Variability of Pasteurella multocida isolated from Icelandic sheep and detection of the toxA gene.

Science.gov (United States)

Einarsdottir, Thorbjorg; Gunnarsson, Eggert; Sigurdardottir, Olof G; Jorundsson, Einar; Fridriksdottir, Vala; Thorarinsdottir, Gudridur E; Hjartardottir, Sigridur

2016-09-01

Pasteurella multocida can be part of the upper respiratory flora of animals, but under conditions of stress or immunocompromisation, the bacteria can cause severe respiratory symptoms. In this study, we compared 10 P. multocida isolates from Icelandic sheep with respiratory symptoms and 19 isolates from apparently healthy abattoir sheep. We examined capsule type, genetic variability and the presence of the toxA gene in the two groups. Surprisingly, we found that all ovine P. multocida isolates examined in this study carried the toxA gene, which markedly differs from what has been published from other studies. Interestingly, all isolates from abattoir animals were capsule type D, whilst bacteria isolated from animals with clinical respiratory symptoms had capsule type A, D or F. Examination of seven housekeeping genes indicated that the clinical respiratory isolates were significantly more heterogeneous than the abattoir isolates (P<0.05, two-tailed Mann-Whitney U test). The results suggest that there may be at least two groups of P. multocida in sheep - a genetically homogeneous group that resides in the respiratory tract and a genetically heterogeneous group that is the predominant cause of disease.

FutureTox III: Bridges for Translation | Science Inventory | US ...

Science.gov (United States)

The present document describes key discussion points and outcomes of a Society of Toxicology (SOT) Contemporary Concepts in Toxicology (CCT) Workshop, entitled FutureTox III1,2 that was held in Crystal City, Virginia, November 19-20, 2015. The workshop built on the many lessons learned from the first 10 years of TT21 and the first two workshops in the FutureTox series (for summary of FutureTox II see (Knudsen et al., 2015); for summary of FutureTox I see (Rowlands et al., 2014)). FutureTox III was attended in person and via webcast by more than 300 scientists from government research and regulatory agencies, research institutes, academia, and the chemical and pharmaceutical industries in Europe, Canada, and the United States. The meeting materials for FutureTox III, currently available to meeting registrants at http://www.toxicology.org/events/shm/cct/meetings.asp#upcoming-pnl-open, will be open to the public on November 29, 2016. At this workshop, participants reviewed and discussed the state of the science in toxicology and human risk and exposure assessment with a focus on moving TT21 science into the arena of regulatory decision-making. This manuscript describes the outcome of the FutureTox III 'contemporary concepts in toxicology' conference of the Society Toxicology, held November 2015 in Crystal City VA.

TOX3 (TNRC9) overexpression in bladder cancer cells decreases cellular proliferation and triggers an interferon-like response

DEFF Research Database (Denmark)

Birkenkamp-Demtröder, Karin; Mansilla, Francisco; Andersen, Lars Dyrskjøt

2013-01-01

Background Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+-dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells overexpressing TOX3 followed by Pathway analysis showed that TOX3 overexpression mainly affected the Interferon Signaling Pathway. TOX3 upregulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 overexpressing...

Cross-species extrapolation of mammalian-based ToxCast Data using Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS)

Science.gov (United States)

In vitro high-throughput screening (HTS) and in silico technologies have emerged as 21st century tools for chemical hazard identification. In 2007 the U.S. Environmental Protection Agency (EPA) launched the ToxCast Program, which has screened thousands of chemicals in hundreds of...

TOX3 (TNRC9) Over Expression in Bladder Cancer Cells Decreases Cellular Proliferation and Triggers an Interferon-Like Response

DEFF Research Database (Denmark)

Birkenkamp-Demtroder, Karin; Mansilla Castaño, Francisco; Dyrskjøt, Lars

2013-01-01

Background: Human TOX3 (TOX high mobility group box family member 3) regulates Ca2+ dependent transcription in neurons and has been associated with breast cancer susceptibility. Aim of the study was to investigate the expression of TOX3 in bladder cancer tissue samples and to identify genes...... urothelium. Microarray expression profiling of human bladder cancer cells over expressing TOX3 followed by Pathway analysis showed that TOX3 Overexpression mainly affected the Interferon Signaling Pathway. TOX3 up regulation induced the expression of several genes with a gamma interferon activation site (GAS......), e.g. STAT1. In vitro functional studies showed that TOX3 was able to bind to the GAS-sequence located at the STAT1 promoter. siRNA mediated knockdown of TOX3 in RT4 bladder cancer cells decreased STAT1 expression suggesting a direct impact of TOX3 on STAT1. Immunoprecipitation of TOX3 over...

ToxRefDB - Release user-friendly web-based tool for mining ToxRefDB

Science.gov (United States)

The updated URL link is for a table of NCCT ToxCast public datasets. The next to last row of the table has the link for the US EPA ToxCast ToxRefDB Data Release October 2014. ToxRefDB provides detailed chemical toxicity data in a publically accessible searchable format. ToxRefD...

Modulation of Xenobiotic Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes by ToxCast Chemicals

Science.gov (United States)

ToxCast chemicals were assessed for induction or suppression of xenobiotic metabolizing enzyme and transporter gene expression using primary human hepatocytes. The mRNA levels of 14 target and 2 control genes were measured: ABCB1, ABCB11, ABCG2, SLCO1B1, CYP1A1, CYP1A2, CYP2B6, C...

ToxCast Workflow: High-throughput screening assay data processing, analysis and management (SOT)

Science.gov (United States)

US EPA’s ToxCast program is generating data in high-throughput screening (HTS) and high-content screening (HCS) assays for thousands of environmental chemicals, for use in developing predictive toxicity models. Currently the ToxCast screening program includes over 1800 unique c...

Deiodinase 1 Screening of ToxCast Phase 1 Chemical Library

Data.gov (United States)

U.S. Environmental Protection Agency — This excel spreadsheet contains the resultant data for over from inhibition assays with human Deiodinase 1 screened against the ToxCast Phase 1 chemical library and...

The Role of TOX in the Development of Innate Lymphoid Cells.

Science.gov (United States)

Seehus, Corey R; Kaye, Jonathan

2015-01-01

TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

The Role of TOX in the Development of Innate Lymphoid Cells

Directory of Open Access Journals (Sweden)

Corey R. Seehus

2015-01-01

Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

Analysis of ToxCast data for food-relevant compounds by ...

Science.gov (United States)

The ToxCast program has generated a wealth of in vitro high throughput screening data, and best approaches for the interpretation and use of these data remain undetermined. We present case studies comparing the ToxCast and in vivo toxicity data for two food contact substances using the RISK21 approach. Available exposure data, toxicity data, and model predictions were analyzed for sodium pyrithione and dibutyltin dichloride. In-vitro to in-vivo extrapolation (IVIVE) was performed to determine oral equivalent doses (OEDs) for the ToxCast data bioactivity. For sodium pyrithione, calculated OEDs corresponded to doses that demonstrated toxicity in animal studies. For dibutyltin dichloride, calculated OEDs were below the doses that demonstrated toxicity in animals, but this was confounded by the conservative estimates used in the IVIVE calculations. These studies highlight the potential of the ToxCast approach while also indicating areas where additional data or predictive tools are needed. We present case studies comparing the ToxCast and in vivo toxicity data for two food contact substances using the RISK21 approach.

“httk”: EPA’s Tool for High Throughput Toxicokinetics (CompTox CoP)

Science.gov (United States)

Thousands of chemicals have been pro?led by high-throughput screening programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics. Toxicokinetic models aid in predicting tissue concentr...

Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.

Directory of Open Access Journals (Sweden)

Salvador Almagro-Moreno

2015-04-01

Full Text Available Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the diarrheal disease, cholera. Two of its primary virulence regulators, TcpP and ToxR, are localized in the inner membrane. TcpP is encoded on the Vibrio Pathogenicity Island (VPI, a horizontally acquired mobile genetic element, and functions primarily in virulence gene regulation. TcpP has been shown to undergo regulated intramembrane proteolysis (RIP in response to environmental conditions that are unfavorable for virulence gene expression. ToxR is encoded in the ancestral genome and is present in non-pathogenic strains of V. cholerae, indicating it has roles outside of the human host. In this study, we show that ToxR undergoes RIP in V. cholerae in response to nutrient limitation at alkaline pH, a condition that occurs during the stationary phase of growth. This process involves the site-2 protease RseP (YaeL, and is dependent upon the RpoE-mediated periplasmic stress response, as deletion mutants for the genes encoding these two proteins cannot proteolyze ToxR under nutrient limitation at alkaline pH. We determined that the loss of ToxR, genetically or by proteolysis, is associated with entry of V. cholerae into a dormant state in which the bacterium is normally found in the aquatic environment called viable but nonculturable (VBNC. Strains that can proteolyze ToxR, or do not encode it, lose culturability, experience a change in morphology associated with cells in VBNC, yet remain viable under nutrient limitation at alkaline pH. On the other hand, mutant strains that cannot proteolyze ToxR remain culturable and maintain the morphology of cells in an active state of growth. Overall, our findings provide a link between the proteolysis of a virulence regulator and the entry of a pathogen into an environmentally persistent state.

The cysteine rich necrotrophic effector SnTox1 produced by Stagonospora nodorum triggers susceptibility of wheat lines harboring Snn1.

Directory of Open Access Journals (Sweden)

Zhaohui Liu

2012-01-01

Full Text Available The wheat pathogen Stagonospora nodorum produces multiple necrotrophic effectors (also called host-selective toxins that promote disease by interacting with corresponding host sensitivity gene products. SnTox1 was the first necrotrophic effector identified in S. nodorum, and was shown to induce necrosis on wheat lines carrying Snn1. Here, we report the molecular cloning and validation of SnTox1 as well as the preliminary characterization of the mechanism underlying the SnTox1-Snn1 interaction which leads to susceptibility. SnTox1 was identified using bioinformatics tools and verified by heterologous expression in Pichia pastoris. SnTox1 encodes a 117 amino acid protein with the first 17 amino acids predicted as a signal peptide, and strikingly, the mature protein contains 16 cysteine residues, a common feature for some avirulence effectors. The transformation of SnTox1 into an avirulent S. nodorum isolate was sufficient to make the strain pathogenic. Additionally, the deletion of SnTox1 in virulent isolates rendered the SnTox1 mutated strains avirulent on the Snn1 differential wheat line. SnTox1 was present in 85% of a global collection of S. nodorum isolates. We identified a total of 11 protein isoforms and found evidence for strong diversifying selection operating on SnTox1. The SnTox1-Snn1 interaction results in an oxidative burst, DNA laddering, and pathogenesis related (PR gene expression, all hallmarks of a defense response. In the absence of light, the development of SnTox1-induced necrosis and disease symptoms were completely blocked. By comparing the infection processes of a GFP-tagged avirulent isolate and the same isolate transformed with SnTox1, we conclude that SnTox1 may play a critical role during fungal penetration. This research further demonstrates that necrotrophic fungal pathogens utilize small effector proteins to exploit plant resistance pathways for their colonization, which provides important insights into the molecular

TOX3 mutations in breast cancer.

Directory of Open Access Journals (Sweden)

James Owain Jones

Full Text Available TOX3 maps to 16q12, a region commonly lost in breast cancers and recently implicated in the risk of developing breast cancer. However, not much is known of the role of TOX3 itself in breast cancer biology. This is the first study to determine the importance of TOX3 mutations in breast cancers. We screened TOX3 for mutations in 133 breast tumours and identified four mutations (three missense, one in-frame deletion of 30 base pairs in six primary tumours, corresponding to an overall mutation frequency of 4.5%. One potentially deleterious missense mutation in exon 3 (Leu129Phe was identified in one tumour (genomic DNA and cDNA. Whilst copy number changes of 16q12 are common in breast cancer, our data show that mutations of TOX3 are present at low frequency in tumours. Our results support that TOX3 should be further investigated to elucidate its role in breast cancer biology.

AMBIT RESTful web services: an implementation of the OpenTox application programming interface

Directory of Open Access Journals (Sweden)

Jeliazkova Nina

2011-05-01

Full Text Available Abstract The AMBIT web services package is one of the several existing independent implementations of the OpenTox Application Programming Interface and is built according to the principles of the Representational State Transfer (REST architecture. The Open Source Predictive Toxicology Framework, developed by the partners in the EC FP7 OpenTox project, aims at providing a unified access to toxicity data and predictive models, as well as validation procedures. This is achieved by i an information model, based on a common OWL-DL ontology ii links to related ontologies; iii data and algorithms, available through a standardized REST web services interface, where every compound, data set or predictive method has a unique web address, used to retrieve its Resource Description Framework (RDF representation, or initiate the associated calculations. The AMBIT web services package has been developed as an extension of AMBIT modules, adding the ability to create (Quantitative Structure-Activity Relationship (QSAR models and providing an OpenTox API compliant interface. The representation of data and processing resources in W3C Resource Description Framework facilitates integrating the resources as Linked Data. By uploading datasets with chemical structures and arbitrary set of properties, they become automatically available online in several formats. The services provide unified interfaces to several descriptor calculation, machine learning and similarity searching algorithms, as well as to applicability domain and toxicity prediction models. All Toxtree modules for predicting the toxicological hazard of chemical compounds are also integrated within this package. The complexity and diversity of the processing is reduced to the simple paradigm "read data from a web address, perform processing, write to a web address". The online service allows to easily run predictions, without installing any software, as well to share online datasets and models. The

AMBIT RESTful web services: an implementation of the OpenTox application programming interface.

Science.gov (United States)

Jeliazkova, Nina; Jeliazkov, Vedrin

2011-05-16

The AMBIT web services package is one of the several existing independent implementations of the OpenTox Application Programming Interface and is built according to the principles of the Representational State Transfer (REST) architecture. The Open Source Predictive Toxicology Framework, developed by the partners in the EC FP7 OpenTox project, aims at providing a unified access to toxicity data and predictive models, as well as validation procedures. This is achieved by i) an information model, based on a common OWL-DL ontology ii) links to related ontologies; iii) data and algorithms, available through a standardized REST web services interface, where every compound, data set or predictive method has a unique web address, used to retrieve its Resource Description Framework (RDF) representation, or initiate the associated calculations.The AMBIT web services package has been developed as an extension of AMBIT modules, adding the ability to create (Quantitative) Structure-Activity Relationship (QSAR) models and providing an OpenTox API compliant interface. The representation of data and processing resources in W3C Resource Description Framework facilitates integrating the resources as Linked Data. By uploading datasets with chemical structures and arbitrary set of properties, they become automatically available online in several formats. The services provide unified interfaces to several descriptor calculation, machine learning and similarity searching algorithms, as well as to applicability domain and toxicity prediction models. All Toxtree modules for predicting the toxicological hazard of chemical compounds are also integrated within this package. The complexity and diversity of the processing is reduced to the simple paradigm "read data from a web address, perform processing, write to a web address". The online service allows to easily run predictions, without installing any software, as well to share online datasets and models. The downloadable web application

ToxCast Profiling in a Human Stem Cell Assay for ...

Science.gov (United States)

Standard practice for assessing disruptions in embryogenesis involves testing pregnant animals of two species, typically rats and rabbits, exposed during major organogenesis and evaluated just prior to term. Under this design the major manifestations of developmental toxicity are observed as one or more apical endpoints including intrauterine death, fetal growth retardation, structural malformations and variations. Alternative approaches to traditional developmental toxicity testing have been proposed in the form of in vitro data (e.g., embryonic stem cells, zebrafish embryos, HTS assays) and in silico models (e.g., computational toxicology). To increase the diversity of assays used to assess developmental toxicity in EPA’s ToxCast program, we tested the chemicals in Stemina’s metabolomics-based platform that utilizes the commecrially available H9 human embryonic stem cell line. The devTOXqP dataset for ToxCast of high-quality based on replicate samples and model performance (82% balanced accuracy, 0.71 sensitivity and 1.00 specificity). To date, 136 ToxCast chemicals (12.8% of 1065 tested) were positive in this platform; 48 triggered the biomarker signal without any change in hESC viability and 88 triggered activity concurrent with effects on cell viability. Work is in progress to complete the STM dataset entry into the TCPL, compare data with results from zFish and mESC platforms, profile bioactivity (ToxCastDB), endpoints (ToxRefDB), chemotypes (DSSTox)

Metabolism Retrofit Strategies for ToxCast Assays (BOSC)

Science.gov (United States)

The EPA’s ToxCast program utilizes a wide variety of high-throughput screening assays (HTS) to assess chemical perturbations of molecular and cellular endpoints. A limitation of many HTS assays used for toxicity assessment is the lack of xenobiotic metabolism (XM) which precludes...

ToxR regulates the production of lipoproteins and the expression of serum resistance in Vibrio cholerae

International Nuclear Information System (INIS)

Parsot, C.; Taxman, E.; Mekalanos, J.J.

1991-01-01

The genes encoding three lipoproteins of Vibrio cholerae were identified by a combination of DNA sequence analysis and [ 3 H]palmitate labeling of hybrid proteins encoded by TnphoA gene fusions. The expression of these three lipoproteins, TagA, AcfD, and TcpC, was controlled by ToxR, the cholera toxin transcriptional activator. The involvement of other bacterial lipoproteins in conferring resistance ot the bactericidal effects of complement prompted us to examine this possibility in V. cholerae. Remarkably, mutations in toxR and tcp genes (including tcpC), involved in the biogenesis of the toxin coregulated pili, rendered V. cholerae about 10 4 - 10 6 times more sensitive to the vibriocidal activity of antibody and complement. Since V. cholerae is a noninvasive organism and toxR and tcp mutants are highly defective in intestinal colonization in animals and humans, these results raise the possibility that resistance to a gut-associated, complement-like bactericidal activity may be a major virulence determinant of V. cholerae and other enterobacterial species

Evaluation of Computational Docking to Identify Pregnane X Receptor Agonists in the ToxCast Database

OpenAIRE

Kortagere, Sandhya; Krasowski, Matthew D.; Reschly, Erica J.; Venkatesh, Madhukumar; Mani, Sridhar; Ekins, Sean

2010-01-01

Background The pregnane X receptor (PXR) is a key transcriptional regulator of many genes [e.g., cytochrome P450s (CYP2C9, CYP3A4, CYP2B6), MDR1] involved in xenobiotic metabolism and excretion. Objectives As part of an evaluation of different approaches to predict compound affinity for nuclear hormone receptors, we used the molecular docking program GOLD and a hybrid scoring scheme based on similarity weighted GoldScores to predict potential PXR agonists in the ToxCast database of pesticides...

Quantitative Structure-Use Relationship Model Predictions to evaluate Tox21 Chemicals as Functional Substitutes and Candidate Alternatives

Data.gov (United States)

U.S. Environmental Protection Agency — This dataset provides a prediction for all Tox21 chemicals with available QSUR descriptors across all 41 valid QSUR models developed with FUse. This dataset is...

77 FR 22321 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

Science.gov (United States)

2012-04-13

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Toxicology Program (NTP) Interagency Center for... (HTS) Assays for the Tox21 Initiative AGENCY: Division of the National Toxicology Program (DNTP...: April 5, 2012. John R. Bucher, Associate Director, National Toxicology Program. [FR Doc. 2012-8942 Filed...

Inverse gene-for-gene interactions contribute additively to tan spot susceptibility in wheat.

Science.gov (United States)

Liu, Zhaohui; Zurn, Jason D; Kariyawasam, Gayan; Faris, Justin D; Shi, Gongjun; Hansen, Jana; Rasmussen, Jack B; Acevedo, Maricelis

2017-06-01

Tan spot susceptibility is conferred by multiple interactions of necrotrophic effector and host sensitivity genes. Tan spot of wheat, caused by Pyrenophora tritici-repentis, is an important disease in almost all wheat-growing areas of the world. The disease system is known to involve at least three fungal-produced necrotrophic effectors (NEs) that interact with the corresponding host sensitivity (S) genes in an inverse gene-for-gene manner to induce disease. However, it is unknown if the effects of these NE-S gene interactions contribute additively to the development of tan spot. In this work, we conducted disease evaluations using different races and quantitative trait loci (QTL) analysis in a wheat recombinant inbred line (RIL) population derived from a cross between two susceptible genotypes, LMPG-6 and PI 626573. The two parental lines each harbored a single known NE sensitivity gene with LMPG-6 having the Ptr ToxC sensitivity gene Tsc1 and PI 626573 having the Ptr ToxA sensitivity gene Tsn1. Transgressive segregation was observed in the population for all races. QTL mapping revealed that both loci (Tsn1 and Tsc1) were significantly associated with susceptibility to race 1 isolates, which produce both Ptr ToxA and Ptr ToxC, and the two genes contributed additively to tan spot susceptibility. For isolates of races 2 and 3, which produce only Ptr ToxA and Ptr ToxC, only Tsn1 and Tsc1 were associated with tan spot susceptibility, respectively. This work clearly demonstrates that tan spot susceptibility in this population is due primarily to two NE-S interactions. Breeders should remove both sensitivity genes from wheat lines to obtain high levels of tan spot resistance.

Analysis of ToxCast data for food-relevant compounds by comparison with in vivo data using the RISK21 approach

Science.gov (United States)

The ToxCast program has generated a wealth of in vitro high throughput screening data, and best approaches for the interpretation and use of these data remain undetermined. We present case studies comparing the ToxCast and in vivo toxicity data for two food contact substances us...

eMolTox: prediction of molecular toxicity with confidence.

Science.gov (United States)

Ji, Changge; Svensson, Fredrik; Zoufir, Azedine; Bender, Andreas

2018-03-07

In this work we present eMolTox, a web server for the prediction of potential toxicity associated with a given molecule. 174 toxicology-related in vitro/vivo experimental datasets were used for model construction and Mondrian conformal prediction was used to estimate the confidence of the resulting predictions. Toxic substructure analysis is also implemented in eMolTox. eMolTox predicts and displays a wealth of information of potential molecular toxicities for safety analysis in drug development. The eMolTox Server is freely available for use on the web at http://xundrug.cn/moltox. chicago.ji@gmail.com or ab454@cam.ac.uk. Supplementary data are available at Bioinformatics online.

RapidTox Dashboard

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The ToxCast Dashboard helps users examine high-throughput assay data to inform chemical safety decisions. To date, it has data on over 9,000 chemicals and information from more than 1,000 high-throughput assay endpoint components.

ToxCast Dashboard

Science.gov (United States)

The ToxCast Dashboard helps users examine high-throughput assay data to inform chemical safety decisions. To date, it has data on over 9,000 chemicals and information from more than 1,000 high-throughput assay endpoint components.

Cheminformatics Analysis of EPA ToxCast Chemical Libraries ...

Science.gov (United States)

An important goal of toxicology research is the development of robust methods that use in vitro and chemical structure information to predict in vivo toxicity endpoints. The US EPA ToxCast program is addressing this goal using ~600 in vitro assays to create bioactivity profiles on a set of 320 compounds, mostly pesticide actives, that have well characterized in vivo toxicity. These 320 compounds (EPA-320 set evaluated in Phase I of ToxCast) are a subset of a much larger set of ~10,000 candidates that are of interest to the EPA (called here EPA-10K). Predictive models of in vivo toxicity are being constructed from the in vitro assay data on the EPA-320 chemical set. These models require validation on additional chemicals prior to wide acceptance, and this will be carried out by evaluating compounds from EPA-10K in Phase II of ToxCast. We have used cheminformatics approaches including clustering, data visualization, and QSAR to develop models for EPA-320 that could help prioritizing EPA-10K validation chemicals. Both chemical descriptors, as well as calculated physicochemical properties have been used. Compounds from EPA-10K are prioritized based on their similarity to EPA-320 using different similarity metrics, with similarity thresholds defining the domain of applicability for the predictive models built for EPA-320 set. In addition, prioritized lists of compounds of increasing dissimilarity from the EPA-320 have been produced, to test the ability of the EPA-320

ADME-Tox profiles of some food additives and pesticides

Science.gov (United States)

Craciun, Dana; Modra, Dorina; Isvoran, Adriana

2015-12-01

Within this study we compute the Absorption, Distribution, Metabolism, Excretion and Toxicity (ADME-Tox) profiles of several commonly used food additives and some pesticides. As expected, all the food additives considered in this study provided to be safe, their ADME-Tox profiles indicating that they have a good oral bioavailability and they do not produce phosphoslipidosis. The ADME-Tox profiles of the pesticides indicate that, with a few exceptions, they are highly toxic (some of them being not approved in the EU, but still used in other countries) and may cause many diseases. Our results are in good agreement with published data concerning the considered food additives and pesticides revealing that the ADME-Tox profiling method may be successfully used to test other chemicals than drug candidates.

OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia.

Science.gov (United States)

Tcheremenskaia, Olga; Benigni, Romualdo; Nikolova, Ivelina; Jeliazkova, Nina; Escher, Sylvia E; Batke, Monika; Baier, Thomas; Poroikov, Vladimir; Lagunin, Alexey; Rautenberg, Micha; Hardy, Barry

2012-04-24

The OpenTox Framework, developed by the partners in the OpenTox project (http://www.opentox.org), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing. The following related ontologies have been developed for OpenTox: a) Toxicological ontology - listing the toxicological endpoints; b) Organs system and Effects ontology - addressing organs, targets/examinations and effects observed in in vivo studies; c) ToxML ontology - representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology- representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink-ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology.OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources.The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists). The OpenTox toxicological ontology projects may be accessed via the OpenTox

Understanding the Biology and Technology of ToxCast and Tox21 Assays

Science.gov (United States)

The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

Applying network analysis and Nebula (neighbor-edges based and unbiased leverage algorithm) to ToxCast data.

Science.gov (United States)

Ye, Hao; Luo, Heng; Ng, Hui Wen; Meehan, Joe; Ge, Weigong; Tong, Weida; Hong, Huixiao

2016-01-01

ToxCast data have been used to develop models for predicting in vivo toxicity. To predict the in vivo toxicity of a new chemical using a ToxCast data based model, its ToxCast bioactivity data are needed but not normally available. The capability of predicting ToxCast bioactivity data is necessary to fully utilize ToxCast data in the risk assessment of chemicals. We aimed to understand and elucidate the relationships between the chemicals and bioactivity data of the assays in ToxCast and to develop a network analysis based method for predicting ToxCast bioactivity data. We conducted modularity analysis on a quantitative network constructed from ToxCast data to explore the relationships between the assays and chemicals. We further developed Nebula (neighbor-edges based and unbiased leverage algorithm) for predicting ToxCast bioactivity data. Modularity analysis on the network constructed from ToxCast data yielded seven modules. Assays and chemicals in the seven modules were distinct. Leave-one-out cross-validation yielded a Q(2) of 0.5416, indicating ToxCast bioactivity data can be predicted by Nebula. Prediction domain analysis showed some types of ToxCast assay data could be more reliably predicted by Nebula than others. Network analysis is a promising approach to understand ToxCast data. Nebula is an effective algorithm for predicting ToxCast bioactivity data, helping fully utilize ToxCast data in the risk assessment of chemicals. Published by Elsevier Ltd.

A Data Analysis Pipeline Accounting for Artifacts in Tox21 Quantitative High-Throughput Screening Assays.

Science.gov (United States)

Hsieh, Jui-Hua; Sedykh, Alexander; Huang, Ruili; Xia, Menghang; Tice, Raymond R

2015-08-01

A main goal of the U.S. Tox21 program is to profile a 10K-compound library for activity against a panel of stress-related and nuclear receptor signaling pathway assays using a quantitative high-throughput screening (qHTS) approach. However, assay artifacts, including nonreproducible signals and assay interference (e.g., autofluorescence), complicate compound activity interpretation. To address these issues, we have developed a data analysis pipeline that includes an updated signal noise-filtering/curation protocol and an assay interference flagging system. To better characterize various types of signals, we adopted a weighted version of the area under the curve (wAUC) to quantify the amount of activity across the tested concentration range in combination with the assay-dependent point-of-departure (POD) concentration. Based on the 32 Tox21 qHTS assays analyzed, we demonstrate that signal profiling using wAUC affords the best reproducibility (Pearson's r = 0.91) in comparison with the POD (0.82) only or the AC(50) (i.e., half-maximal activity concentration, 0.81). Among the activity artifacts characterized, cytotoxicity is the major confounding factor; on average, about 8% of Tox21 compounds are affected, whereas autofluorescence affects less than 0.5%. To facilitate data evaluation, we implemented two graphical user interface applications, allowing users to rapidly evaluate the in vitro activity of Tox21 compounds. © 2015 Society for Laboratory Automation and Screening.

