with the finding of hyperesthesia previously observed in other chronic pain conditions but is in accord with patients with nerve injuries and surgeries. This is the first study to examine peripheral sensory nerve function at the site of injury in patients with chronic pain following lower extremity fractures using quantitative sensory testing and current perception threshold testing.

Potentiated antibodies to mu-opiate receptors: effect on integrative activity of the brain.

PubMed

Geiko, V V; Vorob'eva, T M; Berchenko, O G; Epstein, O I

2003-01-01

The effect of homeopathically potentiated antibodies to mu-receptors (10(-100) wt %) on integrative activity of rat brain was studied using the models of self-stimulation of the lateral hypothalamus and convulsions produced by electric current. Electric current was delivered through electrodes implanted into the ventromedial hypothalamus. Single treatment with potentiated antibodies to mu-receptors increased the rate of self-stimulation and decreased the threshold of convulsive seizures. Administration of these antibodies for 7 days led to further activation of the positive reinforcement system and decrease in seizure thresholds. Distilled water did not change the rate of self-stimulation and seizure threshold.

Analysis of the threshold switching mechanism of a Te-SbO selector device for crosspoint nonvolatile memory applications

NASA Astrophysics Data System (ADS)

Kim, Young Seok; Park, Ji Woon; Lee, Jong Ho; Choi, In Ah; Heo, Jaeyeong; Kim, Hyeong Joon

2017-10-01

The threshold switching mechanism of Te-SbO thin films with a unique microstructure in which a Te nanocluster is present in the SbO matrix is analyzed. During the electro-forming process, amorphous Te filaments are formed in the Te nanocluster. However, unlike conventional Ovonic threshold switching (TS) selector devices, it has been demonstrated that the off-current flows along the filament. Numerical calculations show that the off-current is due to the trap present in the filament. We also observed changes in TS parameters through controls in the strength or volume of the filaments.

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

PubMed

Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

2013-01-01

The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a systematic and science-based approach to identify and qualify leachables, including the concept of safety thresholds. Concepts from this widely accepted approach, formally publicized in 2006, are being extrapolated to parenteral and ophthalmic drug products. This article provides an overview of extractables and leachables in drug products and biologics and discusses the PQRI Work Plan and Protocols developed by the PQRI Parenteral and Ophthalmic Drug Products Leachables and Extractables Working Group.

Should we expect population thresholds for wildlife disease?

USGS Publications Warehouse

Lloyd-Smith, James O.; Cross, P.C.; Briggs, C.J.; Daugherty, M.; Getz, W.M.; Latto, J.; Sanchez, M.; Smith, A.; Swei, A.

2005-01-01

Host population thresholds for invasion or persistence of infectious disease are core concepts of disease ecology, and underlie on-going and controversial disease control policies based on culling and vaccination. Empirical evidence for these thresholds in wildlife populations has been sparse, however, though recent studies have narrowed this gap. Here we review the theoretical bases for population thresholds for disease, revealing why they are difficult to measure and sometimes are not even expected, and identifying important facets of wildlife ecology left out of current theories. We discuss strengths and weaknesses of selected empirical studies that have reported disease thresholds for wildlife, identify recurring obstacles, and discuss implications of our imperfect understanding of wildlife thresholds for disease control policy.

Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex.

PubMed

Sommer, Martin; Norden, Christoph; Schmack, Lars; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

2013-05-01

Directional sensitivity is relevant for the excitability threshold of the human primary motor cortex, but its importance for externally induced plasticity is unknown. To study the influence of current direction on two paradigms inducing neuroplasticity by repetitive transcranial magnetic stimulation (rTMS). We studied short-lasting after-effects induced in the human primary motor cortex of 8 healthy subjects, using 5 Hz rTMS applied in six blocks of 200 pulses each, at 90% active motor threshold. We controlled for intensity, frequency, waveform and spinal effects. Only biphasic pulses with the effective component delivered in an anterioposterior direction (henceforth posteriorly directed) in the brain yielded an increase of motor-evoked potential (MEP) amplitudes outlasting rTMS. MEP latencies and F-wave amplitudes remained unchanged. Biphasic pulses directed posteroanterior (i.e. anteriorly) were ineffective, as were monophasic pulses from either direction. A 1 Hz study in a group of 12 healthy subjects confirmed facilitation after posteriorly directed biphasic pulses only. The anisotropy of the human primary motor cortex is relevant for induction of plasticity by subtreshold rTMS, with a current flow opposite to that providing lowest excitability thresholds. This is consistent with the idea of TMS primarily targeting cortical columns of the phylogenetically new M1 in the anterior bank of the central sulcus. For these, anteriorly directed currents are soma-depolarizing, therefore optimal for low thresholds, whereas posteriorly directed currents are soma-hyperpolarizing, likely dendrite-depolarizing and bested suited for induction of plasticity. Our findings should help focus and enhance rTMS effects in experimental and clinical settings. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibitory effect of aniracetam on N-type calcium current in acutely isolated rat neuronal cells.

PubMed

Koike, H; Saito, H; Matsuki, N

1993-04-01

Effects of aniracetam on whole-cell calcium currents were studied in acutely isolated neuronal cells from postnatal rat ventromedial hypothalamus. There were three types of inward calcium currents, one low-threshold transient current and two high-threshold sustained currents. The nicardipine sensitive L-type current was activated at -20 mV or more depolarized potentials, and the omega-conotoxin sensitive N-type current was recorded at more positive potentials than the L-type. Aniracetam inhibited the N-type current in a dose-dependent manner without affecting the other two types of calcium currents. The effect appeared soon after the addition and lasted for several minutes during washing. Since the N-type current is thought to regulate the release of transmitters, the inhibitory effect may contribute to the nootropic property of aniracetam by modifying the neurotransmission.

Low Threshold Voltage Continuous Wave Vertical-Cavity Surface-Emitting Lasers

DTIC Science & Technology

1993-04-26

Data are presented demonstrating a design and fabrication process for the realization of low- threshold , high-output vertical-cavity surface-emitting...layers), the low series resistance of the design results in a bias voltage on o 1.8 V at a threshold current of 1.9 mA for 10-micrometer-diam devices.... Vertical-cavity surface-emitting lasers.

The European Regulatory Environment of RNA-Based Vaccines.

PubMed

Hinz, Thomas; Kallen, Kajo; Britten, Cedrik M; Flamion, Bruno; Granzer, Ulrich; Hoos, Axel; Huber, Christoph; Khleif, Samir; Kreiter, Sebastian; Rammensee, Hans-Georg; Sahin, Ugur; Singh-Jasuja, Harpreet; Türeci, Özlem; Kalinke, Ulrich

2017-01-01

A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients. In the EU no regulatory guidelines presently exist that specifically address mRNA-based vaccines. The existing regulatory framework, however, clearly defines that mRNA-based vaccines in most cases have to be centrally approved. Interestingly, depending on whether RNA-based vaccines are directed against tumors or infectious disease, they are formally considered gene therapy products or not, respectively. Besides an overview on the current clinical use of mRNA vaccines in various therapeutic areas a detailed discussion of the current regulatory situation is provided and regulatory perspectives are discussed.

Oxide-apertured VCSEL with short period superlattice

NASA Astrophysics Data System (ADS)

Li, Lin; Zhong, Jingchang; Zhang, Yongming; Su, Wei; Zhao, Yingjie; Yan, Changling; Hao, Yongqin; Jiang, Xiaoguang

2004-12-01

Novel distributed Bragg reflectors (DBRs) with 4.5 pairs of GaAs/AlAs short period superlattice (SPS) used in oxide-apertured vertical-cavity surface-emitting lasers (VCSELs) were designed. The structure of a 22-period Al_(0.9)Ga_(0.1)As (69.5 nm)/4.5-pair [GaAs (10 nm)-AlAs (1.9 nm)] DBR was grown on an n+ GaAs substrate (100) 2 deg. off toward <111>A by molecular beam epitaxy. The emitting wavelength was 850 nm with low threshold current of about 2 mA, corresponding to the threshold current density of 2 kA/cm2. The maximum output power was more than 1 mW. The VCSEL device temperature was increased by heating ambient temperature from 20 to 100 (Celsius degree) and the threshold current increased slowly with the increase of temperature.

Strengthening health professions regulation in Cambodia: a rapid assessment.

PubMed

Clarke, David; Duke, Jan; Wuliji, Tana; Smith, Alyson; Phuong, Keat; San, Un

2016-03-10

This paper describes a rapid assessment of Cambodia's current system for regulating its health professions. The assessment forms part of a co-design process to set strategic priorities for strengthening health profession regulation to improve the quality and safety of health services. A health system approach for strengthening health professions' regulation is underway and aims to support the Government of Cambodia's plans for scaling up its health workforce, improving health services' safety and quality, and meeting its Association of South East Asian Nations (ASEAN) obligations to facilitate trade in health care services. The assessment used a mixed methods approach including: A desktop review of key laws, plans, reports and other documents relating to the regulation of the health professions in Cambodia (medicine, dentistry, midwifery, nursing and pharmacy); Key informant interviews with stakeholders in Cambodia (The term "stakeholders" refers to government officials, people working on health professional regulation, people working for the various health worker training institutions and health workers at the national and provincial level); Surveys and questionnaires to assess Cambodian stakeholder knowledge of regulation; Self-assessments by members of the five Cambodian regulatory councils regarding key capacities and activities of high-performing regulatory bodies; and A rapid literature review to identify: The key functions of health professional regulation; The key issues affecting the Cambodian health sector (including relevant developments in the wider ASEAN region); and "Smart" health profession regulation practices of possible relevance to Cambodia. We found that the current regulatory system only partially meets Cambodia's needs. A number of key regulatory functions are being performed, but overall, the current system was not designed with Cambodia's specific needs in mind. The existing system is also overly complex, with considerable duplication and overlap between governance and regulatory arrangements for the five regulated professions. There is considerable scope for reform to the current regulatory system to better align the system to Cambodia's: Current needs and circumstances; Health system strategic priorities; and International obligations. Cambodia is also well placed to base its reformed regulatory system on recent developments of "smart regulatory practices" for health professionals.

The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats

PubMed Central

Martínez-Ladrón de Guevara, Elideth; Pérez-Hernández, Nury; Villalobos-López, Miguel Ángel; Pérez-Ishiwara, David Guillermo; Salas-Benito, Juan Santiago; Martínez Martínez, Alejandro; Hernández-García, Vicente

2016-01-01

This study was designed to examine the effects of lyophilized red delicious apple peel (RDP) on the action potentials (APs) and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode's solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1) The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2) As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3) These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4) RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes. PMID:26839897

[Protective effect of Uncaria rhynchophylla total alkaloids pretreatment on hippocampal neurons after acute hypoxia].

PubMed

Liu, Wei; Zhang, Zhao-qin; Zhao, Xiao-min; Gao, Yun-sheng

2006-05-01

To investigate the effect of Uncaria rhynchophylla total alkaloids (RTA) pretreatment on the voltage-gated sodium currents of the rat hippocampal neurons after acute hypoxia. Primary cultured hippocampal neurons were divided into RTA pre-treated and non-pretreated groups. Patch clamp whole-cell recording was used to compare the voltage-gated sodium current amplitude and threshold with those before hypoxia. After acute hypoxia, sodium current amplitude was significantly decreased and its threshold was upside. RTA pretreatment could inhibit the reduction of sodium current amplitude. RTA pretreatment alleviates the acute hypoxia-induced change of sodium currents, which may be one of the mechanisms for protective effect of RTA on cells.

Computational analysis of thresholds for magnetophosphenes

NASA Astrophysics Data System (ADS)

Laakso, Ilkka; Hirata, Akimasa

2012-10-01

In international guidelines, basic restriction limits on the exposure of humans to low-frequency magnetic and electric fields are set with the objective of preventing the generation of phosphenes, visual sensations of flashing light not caused by light. Measured data on magnetophosphenes, i.e. phosphenes caused by a magnetically induced electric field on the retina, are available from volunteer studies. However, there is no simple way for determining the retinal threshold electric field or current density from the measured threshold magnetic flux density. In this study, the experimental field configuration of a previous study, in which phosphenes were generated in volunteers by exposing their heads to a magnetic field between the poles of an electromagnet, is computationally reproduced. The finite-element method is used for determining the induced electric field and current in five different MRI-based anatomical models of the head. The direction of the induced current density on the retina is dominantly radial to the eyeball, and the maximum induced current density is observed at the superior and inferior sides of the retina, which agrees with literature data on the location of magnetophosphenes at the periphery of the visual field. On the basis of computed data, the macroscopic retinal threshold current density for phosphenes at 20 Hz can be estimated as 10 mA m-2 (-20% to  + 30%, depending on the anatomical model); this current density corresponds to an induced eddy current of 14 μA (-20% to  + 10%), and about 20% of this eddy current flows through each eye. The ICNIRP basic restriction limit for the induced electric field in the case of occupational exposure is not exceeded until the magnetic flux density is about two to three times the measured threshold for magnetophosphenes, so the basic restriction limit does not seem to be conservative. However, the reasons for the non-conservativeness are purely technical: removal of the highest 1% of electric field values by taking the 99th percentile as recommended by the ICNIRP leads to the underestimation of the induced electric field, and there are difficulties in applying the basic restriction limit for the retinal electric field.

Error minimization algorithm for comparative quantitative PCR analysis: Q-Anal.

PubMed

OConnor, William; Runquist, Elizabeth A

2008-07-01

Current methods for comparative quantitative polymerase chain reaction (qPCR) analysis, the threshold and extrapolation methods, either make assumptions about PCR efficiency that require an arbitrary threshold selection process or extrapolate to estimate relative levels of messenger RNA (mRNA) transcripts. Here we describe an algorithm, Q-Anal, that blends elements from current methods to by-pass assumptions regarding PCR efficiency and improve the threshold selection process to minimize error in comparative qPCR analysis. This algorithm uses iterative linear regression to identify the exponential phase for both target and reference amplicons and then selects, by minimizing linear regression error, a fluorescence threshold where efficiencies for both amplicons have been defined. From this defined fluorescence threshold, cycle time (Ct) and the error for both amplicons are calculated and used to determine the expression ratio. Ratios in complementary DNA (cDNA) dilution assays from qPCR data were analyzed by the Q-Anal method and compared with the threshold method and an extrapolation method. Dilution ratios determined by the Q-Anal and threshold methods were 86 to 118% of the expected cDNA ratios, but relative errors for the Q-Anal method were 4 to 10% in comparison with 4 to 34% for the threshold method. In contrast, ratios determined by an extrapolation method were 32 to 242% of the expected cDNA ratios, with relative errors of 67 to 193%. Q-Anal will be a valuable and quick method for minimizing error in comparative qPCR analysis.

Modulation frequency discrimination with single and multiple channels in cochlear implant users

PubMed Central

Galvin, John J.; Oba, Sandy; Başkent, Deniz; Fu, Qian-Jie

2015-01-01

Temporal envelope cues convey important speech information for cochlear implant (CI) users. Many studies have explored CI users’ single-channel temporal envelope processing. However, in clinical CI speech processors, temporal envelope information is processed by multiple channels. Previous studies have shown that amplitude modulation frequency discrimination (AMFD) thresholds are better when temporal envelopes are delivered to multiple rather than single channels. In clinical fitting, current levels on single channels must often be reduced to accommodate multi-channel loudness summation. As such, it is unclear whether the multi-channel advantage in AMFD observed in previous studies was due to coherent envelope information distributed across the cochlea or to greater loudness associated with multi-channel stimulation. In this study, single- and multi-channel AMFD thresholds were measured in CI users. Multi-channel component electrodes were either widely or narrowly spaced to vary the degree of overlap between neural populations. The reference amplitude modulation (AM) frequency was 100 Hz, and coherent modulation was applied to all channels. In Experiment 1, single- and multi-channel AMFD thresholds were measured at similar loudness. In this case, current levels on component channels were higher for single- than for multi-channel AM stimuli, and the modulation depth was approximately 100% of the perceptual dynamic range (i.e., between threshold and maximum acceptable loudness). Results showed no significant difference in AMFD thresholds between similarly loud single- and multi-channel modulated stimuli. In Experiment 2, single- and multi-channel AMFD thresholds were compared at substantially different loudness. In this case, current levels on component channels were the same for single-and multi-channel stimuli (“summation-adjusted” current levels) and the same range of modulation (in dB) was applied to the component channels for both single- and multi-channel testing. With the summation-adjusted current levels, loudness was lower with single than with multiple channels and the AM depth resulted in substantial stimulation below single-channel audibility, thereby reducing the perceptual range of AM. Results showed that AMFD thresholds were significantly better with multiple channels than with any of the single component channels. There was no significant effect of the distribution of electrodes on multi-channel AMFD thresholds. The results suggest that increased loudness due to multi-channel summation may contribute to the multi-channel advantage in AMFD, and that that overall loudness may matter more than the distribution of envelope information in the cochlea. PMID:25746914

Hypoalgesia in response to transcutaneous electrical nerve stimulation (TENS) depends on stimulation intensity.

PubMed

Moran, Fidelma; Leonard, Tracey; Hawthorne, Stephanie; Hughes, Ciara M; McCrum-Gardner, Evie; Johnson, Mark I; Rakel, Barbara A; Sluka, Kathleen A; Walsh, Deirdre M

2011-08-01

Transcutaneous electrical nerve stimulation (TENS) is an electrophysical modality used for pain management. This study investigated the dose response of different TENS intensities on experimentally induced pressure pain. One hundred and thirty TENS naïve healthy individuals (18-64 years old; 65 males, 65 females) were randomly allocated to 5 groups (n = 26 per group): Strong Non Painful TENS; Sensory Threshold TENS; Below Sensory Threshold TENS; No Current Placebo TENS; and Transient Placebo TENS. Active TENS (80 Hz) was applied to the forearm for 30 minutes. Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds (PPT) were recorded from 2 points on the hand and forearm before and after TENS to measure hypoalgesia. There were significant differences between groups at both the hand and forearm (ANOVA; P = .005 and .002). At 30 minutes, there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to: Below Sensory Threshold TENS, No Current Placebo TENS and Transient Placebo TENS groups (P < .0001) at the forearm; Transient Placebo TENS and No Current Placebo TENS groups at the hand (P = .001). There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups. The area under the curve for the changes in PPT significantly correlated with the current amplitude (r(2) = .33, P = .003). These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes. This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect; thus, we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Aluminium in allergen-specific subcutaneous immunotherapy--a German perspective.

PubMed

Kramer, Matthias F; Heath, Matthew D

2014-07-16

We are living in an "aluminium age" with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states. Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged. However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in subcutaneous immunotherapy (SCIT) and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities - evoking the need for more consideration, guidance, and transparency on what is known and not known about its safety in long-course therapy and what measures can be taken to prevent or minimise its risks. The possibility of providing an effective means of measuring aluminium accumulation in patients undergoing long-term SCIT treatment as well as reducing their aluminium body burden is discussed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Primary sex determination of placental mammals: a modelling study uncovers dynamical developmental constraints in the formation of Sertoli and granulosa cells.

PubMed

Sánchez, Lucas; Chaouiya, Claudine

2016-05-26

Primary sex determination in placental mammals is a very well studied developmental process. Here, we aim to investigate the currently established scenario and to assess its adequacy to fully recover the observed phenotypes, in the wild type and perturbed situations. Computational modelling allows clarifying network dynamics, elucidating crucial temporal constrains as well as interplay between core regulatory modules. Relying on a comprehensive revision of the literature, we define a logical model that integrates the current knowledge of the regulatory network controlling this developmental process. Our analysis indicates the necessity for some genes to operate at distinct functional thresholds and for specific developmental conditions to ensure the reproducibility of the sexual pathways followed by bi-potential gonads developing into either testes or ovaries. Our model thus allows studying the dynamics of wild type and mutant XX and XY gonads. Furthermore, the model analysis reveals that the gonad sexual fate results from the operation of two sub-networks associated respectively with an initiation and a maintenance phases. At the core of the process is the resolution of two connected feedback loops: the mutual inhibition of Sox9 and ß-catenin at the initiation phase, which in turn affects the mutual inhibition between Dmrt1 and Foxl2, at the maintenance phase. Three developmental signals related to the temporal activity of those sub-networks are required: a signal that determines Sry activation, marking the beginning of the initiation phase, and two further signals that define the transition from the initiation to the maintenance phases, by inhibiting the Wnt4 signalling pathway on the one hand, and by activating Foxl2 on the other hand. Our model reproduces a wide range of experimental data reported for the development of wild type and mutant gonads. It also provides a formal support to crucial aspects of the gonad sexual development and predicts gonadal phenotypes for mutations not tested yet.

Field Demonstration of Acetone Pretreatment and Composting of Particulate-TNT-Contaminated Soil

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

Radtke, Corey William; Smith, D.; Owen, S.

2002-02-01

Solid fragments of explosives in soil are common in explosives testing and training areas. In this study we initially sieved the upper 6 in of contaminated soil through a 3-mm mesh, and found 2, 4, 6-trinitrotoluene (TNT) fragments. These contributed to an estimated concentration of 1.7 kg per cubic yard soil, or for 2000 ppm TNT in the soil. Most of the fragments ranged 4 mm to 10 mm diameter in size, but explosives particles weighing up to 56 g (about 4 cm diameter) were frequently observed. An acetone pretreatment/composting system was then demonstrated at field scale. The amount ofmore » acetone required for a TNT-dissolving slurry process was controlled by the viscosity of the soil/acetone mix rather than the TNT dissolution rate. The amount needed was estimated at about 55 gallons acetone per cubic yard soil. Smaller, 5- to 10-mm-diameter fragments went into solution in less than 15 min at a mixer speed of 36 rpm, with a minimum of 2 g TNT going into solution per 30 min for the larger chunks. The slurries were than mixed with compost starting materials and composted in a vented 1 yd3 container. After 34 days incubation time TNT was below the site-specific regulatory threshold of 44 ppm. TNT metabolites and acetone were also below their regulatory thresholds established for the site.« less

Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

NASA Technical Reports Server (NTRS)

Gosselink, K. L.; Grindeland, R. E.; Roy, R. R.; Zhong, H.; Bigbee, A. J.; Grossman, E. J.; Edgerton, V. R.

1998-01-01

There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

System and method for quench and over-current protection of superconductor

DOEpatents

Huang, Xianrui; Laskaris, Evangelos Trifon; Sivasubramaniam, Kiruba Haran; Bray, James William; Ryan, David Thomas; Fogarty, James Michael; Steinbach, Albert Eugene

2005-05-31

A system and method for protecting a superconductor. The system may comprise a current sensor operable to detect a current flowing through the superconductor. The system may comprise a coolant temperature sensor operable to detect the temperature of a cryogenic coolant used to cool the superconductor to a superconductive state. The control circuit is operable to estimate the superconductor temperature based on the current flow and the coolant temperature. The system may also be operable to compare the estimated superconductor temperature to at least one threshold temperature and to initiate a corrective action when the superconductor temperature exceeds the at least one threshold temperature.

Effects of N-Acetylcysteine on Thresholds and Otoacoustic Emissions Following Noise Exposure

DTIC Science & Technology

2004-12-01

EFFECTS OF N- ACETYLCYSTEINE ON THRESHOLDS AND OTOACOUSTIC EMISSIONS FOLLOWING NOISE EXPOSURE Barbara Acker-Mills, Ph.D*., CPT Martin Robinette...wearing ear plugs, muffs, etc.. The current study evaluated the effectiveness of one antioxidant, N- acetylcysteine (NAC), on temporary cochlear changes...4. TITLE AND SUBTITLE Effects Of N- Acetylcysteine On Thresholds And Otoacoustic Emissions Following Noise Exposure 5a. CONTRACT NUMBER 5b

Threshold-Voltage-Shift Compensation and Suppression Method Using Hydrogenated Amorphous Silicon Thin-Film Transistors for Large Active Matrix Organic Light-Emitting Diode Displays

NASA Astrophysics Data System (ADS)

Oh, Kyonghwan; Kwon, Oh-Kyong

2012-03-01

A threshold-voltage-shift compensation and suppression method for active matrix organic light-emitting diode (AMOLED) displays fabricated using a hydrogenated amorphous silicon thin-film transistor (TFT) backplane is proposed. The proposed method compensates for the threshold voltage variation of TFTs due to different threshold voltage shifts during emission time and extends the lifetime of the AMOLED panel. Measurement results show that the error range of emission current is from -1.1 to +1.7% when the threshold voltage of TFTs varies from 1.2 to 3.0 V.

Acute effect of ozone exposure on daily mortality in seven cities of Jiangsu Province, China: No clear evidence for threshold.

PubMed

Chen, Kai; Zhou, Lian; Chen, Xiaodong; Bi, Jun; Kinney, Patrick L

2017-05-01

Few multicity studies have addressed the health effects of ozone in China due to the scarcity of ozone monitoring data. A critical scientific and policy-relevant question is whether a threshold exists in the ozone-mortality relationship. Using a generalized additive model and a univariate random-effects meta-analysis, this research evaluated the relationship between short-term ozone exposure and daily total mortality in seven cities of Jiangsu Province, China during 2013-2014. Spline, subset, and threshold models were applied to further evaluate whether a safe threshold level exists. This study found strong evidence that short-term ozone exposure is significantly associated with premature total mortality. A 10μg/m 3 increase in the average of the current and previous days' maximum 8-h average ozone concentration was associated with a 0.55% (95% posterior interval: 0.34%, 0.76%) increase of total mortality. This finding is robust when considering the confounding effect of PM 2.5 , PM 10 , NO 2 , and SO 2 . No consistent evidence was found for a threshold in the ozone-mortality concentration-response relationship down to concentrations well below the current Chinese Ambient Air Quality Standard (CAAQS) level 2 standard (160μg/m 3 ). Our findings suggest that ozone concentrations below the current CAAQS level 2 standard could still induce increased mortality risks in Jiangsu Province, China. Continuous air pollution control measures could yield important health benefits in Jiangsu Province, China, even in cities that meet the current CAAQS level 2 standard. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute effect of ozone exposure on daily mortality in seven cities of Jiangsu Province, China: No clear evidence for threshold

PubMed Central

Chen, Kai; Zhou, Lian; Chen, Xiaodong; Bi, Jun; Kinney, Patrick L.

2017-01-01

Background Few multicity studies have addressed the health effects of ozone in China due to the scarcity of ozone monitoring data. A critical scientific and policy-relevant question is whether a threshold exists in the ozone-mortality relationship. Methods Using a generalized additive model and a univariate random-effects meta-analysis, this research evaluated the relationship between short-term ozone exposure and daily total mortality in seven cities of Jiangsu Province, China during 2013–2014. Spline, subset, and threshold models were applied to further evaluate whether a safe threshold level exists. Results This study found strong evidence that short-term ozone exposure is significantly associated with premature total mortality. A 10 μg/m3 increase in the average of the current and previous days’ maximum 8-h average ozone concentration was associated with a 0.55% (95% posterior interval: 0.34%, 0.76%) increase of total mortality. This finding is robust when considering the confounding effect of PM2.5, PM10, NO2, and SO2. No consistent evidence was found for a threshold in the ozone-mortality concentration-response relationship down to concentrations well below the current Chinese Ambient Air Quality Standard (CAAQS) level 2 standard (160 μg/m3). Conclusions Our findings suggest that ozone concentrations below the current CAAQS level 2 standard could still induce increased mortality risks in Jiangsu Province, China. Continuous air pollution control measures could yield important health benefits in Jiangsu Province, China, even in cities that meet the current CAAQS level 2 standard. PMID:28231551

Perspectives on setting limits for RF contact currents: a commentary.

PubMed

Tell, Richard A; Tell, Christopher A

2018-01-15

Limits for exposure to radiofrequency (RF) contact currents are specified in the two dominant RF safety standards and guidelines developed by the Institute of Electrical and Electronics Engineers (IEEE) and the International Commission on Non-Ionizing Radiation Protection (ICNIRP). These limits are intended to prevent RF burns when contacting RF energized objects caused by high local tissue current densities. We explain what contact currents are and review some history of the relevant limits with an emphasis on so-called "touch" contacts, i.e., contact between a person and a contact current source during touch via a very small contact area. Contact current limits were originally set on the basis of controlling the specific absorption rate resulting from the current flowing through regions of small conductive cross section within the body, such as the wrist or ankle. More recently, contact currents have been based on thresholds of perceived heating. In the latest standard from the IEEE developed for NATO, contact currents have been based on two research studies in which thresholds for perception of thermal warmth or thermal pain have been measured. Importantly, these studies maximized conductive contact between the subject and the contact current source. This factor was found to dominate the response to heating wherein high resistance contact, such as from dry skin, can result in local heating many times that from a highly conductive contact. Other factors such as electrode size and shape, frequency of the current and the physical force associated with contact are found to introduce uncertainty in threshold values when comparing data across multiple studies. Relying on studies in which the contact current is minimized for a given threshold does not result in conservative protection limits. Future efforts to develop limits on contact currents should include consideration of (1) the basis for the limits (perception, pain, tissue damage); (2) understanding of the practical conditions of real world exposure for contact currents such as contact resistance, size and shape of the contact electrode and applied force at the point of contact; (3) consistency of how contact currents are applied in research studies across different researchers; (4) effects of frequency.

Scopolamine in racing horses: trace identifications associated with dietary or environmental exposure.

PubMed

Brewer, Kimberly; Dirikolu, Levent; Hughes, Charlie G; Tobin, Thomas

2014-03-01

Scopolamine (L-hyoscine) identifications, often in small-number clusters, have been reported worldwide in performance horses over the last 30 years. Scopolamine is an Association of Racing Commissioners International (ARCI) class 3, penalty class B, substance with potential to affect performance. As such, scopolamine identification(s) in race or performance horses can result in significant penalties for the connections of the horse(s). Reviewed here is the worldwide distribution of scopolamine containing plants (primarily Datura spp.), with estimates of their potential toxicity to horses through dietary and/or environmental exposure. Also reviewed are the basic pharmacology of scopolamine and its precursor, urinary concentrations following feedstuff exposure, and the probable pharmacological/forensic significance of such findings. Based on an overview of the world literature on scopolamine, the expected characteristics of inadvertent environmental exposure are also presented with a view to making clear the potential of scopolamine identifications, with or without atropine, as a direct and expected outcome of both the worldwide distribution of scopolamine-containing plants and the sensitivity of modern equine drug testing. It is of particular interest that only 2/30 reported post-event equine identifications of scopolamine have been associated with atropine, suggesting that failure to identify atropine is not a biomarker of pharmaceutical administration of scopolamine. Available quantitative information associated with scopolamine identifications is consistent with the 75 ng/mL regulatory threshold for scopolamine currently used in Louisiana racing in the USA and the 30 ng/mL reporting threshold in effect in European racing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of Urine Drug Testing in the Current Opioid Epidemic.

PubMed

Mahajan, Gagan

2017-12-01

While the evidence for urine drug testing for patients on chronic opioid therapy is weak, the guidelines created by numerous medical societies and state and federal regulatory agencies recommend that it be included as one of the tools used to monitor patients for compliance with chronic opioid therapy. To get the most comprehensive results, clinicians should order both an immunoassay screen and confirmatory urine drug test. The immunoassay screen, which can be performed as an in-office point-of-care test or as a laboratory-based test, is a cheap and convenient study to order. Limitations of an immunoassay screen, however, include having a high threshold of detectability and only providing qualitative information about a select number of drug classes. Because of these restrictions, clinicians should understand that immunoassay screens have high false-positive and false-negative rates. Despite these limitations, though, the results can assist the clinician with making preliminary treatment decisions. In comparison, a confirmatory urine drug test, which can only be performed as a laboratory-based test, has a lower threshold of detectability and provides both qualitative and quantitative information. A urine drug test's greater degree of specificity allows for a relatively low false-negative and false-positive rate in contrast to an immunoassay screen. Like any other diagnostic test, an immunoassay screen and a confirmatory urine drug test both possess limitations. Clinicians must keep this in mind when interpreting an unexpected test result and consult with their laboratory when in doubt about the meaning of the test result to avoid making erroneous decisions that negatively impact both the patient and clinician.

Insufficient evidence to support separate BMI definitions for obesity in children and adolescents from south Asian ethnic groups in the UK.

PubMed

Viner, R M; Cole, Tim J; Fry, T; Gupta, S; Kinra, S; McCarthy, D; Saxena, S; Taylor, S; Wells, J C K; Whincup, P; Zaman, M J S

2010-04-01

Re-evaluation of adult obesity thresholds in some ethnic groups has led to the questioning of childhood obesity thresholds. An expert group was convened to examine the representativeness of childhood obesity definitions, evidence for ethnic differences in body composition in UK children and the extent of misclassification of adiposity by current body mass index (BMI) thresholds in south Asian and black groups. The group concluded that the current International Obesity Task Force (IOTF) definitions remained the most appropriate for use in the United Kingdom, but further research was needed on the relationship of body shape, fat mass, metabolic markers and ethnicity in children and adolescents.

Empirical estimation of genome-wide significance thresholds based on the 1000 Genomes Project data set.

PubMed

Kanai, Masahiro; Tanaka, Toshihiro; Okada, Yukinori

2016-10-01

To assess the statistical significance of associations between variants and traits, genome-wide association studies (GWAS) should employ an appropriate threshold that accounts for the massive burden of multiple testing in the study. Although most studies in the current literature commonly set a genome-wide significance threshold at the level of P=5.0 × 10 -8 , the adequacy of this value for respective populations has not been fully investigated. To empirically estimate thresholds for different ancestral populations, we conducted GWAS simulations using the 1000 Genomes Phase 3 data set for Africans (AFR), Europeans (EUR), Admixed Americans (AMR), East Asians (EAS) and South Asians (SAS). The estimated empirical genome-wide significance thresholds were P sig =3.24 × 10 -8 (AFR), 9.26 × 10 -8 (EUR), 1.83 × 10 -7 (AMR), 1.61 × 10 -7 (EAS) and 9.46 × 10 -8 (SAS). We additionally conducted trans-ethnic meta-analyses across all populations (ALL) and all populations except for AFR (ΔAFR), which yielded P sig =3.25 × 10 -8 (ALL) and 4.20 × 10 -8 (ΔAFR). Our results indicate that the current threshold (P=5.0 × 10 -8 ) is overly stringent for all ancestral populations except for Africans; however, we should employ a more stringent threshold when conducting a meta-analysis, regardless of the presence of African samples.

[The new German general threshold limit value for dust--pro and contra the adoption in Austria].

PubMed

Godnic-Cvar, Jasminka; Ponocny, Ivo

2004-01-01

Since it has been realised that inhalation of inert dust is one of the important confounding variables for the development of chronic bronchitis, the threshold values for occupational exposure to these dusts needs to be further decreased. The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK-Commission) has set a new threshold (MAK-Value) for inert dusts (4 mg/m3 for inhalable dust, 1.5 mg/m3 for respirable dust) in 1997. This value is much lower than the threshold values currently used world-wide. The aim of the present article is to assess the scientific plausibility of the methodology (databases and statistics) used to set these new German MAK-Values, regarding their adoption in Austria. Although we believe that it is substantial to lower the MAK-Value for inert dust in order to prevent the development of chronic bronchitis as a consequence of occupational exposure to inert dusts, the applied methodology used by the German MAK-Commission in 1997 to set the new MAK-Values does not justify the reduction of the threshold limit value. A carefully designed study to establish an appropriate scientific basis for setting a new threshold value for inert dusts in the workplace should be carried out. Meanwhile, at least the currently internationally applied threshold values should be adopted in Austria.

Dose-mortality assessment upon reuse and recycling of industrial sludge.

PubMed

Lin, Kae-Long; Chen, Bor-Yann

2007-09-05

This study provides a novel attempt to put forward, in general toxicological terms, quantitative ranking of toxicity of various sources of sludge for possible reusability in further applications. The high leaching concentrations of copper in printed circuit board (PCB) sludge and chromium in leather sludge apparently exceeded current Taiwan's EPA regulatory thresholds and should be classified as hazardous wastes. Dose-mortality analysis indicated that the toxicity ranking of different sources of sludge was PCB sludge>CaF(2) sludge>leather sludge. PCB sludge was also confirmed as a hazardous waste since the toxicity potency of PCB sludge was nearly identical to CdCl(2). However, leather sludge seemed to be much less toxic than as anticipated, perhaps due to a significant decrease of toxic species bioavailable in the aqueous phase to the reporter bacterium Escherichia coli DH5alpha. For possible reusability of sludge, maximum concentrations allowable to be considered "safe" (ca. EC(100)/100) were 9.68, 42.1 and 176 mgL(-1) for CaF(2) sludge, PCB sludge and leather sludge, respectively.

An Optimal Free Energy Dissipation Strategy of the MinCDE Oscillator in Regulating Symmetric Bacterial Cell Division

PubMed Central

Xiong, Liping; Lan, Ganhui

2015-01-01

Sustained molecular oscillations are ubiquitous in biology. The obtained oscillatory patterns provide vital functions as timekeepers, pacemakers and spacemarkers. Models based on control theory have been introduced to explain how specific oscillatory behaviors stem from protein interaction feedbacks, whereas the energy dissipation through the oscillating processes and its role in the regulatory function remain unexplored. Here we developed a general framework to assess an oscillator’s regulation performance at different dissipation levels. Using the Escherichia coli MinCDE oscillator as a model system, we showed that a sufficient amount of energy dissipation is needed to switch on the oscillation, which is tightly coupled to the system’s regulatory performance. Once the dissipation level is beyond this threshold, unlike stationary regulators’ monotonic performance-to-cost relation, excess dissipation at certain steps in the oscillating process damages the oscillator’s regulatory performance. We further discovered that the chemical free energy from ATP hydrolysis has to be strategically assigned to the MinE-aided MinD release and the MinD immobilization steps for optimal performance, and a higher energy budget improves the robustness of the oscillator. These results unfold a novel mode by which living systems trade energy for regulatory function. PMID:26317492

The Control of the Specificity of CD4 T Cell Responses: Thresholds, Breakpoints, and Ceilings

PubMed Central

Sant, Andrea J.; Chaves, Francisco A.; Leddon, Scott A.; Tung, Jacqueline

2013-01-01

It has been known for over 25 years that CD4 T cell responses are restricted to a finite number of peptide epitopes within pathogens or protein vaccines. These selected peptide epitopes are termed “immunodominant.” Other peptides within the antigen that can bind to host MHC molecules and recruit CD4 T cells as single peptides are termed “cryptic” because they fail to induce responses when expressed in complex proteins or when in competition with other peptides during the immune response. In the last decade, our laboratory has evaluated the mechanisms that underlie the preferential specificity of CD4 T cells and have discovered that both intracellular events within antigen presenting cells, particular selective DM editing, and intercellular regulatory pathways, involving IFN-γ, indoleamine 2,3-dioxygenase, and regulatory T cells, play a role in selecting the final peptide specificity of CD4 T cells. In this review, we summarize our findings, discuss the implications of this work on responses to pathogens and vaccines and speculate on the logic of these regulatory events. PMID:24167504

Legal and regulatory responses to innovative treatment.

PubMed

Chan, Tracey Evans

2013-01-01

Developments in medical technology, healthcare delivery, and commercial interests in medicine have increased both the potential for conflicts of interest on the part of physicians, and doubts over the sufficiency of patient autonomy as a justification for administering innovative therapy. The legal and regulatory treatment of innovative therapy is therefore an important question, on which there is a current lack of consensus on a number of issues. This paper discusses recent developments in Singapore and uses them as a springboard to flesh out basic regulatory issues that arise from the deployment of innovative treatment: the distinction between innovative treatment and clinical research, the adequacy of the current post hoc scrutiny of innovative therapy under existing legal principles and the need for further specialised regulatory oversight.

Electrophysiological gap detection thresholds: effects of age and comparison with a behavioral measure.

PubMed

Palmer, Shannon B; Musiek, Frank E

2014-01-01

Temporal processing ability has been linked to speech understanding ability and older adults often complain of difficulty understanding speech in difficult listening situations. Temporal processing can be evaluated using gap detection procedures. There is some research showing that gap detection can be evaluated using an electrophysiological procedure. However, there is currently no research establishing gap detection threshold using the N1-P2 response. The purposes of the current study were to 1) determine gap detection thresholds in younger and older normal-hearing adults using an electrophysiological measure, 2) compare the electrophysiological gap detection threshold and behavioral gap detection threshold within each group, and 3) investigate the effect of age on each gap detection measure. This study utilized an older adult group and younger adult group to compare performance on an electrophysiological and behavioral gap detection procedure. The subjects in this study were 11 younger, normal-hearing adults (mean = 22 yrs) and 11 older, normal-hearing adults (mean = 64.36 yrs). All subjects completed an adaptive behavioral gap detection procedure in order to determine their behavioral gap detection threshold (BGDT). Subjects also completed an electrophysiologic gap detection procedure to determine their electrophysiologic gap detection threshold (EGDT). Older adults demonstrated significantly larger gap detection thresholds than the younger adults. However, EGDT and BGDT were not significantly different in either group. The mean difference between EGDT and BGDT for all subjects was 0.43 msec. Older adults show poorer gap detection ability when compared to younger adults. However, this study shows that gap detection thresholds can be measured using evoked potential recordings and yield results similar to a behavioral measure. American Academy of Audiology.

Spectroscopic study of transparency current in mid-infrared quantum cascade lasers.

PubMed

Revin, Dmitry G; Hassan, Randa S; Krysa, Andrey B; Wang, Yongrui; Belyanin, Alexey; Kennedy, Kenneth; Atkins, Chris N; Cockburn, John W

2012-08-13

We report measurements which give direct insight into the origins of the transparency current for λ ~5 µm In0.6Ga0.4As/In0.42Al0.58As quantum cascade lasers in the temperature range of 80-280 K. The transparency current values have been found from broadband transmission measurements through the laser waveguides under sub-threshold operating conditions. Two active region designs were compared. The active region of the first laser is based on double-LO-phonon relaxation approach, while the second device has only one lower level, without specially designed resonant LO-phonon assisted depopulation. It is shown that transparency current contributes more than 70% to the magnitude of threshold current at high temperatures for both designs.

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

Influence of an anomalous dimension effect on thermal instability in amorphous-InGaZnO thin-film transistors

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

Liu, Kuan-Hsien; Chou, Wu-Ching, E-mail: tcchang3708@gmail.com, E-mail: wuchingchou@mail.nctu.edu.tw; Chang, Ting-Chang, E-mail: tcchang3708@gmail.com, E-mail: wuchingchou@mail.nctu.edu.tw

2014-10-21

This paper investigates abnormal dimension-dependent thermal instability in amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistors. Device dimension should theoretically have no effects on threshold voltage, except for in short channel devices. Unlike short channel drain-induced source barrier lowering effect, threshold voltage increases with increasing drain voltage. Furthermore, for devices with either a relatively large channel width or a short channel length, the output drain current decreases instead of saturating with an increase in drain voltage. Moreover, the wider the channel and the shorter the channel length, the larger the threshold voltage and output on-state current degradation that is observed. Because of themore » surrounding oxide and other thermal insulating material and the low thermal conductivity of the IGZO layer, the self-heating effect will be pronounced in wider/shorter channel length devices and those with a larger operating drain bias. To further clarify the physical mechanism, fast I{sub D}-V{sub G} and modulated peak/base pulse time I{sub D}-V{sub D} measurements are utilized to demonstrate the self-heating induced anomalous dimension-dependent threshold voltage variation and on-state current degradation.« less

Threshold-voltage modulated phase change heterojunction for application of high density memory

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

Yan, Baihan; Tong, Hao, E-mail: tonghao@hust.edu.cn; Qian, Hang

2015-09-28

Phase change random access memory is one of the most important candidates for the next generation non-volatile memory technology. However, the ability to reduce its memory size is compromised by the fundamental limitations inherent in the CMOS technology. While 0T1R configuration without any additional access transistor shows great advantages in improving the storage density, the leakage current and small operation window limit its application in large-scale arrays. In this work, phase change heterojunction based on GeTe and n-Si is fabricated to address those problems. The relationship between threshold voltage and doping concentration is investigated, and energy band diagrams and X-raymore » photoelectron spectroscopy measurements are provided to explain the results. The threshold voltage is modulated to provide a large operational window based on this relationship. The switching performance of the heterojunction is also tested, showing a good reverse characteristic, which could effectively decrease the leakage current. Furthermore, a reliable read-write-erase function is achieved during the tests. Phase change heterojunction is proposed for high-density memory, showing some notable advantages, such as modulated threshold voltage, large operational window, and low leakage current.« less

Single-mode operation of mushroom structure surface emitting lasers

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

Wang, Y.J.; Dziura, T.G.; Wang, S.C.

1991-01-01

Mushroom structure vertical cavity surface emitting lasers with a 0.6 {mu}m GaAs active layer sandwiched by two Al{sub 0.6{sup {minus}}}Ga{sub 0.4}As-Al{sub 0.08}Ga{sub 0.92}As multilayers as top and bottom mirrors exhibit 15 mA pulsed threshold current at 880 nm. Single longitudinal and single transverse mode operation was achieved on lasers with a 5 {mu}m diameter active region at current levels near 2 {times} I{sub th}. The light output above threshold current was linearly polarized with a polarization ratio of 25:1.

High-temperature CW and pulsed operation in constricted double-heterojunction AlGaAs diode lasers

NASA Technical Reports Server (NTRS)

Botez, D.; Connolly, J. C.; Gilbert, D. B.

1981-01-01

The behavior of constricted double-heterojunction (CDH) diode lasers has been investigated up to 170 C CW and 270 C pulsed. It is found that the temperature-dependent current concentration effect responsible for low threshold-current sensitivity and temperature-invariant external differential quantum efficiency in CDH lasers saturates at about 100 C. It is also found that over a wide temperature interval (180-280 C) the threshold current density has a To value of 40-50 C and that the spontaneous emission becomes increasingly sublinear above 220 C. Both effects are believed to reflect Auger recombination.

Timing discriminator using leading-edge extrapolation

DOEpatents

Gottschalk, Bernard

1983-01-01

A discriminator circuit to recover timing information from slow-rising pulses by means of an output trailing edge, a fixed time after the starting corner of the input pulse, which is nearly independent of risetime and threshold setting. This apparatus comprises means for comparing pulses with a threshold voltage; a capacitor to be charged at a certain rate when the input signal is one-third threshold voltage, and at a lower rate when the input signal is two-thirds threshold voltage; current-generating means for charging the capacitor; means for comparing voltage capacitor with a bias voltage; a flip-flop to be set when the input pulse reaches threshold voltage and reset when capacitor voltage reaches the bias voltage; and a clamping means for discharging the capacitor when the input signal returns below one-third threshold voltage.

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.

Gain competition in dual wavelength quantum cascade lasers.

PubMed

Geiser, Markus; Pflügl, Christian; Belyanin, Alexey; Wang, Qi Jie; Yu, Nanfang; Edamura, Tadanaka; Yamanishi, Masamichi; Kan, Hirofumi; Fischer, Milan; Wittmann, Andreas; Faist, Jérôme; Capasso, Federico

2010-05-10

We investigated dual wavelength mid-infrared quantum cascade lasers based on heterogeneous cascades. We found that due to gain competition laser action tends to start in higher order lateral modes. The mid-infrared mode with the lower threshold current reduces population inversion for the second laser with the higher threshold current due to stimulated emission. We developed a rate equation model to quantitatively describe mode interactions due to mutual gain depletion. (c) 2010 Optical Society of America.

Extreme sub-threshold swing in tunnelling relays

NASA Astrophysics Data System (ADS)

AbdelGhany, M.; Szkopek, T.

2014-01-01

We propose and analyze the theory of the tunnelling relay, a nanoscale active device in which tunnelling current is modulated by electromechanical actuation of a suspended membrane above a fixed electrode. The tunnelling current is modulated exponentially with vacuum gap length, permitting an extreme sub-threshold swing of ˜10 mV/decade breaking the thermionic limit. The predicted performance suggests that a significant reduction in dynamic energy consumption over conventional field effect transistors is physically achievable.

International and domestic mobile satellite regulatory proceedings: A comparison of outcomes and discussion of implications

NASA Technical Reports Server (NTRS)

Freibaum, Jerry

1988-01-01

It is argued that we are on the threshold of a new multibillion dollar industry that can enhance economic development, dramatically improve disaster assessment and relief operations, improve rural health care and solve many safety and security concerns of the transportation industry. Further delays in resolving conflicts between vested interests will be extremely costly to users, providers and equipment manufacturers. Conference participants are urged to move quickly and decisively towards solving outstanding problems.

Lead paint removal with high-intensity light pulses.

PubMed

Grapperhaus, Michael J; Schaefer, Raymond B

2006-12-15

This paper presents the results of an initial investigation into using high-intensity incoherent light pulses to strip paint. Measurements of light pulse characteristics, the reflectivity of different paints and initial experiments on the threshold for paint removal, and paint removal are presented, along with an approximate model consistent with experimental results. Paint removal tests include lead paint, the reduction of lead levels to below levels required for lead abatement, as well as air and light emissions measurements that are within regulatory guidelines.

Effect of thermal insulation on the electrical characteristics of NbOx threshold switches

NASA Astrophysics Data System (ADS)

Wang, Ziwen; Kumar, Suhas; Wong, H.-S. Philip; Nishi, Yoshio

2018-02-01

Threshold switches based on niobium oxide (NbOx) are promising candidates as bidirectional selector devices in crossbar memory arrays and building blocks for neuromorphic computing. Here, it is experimentally demonstrated that the electrical characteristics of NbOx threshold switches can be tuned by engineering the thermal insulation. Increasing the thermal insulation by ˜10× is shown to produce ˜7× reduction in threshold current and ˜45% reduction in threshold voltage. The reduced threshold voltage leads to ˜5× reduction in half-selection leakage, which highlights the effectiveness of reducing half-selection leakage of NbOx selectors by engineering the thermal insulation. A thermal feedback model based on Poole-Frenkel conduction in NbOx can explain the experimental results very well, which also serves as a piece of strong evidence supporting the validity of the Poole-Frenkel based mechanism in NbOx threshold switches.

Safety parameter considerations of anodal transcranial Direct Current Stimulation in rats.

PubMed

Jackson, Mark P; Truong, Dennis; Brownlow, Milene L; Wagner, Jessica A; McKinley, R Andy; Bikson, Marom; Jankord, Ryan

2017-08-01

A commonly referenced transcranial Direct Current Stimulation (tDCS) safety threshold derives from tDCS lesion studies in the rat and relies on electrode current density (and related electrode charge density) to support clinical guidelines. Concerns about the role of polarity (e.g. anodal tDCS), sub-lesion threshold injury (e.g. neuroinflammatory processes), and role of electrode montage across rodent and human studies support further investigation into animal models of tDCS safety. Thirty-two anesthetized rats received anodal tDCS between 0 and 5mA for 60min through one of three epicranial electrode montages. Tissue damage was evaluated using hemotoxylin and eosin (H&E) staining, Iba-1 immunohistochemistry, and computational brain current density modeling. Brain lesion occurred after anodal tDCS at and above 0.5mA using a 25.0mm 2 electrode (electrode current density: 20.0A/m 2 ). Lesion initially occurred using smaller 10.6mm 2 or 5.3mm 2 electrodes at 0.25mA (23.5A/m 2 ) and 0.5mA (94.2A/m 2 ), respectively. Histological damage was correlated with computational brain current density predictions. Changes in microglial phenotype occurred in higher stimulation groups. Lesions were observed using anodal tDCS at an electrode current density of 20.0A/m 2 , which is below the previously reported safety threshold of 142.9A/m 2 using cathodal tDCS. The lesion area is not simply predicted by electrode current density (and so not by charge density as duration was fixed); rather computational modeling suggests average brain current density as a better predictor for anodal tDCS. Nonetheless, under the assumption that rodent epicranial stimulation is a hypersensitive model, an electrode current density of 20.0A/m 2 represents a conservative threshold for clinical tDCS, which typically uses an electrode current density of 2A/m 2 when electrodes are placed on the skin (resulting in a lower brain current density). Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2017-05-01

Cannabis Social Clubs (CSCs) are a model of non-profit production and distribution of cannabis among a closed circuit of adult cannabis users. CSCs are now operating in several countries around the world, albeit under very different legal regimes and in different socio-political contexts. In this paper we describe and compare the legal framework and the self-regulatory practices of Cannabis Social Clubs in three countries (Spain, Belgium, and Uruguay). The objective of our comparative analysis is to investigate how CSCs operate in each of these countries. To foster discussions about how one might regulate CSCs to promote public health objectives, we conclude this paper with a discussion on the balance between adequate governmental control and self-regulatory competences of CSCs. The data used for this analysis stem from independently conducted local studies by the authors in their countries. Although the particular designs of the studies differ, the data in all three countries was collected through similar data collection methods: analysis of (legal and other documents), field visits to the clubs, interviews with staff members, media content analysis. We identified a number of similarities and differences among the CSCs' practices in the three countries. Formal registration as non-profit association seems to be a common standard among CSCs. We found nevertheless great variation in terms of the size of these organisations. Generally, only adult nationals and/or residents are able to join the CSCs, upon the payment of a membership fee. While production seems to be guided by consumption estimates of the members (Spain and Belgium) or by the legal framework (Uruguay), the thresholds applied by the clubs vary significantly across countries. Quality control practices remain an issue in the three settings studied here. The CSCs have developed different arrangements with regards to the distribution of cannabis to their members. By uncovering the current practices of CSCs in three key settings, this paper contributes to the understanding of the model, which has to some extent been shaped by the self-regulatory efforts of those involved on the ground. We suggest that some of these self-regulatory practices could be accommodated in future regulation in this area, while other aspects of the functioning of the CSCs may require more formal regulation and monitoring. Decisions on this model should also take into account the local context where the clubs have emerged. Finally, the integration of medical supply within this model warrants further attention. Copyright © 2017 Elsevier B.V. All rights reserved.

PEDOT-CNT coated electrodes stimulate retinal neurons at low voltage amplitudes and low charge densities

NASA Astrophysics Data System (ADS)

Samba, R.; Herrmann, T.; Zeck, G.

2015-02-01

Objective. The aim of this study was to compare two different microelectrode materials—the conductive polymer composite poly-3,4-ethylenedioxythiophene (PEDOT)-carbon nanotube(CNT) and titanium nitride (TiN)—at activating spikes in retinal ganglion cells in whole mount rat retina through stimulation of the local retinal network. Stimulation efficacy of the microelectrodes was analyzed by comparing voltage, current and transferred charge at stimulation threshold. Approach. Retinal ganglion cell spikes were recorded by a central electrode (30 μm diameter) in the planar grid of an electrode array. Extracellular stimulation (monophasic, cathodic, 0.1-1.0 ms) of the retinal network was performed using constant voltage pulses applied to the eight surrounding electrodes. The stimulation electrodes were equally spaced on the four sides of a square (400 × 400 μm). Threshold voltage was determined as the pulse amplitude required to evoke network-mediated ganglion cell spiking in a defined post stimulus time window in 50% of identical stimulus repetitions. For the two electrode materials threshold voltage, transferred charge at threshold, maximum current and the residual current at the end of the pulse were compared. Main results. Stimulation of retinal interneurons using PEDOT-CNT electrodes is achieved with lower stimulation voltage and requires lower charge transfer as compared to TiN. The key parameter for effective stimulation is a constant current over at least 0.5 ms, which is obtained by PEDOT-CNT electrodes at lower stimulation voltage due to its faradaic charge transfer mechanism. Significance. In neuroprosthetic implants, PEDOT-CNT may allow for smaller electrodes, effective stimulation in a safe voltage regime and lower energy-consumption. Our study also indicates, that the charge transferred at threshold or the charge injection capacity per se does not determine stimulation efficacy.

Role of the Excitability Brake Potassium Current IKD in Cold Allodynia Induced by Chronic Peripheral Nerve Injury.

PubMed

González, Alejandro; Ugarte, Gonzalo; Restrepo, Carlos; Herrera, Gaspar; Piña, Ricardo; Gómez-Sánchez, José Antonio; Pertusa, María; Orio, Patricio; Madrid, Rodolfo

2017-03-22

Cold allodynia is a common symptom of neuropathic and inflammatory pain following peripheral nerve injury. The mechanisms underlying this disabling sensory alteration are not entirely understood. In primary somatosensory neurons, cold sensitivity is mainly determined by a functional counterbalance between cold-activated TRPM8 channels and Shaker-like Kv1.1-1.2 channels underlying the excitability brake current I KD Here we studied the role of I KD in damage-triggered painful hypersensitivity to innocuous cold. We found that cold allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in mice, was related to both an increase in the proportion of cold-sensitive neurons (CSNs) in DRGs contributing to the sciatic nerve, and a decrease in their cold temperature threshold. I KD density was reduced in high-threshold CSNs from CCI mice compared with sham animals, with no differences in cold-induced TRPM8-dependent current density. The electrophysiological properties and neurochemical profile of CSNs revealed an increase of nociceptive-like phenotype among neurons from CCI animals compared with sham mice. These results were validated using a mathematical model of CSNs, including I KD and TRPM8, showing that a reduction in I KD current density shifts the thermal threshold to higher temperatures and that the reduction of this current induces cold sensitivity in former cold-insensitive neurons expressing low levels of TRPM8-like current. Together, our results suggest that cold allodynia is largely due to a functional downregulation of I KD in both high-threshold CSNs and in a subpopulation of polymodal nociceptors expressing TRPM8, providing a general molecular and neural mechanism for this sensory alteration. SIGNIFICANCE STATEMENT This paper unveils the critical role of the brake potassium current I KD in damage-triggered cold allodynia. Using a well-known form of nerve injury and combining behavioral analysis, calcium imaging, patch clamping, and pharmacological tools, validated by mathematical modeling, we determined that the functional expression of I KD is reduced in sensory neurons in response to peripheral nerve damage. This downregulation not only enhances cold sensitivity of high-threshold cold thermoreceptors signaling cold discomfort, but it also transforms a subpopulation of polymodal nociceptors signaling pain into neurons activated by mild temperature drops. Our results suggest that cold allodynia is linked to a reduction of I KD in both high-threshold cold thermoreceptors and nociceptors expressing TRPM8, providing a general model for this form of cold-induced pain. Copyright © 2017 the authors 0270-6474/17/373109-18$15.00/0.

Pharmacological and anatomical separation of calcium currents in rat dentate granule neurones in vitro.

PubMed Central

Blaxter, T J; Carlen, P L; Niesen, C

1989-01-01

1. Rat dentate granule neurones in hippocampal slices were voltage-clamped at 21-23 degrees C using CsCl-filled microelectrodes. The perfusate contained TTX and K+ channel blockers to isolate pharmacologically inward Ca2+ currents. 2. From hyperpolarized holding potentials of -65 to -85 mV, depolarizing test potentials to between -50 and -40 mV elicited a transient (100-200 ms) low-threshold (TLT) current which was also elicited from more depolarized holding potentials following hyperpolarizing voltage steps of -40 mV or greater. 3. Larger depolarizing steps from a hyperpolarized holding potential triggered a large (2-6 nA), transient high-threshold (THT) inward current, rapidly peaking and decaying over 500 ms, followed by a sustained inward current component. 4. At depolarized holding potentials (-50 to -20 mV), the THT current was apparently inactivated and a sustained high-threshold (SHT) inward current was evident during depolarizing voltage steps of 10 mV or more. 5. From hyperpolarized holding potentials with depolarizing voltage steps of 10-30 mV, most neurones demonstrated a small-amplitude, sustained low-threshold (SLT) inward current with similar characteristics to the SHT current. 6. Zero-Ca2+ perfusate or high concentrations of Ca2+ channel blockers (Cd2+, Mn2+ or Ni2+) diminished or abolished all inward currents. 7. Repetitive voltage step activation of each current at 0.5 Hz reduced the large THT current to less than 25% of an unconditioned control current, reduced the SHT current by 50%, but had little effect on the TLT current. 8. A low concentration of Cd2+ (50 microM) blocked the THT and SHT currents with little effect on the TLT current. Nimodipine (1 microM) attenuated the SHT current. Ni2+ (100 microM) selectively attenuated the TLT current. 9. In low-Ca2+ perfusate, high concentrations of Ca2+ (10-15 mM), focally applied to different parts of the neurone, increased the THT current when applied to the dendrites, the SHT current when applied to the soma and the TLT current at all locations. Conversely, in regular perfusate, Cd2+ (1-5 mM), focally applied to the dendrites decreased the THT current and somatic applications decreased the SHT current. The TLT current was diminished regardless of the site of Cd2+ application. 10. These results suggest the existence of three different Ca2+ currents in dentate granule cells separable by their activation and inactivation characteristics, pharmacology and site of initiation. PMID:2557433

Self-Regulation across Time of First-Generation Online Learners

ERIC Educational Resources Information Center

Barnard-Brak, Lucy; Paton, Valerie Osland; Lan, William Y.

2010-01-01

Self-regulatory skills have been associated with positive outcomes for learners. In the current study, we examined the self-regulatory skills of students who are first-generation online learners over the course of their first semester of online instruction. The purpose of this study is to determine whether the online self-regulatory skills of…

17 CFR 400.4 - Information concerning associated persons of financial institutions that are government...

Code of Federal Regulations, 2010 CFR

2010-04-01

... completed and current Form U-4 (promulgated by a self-regulatory organization) or Form MSD-4 (as required... regulatory agency for such financial institution, a statement correcting such information. (c) For the... shall: (1) Promptly obtain and, within 10 days thereafter, file with the appropriate regulatory agency...

77 FR 52977 - Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule; Market Risk Capital Rule

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... Corporation 12 CFR Parts 324, 325 Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule... 325 RIN 3064-AD97 Regulatory Capital Rules: Advanced Approaches Risk-Based Capital Rule; Market Risk... the agencies' current capital rules. In this NPR (Advanced Approaches and Market Risk NPR) the...

78 FR 27113 - Generic Drug User Fee Amendments of 2012; Regulatory Science Initiatives Public Hearing; Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

.... FDA-2013-N-0402] Generic Drug User Fee Amendments of 2012; Regulatory Science Initiatives Public... public meeting that will provide an overview of the current status of the regulatory science initiatives... societies, and other interested stakeholders-- as it fulfills its statutory requirement under the Generic...

76 FR 76777 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-08

... fees: (i) For a data set of real-time TRACE disseminated TBA transaction data at the same rates currently in effect for similar real-time TRACE disseminated data sets, and (ii) for a data set of historic TRACE TBA transaction data at the same rates currently in effect for similar Historic TRACE Data sets.\\4...

75 FR 2897 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... of a mutual fund to investors at the fund's current net asset value, plus any applicable sales load... codified as NASD IM-2830-2, that requires members to sell mutual funds at the public offering price not... sell shares of mutual funds to non-member broker-dealers at a price below the current public offering...

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies

PubMed Central

Mahon, Jeffrey L.; Beam, Craig A.; Marcovina, Santica M.; Boulware, David C.; Palmer, Jerry P.; Winter, William E.; Skyler, Jay S.; Krischer, Jeffrey P.

2018-01-01

Background Detection of below-threshold first-phase insulin release or FPIR (1 + 3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR. Methods One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA. Results The insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p < 0.05). Conclusions An insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA. PMID:21843518

Deciphering RNA regulatory elements in trypanosomatids: one piece at a time or genome-wide?

PubMed

Gazestani, Vahid H; Lu, Zhiquan; Salavati, Reza

2014-05-01

Morphological and metabolic changes in the life cycle of Trypanosoma brucei are accomplished by precise regulation of hundreds of genes. In the absence of transcriptional control, RNA-binding proteins (RBPs) shape the structure of gene regulatory maps in this organism, but our knowledge about their target RNAs, binding sites, and mechanisms of action is far from complete. Although recent technological advances have revolutionized the RBP-based approaches, the main framework for the RNA regulatory element (RRE)-based approaches has not changed over the last two decades in T. brucei. In this Opinion, after highlighting the current challenges in RRE inference, we explain some genome-wide solutions that can significantly boost our current understanding about gene regulatory networks in T. brucei. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of Pulse Polarity on Thresholds and on Non-monotonic Loudness Growth in Cochlear Implant Users.

PubMed

Macherey, Olivier; Carlyon, Robert P; Chatron, Jacques; Roman, Stéphane

2017-06-01

Most cochlear implants (CIs) activate their electrodes non-simultaneously in order to eliminate electrical field interactions. However, the membrane of auditory nerve fibers needs time to return to its resting state, causing the probability of firing to a pulse to be affected by previous pulses. Here, we provide new evidence on the effect of pulse polarity and current level on these interactions. In experiment 1, detection thresholds and most comfortable levels (MCLs) were measured in CI users for 100-Hz pulse trains consisting of two consecutive biphasic pulses of the same or of opposite polarity. All combinations of polarities were studied: anodic-cathodic-anodic-cathodic (ACAC), CACA, ACCA, and CAAC. Thresholds were lower when the adjacent phases of the two pulses had the same polarity (ACCA and CAAC) than when they were different (ACAC and CACA). Some subjects showed a lower threshold for ACCA than for CAAC while others showed the opposite trend demonstrating that polarity sensitivity at threshold is genuine and subject- or electrode-dependent. In contrast, anodic (CAAC) pulses always showed a lower MCL than cathodic (ACCA) pulses, confirming previous reports. In experiments 2 and 3, the subjects compared the loudness of several pulse trains differing in current level separately for ACCA and CAAC. For 40 % of the electrodes tested, loudness grew non-monotonically as a function of current level for ACCA but never for CAAC. This finding may relate to a conduction block of the action potentials along the fibers induced by a strong hyperpolarization of their central processes. Further analysis showed that the electrodes showing a lower threshold for ACCA than for CAAC were more likely to yield a non-monotonic loudness growth. It is proposed that polarity sensitivity at threshold reflects the local neural health and that anodic asymmetric pulses should preferably be used to convey sound information while avoiding abnormal loudness percepts.

Attenuation of progressive hearing loss in DBA/2J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4.

PubMed

Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

2015-01-01

Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (-)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing.

Spacer engineered Trigate SOI TFET: An investigation towards harsh temperature environment applications

NASA Astrophysics Data System (ADS)

Mallikarjunarao; Ranjan, Rajeev; Pradhan, K. P.; Artola, L.; Sahu, P. K.

2016-09-01

In this paper, a novel N-channel Tunnel Field Effect Transistor (TFET) i.e., Trigate Silicon-ON-Insulator (SOI) N-TFET with high-k spacer is proposed for better Sub-threshold swing (SS) and OFF-state current (IOFF) by keeping in mind the sensitivity towards temperature. The proposed model can achieve a Sub-threshold swing less than 35 mV/decade at various temperatures, which is desirable for designing low power CTFET for digital circuit applications. In N-TFET source doping has a significant effect on the ON-state current (ION) level; therefore more electrons will tunnel from source to channel region. High-k Spacer i.e., HfO2 is used to enhance the device performance and also it avoids overlapping of transistors in an integrated circuits (IC's). We have designed a reliable device by performing the temperature analysis on Transfer characteristics, Drain characteristics and also on various performance metrics like ON-state current (ION), OFF-state current (IOFF), ION/IOFF, Trans-conductance (gm), Trans-conductance Generation Factor (TGF), Sub-threshold Swing (SS) to observe the applications towards harsh temperature environment.