Defining the taxonomic domain of applicability for mammalian-based high-throughput screening assays

Science.gov (United States)

Cell-based high throughput screening (HTS) technologies are becoming mainstream in chemical safety evaluations. The US Environmental Protection Agency (EPA) Toxicity Forecaster (ToxCastTM) and the multi-agency Tox21 Programs have been at the forefront in advancing this science, m...

CAirTOX, An inter-media transfer model for assessing indirect exposures to hazardous air contaminants

International Nuclear Information System (INIS)

McKone, T.E.

1994-01-01

Risk assessment is a quantitative evaluation of information on potential health hazards of environmental contaminants and the extent of human exposure to these contaminants. As applied to toxic chemical emissions to air, risk assessment involves four interrelated steps. These are (1) determination of source concentrations or emission characteristics, (2) exposure assessment, (3) toxicity assessment, and (4) risk characterization. These steps can be carried out with assistance from analytical models in order to estimate the potential risk associated with existing and future releases. CAirTOX has been developed as a spreadsheet model to assist in making these types of calculations. CAirTOX follows an approach that has been incorporated into the CalTOX model, which was developed for the California Department of Toxic Substances Control, With CAirTOX, we can address how contaminants released to an air basin can lead to contamination of soil, food, surface water, and sediments. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify uncertainty in multimedia, multiple-pathway exposure assessments. The capacity to explicitly address uncertainty has been incorporated into the model in two ways. First, the spreadsheet form of the model makes it compatible with Monte-Carlo add-on programs that are available for uncertainty analysis. Second, all model inputs are specified in terms of an arithmetic mean and coefficient of variation so that uncertainty analyses can be carried out

In vitro screening of environmental chemicals for targeted testing prioritization: the ToxCast project.

Science.gov (United States)

Judson, Richard S; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Mortensen, Holly M; Reif, David M; Rotroff, Daniel M; Shah, Imran; Richard, Ann M; Dix, David J

2010-04-01

Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use, and the thousands of environmental chemicals lacking toxicity data. The U.S. Environmental Protection Agency's ToxCast program aims to address these concerns by screening and prioritizing chemicals for potential human toxicity using in vitro assays and in silico approaches. This project aims to evaluate the use of in vitro assays for understanding the types of molecular and pathway perturbations caused by environmental chemicals and to build initial prioritization models of in vivo toxicity. We tested 309 mostly pesticide active chemicals in 467 assays across nine technologies, including high-throughput cell-free assays and cell-based assays, in multiple human primary cells and cell lines plus rat primary hepatocytes. Both individual and composite scores for effects on genes and pathways were analyzed. Chemicals displayed a broad spectrum of activity at the molecular and pathway levels. We saw many expected interactions, including endocrine and xenobiotic metabolism enzyme activity. Chemicals ranged in promiscuity across pathways, from no activity to affecting dozens of pathways. We found a statistically significant inverse association between the number of pathways perturbed by a chemical at low in vitro concentrations and the lowest in vivo dose at which a chemical causes toxicity. We also found associations between a small set of in vitro assays and rodent liver lesion formation. This approach promises to provide meaningful data on the thousands of untested environmental chemicals and to guide targeted testing of environmental contaminants.

CompTox Chemistry Dashboard webinar

Science.gov (United States)

The CompTox Chemistry Dashboard is part of a suite of dashboards developed by EPA to help evaluate the safety of chemicals. The dashboard provides access to a variety of information on over 700,000 chemicals currently in use. Within the application, users

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

International Nuclear Information System (INIS)

Vedani, Angelo; Dobler, Max; Smieško, Martin

2012-01-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

Energy Technology Data Exchange (ETDEWEB)

Vedani, Angelo, E-mail: angelo.vedani@unibas.ch [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland); Dobler, Max [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Smieško, Martin [Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland)

2012-06-01

The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

Chemical and HTS Profiling of 63 Cleft Palate Teratogens from ToxCast (FutureTox III)

Science.gov (United States)

Cleft palate is a common human birth defect that has been linked to both genetic and environmental factors. To characterize the potential molecular targets and biological processes across mechanistically diverse teratogens that cause cleft palate, we mined the ToxCast high-throug...

Distribution of the ompA-types among ruminant and swine pneumonic strains of Pasteurella multocida exhibiting various cap-locus and toxA patterns.

Science.gov (United States)

Vougidou, C; Sandalakis, V; Psaroulaki, A; Siarkou, V; Petridou, E; Ekateriniadou, L

2015-05-01

Pasteurella multocida is an important pathogen in food-producing animals and numerous virulence genes have been identified in an attempt to elucidate the pathogenesis of pasteurellosis. Currently, some of these genes including the capsule biosynthesis genes, the toxA and the OMPs-encoding genes have been suggested as epidemiological markers. However, the number of studies concerning ruminant isolates is limited, while, no attempt has ever been made to investigate the existence of ompA sequence diversity among P. multocida isolates. The aim of the present study was the comparative analysis of 144 P. multocida pneumonic isolates obtained from sheep, goats, cattle and pigs by determining the distribution of the ompA-types in conjunction with the cap-locus and toxA patterns. The ompA genotypes of the isolates were determined using both a PCR-RFLP method and DNA sequence analysis. The most prevalent capsule biosynthesis gene among the isolates was capA (86.1%); a noticeable, however, rate of capD-positive isolates (38.6%) was found among the ovine isolates that had been associated primarily with the capsule type A in the past. Moreover, an unexpectedly high percentage of toxA-positive pneumonic isolates was noticed among small ruminants (93.2% and 85.7% in sheep and goats, respectively), indicating an important epidemiological role of toxigenic P. multocida for these species. Despite their great heterogeneity, certain ompA-genotypes were associated with specific host species, showing evidence of a host preference. The OmpA-based PCR-RFLP method developed proved to be a valuable tool in typing P. multocida strains. Copyright © 2015 Elsevier GmbH. All rights reserved.

20180416 - Understanding the Biology and Technology of ToxCast and Tox21 Assays (SETAC Durham NC)

Science.gov (United States)

The ToxCast high-throughput toxicity (HTT) testing methods have been developed to evaluate the hazard potential of diverse environmental, industrial and consumer product chemicals. The main goal is prioritizing the compounds of greatest concern for more detailed toxicological stu...

Total Petroleum Hydrocarbons (TPH): ToxFAQs

Science.gov (United States)

... a state: This map displays locations where Total Petroleum Hydrocarbons (TPH) is known to be present. On ... I get more information? ToxFAQs TM for Total Petroleum Hydrocarbons (TPH) ( Hidrocarburos Totales de Petróleo (TPH) ) August ...

Genetic mapping of the regulator gene determining enterotoxin synthesis in Vibrio cholerae

International Nuclear Information System (INIS)

Smirnova, N.I.; Livanova, L.F.; Shaginyan, I.A.; Motin, V.L.

1986-01-01

Data on the genetic mapping of mutation tox-7 (the mutation affecting the synthesis of the cholera toxin) were obtained by conjugation crosses between the atoxigenic donor strain Vibrio cholerae Eltor and the toxigenic recipient strain V. cholera classica. The molecular and genetic analysis of the Tox - recombinants indicated that, when the synthesis of the cholera toxin is disrupted in these strains, the tox-7 mutation (which impairs the regulator gene tox) is gained. Close linkage between the tox-7 and pur-63 mutations was established (during the selection procedure there was 81.1% combined transfer with respect to marker pur-63 situated in the donor strain chromosome more proximal than mutation tox-7). The markers were localized in the following order in the region under investigation: asp-cys-nal-pur-61-trp-his-pur-63-tox-7-ile

Genes for carbon metabolism and the ToxA virulence factor in Pseudomonas aeruginosa are regulated through molecular interactions of PtxR and PtxS.

Directory of Open Access Journals (Sweden)

Abdelali Daddaoua

Full Text Available Homologs of the transcriptional regulator PtxS are omnipresent in Pseudomonas, whereas PtxR homologues are exclusively found in human pathogenic Pseudomonas species. In all Pseudomonas sp., PtxS with 2-ketogluconate is the regulator of the gluconate degradation pathway and controls expression from its own promoter and also from the P(gad and P(kgu for the catabolic operons. There is evidence that PtxS and PtxR play a central role in the regulation of exotoxin A expression, a relevant primary virulence factor of Pseudomonas aeruginosa. We show using DNaseI-footprint analysis that in P. aeruginosa PtxR binds to the -35 region of the P(toxA promoter in front of the exotoxin A gene, whereas PtxS does not bind to this promoter. Bioinformatic and DNaseI-footprint analysis identified a PtxR binding site in the P(kgu and P(gad promoters that overlaps the -35 region, while the PtxS operator site is located 50 bp downstream from the PtxR site. In vitro, PtxS recognises PtxR with nanomolar affinity, but this interaction does not occur in the presence of 2-ketogluconate, the specific effector of PtxS. DNAaseI footprint assays of P(kgu and P(gad promoters with PtxS and PtxR showed a strong region of hyper-reactivity between both regulator binding sites, indicative of DNA distortion when both proteins are bound; however in the presence of 2-ketogluconate no protection was observed. We conclude that PtxS modulates PtxR activity in response to 2-ketogluconate by complex formation in solution in the case of the P(toxA promoter, or via the formation of a DNA loop as in the regulation of gluconate catabolic genes. Data suggest two different mechanisms of control exerted by the same regulator.

5 CFR 451.103 - Agency award program(s).

Science.gov (United States)

2010-01-01

... for employees covered by this subpart. (b) Agencies are encouraged to involve employees in developing such programs. When agencies involve employees, the method of involvement shall be in accordance with... agency financial management controls and delegations of authority; and (2) Documenting justification for...

In silico ADME-Tox modeling: progress and prospects.

Science.gov (United States)

Alqahtani, Saeed

2017-11-01

Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials. Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds. It also provides a comprehensive overview and summarization of the latest modeling methods and algorithms available for the prediction of physicochemical characteristics, ADME properties, and drug toxicity issues. Expert opinion: The in silico models currently available have greatly contributed to the knowledge of screening approaches in the early stages of drug discovery and the development process. As the definitive goal of in silico molding is to predict the pharmacokinetics and disposition of compounds in vivo by assembling all kinetic processes within one global model, PBPK models can serve this purpose. However, much work remains to be done in this area to generate more data and input parameters to build more reliable and accurate prediction models.

Small-molecule inhibitors of toxT expression in Vibrio cholerae.

Science.gov (United States)

Anthouard, Rebecca; DiRita, Victor J

2013-08-06

Vibrio cholerae, a Gram-negative bacterium, infects humans and causes cholera, a severe disease characterized by vomiting and diarrhea. These symptoms are primarily caused by cholera toxin (CT), whose production by V. cholerae is tightly regulated by the virulence cascade. In this study, we designed and carried out a high-throughput chemical genetic screen to identify inhibitors of the virulence cascade. We identified three compounds, which we named toxtazin A and toxtazin B and B', representing two novel classes of toxT transcription inhibitors. All three compounds reduce production of both CT and the toxin-coregulated pilus (TCP), an important colonization factor. We present evidence that toxtazin A works at the level of the toxT promoter and that toxtazins B and B' work at the level of the tcpP promoter. Treatment with toxtazin B results in a 100-fold reduction in colonization in an infant mouse model of infection, though toxtazin A did not reduce colonization at the concentrations tested. These results add to the growing body of literature indicating that small-molecule inhibitors of virulence genes could be developed to treat infections, as alternatives to antibiotics become increasingly needed. V. cholerae caused more than 580,000 infections worldwide in 2011 alone (WHO, Wkly. Epidemiol. Rec. 87:289-304, 2012). Cholera is treated with an oral rehydration therapy consisting of water, glucose, and electrolytes. However, as V. cholerae is transmitted via contaminated water, treatment can be difficult for communities whose water source is contaminated. In this study, we address the need for new therapeutic approaches by targeting the production of the main virulence factor, cholera toxin (CT). The high-throughput screen presented here led to the identification of two novel classes of inhibitors of the virulence cascade in V. cholerae, toxtazin A and toxtazins B and B'. We demonstrate that (i) small-molecule inhibitors of virulence gene production can be

5 CFR 720.204 - Agency programs.

Science.gov (United States)

2010-01-01

... continuing program for the recruitment of minorities and women for positions in the agency and its components... out as part of their periodic performance appraisals. (b) Programs established under this subpart must... underrepresentation in the agency work force. ...

Virtual Liver: Estimating Proliferation and Apoptosis of Hepatocytes Exposed to Environmental Chemicals Using ToxCastTM Data

Science.gov (United States)

The U.S. EPA’s ToxCastTM program has screened over a thousand chemicals for potential toxicity using hundreds of high-throughput, in vitro assays. The U.S. EPA’s Virtual Liver (v-Liver™) is a cellular systems model of hepatic tissues that enables the estimation of in vivo effects...

20180312 - Profiling the ToxCast library with a pluripotent human (H9) embryonic stem cell assay (SOT)

Science.gov (United States)

The Stemina devTOX quickPredict platform (STM) is a human pluripotent H9 stem cell-based assay that predicts developmental toxicants. Using the STM model, we screened 1065 ToxCast chemicals and entered the data into the ToxCast data analysis pipeline. Model performance was 83.3% ...

FutureTox III: Bridges for Translation

Science.gov (United States)

The present document describes key discussion points and outcomes of a Society of Toxicology (SOT) Contemporary Concepts in Toxicology (CCT) Workshop, entitled FutureTox III1,2 that was held in Crystal City, Virginia, November 19-20, 2015. The workshop built on the many lessons l...

ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models.

Science.gov (United States)

Marvel, Skylar W; To, Kimberly; Grimm, Fabian A; Wright, Fred A; Rusyn, Ivan; Reif, David M

2018-03-05

Drawing integrated conclusions from diverse source data requires synthesis across multiple types of information. The ToxPi (Toxicological Prioritization Index) is an analytical framework that was developed to enable integration of multiple sources of evidence by transforming data into integrated, visual profiles. Methodological improvements have advanced ToxPi and expanded its applicability, necessitating a new, consolidated software platform to provide functionality, while preserving flexibility for future updates. We detail the implementation of a new graphical user interface for ToxPi (Toxicological Prioritization Index) that provides interactive visualization, analysis, reporting, and portability. The interface is deployed as a stand-alone, platform-independent Java application, with a modular design to accommodate inclusion of future analytics. The new ToxPi interface introduces several features, from flexible data import formats (including legacy formats that permit backward compatibility) to similarity-based clustering to options for high-resolution graphical output. We present the new ToxPi interface for dynamic exploration, visualization, and sharing of integrated data models. The ToxPi interface is freely-available as a single compressed download that includes the main Java executable, all libraries, example data files, and a complete user manual from http://toxpi.org .

In Silico Prediction of Physicochemical Properties of Environmental Chemicals Using Molecular Fingerprints and Machine Learning

Science.gov (United States)

There are little available toxicity data on the vast majority of chemicals in commerce. High-throughput screening (HTS) studies, such as those being carried out by the U.S. Environmental Protection Agency (EPA) ToxCast program in partnership with the federal Tox21 research progra...

Effect of toxin-g from Tityus serrulatus scorpion venom on gastric emptying in rats

Directory of Open Access Journals (Sweden)

F. Bucaretchi

1999-04-01

Full Text Available The effect of toxin-g from Tityus serrulatus scorpion venom on the gastric emptying of liquids was studied in 176 young adult male Wistar rats (2-3 months of age divided into subgroups of 8 animals each. Toxin-g was injected iv at doses of 25, 37.5, 50 or 100 µg/kg and the effect on gastric emptying was assessed 30 min and 8 h later. A time-course study was also performed by injecting 50 µg of toxin-g /kg and measuring the effect on gastric emptying at times 0.25, 0.5, 1, 2, 4, 8, 24 and 48 h post-venom. Each envenomed animal was paired with its saline control and all received a saline test meal solution containing phenol red (60 µg/ml as a marker. Ten minutes after administering the test meal by gavage the animals were sacrificed and gastric retention was determined by measuring the residual marker concentration of the test meal. A significant delay in gastric emptying, at 30 min and 8 h post-venom, was observed only after 50 and 100 µg of toxin-g /kg compared to control values. The responses to these two doses were significantly different after 8 h post-venom. Toxin-g (50 µg/kg significantly delayed the gastric emptying of liquids at all times studied, with a peak response at 4 h after toxin administration compared to control values. These results indicate that the iv injection of toxin-g may induce a rapid, intense and sustained inhibition of gastric emptying 0.25 to 48 h after envenomation.

CBirTox is a selective antigen-specific agonist of the Treg-IgA-microbiota homeostatic pathway.

Directory of Open Access Journals (Sweden)

Katie L Alexander

Full Text Available Cultivating an environment of mutualism between host cells and the microbiota is vital, and dysregulation of this relationship is associated with multiple immune disorders including metabolic and skin diseases, asthma, allergy, and Inflammatory Bowel Disease (IBD. One prominent mechanism for maintaining homeostasis is the protective regulatory T cell (Treg- Immunoglobulin A (IgA pathway toward microbiota antigens, in which Tregs maintain homeostasis and provide critical survival factors to IgA+ B cells. In order to amplify the Treg-IgA pathway, we have generated a fusion protein, CBirTox, comprised of a portion of the carboxy terminus of CBir1, a microbiota flagellin, genetically coupled to Cholera Toxin B subunit (CTB via the A2 linker of CT. Both dendritic cells (DCs and B cells pulsed with CBirTox selectively induced functional CD4+Foxp3+ Tregs in vitro, and CBirTox augmented CD4+Foxp3+ cell numbers in vivo. The induced Foxp3 expression was independent of retinoic acid (RA signaling but was inhibited by neutralization of TGF-β. CBirTox treatment of B cells downregulated mammalian target of rapamycin (mTOR signaling. Furthermore, CBirTox-pulsed DCs induced substantial production of IgA from naïve B cells. Collectively these data demonstrate that CBirTox represents a novel approach to bolstering the Treg-IgA pathway at the host-microbiota interface.

ProTox: a web server for the in silico prediction of rodent oral toxicity.

Science.gov (United States)

Drwal, Malgorzata N; Banerjee, Priyanka; Dunkel, Mathias; Wettig, Martin R; Preissner, Robert

2014-07-01

Animal trials are currently the major method for determining the possible toxic effects of drug candidates and cosmetics. In silico prediction methods represent an alternative approach and aim to rationalize the preclinical drug development, thus enabling the reduction of the associated time, costs and animal experiments. Here, we present ProTox, a web server for the prediction of rodent oral toxicity. The prediction method is based on the analysis of the similarity of compounds with known median lethal doses (LD50) and incorporates the identification of toxic fragments, therefore representing a novel approach in toxicity prediction. In addition, the web server includes an indication of possible toxicity targets which is based on an in-house collection of protein-ligand-based pharmacophore models ('toxicophores') for targets associated with adverse drug reactions. The ProTox web server is open to all users and can be accessed without registration at: http://tox.charite.de/tox. The only requirement for the prediction is the two-dimensional structure of the input compounds. All ProTox methods have been evaluated based on a diverse external validation set and displayed strong performance (sensitivity, specificity and precision of 76, 95 and 75%, respectively) and superiority over other toxicity prediction tools, indicating their possible applicability for other compound classes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

TOX sets the stage for innate lymphoid cells

NARCIS (Netherlands)

Spits, Hergen

2015-01-01

Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process

Toxicology in the 21st Century (Tox21)

Science.gov (United States)

Tox21 researchers aim to develop better toxicity assessment methods to quickly and efficiently test whether certain chemical compounds have the potential to disrupt processes in the human body that may lead to negative health effects.

TOXsIgN: a cross-species repository for toxicogenomic signatures.

Science.gov (United States)

Darde, Thomas A; Gaudriault, Pierre; Beranger, Rémi; Lancien, Clément; Caillarec-Joly, Annaëlle; Sallou, Olivier; Bonvallot, Nathalie; Chevrier, Cécile; Mazaud-Guittot, Séverine; Jégou, Bernard; Collin, Olivier; Becker, Emmanuelle; Rolland, Antoine D; Chalmel, Frédéric

2018-01-27

At the same time that toxicologists express increasing concern about reproducibility in this field, the development of dedicated databases has already smoothed the path toward improving the storage and exchange of raw toxicogenomic data. Nevertheless, none provides access to analyzed and interpreted data as originally reported in scientific publications. Given the increasing demand for access to this information, we developed TOXsIgN, a repository for TOXicogenomic sIgNatures. The TOXsIgN repository provides a flexible environment that facilitates online submission, storage, and retrieval of toxicogenomic signatures by the scientific community. It currently hosts 754 projects that describe more than 450 distinct chemicals and their 8491 associated signatures. It also provides users with a working environment containing a powerful search engine as well as bioinformatics/biostatistics modules that enable signature comparisons or enrichment analyses. The TOXsIgN repository is freely accessible at http://toxsign.genouest.org. Website implemented in Python, JavaScript, and MongoDB, with all major browsers supported. frederic.chalmel@inserm.fr. Supplementary data are available at Bioinformatics online. © The Author (2018). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Tutorial Video Series: Using Stakeholder Outreach to Increase Usage of ToxCast Data (SETAC EU)

Science.gov (United States)

The limited amount of toxicity data on thousands of chemicals found in consumer products has led to the development of research endeavors such as the U.S. EPA’s Toxicity Forecaster (ToxCast). ToxCast uses high-throughput screening technology to evaluate thousands of chemicals for...

Predicting Developmental Toxicity of ToxCast Phase I Chemicals Using Human Embryonic Stem Cells and Metabolomics

Science.gov (United States)

EPA’s ToxRefDB contains prenatal guideline study data from rats and rabbits for over 240 chemicals that overlap with the ToxCast in vitro high throughput screening project. A subset of these compounds were tested in Stemina Biomarker Discovery's developmental toxicity platform, a...

Highlight report: Launch of a large integrated European in vitro toxicology project: EU-ToxRisk.

Science.gov (United States)

Daneshian, Mardas; Kamp, Hennicke; Hengstler, Jan; Leist, Marcel; van de Water, Bob

2016-05-01

The integrated European project, EU-ToxRisk, proudly sees itself as "flagship" exploring new alternative-to-animal approaches to chemical safety evaluation. It promotes mechanism-based toxicity testing and risk assessment according to the principles laid down for toxicology for the twenty-first century. The project was officially launched in January 2016 with a kickoff meeting in Egmond aan Zee, the Netherlands. Over 100 scientists representing academia and industry as well as regulatory authorities attended the inaugural meeting. The project will integrate advances in in vitro and in silico toxicology, read-across methods, and adverse outcome pathways. EU-ToxRisk will continue to make use of the case study strategy deployed in SEURAT-1, a FP7 initiative ended in December 2015. Even though the development of new non-animal methods is one target of EU-ToxRisk, the project puts special emphasis on their acceptance and implementation in regulatory contexts. This €30 million Horizon 2020 project involves 38 European partners and one from the USA. EU-ToxRisk aims at the "development of a new way of risk assessment."

Toxicology Testing in the 21st Century (Tox21)

Science.gov (United States)

Tox21 researchers aim to develop better toxicity assessment methods to quickly and efficiently test whether certain chemical compounds have the potential to disrupt processes in the human body that may lead to negative health effects.

OpenVirtualToxLab--a platform for generating and exchanging in silico toxicity data.

Science.gov (United States)

Vedani, Angelo; Dobler, Max; Hu, Zhenquan; Smieško, Martin

2015-01-22

The VirtualToxLab is an in silico technology for estimating the toxic potential--endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity--of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of currently 16 proteins, known or suspected to trigger adverse effects: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The toxic potential of a compound--its ability to trigger adverse effects--is derived from its computed binding affinities toward these very proteins: the computationally demanding simulations are executed in client-server model on a Linux cluster of the University of Basel. The graphical-user interface supports all computer platforms, allows building and uploading molecular structures, inspecting and downloading the results and, most important, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. Access to the VirtualToxLab is available free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

An Evaluation of ToxCast Angiogenic Disruptors for Effects on Mitochondrial Bioactivity Profiles (Teratology Society Annual Meeting)

Science.gov (United States)

Angiogenesis is a critical developmental process and a potential target for chemical teratogenesis. Over one-tenth of the Tox21 library of 10,000 compounds have been shown to disrupt mitochondrial function [Attene-Ramos et al., 2015]. Previous studies utilizing ToxCast chemicals ...

Understanding social media program usage in public transit agencies

OpenAIRE

Jenny H. Liu; Wei Shi; O.A. (Sam) Elrahman; Xuegang (Jeff) Ban; Jack M. Reilly

2016-01-01

Social media has been gaining prominence in public transit agencies in their communication strategies and daily management. This study aims to better understand recent trends in social media usage in public transit agencies, to examine which agencies use what kind of social media programs for what purposes, and how they measure their programs. A survey was conducted of the top transit agencies in the nation, and results are examined through descriptive statistical analysis, correlation analys...

Structure Identification Using High Resolution Mass Spectrometry Data and the EPA’s CompTox Chemistry Dashboard (EAS)

Science.gov (United States)

The iCSS CompTox Dashboard is a publicly accessible dashboard provided by the National Center for Computation Toxicology at the US-EPA. It serves a number of purposes, including providing a chemistry database underpinning many of our public-facing projects (e.g. ToxCast and ExpoC...

Extending the Derek-Meteor Workflow to Predict Chemical-Toxicity Space Impacted by Metabolism: Application to ToxCast and Tox21 Chemical Inventories

Science.gov (United States)

A central aim of EPA’s ToxCast project is to use in vitro high-throughput screening (HTS) profiles to build predictive models of in vivo toxicity. Where assays lack metabolic capability, such efforts may need to anticipate the role of metabolic activation (or deactivation). A wo...

Development of a toxR-based loop-mediated isothermal amplification assay for detecting Vibrio parahaemolyticus

Directory of Open Access Journals (Sweden)

Ge Beilei

2010-02-01

Full Text Available Abstract Background Vibrio parahaemolyticus is a leading cause of seafood-related bacterial gastroenteritis and outbreaks worldwide. Sensitive and specific detection methods are needed to better control V. parahaemolyticus infections. This study aimed at developing a highly specific and sensitive loop-mediated isothermal amplification (LAMP assay for detecting V. parahaemolyticus in oysters. A set of five LAMP primers, two outer, two inner, and one loop were designed based on the published V. parahaemolyticus toxR sequence. Specificity of the assay was evaluated using a panel of 36 V. parahaemolyticus and 39 other strains. The assay sensitivity was determined using serial dilutions of V. parahaemolyticus ATCC 27969 culture ranging from 108 CFU/ml to extinction. The assay was also tested in experimentally inoculated oyster samples. Results The toxR-based LAMP assay was able to specifically detect all of the 36 V. parahaemolyticus strains without amplification from 39 other strains. The detection limit was 47-470 cells per reaction in pure culture, up to 100-fold more sensitive than that of toxR-PCR. When applied in spiked oysters, the assay was able to detect 1.1 × 105 V. parahaemolyticus cells per gram of oyster without enrichment, up to 100-fold more sensitive than that of toxR-PCR. Standard curves generated for detecting V. parahaemolyticus in both pure culture and spiked oyster samples showed good linear relationship between cell numbers and the fluorescence or turbidity signals. Conclusions The toxR-based LAMP assay developed in this study was sensitive, specific, and quantitative, holding great potential for future field detection of V. parahaemolyticus in raw oysters.

Value of shared preclinical safety studies - The eTOX database.

Science.gov (United States)

Briggs, Katharine; Barber, Chris; Cases, Montserrat; Marc, Philippe; Steger-Hartmann, Thomas

2015-01-01

A first analysis of a database of shared preclinical safety data for 1214 small molecule drugs and drug candidates extracted from 3970 reports donated by thirteen pharmaceutical companies for the eTOX project (www.etoxproject.eu) is presented. Species, duration of exposure and administration route data were analysed to assess if large enough subsets of homogenous data are available for building in silico predictive models. Prevalence of treatment related effects for the different types of findings recorded were analysed. The eTOX ontology was used to determine the most common treatment-related clinical chemistry and histopathology findings reported in the database. The data were then mined to evaluate sensitivity of established in vivo biomarkers for liver toxicity risk assessment. The value of the database to inform other drug development projects during early drug development is illustrated by a case study.