Voluntary Running-Wheel Exercise Decreases the Threshold for Rewarding Intracranial Self-Stimulation

PubMed Central

Morris, Michael J.; Na, Elisa S.; Johnson, Alan Kim

2015-01-01

Physical exercise has mood-enhancing and antidepressant properties although the mechanisms underlying these effects are not known. The present experiment investigated the effects of prolonged access to a running wheel on electrical self-stimulation of the lateral hypothalamus (LHSS), a measure of hedonic state, in rats. Rats with continuous voluntary access to a running wheel for either 2 or 5 weeks exhibited dramatic leftward shifts in the effective current 50 (ECu50; current value that supports half of maximum responding) of their LHSS current-response functions compared to their baselines, indicating a decrease in reward threshold, whereas control rats current-response functions after 2 or 5 weeks were not significantly different from baseline. An inverse correlation existed between the change in ECu50 from baseline and the amount an animal had run in the day prior to LHSS testing, indicating that animals that exhibited higher levels of running showed a more robust decrease in LHSS threshold. We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties. PMID:22845707

Voluntary running-wheel exercise decreases the threshold for rewarding intracranial self-stimulation.

PubMed

Morris, Michael J; Na, Elisa S; Johnson, Alan Kim

2012-08-01

Physical exercise has mood-enhancing and antidepressant properties although the mechanisms underlying these effects are not known. The present experiment investigated the effects of prolonged access to a running wheel on electrical self-stimulation of the lateral hypothalamus (LHSS), a measure of hedonic state, in rats. Rats with continuous voluntary access to a running wheel for either 2 or 5 weeks exhibited dramatic leftward shifts in the effective current 50 (ECu50; current value that supports half of maximum responding) of their LHSS current-response functions compared to their baselines, indicating a decrease in reward threshold, whereas control rats current-response functions after 2 or 5 weeks were not significantly different from baseline. An inverse correlation existed between the change in ECu50 from baseline and the amount an animal had run in the day prior to LHSS testing, indicating that animals that exhibited higher levels of running showed a more robust decrease in LHSS threshold. We conclude that long-term voluntary exercise increases sensitivity to rewarding stimuli, which may contribute to its antidepressant properties.

Groundwater Quality Data for the Northern Sacramento Valley, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Bennett, Peter A.; Bennett, George L.; Belitz, Kenneth

2009-01-01

Groundwater quality in the approximately 1,180-square-mile Northern Sacramento Valley study unit (REDSAC) was investigated in October 2007 through January 2008 as part of the Priority Basin Project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Project was developed in response to the Groundwater Quality Monitoring Act of 2001, and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw groundwater used for public water supplies within REDSAC and to facilitate statistically consistent comparisons of groundwater quality throughout California. Samples were collected from 66 wells in Shasta and Tehama Counties. Forty-three of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and 23 were selected to aid in evaluation of specific water-quality issues (understanding wells). The groundwater samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOC], pesticides and pesticide degradates, and pharmaceutical compounds), constituents of special interest (perchlorate and N-nitrosodimethylamine [NDMA]), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial constituents. Naturally occurring isotopes (tritium, and carbon-14, and stable isotopes of nitrogen and oxygen in nitrate, stable isotopes of hydrogen and oxygen of water), and dissolved noble gases also were measured to help identify the sources and ages of the sampled ground water. In total, over 275 constituents and field water-quality indicators were investigated. Three types of quality-control samples (blanks, replicates, and sampmatrix spikes) were collected at approximately 8 to 11 percent of the wells, and the results for these samples were used to evaluate the quality of the data obtained from the groundwater samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the groundwater samples. Differences between replicate samples were within acceptable ranges for nearly all compounds, indicating acceptably low variability. Matrix-spike recoveries were within acceptable ranges for most compounds. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, raw groundwater typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw groundwater were compared with regulatory and nonregulatory health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and with aesthetic and technical thresholds established by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and do not indicate compliance or noncompliance with those thresholds. The concentrations of most constituents detected in groundwater samples from REDSAC were below drinking-water thresholds. Volatile organic compounds (VOC) and pesticides were detected in less than one-quarter of the samples and were generally less than a hundredth of any health-based thresholds. NDMA was detected in one grid well above the NL-CA. Concentrations of all nutrients and trace elements in samples from REDSAC wells were below the health-based thresholds except those of arsenic in three samples, which were above the USEPA maximum contaminant level (MCL-US). However

Lead exposure potentiates predatory attack behavior in the cat.

PubMed

Li, Wenjie; Han, Shenggao; Gregg, Thomas R; Kemp, Francis W; Davidow, Amy L; Louria, Donald B; Siegel, Allan; Bogden, John D

2003-07-01

Epidemiologic studies have demonstrated that environmental lead exposure is associated with aggressive behavior in children; however, numerous confounding variables limit the ability of these studies to establish a causal relationship. The study of aggressive behavior using a validated animal model was used to test the hypothesis that there is a causal relationship between lead exposure and aggression in the absence of confounding variables. We studied the effects of lead exposure on a feline model of aggression: predatory (quiet biting) attack of an anesthetized rat. Five cats were stimulated with a precisely controlled electrical current via electrodes inserted into the lateral hypothalamus. The response measure was the predatory attack threshold current (i.e., the current required to elicit an attack response on 50% of the trials). Blocks of trials were administered in which predatory attack threshold currents were measured three times a week for a total of 6-10 weeks, including before, during, and after lead exposure. Lead was incorporated into cat food "treats" at doses of 50-150 mg/kg/day. Two of the five cats received a second period of lead exposure. Blood lead concentrations were measured twice a week and were <1, 21-77, and <20 micro g/dL prior to, during, and after lead exposure, respectively. The predatory attack threshold decreased significantly during initial lead exposure in three of five cats and increased after the cessation of lead exposure in four of the five cats (P<0.01). The predatory attack thresholds and blood lead concentrations for each cat were inversely correlated (r=-0.35 to -0.74). A random-effects mixed model demonstrated a significant (P=0.0019) negative association between threshold current and blood lead concentration. The data of this study demonstrate that lead exposure enhances predatory aggression in the cat and provide experimental support for a causal relationship between lead exposure and aggressive behavior in humans.

Low-threshold field emission in planar cathodes with nanocarbon materials

NASA Astrophysics Data System (ADS)

Zhigalov, V.; Petukhov, V.; Emelianov, A.; Timoshenkov, V.; Chaplygin, Yu.; Pavlov, A.; Shamanaev, A.

2016-12-01

Nanocarbon materials are of great interest as field emission cathodes due to their low threshold voltage. In this work current-voltage characteristics of nanocarbon electrodes were studied. Low-threshold emission was found in planar samples where field enhancement is negligible (<10). Electron work function values, calculated by Fowler-Nordheim theory, are anomalous low (<1 eV) and come into collision with directly measured work function values in fabricated planar samples (4.1-4.4 eV). Non-applicability of Fowler-Nordheim theory for the nanocarbon materials was confirmed. The reasons of low-threshold emission in nanocarbon materials are discussed.

Higgs boson gluon-fusion production beyond threshold in N 3LO QCD

DOE PAGES

Anastasiou, Charalampos; Duhr, Claude; Dulat, Falko; ...

2015-03-18

In this study, we compute the gluon fusion Higgs boson cross-section at N 3LO through the second term in the threshold expansion. This calculation constitutes a major milestone towards the full N 3LO cross section. Our result has the best formal accuracy in the threshold expansion currently available, and includes contributions from collinear regions besides subleading corrections from soft and hard regions, as well as certain logarithmically enhanced contributions for general kinematics. We use our results to perform a critical appraisal of the validity of the threshold approximation at N 3LO in perturbative QCD.

Eccentric figure-eight coils for transcranial magnetic stimulation.

PubMed

Sekino, Masaki; Ohsaki, Hiroyuki; Takiyama, Yoshihiro; Yamamoto, Keita; Matsuzaki, Taiga; Yasumuro, Yoshihiro; Nishikawa, Atsushi; Maruo, Tomoyuki; Hosomi, Koichi; Saitoh, Youichi

2015-01-01

Previously we proposed an eccentric figure-eight coil that can cause threshold stimulation in the brain at lower driving currents. In this study, we performed numerical simulations and magnetic stimulations to healthy subjects for evaluating the advantages of the eccentric coil. The simulations were performed using a simplified spherical brain model and a realistic human brain model. We found that the eccentric coil required a driving current intensity of approximately 18% less than that required by the concentric coil to cause comparable eddy current densities within the brain. The eddy current localization of the eccentric coil was slightly higher than that of the concentric coil. A prototype eccentric coil was designed and fabricated. Instead of winding a wire around a bobbin, we cut eccentric-spiral slits on the insulator cases, and a wire was woven through the slits. The coils were used to deliver magnetic stimulation to healthy subjects; among our results, we found that the current slew rate corresponding to motor threshold values for the concentric and eccentric coils were 86 and 78 A/µs, respectively. The results indicate that the eccentric coil consistently requires a lower driving current to reach the motor threshold than the concentric coil. Future development of compact magnetic stimulators will enable the treatment of some intractable neurological diseases at home. © 2014 Wiley Periodicals, Inc.

Minimum Electric Field Exposure for Seizure Induction with Electroconvulsive Therapy and Magnetic Seizure Therapy.

PubMed

Lee, Won H; Lisanby, Sarah H; Laine, Andrew F; Peterchev, Angel V

2017-05-01

Lowering and individualizing the current amplitude in electroconvulsive therapy (ECT) has been proposed as a means to produce stimulation closer to the neural activation threshold and more focal seizure induction, which could potentially reduce cognitive side effects. However, the effect of current amplitude on the electric field (E-field) in the brain has not been previously linked to the current amplitude threshold for seizure induction. We coupled MRI-based E-field models with amplitude titrations of motor threshold (MT) and seizure threshold (ST) in four nonhuman primates (NHPs) to determine the strength, distribution, and focality of stimulation in the brain for four ECT electrode configurations (bilateral, bifrontal, right-unilateral, and frontomedial) and magnetic seizure therapy (MST) with cap coil on vertex. At the amplitude-titrated ST, the stimulated brain subvolume (23-63%) was significantly less than for conventional ECT with high, fixed current (94-99%). The focality of amplitude-titrated right-unilateral ECT (25%) was comparable to cap coil MST (23%), demonstrating that ECT with a low current amplitude and focal electrode placement can induce seizures with E-field as focal as MST, although these electrode and coil configurations affect differently specific brain regions. Individualizing the current amplitude reduced interindividual variation in the stimulation focality by 40-53% for ECT and 26% for MST, supporting amplitude individualization as a means of dosing especially for ECT. There was an overall significant correlation between the measured amplitude-titrated ST and the prediction of the E-field models, supporting a potential role of these models in dosing of ECT and MST. These findings may guide the development of seizure therapy dosing paradigms with improved risk/benefit ratio.

Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current

PubMed Central

1992-01-01

The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior. PMID:1279097

Management of metal-on-metal hip implant patients: Who, when and how to revise?

PubMed

Berber, Reshid; Skinner, John A; Hart, Alister J

2016-05-18

The debate on how best to manage patients with metal-on-metal (MOM) hip implants continues. With over 1 million patients affected worldwide, the impact is far reaching. The majority of the aggressive failures of MOM hip implants have been dealt with by revision hip surgery, leaving patients with a much more indolent pattern of failure of devices that have been in situ for more than 10 years. The longer-term outcome for such patients remains unknown, and much debate exists on how best to manage these patients. Regulatory guidance is available but remains open to interpretation due to the lack of current evidence and long-term studies. Metal ion thresholds for concern have been suggested at 7 ppb for hip resurfacing arthroplasty and below this level for large diameter total hip arthroplasties. Soft tissue changes including pseudotumours and muscle atrophy have been shown to progress, but this is not consistent. New advanced imaging techniques are helping to diagnose complications with metal hips and the reasons for failure, however these are not widely available. This has led to some centres to tackle difficult cases through multidisciplinary collaboration, for both surgical management decisions and also follow-up decisions. We summarise current evidence and consider who is at risk, when revision should be undertaken and how patients should be managed.

Management of metal-on-metal hip implant patients: Who, when and how to revise?

PubMed Central

Berber, Reshid; Skinner, John A; Hart, Alister J

2016-01-01

The debate on how best to manage patients with metal-on-metal (MOM) hip implants continues. With over 1 million patients affected worldwide, the impact is far reaching. The majority of the aggressive failures of MOM hip implants have been dealt with by revision hip surgery, leaving patients with a much more indolent pattern of failure of devices that have been in situ for more than 10 years. The longer-term outcome for such patients remains unknown, and much debate exists on how best to manage these patients. Regulatory guidance is available but remains open to interpretation due to the lack of current evidence and long-term studies. Metal ion thresholds for concern have been suggested at 7 ppb for hip resurfacing arthroplasty and below this level for large diameter total hip arthroplasties. Soft tissue changes including pseudotumours and muscle atrophy have been shown to progress, but this is not consistent. New advanced imaging techniques are helping to diagnose complications with metal hips and the reasons for failure, however these are not widely available. This has led to some centres to tackle difficult cases through multidisciplinary collaboration, for both surgical management decisions and also follow-up decisions. We summarise current evidence and consider who is at risk, when revision should be undertaken and how patients should be managed. PMID:27190754

Balancing lake ecological condition and agriculture irrigation needs in the Mississippi Alluvial Valley

USGS Publications Warehouse

Miranda, Leandro E.; Omer, A.R.; Killgore, K.J.

2017-01-01

The Mississippi Alluvial Valley includes hundreds of floodplain lakes that support unique fish assemblages and high biodiversity. Irrigation practices in the valley have lowered the water table, increasing the cost of pumping water, and necessitating the use of floodplain lakes as a source of water for irrigation. This development has prompted the need to regulate water withdrawals to protect aquatic resources, but it is unknown how much water can be withdrawn from lakes before ecological integrity is compromised. To estimate withdrawal limits, we examined descriptors of lake water quality (i.e., total nitrogen, total phosphorus, turbidity, Secchi visibility, chlorophyll-a) and fish assemblages (species richness, diversity, composition) relative to maximum depth in 59 floodplain lakes. Change-point regression analysis was applied to identify critical depths at which the relationships between depth and lake descriptors exhibited a rapid shift in slope, suggesting possible thresholds. All our water quality and fish assemblage descriptors showed rapid changes relative to depth near 1.2–2.0 m maximum depth. This threshold span may help inform regulatory decisions about water withdrawal limits. Alternatives to explain the triggers of the observed threshold span are considered.

Health hazards of ultrafine metal and metal oxide powders

NASA Technical Reports Server (NTRS)

Boylen, G. W., Jr.; Chamberlin, R. I.; Viles, F. J.

1969-01-01

Study reveals that suggested threshold limit values are from two to fifty times lower than current recommended threshold limit values. Proposed safe limits of exposure to the ultrafine dusts are based on known toxic potential of various materials as determined in particle size ranges.

Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements

PubMed Central

Tharakaraman, Kannan; Mariño-Ramírez, Leonardo; Sheetlin, Sergey L; Landsman, David; Spouge, John L

2006-01-01

Background Many DNA regulatory elements occur as multiple instances within a target promoter. Gibbs sampling programs for finding DNA regulatory elements de novo can be prohibitively slow in locating all instances of such an element in a sequence set. Results We describe an improvement to the A-GLAM computer program, which predicts regulatory elements within DNA sequences with Gibbs sampling. The improvement adds an optional "scanning step" after Gibbs sampling. Gibbs sampling produces a position specific scoring matrix (PSSM). The new scanning step resembles an iterative PSI-BLAST search based on the PSSM. First, it assigns an "individual score" to each subsequence of appropriate length within the input sequences using the initial PSSM. Second, it computes an E-value from each individual score, to assess the agreement between the corresponding subsequence and the PSSM. Third, it permits subsequences with E-values falling below a threshold to contribute to the underlying PSSM, which is then updated using the Bayesian calculus. A-GLAM iterates its scanning step to convergence, at which point no new subsequences contribute to the PSSM. After convergence, A-GLAM reports predicted regulatory elements within each sequence in order of increasing E-values, so users have a statistical evaluation of the predicted elements in a convenient presentation. Thus, although the Gibbs sampling step in A-GLAM finds at most one regulatory element per input sequence, the scanning step can now rapidly locate further instances of the element in each sequence. Conclusion Datasets from experiments determining the binding sites of transcription factors were used to evaluate the improvement to A-GLAM. Typically, the datasets included several sequences containing multiple instances of a regulatory motif. The improvements to A-GLAM permitted it to predict the multiple instances. PMID:16961919

Ultrasonically triggered ignition at liquid surfaces.

PubMed

Simon, Lars Hendrik; Meyer, Lennart; Wilkens, Volker; Beyer, Michael

2015-01-01

Ultrasound is considered to be an ignition source according to international standards, setting a threshold value of 1mW/mm(2) [1] which is based on theoretical estimations but which lacks experimental verification. Therefore, it is assumed that this threshold includes a large safety margin. At the same time, ultrasound is used in a variety of industrial applications where it can come into contact with explosive atmospheres. However, until now, no explosion accidents have been reported in connection with ultrasound, so it has been unclear if the current threshold value is reasonable. Within this paper, it is shown that focused ultrasound coupled into a liquid can in fact ignite explosive atmospheres if a specific target positioned at a liquid's surface converts the acoustic energy into a hot spot. Based on ignition tests, conditions could be derived that are necessary for an ultrasonically triggered explosion. These conditions show that the current threshold value can be significantly augmented. Copyright © 2014 Elsevier B.V. All rights reserved.

Improved Controller Design of Grid Friendly™ Appliances for Primary Frequency Response

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

Lian, Jianming; Sun, Yannan; Marinovici, Laurentiu D.

2015-09-01

The Grid Friendlymore » $$^\\textrm{TM}$$ Appliance~(GFA) controller, developed at Pacific Northwest National Laboratory, can autonomously switch off the appliances by detecting the under-frequency events. In this paper, the impacts of curtailing frequency threshold on the performance of frequency responsive GFAs are carefully analyzed first. The current method of selecting curtailing frequency thresholds for GFAs is found to be insufficient to guarantee the desired performance especially when the frequency deviation is shallow. In addition, the power reduction of online GFAs could be so excessive that it can even impact the system response negatively. As a remedy to the deficiency of the current controller design, a different way of selecting curtailing frequency thresholds is proposed to ensure the effectiveness of GFAs in frequency protection. Moreover, it is also proposed to introduce a supervisor at each distribution feeder to monitor the curtailing frequency thresholds of online GFAs and take corrective actions if necessary.« less

Specific features of a single-pulse sliding discharge in neon near the threshold for spark breakdown

NASA Astrophysics Data System (ADS)

Trusov, K. K.

2017-08-01

Experimental data on the spatial structure of a single-pulse sliding discharge in neon at voltages below, equal to, and above the threshold for spark breakdown are discussed. The experiments were carried at gas pressures of 30 and 100 kPa and different polarities of the discharge voltage. Photographs of the plasma structure in two discharge chambers with different dimensions of the discharge zone and different thicknesses of an alumina dielectric plate on the surface of which the discharge develops are inspected. Common features of the prebreakdown discharge and its specific features depending on the voltage polarity and gas pressure are analyzed. It is shown that, at voltages below the threshold for spark breakdown, a low-current glow discharge with cathode and anode spots develops in the electrode gap. Above the breakdown threshold, regardless of the voltage polarity, spark channels directed from the cathode to the anode develop against the background of a low-current discharge.

Clinical trials bureaucracy: unintended consequences of well-intentioned policy.

PubMed

Califf, Robert M

2006-01-01

As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects. Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems. We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies. Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians. The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.

Rational expectations, psychology and inductive learning via moving thresholds

NASA Astrophysics Data System (ADS)

Lamba, H.; Seaman, T.

2008-06-01

This paper modifies a previously introduced class of heterogeneous agent models in a way that allows for the inclusion of different types of agent motivations and behaviours in a consistent manner. The agents operate within a highly simplified environment where they are only able to be long or short one unit of the asset. The price of the asset is influenced by both an external information stream and the demand of the agents. The current strategy of each agent is defined by a pair of moving thresholds straddling the current price. When the price crosses either of the thresholds for a particular agent, that agent switches position and a new pair of thresholds is generated. The threshold dynamics can mimic different sources of investor motivation, running the gamut from purely rational information-processing, through rational (but often undesirable) behaviour induced by perverse incentives and moral hazards, to purely psychological effects. The simplest model of this kind precisely conforms to the Efficient Market Hypothesis (EMH) and this allows causal relationships to be established between actions at the agent level and violations of EMH price statistics at the global level. In particular, the effects of herding behaviour and perverse incentives are examined.

A novel gate and drain engineered charge plasma tunnel field-effect transistor for low sub-threshold swing and ambipolar nature

NASA Astrophysics Data System (ADS)

Yadav, Dharmendra Singh; Raad, Bhagwan Ram; Sharma, Dheeraj

2016-12-01

In this paper, we focus on the improvement of figures of merit for charge plasma based tunnel field-effect transistor (TFET) in terms of ON-state current, threshold voltage, sub-threshold swing, ambipolar nature, and gate to drain capacitance which provides better channel controlling of the device with improved high frequency response at ultra-low supply voltages. Regarding this, we simultaneously employ work function engineering on the drain and gate electrode of the charge plasma TFET. The use of gate work function engineering modulates the barrier on the source/channel interface leads to improvement in the ON-state current, threshold voltage, and sub-threshold swing. Apart from this, for the first time use of work function engineering on the drain electrode increases the tunneling barrier for the flow of holes on the drain/channel interface, it results into suppression of ambipolar behavior. The lowering of gate to drain capacitance therefore enhanced high frequency parameters. Whereas, the presence of dual work functionality at the gate electrode and over the drain region improves the overall performance of the charge plasma based TFET.

Robot gripper

NASA Technical Reports Server (NTRS)

Webb, Winston S. (Inventor)

1987-01-01

An electronic force-detecting robot gripper for gripping objects and attaching to an external robot arm is disclosed. The gripper comprises motor apparatus, gripper jaws, and electrical circuits for driving the gripper motor and sensing the amount of force applied by the jaws. The force applied by the jaws is proportional to a threshold value of the motor current. When the motor current exceeds the threshold value, the electrical circuits supply a feedback signal to the electrical control circuit which, in turn, stops the gripper motor.

Timing discriminator using leading-edge extrapolation

DOEpatents

Gottschalk, B.

1981-07-30

A discriminator circuit to recover timing information from slow-rising pulses by means of an output trailing edge, a fixed time after the starting corner of the input pulse, which is nearly independent of risetime and threshold setting is described. This apparatus comprises means for comparing pulses with a threshold voltage; a capacitor to be charged at a certain rate when the input signal is one-third threshold voltage, and at a lower rate when the input signal is two-thirds threshold voltage; current-generating means for charging the capacitor; means for comparing voltage capacitor with a bias voltage; a flip-flop to be set when the input pulse reaches threshold voltage and reset when capacitor voltage reaches the bias voltage; and a clamping means for discharging the capacitor when the input signal returns below one-third threshold voltage.

Regulatory Fit Improves Fitness for People With Low Exercise Experience.

PubMed

Kay, Sophie A; Grimm, Lisa R

2017-04-01

Considering only 20.8% of American adults meet current physical activity recommendations, it is important to examine the psychological processes that affect exercise motivation and behavior. Drawing from regulatory fit theory, this study examined how manipulating regulatory focus and reward structures would affect exercise performance, with a specific interest in investigating whether exercise experience would moderate regulatory fit effects. We predicted that regulatory fit effects would appear only for participants with low exercise experience. One hundred and sixty-five young adults completed strength training exercise tasks (i.e., sit-ups, squats, plank, and wall-sit) in regulatory match or mismatch conditions. Consistent with predictions, only participants low in experience in regulatory match conditions exercised more compared with those in regulatory mismatch conditions. Although this is the first study manipulating regulatory fit in a controlled setting to examine exercise behavior, findings suggest that generating regulatory fit could positively influence those low in exercise experience.

Current Regulations and Regulatory Actions

EPA Pesticide Factsheets

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

Online Self-Regulatory Learning Behaviors as a Mediator in the Relationship between Online Course Perceptions with Achievement

ERIC Educational Resources Information Center

Barnard, Lucy; Paton, Valerie; Lan, William

2008-01-01

Positive perceptions of online course communication and collaboration have been associated with better academic outcomes, while self-regulatory learning behaviors have also been linked to academic achievement and other positive learning outcomes. In the current study, we examined whether self-regulatory learning behaviors may be considered as…

Meta-Analysis of Single-Case Design Research on Self-Regulatory Interventions for Academic Performance

ERIC Educational Resources Information Center

Perry, Valerie; Albeg, Loren; Tung, Catherine

2012-01-01

The current study examined the effects of self-regulatory interventions on reading, writing, and math by conducting a meta-analysis of single-case design research. Self-regulatory interventions have promise as an effective approach that is both minimally invasive and involves minimal resources. Effects of the interventions were analyzed by…

Human Genome Editing in the Clinic: New Challenges in Regulatory Benefit-Risk Assessment.

PubMed

Abou-El-Enein, Mohamed; Cathomen, Toni; Ivics, Zoltán; June, Carl H; Renner, Matthias; Schneider, Christian K; Bauer, Gerhard

2017-10-05

As genome editing rapidly progresses toward the realization of its clinical promise, assessing the suitability of current tools and processes used for its benefit-risk assessment is critical. Although current regulations may initially provide an adequate regulatory framework, improvements are recommended to overcome several existing technology-based safety and efficacy issues. Copyright © 2017 Elsevier Inc. All rights reserved.

Application of Key Events and Analysis to Chemical Carcinogens and Noncarcinogens

EPA Science Inventory

The existence of thresholds for toxicants is a matter of debate in chemical rsk assessment and regulation. Current risk assessment methods are based on the assumption that, in the basense of sufficient data, carcinogenesis does not have a threshold, while non-carcinogenic endpoi...

Transistor biased amplifier minimizes diode discriminator threshold attenuation

NASA Technical Reports Server (NTRS)

Larsen, R. N.

1967-01-01

Transistor biased amplifier has a biased diode discriminator driven by a high impedance /several megohms/ current source, rather than a voltage source with several hundred ohms output impedance. This high impedance input arrangement makes the incremental impedance of the threshold diode negligible relative to the input impedance.

Final Rule: Extremely Hazardous Substance List and Threshold Planning Quantities; Emergency Planning and Release Notification Requirements (52 FR 13378)

EPA Pesticide Factsheets

April 22, 1987: This FR established the list of extremely hazardous substances (EHSs) and their threshold planning quantities (TPQs). Also codified reporting and notification requirements for facilities with EHS. Do not use for current compliance purposes.

78 FR 8054 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

..., dated March 5, 1990) has not been done as of August 31, 2004 (the effective date of AD 2004-15-07... A310 series airplanes. The existing AD currently requires repetitive inspections for fatigue cracking... fatigue threshold and inspection interval resulted in a determination that reduced inspection thresholds...

77 FR 7980 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-13

...The Regulatory Agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The Agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this Agenda.

75 FR 79811 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

...The regulatory agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this agenda.

75 FR 21839 - Department Regulatory Agenda; Semiannual Summary

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-26

...The regulatory agenda is a semiannual summary of all current and projected rulemakings, reviews of existing regulations, and completed actions of the Department. The agenda provides the public with information about the Department of Transportation's regulatory activity. It is expected that this information will enable the public to be more aware of and allow it to more effectively participate in the Department's regulatory activity. The public is also invited to submit comments on any aspect of this agenda.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

NASA Technical Reports Server (NTRS)

Ebert, Douglas; Macias, Brandon; Sargsyan, Ashot; Garcia, Kathleen; Stenger, Michael; Hargens, Alan; Johnston, Smith; Kemp, David; Danielson, Richard

2017-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs and lower body negative pressure (LBNP) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

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

PubMed

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

2016-10-01

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

Compact universal logic gates realized using quantization of current in nanodevices.

PubMed

Zhang, Wancheng; Wu, Nan-Jian; Yang, Fuhua

2007-12-12

This paper proposes novel universal logic gates using the current quantization characteristics of nanodevices. In nanodevices like the electron waveguide (EW) and single-electron (SE) turnstile, the channel current is a staircase quantized function of its control voltage. We use this unique characteristic to compactly realize Boolean functions. First we present the concept of the periodic-threshold threshold logic gate (PTTG), and we build a compact PTTG using EW and SE turnstiles. We show that an arbitrary three-input Boolean function can be realized with a single PTTG, and an arbitrary four-input Boolean function can be realized by using two PTTGs. We then use one PTTG to build a universal programmable two-input logic gate which can be used to realize all two-input Boolean functions. We also build a programmable three-input logic gate by using one PTTG. Compared with linear threshold logic gates, with the PTTG one can build digital circuits more compactly. The proposed PTTGs are promising for future smart nanoscale digital system use.

Phenytoin preferentially inhibits L-type calcium currents in whole-cell patch-clamped cardiac and skeletal muscle cells.

PubMed

Rivet, M; Bois, P; Cognard, C; Raymond, G

1990-10-01

The effect of the anticonvulsant diphenylhydantoin (phenytoin) was tested on the inward calcium currents of whole-cell patch-clamped cells from rat and human muscles and from frog atrium. A concentration of 10 microM phenytoin was required to obtain a threshold inhibitory effect and, even with high concentrations (100 microM), the inhibition was not complete. In skeletal muscle (rat and human cells in culture), phenytoin (30 microM) exerted a more potent effect on the high-threshold calcium current (ICa,L inhibition: 53 +/- 6% mean +/- SDn-1) rather than on the low-threshold one (ICa,T inhibition: 16 +/- 10%). Similar results were obtained on dissociated frog atrial cells. These data are to be contrasted with those previously reported on neuronal cells, where specific inhibition of ICa,T was reported. Thus, the action of phenytoin appears to be different in muscle and nerve so that phenytoin does not appear to be a specific inhibitor of ICa,T.

Study protocol of hypoalgesic effects of low frequency and burst-modulated alternating currents on healthy individuals.

PubMed

Rampazo da Silva, Érika Patrícia; da Silva, Viviane Ribeiro; Bernardes, Anabelly Sato; Matuzawa, Fabio Massao; Liebano, Richard Eloin

2018-03-01

The aim of the study will be to compare different types of analgesic electrical currents in relation to the pressure pain threshold and sensory comfort in healthy individuals. A total of 100 individuals will be randomly assigned to four groups: transcutaneous electrical nerve stimulation, interferential current, Aussie current or placebo. The electrical stimulation will be administered with a strong level for 30 min and to the placebo group, the electrodes will be positioned while the equipment will remain switched off. The pressure pain threshold and sensory comfort will be measured with an algometer and the visual analogue scale, respectively. The level of significance will be p < 0.05. NCT01950728 (clinical trials).

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Environmental Impacts on Spiking Properties in Hodgkin-Huxley Neuron with Direct Current Stimulus

NASA Astrophysics Data System (ADS)

Yuan, Chang-Qing; Zhao, Tong-Jun; Zhan, Yong; Zhang, Su-Hua; Liu, Hui; Zhang, Yu-Hong

2009-11-01

Based on the well accepted Hodgkin-Huxley neuron model, the neuronal intrinsic excitability is studied when the neuron is subject to varying environmental temperatures, the typical impact for its regulating ways. With computer simulation, it is found that altering environmental temperature can improve or inhibit the neuronal intrinsic excitability so as to influence the neuronal spiking properties. The impacts from environmental factors can be understood that the neuronal spiking threshold is essentially influenced by the fluctuations in the environment. With the environmental temperature varying, burst spiking is realized for the neuronal membrane voltage because of the environment-dependent spiking threshold. This burst induced by changes in spiking threshold is different from that excited by input currents or other stimulus.

Feedback from the European Bioanalysis Forum: focus workshop on current analysis of immunogenicity: best practices and regulatory hurdles.

PubMed

Goodman, Joanne; Cowen, Simon; Devanarayan, Viswanath; Egging, David; Emrich, Thomas; Golob, Michaela; Kramer, Daniel; McNally, Jim; Munday, James; Nelson, Robert; Pedras-Vasconcelos, João A; Piironen, Timo; Sickert, Denise; Skibeli, Venke; Fjording, Marianne Scheel; Timmerman, Philip

2018-02-01

European Bioanalysis Forum Workshop, Lisbon, Portugal, September 2016: At the recent European Bioanalysis Forum Focus Workshop, 'current analysis of immunogenicity: best practices and regulatory hurdles', several important challenges facing the bioanalytical community in relation to immunogenicity assays were discussed through a mixture of presentations and panel sessions. The main areas of focus were the evolving regulatory landscape, challenges of assay interferences from either drug or target, cut-point setting and whether alternative assays can be used to replace neutralizing antibody assays. This workshop report captures discussions and potential solutions and/or recommendations made by the speakers and delegates.

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.

GIS-assisted spatial analysis for urban regulatory detailed planning: designer's dimension in the Chinese code system

NASA Astrophysics Data System (ADS)

Yu, Yang; Zeng, Zheng

2009-10-01

By discussing the causes behind the high amendments ratio in the implementation of urban regulatory detailed plans in China despite its law-ensured status, the study aims to reconcile conflict between the legal authority of regulatory detailed planning and the insufficient scientific support in its decision-making and compilation by introducing into the process spatial analysis based on GIS technology and 3D modeling thus present a more scientific and flexible approach to regulatory detailed planning in China. The study first points out that the current compilation process of urban regulatory detailed plan in China employs mainly an empirical approach which renders it constantly subjected to amendments; the study then discusses the need and current utilization of GIS in the Chinese system and proposes the framework of a GIS-assisted 3D spatial analysis process from the designer's perspective which can be regarded as an alternating processes between the descriptive codes and physical design in the compilation of regulatory detailed planning. With a case study of the processes and results from the application of the framework, the paper concludes that the proposed framework can be an effective instrument which provides more rationality, flexibility and thus more efficiency to the compilation and decision-making process of urban regulatory detailed plan in China.

Model for Predicting Passage of Invasive Fish Species Through Culverts

NASA Astrophysics Data System (ADS)

Neary, V.