Characterization of Vibrio parahaemolyticus isolated from oysters in Korea: Resistance to various antibiotics and prevalence of virulence genes.

Science.gov (United States)

Kang, Chang-Ho; Shin, YuJin; Jang, SeokCheol; Yu, HongSik; Kim, SuKyung; An, Sera; Park, Kunbawui; So, Jae-Seong

2017-05-15

Vibrio parahaemolyticus, found frequently in oysters, is the most prevalent gastroenteritis-causing pathogen in Korea and in several other Asian countries. This study monitored changes in the environmental parameters and occurrence of V. parahaemolyticus in oyster aquaculture sites. Of the 44 presumed V. parahaemolyticus isolates obtained, when tested against 16 antibiotics, 90.9, 86.4, and 75.0% of the 44 isolates exhibited resistance to vancomycin, ampicillin, and streptomycin, respectively. PCR analysis for the presence of the toxR gene confirmed 31 of the 44 isolates as being positive V. parahaemolyticus strains. The toxR positive isolates were tested for the presence of thermostable direct hemolysin (tdh) and tdh-related hemolysin (trh) virulence genes. Only 9.1% toxR positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The occurrence of multi drug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conjugated Linoleic Acid Reduces Cholera Toxin Production In Vitro and In Vivo by Inhibiting Vibrio cholerae ToxT Activity.

Science.gov (United States)

Withey, Jeffrey H; Nag, Drubhajyoti; Plecha, Sarah C; Sinha, Ritam; Koley, Hemanta

2015-12-01

The severe diarrheal disease cholera is endemic in over 50 countries. Current therapies for cholera patients involve oral and/or intravenous rehydration, often combined with the use of antibiotics to shorten the duration and intensity of the disease. However, as antibiotic resistance increases, treatment options will become limited. Linoleic acid has been shown to be a potent negative effector of V. cholerae virulence that acts on the major virulence transcription regulator protein, ToxT, to inhibit virulence gene expression. ToxT activates transcription of the two major virulence factors required for disease, cholera toxin (CT) and toxin-coregulated pilus (TCP). A conjugated form of linoleic acid (CLA) is currently sold over the counter as a dietary supplement and is generally recognized as safe by the U.S. Food and Drug Administration. This study examined whether CLA could be used as a new therapy to reduce CT production, which, in turn, would decrease disease duration and intensity in cholera patients. CLA could be used in place of traditional antibiotics and would be very unlikely to generate resistance, as it affects only virulence factor production and not bacterial growth or survival. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Energy Technology Data Exchange (ETDEWEB)

Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

2011-11-15

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

International Nuclear Information System (INIS)

Kleinstreuer, N.C.; Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R.; Weir-Hauptman, A.M.; Palmer, J.A.; Knudsen, T.B.; Dix, D.J.; Donley, E.L.R.; Cezar, G.G.

2011-01-01

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox® model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

Understanding social media program usage in public transit agencies

Directory of Open Access Journals (Sweden)

Jenny H. Liu

2016-10-01

Full Text Available Social media has been gaining prominence in public transit agencies in their communication strategies and daily management. This study aims to better understand recent trends in social media usage in public transit agencies, to examine which agencies use what kind of social media programs for what purposes, and how they measure their programs. A survey was conducted of the top transit agencies in the nation, and results are examined through descriptive statistical analysis, correlation analysis and regression modeling. We found that while most agencies still lack clearly-defined goals and performance metrics to guide their social media development, many are increasing their social media capacity with more structural components. Public transit service usage and the level of transit service provision are the most significant determinants of agencies’ social media programming and resource investments. In contrast, the measurement of social media usage and outcomes is more significantly related to city attributes and demographic characteristics. We anticipate an increase in the usage of social media to convey transit related stories and livability benefits, such as environmental sensitivity or safety improvements, as these programs expand. Public transit agencies’ commitment to measuring social media outcomes underscores the future research need to develop best practices for measuring the impacts and performance of social media communications and investments.

Creating a meaningful infection control program: one home healthcare agency's lessons.

Science.gov (United States)

Poff, Renee McCoy; Browning, Sarah Via

2014-03-01

Creating a meaningful infection control program in the home care setting proved to be challenging for agency leaders of one hospital-based home healthcare agency. Challenges arose when agency leaders provided infection control (IC) data to the hospital's IC Committee. The IC Section Chief asked for national benchmark comparisons to align home healthcare reporting to that of the hospital level. At that point, it was evident that the home healthcare IC program lacked definition and structure. The purpose of this article is to share how one agency built a meaningful IC program.

Causal Inferences from Mining ToxCast Data and the Biomedical Literature for Molecular Pathways and Cellular Processes in Cleft Palate (SOT)

Science.gov (United States)

Sixty-five chemicals in the ToxCast high-throughput screening (HTS) dataset have been linked to cleft palate based on data from ToxRefDB (rat or rabbit prenatal developmental toxicity studies) or from literature reports. These compounds are structurally diverse and thus likely to...

Enhancing Agency through Leadership Development Programs for Faculty

Science.gov (United States)

Templeton, Lindsey; O'Meara, KerryAnn

2018-01-01

The ADVANCE Leadership Fellows Program at the University of Maryland is a yearlong professional development program for faculty aspiring to or recently engaged in leadership roles. Data shows an increase in participants' sense of agency to become academic leaders following the program. We use a comprehensive data set, including program…

Prediction of metabolites of epoxidation reaction in MetaTox.

Science.gov (United States)

Rudik, A V; Dmitriev, A V; Bezhentsev, V M; Lagunin, A A; Filimonov, D A; Poroikov, V V

2017-10-01

Biotransformation is a process of the chemical modifications which may lead to the reactive metabolites, in particular the epoxides. Epoxide reactive metabolites may cause the toxic effects. The prediction of such metabolites is important for drug development and ecotoxicology studies. Epoxides are formed by some oxidation reactions, usually catalysed by cytochromes P450, and represent a large class of three-membered cyclic ethers. Identification of molecules, which may be epoxidized, and indication of the specific location of epoxide functional group (which is called SOE - site of epoxidation) are important for prediction of epoxide metabolites. Datasets from 355 molecules and 615 reactions were created for training and validation. The prediction of SOE is based on a combination of LMNA (Labelled Multilevel Neighbourhood of Atom) descriptors and Bayesian-like algorithm implemented in PASS software and MetaTox web-service. The average invariant accuracy of prediction (AUC) calculated in leave-one-out and 20-fold cross-validation procedures is 0.9. Prediction of epoxide formation based on the created SAR model is included as the component of MetaTox web-service ( http://www.way2drug.com/mg ).

Mass-Spectrometry Based Structure Identification of "Known-Unknowns" Using the EPA's CompTox Dashboard (ACS Spring National Meeting) 4 of 7

Science.gov (United States)

The CompTox Dashboard is a publicly accessible database provided by the National Center for Computational Toxicology at the US-EPA. The dashboard provides access to a database containing ~720,000 chemicals and integrates a number of our public-facing projects (e.g. ToxCast and Ex...

CalTOX, a multimedia total exposure model for hazardous-waste sites

International Nuclear Information System (INIS)

McKone, T.E.

1993-06-01

CalTOX has been developed as a spreadsheet model to assist in health-risk assessments that address contaminated soils and the contamination of adjacent air, surface water, sediments, and ground water. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify and reduce uncertainty in multimedia, multiple-pathway exposure models. This report provides an overview of the CalTOX model components, lists the objectives of the model, describes the philosophy under which the model was developed, identifies the chemical classes for which the model can be used, and describes critical sensitivities and uncertainties. The multimedia transport and transformation model is a dynamic model that can be used to assess time-varying concentrations of contaminants introduced initially to soil layers or for contaminants released continuously to air or water. This model assists the user in examining how chemical and landscape properties impact both the ultimate route and quantity of human contact. Multimedia, multiple pathway exposure models are used in the CalTOX model to estimate average daily potential doses within a human population in the vicinity of a hazardous substances release site. The exposure models encompass twenty-three exposure pathways. The exposure assessment process consists of relating contaminant concentrations in the multimedia model compartments to contaminant concentrations in the media with which a human population has contact (personal air, tap water, foods, household dusts soils, etc.). The average daily dose is the product of the exposure concentrations in these contact media and an intake or uptake factor that relates the concentrations to the distributions of potential dose within the population

NanoE-Tox: New and in-depth database concerning ecotoxicity of nanomaterials

Directory of Open Access Journals (Sweden)

Katre Juganson

2015-08-01

Full Text Available The increasing production and use of engineered nanomaterials (ENMs inevitably results in their higher concentrations in the environment. This may lead to undesirable environmental effects and thus warrants risk assessment. The ecotoxicity testing of a wide variety of ENMs rapidly evolving in the market is costly but also ethically questionable when bioassays with vertebrates are conducted. Therefore, alternative methods, e.g., models for predicting toxicity mechanisms of ENMs based on their physico-chemical properties (e.g., quantitative (nanostructure-activity relationships, QSARs/QNARs, should be developed. While the development of such models relies on good-quality experimental toxicity data, most of the available data in the literature even for the same test species are highly variable. In order to map and analyse the state of the art of the existing nanoecotoxicological information suitable for QNARs, we created a database NanoE-Tox that is available as . The database is based on existing literature on ecotoxicology of eight ENMs with different chemical composition: carbon nanotubes (CNTs, fullerenes, silver (Ag, titanium dioxide (TiO2, zinc oxide (ZnO, cerium dioxide (CeO2, copper oxide (CuO, and iron oxide (FeOx; Fe2O3, Fe3O4. Altogether, NanoE-Tox database consolidates data from 224 articles and lists altogether 1,518 toxicity values (EC50/LC50/NOEC with corresponding test conditions and physico-chemical parameters of the ENMs as well as reported toxicity mechanisms and uptake of ENMs in the organisms. 35% of the data in NanoE-Tox concerns ecotoxicity of Ag NPs, followed by TiO2 (22%, CeO2 (13%, and ZnO (10%. Most of the data originates from studies with crustaceans (26%, bacteria (17%, fish (13%, and algae (11%. Based on the median toxicity values of the most sensitive organism (data derived from three or more articles the toxicity order was as follows: Ag > ZnO > CuO > CeO2 > CNTs > TiO2 > FeOx. We believe NanoE-Tox database contains

Legacy data sharing to improve drug safety assessment: the eTOX project

DEFF Research Database (Denmark)

Sanz, Ferran; Pognan, François; Steger-Hartmann, Thomas

2017-01-01

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through...

Extracorporeal Membrane Oxygenation (ECMO) for Severe Toxicological Exposures: Review of the Toxicology Investigators Consortium (ToxIC).

Science.gov (United States)

Wang, G S; Levitan, R; Wiegand, T J; Lowry, J; Schult, R F; Yin, S

2016-03-01

Although there have been many developments related to specific strategies for treating patients after poisoning exposures, the mainstay of therapy remains symptomatic and supportive care. One of the most aggressive supportive modalities is extracorporeal membrane oxygenation (ECMO). Our goal was to describe the use of ECMO for toxicological exposures reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC). We performed a retrospective review of the ACMT ToxIC Registry from January 1, 2010 to December 31, 2013. Inclusion criteria included patients aged 0 to 89 years, evaluated between January 2010 through December 2013, and received ECMO for toxicological exposure. There were 26,271 exposures (60 % female) reported to the ToxIC Registry, 10 (0.0004 %) received ECMO: 4 pediatric (18 years). Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days. Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2). Four ECMO patients received cardiopulmonary resuscitation (CPR) during their hospital course, and the overall survival rate was 80 %. ECMO was rarely used for poisoning exposures in the ACMT ToxIC Registry. ECMO was utilized for a variety of ages and for pharmaceutical and non-pharmaceutical exposures. In most cases, ECMO was administered prior to cardiovascular failure, and survival rate was high. If available, ECMO may be a valid treatment modality.

Demonstration that Australian Pasteurella multocida isolates from sporadic outbreaks of porcine pneumonia are non-toxigenic (toxA-) and display heterogeneous DNA restriction endonuclease profiles compared with toxigenic isolates from herds with progressive atrophic rhinitis.

Science.gov (United States)

Djordjevic, S P; Eamens, G J; Ha, H; Walker, M J; Chin, J C

1998-08-01

Capsular types A and D of Pasteurella multocida cause economic losses in swine because of their association with progressive atrophic rhinitis (PAR) and enzootic pneumonia. There have been no studies comparing whole-cell DNA profiles of isolates associated with these two porcine respiratory diseases. Twenty-two isolates of P. multocida from diseased pigs in different geographic localities within Australia were characterised genotypically by restriction endonuclease analysis (REA) with the enzyme CfoI. Seven of 12 P. multocida isolates from nasal swabs from pigs in herds where PAR was either present or suspected displayed a capsular type D phenotype. These were shown to possess the toxA gene by polymerase chain reaction (PCR) and Southern hybridisation, and further substantiated by production of cytotoxin in vitro. The CfoI profile of one of these seven isolates, which was from the initial outbreak of PAR in Australia (in Western Australia, WA), was identical with profiles of all six other toxigenic isolates from sporadic episodes in New South Wales (NSW). The evidence suggests that the strain involved in the initial outbreak was responsible for the spread of PAR to the eastern states of Australia. Another 10 isolates, representing both capsular types A and D, were isolated exclusively from porcine lung lesions after sporadic outbreaks of enzootic pneumonia in NSW and WA. CfoI restriction endonuclease profiles of these isolates revealed considerable genomic heterogeneity. Furthermore, none of these possessed the toxA gene. This suggests that P. multocida strains with the toxA gene do not have a competitive survival advantage in the lower respiratory tract or that toxin production does not play a role in the pathology of pneumonic lesions, or both. REA with polyacrylamide gel electrophoresis and silver staining was found to be a practical and discriminatory tool for epidemiological tracing of P. multocida outbreaks associated with PAR or pneumonia in pigs.

CAirTOX: A compartment model for assessing the fate of and human exposure to toxic-chemical emissions to air

Energy Technology Data Exchange (ETDEWEB)

McKone, T.E.

1993-10-01

CAirTOX has been developed as a spreadsheet model to assist in making a risk assessment of toxic air emissions. With CAirTOX, one can address how contaminants released to an air basin can lead to contamination of soil, food, surface water, and sediments. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify uncertainty in multimedia, multiple-pathway exposure assessments. The multimedia transport and transformation model is a steady-state, but non-equilibrium model that can be used to assess concentrations of contaminants released continuously to air. In Part 1, the authors describe the multimedia transport and transformation model used to determine the fate of air emissions. In Part 2, they describe inputs and data needs for CAirTOX and the development of a set of landscape factors, which can be used to represent regional air basin/water-shed systems in California. In Part 3, they describe the multiple-pathway exposure scenarios and exposure algorithms. In Part 4, they compare the HRA approach and results and the CAirTOX exposure equations. In Part 5, they consider model sensitivity and uncertainty to determine how variability and uncertainty in model inputs affects the precision, accuracy, and credibility of the model output.

77 FR 62469 - Defense Logistics Agency Freedom of Information Act Program

Science.gov (United States)

2012-10-15

... DEPARTMENT OF DEFENSE Office of the Secretary 32 CFR Part 300 Defense Logistics Agency 32 CFR Part 1285 RIN 0790-AI87 [Docket ID: DOD-2012-OS-0019] Defense Logistics Agency Freedom of Information Act Program AGENCY: Defense Logistics Agency, DoD. ACTION: Proposed rule. SUMMARY: The Defense Logistics...

Vicia cytogenetic tests for environmental mutagens. A report of the US Environmental Protection Agency gene-tox program

Energy Technology Data Exchange (ETDEWEB)

Ma, T H

1982-01-01

Vicia root-tip mitotic and pollen mother-cell meiotic tests are two major kinds of cytogenetic tests for environmental mutagens. According to the present review, 81 of 85 earlier studies used mitotic tests to determine the frequencies of chromosome or chromatid aberrations and/or sister-chromatid exchange from root-tip meristematic cells; only 4 used meiotic tests to determine the frequencies of chromosome aberration from pollen mother cells. Treatment of root-tip meristem can be done by allowing the newly germinated roots to absorb the chemical mutagens from a water solution. Pollen mother cells can be treated by spraying the solution or pipetting the liquid over the flower buds. After an appropriate recovery time, the samples are fixed and stained, and the slides are prepared for metaphase or anaphase figures for scoring aberration frequencies. Slides for meiotic tests are prepared for metaphase I and/or Anaphase I stages for scoring chromosome aberration frequencies. Results of both cytogenetic tests should be expressed in terms of number of breaks per cell or per 100 cells. Test results of 76 chemicals from 32 classes in this review indicate that the Vicia root-tip mitotic test is reliable, efficient, and relatively inexpensive. These results also reveal that antibiotics are most frequently studied, followed by alkyl sulfones, pyrimidine, and purine derivatives. Of all the agents studied through root-tip mitotic tests, about 90% gave positive responses; antibiotics (phyleomycin and bleomycin) had very high mutagenicity (less than 1 ppM gave positive response).

Evaluation of the on-site immunoassay drug-screening device Triage-TOX in routine forensic autopsy.

Science.gov (United States)

Tominaga, Mariko; Michiue, Tomomi; Maeda, Hitoshi

2015-11-01

Instrumental identification of drugs with quantification is essential in forensic toxicology, while on-site immunoassay urinalysis drug-screening devices conveniently provide preliminary information when adequately used. However, suitable or sufficient urine specimens are not always available. The present study evaluated the efficacy of a new on-site immunoassay drug-screening device Triage-TOX (Alere Inc., San Diego, CA, USA), which has recently been developed to provide objective data on the one-step automated processor, using 51 urine and 19 pericardial fluid samples from 66 forensic autopsy cases, compared with Triage-Drug of Abuse (DOA) and Monitect-9. For benzodiazepines, the positive predictive value and specificity of Triage-TOX were higher than those of Triage-DOA; however, sensitivity was higher with Monitect-9, despite frequent false-positives. The results for the other drugs with the three devices also included a few false-negatives and false-positives. These observations indicate the applicability of Triage-TOX in preliminary drug screening using urine or alternative materials in routine forensic autopsy, when a possible false-negative is considered, especially for benzodiazepines, providing objective information; however, the combined use of another device such as Monitect-9 can help minimize misinterpretation prior to instrumental analysis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

29 CFR 1960.80 - Secretary's evaluations of agency occupational safety and health programs.

Science.gov (United States)

2010-07-01

... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Evaluation of Federal Occupational Safety and Health Programs § 1960.80 Secretary's evaluations of agency occupational safety and health... evaluating an agency's occupational safety and health program. To accomplish this, the Secretary shall...

78 FR 65696 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

Science.gov (United States)

2013-11-01

... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Chief Information... Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number: 2502-0500. Type of... housing finance agencies (HFAs). Under this program, HUD provides full mortgage insurance on multifamily...

78 FR 64145 - 30-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

Science.gov (United States)

2013-10-25

... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Chief Information... Title of Information Collection: Housing Finance Agency Risk- Sharing Program. OMB Approval Number: 2502... sharing with State and local housing finance agencies (HFAs). Under this program, HUD provides full...

Utility Green Tariff Programs: Considerations for Federal Agencies

Energy Technology Data Exchange (ETDEWEB)

Heeter, Jenny

2017-05-08

This FEMP First Thursday presentation will explain the concept of a utility green tariff, how it differs from a green pricing program, and what questions federal agencies should have about participating.

78 FR 52962 - 60-Day Notice of Proposed Information Collection: Housing Finance Agency Risk-Sharing Program

Science.gov (United States)

2013-08-27

... Information Collection: Housing Finance Agency Risk-Sharing Program AGENCY: Office of the Assistant Secretary... Finance Agency Risk- Sharing Program. OMB Approval Number: 2502-0500. Type of Request (i.e. new, revision... Secretary to implement risk sharing with State and local housing finance agencies (HFAs). Under this program...

Using the US EPA's CompTox Dashboard to support identification and screening of emerging organic contaminants in the environment (ACS Spring National meeting) 2 of 7

Science.gov (United States)

The US EPA’s iCSS CompTox Dashboard is a curated, publicly accessible resource provided by the National Center for Computational Toxicology (https://comptox.epa.gov). The Dashboard provides support for toxicology and risk assessment within and external to the EPA (including ToxC...

International Energy Agency Solar Heating and Cooling Program

Science.gov (United States)

Brooks, A. J.

This trip was undertaken to participate in and represent the United States Industry at the International Energy Agency (IEA) Solar Heating and Cooling Program (SHCP) Task 14 Workshop. The meeting took place at the A1 Bani Hotel in Rome Italy.

75 FR 43162 - Tetrahedron, Inc., with Subcontractors: Syracuse Research Corporation; Tox Path, Inc; and...

Science.gov (United States)

2010-07-23

... obligations of the contract. DATES: Tetrahedron, Inc., and its subcontractors: Syracuse Research Corporation... contract to perform work for OPP, and access to this information will enable Tetrahedron, Inc., and its... Contract No. EP-W-10-013, Tetrahedron, Inc., and its subcontractors: Syracuse Research Corporation, Tox...

Use of high-throughput in vitro toxicity screening data in cancer hazard evaluations by IARC Monograph Working Groups.

Science.gov (United States)

Chiu, Weihsueh A; Guyton, Kathryn Z; Martin, Matthew T; Reif, David M; Rusyn, Ivan

2018-01-01

Evidence regarding carcinogenic mechanisms serves a critical role in International Agency for Research on Cancer (IARC) Monograph evaluations. Three recent IARC Working Groups pioneered inclusion of the US Environmental Protection Agency (EPA) ToxCast program high-throughput screening (HTS) data to supplement other mechanistic evidence. In Monograph V110, HTS profiles were compared between perfluorooctanoic acid (PFOA) and prototypical activators across multiple nuclear receptors. For Monograph V112-113, HTS assays were mapped to 10 key characteristics of carcinogens identified by an IARC expert group, and systematically considered as an additional mechanistic data stream. Both individual assay results and ToxPi-based rankings informed mechanistic evaluations. Activation of multiple nuclear receptors in HTS assays showed that PFOA targets not only peroxisome proliferator activated receptors, but also other receptors. ToxCast assays substantially covered 5 of 10 key characteristics, corroborating literature evidence of "induces oxidative stress" and "alters cell proliferation, cell death or nutrient supply" and filling gaps for "modulates receptor-mediated effects." Thus, ToxCast HTS data were useful both in evaluating specific mechanistic hypotheses and in contributing to the overall evaluation of mechanistic evidence. However, additional HTS assays are needed to provide more comprehensive coverage of the 10 key characteristics of carcinogens that form the basis of current IARC mechanistic evaluations.

Deriving Trading Rules Using Gene Expression Programming

Directory of Open Access Journals (Sweden)

Adrian VISOIU

2011-01-01

Full Text Available This paper presents how buy and sell trading rules are generated using gene expression programming with special setup. Market concepts are presented and market analysis is discussed with emphasis on technical analysis and quantitative methods. The use of genetic algorithms in deriving trading rules is presented. Gene expression programming is applied in a form where multiple types of operators and operands are used. This gives birth to multiple gene contexts and references between genes in order to keep the linear structure of the gene expression programming chromosome. The setup of multiple gene contexts is presented. The case study shows how to use the proposed gene setup to derive trading rules encoded by Boolean expressions, using a dataset with the reference exchange rates between the Euro and the Romanian leu. The conclusions highlight the positive results obtained in deriving useful trading rules.

SeqAPASS to evaluate conservation of high-throughput screening targets across non-mammalian species

Science.gov (United States)

Cell-based high-throughput screening (HTS) and computational technologies are being applied as tools for toxicity testing in the 21st century. The U.S. Environmental Protection Agency (EPA) embraced these technologies and created the ToxCast Program in 2007, which has served as a...

Molecular analysis of exotoxin A associated with antimicrobial resistance of Pseudomonas aeruginosa strains isolated from patients in Tehran hospitals

Directory of Open Access Journals (Sweden)

Nour Amirmozafari

2014-12-01

Full Text Available Background and Aim:  Pseudomonas aeruginosa is a unique bacteria that in order to survive in different environments by complex adaptation process can make changes in his virulence genes expression and drug resistance. The aim of this research is the investigation of existence of a logical association between toxA gene and antibiotic resistance in strains possess the gene. Materials and Methods: Antibiogram test by disk diffusion method (Kirby Bauer was performed according to CLSI protocols. In this study, the existence of toxA gene with the help of polymerase chain reaction (PCR in 102 clinical isolates from blood samples, wound, urine and trachea was examined. Chi-square test was used to investigate the relationship between exotoxin A and antibiotic resistance. Results: The 81 strains (79.4% had toxA gene. Frequency of toxA genes in isolated strains from different infections were wound (91.4%, blood (85.7%, trachea (72.7%, and urine (42.1%. Multiple resistance index in strains possess the toxA gene was calculated 75%. Chi 2 test to determine the relationship between drug resistance and gene toxA was significant (P<0.05. Conclusions: The significant chi-square test and an increase in multi-resistant strains possessing the toxA gene, can represent a considerable genetic switch between exotoxin A activity and resistance to antibiotics in the blood, urine, tracheal, wound infections Respectively, which lead to turn genes on of drug resistance regulating in bacteria. The results of this study will be verified by southern blot, analysis of the expression of toxA gene and determine the mechanism of resistance in resistant strains Methods.

ToxPlorerTM: A Comprehensive Knowledgebase of Toxicity Pathways Using Ontology-driven Information Extraction

Science.gov (United States)

Realizing the potential of pathway-based toxicity testing requires a fresh look at how we describe phenomena leading to adverse effects in vivo, how we assess them in vitro and how we extrapolate them in silico across chemicals, doses and species. We developed the ToxPlorer™ fram...

FORUM - FutureTox II: In vitro Data and In Silico Models for Predictive Toxicology

Science.gov (United States)

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo resp...

Automated discovery of functional generality of human gene expression programs.

Directory of Open Access Journals (Sweden)

Georg K Gerber

2007-08-01

Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

Gene expression profiles of Aspergillus flavus isolates responding to oxidative stress in different culture media

Science.gov (United States)

Aflatoxin contamination of peanut by Aspergillus flavus is exacerbated by drought stress. Drought also stimulates the production of reactive oxygen species (ROS) in plant tissues implying a correlation between ROS and aflatoxin production. Here, we performed gene expression analysis by RNAseq of tox...

Single Nucleotide Polymorphisms in Regulator-Encoding Genes Have an Additive Effect on Virulence Gene Expression in a Vibrio cholerae Clinical Isolate.

Science.gov (United States)

Carignan, Bailey M; Brumfield, Kyle D; Son, Mike S

2016-01-01

Vibrio cholerae is the etiological agent of the infectious disease cholera, which is characterized by vomiting and severe watery diarrhea. Recently, V. cholerae clinical isolates have demonstrated increased virulence capabilities, causing more severe symptoms with a much higher rate of disease progression than previously observed. We have identified single nucleotide polymorphisms (SNPs) in four virulence-regulatory genes (hapR, hns, luxO, and vieA) of a hypervirulent V. cholerae clinical isolate, MQ1795. Herein, all SNPs and SNP combinations of interest were introduced into the prototypical El Tor reference strain N16961, and the effects on the production of numerous virulence-related factors, including cholera toxin (CT), the toxin-coregulated pilus (TCP), and ToxT, were analyzed. Our data show that triple-SNP (hapR hns luxO and hns luxO vieA) and quadruple-SNP combinations produced the greatest increases in CT, TCP, and ToxT production. The hns and hns luxO SNP combinations were sufficient for increased TCP and ToxT production. Notably, the hns luxO vieA triple-SNP combination strain produced TCP and ToxT levels similar to those of MQ1795. Certain SNP combinations (hapR and hapR vieA) had the opposite effect on CT, TCP, and ToxT expression. Interestingly, the hns vieA double-SNP combination strain increased TCP production while decreasing CT production. Our findings suggest that SNPs identified in the four regulatory genes, in various combinations, are associated with increased virulence capabilities observed in V. cholerae clinical isolates. These studies provide insight into the evolution of highly virulent strains. IMPORTANCE Cholera, an infectious disease of the small intestine caused by the aquatic bacterium Vibrio cholerae, often results in vomiting and acute watery diarrhea. If left untreated or if the response is too slow, the symptoms can quickly lead to extreme dehydration and ultimately death of the patient. Recent anecdotal evidence of cholera

A Critical Agency Network Model for Building an Integrated Outreach Program

Science.gov (United States)

Kiyama, Judy Marquez; Lee, Jenny J.; Rhoades, Gary

2012-01-01

This study considers a distinct case of a college outreach program that integrates student affairs staff, academic administrators, and faculty across campus. The authors find that social networks and critical agency help to understand the integration of these various professionals and offer a critical agency network model of enacting change.…

A genetic polymorphism in TOX3 is associated with survival of gastric cancer in a Chinese population.