2010-12-01

Conservation efforts to promote or inhibit fish passage include the application of simple fish passage models to determine whether an open channel flow allows passage of a given fish species. Derivations of simple fish passage models for uniform and nonuniform flow conditions are presented. For uniform flow conditions, a model equation is developed that predicts the mean-current velocity threshold in a fishway, or velocity barrier, which causes exhaustion at a given maximum distance of ascent. The derivation of a simple expression for this exhaustion-threshold (ET) passage model is presented using kinematic principles coupled with fatigue curves for threatened and endangered fish species. Mean current velocities at or above the threshold predict failure to pass. Mean current velocities below the threshold predict successful passage. The model is therefore intuitive and easily applied to predict passage or exclusion. The ET model’s simplicity comes with limitations, however, including its application only to uniform flow, which is rarely found in the field. This limitation is addressed by deriving a model that accounts for nonuniform conditions, including backwater profiles and drawdown curves. Comparison of these models with experimental data from volitional swimming studies of fish indicates reasonable performance, but limitations are still present due to the difficulty in predicting fish behavior and passage strategies that can vary among individuals and different fish species.

Ground-Water Quality Data in the Santa Clara River Valley Study Unit, 2007: Results from the California GAMA Program

USGS Publications Warehouse

Montrella, Joseph; Belitz, Kenneth

2009-01-01

Ground-water quality in the approximately 460-square-mile Santa Clara River Valley study unit (SCRV) was investigated from April to June 2007 as part of the statewide Priority Basin project of the Ground-Water Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The study was designed to provide a spatially unbiased assessment of the quality of raw ground water used for public water supplies within SCRV, and to facilitate a statistically consistent basis for comparing water quality throughout California. Fifty-seven ground-water samples were collected from 53 wells in Ventura and Los Angeles Counties. Forty-two wells were selected using a randomized grid-based method to provide statistical representation of the study area (grid wells). Eleven wells (understanding wells) were selected to further evaluate water chemistry in particular parts of the study area, and four depth-dependent ground-water samples were collected from one of the eleven understanding wells to help understand the relation between water chemistry and depth. The ground-water samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOC], pesticides and pesticide degradates, potential wastewater-indicator compounds, and pharmaceutical compounds), a constituent of special interest (perchlorate), naturally occurring inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial constituents. Naturally occurring isotopes (tritium, carbon-13, carbon-14 [abundance], stable isotopes of hydrogen and oxygen in water, stable isotopes of nitrogen and oxygen in nitrate, chlorine-37, and bromine-81), and dissolved noble gases also were measured to help identify the source and age of the sampled ground water. Quality-control samples (blanks or replicates, or samples for matrix spikes) were collected from approximately 26 percent of the wells, and the analyses of these samples were used to evaluate the quality of the data for the ground-water samples. Assessment of the quality-control results showed that the quality of the environmental data was good, with low bias and low variability, and as a result, less than 0.1 percent of the analytes detected in ground-water samples were censored. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, and (or) blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is delivered (or, supplied) to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with regulatory and non-regulatory thresholds established by the U.S. Environmental Protection Agency (USEPA) and the California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Most constituents that were detected in ground-water samples were reported at concentrations below their established health-based thresholds. VOCs, pesticides and pesticide degradates, and potential wastewater-indicator compounds were detected in about 33 percent or less of the 42 SCRV grid wells. Concentrations of all detected organic constituents were below established health-based thresholds. Perchlorate was detected in approximately 12 percent of the SCRV grid wells; all concentrations reported were below the NL-CA threshold. Additional constituents, including major ions, trace elements, and nutrients were collected at 26 wells (16 grid wells and 10 understanding wells) of the 53 wells sampled f

BeZnCdSe quantum-well ridge-waveguide laser diodes under low threshold room-temperature continuous-wave operation

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

Feng, Jijun; Electronics and Photonics Research Institute, National Institute of Advanced Industrial Science and Technology; Akimoto, Ryoichi, E-mail: r-akimoto@aist.go.jp

2015-10-19

Low threshold current ridge-waveguide BeZnCdSe quantum-well laser diodes (LDs) have been developed by completely etching away the top p-type BeMgZnSe/ZnSe:N short-period superlattice cladding layer, which can suppress the leakage current that flows laterally outside of the electrode. The waveguide LDs are covered with a thick SiO{sub 2} layer and planarized with chemical-mechanical polishing and a reactive ion etching process. Room-temperature lasing under continuous-wave condition is achieved with the laser cavity formed by the cleaved waveguide facets coated with high-reflectivity dielectric films. For a 4 μm-wide green LD lasing around a wavelength of 535 nm, threshold current and voltage of 7.07 mA and 7.89 Vmore » are achieved for a cavity length of 300 μm, and the internal differential quantum efficiency, internal absorption loss, gain constant, and nominal transparency current density are estimated to be 27%, 4.09 cm{sup −1}, 29.92 (cm × μm)/kA and 6.35 kA/(cm{sup 2 }× μm), respectively. This compact device can realize a significantly improved performance with much lower threshold power consumption, which would benefit the potential application for ZnSe-based green LDs as light sources in full-color display and projector devices installed in consumer products such as pocket projectors.« less

Novel GM animal technologies and their governance.

PubMed

Bruce, Ann; Castle, David; Gibbs, Corrina; Tait, Joyce; Whitelaw, C Bruce A

2013-08-01

Scientific advances in methods of producing genetically modified (GM) animals continue, yet few such animals have reached commercial production. Existing regulations designed for early techniques of genetic modification pose formidable barriers to commercial applications. Radically improved techniques for producing GM animals invite a re-examination of current regulatory regimes. We critically examine current GM animal regulations, with a particular focus on the European Union, through a framework that recognises the importance of interactions among regulatory regimes, innovation outcomes and industry sectors. The current focus on the regulation of risk is necessary but is unable to discriminate among applications and tends to close down broad areas of application rather than facilitate innovation and positive industry interactions. Furthermore, the fields of innovative animal biosciences appear to lack networks of organisations with co-ordinated future oriented actions. Such networks could drive coherent programmes of innovation towards particular visions and contribute actively to the development of regulatory systems for GM animals. The analysis presented makes the case for regulatory consideration of each animal bioscience related innovation on the basis of the nature of the product itself and not the process by which it was developed.

Speech Recognition Thresholds for Multilingual Populations.

ERIC Educational Resources Information Center

Ramkissoon, Ishara

2001-01-01

This article traces the development of speech audiometry in the United States and reports on the current status, focusing on the needs of a multilingual population in terms of measuring speech recognition threshold (SRT). It also discusses sociolinguistic considerations, alternative SRT stimuli for second language learners, and research on using…

Handwriting Automaticity: The Search for Performance Thresholds

ERIC Educational Resources Information Center

Medwell, Jane; Wray, David

2014-01-01

Evidence is accumulating that handwriting has an important role in written composition. In particular, handwriting automaticity appears to relate to success in composition. This relationship has been little explored in British contexts and we currently have little idea of what threshold performance levels might be. In this paper, we report on two…

On the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith

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

Calabrese, Edward J., E-mail: edwardc@schoolph.umass.edu

This paper is an historical assessment of how prominent radiation geneticists in the United States during the 1940s and 1950s successfully worked to build acceptance for the linear no-threshold (LNT) dose–response model in risk assessment, significantly impacting environmental, occupational and medical exposure standards and practices to the present time. Detailed documentation indicates that actions taken in support of this policy revolution were ideologically driven and deliberately and deceptively misleading; that scientific records were artfully misrepresented; and that people and organizations in positions of public trust failed to perform the duties expected of them. Key activities are described and the rolesmore » of specific individuals are documented. These actions culminated in a 1956 report by a Genetics Panel of the U.S. National Academy of Sciences (NAS) on Biological Effects of Atomic Radiation (BEAR). In this report the Genetics Panel recommended that a linear dose response model be adopted for the purpose of risk assessment, a recommendation that was rapidly and widely promulgated. The paper argues that current international cancer risk assessment policies are based on fraudulent actions of the U.S. NAS BEAR I Committee, Genetics Panel and on the uncritical, unquestioning and blind-faith acceptance by regulatory agencies and the scientific community. - Highlights: • The 1956 recommendation of the US NAS to use the LNT for risk assessment was adopted worldwide. • This recommendation is based on a falsification of the research record and represents scientific misconduct. • The record misrepresented the magnitude of panelist disagreement of genetic risk from radiation. • These actions enhanced public acceptance of their risk assessment policy recommendations.« less

Hazardous waste status of discarded electronic cigarettes

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

Krause, Max J.; Townsend, Timothy G., E-mail: ttown@ufl.edu

Highlights: • Electronic cigarettes were tested using TCLP and WET. • Several electronic cigarette products leached lead at hazardous waste levels. • Lead was the only element that exceeded hazardous waste concentration thresholds. • Nicotine solution may cause hazardous waste classification when discarded unused. - Abstract: The potential for disposable electronic cigarettes (e-cigarettes) to be classified as hazardous waste was investigated. The Toxicity Characteristic Leaching Procedure (TCLP) was performed on 23 disposable e-cigarettes in a preliminary survey of metal leaching. Based on these results, four e-cigarette products were selected for replicate analysis by TCLP and the California Waste Extraction Testmore » (WET). Lead was measured in leachate as high as 50 mg/L by WET and 40 mg/L by TCLP. Regulatory thresholds were exceeded by two of 15 products tested in total. Therefore, some e-cigarettes would be toxicity characteristic (TC) hazardous waste but a majority would not. When disposed in the unused form, e-cigarettes containing nicotine juice would be commercial chemical products (CCP) and would, in the United States (US), be considered a listed hazardous waste (P075). While household waste is exempt from hazardous waste regulation, there are many instances in which such waste would be subject to regulation. Manufactures and retailers with unused or expired e-cigarettes or nicotine juice solution would be required to manage these as hazardous waste upon disposal. Current regulations and policies regarding the availability of nicotine-containing e-cigarettes worldwide were reviewed. Despite their small size, disposable e-cigarettes are consumed and discarded much more quickly than typical electronics, which may become a growing concern for waste managers.« less

Comparison of two insulin assays for first-phase insulin release in type 1 diabetes prediction and prevention studies.

PubMed

Mahon, Jeffrey L; Beam, Craig A; Marcovina, Santica M; Boulware, David C; Palmer, Jerry P; Winter, William E; Skyler, Jay S; Krischer, Jeffrey P

2011-11-20

Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace the less practical but current standard of a radioimmunoassay (RIA) for FPIR. One hundred thirty-three islet autoantibody positive relatives of persons with type 1 diabetes underwent 161 IVGTTs. Insulin concentrations were measured by both assays in 1056 paired samples. A rule classifying FPIR (below-threshold, above-threshold, uncertain) by the IEMA was derived and validated against FPIR by the RIA. The insulin IEMA-based rule accurately classified below- and above-threshold FPIRs by the RIA in 110/161 (68%) IVGTTs, but was uncertain in 51/161 (32%) tests for which FPIR by RIA is needed. An uncertain FPIR by the IEMA was more likely among below-threshold vs above-threshold FPIRs by the RIA (64% [30/47] vs. 18% [21/114], respectively; p<0.05). An insulin IEMA for FPIR in subjects at risk for type 1 diabetes accurately determined below- and above-threshold FPIRs in 2/3 of tests relative to the current standard of the insulin RIA, but could not reliably classify the remaining FPIRs. TrialNet is limiting the insulin RIA for FPIR to the latter given the practical advantages of the more specific IEMA. Copyright © 2011 Elsevier B.V. All rights reserved.

Gender, genetic risk, and criminal behavior.

PubMed

Vaske, Jamie; Wright, John Paul; Boisvert, Danielle; Beaver, Kevin Michael

2011-02-28

The threshold hypothesis asserts that the prevalence of offending is lower among females because females have a higher threshold for risk than males. As a result, females who do offend should exhibit greater concentrations of genetic and environmental risk than male offenders. In light of these statements, the current study examines the role of genetic factors in the etiology of female offending using data from the National Longitudinal Study of Adolescent Health. The results reveal that the genetic risk threshold is higher for females than for males. However, contrary to the threshold hypothesis, female offenders exhibit fewer genetic risks than male offenders. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia.

PubMed

Gogarty, B

2003-04-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001.

Land Development and Subdivision Regulations that Support Access Management

DOT National Transportation Integrated Search

1993-01-01

This report examines the role of the comprehensive plan in developing an access : management program, aspects of current regulatory practice that contribute to : access problems, and regulatory techniques that support access management : principles. ...

Robustness in Regulatory Interaction Networks. A Generic Approach with Applications at Different Levels: Physiologic, Metabolic and Genetic

PubMed Central

Demongeot, Jacques; Ben Amor, Hedi; Elena, Adrien; Gillois, Pierre; Noual, Mathilde; Sené, Sylvain

2009-01-01

Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control. PMID:20057955

Beauty and charm production in fixed target experiments

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

Kidonakis, Nikolaos; Vogt, Ramona

We present calculations of NNLO threshold corrections for beauty and charm production in {pi}{sup -} p and pp interactions at fixed-target experiments. Recent calculations for heavy quark hadroproduction have included next-to-next-to-leading-order (NNLO) soft-gluon corrections [1] to the double differential cross section from threshold resummation techniques [2]. These corrections are important for near-threshold beauty and charm production at fixed-target experiments, including HERA-B and some of the current and future heavy ion experiments.

Severe wind gust thresholds for Meteoalarm derived from uniform return periods in ECA&D

NASA Astrophysics Data System (ADS)

Stepek, A.; Wijnant, I. L.; van der Schrier, G.; van den Besselaar, E. J. M.; Klein Tank, A. M. G.

2012-06-01

In this study we present an alternative wind gust warning guideline for Meteoalarm, the severe weather warning website for Europe. There are unrealistically large differences in levels and issuing frequencies of all warning levels currently in use between neighbouring Meteoalarm countries. This study provides a guide for the Meteoalarm community to review their wind gust warning thresholds. A more uniform warning system is achieved by using one pan-European return period per warning level. The associated return values will be different throughout Europe because they depend on local climate conditions, but they will not change abruptly at country borders as is currently the case for the thresholds. As return values are a measure of the possible danger of an event and its impact on society, they form an ideal basis for a warning system. Validated wind gust measurements from the European Climate Assessment and Dataset (ECA&D, http://www.ecad.eu) were used to calculate return values of the annual maximum wind gust. The current thresholds are compared with return values for 3 different return periods: 10 times a year return periods for yellow warnings, 2 yr periods for orange and 5 yr periods for red warnings. So far 10 countries provide wind gust data to ECA&D. Due to the ECA&D completeness requirements and the fact that some countries provided too few stations to be representative for that country, medians of the return values of annual maximum wind gust could be calculated for 6 of the 10 countries. Alternative guideline thresholds are presented for Norway, Ireland, The Netherlands, Germany, the Czech Republic and Spain and the need to distinguish between coastal, inland and mountainous regions is demonstrated. The new thresholds based on uniform return periods differ significantly from the current ones, particularly for coastal and mountainous areas. We are aware of other, sometimes binding factors (e.g. laws) that prevent participating counties from implementing this climatology based warning system.

Pro-oxidant Induced DNA Damage in Human Lymphoblastoid Cells: Homeostatic Mechanisms of Genotoxic Tolerance

PubMed Central

Seager, Anna L.

2012-01-01

Oxidative stress contributes to many disease etiologies including ageing, neurodegeneration, and cancer, partly through DNA damage induction (genotoxicity). Understanding the i nteractions of free radicals with DNA is fundamental to discern mutation risks. In genetic toxicology, regulatory authorities consider that most genotoxins exhibit a linear relationship between dose and mutagenic response. Yet, homeostatic mechanisms, including DNA repair, that allow cells to tolerate low levels of genotoxic exposure exist. Acceptance of thresholds for genotoxicity has widespread consequences in terms of understanding cancer risk and regulating human exposure to chemicals/drugs. Three pro-oxidant chemicals, hydrogen peroxide (H2O2), potassium bromate (KBrO3), and menadione, were examined for low dose-response curves in human lymphoblastoid cells. DNA repair and antioxidant capacity were assessed as possible threshold mechanisms. H2O2 and KBrO3, but not menadione, exhibited thresholded responses, containing a range of nongenotoxic low doses. Levels of the DNA glycosylase 8-oxoguanine glycosylase were unchanged in response to pro- oxidant stress. DNA repair–focused gene expression arrays reported changes in ATM and BRCA1, involved in double-strand break repair, in response to low-dose pro-oxidant exposure; however, these alterations were not substantiated at the protein level. Determination of oxidatively induced DNA damage in H2O2-treated AHH-1 cells reported accumulation of thymine glycol above the genotoxic threshold. Further, the H2O2 dose-response curve was shifted by modulating the antioxidant glutathione. Hence, observed pro- oxidant thresholds were due to protective capacities of base excision repair enzymes and antioxidants against DNA damage, highlighting the importance of homeostatic mechanisms in “genotoxic tolerance.” PMID:22539617

Hierarchical Approach to 'Atomistic' 3-D MOSFET Simulation

NASA Technical Reports Server (NTRS)

Asenov, Asen; Brown, Andrew R.; Davies, John H.; Saini, Subhash

1999-01-01

We present a hierarchical approach to the 'atomistic' simulation of aggressively scaled sub-0.1 micron MOSFET's. These devices are so small that their characteristics depend on the precise location of dopant atoms within them, not just on their average density. A full-scale three-dimensional drift-diffusion atomistic simulation approach is first described and used to verify more economical, but restricted, options. To reduce processor time and memory requirements at high drain voltage, we have developed a self-consistent option based on a solution of the current continuity equation restricted to a thin slab of the channel. This is coupled to the solution of the Poisson equation in the whole simulation domain in the Gummel iteration cycles. The accuracy of this approach is investigated in comparison to the full self-consistent solution. At low drain voltage, a single solution of the nonlinear Poisson equation is sufficient to extract the current with satisfactory accuracy. In this case, the current is calculated by solving the current continuity equation in a drift approximation only, also in a thin slab containing the MOSFET channel. The regions of applicability for the different components of this hierarchical approach are illustrated in example simulations covering the random dopant-induced threshold voltage fluctuations, threshold voltage lowering, threshold voltage asymmetry, and drain current fluctuations.

Contraction produced by intracellular injection of calcium, strontium, and barium in the single crayfish muscle fibers.

PubMed

Matsumura, M; Mashima, H

1976-01-01

Ca ions were ionophoretically injected through an intracellular microelectrode into the single muscle fiber of a crayfish, and the resulting contraction sphere was observed under a microscope and photographed with a movie camera. The minimum contraction produced by the threshold current involved usually three or four, sometimes two, sarcomers on both sides of the injecting pipette but contraction involving only one sarcomere was not observered. The rheobase of the Ca-injecting current was 3.2 X 10(-9) A. The strength-duration curves were determined for Ca-, Sr-, and Ba-injecting currents; all fitted a similar hyperbolic equation. The threshold amount of Ca above rheobasic injection was 2.1 X 10(-15)mol, and the ratios between threshold amounts were Ca: Sr: Ba=1: 1.9: 3.0. The effects of Ca and Sr were additive for the contraction. More current was required for the Ca-injection to produce the contraction in the K-depolarized-or 15mM-procaine-treated muscle, although less current was sufficient for the muscle treated with 0.5-1.0 mM of caffeine. The participation of the Ca-induced Ca release mechanism in the contraction produced by Ca injection and the role of Sr or Ba as a substitute for Ca were discussed.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis.

PubMed

Lowry, Kathryn P; Gazelle, G Scott; Gilmore, Michael E; Johanson, Colden; Munshi, Vidit; Choi, Sung Eun; Tramontano, Angela C; Kong, Chung Yin; McMahon, Pamela M

2015-05-15

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30-pack-year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack-year thresholds. We used a previously validated simulation model to compare the health benefits of lung cancer screening in current and former smokers ages 55-80 with ≥30 pack-years with hypothetical programs using lower pack-year thresholds for individuals with COPD (≥20, ≥10, and ≥1 pack-years). Calibration targets for COPD prevalence and associated lung cancer risk were derived using the Framingham Offspring Study limited data set. We performed sensitivity analyses to evaluate the stability of results across different rates of adherence to screening, increased competing mortality risk from COPD, and increased surgical ineligibility in individuals with COPD. The primary outcome was projected life expectancy. Programs using lower pack-year thresholds for individuals with COPD yielded the highest life expectancy gains for a given number of screens. Highest life expectancy was achieved when lowering the pack-year threshold to ≥1 pack-year for individuals with COPD, which dominated all other screening strategies. These results were stable across different adherence rates to screening and increases in competing mortality risk for COPD and surgical ineligibility. Current and former smokers with COPD may disproportionately benefit from lung cancer screening. A lower pack-year threshold for screening eligibility may benefit this high-risk patient population. © 2015 American Cancer Society.

Measurement of weak electric currents in copper wire phantoms using MRI: influence of susceptibility enhancement.

PubMed

Huang, Ruiwang; Posnansky, Oleg; Celik, Abdullah; Oros-Peusquens, Ana-Maria; Ermer, Veronika; Irkens, Marco; Wegener, H-Peter; Shah, N Jon

2006-08-01

The use of magnetic resonance imaging (MRI)-based methods for the direct detection of neuronal currents is a topic of intense investigation. Much experimental work has been carried out with the express aim of establishing detection thresholds and sensitivity to flowing currents. However, in most of these experiments, magnetic susceptibility enhancement was ignored. In this work, we present results that show the influence of a susceptibility artefact on the detection threshold and sensitivity. For this purpose, a novel phantom, consisting of a water-filled cylinder with two wires of different materials connected in series, was constructed. Magnitude MR images were acquired from a single slice using a gradient-echo echo planar imaging (EPI) sequence. The data show that the time course of the detected MR signal magnitude correlates very well with the waveform of the input current. The effect of the susceptibility artefacts arising from the two different wires was examined by comparing the magnitudes of the MR signals at different voxel locations. Our results indicate the following: (1) MR signal enhancement arising from the magnetic susceptibility effect influences the detection sensitivity of weak current; (2) the detection threshold and sensitivity are phantom-wire dependent; (3) sub-mu A electric current detection in a phantom is possible on a 1.5-T MR scanner in the presence of susceptibility enhancement.

Non-equilibrium Green's functions study of discrete dopants variability on an ultra-scaled FinFET

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

Valin, R., E-mail: r.valinferreiro@swansea.ac.uk; Martinez, A., E-mail: a.e.Martinez@swansea.ac.uk; Barker, J. R., E-mail: john.barker@glasgow.ac.uk

In this paper, we study the effect of random discrete dopants on the performance of a 6.6 nm channel length silicon FinFET. The discrete dopants have been distributed randomly in the source/drain region of the device. Due to the small dimensions of the FinFET, a quantum transport formalism based on the non-equilibrium Green's functions has been deployed. The transfer characteristics for several devices that differ in location and number of dopants have been calculated. Our results demonstrate that discrete dopants modify the effective channel length and the height of the source/drain barrier, consequently changing the channel control of the charge. Thismore » effect becomes more significant at high drain bias. As a consequence, there is a strong effect on the variability of the on-current, off-current, sub-threshold slope, and threshold voltage. Finally, we have also calculated the mean and standard deviation of these parameters to quantify their variability. The obtained results show that the variability at high drain bias is 1.75 larger than at low drain bias. However, the variability of the on-current, off-current, and sub-threshold slope remains independent of the drain bias. In addition, we have found that a large source to drain current by tunnelling current occurs at low gate bias.« less

In search of functional association from time-series microarray data based on the change trend and level of gene expression

PubMed Central

He, Feng; Zeng, An-Ping

2006-01-01

Background The increasing availability of time-series expression data opens up new possibilities to study functional linkages of genes. Present methods used to infer functional linkages between genes from expression data are mainly based on a point-to-point comparison. Change trends between consecutive time points in time-series data have been so far not well explored. Results In this work we present a new method based on extracting main features of the change trend and level of gene expression between consecutive time points. The method, termed as trend correlation (TC), includes two major steps: 1, calculating a maximal local alignment of change trend score by dynamic programming and a change trend correlation coefficient between the maximal matched change levels of each gene pair; 2, inferring relationships of gene pairs based on two statistical extraction procedures. The new method considers time shifts and inverted relationships in a similar way as the local clustering (LC) method but the latter is merely based on a point-to-point comparison. The TC method is demonstrated with data from yeast cell cycle and compared with the LC method and the widely used Pearson correlation coefficient (PCC) based clustering method. The biological significance of the gene pairs is examined with several large-scale yeast databases. Although the TC method predicts an overall lower number of gene pairs than the other two methods at a same p-value threshold, the additional number of gene pairs inferred by the TC method is considerable: e.g. 20.5% compared with the LC method and 49.6% with the PCC method for a p-value threshold of 2.7E-3. Moreover, the percentage of the inferred gene pairs consistent with databases by our method is generally higher than the LC method and similar to the PCC method. A significant number of the gene pairs only inferred by the TC method are process-identity or function-similarity pairs or have well-documented biological interactions, including 443 known protein interactions and some known cell cycle related regulatory interactions. It should be emphasized that the overlapping of gene pairs detected by the three methods is normally not very high, indicating a necessity of combining the different methods in search of functional association of genes from time-series data. For a p-value threshold of 1E-5 the percentage of process-identity and function-similarity gene pairs among the shared part of the three methods reaches 60.2% and 55.6% respectively, building a good basis for further experimental and functional study. Furthermore, the combined use of methods is important to infer more complete regulatory circuits and network as exemplified in this study. Conclusion The TC method can significantly augment the current major methods to infer functional linkages and biological network and is well suitable for exploring temporal relationships of gene expression in time-series data. PMID:16478547

The effect of sertraline and 8-OH-DPAT on the PTZ_induced seizure threshold: Role of the nitrergic system.

PubMed

Heydari, Azhdar; Davoudi, Shima

2017-02-01

Serotonin is a key regulatory neurotransmitter in the CNS which plays an important role in seizure through different receptors, especially the 5HT 1A subtype. The role of sertraline through the 5HT 1A receptor and nitric oxide interaction on the PTZ-induced seizure threshold was investigated in this study. In this study, 70 white male mice were randomly divided into 10 groups including intact control, sham-control and eight experimental groups which received sertraline, 8-OH-DPAT, WAY100635, WAY100635+sertraline, WAY100635+8-OH-DPAT, L-NAME, L-NAME+sertraline and L-NAME+8-OH-DPAT. After 14days of treatment in different groups, the PTZ-induced seizure threshold was assessed and the measurement of nitric oxide metabolites in the brain tissue was done with the Greiss method. The seizure threshold was significantly increased in the sertraline and 8OH-DPAT receiving groups compared to the sham group (P<0.001). In the presence of WAY100635, the effect of both sertraline and 8-OH-DPAT in raising the seizure threshold was more prominent (P<0.001) but on the other hand, in the presence of L-NAME, an increase in the anticonvulsant effect of 8-OH-DPAT was observed, while L-NAME alone had no effect on the seizure threshold (P<0.001). The NO X concentration was significantly decreased in the 8-OH-DPAT_treated group (P<0.01), while the WAY100657 reversed it and the combination of 8-OH-DPAT with L-NAME reduced the NO X levels (P<0.001). These findings support the anticonvulsant effect of SSRIs and selective 5HT 1A receptors, although serotonin receptors other than 5HT 1A subtype may be involved and also it is probable that some anticonvulsant effects of the sertraline and 8-OH-DPAT are through the modulation of nitrergic system. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

A comparison of the antinociceptive effects of xylazine, detomidine and romifidine on experimental pain in horses.

PubMed

Moens, Yves; Lanz, Francisca; Doherr, Marcus G; Schatzmann, Urs

2003-07-01

To study the analgesic potency of the alpha2-agonist romifidine in the horse using both an electrical current and a mechanical pressure model for nociceptive threshold testing. In addition, a comparison was made with doses of detomidine and xylazine that produce equivalent degrees of sedation. Randomized, placebo-controlled, blinded cross-over study. Six adult Swiss warmblood horses, one mare and five geldings, weighing from 530 to 650 kg and aged 6-15 years. Nociceptive thresholds were measured using an electrical stimulus applied to the coronary band and using a pneumatically operated pin pressing on the cannon bone. Measurements were made immediately before and every 15 minutes for 2 hours after IV injection of the test substances. Lifting of the foot indicated the test end point. The three alpha2-agonists caused a temporary increase in nociceptive thresholds with a maximal effect within 15 minutes and a return to baseline levels within 1 hour. Using electrical current testing nociceptive thresholds were significantly different from placebo (mean +/- SD) for detomidine at 15 minutes (from control 5.8 +/- 0.9 to 23.3 +/- 3.9 mA, p = 0.0066) and 30 minutes (from control 6.6 +/- 1.1 to 18.8 +/- 3.3 mA, p = 0.0091). The difference was significant for romifidine at 15 minutes only (from control 5.8 +/- 0.9 to 18.7 +/- 3.8 mA, p = 0.0066). With mechanical pressure testing nociceptive thresholds were significantly different from control for detomidine at 15 minutes (from 3.2 +/- 0.2 to 6.2 +/- 0.5 N, p = 0.00076) and 30 minutes (from 3.2 +/- 0.7 to 5.7 +/- 0.8 N, p = 0.0167). The difference was significant for xylazine at 15 minutes (from control 3.2 +/- 0.2 to 5.6 +/- 0.7 N, p = 0.0079). At 15 minutes the order of magnitude of the measured antinociceptive effect was significantly different between the two pain tests for both romifidine and detomidine, but not for xylazine. For romifidine, the increase of mean thresholds compared to placebo was 4.0 +/- 1.3 times placebo levels with the electrical current test compared to 1.3 +/- 0.3 times for the mechanical pressure test (p = 0.037). For detomidine, the increase of mean thresholds compared to placebo was 5.4 +/- 1.7 times control levels with the electrical current test compared to 2.0 +/- 0.2 times for the mechanical pressure test (p = 0.040). This represents a 2.7 (romifidine) and 3.4 times (detomidine) greater increase in thresholds using electrical current testing compared to the use of mechanical pressure testing. This study demonstrates the analgesic potential of alpha2-agonists in the horse for somatic pain and that they can have quantitatively different antinociceptive effects according to the antinociceptive test used.

Identifying failure in a tree network of a parallel computer

DOEpatents

Archer, Charles J.; Pinnow, Kurt W.; Wallenfelt, Brian P.

2010-08-24

Methods, parallel computers, and products are provided for identifying failure in a tree network of a parallel computer. The parallel computer includes one or more processing sets including an I/O node and a plurality of compute nodes. For each processing set embodiments include selecting a set of test compute nodes, the test compute nodes being a subset of the compute nodes of the processing set; measuring the performance of the I/O node of the processing set; measuring the performance of the selected set of test compute nodes; calculating a current test value in dependence upon the measured performance of the I/O node of the processing set, the measured performance of the set of test compute nodes, and a predetermined value for I/O node performance; and comparing the current test value with a predetermined tree performance threshold. If the current test value is below the predetermined tree performance threshold, embodiments include selecting another set of test compute nodes. If the current test value is not below the predetermined tree performance threshold, embodiments include selecting from the test compute nodes one or more potential problem nodes and testing individually potential problem nodes and links to potential problem nodes.

Electrical leakage detection circuit

DOEpatents

Wild, Arthur

2006-09-05

A method is provided for detecting electrical leakage between a power supply and a frame of a vehicle or machine. The disclosed method includes coupling a first capacitor between a frame and a first terminal of a power supply for a predetermined period of time. The current flowing between the frame and the first capacitor is limited to a predetermined current limit. It is determined whether the voltage across the first capacitor exceeds a threshold voltage. A first output signal is provided when the voltage across the capacitor exceeds the threshold voltage.

Temperature dependence of spontaneous emission in GaAs-AlGaAs quantum well lasers

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

Blood, P.; Kucharska, A.I.; Foxon, C.T.

1989-09-18

Using quantum well laser devices with a window in the {ital p}-type contact, we have measured the relative change of spontaneous emission intensity at threshold with temperature for 58-A-wide GaAs wells. Over the range 250--340 K the data are in good agreement with the linear relation obtained from a gain-current calculation which includes transition broadening. This linear behavior contrasts with the stronger temperature dependence of the total measured threshold current of the same devices which includes nonradiative barrier recombination processes.

75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... has proposed this rule change in order to preserve FINRA's current quorum requirements in anticipation.... Sec. 19 (2010). In anticipation of the foregoing amendment to the General Corporation Law, FINRA has...

Development of drugs for celiac disease: review of endpoints for Phase 2 and 3 trials

PubMed Central

Gottlieb, Klaus; Dawson, Jill; Hussain, Fez; Murray, Joseph A.

2015-01-01

Celiac disease is a lifelong disorder for which there is currently only one known, effective treatment: a gluten-free diet. New treatment approaches have recently emerged; several drugs are in Phase 2 trials and results appear promising; however, discussion around regulatory endpoints is in its infancy. We will briefly discuss the drugs that are under development and then shift our attention to potential trial endpoints, such as patient-reported outcomes, histology, serology, gene expression analysis and other tests. We will outline the differing requirements for proof-of-concept Phase 2 trials and Phase 3 registration trials, with a particular emphasis on current thinking in regulatory agencies. We conclude our paper with recommendations and a glossary of regulatory terms, to enable readers who are less familiar with regulatory language to take maximum advantage of this review. PMID:25725041

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

Pak, S.; Sites, J.R.