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Xiaojing Zhang

Full Text Available PURPOSE: Recently, genetic polymorphism (rs3803662C>T in TOX3 was reported to induce the risk of breast cancer. In this study, we hypothesized that rs3803662 could influence gastric cancer survival outcomes. METHODS: With multiplex SNaPshot method, we genotyped TOX3 rs3803662 in 880 gastric patients with surgical resection. The association between genotype and survival outcomes was performed by the Kaplan-Meier method, Cox regression analysis models and the log-rank test. RESULTS: There was no association in the analyses of rs3803662 and survival of gastric cancer. However, the stratified analysis by histology showed that rs3803662 CT/TT genotype was associated with a significantly better survival for diffuse-type gastric cancer (log-rank p = 0.030, hazard ratio [HR]  = 0.67, 95% confidence interval [CI]  = 0.46-0.96, than the CC genotype. In addition, this favorable effect was especially obvious among gastric cancer patients with tumor size >5 cm, T3 and T4 depth of invasion, lymph node metastasis, no drinking, no distant metastasis, no chemotherapy and gastric cardia cancer. CONCLUSIONS: TOX3 rs3803662 might play an important role in the prognostic outcome and treatment of gastric cancer, especially perhaps further help in explaining the reduced risk of death associated with diffuse-type gastric cancer.

R and D programs of the International Energy Agency

International Nuclear Information System (INIS)

Dyne, P.J.

1989-01-01

This paper provides a description of the collaborative research program of the International Energy Agency. Focusing on the organization of the program, rather than attempting to cover the technical content of the research, the discussion conveys how its operation is facilitated through a framework that takes account of the interests of participating governments as well as technical objectives. Some Canadian activities in the IEA program are briefly described as illustration and a list of current IEA Research Agreements and associated activities is presented in an Appendix

Metal mixture toxicity to aquatic biota in laboratory experiments: Application of the WHAM-F{sub TOX} model

Energy Technology Data Exchange (ETDEWEB)

Tipping, E., E-mail: et@ceh.ac.uk; Lofts, S.

2013-10-15

Highlights: •Metal accumulation by living organisms is successfully simulated with WHAM. •Modelled organism-bound metal provides a measure of toxic exposure. •The toxic potency of individual bound metals is quantified by fitting toxicity data. •Eleven laboratory mixture toxicity data sets were parameterised. •Relatively little variability amongst individual test organisms is indicated. -- Abstract: The WHAM-F{sub TOX} model describes the combined toxic effects of protons and metal cations towards aquatic organisms through the toxicity function (F{sub TOX}), a linear combination of the products of organism-bound cation and a toxic potency coefficient (α{sub i}) for each cation. Organism-bound, metabolically-active, cation is quantified by the proxy variable, amount bound by humic acid (HA), as predicted by the WHAM chemical speciation model. We compared published measured accumulations of metals by living organisms (bacteria, algae, invertebrates) in different solutions, with WHAM predictions of metal binding to humic acid in the same solutions. After adjustment for differences in binding site density, the predictions were in reasonable line with observations (for logarithmic variables, r{sup 2} = 0.89, root mean squared deviation = 0.44), supporting the use of HA binding as a proxy. Calculated loadings of H{sup +}, Al, Cu, Zn, Cd, Pb and UO{sub 2} were used to fit observed toxic effects in 11 published mixture toxicity experiments involving bacteria, macrophytes, invertebrates and fish. Overall, WHAM-F{sub TOX} gave slightly better fits than a conventional additive model based on solution concentrations. From the derived values of α{sub i}, the toxicity of bound cations can tentatively be ranked in the order: H < Al < (Zn–Cu–Pb–UO{sub 2}) < Cd. The WHAM-F{sub TOX} analysis indicates much narrower ranges of differences amongst individual organisms in metal toxicity tests than was previously thought. The model potentially provides a means to

A Family Agency's Approach to Providing Employee Assistance Programs in Industry.

Science.gov (United States)

Keohane, Raymond G.; Newman, Carrie E.

1984-01-01

Describes the Employee Services Network (ESN), an employee assistance program developed within the Family and Children's Service of Richmond, Virginia. Demonstrates how a not-for-profit agency can develop, structure, and implement a program of services for the corporate community. (LLL)

Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells.

Science.gov (United States)

Developing predictions of in vivo developmental toxicity of ToxCast chemicals using mouse embryonic stem cells S. Hunter, M. Rosen, M. Hoopes, H. Nichols, S. Jeffay, K. Chandler1, Integrated Systems Toxicology Division, National Health and Environmental Effects Research Labor...

CalTOX, a multimedia total exposure model for hazardous-waste sites; Part 1, Executive summary

Energy Technology Data Exchange (ETDEWEB)

McKone, T.E.

1993-06-01

CalTOX has been developed as a spreadsheet model to assist in health-risk assessments that address contaminated soils and the contamination of adjacent air, surface water, sediments, and ground water. The modeling effort includes a multimedia transport and transformation model, exposure scenario models, and efforts to quantify and reduce uncertainty in multimedia, multiple-pathway exposure models. This report provides an overview of the CalTOX model components, lists the objectives of the model, describes the philosophy under which the model was developed, identifies the chemical classes for which the model can be used, and describes critical sensitivities and uncertainties. The multimedia transport and transformation model is a dynamic model that can be used to assess time-varying concentrations of contaminants introduced initially to soil layers or for contaminants released continuously to air or water. This model assists the user in examining how chemical and landscape properties impact both the ultimate route and quantity of human contact. Multimedia, multiple pathway exposure models are used in the CalTOX model to estimate average daily potential doses within a human population in the vicinity of a hazardous substances release site. The exposure models encompass twenty-three exposure pathways. The exposure assessment process consists of relating contaminant concentrations in the multimedia model compartments to contaminant concentrations in the media with which a human population has contact (personal air, tap water, foods, household dusts soils, etc.). The average daily dose is the product of the exposure concentrations in these contact media and an intake or uptake factor that relates the concentrations to the distributions of potential dose within the population.

76 FR 41186 - Salmonella Verification Sampling Program: Response to Comments on New Agency Policies and...

Science.gov (United States)

2011-07-13

... Service [Docket No. FSIS-2008-0008] Salmonella Verification Sampling Program: Response to Comments on New Agency Policies and Clarification of Timeline for the Salmonella Initiative Program (SIP) AGENCY: Food... Federal Register notice (73 FR 4767- 4774), which described upcoming policy changes in the FSIS Salmonella...

Tox21: Putting a Lens on the Vision of Toxicity Testing in the 21st Century

Science.gov (United States)

In response to the release of the NRC report on "Toxicity Testing in the 21st Century, a Vision and Strategy" (NRC, 2007), two NIH institutes and EPA formed a collaboration (Tox21) to 1) identify mechanisms of chemically induced biological activity, 2) prioritize chemicals for mo...

Human Pluripotent Stem Cell-Based Assay Predicts Developmental Toxicity Potential of ToxCast Chemicals (ACT meeting)

Science.gov (United States)

Worldwide initiatives to screen for toxicity potential among the thousands of chemicals currently in use require inexpensive and high-throughput in vitro models to meet their goals. The devTOX quickPredict platform is an in vitro human pluripotent stem cell-based assay used to as...

National Nanotechnology Initiative Investments by Agency and Program Component Area

Data.gov (United States)

Office of Science and Technology Policy, Executive Office of the President — Data represents National Nanotechnology Initiative investments by agency and program component area (PCA) from FY 2001 through FY 2010 (requested). While this data...

Toxicokinetiek van benzo(a)pyreen bij de Riv:TOX rat na herhaalde orale toediening

NARCIS (Netherlands)

Olling M; Lusthof KJ; Kroese ED; Beenen J; Klaassen R; BFT

1995-01-01

Benzo(a)pyrene was administered once daily (30 mg/kg) by gavage to 12 male and 12 female Riv:TOX rats, for 15 days on five successive days per week, in the form of a solution in soy oil. Blood samples were taken over a period of 12 hours on the first day of administration (day 1) and on day 12 from

TOXPERT: An Expert System for Risk Assessment

Science.gov (United States)

Soto, R. J.; Osimitz, T. G.; Oleson, A.

1988-01-01

TOXPERT is an artificial intelligence based system used to model product safety, toxicology (TOX) and regulatory (REG) decision processes. An expert system shell uses backward chaining rule control to link “marketing approval” goals to the type of product, REG agency, exposure conditions and TOX. Marketing risks are primarily a function of the TOX, hazards and exposure potential. The method employed differentiates between REG requirements in goal seeking control for various types of products. This is accomplished by controlling rule execution by defining frames for each REG agency. In addition, TOXPERT produces classifications of TOX ratings and suggested product labeling. This production rule system uses principles of TOX, REGs, corporate guidelines and internal “rules of thumb.” TOXPERT acts as an advisor for this narrow domain. Advantages are that it can make routine decisions freeing professional's time for more complex problem solving, provide backup and training.

A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro

Directory of Open Access Journals (Sweden)

Craig L. Parfett

2017-06-01

Full Text Available An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs. effect data extrapolated to human in vivo concentrations. Much direct experimental evidence now shows that disruption of epigenetic processes by chemicals is a carcinogenic mode of action that leads to altered gene functions playing causal roles in cancer initiation and progression. In assessing chemical safety, it would therefore be advantageous to consider an emerging class of carcinogens, the epigenotoxicants, with the ability to change chromatin and/or DNA marks by direct or indirect effects on the activities of enzymes (writers, erasers/editors, remodelers and readers that convey the epigenetic information. Evidence is reviewed supporting a strategy for in vitro hazard identification of carcinogens that induce toxicity through disturbance of functional epigenetic pathways in human somatic cells, leading to inactivated tumour suppressor genes and carcinogenesis. In the context of human cell transformation models, these in vitro pathway measurements ensure high biological relevance to the apical endpoint of cancer. Four causal mechanisms participating in pathways to persistent epigenetic gene silencing were considered: covalent histone modification, nucleosome remodeling, non-coding RNA interaction and DNA methylation. Within these four interacting mechanisms, 25 epigenetic toxicity pathway components (SET1, MLL1, KDM5, G9A, SUV39H1, SETDB1, EZH2, JMJD3, CBX7, CBX8, BMI, SUZ12, HP1, MPP8, DNMT1, DNMT3A, DNMT3B, TET1, MeCP2, SETDB2, BAZ2

Benchmarking of gene prediction programs for metagenomic data.

Science.gov (United States)

Yok, Non; Rosen, Gail

2010-01-01

This manuscript presents the most rigorous benchmarking of gene annotation algorithms for metagenomic datasets to date. We compare three different programs: GeneMark, MetaGeneAnnotator (MGA) and Orphelia. The comparisons are based on their performances over simulated fragments from one hundred species of diverse lineages. We defined four different types of fragments; two types come from the inter- and intra-coding regions and the other types are from the gene edges. Hoff et al. used only 12 species in their comparison; therefore, their sample is too small to represent an environmental sample. Also, no predecessors has separately examined fragments that contain gene edges as opposed to intra-coding regions. General observations in our results are that performances of all these programs improve as we increase the length of the fragment. On the other hand, intra-coding fragments of our data show low annotation error in all of the programs if compared to the gene edge fragments. Overall, we found an upper-bound performance by combining all the methods.

Toxicity Reference Database

Data.gov (United States)

U.S. Environmental Protection Agency — The Toxicity Reference Database (ToxRefDB) contains approximately 30 years and $2 billion worth of animal studies. ToxRefDB allows scientists and the interested...

The CompTox Chemistry Dashboard: a community data resource for environmental chemistry.

Science.gov (United States)

Williams, Antony J; Grulke, Christopher M; Edwards, Jeff; McEachran, Andrew D; Mansouri, Kamel; Baker, Nancy C; Patlewicz, Grace; Shah, Imran; Wambaugh, John F; Judson, Richard S; Richard, Ann M

2017-11-28

Despite an abundance of online databases providing access to chemical data, there is increasing demand for high-quality, structure-curated, open data to meet the various needs of the environmental sciences and computational toxicology communities. The U.S. Environmental Protection Agency's (EPA) web-based CompTox Chemistry Dashboard is addressing these needs by integrating diverse types of relevant domain data through a cheminformatics layer, built upon a database of curated substances linked to chemical structures. These data include physicochemical, environmental fate and transport, exposure, usage, in vivo toxicity, and in vitro bioassay data, surfaced through an integration hub with link-outs to additional EPA data and public domain online resources. Batch searching allows for direct chemical identifier (ID) mapping and downloading of multiple data streams in several different formats. This facilitates fast access to available structure, property, toxicity, and bioassay data for collections of chemicals (hundreds to thousands at a time). Advanced search capabilities are available to support, for example, non-targeted analysis and identification of chemicals using mass spectrometry. The contents of the chemistry database, presently containing ~ 760,000 substances, are available as public domain data for download. The chemistry content underpinning the Dashboard has been aggregated over the past 15 years by both manual and auto-curation techniques within EPA's DSSTox project. DSSTox chemical content is subject to strict quality controls to enforce consistency among chemical substance-structure identifiers, as well as list curation review to ensure accurate linkages of DSSTox substances to chemical lists and associated data. The Dashboard, publicly launched in April 2016, has expanded considerably in content and user traffic over the past year. It is continuously evolving with the growth of DSSTox into high-interest or data-rich domains of interest to EPA, such

25 CFR 36.51 - Standard XVIII-Office of Indian Education Programs and Agency monitoring and evaluation...

Science.gov (United States)

2010-04-01

... XVIII—Office of Indian Education Programs and Agency monitoring and evaluation responsibilities. (a) The... 25 Indians 1 2010-04-01 2010-04-01 false Standard XVIII-Office of Indian Education Programs and Agency monitoring and evaluation responsibilities. 36.51 Section 36.51 Indians BUREAU OF INDIAN AFFAIRS...

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Science.gov (United States)

Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

(ENVIRONMENTAL SCIENCE and TECHNOLOGY) An Intuitive Approach for Predicting Human Risk with the Tox21 10k Library

Science.gov (United States)

In vitro to in vivo extrapolation (IVIVE) analyses translating high-throughput screening (HTS) data to human relevance have been limited. This is the first time IVIVE approaches and exposure comparisons have explored the entire Tox21 federal collaboration’s 10,000 chemi...

Tools to Minimize Inter-Laboratory Variability in Vitellogenin Gene Expression Monitoring Programs

Data.gov (United States)

U.S. Environmental Protection Agency — All data files are in excel format. Files with names CSU are different mesocosms qPCR data results for vitellogen gene and 18s a house keeping gene. Data files...

Development and Evaluation of a Hyperbaric Toxic Gas Monitor (SubTox) for Disabled Submarines

Science.gov (United States)

2013-08-01

air near the CO2 scrubbers was sampled, the common amine/ ammonia smell was present. And while no NH3 sensor was installed in the SubTox, no monitored...under pressure, the eight gases — ammonia , carbon monoxide, chlorine, hydrogen chloride, hydrogen cyanide, hydrogen sulfide, nitrogen dioxide, and...gases for which SEALs have been defined: ammonia (NH3), carbon monoxide (CO), chlorine (Cl2), hydrogen chloride (HCl), hydrogen cyanide (HCN

76 FR 5186 - National Protection and Programs Directorate; Agency Information Collection Activities; Office of...

Science.gov (United States)

2011-01-28

... DEPARTMENT OF HOMELAND SECURITY [Docket No. DHS-2010-0084] National Protection and Programs... Protection Stakeholder Input Project--Generic Clearance AGENCY: National Protection and Programs Directorate.... SUMMARY: The Department of Homeland Security (DHS), National Protection and Programs Directorate (NPPD...

E-SovTox: An online database of the main publicly-available sources of toxicity data concerning REACH-relevant chemicals published in the Russian language.

Science.gov (United States)

Sihtmäe, Mariliis; Blinova, Irina; Aruoja, Villem; Dubourguier, Henri-Charles; Legrand, Nicolas; Kahru, Anne

2010-08-01

A new open-access online database, E-SovTox, is presented. E-SovTox provides toxicological data for substances relevant to the EU Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system, from publicly-available Russian language data sources. The database contains information selected mainly from scientific journals published during the Soviet Union era. The main information source for this database - the journal, Gigiena Truda i Professional'nye Zabolevania [Industrial Hygiene and Occupational Diseases], published between 1957 and 1992 - features acute, but also chronic, toxicity data for numerous industrial chemicals, e.g. for rats, mice, guinea-pigs and rabbits. The main goal of the abovementioned toxicity studies was to derive the maximum allowable concentration limits for industrial chemicals in the occupational health settings of the former Soviet Union. Thus, articles featured in the database include mostly data on LD50 values, skin and eye irritation, skin sensitisation and cumulative properties. Currently, the E-SovTox database contains toxicity data selected from more than 500 papers covering more than 600 chemicals. The user is provided with the main toxicity information, as well as abstracts of these papers in Russian and in English (given as provided in the original publication). The search engine allows cross-searching of the database by the name or CAS number of the compound, and the author of the paper. The E-SovTox database can be used as a decision-support tool by researchers and regulators for the hazard assessment of chemical substances. 2010 FRAME.

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships (MCBIOS)

Science.gov (United States)

Comparative Analysis of Predictive Models for Liver Toxicity Using ToxCast Assays and Quantitative Structure-Activity Relationships Jie Liu1,2, Richard Judson1, Matthew T. Martin1, Huixiao Hong3, Imran Shah1 1National Center for Computational Toxicology (NCCT), US EPA, RTP, NC...

Can Thrifty Gene(s or Predictive Fetal Programming for Thriftiness Lead to Obesity?

Directory of Open Access Journals (Sweden)

Ulfat Baig

2011-01-01

Full Text Available Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation.

48 CFR 719.273 - The U.S. Agency for International Development (USAID) Mentor-Protégé Program.

Science.gov (United States)

2010-10-01

... International Development (USAID) Mentor-Protégé Program. 719.273 Section 719.273 Federal Acquisition.... Agency for International Development (USAID) Mentor-Protégé Program 719.273 The U.S. Agency for International Development (USAID) Mentor-Protégé Program. ...

Comparative analysis of the survival and gene expression of pathogenic strains Vibrio harveyi after starvation.

Science.gov (United States)

Sun, Jingjing; Gao, Xiaojian; Qun, Jiang; Du, Xuedi; Bi, Keran; Zhang, Xiaojun; Lin, Li

2016-11-01

This study aimed to evaluate the survival and gene expression of Vibrio harveyi under starvation conditions. The microcosms V. harveyi were incubated in sterilized seawater for 4 weeks at room temperature. Overall, the cell numeration declined rapidly about 10 3 CFU/ml during starvation, with a tiny rebound at day 21. Scanning electron microscopy revealed that rod-shaped cells became sphere with a rippled cell surface. By polymerase chain reaction (PCR) assay, nine genes, named luxR, toxR, vhhB, flaA, topA, fur, rpoS, mreB and ftsZ, were detected in the non-starved cells. In the starved cells, the expression levels of the detected genes declined substantially ranging from 0.005-fold to 0.028-fold compared to the non-starved cells performed by reverse transcription quantitative real-time PCR with 16S rRNA as the internal control. In the recovering cells, the expression levels of the detected genes, except luxR and mreB, were upregulated dramatically compared to the wild, especially topA (23.720-fold), fur (39.400-fold) and toxR (9.837-fold), validating that the expressions of both the metabolism and virulence genes were important for growth and survival of V. harveyi. The results may shed a new light on understanding of stress adaptation in bacteria. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Defense Logistics Agency Disposition Services Needs to Improve Demilitarization Program Self-Assessment Evaluations - Redacted

Science.gov (United States)

2016-12-20

from mandatory disclosure under the Freedom of Information Act. Defense Logistics Agency Disposition Services Needs to Improve Demilitarization...Project No. D2016-D000RD-0057.000) │ i Results in Brief Defense Logistics Agency Disposition Services Needs to Improve Demilitarization Program Self...Assessment Evaluations Visit us at www.dodig.mil December 20, 2016 Objective Our audit objective was to determine whether the Defense Logistics Agency

Overview of Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard

Science.gov (United States)

This poster provides an overview of three key lines of ongoing work at EPA/ORD/NCEA-CIN: Provisional Peer-Reviewed Toxicity Values (PPRTVs), Alternative Methods in Human Health Risk Assessment, and the RapidTox Dashboard collaboration.

78 FR 23290 - Renewal of Agency Information Collection for Energy Resource Development Program Grants

Science.gov (United States)

2013-04-18

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs [DR.5B813.IA001113] Renewal of Agency Information Collection for Energy Resource Development Program Grants AGENCY: Bureau of Indian Affairs... 1995, the Assistant Secretary--Indian Affairs is seeking comments on the renewal of Office of...

78 FR 4867 - Renewal of Agency Information Collection for Energy Resource Development Program Grants

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2013-01-23

... DEPARTMENT OF THE INTERIOR Bureau of Indian Affairs Renewal of Agency Information Collection for Energy Resource Development Program Grants AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of... Secretary--Indian Affairs is seeking comments on the renewal of Office of Management and Budget (OMB...

Report of cooperative research programs in the field of ion-beam breeding between Japan Atomic Energy Agency and Malaysian Nuclear Agency (Bilateral cooperative research)

International Nuclear Information System (INIS)

Ahmad, Zaiton; Oono, Yutaka

2016-03-01

This report summarizes Bilateral Cooperative Research between Japan Atomic Energy Agency and Malaysian Nuclear Agency (a representative of the Government of Malaysia) implemented from 2002 to 2012 under 'THE IMPLEMENTING ARRANGEMENT BETWEEN THE GOVERNMENT OF MALAYSIA AND THE JAPAN ATOMIC ENERGY AGENCY ON THE RESEARCH COOPERATION IN THE FIELD OF RADIATION PROCESSING'. The research activities in two Cooperative Research Programs, 'Mutation Induction of Orchid Plants by Ion Beams' and 'Generating New Ornamental Plant Varieties Using Ion Beams' performed 2002-2007 and 2007-2012, respectively, are contained. The lists of steering committee meetings, irradiation experiments, and publications/presentations of each program are also attached in the Appendixes. (author)

The Vitotox and ToxTracker assays: A two-test combination for quick and reliable assessment of genotoxic hazards.

Science.gov (United States)

Ates, Gamze; Favyts, Dorien; Hendriks, Giel; Derr, Remco; Mertens, Birgit; Verschaeve, Luc; Rogiers, Vera; Y Doktorova, Tatyana

2016-11-01

To ensure safety for humans, it is essential to characterize the genotoxic potential of new chemical entities, such as pharmaceutical and cosmetic substances. In a first tier, a battery of in vitro tests is recommended by international regulatory agencies. However, these tests suffer from inadequate specificity: compounds may be wrongly categorized as genotoxic, resulting in unnecessary, time-consuming, and expensive in vivo follow-up testing. In the last decade, novel assays (notably, reporter-based assays) have been developed in an attempt to overcome these drawbacks. Here, we have investigated the performance of two in vitro reporter-based assays, Vitotox and ToxTracker. A set of reference compounds was selected to span a variety of mechanisms of genotoxic action and applicability domains (e.g., pharmaceutical and cosmetic ingredients). Combining the performance of the two assays, we achieved 93% sensitivity and 79% specificity for prediction of gentoxicity for this set of compounds. Both assays permit quick high-throughput analysis of drug candidates, while requiring only small quantities of the test substances. Our study shows that these two assays, when combined, can be a reliable method for assessment of genotoxicity hazard. Copyright © 2016 Elsevier B.V. All rights reserved.

National Geospatial-Intelligence Agency Academic Research Program

Science.gov (United States)

Loomer, S. A.

2004-12-01

"Know the Earth.Show the Way." In fulfillment of its vision, the National Geospatial-Intelligence Agency (NGA) provides geospatial intelligence in all its forms and from whatever source-imagery, imagery intelligence, and geospatial data and information-to ensure the knowledge foundation for planning, decision, and action. To achieve this, NGA conducts a multi-disciplinary program of basic research in geospatial intelligence topics through grants and fellowships to the leading investigators, research universities, and colleges of the nation. This research provides the fundamental science support to NGA's applied and advanced research programs. The major components of the NGA Academic Research Program (NARP) are: - NGA University Research Initiatives (NURI): Three-year basic research grants awarded competitively to the best investigators across the US academic community. Topics are selected to provide the scientific basis for advanced and applied research in NGA core disciplines. - Historically Black College and University - Minority Institution Research Initiatives (HBCU-MI): Two-year basic research grants awarded competitively to the best investigators at Historically Black Colleges and Universities, and Minority Institutions across the US academic community. - Director of Central Intelligence Post-Doctoral Research Fellowships: Fellowships providing access to advanced research in science and technology applicable to the intelligence community's mission. The program provides a pool of researchers to support future intelligence community needs and develops long-term relationships with researchers as they move into career positions. This paper provides information about the NGA Academic Research Program, the projects it supports and how other researchers and institutions can apply for grants under the program.

77 FR 71016 - Renewal of Agency Information Collection for Tribal Self-Governance Program

Science.gov (United States)

2012-11-28

... Tribal Self- Governance Program AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of submission... collection of information for Tribal Self-Governance Program. The information collection is currently... send a copy of your comments to Ken Reinfeld, Office of Self-Governance, 1951 Constitution Avenue NW...

Probing the ToxCastTM Chemical Library for Predictive Signatures of Developmental Toxicity - Poster at Teratology Society Annual Meeting

Science.gov (United States)

EPA’s ToxCast™ project is profiling the in vitro bioactivity of chemical compounds to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesize that cell signaling pathways are primary targets for diverse environmental chemicals ...

20 CFR 422.305 - Report of overdue program overpayment debts to consumer reporting agencies.

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2010-04-01

... debts to consumer reporting agencies. (a) Debts we will report. We will report to consumer reporting... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Report of overdue program overpayment debts to consumer reporting agencies. 422.305 Section 422.305 Employees' Benefits SOCIAL SECURITY...

77 FR 43353 - Renewal of Agency Information Collection for Tribal Self-Governance Program

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2012-07-24

... Tribal Self- Governance Program AGENCY: Bureau of Indian Affairs, Interior. ACTION: Notice of request for... collection of information for Tribal Self-Governance Program authorized by OMB Control Number 1076-0143. This... Self-Governance, 1951 Constitution Avenue NW., Mail Stop 355-G SIB, Washington, DC 20240; telephone...

Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans.

Science.gov (United States)

McEwan, Deborah L; Kirienko, Natalia V; Ausubel, Frederick M

2012-04-19

Intestinal epithelial cells are exposed to both innocuous and pathogenic microbes, which need to be distinguished to mount an effective immune response. To understand the mechanisms underlying pathogen recognition, we investigated how Pseudomonas aeruginosa triggers intestinal innate immunity in Caenorhabditis elegans, a process independent of Toll-like pattern recognition receptors. We show that the P. aeruginosa translational inhibitor Exotoxin A (ToxA), which ribosylates elongation factor 2 (EF2), upregulates a significant subset of genes normally induced by P. aeruginosa. Moreover, immune pathways involving the ATF-7 and ZIP-2 transcription factors, which protect C. elegans from P. aeruginosa, are required for preventing ToxA-mediated lethality. ToxA-responsive genes are not induced by enzymatically inactive ToxA protein but can be upregulated independently of ToxA by disruption of host protein translation. Thus, C. elegans has a surveillance mechanism to recognize ToxA through its effect on protein translation rather than by direct recognition of either ToxA or ribosylated EF2. Copyright © 2012 Elsevier Inc. All rights reserved.