A Kaufman-type broad beam ion source, used for sputtering and etching purposes, has been operated with Ar, Kr,O/sub 2/ and N/sub 2/ gas inputs over a wide range of beam energies (200-1200 eV) and gas flow rates (1-10 sccm). The maximum ion beam current density for each gas saturates at about 2.5 mA/sq. cm. as gas flow is increased. The discharge threshold voltage necessary to produce a beam and the beam efficiency (beam current/molecular current), however, varied considerably. Kr had the lowest threshold and highest efficiency, Ar next, then N/sub 2/ and O/sub 2/. The ion beam current varied onlymore » weakly with beam energy for low gas flow rates, but showed a factor of two increase when the gas flow was higher.« less

Method and apparatus for clockless analog-to-digital conversion and peak detection

DOEpatents

DeGeronimo, Gianluigi

2007-03-06

An apparatus and method for analog-to-digital conversion and peak detection includes at least one stage, which includes a first switch, second switch, current source or capacitor, and discriminator. The discriminator changes state in response to a current or charge associated with the input signal exceeding a threshold, thereby indicating whether the current or charge associated with the input signal is greater than the threshold. The input signal includes a peak or a charge, and the converter includes a peak or charge detect mode in which a state of the switch is retained in response to a decrease in the current or charge associated with the input signal. The state of the switch represents at least a portion of a value of the peak or of the charge.

Sub-100 fJ and sub-nanosecond thermally driven threshold switching in niobium oxide crosspoint nanodevices.

PubMed

Pickett, Matthew D; Williams, R Stanley

2012-06-01

We built and measured the dynamical current versus time behavior of nanoscale niobium oxide crosspoint devices which exhibited threshold switching (current-controlled negative differential resistance). The switching speeds of 110 × 110 nm(2) devices were found to be Δt(ON) = 700 ps and Δt(OFF) = 2:3 ns while the switching energies were of the order of 100 fJ. We derived a new dynamical model based on the Joule heating rate of a thermally driven insulator-to-metal phase transition that accurately reproduced the experimental results, and employed the model to estimate the switching time and energy scaling behavior of such devices down to the 10 nm scale. These results indicate that threshold switches could be of practical interest in hybrid CMOS nanoelectronic circuits.

A theoretical approach to study the optical sensitivity of a MESFET

NASA Astrophysics Data System (ADS)

Dutta, Sutanu

2018-05-01

A theoretical model to study the optical sensitivity of a metal-semiconductor field effect transistor has been proposed for a relatively high drain field. An analytical expression of drain current of the device has been derived for a MESFET under optical illumination considering field dependent mobility of electrons across the channel. The variation of drain current with and without optical illumination has been studied with drain and gate voltages. The optical sensitivity of the drain current has been studied for different biasing conditions and gate lengths. In addition, the shift in threshold voltage of a MESFET under optical illumination is determined and optical sensitivity of the device in terms of its threshold voltage has been studied.

Effects of arc current on the life in burner rig thermal cycling of plasma sprayed ZrOsub2-Ysub2Osub3

NASA Technical Reports Server (NTRS)

Hendricks, R. C.; Mcdonald, G.

1982-01-01

An analysis of thermal cycle life data for four sets of eight thermal barrier coated specimens representing arc currents (plasma gun power) of 525, 600, 800, or 950 amps is presented. The ZrO2-8Y2O3/NiCrAlY plasma spray coated Rene 41 rods were thermal cycled to 1040 C in a Mach 0.3-Jet A/air burner flame. The experimental results indicate the existance of a minimum or threshold power level which coating life expectancy is less than 500 cycles. Above the threshold power level, coating life expectancy more than doubles and increases with arc current.

Evaluation of an Impedance Threshold Device as a VIIP Countermeasure

NASA Technical Reports Server (NTRS)

Ebert, D.; Macias, B.; Sargsyan, A.; Garcia, K.; Stenger, M.; Kemp, D.; Hargens, A.; Johnston, S.

2017-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a top human spaceflight risk for which NASA does not currently have a proven mitigation strategy. Thigh cuffs (Braslets) and lower body negative pressure (LBNP; Chibis) devices have been or are currently being evaluated as a means to reduce VIIP signs and symptoms, but these methods alone may not provide sufficient relief of cephalic venous congestion and VIIP symptoms. Additionally, current LBNP devices are too large and cumbersome for their systematic use as a countermeasure. Therefore, a novel approach is needed that is easy to implement and provides specific relief of symptoms. This investigation will evaluate an impedance threshold device (ITD) as a VIIP countermeasure.

Effects of arc current on the life in burner rig thermal cycling of plasma sprayed ZrOsub2-Ysub2Osub3

NASA Astrophysics Data System (ADS)

Hendricks, R. C.; McDonald, G.

1982-02-01

An analysis of thermal cycle life data for four sets of eight thermal barrier coated specimens representing arc currents (plasma gun power) of 525, 600, 800, or 950 amps is presented. The ZrO2-8Y2O3/NiCrAlY plasma spray coated Rene 41 rods were thermal cycled to 1040 C in a Mach 0.3-Jet A/air burner flame. The experimental results indicate the existance of a minimum or threshold power level which coating life expectancy is less than 500 cycles. Above the threshold power level, coating life expectancy more than doubles and increases with arc current.

Low threshold interband cascade lasers operating above room temperature

NASA Technical Reports Server (NTRS)

Hill, C. J.; Yang, B.; Yang, R. Q.

2003-01-01

Mid-IR type-II interband cascade lasers were demonstrated in pulsed mode at temperatures up to 325 K and in continuous mode up to 200 K. At 80 K, the threshold current density was 8.9 A/cm2 and a cw outpout power of 140 mW/facet was obtained.

Challenges posed to the European pharmaceutical regulatory system by highly personalized medicines.

PubMed

Johnston, John D; Feldschreiber, Peter

2014-03-01

The European pharmaceutical regulatory system has not yet been challenged by issues related to highly personalized medicines such as those to be found with active substances that affect RNA biochemistry. We review the current status of RNA-based pharmacology and present three possible case histories. The implications for the European pharmaceutical regulatory system are discussed. © 2013 The British Pharmacological Society.

EPA office of solid waste (OSW) report to Congress

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

Derkics, D.

1996-12-31

An EPA Office of Solid Waste Report to Congress is presented in outline form. The following topics are discussed: special waste chronology; statutory hazardous waste exemption; 1988 report to Congress findings; 1993 regulatory determination; current (1996), regulatory status of fossil fuel combustion wastes; co-management study; Electric Power Research Institute (EPRI) activities; EPRI coal ash field study sites; oil ash total combustion; fossil fuel combustion; current EPA activities; and Federal Register Notice.

Pharmaceutical liposomal drug delivery: a review of new delivery systems and a look at the regulatory landscape.

PubMed

Zylberberg, Claudia; Matosevic, Sandro

2016-11-01

Liposomes were the first nanoscale drug to be approved for clinical use in 1995. Since then, the technology has grown considerably, and pioneering recent work in liposome-based delivery systems has brought about remarkable developments with significant clinical implications. This includes long-circulating liposomes, stimuli-responsive liposomes, nebulized liposomes, elastic liposomes for topical, oral and transdermal delivery and covalent lipid-drug complexes for improved drug plasma membrane crossing and targeting to specific organelles. While the regulatory bodies' opinion on liposomes is well-documented, current guidance that address new delivery systems are not. This review describes, in depth, the current state-of-the-art of these new liposomal delivery systems and provides a critical overview of the current regulatory landscape surrounding commercialization efforts of higher-level complexity systems, the expected requirements and the hurdles faced by companies seeking to bring novel liposome-based systems for clinical use to market.

Speech-in-Noise Tests and Supra-threshold Auditory Evoked Potentials as Metrics for Noise Damage and Clinical Trial Outcome Measures.

PubMed

Le Prell, Colleen G; Brungart, Douglas S

2016-09-01

In humans, the accepted clinical standards for detecting hearing loss are the behavioral audiogram, based on the absolute detection threshold of pure-tones, and the threshold auditory brainstem response (ABR). The audiogram and the threshold ABR are reliable and sensitive measures of hearing thresholds in human listeners. However, recent results from noise-exposed animals demonstrate that noise exposure can cause substantial neurodegeneration in the peripheral auditory system without degrading pure-tone audiometric thresholds. It has been suggested that clinical measures of auditory performance conducted with stimuli presented above the detection threshold may be more sensitive than the behavioral audiogram in detecting early-stage noise-induced hearing loss in listeners with audiometric thresholds within normal limits. Supra-threshold speech-in-noise testing and supra-threshold ABR responses are reviewed here, given that they may be useful supplements to the behavioral audiogram for assessment of possible neurodegeneration in noise-exposed listeners. Supra-threshold tests may be useful for assessing the effects of noise on the human inner ear, and the effectiveness of interventions designed to prevent noise trauma. The current state of the science does not necessarily allow us to define a single set of best practice protocols. Nonetheless, we encourage investigators to incorporate these metrics into test batteries when feasible, with an effort to standardize procedures to the greatest extent possible as new reports emerge.

A contraction-related component of slow inward current in dog ventricular muscle and its relation to Na(+)-Ca2+ exchange.

PubMed Central

Simurda, J; Simurdová, M; Bravený, P; Sumbera, J

1992-01-01

1. The slow inward current component related to contraction (Isic) was studied in voltage clamp experiments on canine ventricular trabeculae at 30 degrees C with the aims of (a) estimating its relation to electrogenic Na(+)-Ca2+ exchange and (b) comparing it with similar currents as reported in cardiac myocytes. 2. Isic may be recorded under conditions of augmented contractility in response to depolarizing pulses below the threshold of the classic slow inward current (presumably mediated by L-type Ca2+ channels). In responses to identical depolarizing clamp pulses the peak value of Isic is directly related to the amplitude of contraction (Fmax). Isic peaks about 60 ms after the onset of depolarization and declines with a half-time of about 110 ms. 3. The voltage threshold of Isic activation is the same as the threshold of contraction. The positive inotropic clamp preconditions shift both thresholds to more negative values of membrane voltage, i.e. below the threshold of the classic slow inward current. 4. Isic may also be recorded as a slowly decaying inwardly directed current 'tail' after depolarizing pulses. In this representation the peak value of Isic changes with duration of the depolarizing pulses, again in parallel with Fmax. In response to pulses shorter than 100 ms both variables increase with depolarization time. If initial conditions remain constant, further prolongation of the pulse does not significantly influence either one (tail currents follow a common envelope). 5. Isic differs from classic slow inward current by: (a) its direct relation to contraction, (b) the slower decay of the current tail on repolarization, (c) slower restitution corresponding to the mechanical restitution, (d) its relative insensitivity to Ca(2+)-blocking agents (the decrease of Isic is secondary to the negative inotropic of Ca(2+)-blocking agents (the decrease of Isic is secondary to the negative inotropic effect) and (e) its disappearance after Sr2+ substitution for Ca2+. 6. The manifestations of Isic in multicellular preparations do not differ significantly from those reported in isolated myocytes (in contrast to calcium current). 7. The analysis of the correlation between Isic and Fmax transients during trains of identical test depolarizing pulses at variable extra- and intracellular ionic concentrations (changes of [Ca2+]o, 50% Li+ substitution for Na+, strophanthidin) indicate that the observed effects conform to the predictions based on a quantitative model of Na(+)-Ca2+ exchange. 8. It is concluded that Isic is activated by a transient increase of [Ca2+]i, in consequence of the release from the reticular stores.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1293284

Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

PubMed Central

Pape, H C; Budde, T; Mager, R; Kisvárday, Z F

1994-01-01

1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole-cell voltage-clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from -110 mV evoked inward currents resembling IT in relay cells and small outward currents indicative of IA in local circuit neurones. After blockade of IA with 4-aminopyridine (4-AP), the same pulse protocol produced IT in both types of neurones. Under current clamp, 4-AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 1 PMID:7965855

Economic Implications of Potential Changes to Regulatory and Reimbursement Policies for Medical Devices

PubMed Central

Reed, Shelby D.; Shea, Alisa M.

2007-01-01

Objective To evaluate the impact of regulatory scenarios on the financial viability of medical device companies. Design We developed a model to calculate the expected net present value of a hypothetical product throughout preclinical development, clinical testing, regulatory approval, and postmarketing. We tested 3 scenarios: (1) the current regulatory environment; (2) a scenario in which medical devices are subject to the same evidence standards required for pharmaceuticals; and (3) a scenario consistent with the Coverage with Evidence Development: Coverage with Study Participation (CSP) policy proposed by the Centers for Medicare and Medicaid Services, whereby Medicare will pay for beneficiaries to receive new devices that are not currently determined to be “reasonable and necessary” if the patients participate in clinical studies or registries. Measurements and Main results When applying assumptions consistent with the implantable cardioverter-defibrillator market, the net present value at the start of development was an estimated $553 million in the current regulatory environment, $322 million in the pharmaceutical scenario, and $403 million in the CSP scenario. Sensitivity analyses showed that the device industry would likely be profitable in all 3 scenarios over a range of assumptions. Conclusions The environment in which the medical device industry operates is financially attractive. Furthermore, when compared with the alternative of applying the same evidence standards for pharmaceuticals to medical devices, the CSP policy offers improved financial incentives for medical device companies. PMID:18095045

No more business as usual: enticing companies to sharply lower the public health costs of the products they sell.

PubMed

Sugarman, S

2009-03-01

Cigarettes, alcohol, junk food and motor vehicles cause a staggeringly high level of death, injury and disease. Business leaders from the industries that make these products currently try to frame these negative outcomes as 'collateral damage' that is someone else's problem. That framing is not only morally objectionable, but also overlooks the possibility that, with proper prodding, industry could substantially mitigate these public health disasters. A promising regulatory tool called 'performance-based regulation' is a new approach to combating the problem. Simply put, performance-based regulation would impose a legal obligation on manufacturers to reduce their negative social costs. Rather than suing the firms for damages, or telling them how they should run their businesses differently (as typical 'command and control' regimes do), performance-based regulation allows the firms to determine how best to decrease today's negative public health consequences. Like other public health strategies, performance-based regulation shifts the focus away from individual consumers on to those who are far more likely to achieve real public health gains. Analogous to a tax on causing harm that exceeds a threshold level, performance-based regulation seeks to harness private initiative in pursuit of the public good.

Thresholds for protecting Pacific Northwest ecosystems from atmospheric deposition of nitrogen: state of knowledge report

USGS Publications Warehouse

Cummings, Tonnie; Blett, Tamara; Porter, Ellen; Geiser, Linda; Graw, Rick; McMurray, Jill; Perakis, Steven S.; Rochefort, Regina

2014-01-01

The National Park Service and U.S. Forest Service manage areas in the states of Idaho, Oregon, and Washington – collectively referred to in this report as the Pacific Northwest - that contain significant natural resources and provide many recreational opportunities. The agencies are mandated to protect the air quality and air pollution-sensitive resources on these federal lands. Human activity has greatly increased the amount of nitrogen emitted to the atmosphere, resulting in elevated amounts of nitrogen being deposited in park and forest ecosystems. There is limited information in the Pacific Northwest about the levels of nitrogen that negatively affect natural systems, i.e., the critical loads. The National Park Service and U.S. Forest Service, with scientific input from the U.S. Geological Survey, have developed an approach for accumulating additional nitrogen critical loads information in the Pacific Northwest and using the data in planning and regulatory arenas. As a first step in that process, this report summarizes the current state of knowledge about nitrogen deposition, effects, and critical loads in the region. It also describes ongoing research efforts and identifies and prioritizes additional data needs.

Affordability of residential water tariffs: alternative measurement and explanatory factors in southern Spain.

PubMed

García-Valiñas, Maria A; Martínez-Espiñeira, Roberto; González-Gómez, Francisco

2010-12-01

Using information on a basic or "lifeline" level of domestic water use obtained from a water demand function based on a Stone-Geary utility function, a minimum water threshold of 128 m(3) per household per year was estimated in a sample of municipalities in Southern Spain. As a second objective, water affordability indexes were then calculated that relate the cost of such lifeline to average municipal income levels. The analysis of the factors behind the differences in that ratio across Andalusian municipalities shows that the relative cost of purchasing the lifeline appears inversely related to average income levels, revealing an element of regressivity in the component of water tariffs affecting the least superfluous part of the household's consumption. The main policy recommendation would involve redesigning water tariffs in order to improve access for lower income households to an amount of water sufficient to cover their basic needs. The proposed methodology could be applied to other geographical areas, both from developed and from developing countries, in order to analyze the degree of progressivity of the water tariffs currently in effect and in order to guide the design of more equitable regulatory policies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Selective control of cortical axonal spikes by a slowly inactivating K+ current

PubMed Central

Shu, Yousheng; Yu, Yuguo; Yang, Jing; McCormick, David A.

2007-01-01

Neurons are flexible electrophysiological entities in which the distribution and properties of ionic channels control their behaviors. Through simultaneous somatic and axonal whole-cell recording of layer 5 pyramidal cells, we demonstrate a remarkable differential expression of slowly inactivating K+ currents. Depolarizing the axon, but not the soma, rapidly activated a low-threshold, slowly inactivating, outward current that was potently blocked by low doses of 4-aminopyridine, α-dendrotoxin, and rTityustoxin-Kα. Block of this slowly inactivating current caused a large increase in spike duration in the axon but only a small increase in the soma and could result in distal axons generating repetitive discharge in response to local current injection. Importantly, this current was also responsible for slow changes in the axonal spike duration that are observed after somatic membrane potential change. These data indicate that low-threshold, slowly inactivating K+ currents, containing Kv1.2 α subunits, play a key role in the flexible properties of intracortical axons and may contribute significantly to intracortical processing. PMID:17581873

Revealed willingness-to-pay versus standard cost-effectiveness thresholds: Evidence from the South African HIV Investment Case.

PubMed

Meyer-Rath, Gesine; van Rensburg, Craig; Larson, Bruce; Jamieson, Lise; Rosen, Sydney

2017-01-01

The use of cost-effectiveness thresholds based on a country's income per capita has been criticized for not being relevant to decision making, in particular in middle-income countries such as South Africa. The recent South African HIV Investment Case produced an alternative cost-effectiveness threshold for HIV prevention and treatment interventions based on estimates of life years saved and the country's committed HIV budget. We analysed the optimal mix of HIV interventions over a baseline of the current HIV programme under the committed HIV budget for 2016-2018. We calculated the incremental cost-effectiveness ratio (ICER) as cost per life-year saved (LYS) of 16 HIV prevention and treatment interventions over 20 years (2016-2035). We iteratively evaluated the most cost effective option (defined by an intervention and its coverage) over a rolling baseline to which the more cost effective options had already been added, thereby allowing for diminishing marginal returns to interventions. We constrained the list of interventions to those whose combined cost was affordable under the current HIV budget. Costs are presented from the government perspective, unadjusted for inflation and undiscounted, in 2016 USD. The current HIV budget of about $1.6 billion per year was sufficient to pay for the expansion of condom availability, medical male circumcision, universal treatment, and infant testing at 6 weeks to maximum coverage levels, while also implementing a social and behavior change mass media campaign with a message geared at increasing testing uptake and reducing the number of sexual partners. The combined ICER of this package of services was $547/ LYS. The ICER of the next intervention that was above the affordability threshold was $872/LYS. The results of the South African HIV Investment Case point to an HIV cost-effectiveness threshold based on affordability under the current budget of $547-872 per life year saved, a small fraction of the country's GDP per capita of about $6,000.

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...

Thresholds in chemical respiratory sensitisation.

PubMed

Cochrane, Stella A; Arts, Josje H E; Ehnes, Colin; Hindle, Stuart; Hollnagel, Heli M; Poole, Alan; Suto, Hidenori; Kimber, Ian

2015-07-03

There is a continuing interest in determining whether it is possible to identify thresholds for chemical allergy. Here allergic sensitisation of the respiratory tract by chemicals is considered in this context. This is an important occupational health problem, being associated with rhinitis and asthma, and in addition provides toxicologists and risk assessors with a number of challenges. In common with all forms of allergic disease chemical respiratory allergy develops in two phases. In the first (induction) phase exposure to a chemical allergen (by an appropriate route of exposure) causes immunological priming and sensitisation of the respiratory tract. The second (elicitation) phase is triggered if a sensitised subject is exposed subsequently to the same chemical allergen via inhalation. A secondary immune response will be provoked in the respiratory tract resulting in inflammation and the signs and symptoms of a respiratory hypersensitivity reaction. In this article attention has focused on the identification of threshold values during the acquisition of sensitisation. Current mechanistic understanding of allergy is such that it can be assumed that the development of sensitisation (and also the elicitation of an allergic reaction) is a threshold phenomenon; there will be levels of exposure below which sensitisation will not be acquired. That is, all immune responses, including allergic sensitisation, have threshold requirement for the availability of antigen/allergen, below which a response will fail to develop. The issue addressed here is whether there are methods available or clinical/epidemiological data that permit the identification of such thresholds. This document reviews briefly relevant human studies of occupational asthma, and experimental models that have been developed (or are being developed) for the identification and characterisation of chemical respiratory allergens. The main conclusion drawn is that although there is evidence that the acquisition of sensitisation to chemical respiratory allergens is a dose-related phenomenon, and that thresholds exist, it is frequently difficult to define accurate numerical values for threshold exposure levels. Nevertheless, based on occupational exposure data it may sometimes be possible to derive levels of exposure in the workplace, which are safe. An additional observation is the lack currently of suitable experimental methods for both routine hazard characterisation and the measurement of thresholds, and that such methods are still some way off. Given the current trajectory of toxicology, and the move towards the use of non-animal in vitro and/or in silico) methods, there is a need to consider the development of alternative approaches for the identification and characterisation of respiratory sensitisation hazards, and for risk assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A new evaluation method of electron optical performance of high beam current probe forming systems.

PubMed

Fujita, Shin; Shimoyama, Hiroshi

2005-10-01

A new numerical simulation method is presented for the electron optical property analysis of probe forming systems with point cathode guns such as cold field emitters and the Schottky emitters. It has long been recognized that the gun aberrations are important parameters to be considered since the intrinsically high brightness of the point cathode gun is reduced due to its spherical aberration. The simulation method can evaluate the 'threshold beam current I(th)' above which the apparent brightness starts to decrease from the intrinsic value. It is found that the threshold depends on the 'electron gun focal length' as well as on the spherical aberration of the gun. Formulas are presented to estimate the brightness reduction as a function of the beam current. The gun brightness reduction must be included when the probe property (the relation between the beam current l(b) and the probe size on the sample, d) of the entire electron optical column is evaluated. Formulas that explicitly consider the gun aberrations into account are presented. It is shown that the probe property curve consists of three segments in the order of increasing beam current: (i) the constant probe size region, (ii) the brightness limited region where the probe size increases as d approximately I(b)(3/8), and (iii) the angular current intensity limited region in which the beam size increases rapidly as d approximately I(b)(3/2). Some strategies are suggested to increase the threshold beam current and to extend the effective beam current range of the point cathode gun into micro ampere regime.

NASA GRC and MSFC Space-Plasma Arc Testing Procedures

NASA Technical Reports Server (NTRS)

Ferguson, Dale C.; Vayner, Boris V.; Galofaro, Joel T,; Hillard, G. Barry; Vaughn, Jason; Schneider, Todd

2005-01-01

Tests of arcing and current collection in simulated space plasma conditions have been performed at the NASA Glenn Research Center (GRC) in Cleveland, Ohio, for over 30 years and at the Marshall Space Flight Center (MSFC) in Huntsville, Alabama, for almost as long. During this period, proper test conditions for accurate and meaningful space simulation have been worked out, comparisons with actual space performance in spaceflight tests and with real operational satellites have been made, and NASA has achieved our own internal standards for test protocols. It is the purpose of this paper to communicate the test conditions, test procedures, and types of analysis used at NASA GRC and MSFC to the space environmental testing community at large, to help with international space-plasma arcing-testing standardization. To be discussed are: 1.Neutral pressures, neutral gases, and vacuum chamber sizes. 2. Electron and ion densities, plasma uniformity, sample sizes, and Debuy lengths. 3. Biasing samples versus self-generated voltages. Floating samples versus grounded. 4. Power supplies and current limits. Isolation of samples from power supplies during arcs. 5. Arc circuits. Capacitance during biased arc-threshold tests. Capacitance during sustained arcing and damage tests. Arc detection. Prevention sustained discharges during testing. 6. Real array or structure samples versus idealized samples. 7. Validity of LEO tests for GEO samples. 8. Extracting arc threshold information from arc rate versus voltage tests. 9. Snapover and current collection at positive sample bias. Glows at positive bias. Kapon (R) pyrolisis. 10. Trigger arc thresholds. Sustained arc thresholds. Paschen discharge during sustained arcing. 11. Testing for Paschen discharge threshold. Testing for dielectric breakdown thresholds. Testing for tether arcing. 12. Testing in very dense plasmas (ie thruster plumes). 13. Arc mitigation strategies. Charging mitigation strategies. Models. 14. Analysis of test results. Finally, the necessity of testing will be emphasized, not to the exclusion of modeling, but as part of a complete strategy for determining when and if arcs will occur, and preventing them from occurring in space.

NASA GRC and MSFC Space-Plasma Arc Testing Procedures

NASA Technical Reports Server (NTRS)

Ferguson, Dale C.a; Vayner, Boris V.; Galofaro, Joel T.; Hillard, G. Barry; Vaughn, Jason; Schneider, Todd

2005-01-01

Tests of arcing and current collection in simulated space plasma conditions have been performed at the NASA Glenn Research Center (GRC) in Cleveland, Ohio, for over 30 years and at the Marshall Space flight Center (MSFC) for almost as long. During this period, proper test conditions for accurate and meaningful space simulation have been worked out, comparisons with actual space performance in spaceflight tests and with real operational satellites have been made, and NASA has achieved our own internal standards for test protocols. It is the purpose of this paper to communicate the test conditions, test procedures, and types of analysis used at NASA GRC and MSFC to the space environmental testing community at large, to help with international space-plasma arcing testing standardization. To be discussed are: 1. Neutral pressures, neutral gases, and vacuum chamber sizes. 2. Electron and ion densities, plasma uniformity, sample sizes, and Debye lengths. 3. Biasing samples versus self-generated voltages. Floating samples versus grounded. 4. Power supplies and current limits. Isolation of samples from power supplies during arcs. Arc circuits. Capacitance during biased arc-threshold tests. Capacitance during sustained arcing and damage tests. Arc detection. Preventing sustained discharges during testing. 5. Real array or structure samples versus idealized samples. 6. Validity of LEO tests for GEO samples. 7. Extracting arc threshold information from arc rate versus voltage tests. 8 . Snapover and current collection at positive sample bias. Glows at positive bias. Kapton pyrolization. 9. Trigger arc thresholds. Sustained arc thresholds. Paschen discharge during sustained arcing. 10. Testing for Paschen discharge thresholds. Testing for dielectric breakdown thresholds. Testing for tether arcing. 11. Testing in very dense plasmas (ie thruster plumes). 12. Arc mitigation strategies. Charging mitigation strategies. Models. 13. Analysis of test results. Finally, the necessity of testing will be emphasized, not to the exclusion of modeling, but as part of a complete strategy for determining when and if arcs will occur, and preventing them from occurring in space.

Optimal Dynamic Sub-Threshold Technique for Extreme Low Power Consumption for VLSI

NASA Technical Reports Server (NTRS)

Duong, Tuan A.

2012-01-01

For miniaturization of electronics systems, power consumption plays a key role in the realm of constraints. Considering the very large scale integration (VLSI) design aspect, as transistor feature size is decreased to 50 nm and below, there is sizable increase in the number of transistors as more functional building blocks are embedded in the same chip. However, the consequent increase in power consumption (dynamic and leakage) will serve as a key constraint to inhibit the advantages of transistor feature size reduction. Power consumption can be reduced by minimizing the voltage supply (for dynamic power consumption) and/or increasing threshold voltage (V(sub th), for reducing leakage power). When the feature size of the transistor is reduced, supply voltage (V(sub dd)) and threshold voltage (V(sub th)) are also reduced accordingly; then, the leakage current becomes a bigger factor of the total power consumption. To maintain low power consumption, operation of electronics at sub-threshold levels can be a potentially strong contender; however, there are two obstacles to be faced: more leakage current per transistor will cause more leakage power consumption, and slow response time when the transistor is operated in weak inversion region. To enable low power consumption and yet obtain high performance, the CMOS (complementary metal oxide semiconductor) transistor as a basic element is viewed and controlled as a four-terminal device: source, drain, gate, and body, as differentiated from the traditional approach with three terminals: i.e., source and body, drain, and gate. This technique features multiple voltage sources to supply the dynamic control, and uses dynamic control to enable low-threshold voltage when the channel (N or P) is active, for speed response enhancement and high threshold voltage, and when the transistor channel (N or P) is inactive, to reduce the leakage current for low-leakage power consumption.

Domain wall dynamics driven by spin transfer torque and the spin-orbit field.

PubMed

Hayashi, Masamitsu; Nakatani, Yoshinobu; Fukami, Shunsuke; Yamanouchi, Michihiko; Mitani, Seiji; Ohno, Hideo

2012-01-18

We have studied current-driven dynamics of domain walls when an in-plane magnetic field is present in perpendicularly magnetized nanowires using an analytical model and micromagnetic simulations. We model an experimentally studied system, ultrathin magnetic nanowires with perpendicular anisotropy, where an effective in-plane magnetic field is developed when current is passed along the nanowire due to the Rashba-like spin-orbit coupling. Using a one-dimensional model of a domain wall together with micromagnetic simulations, we show that the existence of such in-plane magnetic fields can either lower or raise the threshold current needed to cause domain wall motion. In the presence of the in-plane field, the threshold current differs for positive and negative currents for a given wall chirality, and the wall motion becomes sensitive to out-of-plane magnetic fields. We show that large non-adiabatic spin torque can counteract the effect of the in-plane field.

Sensitivity of frozen section histology for identifying Propionibacterium acnes infections in revision shoulder arthroplasty.

PubMed

Grosso, Matthew J; Frangiamore, Salvatore J; Ricchetti, Eric T; Bauer, Thomas W; Iannotti, Joseph P

2014-03-19

Propionibacterium acnes is a clinically relevant pathogen with total shoulder arthroplasty. The purpose of this study was to determine the sensitivity of frozen section histology in identifying patients with Propionibacterium acnes infection during revision total shoulder arthroplasty and investigate various diagnostic thresholds of acute inflammation that may improve frozen section performance. We reviewed the results of forty-five patients who underwent revision total shoulder arthroplasty. Patients were divided into the non-infection group (n = 15), the Propionibacterium acnes infection group (n = 18), and the other infection group (n = 12). Routine preoperative testing was performed and intraoperative tissue culture and frozen section histology were collected for each patient. The histologic diagnosis was determined by one pathologist for each of the four different thresholds. The absolute maximum polymorphonuclear leukocyte concentration was used to construct a receiver operating characteristics curve to determine a new potential optimal threshold. Using the current thresholds for grading frozen section histology, the sensitivity was lower for the Propionibacterium acnes infection group (50%) compared with the other infection group (67%). The specificity of frozen section was 100%. Using a receiver operating characteristics curve, an optimized threshold was found at a total of ten polymorphonuclear leukocytes in five high-power fields (400×). Using this threshold, the sensitivity of frozen section for Propionibacterium acnes was increased to 72%, and the specificity remained at 100%. Using current histopathology grading systems, frozen sections were specific but showed low sensitivity with respect to the Propionibacterium acnes infection. A new threshold value of a total of ten or more polymorphonuclear leukocytes in five high-power fields may increase the sensitivity of frozen section, with minimal impact on specificity.

Energy Switching Threshold for Climatic Benefits

NASA Astrophysics Data System (ADS)

Zhang, X.; Cao, L.; Caldeira, K.

2013-12-01

Climate change is one of the great challenges facing humanity currently and in the future. Its most severe impacts may still be avoided if efforts are made to transform current energy systems (1). A transition from the global system of high Greenhouse Gas (GHG) emission electricity generation to low GHG emission energy technologies is required to mitigate climate change (2). Natural gas is increasingly seen as a choice for transitions to renewable sources. However, recent researches in energy and climate puzzled about the climate implications of relying more energy on natural gas. On one hand, a shift to natural gas is promoted as climate mitigation because it has lower carbon per unit energy than coal (3). On the other hand, the effect of switching to natural gas on nuclear-power and other renewable energies development may offset benefits from fuel-switching (4). Cheap natural gas is causing both coal plants and nuclear plants to close in the US. The objective of this study is to measure and evaluate the threshold of energy switching for climatic benefits. We hypothesized that the threshold ratio of energy switching for climatic benefits is related to GHGs emission factors of energy technologies, but the relation is not linear. A model was developed to study the fuel switching threshold for greenhouse gas emission reduction, and transition from coal and nuclear electricity generation to natural gas electricity generation was analyzed as a case study. The results showed that: (i) the threshold ratio of multi-energy switching for climatic benefits changes with GHGs emission factors of energy technologies. (ii)The mathematical relation between the threshold ratio of energy switching and GHGs emission factors of energies is a curved surface function. (iii) The analysis of energy switching threshold for climatic benefits can be used for energy and climate policy decision support.

Assessment of the current D-dimer cutoff point in pulmonary embolism workup at a single institution: Retrospective study.

PubMed

Alhassan, S; Bihler, E; Patel, K; Lavudi, S; Young, M; Balaan, M

2018-06-06

The currently used D-dimer (DD) cutoff point is associated with a large number of negative CT-pulmonary angiographies (CTPA). We hypothesized presence of deficiency in the current cutoff and a need to look for a better DD threshold. We conducted a retrospective medical records analysis of all patients who had a CTPA as part of pulmonary embolism (PE) workup over a 1-year period. All emergency room (ER) patients who had DD assay checked prior to CTPA were included in the analysis. We assessed our institutional cutoff point and tried to test other presumptive DD thresholds retrospectively. At our institution 1591 CTPA were performed in 2014, with 1220 scans (77%) performed in the ER. DD test was ordered prior to CTPA imaging in 238 ER patients (19.5%) as part of the PE workup. PE was diagnosed in 14 cases (6%). The sensitivity and specificity of the currently used DD cutoff (0.5 mcg/mL) were found to be 100% and 13%, respectively. Shifting the cutoff value from 0.5 to 0.85 mcg/mL would result in a significant increase in the specificity from 13% to 51% while maintaining the same sensitivity of 100%. This would make theoretically 84 CTPA scans, corresponding to 35% of CTPA imaging, unnecessary because DD would be considered negative based on this presumptive threshold. Our results suggest a significant deficiency in the institutional DD cutoff point with the need to find a better threshold through a large multicenter prospective trial to minimize unnecessary CTPA scans and to improve patient safety.