41 CFR 102-194.30 - What role does my agency play in the Standard and Optional Forms Management Program?

Science.gov (United States)

2010-07-01

... What role does my agency play in the Standard and Optional Forms Management Program? Your agency head... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What role does my agency play in the Standard and Optional Forms Management Program? 102-194.30 Section 102-194.30 Public...

CompNanoTox2015: novel perspectives from a European conference on computational nanotoxicology on predictive nanotoxicology

Energy Technology Data Exchange (ETDEWEB)

Bañares, Miguel A. [Instituto de Catalisis y Petroleoquimica, ICP, CSIC, Madrid, Spain,; Haase, Andrea [German Federal Institute for Risk Assessment (BfR), Department of Chemical and Product Safety, Berlin, Germany,; Tran, Lang [Statistics and Toxicology Section, Institute of Occupational Medicine, Edinburgh, UK,; Lobaskin, Vladimir [School of Physics, University College Dublin, Dublin, Ireland,; Oberdörster, Günter [Department of Environmental Medicine, University of Rochester, Rochester, NY, USA,; Rallo, Robert [Departament d’Enginyeria Informatica i Matematiques, Universitat Rovira i Virgili, Tarragona, Spain,; Advanced Computing, Mathematics, and Data Division, Pacific Northwest National Laboratory, Richland, WA, USA,; Leszczynski, Jerzy [Interdisciplinary Nanotoxicity Center, Jackson State University, Jackson, MS, USA,; Hoet, Peter [Public Health, Unit Lung Toxicology, K. U. Leuven, Leuven, Belgium,; Korenstein, Rafi [Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel,; Hardy, Barry [Technology Park Basel, Douglas Connect GmbH, Basel, Switzerland,; Puzyn, Tomasz [Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdansk, Gdansk, Poland

2017-08-09

A first European Conference on Computational Nanotoxicology, CompNanoTox, was held in November 2015 in Benahavís, Spain with the objectives to disseminate and integrate results from the European modeling and database projects (NanoPUZZLES, ModENPTox, PreNanoTox, MembraneNanoPart, MODERN, eNanoMapper and EU COST TD1204 MODENA) as well as to create synergies within the European NanoSafety Cluster. This conference was supported by the COST Action TD1204 MODENA on developing computational methods for toxicological risk assessment of engineered nanoparticles and provided a unique opportunity for crossfertilization among complementary disciplines. The efforts to develop and validate computational models crucially depend on high quality experimental data and relevant assays which will be the basis to identify relevant descriptors. The ambitious overarching goal of this conference was to promote predictive nanotoxicology, which can only be achieved by a close collaboration between the computational scientists (e.g. database experts, modeling experts for structure, (eco) toxicological effects, performance and interaction of nanomaterials) and experimentalists from different areas (in particular toxicologists, biologists, chemists and material scientists, among others). The main outcome and new perspectives of this conference are summarized here.

Defense Special Weapons Agency Advisory Panel on the Nuclear Weapon Effects Program

National Research Council Canada - National Science Library

1998-01-01

We performed the audit in response to allegations made to the Defense Hotline concerning conflicts of interest among members of the Defense Special Weapons Agency Advisory Panel on the Nuclear Weapon Effects Program...

41 CFR 102-38.360 - What must an executive agency do to implement the eFAS program?

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2010-07-01

... PROPERTY 38-SALE OF PERSONAL PROPERTY Implementation of the Federal Asset Sales Program § 102-38.360 What must an executive agency do to implement the eFAS program? (a) An executive agency must review the effectiveness of all sales solutions, and compare them to the effectiveness (e.g., cost, level of service, and...

78 FR 64022 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Program To...

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2013-10-25

... for OMB Review; Comment Request; Program To Prevent Smoking in Hazardous Areas of Underground Coal... Administration (MSHA) sponsored information collection request (ICR) titled, ``Program to Prevent Smoking in... electronic submission of responses. Agency: DOL-MSHA. Title of Collection: Program To Prevent Smoking in...

75 FR 16821 - Housing Finance Agency Risk-Sharing Program

Science.gov (United States)

2010-04-02

...The proposed information collection requirement described below has been submitted to the Office of Management and Budget (OMB) for review, as required by the Paperwork Reduction Act. The Department is soliciting public comments on the subject proposal. Section 542(c) of the Risk Sharing Program authorizes qualified Housing Finance Agencies (HFAs) to underwrite and process loans. HUD provides full mortgage insurance on affordable multifamily housing project processed by HFAs under this program. Qualified HFAs are vested with the maximum amount of processing responsibilities. By entering into Risk-Sharing Agreement with HUD, HFAs contract to reimburse HUD for a portion of the loss from any defaults that occur while HUD insurance is in force.

Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage.

Directory of Open Access Journals (Sweden)

Jui-Hua Hsieh

Full Text Available Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2 using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo while the other evaluates cell membrane integrity (i.e., cell death, flor. Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our

LiverTox: Advanced QSAR and Toxicogeomic Software for Hepatotoxicity Prediction

Energy Technology Data Exchange (ETDEWEB)

Lu, P-Y.; Yuracko, K. (YAHSGS, LLC)

2011-02-25

YAHSGS LLC and Oak Ridge National Laboratory (ORNL) established a CRADA in an attempt to develop a predictive system using a pre-existing ORNL computational neural network and wavelets format. This was in the interest of addressing national needs for toxicity prediction system to help overcome the significant drain of resources (money and time) being directed toward developing chemical agents for commerce. The research project has been supported through an STTR mechanism and funded by the National Institute of Environmental Health Sciences beginning Phase I in 2004 (CRADA No. ORNL-04-0688) and extending Phase II through 2007 (ORNL NFE-06-00020). To attempt the research objectives and aims outlined under this CRADA, state-of-the-art computational neural network and wavelet methods were used in an effort to design a predictive toxicity system that used two independent areas on which to base the system’s predictions. These two areas were quantitative structure-activity relationships and gene-expression data obtained from microarrays. A third area, using the new Massively Parallel Signature Sequencing (MPSS) technology to assess gene expression, also was attempted but had to be dropped because the company holding the rights to this promising MPSS technology went out of business. A research-scale predictive toxicity database system called Multi-Intelligent System for Toxicogenomic Applications (MISTA) was developed and its feasibility for use as a predictor of toxicological activity was tested. The fundamental focus of the CRADA was an attempt and effort to operate the MISTA database using the ORNL neural network. This effort indicated the potential that such a fully developed system might be used to assist in predicting such biological endpoints as hepatotoxcity and neurotoxicity. The MISTA/LiverTox approach if eventually fully developed might also be useful for automatic processing of microarray data to predict modes of action. A technical paper describing the

76 FR 24041 - Notice of Proposed Information Collection: Comment Request; HUD Housing Counseling Program-Agency...

Science.gov (United States)

2011-04-29

... a HUD-approved intermediary or multi-state organization, or be a state housing finance agency or affiliate or sub grantee of a state housing finance agency. Participation in the program entails meeting.... Additionally, this information helps HUD staff to assess whether participating organizations are meeting basic...

Cheminformatics and Data Mining Approaches for Exploring the Alternatives Testing Landscsape: Case Studies in ToxCast and Skin Sensitization (BOSC CSS)

Science.gov (United States)

Cheminformatics approaches and structure-based rules are being used to evaluate and explore the ToxCast chemical landscape and associated high-throughput screening (HTS) data. We have shown that the library provides comprehensive coverage of the knowledge domains and target inven...

Multi-agency data linkage- How to and lessons learnt through the Western Australian Developmental Pathways Program

Directory of Open Access Journals (Sweden)

Rebecca Glauert

2017-04-01

This Program is the largest data linkage program in Australia, and is continually expanding with new agencies coming on board every year. Here we will provide a useful overview of the Program, along with key lessons learnt.

Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons

Science.gov (United States)

Evaluation of the Neuroactivity of ToxCast Compounds Using Multi-well Microelectrode Array Recordings in Primary Cortical Neurons P Valdivia1, M Martin2, WR LeFew3, D Hall3, J Ross1, K Houck2 and TJ Shafer3 1Axion Biosystems, Atlanta GA and 2NCCT, 3ISTD, NHEERL, ORD, US EPA, RT...

77 FR 67804 - Agency Information Collection Activities; Comment Request; Application for Client Assistance Program

Science.gov (United States)

2012-11-14

...; Comment Request; Application for Client Assistance Program AGENCY: Department of Education (ED), Office of... of Collection: Application for Client Assistance Program. OMB Control Number: 1820-0520. Type of... Burden Hours: 9. Abstract: This form is used by states to request funds to establish and carry out Client...

Predicting dermal penetration for ToxCast chemicals using in silico estimates for diffusion in combination with physiologically based pharmacokinetic (PBPK) modeling.

Science.gov (United States)

Predicting dermal penetration for ToxCast chemicals using in silico estimates for diffusion in combination with physiologically based pharmacokinetic (PBPK) modeling.Evans, M.V., Sawyer, M.E., Isaacs, K.K, and Wambaugh, J.With the development of efficient high-throughput (HT) in ...

The US EPA CompTox Chemistry Dashboard as a source of data to fill data gaps for chemical sources of risk

Science.gov (United States)

Chemical risk assessment is both time-consuming and difficult because it requires the assembly of data for chemicals generally distributed across multiple sources. The US EPA CompTox Chemistry Dashboard is a publicly accessible web-based application providing access to various da...

Multiobjective optimization in Gene Expression Programming for Dew Point

OpenAIRE

Shroff, Siddharth; Dabhi, Vipul

2013-01-01

The processes occurring in climatic change evolution and their variations play a major role in environmental engineering. Different techniques are used to model the relationship between temperatures, dew point and relative humidity. Gene expression programming is capable of modelling complex realities with great accuracy, allowing, at the same time, the extraction of knowledge from the evolved models compared to other learning algorithms. This research aims to use Gene Expression Programming ...

Biocontrol of the Sugarcane Borer Eldana saccharina by Expression of the Bacillus thuringiensis cry1Ac7 and Serratia marcescens chiA Genes in Sugarcane-Associated Bacteria

Science.gov (United States)

Downing, Katrina J.; Leslie, Graeme; Thomson, Jennifer A.

2000-01-01

The cry1Ac7 gene of Bacillus thuringiensis strain 234, showing activity against the sugarcane borer Eldana saccharina, was cloned under the control of the tac promoter. The fusion was introduced into the broad-host-range plasmid pKT240 and the integration vector pJFF350 and without the tac promoter into the broad-host-range plasmids pML122 and pKmM0. These plasmids were introduced into a Pseudomonas fluorescens strain isolated from the phylloplane of sugarcane and the endophytic bacterium Herbaspirillum seropedicae found in sugarcane. The ptac-cry1Ac7 construct was introduced into the chromosome of P. fluorescens using the integration vector pJFF350 carrying the artificial interposon Omegon-Km. Western blot analysis showed that the expression levels of the integrated cry1Ac7 gene were much higher under the control of the tac promoter than under the control of its endogenous promoter. It was also determined that multicopy expression in P. fluorescens and H. seropedicae of ptac-cry1Ac7 carried on pKT240 caused plasmid instability with no detectable protein expression. In H. seropedicae, more Cry1Ac7 toxin was produced when the gene was cloned under the control of the Nmr promoter on pML122 than in the opposite orientation and bioassays showed that the former resulted in higher mortality of E. saccharina larvae than the latter. P. fluorescens 14::ptac-tox resulted in higher mortality of larvae than did P. fluorescens 14::tox. An increased toxic effect was observed when P. fluorescens 14::ptac-tox was combined with P. fluorescens carrying the Serratia marcescens chitinase gene chiA, under the control of the tac promoter, integrated into the chromosome. PMID:10877771

Real-time prediction of Physicochemical and Toxicological Endpoints Using the Web-based CompTox Chemistry Dashboard (ACS Fall meeting) 10 of 12

Science.gov (United States)

The EPA CompTox Chemistry Dashboard developed by the National Center for Computational Toxicology (NCCT) provides access to data for ~750,000 chemical substances. The data include experimental and predicted data for physicochemical, environmental fate and transport and toxicologi...

The International Atomic Energy Agency's program on decontamination and decommissioning

International Nuclear Information System (INIS)

Feraday, M.A.

1989-01-01

The International Atomic energy Agency (IAEA) is developing an integrated information base that will systematically cover the technical, regulatory, radiation protection, planning, and economic aspects related to the decontamination and decommissioning (D/D) of nuclear facilities. The object of this program is to assist member states in developing the required expertise, equipment, and programs so that they can decommission their nuclear facilities in a safe, timely, and cost-effective manner. In addition to providing information, the IAEA encourages research and provides technical assistance in the form of expert missions, equipment design and procurement, etc., to assist member states in implementing their D/D programs. The technology contained in some recent IAEA reports is reviewed, including the decontamination, segmentation, and demolition of concrete and steel; the recycle/reuse of components from decommissioning; and the reduction of occupational exposures in D/D and the regulatory process in decommissioning. The IAEA's future program is briefly reviewed

GPAW optimized for Blue Gene/P using hybrid programming

DEFF Research Database (Denmark)

Kristensen, Mads Ruben Burgdorff; Happe, Hans Henrik; Vinter, Brian

2009-01-01

In this work we present optimizations of a Grid-based projector-augmented wave method software, GPAW for the Blue Gene/P architecture. The improvements are achieved by exploring the advantage of shared and distributed memory programming also known as hybrid programming. The work focuses on optimi......In this work we present optimizations of a Grid-based projector-augmented wave method software, GPAW for the Blue Gene/P architecture. The improvements are achieved by exploring the advantage of shared and distributed memory programming also known as hybrid programming. The work focuses...... on optimizing a very time consuming operation in GPAW, the finite-different stencil operation, and different hybrid programming approaches are evaluated. The work succeeds in demonstrating a hybrid programming model which is clearly beneficial compared to the original flat programming model. In total...... an improvement of 1.94 compared to the original implementation is obtained. The results we demonstrate here are reasonably general and may be applied to other finite difference codes....

76 FR 41813 - Renewal of Agency Information Collection for Higher Education Grant Program Application; Request...

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2011-07-15

... Higher Education Grant Program Application; Request for Comments AGENCY: Bureau of Indian Affairs... and Budget (OMB) approval for the collection of information for the Higher Education Grant Program... Number: 1076-0101. Title: Higher Education Grant Application, 25 CFR part 40. Brief Description of...

The US program of technical assistance to the Atomic Energy Agency of the Republic of Kazakstan

International Nuclear Information System (INIS)

Tittemore, G.; Kuzmycz, G.; Caudill, S.

1995-01-01

In the summer of 1993, the US Department of Energy (US government) received a formal invitation from the Atomic Energy Agency of the Republic of Kazakstan (AEARK) to visit Kazakstan to prepare a program for US cooperation with the AEARK to improve material protection, control, and accounting (MPCA) at Kazakstani nuclear facilities. As a result of this visit, an agreement for such cooperation was prepared and a program plan was formulated. The Program Plan includes provisions for Technical Working Group meetings, a site survey of a Kazakstani nuclear facility for possible upgrades in MPCA, assistance to AEARK in the regulatory area, training courses to familiarize AEARK and nuclear facility personnel with US safeguards practices, and supply of US safeguards equipment. This cooperative program is funded by the Nunn-Lugar program and the Department of Energy. The program is coordinated with the International Atomic Energy Agency and similar programs of other donor countries (Sweden, Japan, and the United Kingdom). This paper summarizes accomplishments of the program to date and future plans

TIC-Tox: A preliminary discussion on identifying the forcing agents of DBP-mediated toxicity of disinfected water.

Science.gov (United States)

Plewa, Michael J; Wagner, Elizabeth D; Richardson, Susan D

2017-08-01

The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products (DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment. Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes (THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water. Copyright © 2017. Published by Elsevier B.V.

LuminoTox : a tool for the rapid detection of PAH, BPC and chlorobenzenes in waste water and sediments

Energy Technology Data Exchange (ETDEWEB)

Bellemare, F.; Boucher, N.; Lorrain, L.; Rouette, M.E.; Perron, E. [Lab-bell Inc., Shawnigan, PQ (Canada)

2005-07-01

The LuminoTox is a portable fluorimetric detection device capable of assessing water toxicity in 10 to 15 minutes. The toxicity of a water sample is indicated by the modification of fluorescence parameters within isolated both isolated photosynthetic complexes (PECs) and photosynthetic algae (SAPs). An array of 4 LEDs and photodetectors is used to determine fluorescence emissions from PEPs and SAPs. Fluorescence data is then transferred to a computer for analysis. A kinetic detection mode is currently being developed for the tool. This paper provided details of a test conducted to demonstrate the kinetic detection capabilities of the new design. Sediment containing polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls, and chlorobenzene were used in the analysis. Results showed that the fluorescence kinetic mode yielded improved sensitivity with molecules acting on the electron transport chain downstream from the tool's photosystem. The test demonstrated that the LuminoTox technology is capable of accurately monitoring the presence of PAHs, PCBs, and chlorobenzenes. It was concluded that the tool is sensitive to a wide range of pollutants and can be used to analyze complex waste water and slurries. 15 refs., 2 tabs., 1 fig.

EU Framework 6 Project: Predictive Toxicology (PredTox)-overview and outcome

International Nuclear Information System (INIS)

Suter, Laura; Schroeder, Susanne; Meyer, Kirstin; Gautier, Jean-Charles; Amberg, Alexander; Wendt, Maria; Gmuender, Hans; Mally, Angela; Boitier, Eric; Ellinger-Ziegelbauer, Heidrun; Matheis, Katja; Pfannkuch, Friedlieb

2011-01-01

In this publication, we report the outcome of the integrated EU Framework 6 Project: Predictive Toxicology (PredTox), including methodological aspects and overall conclusions. Specific details including data analysis and interpretation are reported in separate articles in this issue. The project, partly funded by the EU, was carried out by a consortium of 15 pharmaceutical companies, 2 SMEs, and 3 universities. The effects of 16 test compounds were characterized using conventional toxicological parameters and 'omics' technologies. The three major observed toxicities, liver hypertrophy, bile duct necrosis and/or cholestasis, and kidney proximal tubular damage were analyzed in detail. The combined approach of 'omics' and conventional toxicology proved a useful tool for mechanistic investigations and the identification of putative biomarkers. In our hands and in combination with histopathological assessment, target organ transcriptomics was the most prolific approach for the generation of mechanistic hypotheses. Proteomics approaches were relatively time-consuming and required careful standardization. NMR-based metabolomics detected metabolite changes accompanying histopathological findings, providing limited additional mechanistic information. Conversely, targeted metabolite profiling with LC/GC-MS was very useful for the investigation of bile duct necrosis/cholestasis. In general, both proteomics and metabolomics were supportive of other findings. Thus, the outcome of this program indicates that 'omics' technologies can help toxicologists to make better informed decisions during exploratory toxicological studies. The data support that hypothesis on mode of action and discovery of putative biomarkers are tangible outcomes of integrated 'omics' analysis. Qualification of biomarkers remains challenging, in particular in terms of identification, mechanistic anchoring, appropriate specificity, and sensitivity.

The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

Science.gov (United States)

Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

2013-01-01

The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of food-relevant chemicals in the ToxCast high-throughput screening program

Data.gov (United States)

U.S. Environmental Protection Agency — Thousands of chemicals are directly added to or come in contact with food, many of which have undergone little to no toxicological evaluation. The landscape of the...

Shifting contours of boundaries: an exploration of inter-agency integration between hospital and community interprofessional diabetes programs.

Science.gov (United States)

Wong, Rene; Breiner, Petra; Mylopoulos, Maria

2014-09-01

This article reports on research into the relationships that emerged between hospital-based and community-based interprofessional diabetes programs involved in inter-agency care. Using constructivist grounded theory methodology we interviewed a purposive theoretical sample of 21 clinicians and administrators from both types of programs. Emergent themes were identified through a process of constant comparative analysis. Initial boundaries were constructed based on contrasts in beliefs, practices and expertise. In response to bureaucratic and social pressures, boundaries were redefined in a way that created role uncertainty and disempowered community programs, ultimately preventing collaboration. We illustrate the dynamic and multi-dimensional nature of social and symbolic boundaries in inter-agency diabetes care and the tacit ways in which hospitals can maintain a power position at the expense of other actors in the field. As efforts continue in Canada and elsewhere to move knowledge and resources into community sectors, we highlight the importance of hospitals seeing beyond their own interests and adopting more altruistic models of inter-agency integration.

A Bistable Switch and Anatomical Site Control Vibrio cholerae Virulence Gene Expression in the Intestine

DEFF Research Database (Denmark)

Nielsen, Alex Toftgaard; Dolganov, N. A.; Rasmussen, Thomas

2010-01-01

A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene...... expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP) and cholera toxin (CT) were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co......, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal...

U.S. ENVIRONMENTAL PROTECTION AGENCY (EPA) ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) PROGRAM: ARSENIC MONITORING TECHNOLOGIES

Science.gov (United States)

The U.S. Environmental Protection Agency Environmental Technology Verification (ETV) program evaluates the performance of innovative air, water, pollution prevention and monitoring technologies that have the potential to improve human health and the environment. This technology ...

Analysis of Ingredient Lists to Quantitatively Characterize ...

Science.gov (United States)

The EPA’s ExpoCast program is developing high throughput (HT) approaches to generate the needed exposure estimates to compare against HT bioactivity data generated from the US inter-agency Tox21 and the US EPA ToxCast programs. Assessing such exposures for the thousands of chemicals in consumer products requires data on product composition. This is a challenge since quantitative product composition data are rarely available. We developed methods to predict the weight fractions of chemicals in consumer products from weight fraction-ordered chemical ingredient lists, and curated a library of such lists from online manufacturer and retailer sites. The probabilistic model predicts weight fraction as a function of the total number of reported ingredients, the rank of the ingredient in the list, the minimum weight fraction for which ingredients were reported, and the total weight fraction of unreported ingredients. Weight fractions predicted by the model compared very well to available quantitative weight fraction data obtained from Material Safety Data Sheets for products with 3-8 ingredients. Lists were located from the online sources for 5148 products containing 8422 unique ingredient names. A total of 1100 of these names could be located in EPA’s HT chemical database (DSSTox), and linked to 864 unique Chemical Abstract Service Registration Numbers (392 of which were in the Tox21 chemical library). Weight fractions were estimated for these 864 CASRN. Using a

76 FR 71417 - Privacy Act of 1974, as Amended; Computer Matching Program (SSA/Law Enforcement Agencies (LEA...

Science.gov (United States)

2011-11-17

...; Computer Matching Program (SSA/ Law Enforcement Agencies (LEA)) Match Number 5001 AGENCY: Social Security... protections for such persons. The Privacy Act, as amended, regulates the use of computer matching by Federal... accordance with the Privacy Act of 1974, as amended by the Computer Matching and Privacy Protection Act of...

The eTOX Data-Sharing Project to Advance in Silico Drug-Induced Toxicity Prediction

Directory of Open Access Journals (Sweden)

Montserrat Cases

2014-11-01

Full Text Available The high-quality in vivo preclinical safety data produced by the pharmaceutical industry during drug development, which follows numerous strict guidelines, are mostly not available in the public domain. These safety data are sometimes published as a condensed summary for the few compounds that reach the market, but the majority of studies are never made public and are often difficult to access in an automated way, even sometimes within the owning company itself. It is evident from many academic and industrial examples, that useful data mining and model development requires large and representative data sets and careful curation of the collected data. In 2010, under the auspices of the Innovative Medicines Initiative, the eTOX project started with the objective of extracting and sharing preclinical study data from paper or pdf archives of toxicology departments of the 13 participating pharmaceutical companies and using such data for establishing a detailed, well-curated database, which could then serve as source for read-across approaches (early assessment of the potential toxicity of a drug candidate by comparison of similar structure and/or effects and training of predictive models. The paper describes the efforts undertaken to allow effective data sharing intellectual property (IP protection and set up of adequate controlled vocabularies and to establish the database (currently with over 4000 studies contributed by the pharma companies corresponding to more than 1400 compounds. In addition, the status of predictive models building and some specific features of the eTOX predictive system (eTOXsys are presented as decision support knowledge-based tools for drug development process at an early stage.

U.S. ENVIRONMENTAL PROTECTION AGENCY (EPA) ENVIRONMENTAL TECHNOLOGY VERIFICATION (ETV) PROGRAM: ARSENIC TREATMENT TECHNOLOGIES

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The U.S. Environmental Protection Agency (EPA) Environmental Technology Verification (ETV) program evaluates the performance of innovative air, water, pollution prevention and monitoring technologies that have the potential to improve human health and the environment. This techn...

A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.

Directory of Open Access Journals (Sweden)

Alex T Nielsen

2010-09-01

Full Text Available A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP and cholera toxin (CT were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co-localize with virulence gene expression. Significant heterogeneity in the expression of tcpA, the repeating subunit of TCP, was observed late in the infectious process. The expression of tcpA, studied in single cells in a homogeneous medium, demonstrated unimodal induction of tcpA after addition of bicarbonate, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal master regulator of virulence gene expression also exhibited the bifurcation phenotype. The bifurcation phenotype was found to be reversible, epigenetic and to persist after removal of bicarbonate, features consistent with bistable switches. The bistable switch requires the positive-feedback circuit controlling ToxT expression and formation of the CRP-cAMP complex during entry into stationary phase. Key features of this bistable switch also were demonstrated in vivo, where striking heterogeneity in tcpA expression was observed in luminal fluid in later stages of the infection. When this fluid was diluted into artificial seawater, bacterial aggregates continued to express tcpA for prolonged periods of time. The bistable control of virulence gene expression points to a

Tox_esterase_2016

Data.gov (United States)

U.S. Environmental Protection Agency — individual values for liver detoxification for each human sample and for each chemical. This dataset is associated with the following publication: Moser, G., and S....

Computation Modeling of Limb-bud Dysmorphogenesis: Predicting Cellular Dynamics and Key Events in Developmental Toxicity with a Multicellular Systems Model (FutureToxII)

Science.gov (United States)

Congenital limb malformations are among the most frequent malformation occurs in humans, with a frequency of about 1 in 500 to 1 in 1000 human live births. ToxCast is profiling the bioactivity of thousands of chemicals based on high-throughput (HTS) and computational methods that...

Evaluating Performance Measurement Systems in Nonprofit Agencies: The Program Accountability Quality Scale (PAQS).

Science.gov (United States)

Poole, Dennis L.; Nelson, Joan; Carnahan, Sharon; Chepenik, Nancy G.; Tubiak, Christine

2000-01-01

Developed and field tested the Performance Accountability Quality Scale (PAQS) on 191 program performance measurement systems developed by nonprofit agencies in central Florida. Preliminary findings indicate that the PAQS provides a structure for obtaining expert opinions based on a theory-driven model about the quality of proposed measurement…

77 FR 2350 - Agency Information Collection (Request for Change of Program or Place of Training): Activity...

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2012-01-17

..., OMB Human Resources and Housing Branch, New Executive Office Building, Room 10235, Washington, DC... for Change of Program or Place of Training): Activity Under OMB Review AGENCY: Veterans Benefits... Program or Place of Training, VA Form 22-1995. OMB Control Number: 2900-0074. Type of Review: Extension of...

Gene expression programming for power system static security ...

African Journals Online (AJOL)

user

Keywords: static security, gene expression programming, probabilistic neural network ... Hence digital computers are usually installed in operations control centers to gather ...... power system protection, and applications of AI in power systems.

Evaluating bacterial gene-finding HMM structures as probabilistic logic programs.

Science.gov (United States)

Mørk, Søren; Holmes, Ian

2012-03-01

Probabilistic logic programming offers a powerful way to describe and evaluate structured statistical models. To investigate the practicality of probabilistic logic programming for structure learning in bioinformatics, we undertook a simplified bacterial gene-finding benchmark in PRISM, a probabilistic dialect of Prolog. We evaluate Hidden Markov Model structures for bacterial protein-coding gene potential, including a simple null model structure, three structures based on existing bacterial gene finders and two novel model structures. We test standard versions as well as ADPH length modeling and three-state versions of the five model structures. The models are all represented as probabilistic logic programs and evaluated using the PRISM machine learning system in terms of statistical information criteria and gene-finding prediction accuracy, in two bacterial genomes. Neither of our implementations of the two currently most used model structures are best performing in terms of statistical information criteria or prediction performances, suggesting that better-fitting models might be achievable. The source code of all PRISM models, data and additional scripts are freely available for download at: http://github.com/somork/codonhmm. Supplementary data are available at Bioinformatics online.

Gene program-specific regulation of PGC-1{alpha} activity

DEFF Research Database (Denmark)

Schmidt, Søren F; Mandrup, Susanne

2011-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1 α (PGC-1α) activation coordinates induction of the hepatic fasting response through coactivation of numerous transcription factors and gene programs. In the June 15, 2011, issue of Genes & Development, Lustig and colleagues (pp....... 1232-1244) demonstrated that phosphorylation of PGC-1α by the p70 ribosomal protein S6 kinase 1 (S6K1) specifically interfered with the interaction between PGC-1α and HNF4α in liver and blocked the coactivation of the gluconeogenic target genes. This demonstrates how independent fine-tuning of gene...

The EPA CompTox Dashboard and Underpinning Software Architecture – a platform for data integration for environmental chemistry data (ACS Fall Meeting 7 of 12)

Science.gov (United States)

The CompTox Dashboard was developed by the Environmental Protection Agency’s National Center for Computational Toxicology. This dashboard has been architected in a manner that allows for the deployment of multiple “applications”, both as publicly available databases, and for dep...

77 FR 22347 - Agency Information Collection Agencies: Proposed Collection; Comments Requested Reinstatement...

Science.gov (United States)

2012-04-13

... Approval Has Expired: Survey of General Purpose Law Enforcement Agencies, 2012 ACTION: 60-Day notice of information collection under review. The Department of Justice, Office of Justice Programs, Bureau of Justice... DEPARTMENT OF JUSTICE [OMB Number 1121-0240] Agency Information Collection Agencies: Proposed...

Notification: Review of the U.S. Environmental Protection Agency's Purchase Card and Convenience Check Program

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Project #OA-FY13-0116, December 20, 2012. The U.S. Environmental Protection Agency, Office of Inspector General, plans to begin preliminary research for an audit of the agency’s purchase card and convenience check programs.

48 CFR 15.604 - Agency points of contact.

Science.gov (United States)

2010-10-01

... agency: upcoming solicitations; Broad Agency Announcements; Small Business Innovation Research programs; Small Business Technology Transfer Research programs; Program Research and Development Announcements; or... CONTRACTING METHODS AND CONTRACT TYPES CONTRACTING BY NEGOTIATION Unsolicited Proposals 15.604 Agency points...

Evaluation and comparison of bisphenol A analog activity ...

Science.gov (United States)

Bisphenol A (BPA) is used in consumer products and industrial applications, primarily in plastics, and has been detected in the environment, human urine, blood, and breast milk. Mainly studied as an endocrine disruptor, other toxicities, including obesity, metabolic conditions such as diabetes, and neurodevelopmental effects have also been associated with exposure to BPA, indicating that its effects may not be limited to estrogenicity. In addition, a number of BPA analogs are in use and may exhibit other additional toxicities. To address these unknowns, we examined the bioactivity of 21 BPA analogs across a selection of ToxCast/Tox21 assays grouped by 7 gene sets including estrogen receptor (ER), androgen receptor (AR), thyroid receptor (TR), peroxisome proliferator-activated receptor (PPAR), pregnane x receptor (PXR), aromatase (AROM), and aryl hydrocarbon receptor (AHR). The most active compounds were bisphenol AF (BPAF) (ER, AR, AROM, AHR), bisphenol A glycidyl methacrylate (TR), 3,3’,5,5’-tetrabromobisphenol A (PPAR) and bisphenol B (BPB) (PXR). We used these data to produce toxicological prioritization index (ToxPi) scores and images to integrate and visually compare the toxicity profiles across all gene sets. The compounds with highest ToxPi scores were BPAF, BPA and BPB. We also mapped the intended gene targets for all ToxCast assays to their associated KEGG BRITE protein families in order to characterize their toxicity profiles on a broader spectr

24 CFR 214.305 - Agency profile changes.

Science.gov (United States)

2010-04-01

...) of its branches and affiliates; (2) Staff personnel responsible for the Housing Counseling program... URBAN DEVELOPMENT MORTGAGE AND LOAN INSURANCE PROGRAMS UNDER NATIONAL HOUSING ACT AND OTHER AUTHORITIES HOUSING COUNSELING PROGRAM Program Administration § 214.305 Agency profile changes. Participating agencies...

Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes

NARCIS (Netherlands)

Elferink, M. G. L.; Olinga, P.; van Leeuwen, E. M.; Bauerschmidt, S.; Polman, J.; Schoonen, W. G.; Heisterkamp, S. H.; Groothuis, G. M. M.

2011-01-01

In the process of drug development it is of high importance to test the safety of new drugs with predictive value for human toxicity. A promising approach of toxicity testing is based on shifts in gene expression profiling of the liver. Toxicity screening based on animal liver cells cannot be

Quality Assurance of Joint Degree Programs from the Perspective of Quality Assurance Agencies: Experience in East Asia

Science.gov (United States)

Hou, Yung-Chi; Ince, Martin; Tsai, Sandy; Wang, Wayne; Hung, Vicky; Lin Jiang, Chung; Chen, Karen Hui-Jung

2016-01-01

Joint degree programs have gained popularity in East Asia, due to the growth of transnational higher education in the region since 2000. However, the external quality assurance (QA) and accreditation of joint degree programs is a challenge for QA agencies, as it normally involves the engagement of several institutions and multiple national…

77 FR 56712 - Agency Information Collection (Homeless Providers Grant and Per Diem Program) Activities Under...

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2012-09-13

... Providers Grant and Per Diem Program) Activities Under OMB Review AGENCY: Veterans Health Administration... Resources and Housing Branch, New Executive Office Building, Room 10235, Washington, DC 20503, (202) 395... . Please refer to ``OMB Control No. 2900-0554.'' SUPPLEMENTARY INFORMATION: Titles: a. Homeless Providers...

Using semi-automated curation workflows to collect, organize, and curate the data and models necessary to support the EPA CompTox chemical dashboard (ACS Spring meeting)

Science.gov (United States)

With the increasing need to leverage data and models to perform cutting edge analyses within the environmental science community, collection and organization of that data into a readily accessible format for consumption is a pressing need. The EPA CompTox chemical dashboard is i...

ADME-Tox profiling of some low molecular weight water soluble chitosan derivatives

Directory of Open Access Journals (Sweden)

Adriana Isvoran

2017-09-01

Full Text Available Within this study we use a few computational tools for predicting absorption, distribution, metabolism, excretion and toxicity (ADME-Tox, pharmacokinetics profiles, toxic/adverse effects, carcinogenicity, cardiotoxicity and endocrine disruption of some of low molecular weight water soluble derivatives of chitosan that are used in wound healing. Investigated compounds do not possess drug-like properties, their pharmacokinetics profiles reveal poor gastrointestinal absorption and low skin penetration. Chitosan derivatives cannot pass the blood-brain barrier and they are not able to inhibit the enzymes of the cytochrome P450 that are involved in the metabolism of xenobiotics. They do not reflect carcinogenicity and cardiotoxicity and reveal only a low probability to be endocrine disruptors. The main side effects in humans of the investigated compounds are: weight loss, acidosis, gastrointestinal toxicity, respiratory failure. This information is especially important for professional exposure and accidental contamination with these compounds.

Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.

Science.gov (United States)

Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L; Merrick, B Alex; Teng, Christina T; Tice, Raymond R

2015-10-01

Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gene doping.

Science.gov (United States)

Haisma, H J; de Hon, O

2006-04-01

Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.

[Ideas and methods on efficient screening of traditional medicines for anti-osteoporosis activity based on M-Act/Tox integrated evaluation using zebrafish].

Science.gov (United States)

Wang, Mo; Ling, Jie; Chen, Ying; Song, Jie; Sun, E; Shi, Zi-Qi; Feng, Liang; Jia, Xiao-Bin; Wei, Ying-Jie

2017-11-01

The increasingly apparent liver injury problems of bone strengthening Chinese medicines have brought challenges for clinical application, and it is necessary to consider both effectiveness and safety in screening anti-osteoporosis Chinese medicines. Metabolic transformation is closely related to drug efficacy and toxicity, so it is significant to comprehensively consider metabolism-action/toxicity(M-Act/Tox) for screening anti-osteoporosis Chinese medicines. The current evaluation models and the number of compounds(including metabolites) severely restrict efficient screening in vivo. By referring to previous relevant research and domestic and abroad literature, zebrafish M-Act/Tox integrative method was put forward for efficiently screening anti-osteoporosis herb medicines, which has organically integrated zebrafish metabolism model, osteoporosis model and toxicity evaluation method. This method can break through the bottleneck and blind spots that trace compositions can't achieve efficient and integrated in vivo evaluation, and realize both efficient and comprehensive screening on anti-osteoporosis traditional medicines based on in vivo process taking both safety and effectiveness into account, which is significant to accelerate discovery of effective and safe innovative traditional Chinese medicines for osteoporosis. Copyright© by the Chinese Pharmaceutical Association.

Quorum-sensing regulators control virulence gene expression in Vibrio cholerae

OpenAIRE

Zhu, Jun; Miller, Melissa B.; Vance, Russell E.; Dziejman, Michelle; Bassler, Bonnie L.; Mekalanos, John J.

2002-01-01

The production of virulence factors including cholera toxin and the toxin-coregulated pilus in the human pathogen Vibrio cholerae is strongly influenced by environmental conditions. The well-characterized ToxR signal transduction cascade is responsible for sensing and integrating the environmental information and controlling the virulence regulon. We show here that, in addition to the known components of the ToxR signaling circuit, quorum-sensing regulators are involved in regulation of V. ch...

Association of mandated language access programming and quality of care provided by mental health agencies.

Science.gov (United States)

McClellan, Sean R; Snowden, Lonnie

2015-01-01

This study examined the association between language access programming and quality of psychiatric care received by persons with limited English proficiency (LEP). In 1999, the California Department of Mental Health required county Medicaid agencies to implement a "threshold language access policy" to meet the state's Title VI obligations. This policy required Medi-Cal agencies to provide language access programming, including access to interpreters and translated written material, to speakers of languages other than English if the language was spoken by at least 3,000, or 5%, of the county's Medicaid population. Using a longitudinal study design with a nonequivalent control group, this study examined the quality of care provided to Spanish speakers with LEP and a severe mental illness before and after implementation of mandatory language access programming. Quality was measured by receipt of at least two follow-up medication visits within 90 days or three visits within 180 days of an initial medication visit over a period of 38 quarter-years. On average, only 40% of Spanish-speaking clients received at least three medication follow-up visits within 180 days. In multivariate analyses, language access programming was not associated with receipt of at least two medication follow-up visits within 90 days or at least three visits within 180 days. This study found no evidence that language access programming led to increased rates of follow-up medication visits for clients with LEP.

Chromosome structures: reduction of certain problems with unequal gene content and gene paralogs to integer linear programming.

Science.gov (United States)

Lyubetsky, Vassily; Gershgorin, Roman; Gorbunov, Konstantin

2017-12-06

Chromosome structure is a very limited model of the genome including the information about its chromosomes such as their linear or circular organization, the order of genes on them, and the DNA strand encoding a gene. Gene lengths, nucleotide composition, and intergenic regions are ignored. Although highly incomplete, such structure can be used in many cases, e.g., to reconstruct phylogeny and evolutionary events, to identify gene synteny, regulatory elements and promoters (considering highly conserved elements), etc. Three problems are considered; all assume unequal gene content and the presence of gene paralogs. The distance problem is to determine the minimum number of operations required to transform one chromosome structure into another and the corresponding transformation itself including the identification of paralogs in two structures. We use the DCJ model which is one of the most studied combinatorial rearrangement models. Double-, sesqui-, and single-operations as well as deletion and insertion of a chromosome region are considered in the model; the single ones comprise cut and join. In the reconstruction problem, a phylogenetic tree with chromosome structures in the leaves is given. It is necessary to assign the structures to inner nodes of the tree to minimize the sum of distances between terminal structures of each edge and to identify the mutual paralogs in a fairly large set of structures. A linear algorithm is known for the distance problem without paralogs, while the presence of paralogs makes it NP-hard. If paralogs are allowed but the insertion and deletion operations are missing (and special constraints are imposed), the reduction of the distance problem to integer linear programming is known. Apparently, the reconstruction problem is NP-hard even in the absence of paralogs. The problem of contigs is to find the optimal arrangements for each given set of contigs, which also includes the mutual identification of paralogs. We proved that these

Risk-Association of Five SNPs in TOX3/LOC643714 with Breast Cancer in Southern China

Directory of Open Access Journals (Sweden)

Xuanqiu He

2014-01-01

Full Text Available The specific mechanism by which low-risk genetic variants confer breast cancer risk is currently unclear, with contradictory evidence on the role of single nucleotide polymorphisms (SNPs in TOX3/LOC643714 as a breast cancer susceptibility locus. Investigations of this locus using a Chinese population may indicate whether the findings initially identified in a European population are generalizable to other populations, and may provide new insight into the role of genetic variants in the etiology of breast cancer. In this case-control study, 623 Chinese female breast cancer patients and 620 cancer-free controls were recruited to investigate the role of five SNPs in TOX3/LOC643714 (rs8051542, rs12443621, rs3803662, rs4784227, and rs3112612; Linkage disequilibrium (LD pattern analysis was performed. Additionally, we evaluated how these common SNPs influence the risk of specific types of breast cancer, as defined by estrogen receptor (ER status, progesterone receptor (PR status and human epidermal growth factor receptor 2 (HER2 status. Significant associations with breast cancer risk were observed for rs4784227 and rs8051542 with odds ratios (OR of 1.31 ((95% confidence intervals (CI, 1.10–1.57 and 1.26 (95% CI, 1.02–1.56, respectively, per T allele. The T-rs8051542 allele was significantly associated with ER-positive and HER2-negative carriers. No significant association existed between rs12443621, rs3803662, and rs3112612 polymorphisms and risk of breast cancer. Our results support the hypothesis that the applicability of a common susceptibility locus must be confirmed among genetically different populations, which may together explain an appreciable fraction of the genetic etiology of breast cancer.

Prioritizing Environmental Chemicals for Obesity and Diabetes ...

Science.gov (United States)

Background: Diabetes and obesity are major threats to public health in the US and abroad. Understanding the role chemicals in our environment play in the development of these conditions is an emerging issue in environmental health, although identifying and prioritizing chemicals for testing beyond those already implicated in the literature is a challenge. This review is intended to help researchers generate hypotheses about chemicals potentially contributing to diabetes and obesity-related health outcomes by summarizing relevant findings from the US Environmental Protection Agency (EPA) ToxCast high-throughput screening (HTS) program. Objectives: To develop new hypotheses around environmental chemicals of potential interest for diabetes- or obesity-related outcomes using high throughput screening data. Methods: Identify ToxCast assay targets relevant to several biological processes related to diabetes and obesity (insulin sensitivity in peripheral tissue, pancreatic islet and beta cell function, adipocyte dierentiation, and feeding behavior) and present chemical screening data against those assay targets to identify chemicals of potential interest. Discussion: Results of this screening-level analysis suggest that the spectrum of environmental chemicals to consider in research related to diabetes and obesity is much broader than indicated from research papers and reviews published in the peer-reviewed literature. Testing of hypotheses based on ToxCast data will a

ToxCast Phase I

Data.gov (United States)

U.S. Environmental Protection Agency — Background: Chemical toxicity testing is being transformed by advances in biology and computer modeling, concerns over animal use and the thousands of environmental...

Tradescantia cytogenetic tests (root-tip mitosis, pollen mitosis, pollen mother-cell meiosis). A report of the US Environmental Protection Agency gene-tox program

Energy Technology Data Exchange (ETDEWEB)

Ma, T H

1982-01-01

3 kinds of cytogenetic tests for screening of environmental mutagens were established for Tradescantia, namely, root-tip mitosis, pollen mitosis, and pollen mother-cell meiosis (commonly referred to as the Tradescantia-micronucleus (Trad-MCN) test). All these tests are technically simple, inexpensive, and can yield reliable results in a relatively short time (36 to 72 h). The root-tip mitosis test is suitable only for liquid agents, while pollen mitosis is suitable for both liquid and gaseous agents. Pollen tube mitotic chromosomes are extremely sensitive to mutagens; therefore, they are good materials for detecting very low concentrations of mutagens. Both root-tip mitosis and pollen mitosis tests use chromosome and/or chromatid aberrations as end points for scoring. The Trad-MCN test is suitable for both liquid and gaseous agents. In addition, it is especially suitable for in situ monitoring of water and air pollutants. Of the 12 chemicals tested, 5-fluorouracil and 1,2-dibromoethane indicate that they are very potent mutagens based on the effective dosages used to produce a positive response. Sulfur dioxide, ethyl methanesulfonate, sodium azide, Phosdrin, and Bladex rank next in potency.

Host-selective toxins of Pyrenophora tritici-repentis induce common responses associated with host susceptibility.

Directory of Open Access Journals (Sweden)

Iovanna Pandelova

Full Text Available Pyrenophora tritici-repentis (Ptr, a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA and Ptr ToxB (ToxB, are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death.

13 CFR 121.903 - How may an agency use size standards for its programs that are different than those established...

Science.gov (United States)

2010-01-01

... suitable for their programs, then agency heads may establish a more appropriate small business definition... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How may an agency use size... Business Credit and Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS SIZE REGULATIONS Size...

76 FR 71993 - Extension of Agency Information Collection Activity Under OMB Review: TSA Claims Management Program

Science.gov (United States)

2011-11-21

... Information Collection Activity Under OMB Review: TSA Claims Management Program AGENCY: Transportation... Security Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management... the nature of the information collection and its expected burden. TSA published a Federal Register...

DupTree: a program for large-scale phylogenetic analyses using gene tree parsimony.

Science.gov (United States)

Wehe, André; Bansal, Mukul S; Burleigh, J Gordon; Eulenstein, Oliver

2008-07-01

DupTree is a new software program for inferring rooted species trees from collections of gene trees using the gene tree parsimony approach. The program implements a novel algorithm that significantly improves upon the run time of standard search heuristics for gene tree parsimony, and enables the first truly genome-scale phylogenetic analyses. In addition, DupTree allows users to examine alternate rootings and to weight the reconciliation costs for gene trees. DupTree is an open source project written in C++. DupTree for Mac OS X, Windows, and Linux along with a sample dataset and an on-line manual are available at http://genome.cs.iastate.edu/CBL/DupTree

Array data extractor (ADE): a LabVIEW program to extract and merge gene array data.

Science.gov (United States)

Kurtenbach, Stefan; Kurtenbach, Sarah; Zoidl, Georg

2013-12-01

Large data sets from gene expression array studies are publicly available offering information highly valuable for research across many disciplines ranging from fundamental to clinical research. Highly advanced bioinformatics tools have been made available to researchers, but a demand for user-friendly software allowing researchers to quickly extract expression information for multiple genes from multiple studies persists. Here, we present a user-friendly LabVIEW program to automatically extract gene expression data for a list of genes from multiple normalized microarray datasets. Functionality was tested for 288 class A G protein-coupled receptors (GPCRs) and expression data from 12 studies comparing normal and diseased human hearts. Results confirmed known regulation of a beta 1 adrenergic receptor and further indicate novel research targets. Although existing software allows for complex data analyses, the LabVIEW based program presented here, "Array Data Extractor (ADE)", provides users with a tool to retrieve meaningful information from multiple normalized gene expression datasets in a fast and easy way. Further, the graphical programming language used in LabVIEW allows applying changes to the program without the need of advanced programming knowledge.

ACToR - Aggregated Computational Toxicology Resource

International Nuclear Information System (INIS)

Judson, Richard; Richard, Ann; Dix, David; Houck, Keith; Elloumi, Fathi; Martin, Matthew; Cathey, Tommy; Transue, Thomas R.; Spencer, Richard; Wolf, Maritja

2008-01-01

ACToR (Aggregated Computational Toxicology Resource) is a database and set of software applications that bring into one central location many types and sources of data on environmental chemicals. Currently, the ACToR chemical database contains information on chemical structure, in vitro bioassays and in vivo toxicology assays derived from more than 150 sources including the U.S. Environmental Protection Agency (EPA), Centers for Disease Control (CDC), U.S. Food and Drug Administration (FDA), National Institutes of Health (NIH), state agencies, corresponding government agencies in Canada, Europe and Japan, universities, the World Health Organization (WHO) and non-governmental organizations (NGOs). At the EPA National Center for Computational Toxicology, ACToR helps manage large data sets being used in a high-throughput environmental chemical screening and prioritization program called ToxCast TM

Profiling of the Tox21 Chemical Collection for Mitochondrial Function to Identify Compounds that Acutely Decrease Mitochondrial Membrane Potential

Science.gov (United States)

Attene-Ramos, Matias S.; Huang, Ruili; Michael, Sam; Witt, Kristine L.; Richard, Ann; Tice, Raymond R.; Simeonov, Anton; Austin, Christopher P.

2014-01-01

Background: Mitochondrial dysfunction has been implicated in the pathogenesis of a variety of disorders including cancer, diabetes, and neurodegenerative and cardiovascular diseases. Understanding whether different environmental chemicals and druglike molecules impact mitochondrial function represents an initial step in predicting exposure-related toxicity and defining a possible role for such compounds in the onset of various diseases. Objectives: We sought to identify individual chemicals and general structural features associated with changes in mitochondrial membrane potential (MMP). Methods: We used a multiplexed [two end points in one screen; MMP and adenosine triphosphate (ATP) content] quantitative high throughput screening (qHTS) approach combined with informatics tools to screen the Tox21 library of 10,000 compounds (~ 8,300 unique chemicals) at 15 concentrations each in triplicate to identify chemicals and structural features that are associated with changes in MMP in HepG2 cells. Results: Approximately 11% of the compounds (913 unique compounds) decreased MMP after 1 hr of treatment without affecting cell viability (ATP content). In addition, 309 compounds decreased MMP over a concentration range that also produced measurable cytotoxicity [half maximal inhibitory concentration (IC50) in MMP assay/IC50 in viability assay ≤ 3; p Tice RR, Simeonov A, Austin CP, Xia M. 2015. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. Environ Health Perspect 123:49–56; http://dx.doi.org/10.1289/ehp.1408642 PMID:25302578

7 CFR 1901.260 - Coordination with other agencies.

Science.gov (United States)

2010-01-01

... 7 Agriculture 12 2010-01-01 2010-01-01 false Coordination with other agencies. 1901.260 Section... AGRICULTURE PROGRAM REGULATIONS PROGRAM-RELATED INSTRUCTIONS Procedures for the Protection of Historical and Archeological Properties § 1901.260 Coordination with other agencies. (a) When other Agencies are directly...

76 FR 70469 - Extension of Agency Information Collection Activity Under OMB Review: TSA Airspace Waiver Program

Science.gov (United States)

2011-11-14

... Information Collection Activity Under OMB Review: TSA Airspace Waiver Program AGENCY: Transportation Security... Administration (TSA) has forwarded the Information Collection Request (ICR), Office of Management and Budget (OMB... information collection and its expected burden. TSA published a Federal Register notice, with a 60-day comment...

Computer simulations and modeling-assisted ToxR screening in deciphering 3D structures of transmembrane α-helical dimers: ephrin receptor A1

International Nuclear Information System (INIS)

Volynsky, P E; Mineeva, E A; Goncharuk, M V; Ermolyuk, Ya S; Arseniev, A S; Efremov, R G

2010-01-01

Membrane-spanning segments of numerous proteins (e.g. receptor tyrosine kinases) represent a novel class of pharmacologically important targets, whose activity can be modulated by specially designed artificial peptides, the so-called interceptors. Rational construction of such peptides requires understanding of the main factors driving peptide–peptide association in lipid membranes. Here we present a new method for rapid prediction of the spatial structure of transmembrane (TM) helix–helix complexes. It is based on computer simulations in membrane-like media and subsequent refinement/validation of the results using experimental studies of TM helix dimerization in a bacterial membrane by means of the ToxR system. The approach was applied to TM fragments of the ephrin receptor A1 (EphA1). A set of spatial structures of the dimer was proposed based on Monte Carlo simulations in an implicit membrane followed by molecular dynamics relaxation in an explicit lipid bilayer. The resulting models were employed for rational design of wild-type and mutant genetic constructions for ToxR assays. The computational and the experimental data are self-consistent and provide an unambiguous spatial model of the TM dimer of EphA1. The results of this work can be further used to develop new biologically active 'peptide interceptors' specifically targeting membrane domains of proteins

Characterization of ToxCast Phase II compounds disruption of ...

Science.gov (United States)

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used to determine compound effects on both neural function and cell health in primary cortical networks grown on mwMEA plates following exposure to ~1100 compounds from EPA’s Phase II ToxCast libraries. On DIV 13, baseline activity (40 min) was recorded prior to exposure to each compound at 40 µM. DMSO and the GABAA antagonist bicuculline (BIC) were included as controls on each mwMEA plate. Changes in spontaneous network activity (mean firing rate; MFR) and cell viability (lactate dehydrogenase; LDH and CellTiter Blue; CTB) were assessed within the same well following compound exposure. Activity calls (“hits”) were established using the 90th and 20th percentiles of the compound-induced change in MFR (medians of triplicates) across all tested compounds; compounds above (top 10% of compounds increasing MFR), and below (bottom 20% of compounds decreasing MFR) these thresholds, respectively were considered hits. MFR was altered beyond one of these thresholds by 322 compounds. Four compound categories accounted for 66% of the hits, including: insecticides (e.g. abamectin, lindane, prallethrin), pharmaceuticals (e.g. haloperidol, reserpine), fungicides (e.g. hexaconazole, fenamidone), and h

The EPA CompTox Chemistry Dashboard - an online resource for environmental chemists (ACS Spring Meeting)

Science.gov (United States)

The U.S. Environmental Protection Agency (EPA) Computational Toxicology Program integrates advances in biology, chemistry, and computer science to help prioritize chemicals for further research based on potential human health risks. This work involves computational and data drive...

The Texts of the Instruments relating to a Project for a Joint Agency-Norwegian Program of Research with the Zero Power Reactor 'NORA'

Energy Technology Data Exchange (ETDEWEB)

NONE

1961-06-22

The text of the Supply Agreement between the Agency and the Governments of Norway and of the United States of America, and the text of the related Project Agreement between the Agency and the Government of Norway concerning an Agency project for cooperation in carrying out a joint program of research in reactor physics with the zero power reactor 'NORA', are reproduced in this document for the information of all Members of the Agency.

The Texts of the Instruments relating to a Project for a Joint Agency-Norwegian Program of Research with the Zero Power Reactor 'NORA'

International Nuclear Information System (INIS)

1961-01-01

The text of the Supply Agreement between the Agency and the Governments of Norway and of the United States of America, and the text of the related Project Agreement between the Agency and the Government of Norway concerning an Agency project for cooperation in carrying out a joint program of research in reactor physics with the zero power reactor 'NORA', are reproduced in this document for the information of all Members of the Agency

29 CFR 1614.102 - Agency program.

Science.gov (United States)

2010-07-01

... and the instructions contained in the Commission's Management Directives; (3) Conduct a continuing..., sex, national origin, age, disability, or genetic information, and solicit their recruitment... made without undue hardship on the business of the agency; (8) Make reasonable accommodation to the...

HTTK: R Package for High-Throughput Toxicokinetics

Science.gov (United States)

Thousands of chemicals have been profiled by high-throughput screening programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics. Toxicokinetic models aid in predicting tissue concent...

Fun with High Throughput Toxicokinetics (CalEPA webinar)

Science.gov (United States)

Thousands of chemicals have been profiled by high-throughput screening (HTS) programs such as ToxCast and Tox21. These chemicals are tested in part because there are limited or no data on hazard, exposure, or toxicokinetics (TK). TK models aid in predicting tissue concentrations ...

75 FR 70083 - Emergency Forest Restoration Program and Emergency Conservation Program

Science.gov (United States)

2010-11-17

... Restoration Program and Emergency Conservation Program AGENCY: Farm Service Agency, USDA. ACTION: Interim rule. SUMMARY: The Farm Service Agency (FSA) is amending regulations as required by the Food, Conservation, and... as follows: PART 701--EMERGENCY CONSERVATION PROGRAM, EMERGENCY FOREST RESTORATION PROGRAM, AND...