Ground-Water Quality Data in the Central Sierra Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Ferrari, Matthew J.; Fram, Miranda S.; Belitz, Kenneth

2008-01-01

Ground-water quality in the approximately 950 square kilometer (370 square mile) Central Sierra study unit (CENSIE) was investigated in May 2006 as part of the Priority Basin Assessment project of the Groundwater Ambient Monitoring and Assessment (GAMA) Program. The GAMA Priority Basin Assessment project was developed in response to the Ground-Water Quality Monitoring Act of 2001, and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). This study was designed to provide a spatially unbiased assessment of the quality of raw ground water used for drinking-water supplies within CENSIE, and to facilitate statistically consistent comparisons of ground-water quality throughout California. Samples were collected from thirty wells in Madera County. Twenty-seven of the wells were selected using a spatially distributed, randomized grid-based method to provide statistical representation of the study area (grid wells), and three were selected to aid in evaluation of specific water-quality issues (understanding wells). Ground-water samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOCs], gasoline oxygenates and degradates, pesticides and pesticide degradates), constituents of special interest (N-nitrosodimethylamine, perchlorate, and 1,2,3-trichloropropane), naturally occurring inorganic constituents [nutrients, major and minor ions, and trace elements], radioactive constituents, and microbial indicators. Naturally occurring isotopes [tritium, and carbon-14, and stable isotopes of hydrogen, oxygen, nitrogen, and carbon], and dissolved noble gases also were measured to help identify the sources and ages of the sampled ground water. In total, over 250 constituents and water-quality indicators were investigated. Quality-control samples (blanks, replicates, and samples for matrix spikes) were collected at approximately one-sixth of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Results from field blanks indicated contamination was not a noticeable source of bias in the data for ground-water samples. Differences between replicate samples were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most constituents. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain water quality. Regulatory thresholds apply to water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH), and thresholds established for aesthetic concerns (Secondary Maximum Contaminant Levels, SMCL-CA) by CDPH. Therefore, any comparisons of the results of this study to drinking-water standards only is for illustrative purposes and is not indicative of compliance or non-compliance to those standards. Most constituents that were detected in ground-water samples were found at concentrations below drinking-water standards or thresholds. Six constituents? fluoride, arsenic, molybdenum, uranium, gross-alpha radioactivity, and radon-222?were detected at concentrations higher than thresholds set for health-based regulatory purposes. Three additional constituents?pH, iron and manganese?were detected at concentrations above thresholds set for aesthetic concerns. Volatile organic compounds (VOCs) and pesticides, were detected in less than one-third of the samples and generally at less than one one-hundredth of a health-based threshold.

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

PubMed

Bierer, Julie Arenberg; Faulkner, Kathleen F

2010-04-01

The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a narrow, pTP stimulus, had significantly broader PTCs than the lowest threshold channels. In two subjects, the tips of the tuning curves were shifted away from the probe channel. Tuning curves were also wider for the monopolar probes than with pTP probes for both the highest and lowest threshold channels. These results suggest that single-channel thresholds measured with a restricted stimulus can be used to identify cochlear implant channels with poor spatial selectivity. Channels having wide or tip-shifted tuning characteristics would likely not deliver the appropriate spectral information to the intended auditory neurons, leading to suboptimal perception. As a clinical tool, quick identification of impaired channels could lead to patient-specific mapping strategies and result in improved speech and music perception.

Reciprocal Modulation of IK1–INa Extends Excitability in Cardiac Ventricular Cells

PubMed Central

Varghese, Anthony

2016-01-01

The inwardly rectifying potassium current (IK1) and the fast inward sodium current (INa) are reciprocally modulated in mammalian ventricular myocytes. An increase in the expression of channels responsible for one of these two currents results in a corresponding increase in expression of the other. These currents are critical in the propagation of action potentials (AP) during the normal functioning of the heart. This study identifies a physiological role for IK1–INa reciprocal modulation in ventricular fiber activation thresholds and conduction. Simulations of action potentials in single cells and propagating APs in cardiac fibers were carried out using an existing model of electrical activity in cardiac ventricular myocytes. The conductances, GK1, of the inwardly rectifying potassium current, and GNa, of the fast inward sodium current were modified independently and in tandem to simulate reciprocal modulation. In single cells, independent modulation of GK1 alone resulted in changes in activation thresholds that were qualitatively similar to those for reciprocal GK1–GNa modulation and unlike those due to independent modulation of GNa alone, indicating that GK1 determines the cellular activation threshold. On the other hand, the variations in conduction velocity in cardiac cell fibers were similar for independent GNa modulation and for tandem changes in GK1–GNa, suggesting that GNa is primarily responsible for setting tissue AP conduction velocity. Conduction velocity dependence on GK1–GNa is significantly affected by the intercellular gap junction conductance. While the effects on the passive fiber space constant due to changes in both GK1 and the intercellular gap junction conductance, Ggj, were in line with linear cable theory predictions, both conductances had surprisingly large effects on fiber activation thresholds. Independent modulation of GK1 rendered cardiac fibers inexcitable at higher levels of GK1 whereas tandem GK1–GNa changes allowed fibers to remain excitable at high GK1 values. Reciprocal modulation of the inwardly rectifying potassium current and the fast inward sodium current may have a functional role in allowing cardiac tissue to remain excitable when IK1 is upregulated. PMID:27895596

Center conductor diagnostic for multipactor detection in inaccessible geometries

NASA Astrophysics Data System (ADS)

Chaplin, Vernon H.; Hubble, Aimee A.; Clements, Kathryn A.; Graves, Timothy P.

2017-01-01

Electron collecting current probes are the most reliable diagnostic of multipactor and radiofrequency (RF) ionization breakdown; however, stand-alone probes can only be used in test setups where the breakdown region is physically accessible. This paper describes techniques for measuring multipactor current directly on the center conductor of a coaxial RF device (or more generally, on the signal line in any two-conductor RF system) enabling global multipactor detection with improved sensitivity compared to other common diagnostics such as phase null, third harmonic, and reflected power. The center conductor diagnostic may be AC coupled for use in systems with a low DC impedance between the center conductor and ground. The effect of DC bias on the breakdown threshold was studied: in coaxial geometry, the change in threshold was <1 dB for positive biases satisfying VD C/VR F 0 <0.8 , where VRF0 is the RF voltage amplitude at the unperturbed breakdown threshold. In parallel plate geometry, setting VD C/VR F 0 <0.2 was necessary to avoid altering the threshold by more than 1 dB. In most cases, the center conductor diagnostic functions effectively with no bias at all—this is the preferred implementation, but biases in the range VD C=0 -10 V may be applied if necessary. The polarity of the detected current signal may be positive or negative depending on whether there is net electron collection or emission globally.

Center conductor diagnostic for multipactor detection in inaccessible geometries.

PubMed

Chaplin, Vernon H; Hubble, Aimee A; Clements, Kathryn A; Graves, Timothy P

2017-01-01

Electron collecting current probes are the most reliable diagnostic of multipactor and radiofrequency (RF) ionization breakdown; however, stand-alone probes can only be used in test setups where the breakdown region is physically accessible. This paper describes techniques for measuring multipactor current directly on the center conductor of a coaxial RF device (or more generally, on the signal line in any two-conductor RF system) enabling global multipactor detection with improved sensitivity compared to other common diagnostics such as phase null, third harmonic, and reflected power. The center conductor diagnostic may be AC coupled for use in systems with a low DC impedance between the center conductor and ground. The effect of DC bias on the breakdown threshold was studied: in coaxial geometry, the change in threshold was <1 dB for positive biases satisfying V DC /V RF0 <0.8, where V RF0 is the RF voltage amplitude at the unperturbed breakdown threshold. In parallel plate geometry, setting V DC /V RF0 <0.2 was necessary to avoid altering the threshold by more than 1 dB. In most cases, the center conductor diagnostic functions effectively with no bias at all-this is the preferred implementation, but biases in the range V DC =0-10V may be applied if necessary. The polarity of the detected current signal may be positive or negative depending on whether there is net electron collection or emission globally.

Development of a wave-induced forcing threshold for nearshore impact of Wave Energy Converter arrays

NASA Astrophysics Data System (ADS)

O'Dea, A.; Haller, M. C.; Ozkan-Haller, H. T.

2016-02-01

Wave-induced forcing is a function of spatial gradients in the wave radiation stresses and is the main driver of alongshore currents, rip currents, and nearshore sediment transport. The installation of nearshore Wave Energy Converter (WEC) arrays may cause significant changes in the surf zone radiation stresses and could therefore impact nearshore littoral processes. In the first part of this study, a new threshold for nearshore hydrodynamic impact due to the presence of WEC devices is established based on changes in the alongshore radiation stress gradients shoreward of WEC arrays. The threshold is defined based on the relationship between nearshore radiation stresses and alongshore currents as observed in field data. Next, we perform a parametric study of the nearshore impact of WEC arrays using the SWAN wave model. Trials are conducted on an idealized, alongshore-uniform beach with a range of WEC array configurations, locations, and incident wave conditions, and conditions that generate radiation stress gradients above the impact threshold are identified. Finally, the same methodology is applied to two wave energy test sites off the coast of Newport, OR with more complicated bathymetries. Although the trends at the field sites are similar to those seen in the parametric study, the location and extent of the changes in the alongshore radiation stress gradients appear to be heavily influenced by the local bathymetry.

Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data

PubMed Central

Liu, Zhi-Ping

2015-01-01

Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented. PMID:25937810

Regulatory sequence analysis tools.

PubMed

van Helden, Jacques

2003-07-01

The web resource Regulatory Sequence Analysis Tools (RSAT) (http://rsat.ulb.ac.be/rsat) offers a collection of software tools dedicated to the prediction of regulatory sites in non-coding DNA sequences. These tools include sequence retrieval, pattern discovery, pattern matching, genome-scale pattern matching, feature-map drawing, random sequence generation and other utilities. Alternative formats are supported for the representation of regulatory motifs (strings or position-specific scoring matrices) and several algorithms are proposed for pattern discovery. RSAT currently holds >100 fully sequenced genomes and these data are regularly updated from GenBank.

Transcranial electric stimulation for intraoperative motor evoked potential monitoring: dependence of required stimulation current on interstimulus interval value.

PubMed

Joksimovic, Boban; Szelenyi, Andrea; Seifert, Volker; Damjanovic, Aleksandar; Damjanovic, Aleksandra; Rasulic, Lukas

2015-05-01

To evaluate the relationship between stimulus intensity by constant current transcranial electric stimulation and interstimulus interval (ISI) for eliciting muscle motor evoked potentials (MEPs) in three different hand muscles and the tibialis anterior muscles. We tested intraoperatively different monophasic constant current pulses and ISIs in 22 patients with clinically normal motor function. Motor thresholds of contralateral muscle MEPs were determined at 0.5 milliseconds (ms) pulse duration and ISIs of 1, 2, 3, 4, 5, and 10 ms using a train of 2, 3, and 5 monophasic constant current pulses of 62 to 104 mA before craniotomy and after closure of the dura mater. The lowest stimulation threshold to elicit MEPs in the examined muscles was achieved with a train of 5 pulses (ISI: 3 ms) before craniotomy, which was statistically significant compared with 2 pulses (ISI: 3 ms) as well as 3 pulses (ISIs: 3 and 10 ms). An ISI of 3 ms gave the lowest motor thresholds with statistical significance compared with the ISIs of 4 ms (2 pulses) and of 1 ms (3 pulses). All current intensity (mA) and ISI (ms) relationship graphs had a trend of the exponential function as y = a + bx + c ρ (x), where y is intensity (mA) and x is ISI (ms). The minimum of the function was determined for each patient and each muscle. The difference was statistically significant between 3 and 5 pulses before craniotomy and between 3 and 5 pulses and 2 and 5 pulses after closure of the dura mater. In adult neurosurgical patients with a normal motor status, a train of 5 pulses and an ISI of 3 ms provide the lowest motor thresholds. We provided evidence of the dependence of required stimulation current on ISI. Georg Thieme Verlag KG Stuttgart · New York.

What exactly is an exact copy? And why it matters when trying to ban human reproductive cloning in Australia

PubMed Central

Gogarty, B

2003-01-01

This paper examines the current Australian regulatory response to human reproductive cloning. The central consideration is the capacity of the current regulatory regime to effectively deter human cloning efforts. A legislative prohibition on human cloning must be both effective and clear enough to allow researchers to know what practices are acceptable. This paper asks whether the current Australian regime evinces these qualities and suggests that Australia should follow the example set in the UK by the enactment of the Human Reproductive Cloning Act 2001. PMID:12672887

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

PubMed

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

2015-08-01

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

Current NRC Perspectives Concerning Primary Water Stress Corrosion Cracking

NASA Astrophysics Data System (ADS)

Alley, David; Dunn, Darrell

Materials currently used in nuclear power plants are reliable and are generally resistant to environmental degradation. However, occurrences of environmental degradation have been observed as the current fleet of reactors ages. Primary water stress corrosion cracking (PWSCC) is of particular interest to the US Nuclear Regulatory Commission (NRC). This paper provides a historical assessment of operating experience associated with PWSCC and welding issues associated with PWSCC resistant materials. The paper also considers the regulatory issues associated with PWSCC, especially those associated with gaps in the understanding of the behavior of PWSCC resistant material under actual reactor conditions.

Health related guide values for drinking-water since 1993 as guidance to assess presence of new analytes in drinking-water.

PubMed

Dieter, Hermann H

2014-03-01

Regulatory toxicologists, when going into assessment of a new analyte in drinking-water, very often miss the occasion to revert to scientifically consensual virtually safe lifetime exposure reference doses and corresponding health-related guide values (HRGV) for drinking-water, be those derived either to avoid concern over "threshold effects" or concern over exceedance of an unacceptable non-threshold cancer risk level. They then need a more restrictive precautionary yet science-compatible approach to directly avoid concern over the presence (measured concentration) of a new analyte in drinking-water. Therefore, the German Environment Agency (UBA, Umweltbundesamt) decided in 2003 to extrapolate international toxicological expertise collected since 1993 from assessing "old" analytes in drinking-water on new ones in form of five HRIV=health related indication values. They indicate the reasonable lowest maximal concentration from which on tiered or stepwise human toxicological evaluation of a new analyte might be necessary and meaningful. Their regulatory-toxicological function is that of placeholders as long as a possibly higher scientific HRGV or a surrogate value based on a threshold of toxicological concern (TTC) was not broadly agreed by science. The five-step HRIV scale between 0.01 and 3.0 μg/l combines international toxicological experience gained from "old" analytes since 1993 with the concepts of safety factors (SF(D)) to assess database deficiency and science-related extrapolation factors (EF) to extrapolate experimental data on humans. Each HRIV is valid and safe for a 2 l/day drinking-water exposure scenario either counting for 10% relative source contribution (compounds with threshold effects) or for a lifetime non-threshold cancer risk of up to 10(-6) and is the higher the more positive information exists regarding possible effects at critical toxic endpoints and for length of possible exposure. Past (historical) and present evaluations of "old" analytes were available in form of hundreds of HRGVs to count in 2 liters per day and person for 10% RSC or a 10(-6) non-threshold risk. These HRGVs were calculated by the present author either from ADI-, TDI- or RfD-values derived since 1993 by six large health authorities or they were identified directly at their websites or in the literature, always looking for confirmed or assumed worldwide relevance for drinking-water (resources). 36 of these up to 200 "old" analytes were ascribed since 1993 at least once an HRGV at or below 1 μg/l for (confirmed or provisionally assumed) "high" or "very high" threshold chronic toxicity. None but one of the corresponding 113 scientific HRGVs fell distinctly short of 0.3 μg/l. Only 14 carcinogens turned out as being relevant for drinking-water due to confirmed occurrence and coincident toxicological significance there. 13 of these exhibited a structural alert for genotoxicity. Ten of these 13 were "high-potency" genotoxic carcinogens with presently calculated non-threshold 10(-6) risk minimal HRGVs between 0.06 μg/l and 0.005 μg/l (9 compounds) or possibly down to 0.0007 μg/l (1 compound). This motivated UBA to propose a precautionary range between a minimal HRIV0=0.01 and a HRIV1=0.1 μg/l to assess new analytes bearing a structural alert for genotoxicity. The HRGVs for the remaining three (from 13) carcinogens with alerts for genotoxicity were at best similar for both genotoxic and non-genotoxic effects and higher or equal to 0.3 μg/l. Therefore, a minimal HRIV of 0.01 μg/l (HRIV0) or even 0.1 μg/l (HRIV1) would have appeared too low for assessing the presence in drinking-water of new analytes with no other human toxicity data than proven absence of both genotoxicity and of structural alerts for such. Instead, UBA proposes to provisionally assess such compounds by its next higher precautionary of HRIV3=0.3 μg/l. Any value once set is open for falsification upwards to either 1.0 μg/l (HRIV4) or 3.0 μg/l (HRIV5) or even for being replaced by an HRGV>3.0 μg/l if pertinent high toxicity effect potentials different from genotoxicity are similarly ruled out by either mechanistic and TTC-based arguments or a tiered experimental (in vitro and/or in vivo) approach. Regulatory-toxicological expertise gained since 1993 with "old" analytes in drinking-water (resources) and its extrapolation by analogy on new analytes with patchy human toxicological database allows for provisional assessment of their presence in drinking-water in form of five precautionary HRIVs. Selecting a HRIV, instead referring to a TTC or a virtually safe reference dose, just asks an expert judgment on the degree of formal completeness and informational potential of a new analyte's human toxicity database. Exceedance of a HRIV indicates need for supplementary toxicological data to improve assessment, their nature and comprehensiveness depending on degree and expected length of exceedance. The regulatory function of a HRIV is that of a placeholder for a possibly higher TTC-based surrogate HRGVTTC or a highest possible science-based HRGV. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

PubMed

Belkaid, Yasmine; Tarbell, Kristin

2009-01-01

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

Protecting workers and the environment: An environmental NGO's perspective on nanotechnology

NASA Astrophysics Data System (ADS)

Balbus, John M.; Florini, Karen; Denison, Richard A.; Walsh, Scott A.

2007-01-01

Nanotechnology, the design and manipulation of materials at the atomic scale, may well revolutionize many of the ways our society manufactures products, produces energy, and treats diseases. New materials based on nanotechnology are already reaching the market in a wide variety of consumer products. Some of the observed properties of nanomaterials call into question the adequacy of current methods for determining hazard and exposure and for controlling resulting risks. Given the limitations of existing regulatory tools and policies, we believe two distinct kinds of initiatives are needed: first, a major increase in the federal investment in nanomaterial risk research; second, rapid development and implementation of voluntary standards of care pending development of adequate regulatory safeguards in the longer term. Several voluntary programs are currently at various stages of evolution, though the eventual outputs of each of these are still far from clear. Ultimately, effective regulatory safeguards are necessary to provide a level playing field for industry while adequately protecting human health and the environment. This paper reviews the existing toxicological literature on nanomaterials, outlines and analyzes the current regulatory framework, and provides our recommendations, as an environmental non-profit organization, for safe nanotechnology development.

RNAi technologies in agricultural biotechnology: The Toxicology Forum 40th Annual Summer Meeting.

PubMed

Sherman, James H; Munyikwa, Tichafa; Chan, Stephen Y; Petrick, Jay S; Witwer, Kenneth W; Choudhuri, Supratim

2015-11-01

During the 40th Annual Meeting of The Toxicology Forum, the current and potential future science, regulations, and politics of agricultural biotechnology were presented and discussed. The meeting session described herein focused on the technology of RNA interference (RNAi) in agriculture. The general process by which RNAi works, currently registered RNAi-based plant traits, example RNAi-based traits in development, potential use of double stranded RNA (dsRNA) as topically applied pesticide active ingredients, research related to the safety of RNAi, biological barriers to ingested dsRNA, recent regulatory RNAi science reviews, and regulatory considerations related to the use of RNAi in agriculture were discussed. Participants generally agreed that the current regulatory framework is robust and appropriate for evaluating the safety of RNAi employed in agricultural biotechnology and were also supportive of the use of RNAi to develop improved crop traits. However, as with any emerging technology, the potential range of future products, potential future regulatory frameworks, and public acceptance of the technology will continue to evolve. As such, continuing dialogue was encouraged to promote education of consumers and science-based regulations. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Anastasiou, Charalampos; Duhr, Claude; Dulat, Falko

In this study, we compute the gluon fusion Higgs boson cross-section at N 3LO through the second term in the threshold expansion. This calculation constitutes a major milestone towards the full N 3LO cross section. Our result has the best formal accuracy in the threshold expansion currently available, and includes contributions from collinear regions besides subleading corrections from soft and hard regions, as well as certain logarithmically enhanced contributions for general kinematics. We use our results to perform a critical appraisal of the validity of the threshold approximation at N 3LO in perturbative QCD.

Water Systems Project 1: Current Systems and Regulatory Support

EPA Science Inventory

Water Systems Project 1 objectives: 1) Supply research results to support federal regulations and guidance; 2) provide strategies to regions, states, and communities for improved regulatory compliance, and 3) provide rapid and effective emergency response where appropriate (e.g. ...

Research on Current Water Systems and Regulatory Support

EPA Science Inventory

This project will supply research results to support federal regulations and guidance. It will also provide strategies to regions, states, and communities for improved regulatory compliance and rapid and effective emergency response where appropriate (e.g. harmful algal bloom out...

Oscillatory dependence of current driven domain wall motion on current pulse length

NASA Astrophysics Data System (ADS)

Thomas, Luc

2007-03-01

The motion of domain walls (DW) in magnetic nanowires driven by spin torque from spin-polarized current is of considerable interest. Most previous work has considered the effect of dc or ˜microsecond long current pulses. Here, we show that the dynamics of DWs driven by nanosecond-long current pulses is unexpectedly complex. In particular, we show that the current driven motion of a DW, confined to a pinning site in a permalloy nanowire, exhibits an oscillatory dependence on the current pulse length with a period of just a few nanoseconds [1]. This behavior can be understood within a surprisingly straightforward one dimensional analytical model of the DW's motion. When a current pulse is applied, the DW's position oscillates within the pinning potential out of phase with the DW's out-of-plane magnetization, where the latter acts like the DW's momentum. Thus, the current driven motion of the DW is akin to a harmonic oscillator, whose frequency is determined by the ``mass'' of the DW and where the restoring force is related to the slope of the pinning potential. Remarkably, when the current pulse is turned off during phases of the DW motion when it has enough momentum, the amplitude of the oscillations can be amplified such that the DW exits the pinning potential well after the pulse is turned off. This oscillatory depinning occurs for currents smaller than the dc threshold current, and, moreover, the DW moves against the electron flow, opposite to the propagation direction above the dc threshold. These effects can be further amplified by using trains of current pulses whose lengths and separations are matched to the DW's oscillation period. In this way, we have demonstrated a five fold reduction in the threshold current required to move a DW out of a pinning site, making this effect potentially important for technological applications. [1] L. Thomas, M. Hayashi, X. Jiang, R. Moriya, C. Rettner and S.S.P. Parkin, Nature 443, 197 (2006).

Kv1 channels control spike threshold dynamics and spike timing in cortical pyramidal neurones

PubMed Central

Higgs, Matthew H; Spain, William J

2011-01-01

Abstract Previous studies showed that cortical pyramidal neurones (PNs) have a dynamic spike threshold that functions as a high-pass filter, enhancing spike timing in response to high-frequency input. While it is commonly assumed that Na+ channel inactivation is the primary mechanism of threshold accommodation, the possible role of K+ channel activation in fast threshold changes has not been well characterized. The present study tested the hypothesis that low-voltage activated Kv1 channels affect threshold dynamics in layer 2–3 PNs, using α-dendrotoxin (DTX) or 4-aminopyridine (4-AP) to block these conductances. We found that Kv1 blockade reduced the dynamic changes of spike threshold in response to a variety of stimuli, including stimulus-evoked synaptic input, current steps and ramps of varied duration, and noise. Analysis of the responses to noise showed that Kv1 channels increased the coherence of spike output with high-frequency components of the stimulus. A simple model demonstrates that a dynamic spike threshold can account for this effect. Our results show that the Kv1 conductance is a major mechanism that contributes to the dynamic spike threshold and precise spike timing of cortical PNs. PMID:21911608

New developments in supra-threshold perimetry.

PubMed

Henson, David B; Artes, Paul H

2002-09-01

To describe a series of recent enhancements to supra-threshold perimetry. Computer simulations were used to develop an improved algorithm (HEART) for the setting of the supra-threshold test intensity at the beginning of a field test, and to evaluate the relationship between various pass/fail criteria and the test's performance (sensitivity and specificity) and how they compare with modern threshold perimetry. Data were collected in optometric practices to evaluate HEART and to assess how the patient's response times can be analysed to detect false positive response errors in visual field test results. The HEART algorithm shows improved performance (reduced between-eye differences) over current algorithms. A pass/fail criterion of '3 stimuli seen of 3-5 presentations' at each test location reduces test/retest variability and combines high sensitivity and specificity. A large percentage of false positive responses can be detected by comparing their latencies to the average response time of a patient. Optimised supra-threshold visual field tests can perform as well as modern threshold techniques. Such tests may be easier to perform for novice patients, compared with the more demanding threshold tests.

A New Regulatory Policy for FTTx-Based Next-Generation Access Networks

NASA Astrophysics Data System (ADS)

Makarovič, Boštjan

2013-07-01

This article critically assesses the latest European Commission policies in relation to next-generation access investment that put focus on regulated prices and relaxing of wholesale access obligations. Pointing at the vital socio-legal and economic arguments, it further challenges the assumptions of the current EU regulatory framework and calls for a more contractual utility-based model of regulation instead of the current system that overly relies on market-driven infrastructure-based competition.

Regulation of stem cell-based therapies in Canada: current issues and concerns.

PubMed

von Tigerstrom, Barbara; Nguyen, Thu Minh; Knoppers, Bartha Maria

2012-09-01

Stem cell therapies offer enormous potential for the treatment of a wide range of diseases and conditions. Despite the excitement over such advances, regulators are faced with the challenge of determining criteria to ensure stem cells and their products are safe and effective for human use. However, stem cell-based products and therapies present unique regulatory challenges because standard drug development models do not wholly apply given the complexity and diversity of these products and therapies. As a result, regulatory requirements are often unclear and ambiguous creating unnecessary barriers for research. In order to better understand the barriers that might affect Canadian stem cell researchers, we sought feedback from stakeholders regarding areas of uncertainty or concern about existing regulatory oversight of cell therapies. A selection of Canadian researchers and clinicians working in the area of stem cell research were interviewed to assess certain key questions: 1) whether current regulatory requirements are easily accessible and well understood; 2) whether regulatory requirements create important challenges or barriers; and 3) whether there is a need for further guidance on the issue. The results of this survey are summarized and compared to issues and concerns experienced in other countries, as reported in the literature, to identify challenges which may be on the horizon and to provide possible solutions for regulatory reform.

Interplay of Dysphoria and Anxiety Sensitivity in Relation to Emotion Regulatory Cognitions of Smoking Among Treatment-seeking Smokers

PubMed Central

Garey, Lorra; Bakhshaie, Jafar; Brandt, Charles P.; Langdon, Kirsten J.; Kauffman, Brooke Y.; Schmidt, Norman B.; Leventhal, Adam M.; Zvolensky, Michael J.

2017-01-01

Background and Objectives There is evidence that anxiety sensitivity (AS) plays a role in the maintenance of smoking, yet there is little understanding of how AS interplays with other affective symptomatology variables that are also related to smoking, such as dysphoria. Therefore, the current cross-sectional study evaluated the interactive effects of AS and dysphoria on emotion regulatory cognitions, including smoking negative affect reduction expectancies, perceived barriers for cessation, and smoking-specific experiential avoidance. Method A total of 448 adult treatment-seeking daily smokers, who responded to study advertisements, were recruited to participate in a smoking cessation treatment trial (47.8% female; Mage = 37.2, SD =13.5). The current study utilized self-report baseline data from trial participants. Results After accounting for covariates, simple slope analyses revealed that AS was positively related to negative affect reduction expectancies (β = .03, p =.01), perceived barriers to cessation (β =.22, p = .002), and smoking avoidance and inflexibility (β =.07, p = .04), among smokers with lower (versus higher) levels of dysphoria. Conclusions The current findings suggest that higher levels of dysphoria may mitigate the relation between AS and emotion regulatory cognitions of smoking. Scientific Significance The current findings highlight the unique and additive clinical relevance of AS and dysphoria regarding emotion regulatory smoking cognitions that may impede quit success. PMID:27122303

Stability of plasma cylinder with current in a helical plasma flow

NASA Astrophysics Data System (ADS)

Leonovich, Anatoly S.; Kozlov, Daniil A.; Zong, Qiugang

2018-04-01

Stability of a plasma cylinder with a current wrapped by a helical plasma flow is studied. Unstable surface modes of magnetohydrodynamic (MHD) oscillations develop at the boundary of the cylinder enwrapped by the plasma flow. Unstable eigenmodes can also develop for which the plasma cylinder is a waveguide. The growth rate of the surface modes is much higher than that for the eigenmodes. It is shown that the asymmetric MHD modes in the plasma cylinder are stable if the velocity of the plasma flow is below a certain threshold. Such a plasma flow velocity threshold is absent for the symmetric modes. They are unstable in any arbitrarily slow plasma flows. For all surface modes there is an upper threshold for the flow velocity above which they are stable. The helicity index of the flow around the plasma cylinder significantly affects both the Mach number dependence of the surface wave growth rate and the velocity threshold values. The higher the index, the lower the upper threshold of the velocity jump above which the surface waves become stable. Calculations have been carried out for the growth rates of unstable oscillations in an equilibrium plasma cylinder with current serving as a model of the low-latitude boundary layer (LLBL) of the Earth's magnetic tail. A tangential discontinuity model is used to simulate the geomagnetic tail boundary. It is shown that the magnetopause in the geotail LLBL is unstable to a surface wave (having the highest growth rate) in low- and medium-speed solar wind flows, but becomes stable to this wave in high-speed flows. However, it can remain weakly unstable to the radiative modes of MHD oscillations.

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

PubMed

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

2016-08-25

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

Detecting fatigue thresholds from electromyographic signals: A systematic review on approaches and methodologies.

PubMed

Ertl, Peter; Kruse, Annika; Tilp, Markus

2016-10-01

The aim of the current paper was to systematically review the relevant existing electromyographic threshold concepts within the literature. The electronic databases MEDLINE and SCOPUS were screened for papers published between January 1980 and April 2015 including the keywords: neuromuscular fatigue threshold, anaerobic threshold, electromyographic threshold, muscular fatigue, aerobic-anaerobictransition, ventilatory threshold, exercise testing, and cycle-ergometer. 32 articles were assessed with regard to their electromyographic methodologies, description of results, statistical analysis and test protocols. Only one article was of very good quality. 21 were of good quality and two articles were of very low quality. The review process revealed that: (i) there is consistent evidence of one or two non-linear increases of EMG that might reflect the additional recruitment of motor units (MU) or different fiber types during fatiguing cycle ergometer exercise, (ii) most studies reported no statistically significant difference between electromyographic and metabolic thresholds, (iii) one minute protocols with increments between 10 and 25W appear most appropriate to detect muscular threshold, (iv) threshold detection from the vastus medialis, vastus lateralis, and rectus femoris is recommended, and (v) there is a great variety in study protocols, measurement techniques, and data processing. Therefore, we recommend further research and standardization in the detection of EMGTs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifying and Overcoming Threshold Concepts and Conceptions: Introducing a Conception-Focused Curriculum to Course Design

ERIC Educational Resources Information Center

Burch, Gerald F.; Burch, Jana J.; Bradley, Thomas P.; Heller, Nathan A.

2015-01-01

Educators have been challenged to identify threshold concepts and develop transformed students. This stands in stark contrast to many curriculum design and delivery models that currently view students as repositories of knowledge. In this article, we argue that educators can reach both goals, identify stumbling blocks and transforming students,…

Olfactory Detection Thresholds and Adaptation in Adults with Autism Spectrum Condition

ERIC Educational Resources Information Center

Tavassoli, T.; Baron-Cohen, S.

2012-01-01

Sensory issues have been widely reported in Autism Spectrum Conditions (ASC). Since olfaction is one of the least investigated senses in ASC, the current studies explore olfactory detection thresholds and adaptation to olfactory stimuli in adults with ASC. 80 participants took part, 38 (18 females, 20 males) with ASC and 42 control participants…

Dietary Toxicity Thresholds and Ecological Risks for Birds and Mammals Based on Species Sensitivity Distributions.

PubMed

Korsman, John C; Schipper, Aafke M; Hendriks, A Jan

2016-10-04

Species sensitivity distributions (SSDs) are commonly used in regulatory procedures and ecological risk assessments. Yet, most toxicity threshold and risk assessment studies are based on invertebrates and fish. In the present study, no observed effect concentrations (NOECs) specific to birds and mammals were used to derive SSDs and corresponding hazardous concentrations for 5% of the species (HC5 values). This was done for 41 individual substances as well as for subsets of substances aggregated based on their toxic Mode of Action (MoA). In addition, potential differences in SSD parameters (mean and standard deviation) were investigated in relation to MoA and end point (growth, reproduction, and survival). The means of neurotoxic and respirotoxic compounds were significantly lower than those of narcotics, whereas no differences were found between end points. The standard deviations of the SSDs were similar across MoA's and end points. Finally, the SSDs obtained were used in a case study by calculating Ecological Risks (ER) and multisubstance Potentially Affected Fractions of species (msPAF) based on 19 chemicals in 10 Northwestern European estuaries and coastal areas. The assessment showed that the risks were all below 2.6 × 10 -2 . However, the calculated risks underestimate the actual risks of chemicals in these areas because the potential impacts of substances that were not measured in the field or for which no SSD was available were not included in the risk assessment. The SSDs obtained can be used in regulatory procedures and for assessing the impacts of contaminants on birds and mammals from fish contaminants monitoring programs.