Developmental Effects of the ToxCast™ Phase I and Phase II Chemicals in Caenorhabditis elegans and Corresponding Responses in Zebrafish, Rats, and Rabbits

Science.gov (United States)

Boyd, Windy A.; Smith, Marjolein V.; Co, Caroll A.; Pirone, Jason R.; Rice, Julie R.; Shockley, Keith R.; Freedman, Jonathan H.

2015-01-01

Background: Modern toxicology is shifting from an observational to a mechanistic science. As part of this shift, high-throughput toxicity assays are being developed using alternative, nonmammalian species to prioritize chemicals and develop prediction models of human toxicity. Methods: The nematode Caenorhabditis elegans (C. elegans) was used to screen the U.S. Environmental Protection Agency’s (EPA’s) ToxCast™ Phase I and Phase II libraries, which contain 292 and 676 chemicals, respectively, for chemicals leading to decreased larval development and growth. Chemical toxicity was evaluated using three parameters: a biologically defined effect size threshold, half-maximal activity concentration (AC50), and lowest effective concentration (LEC). Results: Across both the Phase I and Phase II libraries, 62% of the chemicals were classified as active ≤ 200 μM in the C. elegans assay. Chemical activities and potencies in C. elegans were compared with those from two zebrafish embryonic development toxicity studies and developmental toxicity data for rats and rabbits. Concordance of chemical activity was higher between C. elegans and one zebrafish assay across Phase I chemicals (79%) than with a second zebrafish assay (59%). Using C. elegans or zebrafish to predict rat or rabbit developmental toxicity resulted in balanced accuracies (the average value of the sensitivity and specificity for an assay) ranging from 45% to 53%, slightly lower than the concordance between rat and rabbit (58%). Conclusions: Here, we present an assay that quantitatively and reliably describes the effects of chemical toxicants on C. elegans growth and development. We found significant overlap in the activity of chemicals in the ToxCast™ libraries between C. elegans and zebrafish developmental screens. Incorporating C. elegans toxicological assays as part of a battery of in vitro and in vivo assays provides additional information for the development of models to predict a chemical�

High Throughput PBTK: Evaluating EPA’s Open-Source Data and Tools for Dosimetry and Exposure Reconstruction

Science.gov (United States)

Thousands of chemicals have been profiled by high-throughput screening (HTS) programs such as ToxCast and Tox21; these chemicals are tested in part because most of them have limited or no data on hazard, exposure, or toxicokinetics (TK). While HTS generates in vitro bioactivity d...

77 FR 3842 - Agency Information Collection (Mentor-Protégé Program Application and Reports) Activities Under...

Science.gov (United States)

2012-01-25

... DEPARTMENT OF VETERANS AFFAIRS [OMB Control No. 2900-0723] Agency Information Collection (Mentor... will be used to institute a mentor-prot[eacute]g[eacute] program whereby large businesses agree to... developmental plan contained in the approved agreement and to report the specific actions taken by the mentor to...

ACToR Chemical Structure processing using Open Source ...

Science.gov (United States)

ACToR (Aggregated Computational Toxicology Resource) is a centralized database repository developed by the National Center for Computational Toxicology (NCCT) at the U.S. Environmental Protection Agency (EPA). Free and open source tools were used to compile toxicity data from over 1,950 public sources. ACToR contains chemical structure information and toxicological data for over 558,000 unique chemicals. The database primarily includes data from NCCT research programs, in vivo toxicity data from ToxRef, human exposure data from ExpoCast, high-throughput screening data from ToxCast and high quality chemical structure information from the EPA DSSTox program. The DSSTox database is a chemical structure inventory for the NCCT programs and currently has about 16,000 unique structures. Included are also data from PubChem, ChemSpider, USDA, FDA, NIH and several other public data sources. ACToR has been a resource to various international and national research groups. Most of our recent efforts on ACToR are focused on improving the structural identifiers and Physico-Chemical properties of the chemicals in the database. Organizing this huge collection of data and improving the chemical structure quality of the database has posed some major challenges. Workflows have been developed to process structures, calculate chemical properties and identify relationships between CAS numbers. The Structure processing workflow integrates web services (PubChem and NIH NCI Cactus) to d

High-Throughput Screening and Quantitative Chemical Ranking for Sodium-Iodide Symporter Inhibitors in ToxCast Phase I Chemical Library.

Science.gov (United States)

Wang, Jun; Hallinger, Daniel R; Murr, Ashley S; Buckalew, Angela R; Simmons, Steven O; Laws, Susan C; Stoker, Tammy E

2018-05-01

Thyroid uptake of iodide via the sodium-iodide symporter (NIS) is the first step in the biosynthesis of thyroid hormones that are critical for health and development in humans and wildlife. Despite having long been a known target of endocrine disrupting chemicals such as perchlorate, information regarding NIS inhibition activity is still unavailable for the vast majority of environmental chemicals. This study applied a previously validated high-throughput approach to screen for NIS inhibitors in the ToxCast phase I library, representing 293 important environmental chemicals. Here 310 blinded samples were screened in a tiered-approach using an initial single-concentration (100 μM) radioactive-iodide uptake (RAIU) assay, followed by 169 samples further evaluated in multi-concentration (0.001 μM-100 μM) testing in parallel RAIU and cell viability assays. A novel chemical ranking system that incorporates multi-concentration RAIU and cytotoxicity responses was also developed as a standardized method for chemical prioritization in current and future screenings. Representative chemical responses and thyroid effects of high-ranking chemicals are further discussed. This study significantly expands current knowledge of NIS inhibition potential in environmental chemicals and provides critical support to U.S. EPA's Endocrine Disruptor Screening Program (EDSP) initiative to expand coverage of thyroid molecular targets, as well as the development of thyroid adverse outcome pathways (AOPs).

O período toxêmico da esquistossomose

Directory of Open Access Journals (Sweden)

J. Leocádio

1969-06-01

Full Text Available O A. apresenta seis casos de pacientes observados durante o período toxêmico da esquistosomose mansônica. Dêstes, um foi de mulher cuja sintomatologia datava de um ano. Concebeu e deu à luz durante a enfermidade. Apresentava sinais de fibrose hepática quando do primeiro exame, ainda na vigência de sintomas do período agudo da enfermidade. Todos êstes pacientes apresentavam febre, dores abdominais, hepatoesplenomegalia e outras manifestações que têm sido descritas neste período da parasitose. Como notas dominantes no hemograma, leucocitose com eosinofilia, como ocorre nas infecções por helmintos com ciclo textrino, e anemia. Esta, nem todos apresentavam. Além de alterações do equilíbrio proteico e de resultados da exploração funcional do fígado, o A. chamou a atenção para a hípoglicemia e hipocolesterolemia encontradas em alguns dos observados. Foi digno de registro, também, a positividade tardia da intradermorreação para diagnóstico da esquistosomose. Todos os pacientes foram submetidos a tratamento antimonial, com bom resultado. Como reação colateral devemos mencionar a exacerbação da febre forçando, por vêzes à interrupção do mesmo. O A. faz referências a outros recursos terapêuticos empregados no Oriente: o F30.066, um nitrofurano de uso oral, e as sementes de Cucurbita moshata. Sugere a investigação em animais e no homem com sementes de abóbora outrora empregadas como tenifugo

Community Agency Voice and Benefit in Service-Learning

Science.gov (United States)

Miron, Devi; Moely, Barbara E.

2006-01-01

Supervisors from 40 community agencies working with a university-based service-learning program were interviewed regarding the extent of their input in service-learning program planning and implementation "(Agency Voice), Interpersonal Relations" with service-learning students, "Perceived Benefit" of the service-learning…

Southern states' routing agency report

International Nuclear Information System (INIS)

1989-02-01

The Southern states' routing agency report is a compendium of 16-southern states' routing programs relative to the transportation of high-level radioactive materials. The report identifies the state-designated routing agencies as defined under 49 Code of Federal Regulations (CFR) Part 171 and provides a reference to the source ad scope of the agencies' rulemaking authority. Additionally, the state agency and contact designated by the state's governor to receive advance notification and shipment routing information under 10 CFR Parts 71 and 73 are also listed

Southern States' Routing Agency Report

International Nuclear Information System (INIS)

1990-03-01

The Southern States' Routing Agency Report is a compendium of 16-southern states' routing program for the transportation of high-level radioactive materials. The report identifies the state-designated routing agencies as defined under 49 Code of Federal Regulations (CFR) Part 171 and provides a reference to the source and scope of the agencies' rulemaking authority. Additionally, the state agency and contact designated by the state's governor to receive advance notification and shipment routing information under 10 CFR Parts 71 and 73 are also listed

40 CFR 7.125 - Coordination with other agencies.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Coordination with other agencies. 7.125 Section 7.125 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL NONDISCRIMINATION IN PROGRAMS OR ACTIVITIES RECEIVING FEDERAL ASSISTANCE FROM THE ENVIRONMENTAL PROTECTION AGENCY Agency...

Functional Use Database (FUse)

Data.gov (United States)

U.S. Environmental Protection Agency — There are five different files for this dataset: 1. A dataset listing the reported functional uses of chemicals (FUse) 2. All 729 ToxPrint descriptors obtained from...

Quantitative Structure-Use Relationship (QSUR) Model Descriptors

Data.gov (United States)

U.S. Environmental Protection Agency — This data set contains ToxPrint finger prints for all chemicals in FUse that had QSAR-ready SMILES strings as well as select physicochemical properties from the...

ToxGen: an improved reference database for the identification of type B-trichothecene genotypes in Fusarium

Directory of Open Access Journals (Sweden)

Tomasz Kulik

2017-02-01

Full Text Available Type B trichothecenes, which pose a serious hazard to consumer health, occur worldwide in grains. These mycotoxins are produced mainly by three different trichothecene genotypes/chemotypes: 3ADON (3-acetyldeoxynivalenol, 15ADON (15-acetyldeoxynivalenol and NIV (nivalenol, named after these three major mycotoxin compounds. Correct identification of these genotypes is elementary for all studies relating to population surveys, fungal ecology and mycotoxicology. Trichothecene producers exhibit enormous strain-dependent chemical diversity, which may result in variation in levels of the genotype’s determining toxin and in the production of low to high amounts of atypical compounds. New high-throughput DNA-sequencing technologies promise to boost the diagnostics of mycotoxin genotypes. However, this requires a reference database containing a satisfactory taxonomic sampling of sequences showing high correlation to actually produced chemotypes. We believe that one of the most pressing current challenges of such a database is the linking of molecular identification with chemical diversity of the strains, as well as other metadata. In this study, we use the Tri12 gene involved in mycotoxin biosynthesis for identification of Tri genotypes through sequence comparison. Tri12 sequences from a range of geographically diverse fungal strains comprising 22 Fusarium species were stored in the ToxGen database, which covers descriptive and up-to-date annotations such as indication on Tri genotype and chemotype of the strains, chemical diversity, information on trichothecene-inducing host, substrate or media, geographical locality, and most recent taxonomic affiliations. The present initiative bridges the gap between the demands of comprehensive studies on trichothecene producers and the existing nucleotide sequence databases, which lack toxicological and other auxiliary data. We invite researchers working in the fields of fungal taxonomy, epidemiology and

ToxGen: an improved reference database for the identification of type B-trichothecene genotypes in Fusarium.

Science.gov (United States)

Kulik, Tomasz; Abarenkov, Kessy; Buśko, Maciej; Bilska, Katarzyna; van Diepeningen, Anne D; Ostrowska-Kołodziejczak, Anna; Krawczyk, Katarzyna; Brankovics, Balázs; Stenglein, Sebastian; Sawicki, Jakub; Perkowski, Juliusz

2017-01-01

Type B trichothecenes, which pose a serious hazard to consumer health, occur worldwide in grains. These mycotoxins are produced mainly by three different trichothecene genotypes/chemotypes: 3ADON (3-acetyldeoxynivalenol), 15ADON (15-acetyldeoxynivalenol) and NIV (nivalenol), named after these three major mycotoxin compounds. Correct identification of these genotypes is elementary for all studies relating to population surveys, fungal ecology and mycotoxicology. Trichothecene producers exhibit enormous strain-dependent chemical diversity, which may result in variation in levels of the genotype's determining toxin and in the production of low to high amounts of atypical compounds. New high-throughput DNA-sequencing technologies promise to boost the diagnostics of mycotoxin genotypes. However, this requires a reference database containing a satisfactory taxonomic sampling of sequences showing high correlation to actually produced chemotypes. We believe that one of the most pressing current challenges of such a database is the linking of molecular identification with chemical diversity of the strains, as well as other metadata. In this study, we use the Tri12 gene involved in mycotoxin biosynthesis for identification of Tri genotypes through sequence comparison. Tri12 sequences from a range of geographically diverse fungal strains comprising 22 Fusarium species were stored in the ToxGen database, which covers descriptive and up-to-date annotations such as indication on Tri genotype and chemotype of the strains, chemical diversity, information on trichothecene-inducing host, substrate or media, geographical locality, and most recent taxonomic affiliations. The present initiative bridges the gap between the demands of comprehensive studies on trichothecene producers and the existing nucleotide sequence databases, which lack toxicological and other auxiliary data. We invite researchers working in the fields of fungal taxonomy, epidemiology and mycotoxicology to join the

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Maria C Ow

2018-02-01

Full Text Available Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw" transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.

Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

Science.gov (United States)

Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

2018-01-01

Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

Science, Technology, Engineering, and Mathematics Education: Strategic Planning Needed to Better Manage Overlapping Programs across Multiple Agencies. Report to Congressional Requesters. GAO-12-108

Science.gov (United States)

Scott, George A.

2012-01-01

Science, technology, engineering, and mathematics (STEM) education programs help to enhance the nation's global competitiveness. Many federal agencies have been involved in administering these programs. Concerns have been raised about the overall effectiveness and efficiency of STEM education programs. GAO examined (1) the number of federal…

Multi-gene genetic programming based predictive models for municipal solid waste gasification in a fluidized bed gasifier.

Science.gov (United States)

Pandey, Daya Shankar; Pan, Indranil; Das, Saptarshi; Leahy, James J; Kwapinski, Witold

2015-03-01

A multi-gene genetic programming technique is proposed as a new method to predict syngas yield production and the lower heating value for municipal solid waste gasification in a fluidized bed gasifier. The study shows that the predicted outputs of the municipal solid waste gasification process are in good agreement with the experimental dataset and also generalise well to validation (untrained) data. Published experimental datasets are used for model training and validation purposes. The results show the effectiveness of the genetic programming technique for solving complex nonlinear regression problems. The multi-gene genetic programming are also compared with a single-gene genetic programming model to show the relative merits and demerits of the technique. This study demonstrates that the genetic programming based data-driven modelling strategy can be a good candidate for developing models for other types of fuels as well. Copyright © 2014 Elsevier Ltd. All rights reserved.

41 CFR 102-192.175 - What types of support does GSA offer to Federal agency mail management programs?

Science.gov (United States)

2010-07-01

... in mail management and mail operations; (b) Identifying better business practices and sharing them... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What types of support does GSA offer to Federal agency mail management programs? 102-192.175 Section 102-192.175 Public...

Biochemical Characterization and Structural Basis of Reactivity and Regioselectivity Differences between Burkholderia thailandensis and Burkholderia glumae 1,6-Didesmethyltoxoflavin N-Methyltransferase.

Science.gov (United States)

Fenwick, Michael K; Almabruk, Khaled H; Ealick, Steven E; Begley, Tadhg P; Philmus, Benjamin

2017-08-01

Burkholderia glumae converts the guanine base of guanosine triphosphate into an azapteridine and methylates both the pyrimidine and triazine rings to make toxoflavin. Strains of Burkholderia thailandensis and Burkholderia pseudomallei have a gene cluster encoding seven putative biosynthetic enzymes that resembles the toxoflavin gene cluster. Four of the enzymes are similar in sequence to BgToxBCDE, which have been proposed to make 1,6-didesmethyltoxoflavin (1,6-DDMT). One of the remaining enzymes, BthII1283 in B. thailandensis E264, is a predicted S-adenosylmethionine (SAM)-dependent N-methyltransferase that shows a low level of sequence identity to BgToxA, which sequentially methylates N6 and N1 of 1,6-DDMT to form toxoflavin. Here we show that, unlike BgToxA, BthII1283 catalyzes a single methyl transfer to N1 of 1,6-DDMT in vitro. In addition, we investigated the differences in reactivity and regioselectivity by determining crystal structures of BthII1283 with bound S-adenosylhomocysteine (SAH) or 1,6-DDMT and SAH. BthII1283 contains a class I methyltransferase fold and three unique extensions used for 1,6-DDMT recognition. The active site structure suggests that 1,6-DDMT is bound in a reduced form. The plane of the azapteridine ring system is orthogonal to its orientation in BgToxA. In BthII1283, the modeled SAM methyl group is directed toward the p orbital of N1, whereas in BgToxA, it is first directed toward an sp 2 orbital of N6 and then toward an sp 2 orbital of N1 after planar rotation of the azapteridine ring system. Furthermore, in BthII1283, N1 is hydrogen bonded to a histidine residue whereas BgToxA does not supply an obvious basic residue for either N6 or N1 methylation.

Combating hidden hunger: the role of international agencies.

Science.gov (United States)

Dalmiya, Nita; Schultink, Werner

2003-12-01

The importance of micronutrient deficiencies or "hidden hunger" was clearly emphasized by the inclusion of specific goals on iron, vitamin A, and iodine deficiency at the 1990 World Summit for Children and other major international nutrition conferences. Significant progress has since been made toward eliminating vitamin A and iodine deficiencies, with less progress made toward reducing the burden of iron-deficiency anemia. The role of international agencies, such as the World Health Organization, United Nations Children's Fund, Food and Agricultural Organization, and World Bank in assisting countries to make progress toward the World Summit for Children goals has been very important. International agencies have played a critical role in advocating for and raising awareness of these issues at the international, regional, and national levels among policymakers and the general population. Using a rights-based approach, UNICEF and other agencies have been instrumental in elevating to the highest political level the discussion of every child's right to adequate nutrition. International agencies have also been very supportive at the national level in providing technical guidance for programs, including monitoring and evaluation. These agencies have played a critical role in engaging the cooperation of other partners, including bilateral donors, non-governmental organizations, and the private sector for micronutrient programs. Furthermore, international agencies provide financial and material support for micronutrient programs. In the future, such agencies must continue to be heavily involved in programs to achieve the newly confirmed goals for 2010. The present paper focuses on the role of international agencies in combating micronutrient deficiencies, drawing on the lessons learned over the last decade. The first section of the paper summarizes the progress achieved since 1990, and the second section describes the specific role of international agencies in contributing

Virulence Genes and Antimicrobial Resistance Profiles of Pasteurella multocida Strains Isolated from Rabbits in Brazil

Directory of Open Access Journals (Sweden)

Thais Sebastiana Porfida Ferreira

2012-01-01

Full Text Available Pasteurella multocida is responsible for a wide range of diseases in domestic animals. In rabbits, the agent is related to nasal discharge, pneumonia, otitis media, pyometra, orchitis, abscess, and septicemia. One hundred and forty rabbits with respiratory diseases from four rabbitries in São Paulo State, Brazil were evaluated for the detection of P. multocida in their nasal cavities. A total of twenty-nine animals were positive to P. multocida isolation, and 46 strains were selected and characterized by means of biochemical tests and PCR. P. multocida strains were tested for capsular type, virulence genes, and resistance profile. A total of 45.6% (21/46 of isolates belonged to capsular type A, and 54.34% (25/46 of the isolates were untypeable. None of the strains harboured toxA or pfhA genes. The frequency of the other twenty genes tested was variable, and the data generated was used to build a dendrogram, showing the relatedness of strains, which were clustered according to origin. Resistance revealed to be more common against sulfonamides and cotrimoxazole, followed by erythromycin, penicillin, and amoxicillin.

More than genes: the advanced fetal programming hypothesis.

Science.gov (United States)

Hocher, Berthold

2014-10-01

Many lines of data, initial epidemiologic studies as well as subsequent extensive experimental studies, indicate that early-life events play a powerful role in influencing later suceptibility to certain chronic diseases. Such events might be over- or undernutrition, exposure to environmental toxins, but also changes in hormones, in particular stress hormones. Typically, those events are triggered by the environmental challenges of the mother. However, recent studies have shown that paternal environmental or nutritional factors affect the phenotype of the offspring as well. The maternal and paternal environmental factors act on the phenotype of the offspring via epigenetic modification of its genome. The advanced fetal programming hypothesis proposes an additional non-environmentally driven mechanism: maternal and also paternal genes may influence the maturating sperm, the oocyte, and later the embryo/fetus, leading to their epigenetic alteration. Thus, the observed phenotype of the offspring may be altered by maternal/paternal genes independent of the fetal genome. Meanwhile, several independent association studies in humans dealing with metabolic and neurological traits also suggest that maternal genes might affect the offspring phenotype independent of the transmission of that particular gene to the offspring. Considering the implications of this hypothesis, some conclusions drawn from transgenic or knockout animal models and based on the causality between a genetic alteration and a phenotype, need to be challenged. Possible implications for the development, diagnostic and therapy of human genetic diseases have to be investigated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stunned Silence: Gene Expression Programs in Human Cells Infected with Monkeypox or Vaccinia Virus

Science.gov (United States)

Rubins, Kathleen H.; Hensley, Lisa E.; Relman, David A.; Brown, Patrick O.

2011-01-01

Poxviruses use an arsenal of molecular weapons to evade detection and disarm host immune responses. We used DNA microarrays to investigate the gene expression responses to infection by monkeypox virus (MPV), an emerging human pathogen, and Vaccinia virus (VAC), a widely used model and vaccine organism, in primary human macrophages, primary human fibroblasts and HeLa cells. Even as the overwhelmingly infected cells approached their demise, with extensive cytopathic changes, their gene expression programs appeared almost oblivious to poxvirus infection. Although killed (gamma-irradiated) MPV potently induced a transcriptional program characteristic of the interferon response, no such response was observed during infection with either live MPV or VAC. Moreover, while the gene expression response of infected cells to stimulation with ionomycin plus phorbol 12-myristate 13-acetate (PMA), or poly (I-C) was largely unimpaired by infection with MPV, a cluster of pro-inflammatory genes were a notable exception. Poly(I-C) induction of genes involved in alerting the innate immune system to the infectious threat, including TNF-alpha, IL-1 alpha and beta, CCL5 and IL-6, were suppressed by infection with live MPV. Thus, MPV selectively inhibits expression of genes with critical roles in cell-signaling pathways that activate innate immune responses, as part of its strategy for stealthy infection. PMID:21267444

Automated Eukaryotic Gene Structure Annotation Using EVidenceModeler and the Program to Assemble Spliced Alignments

Energy Technology Data Exchange (ETDEWEB)

Haas, B J; Salzberg, S L; Zhu, W; Pertea, M; Allen, J E; Orvis, J; White, O; Buell, C R; Wortman, J R

2007-12-10

EVidenceModeler (EVM) is presented as an automated eukaryotic gene structure annotation tool that reports eukaryotic gene structures as a weighted consensus of all available evidence. EVM, when combined with the Program to Assemble Spliced Alignments (PASA), yields a comprehensive, configurable annotation system that predicts protein-coding genes and alternatively spliced isoforms. Our experiments on both rice and human genome sequences demonstrate that EVM produces automated gene structure annotation approaching the quality of manual curation.

Civilian Agency Industry Working Group EVM World Update

Science.gov (United States)

Kerby, Jerald

2013-01-01

Objectives include: Promote the use of standards ]based, objective, and quantitative systems for managing projects and programs in the federal government. Understand how civilian agencies in general, manage their projects and programs. Project management survey expected to go out soon to civilian agencies. Describe how EVM and other best practices can be applied by the government to better manage its project and programs irrespective of whether work is contracted out or the types of contracts employed. Develop model policies aimed at project and program managers that are transportable across the government.

Reaction of Global Collection of Rye (Secale cereale L. to Tan Spot and Pyrenophora tritici-repentis Races in South Dakota

Directory of Open Access Journals (Sweden)

Sidrat Abdullah

2017-06-01

Full Text Available Rye (Secale cereale L. serves as an alternative host of Pyrenophora tritici-repentis (PTR the cause of tan spot on wheat. Rye is cultivated as a forage or cover crop and overlaps with a significant portion of wheat acreage in the U.S. northern Great Plains; however, it is not known whether the rye crop influences the evolution of PTR races. We evaluated a global collection of 211 rye accessions against tan spot and assessed the diversity in PTR population on rye in South Dakota. All the rye genotypes were inoculated with PTR races 1 and 5, and infiltrated with Ptr ToxA and Ptr ToxB, at seedling stage. We observed 21% of the genotypes exhibited susceptibility to race 1, whereas, 39% were susceptible to race 5. All 211 accessions were insensitive to both the Ptr toxins. It indicates that though rye exhibits diversity in reaction to tan spot, it lacks Ptr ToxA and ToxB sensitivity genes. This suggests that unknown toxins or other factors can lead to PTR establishment in rye. We characterized the race structure of 103 PTR isolates recovered from rye in South Dakota. Only 22% of the isolates amplified Ptr ToxA gene and were identified as race 1 based on their phenotypic reaction on the differential set. The remaining 80 isolates were noted to be race 4. Our results show that races 1 and 4 are prevalent on rye in South Dakota with a higher frequency of race 4, suggesting a minimal role of rye in the disease epidemiology.

Reaction of Global Collection of Rye (Secale cereale L.) to Tan Spot and Pyrenophora tritici-repentis Races in South Dakota.

Science.gov (United States)

Abdullah, Sidrat; Sehgal, Sunish K; Glover, Karl D; Ali, Shaukat

2017-06-01

Rye ( Secale cereale L.) serves as an alternative host of Pyrenophora tritici-repentis ( PTR ) the cause of tan spot on wheat. Rye is cultivated as a forage or cover crop and overlaps with a significant portion of wheat acreage in the U.S. northern Great Plains; however, it is not known whether the rye crop influences the evolution of PTR races. We evaluated a global collection of 211 rye accessions against tan spot and assessed the diversity in PTR population on rye in South Dakota. All the rye genotypes were inoculated with PTR races 1 and 5, and infiltrated with Ptr ToxA and Ptr ToxB, at seedling stage. We observed 21% of the genotypes exhibited susceptibility to race 1, whereas, 39% were susceptible to race 5. All 211 accessions were insensitive to both the Ptr toxins. It indicates that though rye exhibits diversity in reaction to tan spot, it lacks Ptr ToxA and ToxB sensitivity genes. This suggests that unknown toxins or other factors can lead to PTR establishment in rye. We characterized the race structure of 103 PTR isolates recovered from rye in South Dakota. Only 22% of the isolates amplified Ptr ToxA gene and were identified as race 1 based on their phenotypic reaction on the differential set. The remaining 80 isolates were noted to be race 4. Our results show that races 1 and 4 are prevalent on rye in South Dakota with a higher frequency of race 4, suggesting a minimal role of rye in the disease epidemiology.

Hazardous-waste landfill research, US EPA (United States Environmental Protection Agency) program

Energy Technology Data Exchange (ETDEWEB)

Schomaker, N.B.

1988-08-01

The Land Pollution Control Division (LPCD), Hazardous Waste Engineering Research Lab. (HWERL), U.S. Environmental Protection Agency, in Cincinnati, Ohio, has responsibility for research in solid- and hazardous-waste management with respect to land disposal of wastes. To fulfill the responsibility, the LPCD is developing concepts and is documenting the environmental effects of various waste-disposal practices; and is collecting data necessary to support implementation of disposal guidelines mandated by the Hazardous and Solid Waste Amendments of 1984 (HSWA). This paper presents an overview of the land-disposal research associated with the LPCD hazardous waste program plan and will report the current status of work in the following categorical areas: Hazardous-waste facilities - landfills and surface impoundments; Non-Hazardous waste facilities; and Technology transfer.