Fish embryo toxicity test, threshold approach, and moribund as approaches to implement 3R principles to the acute fish toxicity test.

PubMed

Dang, ZhiChao; van der Ven, Leo T M; Kienhuis, Anne S

2017-11-01

The acute fish toxicity test (AFT) is requested by EU legal frameworks for hazard classification and risk assessment. AFT is one of the few regulatory required tests using death as an endpoint. This paper reviews efforts made to reduce, refine and replace (3Rs) AFT. We make an inventory of information requirements for AFT, summarize studies on 3Rs of AFT and give recommendations. The fish embryo toxicity test (FET) is proposed as a replacement of AFT and analyses have focused on two aspects: assessing the capacity of FET in predicting AFT and defining the applicability domain of FET. Six comparison studies have consistently shown a strong correlation of FET and AFT. In contrast, the applicability domain of FET has not yet been fully defined. FET has not yet been accepted as a replacement of AFT by any EU legal frameworks to fulfill information requirements because FET is insensitive to some chemicals. It is recommended that the outlier chemicals that do not correlate between FET and AFT should be further investigated. When necessary, additional FET data should be generated. Another effort to reduce and refine AFT is incorporation of FET into the threshold approach. Furthermore, moribund as an endpoint of fish death has been introduced in revising AFT guideline to reduce the duration of suffering for refinement. This endpoint, however, needs further work on the link of moribund and death. Global regulatory acceptance of the moribund endpoint would be critical for this development. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Michael, Stephan; Chow, Weng; Schneider, Hans

In the framework of a microscopic model for intersubband gain from electrically pumped quantum-dot structures we investigate electrically pumped quantum-dots as active material for a mid-infrared quantum cascade laser. Our previous calculations have indicated that these structures could operate with reduced threshold current densities while also achieving a modal gain comparable to that of quantum well active materials. We study the influence of two important quantum-dot material parameters, here, namely inhomogeneous broadening and quantum-dot sheet density, on the performance of a proposed quantum cascade laser design. In terms of achieving a positive modal net gain, a high quantum-dot density canmore » compensate for moderately high inhomogeneous broadening, but at a cost of increased threshold current density. By minimizing quantum-dot density with presently achievable inhomogeneous broadening and total losses, significantly lower threshold densities than those reported in quantum-well quantum-cascade lasers are predicted by our theory.« less

Improvement in Brightness Uniformity by Compensating for the Threshold Voltages of Both the Driving Thin-Film Transistor and the Organic Light-Emitting Diode for Active-Matrix Organic Light-Emitting Diode Displays

NASA Astrophysics Data System (ADS)

Ching-Lin Fan,; Hui-Lung Lai,; Jyu-Yu Chang,

2010-05-01

In this paper, we propose a novel pixel design and driving method for active-matrix organic light-emitting diode (AM-OLED) displays using low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs). The proposed threshold voltage compensation circuit, which comprised five transistors and two capacitors, has been verified to supply uniform output current by simulation work using the automatic integrated circuit modeling simulation program with integrated circuit emphasis (AIM-SPICE) simulator. The driving scheme of this voltage programming method includes four periods: precharging, compensation, data input, and emission. The simulated results demonstrate excellent properties such as low error rate of OLED anode voltage variation (<1%) and high output current. The proposed pixel circuit shows high immunity to the threshold voltage deviation characteristics of both the driving poly-Si TFT and the OLED.

Image intensifier gain uniformity improvements in sealed tubes by selective scrubbing

DOEpatents

Thomas, S.W.

1995-04-18

The gain uniformity of sealed microchannel plate image intensifiers (MCPIs) is improved by selectively scrubbing the high gain sections with a controlled bright light source. Using the premise that ions returning to the cathode from the microchannel plate (MCP) damage the cathode and reduce its sensitivity, a HeNe laser beam light source is raster scanned across the cathode of a microchannel plate image intensifier (MCPI) tube. Cathode current is monitored and when it exceeds a preset threshold, the sweep rate is decreased 1000 times, giving 1000 times the exposure to cathode areas with sensitivity greater than the threshold. The threshold is set at the cathode current corresponding to the lowest sensitivity in the active cathode area so that sensitivity of the entire cathode is reduced to this level. This process reduces tube gain by between 10% and 30% in the high gain areas while gain reduction in low gain areas is negligible. 4 figs.

Image intensifier gain uniformity improvements in sealed tubes by selective scrubbing

DOEpatents

Thomas, Stanley W.

1995-01-01

The gain uniformity of sealed microchannel plate image intensifiers (MCPIs) is improved by selectively scrubbing the high gain sections with a controlled bright light source. Using the premise that ions returning to the cathode from the microchannel plate (MCP) damage the cathode and reduce its sensitivity, a HeNe laser beam light source is raster scanned across the cathode of a microchannel plate image intensifier (MCPI) tube. Cathode current is monitored and when it exceeds a preset threshold, the sweep rate is decreased 1000 times, giving 1000 times the exposure to cathode areas with sensitivity greater than the threshold. The threshold is set at the cathode current corresponding to the lowest sensitivity in the active cathode area so that sensitivity of the entire cathode is reduced to this level. This process reduces tube gain by between 10% and 30% in the high gain areas while gain reduction in low gain areas is negligible.

Stable Extraction of Threshold Voltage Using Transconductance Change Method for CMOS Modeling, Simulation and Characterization

NASA Astrophysics Data System (ADS)

Choi, Woo Young; Woo, Dong-Soo; Choi, Byung Yong; Lee, Jong Duk; Park, Byung-Gook

2004-04-01

We proposed a stable extraction algorithm for threshold voltage using transconductance change method by optimizing node interval. With the algorithm, noise-free gm2 (=dgm/dVGS) profiles can be extracted within one-percent error, which leads to more physically-meaningful threshold voltage calculation by the transconductance change method. The extracted threshold voltage predicts the gate-to-source voltage at which the surface potential is within kT/q of φs=2φf+VSB. Our algorithm makes the transconductance change method more practical by overcoming noise problem. This threshold voltage extraction algorithm yields the threshold roll-off behavior of nanoscale metal oxide semiconductor field effect transistor (MOSFETs) accurately and makes it possible to calculate the surface potential φs at any other point on the drain-to-source current (IDS) versus gate-to-source voltage (VGS) curve. It will provide us with a useful analysis tool in the field of device modeling, simulation and characterization.

Comparison of alternatives to amplitude thresholding for onset detection of acoustic emission signals

NASA Astrophysics Data System (ADS)

Bai, F.; Gagar, D.; Foote, P.; Zhao, Y.

2017-02-01

Acoustic Emission (AE) monitoring can be used to detect the presence of damage as well as determine its location in Structural Health Monitoring (SHM) applications. Information on the time difference of the signal generated by the damage event arriving at different sensors in an array is essential in performing localisation. Currently, this is determined using a fixed threshold which is particularly prone to errors when not set to optimal values. This paper presents three new methods for determining the onset of AE signals without the need for a predetermined threshold. The performance of the techniques is evaluated using AE signals generated during fatigue crack growth and compared to the established Akaike Information Criterion (AIC) and fixed threshold methods. It was found that the 1D location accuracy of the new methods was within the range of < 1 - 7.1 % of the monitored region compared to 2.7% for the AIC method and a range of 1.8-9.4% for the conventional Fixed Threshold method at different threshold levels.

Modeling and analysis of sub-surface leakage current in nano-MOSFET under cutoff regime

NASA Astrophysics Data System (ADS)

Swami, Yashu; Rai, Sanjeev

2017-02-01

The high leakage current in nano-meter regimes is becoming a significant portion of power dissipation in nano-MOSFET circuits as threshold voltage, channel length, and gate oxide thickness are scaled down to nano-meter range. Precise leakage current valuation and meticulous modeling of the same at nano-meter technology scale is an increasingly a critical work in designing the low power nano-MOSFET circuits. We present a specific compact model for sub-threshold regime leakage current in bulk driven nano-MOSFETs. The proposed logical model is instigated and executed into the latest updated PTM bulk nano-MOSFET model and is found to be in decent accord with technology-CAD simulation data. This paper also reviews various transistor intrinsic leakage mechanisms for nano-MOSFET exclusively in weak inversion, like drain-induced barricade lowering (DIBL), gate-induced drain leakage (GIDL), gate oxide tunneling (GOT) leakage etc. The root cause of the sub-surface leakage current is mainly due to the nano-scale short channel length causing source-drain coupling even in sub-threshold domain. Consequences leading to carriers triumphing the barricade between the source and drain. The enhanced model effectively considers the following parameter dependence in the account for better-quality value-added results like drain-to-source bias (VDS), gate-to-source bias (VGS), channel length (LG), source/drain junction depth (Xj), bulk doping concentration (NBULK), and operating temperature (Top).

Comparative investigation of novel hetero gate dielectric and drain engineered charge plasma TFET for improved DC and RF performance

NASA Astrophysics Data System (ADS)

Yadav, Dharmendra Singh; Verma, Abhishek; Sharma, Dheeraj; Tirkey, Sukeshni; Raad, Bhagwan Ram

2017-11-01

Tunnel-field-effect-transistor (TFET) has emerged as one of the most prominent devices to replace conventional MOSFET due to its ability to provide sub-threshold slope below 60 mV/decade (SS ≤ 60 mV/decade) and low leakage current. Despite this, TFETs suffer from ambipolar behavior, lower ON-state current, and poor RF performance. To address these issues, we have introduced drain and gate work function engineering with hetero gate dielectric for the first time in charge plasma based doping-less TFET (DL TFET). In this, the usage of dual work functionality over the drain region significantly reduces the ambipolar behavior of the device by varying the energy barrier at drain/channel interface. Whereas, the presence of dual work function at the gate terminal increases the ON-state current (ION). The combined effect of dual work function at the gate and drain electrode results in the increment of ON-state current (ION) and decrement of ambipolar conduction (Iambi) respectively. Furthermore, the incorporation of hetero gate dielectric along with dual work functionality at the drain and gate electrode provides an overall improvement in the performance of the device in terms of reduction in ambipolarity, threshold voltage and sub-threshold slope along with improved ON-state current and high frequency figures of merit.

Threshold fluctuations in a superconducting current-carrying bridge

NASA Astrophysics Data System (ADS)

Marychev, P. M.; Vodolazov, D. Yu

2017-07-01

We calculate the energy of threshold fluctuation δ {F}{{thr}} which triggers the transition of a superconducting current-carrying bridge to the resistive state. We show that the dependence δ {F}{{thr}}{(I)\\propto {I}{{dep}}{\\hslash }(1-I/{I}{{dep}})}5/4/e, found by Langer and Ambegaokar for a long bridge with length L\\gg ξ , holds far below the critical temperature in both dirty and clean limits (here I dep is the depairing current of the bridge and ξ is a coherence length). We also find that even a ‘weak’ local defect (leading to a small suppression of the critical current of the bridge {I}{{c}}≲ {I}{{dep}}) provides δ {F}{{thr}}\\propto {I}{{c}}{\\hslash }{(1-I/{I}{{c}})}3/2/e, typical for a short bridge with L\\ll ξ or a Josephson junction.

Two-Color Coherent Control of Femtosecond Above-Threshold Photoemission from a Tungsten Nanotip.

PubMed

Förster, Michael; Paschen, Timo; Krüger, Michael; Lemell, Christoph; Wachter, Georg; Libisch, Florian; Madlener, Thomas; Burgdörfer, Joachim; Hommelhoff, Peter

2016-11-18

We demonstrate coherent control of multiphoton and above-threshold photoemission from a single solid-state nanoemitter driven by a fundamental and a weak second harmonic laser pulse. Depending on the relative phase of the two pulses, electron emission is modulated with a contrast of the oscillating current signal of up to 94%. Electron spectra reveal that all observed photon orders are affected simultaneously and similarly. We confirm that photoemission takes place within 10 fs. Accompanying simulations indicate that the current modulation with its large contrast results from two interfering quantum pathways leading to electron emission.

INTERNATIONAL CONFERENCE ON SEMICONDUCTOR INJECTION LASERS SELCO-87: Low-threshold ridge-waveguide 1.3-μm laser

NASA Astrophysics Data System (ADS)

Kortàn, J.; Nohavica, D.; Sarma, J.

1988-11-01

A description is given of the fabrication and of the main properties of 1.3-μm GaInAsP lasers with a ridge (rib) waveguide structure used for lateral confinement of transverse modes and of the current. Such lasers were made by the method of ion-beam etching and self-alignment photolithography. Narrow ridges (3-5 μm) formed in this way carried Ti-Au Schottky contacts. These lasers were simple to fabricate and their threshold currents were comparable with those in much more complex lasers with buried waveguide structures.

Experimental and theoretical investigations concerning a frequency filter behavior of the human retina regarding electric pulse currents. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Meier-Koll, A.

1979-01-01

Investigation involving patients with injuries in the visual nervous system are discussed. This led to the identification of the epithelial ganglion of the retina as a frequency filter. Threshold curves of the injured visual organs were compared with threshold curves obtained with a control group as a basis for identification. A model which considers the epithelial ganglion as a homogeneous cell layer in which adjacent neurons interact is discussed. It is shown the behavior of the cells against alternating exciting currents can be explained.

The laboratory diagnosis of testosterone deficiency.

PubMed

Paduch, Darius A; Brannigan, Robert E; Fuchs, Eugene F; Kim, Edward D; Marmar, Joel L; Sandlow, Jay I

2014-05-01

The evaluation and treatment of hypogonadal men has become an important part of urologic practice. Fatigue, loss of libido, and erectile dysfunction are commonly reported, but nonspecific symptoms and laboratory verification of low testosterone (T) are an important part of evaluation in addition to a detailed history and physical examination. Significant intraindividual fluctuations in serum T levels, biologic variation of T action on end organs, the wide range of T levels in human serum samples, and technical limitations of currently available assays have led to poor reliability of T measurements in the clinical laboratory setting. There is no universally accepted threshold of T concentration that distinguishes eugonadal from hypogonadal men; thus, laboratory results have to be interpreted in the appropriate clinical setting. This review focuses on clinical, biological, and technological challenges that affect serum T measurements to educate clinicians regarding technological advances and limitations of the currently available laboratory methods to diagnose hypogonadism. A collaborative effort led by the American Urological Association between practicing clinicians, patient advocacy groups, government regulatory agencies, industry, and professional societies is underway to provide optimized assay platforms and evidence-based normal assay ranges to guide clinical decision making. Until such standardization is commonplace in clinical laboratories, the decision to treat should be based on the presence of signs and symptoms in addition to serum T measurements. Rigid interpretation of T ranges should not dictate clinical decision making or define coverage of treatment by third party payers. Copyright © 2014 Elsevier Inc. All rights reserved.

Atmospheric deposition and critical loads for nitrogen and metals in Arctic Alaska: Review and current status

USGS Publications Warehouse

Linder, Greg L.; Brumbaugh, William G.; Neitlich, Peter; Little, Edward

2013-01-01

To protect important resources under their bureau’s purview, the United States National Park Service’s (NPS) Arctic Network (ARCN) has developed a series of “vital signs” that are to be periodically monitored. One of these vital signs focuses on wet and dry deposition of atmospheric chemicals and further, the establishment of critical load (CL) values (thresholds for ecological effects based on cumulative depositional loadings) for nitrogen (N), sulfur, and metals. As part of the ARCN terrestrial monitoring programs, samples of the feather moss Hylocomium splendens are being col- lected and analyzed as a cost-effective means to monitor atmospheric pollutant deposition in this region. Ultimately, moss data combined with refined CL values might be used to help guide future regulation of atmospheric contaminant sources potentially impacting Arctic Alaska. But first, additional long-term studies are needed to determine patterns of contaminant deposition as measured by moss biomonitors and to quantify ecosystem responses at particular loadings/ ranges of contaminants within Arctic Alaska. Herein we briefly summarize 1) current regulatory guidance related to CL values 2) derivation of CL models for N and metals, 3) use of mosses as biomonitors of atmospheric deposition and loadings, 4) preliminary analysis of vulnerabilities and risks associated with CL estimates for N, 5) preliminary analysis of existing data for characterization of CL values for N for interior Alaska and 6) implications for managers and future research needs.

Algorithm for measuring the internal quantum efficiency of individual injection lasers

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

Sommers, H.S. Jr.

1978-05-01

A new algorithm permits determination of the internal quantum efficiency eta/sub i/ of individual lasers. Above threshold, the current is partitioned into a ''coherent'' component driving the lasing modes and the ''noncoherent'' remainder. Below threshold the current is known to grow as exp(qV/n/sub 0/KT); the algorithm proposes that extrapolation of this equation into the lasing region measures the noncoherent remainder, enabling deduction of the coherent component and of its current derivative eta/sub i/. Measurements on five (AlGa)As double-heterojunction lasers cut from one wafer demonstrate the power of the new method. Comparison with band calculations of Stern shows that n/sub 0/more » originates in carrier degeneracy.« less

Cyclic-nucleotide–gated cation current and Ca2+-activated Cl current elicited by odorant in vertebrate olfactory receptor neurons

PubMed Central

Li, Rong-Chang; Ben-Chaim, Yair; Yau, King-Wai; Lin, Chih-Chun

2016-01-01

Olfactory transduction in vertebrate olfactory receptor neurons (ORNs) involves primarily a cAMP-signaling cascade that leads to the opening of cyclic-nucleotide–gated (CNG), nonselective cation channels. The consequent Ca2+ influx triggers adaptation but also signal amplification, the latter by opening a Ca2+-activated Cl channel (ANO2) to elicit, unusually, an inward Cl current. Hence the olfactory response has inward CNG and Cl components that are in rapid succession and not easily separable. We report here success in quantitatively separating these two currents with respect to amplitude and time course over a broad range of odorant strengths. Importantly, we found that the Cl current is the predominant component throughout the olfactory dose–response relation, down to the threshold of signaling to the brain. This observation is very surprising given a recent report by others that the olfactory-signal amplification effected by the Ca2+-activated Cl current does not influence the behavioral olfactory threshold in mice. PMID:27647918

Regulatory Impact Analysis (RIA) for the Proposed Revisions to the Sulfur Dioxide National Ambient Air Quality Standards (NAAQS)

EPA Pesticide Factsheets

This Regulatory Impact Analysis (RIA) provides estimates of the incremental costs and monetized human health benefits of attaining a revised short‐term Sulfur Dioxide (SO2) NAAQS within the current monitoring network.

Best Practices for Use of Historical Control Data of Proliferative Rodent Lesions.

EPA Science Inventory

The Historical Control Data Working Group under the direction of the Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) was tasked with reviewing the current scientific practices, regulatory guidance and relevant literature pertaining ...

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...

Contribution of near-threshold currents to intrinsic oscillatory activity in rat medial entorhinal cortex layer II stellate cells

PubMed Central

Boehlen, Anne; Henneberger, Christian; Erchova, Irina

2013-01-01

The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells (SCs) in layer II of the entorhinal cortex are thought to contribute to network oscillations and thereby to the encoding of spatial information. Generation of both MPOs and resonance relies on the expression of specific voltage-dependent ion currents such as the hyperpolarization-activated cation current (IH), the persistent sodium current (INaP), and the noninactivating muscarine-modulated potassium current (IM). However, the differential contributions of these currents remain a matter of debate. We therefore examined how they modify neuronal excitability near threshold and generation of near-threshold MPOs and resonance in vitro. We found that resonance mainly relied on IH and was reduced by IH blockers and modulated by cAMP and an IM enhancer but that neither of the currents exhibited full control over MPOs in these cells. As previously reported, IH controlled a theta-frequency component of MPOs such that blockade of IH resulted in fewer regular oscillations that retained low-frequency components and high peak amplitude. However, pharmacological inhibition and augmentation of IM also affected MPO frequencies and amplitudes. In contrast to other cell types, inhibition of INaP did not result in suppression of MPOs but only in a moderation of their properties. We reproduced the experimentally observed effects in a single-compartment stochastic model of SCs, providing further insight into the interactions between different ionic conductances. PMID:23076110

Motor output evoked by subsaccadic stimulation of primate frontal eye fields.

PubMed

Corneil, Brian D; Elsley, James K; Nagy, Benjamin; Cushing, Sharon L

2010-03-30

In addition to its role in shifting the line of sight, the oculomotor system is also involved in the covert orienting of visuospatial attention. Causal evidence supporting this premotor theory of attention, or oculomotor readiness hypothesis, comes from the effect of subsaccadic threshold stimulation of the oculomotor system on behavior and neural activity in the absence of evoked saccades, which parallels the effects of covert attention. Here, by recording neck-muscle activity from monkeys and systematically titrating the level of stimulation current delivered to the frontal eye fields (FEF), we show that such subsaccadic stimulation is not divorced from immediate motor output but instead evokes neck-muscle responses at latencies that approach the minimal conduction time to the motor periphery. On average, neck-muscle thresholds were approximately 25% lower than saccade thresholds, and this difference is larger for FEF sites associated with progressively larger saccades. Importantly, we commonly observed lower neck-muscle thresholds even at sites evoking saccades

Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

NASA Astrophysics Data System (ADS)

Jensen, Ralph J.; Rizzo, Joseph F., III

2011-06-01

An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

Doctoral conceptual thresholds in cellular and molecular biology

NASA Astrophysics Data System (ADS)

Feldon, David F.; Rates, Christopher; Sun, Chongning

2017-12-01

In the biological sciences, very little is known about the mechanisms by which doctoral students acquire the skills they need to become independent scientists. In the postsecondary biology education literature, identification of specific skills and effective methods for helping students to acquire them are limited to undergraduate education. To establish a foundation from which to investigate the developmental trajectory of biologists' research skills, it is necessary to identify those skills which are integral to doctoral study and distinct from skills acquired earlier in students' educational pathways. In this context, the current study engages the framework of threshold concepts to identify candidate skills that are both obstacles and significant opportunities for developing proficiency in conducting research. Such threshold concepts are typically characterised as transformative, integrative, irreversible, and challenging. The results from interviews and focus groups with current and former doctoral students in cellular and molecular biology suggest two such threshold concepts relevant to their subfield: the first is an ability to effectively engage primary research literature from the biological sciences in a way that is critical without dismissing the value of its contributions. The second is the ability to conceptualise appropriate control conditions necessary to design and interpret the results of experiments in an efficient and effective manner for research in the biological sciences as a discipline. Implications for prioritising and sequencing graduate training experiences are discussed on the basis of the identified thresholds.

Intrinsic Plasticity Induced by Group II Metabotropic Glutamate Receptors via Enhancement of High Threshold KV Currents in Sound Localizing Neurons

PubMed Central

Hamlet, William R.; Lu, Yong

2016-01-01

Intrinsic plasticity has emerged as an important mechanism regulating neuronal excitability and output under physiological and pathological conditions. Here, we report a novel form of intrinsic plasticity. Using perforated patch clamp recordings, we examined the modulatory effects of group II metabotropic glutamate receptors (mGluR II) on voltage-gated potassium (KV) currents and the firing properties of neurons in the chicken nucleus laminaris (NL), the first central auditory station where interaural time cues are analyzed for sound localization. We found that activation of mGluR II by synthetic agonists resulted in a selective increase of the high threshold KV currents. More importantly, synaptically released glutamate (with reuptake blocked) also enhanced the high threshold KV currents. The enhancement was frequency-coding region dependent, being more pronounced in low frequency neurons compared to middle and high frequency neurons. The intracellular mechanism involved the Gβγ signaling pathway associated with phospholipase C and protein kinase C. The modulation strengthened membrane outward rectification, sharpened action potentials, and improved the ability of NL neurons to follow high frequency inputs. These data suggest that mGluR II provides a feedforward modulatory mechanism that may regulate temporal processing under the condition of heightened synaptic inputs. PMID:26964678

A Secure and Efficient Threshold Group Signature Scheme

NASA Astrophysics Data System (ADS)

Zhang, Yansheng; Wang, Xueming; Qiu, Gege

The paper presents a secure and efficient threshold group signature scheme aiming at two problems of current threshold group signature schemes: conspiracy attack and inefficiency. Scheme proposed in this paper takes strategy of separating designed clerk who is responsible for collecting and authenticating each individual signature from group, the designed clerk don't participate in distribution of group secret key and has his own public key and private key, designed clerk needs to sign part information of threshold group signature after collecting signatures. Thus verifier has to verify signature of the group after validating signature of the designed clerk. This scheme is proved to be secure against conspiracy attack at last and is more efficient by comparing with other schemes.

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.

Biological mechanisms of non-linear dose-response for respirable mineral fibers.

PubMed

Cox, Louis Anthony Tony

2018-06-19

Sufficiently high and prolonged inhalation exposures to some respirable elongated mineral particles (REMPs), notably including amphibole asbestos fibers, can increase risk of inflammation-mediated diseases including malignant mesothelioma, pleural diseases, fibrosis, and lung cancer. Chronic inflammation involves ongoing activation of the NLRP3 inflammasome, which enables immune cells to produce potent proinflammatory cytokines IL-1β and IL-18. Reactive oxygen species (ROS) (in particular, mitochondrial ROS) contribute to NRLP3 activation via a well-elucidated mechanism involving oxidation of reduced thioredoxin and association of thioredoxin-interacting protein with NLRP3. Lysosomal destabilization, efflux of cytosolic potassium ions and influx of calcium ions, signals from damaged mitochondria, both translational and post-translational controls, and prion-like polymerization have increasingly clear roles in regulating NLRP3 activation. As the molecular biology of inflammation-mediated responses to REMP exposure becomes clearer, a practical question looms: What do these mechanisms imply for the shape of the dose-response function relating exposure concentrations and durations for EMPs to risk of pathological responses? Dose-response thresholds or threshold-like nonlinearities can arise from (a) Cooperativity in assembly of supramolecular signaling complexes; (b) Positive feedback loops and bistability in regulatory networks; (c) Overwhelming of defensive barriers maintaining homeostasis; and (d) Damage thresholds, as in lysosome destabilization-induced activation of NLRP3. Each of these mechanisms holds for NLRP3 activation in response to stimuli such as REMP exposures. It is therefore timely to consider the implications of these advances in biological understanding for human health risk assessment with dose-response thresholds. Copyright © 2018. Published by Elsevier Inc.

Detection and traceability of genetically modified organisms in the food production chain.

PubMed

Miraglia, M; Berdal, K G; Brera, C; Corbisier, P; Holst-Jensen, A; Kok, E J; Marvin, H J P; Schimmel, H; Rentsch, J; van Rie, J P P F; Zagon, J

2004-07-01

Both labelling and traceability of genetically modified organisms are current issues that are considered in trade and regulation. Currently, labelling of genetically modified foods containing detectable transgenic material is required by EU legislation. A proposed package of legislation would extend this labelling to foods without any traces of transgenics. These new legislations would also impose labelling and a traceability system based on documentation throughout the food and feed manufacture system. The regulatory issues of risk analysis and labelling are currently harmonised by Codex Alimentarius. The implementation and maintenance of the regulations necessitates sampling protocols and analytical methodologies that allow for accurate determination of the content of genetically modified organisms within a food and feed sample. Current methodologies for the analysis of genetically modified organisms are focused on either one of two targets, the transgenic DNA inserted- or the novel protein(s) expressed- in a genetically modified product. For most DNA-based detection methods, the polymerase chain reaction is employed. Items that need consideration in the use of DNA-based detection methods include the specificity, sensitivity, matrix effects, internal reference DNA, availability of external reference materials, hemizygosity versus homozygosity, extrachromosomal DNA, and international harmonisation. For most protein-based methods, enzyme-linked immunosorbent assays with antibodies binding the novel protein are employed. Consideration should be given to the selection of the antigen bound by the antibody, accuracy, validation, and matrix effects. Currently, validation of detection methods for analysis of genetically modified organisms is taking place. In addition, new methodologies are developed, including the use of microarrays, mass spectrometry, and surface plasmon resonance. Challenges for GMO detection include the detection of transgenic material in materials with varying chromosome numbers. The existing and proposed regulatory EU requirements for traceability of genetically modified products fit within a broader tendency towards traceability of foods in general and, commercially, towards products that can be distinguished from each other. Traceability systems document the history of a product and may serve the purpose of both marketing and health protection. In this framework, segregation and identity preservation systems allow for the separation of genetically modified and non-modified products from "farm to fork". Implementation of these systems comes with specific technical requirements for each particular step of the food processing chain. In addition, the feasibility of traceability systems depends on a number of factors, including unique identifiers for each genetically modified product, detection methods, permissible levels of contamination, and financial costs. In conclusion, progress has been achieved in the field of sampling, detection, and traceability of genetically modified products, while some issues remain to be solved. For success, much will depend on the threshold level for adventitious contamination set by legislation. Copryright 2004 Elsevier Ltd.

Attenuation of Progressive Hearing Loss in DBA/2J Mice by Reagents that Affect Epigenetic Modifications Is Associated with Up-Regulation of the Zinc Importer Zip4

PubMed Central

Mutai, Hideki; Miya, Fuyuki; Fujii, Masato; Tsunoda, Tatsuhiko; Matsunaga, Tatsuo

2015-01-01

Various factors that are important for proper hearing have been identified, including serum levels of zinc. Here we investigated whether epigenetic regulatory pathways, which can be modified by environmental factors, could modulate hearing. RT-PCR detected expression of genes encoding DNA methyltransferase and histone deacetylase (Hdac) in the postnatal as well as adult mouse auditory epithelium. DBA/2J mice, which are a model for progressive hearing loss, were injected subcutaneously with one or a combination of the following reagents: L-methionine as a methyl donor, valproic acid as a pan-Hdac inhibitor, and folic acid and vitamin B12 as putative factors involved in age-related hearing loss. The mice were treated from ages 4 to 12 weeks (N ≥ 5), and auditory brainstem response (ABR) thresholds were measured at 8, 16, and 32 kHz. Treatment of the mice with a combination of L-methionine and valproic acid (M+V) significantly reduced the increase in the ABR threshold at 32 kHz. Treatment with any of these reagents individually produced no such effect. Microarray analyses detected 299 gene probes that were significantly up- or down-regulated in the cochleae of mice treated with M+V compared with the control vehicle-treated mice. Quantitative RT-PCR confirmed significant up-regulation of a zinc importer gene, Zip4, in the cochleae of mice treated with M+V. Immunohistochemistry demonstrated an intense Zip4 signal in cochlear tissues such as the lateral wall, organ of Corti, and spiral ganglion. Finally, mice treated with the Zip4 inducer (–)-epigallocatechin-3-O-gallate showed a significant reduction in the increase of the ABR threshold at 32 kHz and up-regulation of Zip4 expression in the cochlea. This study suggests that epigenetic regulatory pathways can modify auditory function and that zinc intake in the cochlea via Zip4 mediates maintenance of mammalian hearing. PMID:25875282

Bottom-up GGM algorithm for constructing multiple layered hierarchical gene regulatory networks

USDA-ARS?s Scientific Manuscript database

Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. A bottom-up graphic Gaus...

76 FR 11395 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... identify specific current regulations that may be outdated, ineffective, or excessively burdensome. The purpose of this regulatory review is to make the Department's regulations more effective and less... review existing significant regulations to determine if they are outmoded, ineffective, insufficient or...

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

PubMed Central

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

2013-01-01

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

Immunological self-tolerance: Lessons from mathematical modeling

NASA Astrophysics Data System (ADS)

Carneiro, Jorge; Paixao, Tiago; Milutinovic, Dejan; Sousa, Joao; Leon, Kalet; Gardner, Rui; Faro, Jose

2005-12-01

One of the fundamental properties of the immune system is its capacity to avoid autoimmune diseases. The mechanism underlying this process, known as self-tolerance, is hitherto unresolved but seems to involve the control of clonal expansion of autoreactive lymphocytes. This article reviews mathematical modeling of self-tolerance, addressing two specific hypotheses. The first hypothesis posits that self-tolerance is mediated by tuning of activation thresholds, which makes autoreactive T lymphocytes reversibly "anergic" and unable to proliferate. The second hypothesis posits that the proliferation of autoreactive T lymphocytes is instead controlled by specific regulatory T lymphocytes. Models representing the population dynamics of autoreactive T lymphocytes according to these two hypotheses were derived. For each model we identified how cell density affects tolerance, and predicted the corresponding phase spaces and bifurcations. We show that the simple induction of proliferative anergy, as modeled here, has a density dependence that is only partially compatible with adoptive transfers of tolerance, and that the models of tolerance mediated by specific regulatory T cells are closer to the observations.

Medicaid program; health care-related taxes.

PubMed

2008-02-22

This final rule revises the collection threshold under the regulatory indirect guarantee hold harmless arrangement test to reflect the provisions of the Tax Relief and Health Care Act of 2006. When determining whether there is an indirect guarantee under the 2-prong test for portions of fiscal years beginning on or after January 1, 2008 and before October 1, 2011, the allowable amount that can be collected from a health care-related tax is reduced from 6 to 5.5 percent of net patient revenues received by the taxpayers. This final rule also clarifies the standard for determining the existence of a hold harmless arrangement under the positive correlation test, Medicaid payment test, and the guarantee test (with conforming changes to parallel provisions concerning hold harmless arrangements with respect to provider-related donations); codifies changes to permissible class of health care items or services related to managed care organizations as enacted by the Deficit Reduction Act of 2005; and, removes obsolete transition period regulatory language.

The regulatory system for diabetes mellitus: Modeling rates of glucose infusions and insulin injections

NASA Astrophysics Data System (ADS)

Yang, Jin; Tang, Sanyi; Cheke, Robert A.

2016-08-01

Novel mathematical models with open and closed-loop control for type 1 or type 2 diabetes mellitus were developed to improve understanding of the glucose-insulin regulatory system. A hybrid impulsive glucose-insulin model with different frequencies of glucose infusions and insulin injections was analyzed, and the existence and uniqueness of the positive periodic solution for type 1 diabetes, which is globally asymptotically stable, was studied analytically. Moreover, permanence of the system for type 2 diabetes was demonstrated which showed that the glucose concentration level is uniformly bounded above and below. To investigate how to prevent hyperinsulinemia and hyperglycemia being caused by this system, we developed a model involving periodic intakes of glucose with insulin injections applied only when the blood glucose level reached a given critical glucose threshold. In addition, our numerical analysis revealed that the period, the frequency and the dose of glucose infusions and insulin injections are crucial for insulin therapies, and the results provide clinical strategies for insulin-administration practices.

Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control.

PubMed

Dong, Peng; Maddali, Manoj V; Srimani, Jaydeep K; Thélot, François; Nevins, Joseph R; Mathey-Prevot, Bernard; You, Lingchong

2014-09-01

A body of evidence has shown that the control of E2F transcription factor activity is critical for determining cell cycle entry and cell proliferation. However, an understanding of the precise determinants of this control, including the role of other cell-cycle regulatory activities, has not been clearly defined. Here, recognizing that the contributions of individual regulatory components could be masked by heterogeneity in populations of cells, we model the potential roles of individual components together with the use of an integrated system to follow E2F dynamics at the single-cell level and in real time. These analyses reveal that crossing a threshold amplitude of E2F accumulation determines cell cycle commitment. Importantly, we find that Myc is critical in modulating the amplitude, whereas cyclin D/E activities have little effect on amplitude but do contribute to the modulation of duration of E2F activation, thereby affecting the pace of cell cycle progression.

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

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

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

1999-01-04

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

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.

Does presence of metabolic syndrome impact anxiety and depressive disorder screening results in middle aged and elderly individuals? A population based study.

PubMed

Butnoriene, Jurate; Steibliene, Vesta; Saudargiene, Ausra; Bunevicius, Adomas

2018-01-08

Depressive and anxiety disorders are common in primary care setting but often remain undiagnosed. Metabolic syndrome (MetS) is also prevalent in the general population and can impair recognition of common mental disorders due to significant co-morbidity and overlap with psychiatric symptoms included in self-reported depression/anxiety screening tools. We investigated if MetS has an impact on the accuracy of current major depressive disorder (MDD) and generalized anxiety disorder (GAD) screening results using the Hospital Anxiety and Depression scale (HADS). A total of 1115 (562 men; mean age 62.0 ± 9.6 years) individuals of 45+ years of age were randomly selected from the general population and evaluated for current MetS; depressive and anxiety symptoms (HADS); and current MDD and GAD (Mini International Neuropsychiatric Interview [MINI]). The MetS was diagnosed in 34.4% of the study participants. Current MDD and GAD were more common in individuals with MetS relative to individuals without MetS (25.3% vs 14.2%, respectively, p < 0.001; and 30.2% vs 20.9%, respectively, p < 0.001). The ROC analyses demonstrated that optimal thresholds of the HADS-Depression subscale for current MDE were ≥9 in individuals with MetS (sensitivity = 87%, specificity = 73% and PPV = 52%) and ≥8 in individuals without MetS (sensitivity = 81%, specificity = 78% and PPV = 38%). At threshold of ≥9 the HADS-Anxiety subscale demonstrated optimal psychometric properties for current GAD screening in individuals with MetS (sensitivity = 91%, specificity = 85% and PPV = 72%) and without MetS (sensitivity = 84%, specificity = 83% and PPV = 56%). The HADS is a reliable screening tool for current MDE and GAD in middle aged and elderly population with and without MetS. Optimal thresholds of the HADS-Depression subscale for current MDD is ≥9 for individuals with MetS and ≥8 - without MetS. Optimal threshold of the HADS-Anxiety subscale is ≥9 for current GAD in individuals with and without MetS. The presence of MetS should be considered when interpreting depression screening results.

Toward Advancing Nano-Object Count Metrology: A Best Practice Framework

PubMed Central

Boyko, Volodymyr; Meyers, Greg; Voetz, Matthias; Wohlleben, Wendel

2013-01-01

Background: A movement among international agencies and policy makers to classify industrial materials by their number content of sub–100-nm particles could have broad implications for the development of sustainable nanotechnologies. Objectives: Here we highlight current particle size metrology challenges faced by the chemical industry due to these emerging number percent content thresholds, provide a suggested best-practice framework for nano-object identification, and identify research needs as a path forward. Discussion: Harmonized methods for identifying nanomaterials by size and count for many real-world samples do not currently exist. Although particle size remains the sole discriminating factor for classifying a material as “nano,” inconsistencies in size metrology will continue to confound policy and decision making. Moreover, there are concerns that the casting of a wide net with still-unproven metrology methods may stifle the development and judicious implementation of sustainable nanotechnologies. Based on the current state of the art, we propose a tiered approach for evaluating materials. To enable future risk-based refinements of these emerging definitions, we recommend that this framework also be considered in environmental and human health research involving the implications of nanomaterials. Conclusion: Substantial scientific scrutiny is needed in the area of nanomaterial metrology to establish best practices and to develop suitable methods before implementing definitions based solely on number percent nano-object content for regulatory purposes. Strong cooperation between industry, academia, and research institutions will be required to fully develop and implement detailed frameworks for nanomaterial identification with respect to emerging count-based metrics. Citation: Brown SC, Boyko V, Meyers G, Voetz M, Wohlleben W. 2013. Toward advancing nano-object count metrology: a best practice framework. Environ Health Perspect 121:1282–1291; http://dx.doi.org/10.1289/ehp.1306957 PMID:24076973

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

PubMed

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

2018-05-01

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

Interpreting the biological relevance of bioinformatic analyses with T-DNA sequence for protein allergenicity.

PubMed

Harper, B; McClain, S; Ganko, E W

2012-08-01

Global regulatory agencies require bioinformatic sequence analysis as part of their safety evaluation for transgenic crops. Analysis typically focuses on encoded proteins and adjacent endogenous flanking sequences. Recently, regulatory expectations have expanded to include all reading frames of the inserted DNA. The intent is to provide biologically relevant results that can be used in the overall assessment of safety. This paper evaluates the relevance of assessing the allergenic potential of all DNA reading frames found in common food genes using methods considered for the analysis of T-DNA sequences used in transgenic crops. FASTA and BLASTX algorithms were used to compare genes from maize, rice, soybean, cucumber, melon, watermelon, and tomato using international regulatory guidance. Results show that BLASTX for maize yielded 7254 alignments that exceeded allergen similarity thresholds and 210,772 alignments that matched eight or more consecutive amino acids with an allergen; other crops produced similar results. This analysis suggests that each nontransgenic crop has a much greater potential for allergenic risk than what has been observed clinically. We demonstrate that a meaningful safety assessment is unlikely to be provided by using methods with inherently high frequencies of false positive alignments when broadly applied to all reading frames of DNA sequence. Copyright © 2012 Elsevier Inc. All rights reserved.

Future Needs and Recommendations in the Development of ...

EPA Pesticide Factsheets

A species sensitivity distribution (SSD) is a probability model of the variation of species sensitivities to a stressor, in particular chemical exposure. The SSD approach has been used as a decision support tool in environmental protection and management since the 1980s, and the ecotoxicological, statistical and regulatory basis and applications continue to evolve. This article summarizes the findings of a 2014 workshop held by ECETOC (the European Center for Toxicology and Ecotoxicology of Chemicals) and the UK Environment Agency in Amsterdam, the Netherlands on the ecological relevance, statistical basis, and regulatory applications of SSDs. An array of research recommendations categorized under the topical areas of Use of SSDs, Ecological Considerations, Guideline Considerations, Method Development and Validation, Toxicity Data, Mechanistic Understanding and Uncertainty were identified and prioritized. A rationale for the most critical research needs identified in the workshop is provided. The workshop reviewed the technical basis and historical development and application of SSDs, described approaches to estimating generic and scenario specific SSD-based thresholds, evaluated utility and application of SSDs as diagnostic tools, and presented new statistical approaches to formulate SSDs. Collectively, these address many of the research needs to expand and improve their application. The highest priority work, from a pragmatic regulatory point of view, is t

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

PubMed

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

2004-03-01

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

Regulatory design governing progression of population growth phases in bacteria.

PubMed

Martínez-Antonio, Agustino; Lomnitz, Jason G; Sandoval, Santiago; Aldana, Maximino; Savageau, Michael A

2012-01-01

It has long been noted that batch cultures inoculated with resting bacteria exhibit a progression of growth phases traditionally labeled lag, exponential, pre-stationary and stationary. However, a detailed molecular description of the mechanisms controlling the transitions between these phases is lacking. A core circuit, formed by a subset of regulatory interactions involving five global transcription factors (FIS, HNS, IHF, RpoS and GadX), has been identified by correlating information from the well- established transcriptional regulatory network of Escherichia coli and genome-wide expression data from cultures in these different growth phases. We propose a functional role for this circuit in controlling progression through these phases. Two alternative hypotheses for controlling the transition between the growth phases are first, a continuous graded adjustment to changing environmental conditions, and second, a discontinuous hysteretic switch at critical thresholds between growth phases. We formulate a simple mathematical model of the core circuit, consisting of differential equations based on the power-law formalism, and show by mathematical and computer-assisted analysis that there are critical conditions among the parameters of the model that can lead to hysteretic switch behavior, which--if validated experimentally--would suggest that the transitions between different growth phases might be analogous to cellular differentiation. Based on these provocative results, we propose experiments to test the alternative hypotheses.

The Irish Cost-Effectiveness Threshold: Does it Support Rational Rationing or Might it Lead to Unintended Harm to Ireland's Health System?

PubMed

O'Mahony, James F; Coughlan, Diarmuid

2016-01-01

Ireland is one of the few countries worldwide to have an explicit cost-effectiveness threshold. In 2012, an agreement between government and the pharmaceutical industry that provided substantial savings on existing medications set the threshold at €45,000/quality-adjusted life-year (QALY). This replaced a previously unofficial threshold of €20,000/QALY. According to the agreement, drugs within the threshold will be granted reimbursement, whereas those exceeding it may still be approved following further negotiation. A number of drugs far exceeding the threshold have been approved recently. The agreement only applies to pharmaceuticals. There are four reasons for concern regarding Ireland's threshold. The absence of an explicit threshold for non-drug interventions leaves it unclear if there is parity in willingness to pay across all interventions. As the threshold resembles a price floor rather than a ceiling, in principle it only offers a weak barrier to cost-ineffective interventions. It has no empirical basis. Finally, it is probably too high given recent estimates of a threshold for the UK based on the cost effectiveness of services forgone of approximately £13,000/QALY. An excessive threshold risks causing the Irish health system unintended harm. The lack of an empirically informed threshold means the policy recommendations of cost-effectiveness analysis cannot be considered as fully evidence- based rational rationing. Policy makers should consider these issues and recent Irish legislation that defined cost effectiveness in terms of the opportunity cost of services forgone when choosing what threshold to apply once the current industry agreement expires at the end of 2015

Laser-induced retinal injury thresholds: variation with retinal irradiated area

NASA Astrophysics Data System (ADS)

Lund, David J.; Schulmeister, Karl; Seiser, Bernhard; Edthofer, Florian

2005-04-01

The retinal injury threshold for exposure to a laser source varies as a function of the irradiated area on the retina. Currently accepted guidelines for the safe use of lasers provide that the MPE will increase as the diameter of the irradiated area for retinal diameters between 25 mm and 1700 mm, based on the ED50 data available in the late 1970s. Recent studies by Zuclich and Lund produced data showing that the ED50 for ns-duration exposures at 532 nm and ms duration exposures at 590 nm varied as the square of the diameter of the irradiated area on the retina. This paper will discuss efforts to resolve the disagreement between the new data and the earlier data though an analysis of all accessible data relating the retinal injury threshold to the diameter of the incident beam on the retina and through simulations using computer models of laser-induced injury. The results show that the retinal radiant exposure required to produce retinal injury is a function of both exposure duration and retinal irradiance diameter and that the current guidelines for irradiance diameter dependence do not accurately reflect the variation of the threshold data.

Health claims on food products in Southeast Asia: regulatory frameworks, barriers, and opportunities.

PubMed

Tan, Karin Y M; van der Beek, Eline M; Chan, M Y; Zhao, Xuejun; Stevenson, Leo

2015-09-01

The Association of Southeast Asian Nations aims to act as a single market and allow free movement of goods, services, and manpower. The purpose of this article is to present an overview of the current regulatory framework for health claims in Southeast Asia and to highlight the current barriers and opportunities in the regulatory frameworks in the Association of Southeast Asian Nations. To date, 5 countries in Southeast Asia, i.e., Indonesia, Malaysia, the Philippines, Singapore, and Thailand, have regulations and guidelines to permit the use of health claims on food products. There are inconsistencies in the regulations and the types of evidence required for health claim applications in these countries. A clear understanding of the regulatory frameworks in these countries may help to increase trade in this fast-growing region and to provide direction for the food industry and the regulatory community to develop and market food products with better nutritional quality tailored to the needs of Southeast Asian consumers. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The regulatory battleground: A briefing for commanders

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

Wirick, D.

1995-12-31

This imperfect analogy likens the history and current status of public utility regulation to a military campaign. Clearly, the relationship between regulators and utilities has not always been combative, but intermittent conflict has necessarily characterized the relationship. Nonetheless, this military analogy describes some of the elements of the history of regulation and may have implications for regulatory policy in the near term. The scene is a battlefield headquarters not far from the heat of the conflict. The commanders of regulatory units are gathered. In the distance, the low rumble of troop movements can be heard. Ladies and gentlemen, please takemore » your seats. As you are aware, recent developments have placed regulatory forces in extreme jeopardy. Our forces are under stress, and though they continue to fight, the confusion of the current situation is beginning to take its toll. In most cases, reinforcements have been denied and our lines of logistical support have been weakened. Without effective and rapid action on our part, the regulatory battle will be lost and we will be driven from the field. Until consumers are well-enough armed to protect themselves, a process that is certainly suspect and potentially time-consuming, they will be powerless and undoubtedly victimized.« less

Trajectories of regulatory behaviors in early infancy: Determinants of infant self-distraction and self-comforting.

PubMed

Planalp, Elizabeth M; Braungart-Rieker, Julia M

2015-03-01

The ability to effectively regulate emotions is an important marker for early socioemotional development. The uses of self-comforting behaviors and self-distraction have been empirically supported as effective regulatory strategies for infants, though research on determinants of such behaviors is scarce. Thus, a more thorough examination of the development of regulatory behaviors is needed. For the current study, 135 mothers, fathers, and their infants participated in laboratory visits at 3-, 5-, and 7-months of age where parent sensitivity and infant regulatory strategies were coded from the Still Face Paradigm. Parents also filled out questionnaires about infant temperament and parental involvement. Using multi-level modeling to examine levels and trajectories of self-comforting and self-distraction, the current study found: 1) infants higher in temperamental surgency used more self-distraction and self-comforting, 2) infants lower in surgency with highly involved parents increased in self-distraction at a faster rate, particularly with highly involved fathers, and 3) infants used self-comforting more than average with fathers when the infant was also lower in temperamental regulation. In addition, we examined trajectories of parent involvement and temperament in relation to infant regulatory strategy.

Section 210 of PURPA and solar-thermal-energy development: the current regulatory environment and suggestions for future action. Task III report

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

Not Available

Section 210 of the Public Utility Regulatory Policies Act of 1978 (PURPA) (16 U.S.C. Section 824a-3) (Attachment 1) was enacted to overcome certain institutional barriers and to provide a favorable, non-discriminatory regulatory environment for the integration of electricity-producing solar thermal and other qualifying technologies into the electric utility network. PURPA Section 210 is designed to reduce these institutional barriers for qualifying cogeneration and small power production facilities (QF's) - terminology which includes solar thermal facilities producing electricity for sale, if other prerequisites are met - by exempting certain QF's from economically burdensome legal requirements applicable to electric utilities, and bymore » requiring utilities to offer to purchase electricity from, and sell electricity to, QF's at reasonable and non-discriminatory rates. The present and future PURPA Section 210 regulatory implications for solar thermal QF's are explored. The current PURPA Section 210 regulatory environment and its consequences for solar thermal energy development are outlined. Legislation pending before Congress to amend PURPA Section 210 is described. Possible amendments to PURPA Section 210 that might further stimulate construction and operation of economically sound solar thermal facilities are explored.« less

Environmental impacts and regulatory policy implications of spray disposal of dredged material in Louisiana wetlands

USGS Publications Warehouse

Cahoon, D.R.; Cowan, J.H.

1988-01-01

The capabilities of a new wetland dredging technology were assessed along with associated newly developed state and federal regulatory policies to determine if policy expectations realistically match the technological achievement. Current regulatory practices require amelioration of spoil bank impacts upon abandonment of an oil/gas well, but this may not occur for many years or decades, if at all. Recently, a dreding method (high-pressure spray spoil disposal) was developed that does not create a spoil bank in the traditional sense. Its potential for reducing environmental impacts was recognized immediately by regulatory agencies for whom minimizing spoil bank impacts is a major concern. The use of high-pressure spray disposal as a suitable alternative to traditional dreding technology has been adopted as policy even though its value as a management tool has never been tested or verified. A qualitative evaluation at two spoil disposal sites in saline marsh indicates that high-pressure spray disposal may indeed have great potential to minimize impacts, but most of this potential remains unverified. Also, some aspects of current regulatory policy may be based on unrealistic expectations as to the ability of this new technology to minimize or eliminate spoil bank impacts.

Ground-Water Quality Data in the Middle Sacramento Valley Study Unit, 2006 - Results from the California GAMA Program

USGS Publications Warehouse

Schmitt, Stephen J.; Fram, Miranda S.; Milby Dawson, Barbara J.; Belitz, Kenneth

2008-01-01

Ground-water quality in the approximately 3,340 square mile Middle Sacramento Valley study unit (MSACV) was investigated from June through September, 2006, as part of the California Groundwater Ambient Monitoring and Assessment (GAMA) program. The GAMA Priority Basin Assessment project was developed in response to the Groundwater Quality Monitoring Act of 2001 and is being conducted by the U.S. Geological Survey (USGS) in cooperation with the California State Water Resources Control Board (SWRCB). The Middle Sacramento Valley study was designed to provide a spatially unbiased assessment of raw ground-water quality within MSACV, as well as a statistically consistent basis for comparing water quality throughout California. Samples were collected from 108 wells in Butte, Colusa, Glenn, Sutter, Tehama, Yolo, and Yuba Counties. Seventy-one wells were selected using a randomized grid-based method to provide statistical representation of the study unit (grid wells), 15 wells were selected to evaluate changes in water chemistry along ground-water flow paths (flow-path wells), and 22 were shallow monitoring wells selected to assess the effects of rice agriculture, a major land use in the study unit, on ground-water chemistry (RICE wells). The ground-water samples were analyzed for a large number of synthetic organic constituents (volatile organic compounds [VOCs], gasoline oxygenates and degradates, pesticides and pesticide degradates, and pharmaceutical compounds), constituents of special interest (perchlorate, N-nitrosodimethylamine [NDMA], and 1,2,3-trichloropropane [1,2,3-TCP]), inorganic constituents (nutrients, major and minor ions, and trace elements), radioactive constituents, and microbial indicators. Naturally occurring isotopes (tritium, and carbon-14, and stable isotopes of hydrogen, oxygen, nitrogen, and carbon), and dissolved noble gases also were measured to help identify the sources and ages of the sampled ground water. Quality-control samples (blanks, replicates, laboratory matrix spikes) were collected at approximately 10 percent of the wells, and the results for these samples were used to evaluate the quality of the data for the ground-water samples. Field blanks rarely contained detectable concentrations of any constituent, suggesting that contamination was not a noticeable source of bias in the data for the ground-water samples. Differences between replicate samples were within acceptable ranges, indicating acceptably low variability. Matrix spike recoveries were within acceptable ranges for most constituents. This study did not attempt to evaluate the quality of water delivered to consumers; after withdrawal from the ground, water typically is treated, disinfected, or blended with other waters to maintain acceptable water quality. Regulatory thresholds apply to treated water that is served to the consumer, not to raw ground water. However, to provide some context for the results, concentrations of constituents measured in the raw ground water were compared with health-based thresholds established by the U.S. Environmental Protection Agency (USEPA) and California Department of Public Health (CDPH) and thresholds established for aesthetic concerns (secondary maximum contaminant levels, SMCL-CA) by CDPH. Comparisons between data collected for this study and drinking-water thresholds are for illustrative purposes only and are not indicative of compliance or noncompliance with regulatory thresholds. Most constituents that were detected in ground-water samples were found at concentrations below drinking-water thresholds. VOCs were detected in less than one-third and pesticides and pesticide degradates in just over one-half of the grid wells, and all detections of these constituents in samples from all wells of the MSACV study unit were below health-based thresholds. All detections of trace elements in samples from MSACV grid wells were below health-based thresholds, with the exceptions of arsenic and boro

Confronting Regulatory Cost and Quality Expectations. An Exploration of Technical Change in Minimum Efficiency Performance Standards

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

Taylor, Margaret; Spurlock, C. Anna; Yang, Hung-Chia

The dual purpose of this project was to contribute to basic knowledge about the interaction between regulation and innovation and to inform the cost and benefit expectations related to technical change which are embedded in the rulemaking process of an important area of national regulation. The area of regulation focused on here is minimum efficiency performance standards (MEPS) for appliances and other energy-using products. Relevant both to U.S. climate policy and energy policy for buildings, MEPS remove certain product models from the market that do not meet specified efficiency thresholds.

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves

PubMed Central

Bierer, Julie Arenberg; Faulkner, Kathleen F.

2010-01-01

Objectives The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar electrode configuration are predictive of wide or tip-shifted psychophysical tuning curves. Design Data were collected from five cochlear implant listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the partial tripolar configuration, for which a fraction of current (σ) from a center active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked psychophysical tuning curves were obtained for channels with the highest, lowest, and median tripolar (σ=1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (σ=0) or a more focused partial tripolar (σ ≥ 0.55) configuration. The masker channel and level were varied while the configuration was fixed to σ = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Results Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, σ, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a narrow, partial tripolar stimulus, had significantly broader psychophysical tuning curves than the lowest threshold channels. In two subjects, the tips of the tuning curves were shifted away from the probe channel. Tuning curves were also wider for the monopolar probes than with partial tripolar probes, for both the highest and lowest threshold channels. Conclusions These results suggest that single-channel thresholds measured with a restricted stimulus can be used to identify cochlear implant channels with poor spatial selectivity. Channels having wide or tip-shifted tuning characteristics would likely not deliver the appropriate spectral information to the intended auditory neurons, leading to suboptimal perception. As a clinical tool, quick identification of impaired channels could lead to patient-specific mapping strategies and result in improved speech and music perception. PMID:20090533

Low-income minority fathers' control strategies and children's regulatory skills

PubMed Central

Malin, Jenessa L.; Cabrera, Natasha J.; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith

2015-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24-months and children's regulatory skills at pre-kindergarten (pre-K). Using a sample of low-income minority families with 2-year-olds from the Early Head Start Evaluation Research Program (n = 71) we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24-months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at pre-kindergarten. There were three main findings. First, fathers' overwhelmingly use commands (e.g., do that) to promote compliance in their 24-month old children. Second, children's vocabulary skills predict fathers' regulatory behaviors during a father-child interaction, whereas children's gender predicts fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24-months predict children's sustained attention at pre-kindergarten whereas fathers' regulatory language at 24-months predicts children's emotion regulation at pre-kindergarten. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. PMID:25798496

Low-income, minority fathers' control strategies and their children's regulatory skills.

PubMed

Malin, Jenessa L; Cabrera, Natasha J; Karberg, Elizabeth; Aldoney, Daniela; Rowe, Meredith L

2014-01-01

The current study explored the bidirectional association of children's individual characteristics, fathers' control strategies at 24 months, and children's regulatory skills at prekindergarten (pre-K). Using a sample of low-income, minority families with 2-year-olds from the Early Head Start Research and Evaluation Project (n = 71), we assessed the association between child gender and vocabulary skills, fathers' control strategies at 24 months (e.g., regulatory behavior and regulatory language), and children's sustained attention and emotion regulation at prekindergarten. There were three main findings. First, fathers overwhelmingly used commands (e.g., "Do that.") to promote compliance in their 24-month-old children. Second, children's vocabulary skills predicted fathers' regulatory behaviors during a father-child interaction whereas children's gender predicted fathers' regulatory language during an interaction. Third, controlling for maternal supportiveness, fathers' regulatory behaviors at 24 months predicted children's sustained attention at pre-K whereas fathers' regulatory language at 24 months predicted children's emotion regulation at pre-K. Our findings highlight the importance of examining paternal contributions to children's regulatory skills. © 2014 Michigan Association for Infant Mental Health.

Mode control in a high-gain relativistic klystron amplifier

NASA Astrophysics Data System (ADS)

Li, Zheng-Hong; Zhang, Hong; Ju, Bing-Quan; Su, Chang; Wu, Yang

2010-05-01

Middle cavities between the input and output cavity can be used to decrease the required input RF power for the relativistic klystron amplifier. Meanwhile higher modes, which affect the working mode, are also easy to excite in a device with more middle cavities. In order for the positive feedback process for higher modes to be excited, a special measure is taken to increase the threshold current for such modes. Higher modes' excitation will be avoided when the threshold current is significantly larger than the beam current. So a high-gain S-band relativistic klystron amplifier is designed for the beam of current 5 kA and beam voltage 600 kV. Particle in cell simulations show that the gain is 1.6 × 105 with the input RF power of 6.8 kW, and that the output RF power reaches 1.1 GW.

RF Noise Generation in High-Pressure Short-Arc DC Xenon Lamps

NASA Astrophysics Data System (ADS)

Minayeva, Olga; Doughty, Douglas

2007-10-01

Continuous direct current xenon arcs will generate RF noise under certain circumstance, which can lead to excessive electro- magnetic interference in systems that use these arcs as light sources. Phenomenological observations are presented for xenon arcs having arc gaps ˜1 mm, cold fill pressures of ˜2.5 MPa, and currents up to 30 amps. Using a loop antenna in the vicinity of an operating lamp, it is observed that as the current to the arc is lowered there is a reproducible threshold at which the RF noise generation begins. This threshold is accompanied by a small abrupt drop in voltage (˜0.2 volts). The RF emission appears in pulses ˜150 nsec wide separated by ˜300 nec - the pulse interval decreases with decreasing current. The properties of the RF emission as a function of arc parameters (such as pressure, arc gap, electrode design) will be discussed and a semi-quantitative model presented.

COUNCIL FOR REGULATORY ENVIRONMENTAL MODELING (CREM) PILOT WATER QUALITY MODEL SELECTION TOOL

EPA Science Inventory

EPA's Council for Regulatory Environmental Modeling (CREM) is currently supporting the development of a pilot model selection tool that is intended to help the states and the regions implement the total maximum daily load (TMDL) program. This tool will be implemented within the ...

77 FR 26768 - Food and Drug Administration/International Society for Pharmaceutical Engineering Cosponsorship...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-07

... year, FDA speakers provide updates on current efforts affecting the development of global regulatory strategies, while industry professionals from some of today's leading pharmaceutical companies present case... hear directly from FDA experts and representatives of global regulatory authorities on best practices...

Issues in mass spectrometry between bench chemists and regulatory laboratory managers

USDA-ARS?s Scientific Manuscript database

At the 123rd AOAC Annual Meeting in Philadelphia, 45 residue chemists gathered for a roundtable discussion of mass spectrometry (MS) for regulatory purposes involving chemical residues analysis. The session was conceived to address current technical and communication issues about MS between “bench ...

Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

PubMed

Seabroke, Suzie; Wise, Lesley; Waller, Patrick

2013-10-01

The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations. Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA). An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action. The priority assigned by the tool was compared with the priority decided by collective judgement at the meeting. Once an acceptable level of concordance between the tool and the meeting had been achieved, the finalised tool was implemented into routine use at the MHRA, with an evaluation of its performance conducted after the first year. The Regulatory Pharmacovigilance Prioritisation System (RPPS) tool prioritises pharmacovigilance issues according to the following four broad categories, each with four inputs: strength of evidence, public health implications, agency regulatory obligations and public perceptions. A weighted scoring system links the inputs to a pre-defined number of points where if a threshold is reached then the points are awarded. The overall priority is determined by the sum of all points obtained from each of the inputs. The pilot study included a total of 73 pharmacovigilance issues during the 10-month study period, with an overall exact agreement between the RPPS priority and the collective judgement of the meeting of 60.3 %. Where exact agreement was not obtained, the RPPS generally prioritised the issues slightly higher than the meeting. Over the first year following implementation, the RPPS achieved an overall exact agreement of 82.2 %. Following the pilot study and implementation at the UK MHRA, the RPPS has provided a systematic approach to drug safety issue prioritisation that should help to reduce the subjectivity of reliance on individual judgement.

Prediction of spatially explicit rainfall intensity–duration thresholds for post-fire debris-flow generation in the western United States

USGS Publications Warehouse

Staley, Dennis M.; Negri, Jacquelyn; Kean, Jason W.; Laber, Jayme L.; Tillery, Anne C.; Youberg, Ann M.

2017-01-01

Early warning of post-fire debris-flow occurrence during intense rainfall has traditionally relied upon a library of regionally specific empirical rainfall intensity–duration thresholds. Development of this library and the calculation of rainfall intensity-duration thresholds often require several years of monitoring local rainfall and hydrologic response to rainstorms, a time-consuming approach where results are often only applicable to the specific region where data were collected. Here, we present a new, fully predictive approach that utilizes rainfall, hydrologic response, and readily available geospatial data to predict rainfall intensity–duration thresholds for debris-flow generation in recently burned locations in the western United States. Unlike the traditional approach to defining regional thresholds from historical data, the proposed methodology permits the direct calculation of rainfall intensity–duration thresholds for areas where no such data exist. The thresholds calculated by this method are demonstrated to provide predictions that are of similar accuracy, and in some cases outperform, previously published regional intensity–duration thresholds. The method also provides improved predictions of debris-flow likelihood, which can be incorporated into existing approaches for post-fire debris-flow hazard assessment. Our results also provide guidance for the operational expansion of post-fire debris-flow early warning systems in areas where empirically defined regional rainfall intensity–duration thresholds do not currently exist.

Prediction of spatially explicit rainfall intensity-duration thresholds for post-fire debris-flow generation in the western United States

NASA Astrophysics Data System (ADS)

Staley, Dennis M.; Negri, Jacquelyn A.; Kean, Jason W.; Laber, Jayme L.; Tillery, Anne C.; Youberg, Ann M.

2017-02-01

Early warning of post-fire debris-flow occurrence during intense rainfall has traditionally relied upon a library of regionally specific empirical rainfall intensity-duration thresholds. Development of this library and the calculation of rainfall intensity-duration thresholds often require several years of monitoring local rainfall and hydrologic response to rainstorms, a time-consuming approach where results are often only applicable to the specific region where data were collected. Here, we present a new, fully predictive approach that utilizes rainfall, hydrologic response, and readily available geospatial data to predict rainfall intensity-duration thresholds for debris-flow generation in recently burned locations in the western United States. Unlike the traditional approach to defining regional thresholds from historical data, the proposed methodology permits the direct calculation of rainfall intensity-duration thresholds for areas where no such data exist. The thresholds calculated by this method are demonstrated to provide predictions that are of similar accuracy, and in some cases outperform, previously published regional intensity-duration thresholds. The method also provides improved predictions of debris-flow likelihood, which can be incorporated into existing approaches for post-fire debris-flow hazard assessment. Our results also provide guidance for the operational expansion of post-fire debris-flow early warning systems in areas where empirically defined regional rainfall intensity-duration thresholds do not currently exist.

Highly temperature insensitive, low threshold-current density (λ = 8.7–8.8 μm) quantum cascade lasers

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

Kirch, J. D.; Chang, C.-C.; Boyle, C.

2015-04-13

By stepwise tapering, both the barrier heights and quantum-well depths in the active regions of 8.7–8.8 μm-emitting quantum-cascade-laser (QCL) structures, virtually complete carrier-leakage suppression is achieved. Such step-taper active-region-type QCLs possess, for 3 mm-long devices with high-reflectivity-coated back facets, threshold-current characteristic temperature coefficients, T{sub 0}, as high as 283 K and slope-efficiency characteristic temperature coefficients, T{sub 1}, as high as 561 K, over the 20–60 °C heatsink-temperature range. These high T{sub 0} and T{sub 1} values reflect at least a factor of four reduction in carrier-leakage current compared to conventional 8–9 μm-emitting QCLs. Room temperature, pulsed, threshold-current densities are 1.58 kA/cm{sup 2}; values comparable to those formore » 35-period conventional QCLs of similar injector-region doping level. Superlinear behavior of the light-current curves is shown to be the result of the onset of resonant extraction from the lower laser level at a drive level of ∼1.3× threshold. Maximum room-temperature slope efficiencies are 1.23 W/A; that is, slope efficiency per period values of 35 mW/A, which are 37%–40% higher than for same-geometry conventional 8–9 μm-emitting QCLs. Since the waveguide-loss coefficients are very similar, we estimate that the internal differential efficiency is at least 30% higher than in conventional QCLs. Such high internal differential efficiency values reflect the combined effect of nearly complete carrier-leakage suppression and high differential efficiency of the laser transition (∼90%), due to resonant extraction from the lower laser level.« less