Virulence Genotyping of Pasteurella multocida Isolated from Multiple Hosts from India

Directory of Open Access Journals (Sweden)

Laxmi Narayan Sarangi

2014-01-01

Full Text Available In this study, 108 P. multocida isolates recovered from various host animals such as cattle, buffalo, swine, poultry (chicken, duck, and emu and rabbits were screened for carriage of 8 virulence associated genes. The results revealed some unique information on the prevalence of virulence associated genes among Indian isolates. With the exception of toxA gene, all other virulence associated genes were found to be regularly distributed among host species. Association study between capsule type and virulence genes suggested that pfhA, nanB, and nanH genes were regularly distributed among all serotypes with the exception of CapD, whereas toxA gene was found to be positively associated with CapD and CapA. The frequency of hgbA and nanH genes among swine isolates of Indian origin was found to be less in comparison to its equivalents around the globe. Interestingly, very high prevalence of tbpA gene was observed among poultry, swine, and rabbit isolates. Likewise, very high prevalence of pfhA gene (95.3% was observed among Indian isolates, irrespective of host species origin.

Virulence genotyping of Pasteurella multocida isolated from multiple hosts from India.

Science.gov (United States)

Sarangi, Laxmi Narayan; Priyadarshini, Adyasha; Kumar, Santosh; Thomas, Prasad; Gupta, Santosh Kumar; Nagaleekar, Viswas Konasagara; Singh, Vijendra Pal

2014-01-01

In this study, 108 P. multocida isolates recovered from various host animals such as cattle, buffalo, swine, poultry (chicken, duck, and emu) and rabbits were screened for carriage of 8 virulence associated genes. The results revealed some unique information on the prevalence of virulence associated genes among Indian isolates. With the exception of toxA gene, all other virulence associated genes were found to be regularly distributed among host species. Association study between capsule type and virulence genes suggested that pfhA, nanB, and nanH genes were regularly distributed among all serotypes with the exception of CapD, whereas toxA gene was found to be positively associated with CapD and CapA. The frequency of hgbA and nanH genes among swine isolates of Indian origin was found to be less in comparison to its equivalents around the globe. Interestingly, very high prevalence of tbpA gene was observed among poultry, swine, and rabbit isolates. Likewise, very high prevalence of pfhA gene (95.3%) was observed among Indian isolates, irrespective of host species origin.

Production Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Information on the number of smolts received into the program is...

EnviroAtlas - Acres of USDA Farm Service Agency Conservation Reserve Program land by 12-Digit HUC for the Conterminous United States.

Data.gov (United States)

U.S. Environmental Protection Agency — This EnviroAtlas dataset shows the acres of land enrolled in the US Department of Agriculture (USDA)'s Conservation Reserve Program (CRP). The CRP is administered by...

Applying physical science techniques and CERN technology to an unsolved problem in radiation treatment for cancer: the multidisciplinary 'VoxTox' research programme.

Science.gov (United States)

Burnet, Neil G; Scaife, Jessica E; Romanchikova, Marina; Thomas, Simon J; Bates, Amy M; Wong, Emma; Noble, David J; Shelley, Leila Ea; Bond, Simon J; Forman, Julia R; Hoole, Andrew Cf; Barnett, Gillian C; Brochu, Frederic M; Simmons, Michael Pd; Jena, Raj; Harrison, Karl; Yeap, Ping Lin; Drew, Amelia; Silvester, Emma; Elwood, Patrick; Pullen, Hannah; Sultana, Andrew; Seah, Shannon Yk; Wilson, Megan Z; Russell, Simon G; Benson, Richard J; Rimmer, Yvonne L; Jefferies, Sarah J; Taku, Nicolette; Gurnell, Mark; Powlson, Andrew S; Schönlieb, Carola-Bibiane; Cai, Xiaohao; Sutcliffe, Michael Pf; Parker, Michael A

2017-06-01

The VoxTox research programme has applied expertise from the physical sciences to the problem of radiotherapy toxicity, bringing together expertise from engineering, mathematics, high energy physics (including the Large Hadron Collider), medical physics and radiation oncology. In our initial cohort of 109 men treated with curative radiotherapy for prostate cancer, daily image guidance computed tomography (CT) scans have been used to calculate delivered dose to the rectum, as distinct from planned dose, using an automated approach. Clinical toxicity data have been collected, allowing us to address the hypothesis that delivered dose provides a better predictor of toxicity than planned dose.

13 CFR 105.403 - Designated Agency Ethics Officials.

Science.gov (United States)

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Designated Agency Ethics Officials... Agency Ethics Officials. The Designated Agency Ethics Official and Alternates administer the program for... advice and counsel regarding matters relating to the Ethics in Government Act of 1978 and its...

Stunned silence: gene expression programs in human cells infected with monkeypox or vaccinia virus.

Directory of Open Access Journals (Sweden)

Kathleen H Rubins

2011-01-01

Full Text Available Poxviruses use an arsenal of molecular weapons to evade detection and disarm host immune responses. We used DNA microarrays to investigate the gene expression responses to infection by monkeypox virus (MPV, an emerging human pathogen, and Vaccinia virus (VAC, a widely used model and vaccine organism, in primary human macrophages, primary human fibroblasts and HeLa cells. Even as the overwhelmingly infected cells approached their demise, with extensive cytopathic changes, their gene expression programs appeared almost oblivious to poxvirus infection. Although killed (gamma-irradiated MPV potently induced a transcriptional program characteristic of the interferon response, no such response was observed during infection with either live MPV or VAC. Moreover, while the gene expression response of infected cells to stimulation with ionomycin plus phorbol 12-myristate 13-acetate (PMA, or poly (I-C was largely unimpaired by infection with MPV, a cluster of pro-inflammatory genes were a notable exception. Poly(I-C induction of genes involved in alerting the innate immune system to the infectious threat, including TNF-alpha, IL-1 alpha and beta, CCL5 and IL-6, were suppressed by infection with live MPV. Thus, MPV selectively inhibits expression of genes with critical roles in cell-signaling pathways that activate innate immune responses, as part of its strategy for stealthy infection.

INVESTIGATION OF THE TOTAL ORGANIC HALOGEN ANALYTICAL METHOD AT THE WASTE SAMPLING AND CHARACTERIZATION FACILITY

International Nuclear Information System (INIS)

Douglas, J.G.; Meznarich, H.K.; Olsen, J.R.; Ross, G.A.; Stauffer, M.

2009-01-01

Total organic halogen (TOX) is used as a parameter to screen groundwater samples at the Hanford Site. Trending is done for each groundwater well, and changes in TOX and other screening parameters can lead to costly changes in the monitoring protocol. The Waste Sampling and Characterization Facility (WSCF) analyzes groundwater samples for TOX using the United States Environmental Protection Agency (EPA) SW-S46 method 9020B (EPA 1996a). Samples from the Soil and Groundwater Remediation Project (SGRP) are submitted to the WSCF for analysis without information regarding the source of the sample; each sample is in essence a ''blind'' sample to the laboratory. Feedback from the SGRP indicated that some of the WSCF-generated TOX data from groundwater wells had a number of outlier values based on the historical trends (Anastos 200Sa). Additionally, analysts at WSCF observed inconsistent TOX results among field sample replicates. Therefore, the WSCF lab performed an investigation of the TOX analysis to determine the cause of the outlier data points. Two causes were found that contributed to generating out-of-trend TOX data: (1) The presence of inorganic chloride in the groundwater samples: at inorganic chloride concentrations greater than about 10 parts per million (ppm), apparent TOX values increase with increasing chloride concentration. A parallel observation is the increase in apparent breakthrough of TOX from the first to the second activated-carbon adsorption tubes with increasing inorganic chloride concentration. (2) During the sample preparation step, excessive purging of the adsorption tubes with oxygen pressurization gas after sample loading may cause channeling in the activated carbon bed. This channeling leads to poor removal of inorganic chloride during the subsequent wash step with aqueous potassium nitrate. The presence of this residual inorganic chloride then produces erroneously high TOX values. Changes in sample preparation were studied to more effectively

Fiscal loss and program fidelity: impact of the economic downturn on HIV/STI prevention program fidelity.

Science.gov (United States)

Catania, Joseph A; Dolcini, M Margaret; Gandelman, Alice A; Narayanan, Vasudha; McKay, Virginia R

2014-03-01

The economic downturn of 2007 created significant fiscal losses for public and private agencies conducting behavioral prevention. Such macro-economic changes may influence program implementation and sustainability. We examined how public and private agencies conducting RESPECT, a brief HIV/STI (sexually transmitted infection) counseling and testing intervention, adapted to fiscal loss and how these adaptations impacted program fidelity. We collected qualitative and quantitative data in a national sample of 15 agencies experiencing fiscal loss. Using qualitative analyses, we examined how program fidelity varied with different types of adaptations. Agencies reported three levels of adaptation: agency-level, program-level, and direct fiscal remedies. Private agencies tended to use direct fiscal remedies, which were associated with higher fidelity. Some agency-level adaptations contributed to reductions in procedural fit, leading to negative staff morale and decreased confidence in program effectiveness, which in turn, contributed to poor fidelity. Findings describe a "work stress pathway" that links program fiscal losses to poor staff morale and low program fidelity.

Use of High Throughput Screening Data in IARC Monograph ...

Science.gov (United States)

Purpose: Evaluation of carcinogenic mechanisms serves a critical role in IARC monograph evaluations, and can lead to “upgrade” or “downgrade” of the carcinogenicity conclusions based on human and animal evidence alone. Three recent IARC monograph Working Groups (110, 112, and 113) pioneered analysis of high throughput in vitro screening data from the U.S. Environmental Protection Agency’s ToxCast program in evaluations of carcinogenic mechanisms. Methods: For monograph 110, ToxCast assay data across multiple nuclear receptors were used to test the hypothesis that PFOA acts exclusively through the PPAR family of receptors, with activity profiles compared to several prototypical nuclear receptor-activating compounds. For monographs 112 and 113, ToxCast assays were systematically evaluated and used as an additional data stream in the overall evaluation of the mechanistic evidence. Specifically, ToxCast assays were mapped to 10 “key characteristics of carcinogens” recently identified by an IARC expert group, and chemicals’ bioactivity profiles were evaluated both in absolute terms (number of relevant assays positive for bioactivity) and relative terms (ranking with respect to other compounds evaluated by IARC, using the ToxPi methodology). Results: PFOA activates multiple nuclear receptors in addition to the PPAR family in the ToxCast assays. ToxCast assays offered substantial coverage for 5 of the 10 “key characteristics,” with the greates

Analysis of Chemical Bioactivity through In Vitro Profiling ...

Science.gov (United States)

Safety assessment of drugs and environmental chemicals relies extensively on animal testing. However, the quantity of chemicals needing assessment and challenges of species extrapolation drive the development of alternative approaches. The EPA’s ToxCast and the multiagency Tox21 programs address this through use of an extensive in vitro screening program to generate data on a large library of important environmental chemicals. These in vitro assays encompass both cell-free, biochemical assays targeting proteins that may be potential molecular initiating events and cellular assays that provide coverage of critical signaling pathways and toxicity phenotypes. Effects on model organisms such as the developing zebrafish, are also part of the testing strategy. A variety of computational approaches are used to analyze the resulting complex data sets to gain insight in to inherent biological activity of chemicals and possible mechanisms of toxicity. Several case studies including identification of modulators of estrogen receptor and aromatic hydrocarbon receptor pathways with effects in primary human cell systems will be described. In addition, existing in vivo data from a subset of the chemicals was used to anchor predictive models using in vitro data for a number of adverse endpoints including reproductive and developmental toxicities. The strengths and weaknesses of this approach will be described. This work does not necessarily reflect official Agency policy. Pres

75 FR 56663 - Agency Information Collection (Quarterly Report of State Approving Agency Activities); Activity...

Science.gov (United States)

2010-09-16

... a currently approved collection. Abstract: VA reimburses State Approving Agencies (SAAs) for expenses incurred in the approval and supervision of education and training programs. SAAs are required to...

Collaborative development of predictive toxicology applications.

Science.gov (United States)

Hardy, Barry; Douglas, Nicki; Helma, Christoph; Rautenberg, Micha; Jeliazkova, Nina; Jeliazkov, Vedrin; Nikolova, Ivelina; Benigni, Romualdo; Tcheremenskaia, Olga; Kramer, Stefan; Girschick, Tobias; Buchwald, Fabian; Wicker, Joerg; Karwath, Andreas; Gütlein, Martin; Maunz, Andreas; Sarimveis, Haralambos; Melagraki, Georgia; Afantitis, Antreas; Sopasakis, Pantelis; Gallagher, David; Poroikov, Vladimir; Filimonov, Dmitry; Zakharov, Alexey; Lagunin, Alexey; Gloriozova, Tatyana; Novikov, Sergey; Skvortsova, Natalia; Druzhilovsky, Dmitry; Chawla, Sunil; Ghosh, Indira; Ray, Surajit; Patel, Hitesh; Escher, Sylvia

2010-08-31

OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative) Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs) for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals.The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation.Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure-activity relationship modelling of REACH

76 FR 38143 - Proposed Agency Information Collection

Science.gov (United States)

2011-06-29

..., Solar Energy Technologies Program, Office of Energy Efficiency and Renewable Energy. [FR Doc. 2011-16307... DEPARTMENT OF ENERGY Office of Energy Efficiency and Renewable Energy Proposed Agency Information Collection AGENCY: U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy. ACTION...

Promoting children's agency and communication skills in an informal science program

Science.gov (United States)

Wulf, Rosemary; Hinko, Kathleen; Finkelstein, Noah

2013-01-01

The Partnerships for Informal Science Education in the Community (PISEC) program at the University of Colorado Boulder brings together university and community institutions to create an environment where K-12 students join with university educators to engage in inquiry-based scientific practices after school. In our original framing, these afterschool activities were developed to reinforce the traditional learning goals of the classroom, including mastering scientific content, skills and processes. Recently, the primary focus of the PISEC curriculum has been shifted towards the development of students' scientific identity, an explicit objective of informal learning environments. The new curriculum offers students more activity choices, affords opportunities for scientific drawings and descriptions, and provides incentive for students to design their own experiments. We have analyzed student science notebooks from both old and new curricula and find that with the redesigned curriculum, students exhibit increased agency and more instances of scientific communication while still demonstrating substantial content learning gains.

An evaluation of human sperm as indicators of chemically induced alterations of spermatogenic function. A report of the U. S. Environmental Protection Agency Gene-Tox Program

Energy Technology Data Exchange (ETDEWEB)

Wyrobek, A.J.; Gordon, L.A.; Burkhart, J.G.; Francis, M.W.; Kapp, R.W. Jr.; Letz, G.; Malling, H.V.; Topham, J.C.; Whorton, M.D.

1983-05-01

To evaluate the utility of sperm tests as indichangesators of chemical effects on human spermatogenesis, the literature on 4 sperm tests used to assess chemically induced testicular dysfunction was reviewed. The tests surveyed included sperm count, motility, morphology (seminal cytology), and double Y-body (a fluorescence-based test thought to detect Y-chromosomal nondisjunction). There were 132 papers that provided sufficient data for evaluation. These reports encompassed 89 different chemical exposures: 53 were to single agents; 14 to complex mixtures; and 22 to combinations of 2 or more identified agents. Approximately 85% of the exposures were to experimental or therapeutic drugs, 10% were to occupational or environmental agents, and 5% were to drugs for personal use. The most common sperm parameter studied was sperm count. The 89 exposures reviewed were grouped into 4 classes: those which adversely effected spermatogenesis, as measured by one or more of the sperm test; those suggestive of improving semen quality; those showing inconclusive evidence of adverse effects from exposure; and those showing no significant changes. Since the reviewed reports had a large variety of study designs, and since every attempt was made to include all reports with interpretable data, these classifications were based on reviewing committee decisions rather than on uniform statistical criteria. This review gives strong evidence that human sperm tests can be used to identify chemicals that affect sperm production, but because of our limited understanding of underlying mechanisms, the extent to which they can detect mutagens, carcinogens or agents that affect fertility remains uncertain. For the very few agents studied with both human and mouse sperm tests, similar test-responses were seen. An overall comparison of the 4 human sperm tests suggests that no one test is biologically more responsive than another.

Radiation oncology and medical physicists quality assurance in British Columbia Cancer Agency Provincial Prostate Brachytherapy Program.

Science.gov (United States)

Keyes, Mira; Morris, William James; Spadinger, Ingrid; Araujo, Cynthia; Cheung, Arthur; Chng, Nick; Crook, Juanita; Halperin, Ross; Lapointe, Vince; Miller, Stacy; Pai, Howard; Pickles, Tom

2013-01-01

To describe in detail British Columbia (BC) Cancer Agency (BCCA) Provincial Prostate Brachytherapy (PB) Quality Assurance (QA) Program. The BCCA PB Program was established in 1997. It operates as one system, unified and supported by electronic and information systems, making it a single PB treatment provider for province of BC and Yukon. To date, >4000 patients have received PB (450 implants in 2011), making it the largest program in Canada. The Program maintains a large provincial prospective electronic database with records on all patients, including disease characteristics, risk stratification, pathology, preplan and postimplant dosimetric data, follow-up of prostate-specific antigen, and toxicity outcomes. QA was an integral part of the program since its inception. A formal QA Program was established in 2002, with key components that include: unified eligibility criteria and planning system, comprehensive database, physics and oncologist training and mentorship programs, peer review process, individual performance outcomes and feedback process, structured continuing education and routine assessment of the program's dosimetry, toxicity and prostate-specific antigen outcomes, administration and program leadership that promotes a strong culture of patient safety. The emphasis on creating a robust, broad-based network of skilled providers has been achieved by the program's requirements for training, education, and the QA process. The formal QA process is considered a key factor for the success of cancer control outcomes achieved at BCCA. Although this QA model may not be wholly transferable to all PB programs, some of its key components may be applicable to other programs to ensure quality in PB and patient safety. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

76 FR 27986 - Funding for the Conservation Loan Program; Farm Loan Programs

Science.gov (United States)

2011-05-13

... for the Conservation Loan Program; Farm Loan Programs AGENCY: Farm Service Agency, USDA. ACTION... or guaranteed loan applications for the Conservation Loan (CL) Program because of lack of program... provisions to the existing direct and guaranteed loan regulations found in 7 CFR parts 761, 762, 764, 765...

Peak flood estimation using gene expression programming

Science.gov (United States)

Zorn, Conrad R.; Shamseldin, Asaad Y.

2015-12-01

As a case study for the Auckland Region of New Zealand, this paper investigates the potential use of gene-expression programming (GEP) in predicting specific return period events in comparison to the established and widely used Regional Flood Estimation (RFE) method. Initially calibrated to 14 gauged sites, the GEP derived model was further validated to 10 and 100 year flood events with a relative errors of 29% and 18%, respectively. This is compared to the RFE method providing 48% and 44% errors for the same flood events. While the effectiveness of GEP in predicting specific return period events is made apparent, it is argued that the derived equations should be used in conjunction with those existing methodologies rather than as a replacement.

Youth and administrator perspectives on transition in Kentucky's state agency schools.

Science.gov (United States)

Marshall, Amy; Powell, Norman; Pierce, Doris; Nolan, Ronnie; Fehringer, Elaine

2012-01-01

Students, a large percentage with disabilities, are at high risk for poor post-secondary outcomes in state agency education programs. This mixed-methods study describes the understandings of student transitions in state agency education programs from the perspectives of youth and administrators. Results indicated that: transition is more narrowly defined within alternative education programs; key strengths of transition practice are present in nontraditional schools; and the coordination barriers within this fluid inter-agency transition system are most apparent in students' frequent inter-setting transitions between nontraditional and home schools.

Tribbles ortholog NIPI-3 and bZIP transcription factor CEBP-1 regulate a Caenorhabditis elegans intestinal immune surveillance pathway.

Science.gov (United States)

McEwan, Deborah L; Feinbaum, Rhonda L; Stroustrup, Nicholas; Haas, Wilhelm; Conery, Annie L; Anselmo, Anthony; Sadreyev, Ruslan; Ausubel, Frederick M

2016-12-07

Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P. aeruginosa or ToxA. We find that NIPI-3 mediates the post-developmental expression of intestinal immune genes and proteins and primarily functions in parallel to known immune pathways, including p38 MAPK signaling. Through mutagenesis screening, we identify mutants of the bZIP C/EBP transcription factor cebp-1 that suppress the hypersusceptibility defects of nipi-3 mutants. NIPI-3 is a negative regulator of CEBP-1, which in turn negatively regulates protective immune mechanisms. This pathway represents a previously unknown innate immune signaling pathway in intestinal epithelial cells that is involved in the surveillance of cellular homeostasis. Because NIPI-3 and CEBP-1 are also essential for C. elegans development, NIPI-3 is analogous to other key innate immune signaling molecules such as the Toll receptors in Drosophila that have an independent role during development.

French local agencies of energy control; Agences locales francaise de maitrise de l'energie

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

In the framework of the SAVE program, the European Commission brings financial assistance to the creation of local or regional agencies of energy control in municipalities and regions. The main criteria are the impacts on the energy demand, the reinforcement of the economic and social cohesion, the environmental quality and the contribution to the economic development and the employment creation. In this document, realized by Energie-Cites, the Ademe objective is to present a state of the art of french local agencies. Ten agencies are presented as case study. Each case deals with the following topics: the main context of the action which details the energy and the environmental policy of the municipality, the creation and the description of the agency, the implemented actions and the perspectives. (A.L.B.)

34 CFR 300.12 - Educational service agency.

Science.gov (United States)

2010-07-01

... schools and secondary schools of the State; (b) Includes any other public institution or agency having administrative control and direction over a public elementary school or secondary school; and (c) Includes... develop, manage, and provide services or programs to LEAs; (2) Recognized as an administrative agency for...

The U.S. National Library of Medicine's Toxicology and Environmental Health Information Program

International Nuclear Information System (INIS)

Wexler, Philip

2004-01-01

For nearly 40 years, the National Library of Medicine's (NLM) Toxicology and Environmental Health Information Program (TEHIP) has been a significant leader in organizing and providing public access to an extensive storehouse of toxicological information through its online databases. With the advent of the Internet, TEHIP has expanded its role to also serve as a pre-eminent portal to toxicological information worldwide. Its primary databases reside within the web-based TOXNET system, and include the scientifically peer-reviewed Hazardous Substances Data Bank (HSDB), the U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) and Toxics Release Inventory, the National Cancer Institute's Chemical Carcinogenesis Research Information System (CCRIS) and the TOXLINE file of over 3 million bibliographic references. TEHIP's ChemIDplus is an extensive chemical dictionary that extends beyond simple nomenclature to offer displays of molecular structures and links from particular chemicals to other databases containing more information. Specialty files in occupational safety and health, and household products have recently been added to TEHIP's suite of resources. Additional databases in risk assessment, drugs, toxicology education, and global resources, are under development. ''Special Topics'' pages lead users to structured summaries and links in areas such as arsenic, chemical warfare agents, biological warfare, and West Nile Virus. A database on alternatives to the use of live animals, a three-module toxicology tutor, and a glossary of terms in toxicology are among TEHIP's other information aids, as well an increasing commitment to serving consumers, as witnessed by the animated ToxTown program. Outside the sphere of TEHIP, NLM offers additional databases, such as PubMed, of significant value to toxicology researchers

From Classical Toxicology to Tox21: Some Critical Conceptual and Technological Advances in the Molecular Understanding of the Toxic Response Beginning From the Last Quarter of the 20th Century.

Science.gov (United States)

Choudhuri, Supratim; Patton, Geoffrey W; Chanderbhan, Ronald F; Mattia, Antonia; Klaassen, Curtis D

2018-01-01

Toxicology has made steady advances over the last 60+ years in understanding the mechanisms of toxicity at an increasingly finer level of cellular organization. Traditionally, toxicological studies have used animal models. However, the general adoption of the principles of 3R (Replace, Reduce, Refine) provided the impetus for the development of in vitro models in toxicity testing. The present commentary is an attempt to briefly discuss the transformation in toxicology that began around 1980. Many genes important in cellular protection and metabolism of toxicants were cloned and characterized in the 80s, and gene expression studies became feasible, too. The development of transgenic and knockout mice provided valuable animal models to investigate the role of specific genes in producing toxic effects of chemicals or protecting the organism from the toxic effects of chemicals. Further developments in toxicology came from the incorporation of the tools of "omics" (genomics, proteomics, metabolomics, interactomics), epigenetics, systems biology, computational biology, and in vitro biology. Collectively, the advances in toxicology made during the last 30-40 years are expected to provide more innovative and efficient approaches to risk assessment. A goal of experimental toxicology going forward is to reduce animal use and yet be able to conduct appropriate risk assessments and make sound regulatory decisions using alternative methods of toxicity testing. In that respect, Tox21 has provided a big picture framework for the future. Currently, regulatory decisions involving drugs, biologics, food additives, and similar compounds still utilize data from animal testing and human clinical trials. In contrast, the prioritization of environmental chemicals for further study can be made using in vitro screening and computational tools. Published by Oxford University Press on behalf of the Society of Toxicology 2017. This work is written by US Government employees and is in the

Application of a bacterial whole cell biosensor for the rapid detection of cytotoxicity in heavy metal contaminated seawater.

Science.gov (United States)

Cui, Zhisong; Luan, Xiao; Jiang, Huichao; Li, Qian; Xu, Guangfei; Sun, Chengjun; Zheng, Li; Song, Yizhi; Davison, Paul A; Huang, Wei E

2018-06-01

A toxicity biosensor Acinetobacter baylyi Tox2 was constructed with the host strain A. baylyi ADP1 harboring a new and medium-copy-number plasmid pWH1274_lux, and was applied to detect the cytotoxicity of heavy metal contaminated seawater. The gene cassette luxCDABE was controlled by constitutively expressed promoter P tet on pWH1274_lux and the bioluminescence intensity of the biosensor reduces in proportional to the concentrations of toxic compounds. A. baylyi Tox2 exhibits tolerance to salinity, hence it is applicable to seawater samples. A. baylyi Tox2 and Mugilogobius chulae were exposed to different concentrations of heavy metals (Hg 2+ , Zn 2+ , Cu 2+ , and Cd 2+ ) in artificial seawater for performance comparison and Pearson correlation analysis showed a significant correlation (p heavy metal contaminated seawater. Furthermore, A. baylyi Tox2 was used to evaluate cytotoxicity of field-collected seawater samples. The results indicate that there was a significant correlation between the luminescence inhibition ratio (IR) of A. baylyi Tox2 and heavy metal concentrations detected by ICP-MS in the samples. Two seawater samples, which contained a high concentration of total heavy metals, exhibited stronger cytotoxicity than the samples containing low concentrations of heavy metals. In conclusion, A. baylyi Tox2 can be used as an alternative tool to aquatic animals for the evaluation of the cytotoxicity of heavy metal contamination in the marine environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

FutureTox II: in vitro data and in silico models for predictive toxicology.

Science.gov (United States)

Knudsen, Thomas B; Keller, Douglas A; Sander, Miriam; Carney, Edward W; Doerrer, Nancy G; Eaton, David L; Fitzpatrick, Suzanne Compton; Hastings, Kenneth L; Mendrick, Donna L; Tice, Raymond R; Watkins, Paul B; Whelan, Maurice

2015-02-01

FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Gene Expression Program for the Formation of Wing Cuticle in Drosophila.

Directory of Open Access Journals (Sweden)

Lukasz F Sobala

2016-05-01

Full Text Available The cuticular exoskeleton of insects and other arthropods is a remarkably versatile material with a complex multilayer structure. We made use of the ability to isolate cuticle synthesizing cells in relatively pure form by dissecting pupal wings and we used RNAseq to identify genes expressed during the formation of the adult wing cuticle. We observed dramatic changes in gene expression during cuticle deposition, and combined with transmission electron microscopy, we were able to identify candidate genes for the deposition of the different cuticular layers. Among genes of interest that dramatically change their expression during the cuticle deposition program are ones that encode cuticle proteins, ZP domain proteins, cuticle modifying proteins and transcription factors, as well as genes of unknown function. A striking finding is that mutations in a number of genes that are expressed almost exclusively during the deposition of the envelope (the thin outermost layer that is deposited first result in gross defects in the procuticle (the thick chitinous layer that is deposited last. An attractive hypothesis to explain this is that the deposition of the different cuticle layers is not independent with the envelope instructing the formation of later layers. Alternatively, some of the genes expressed during the deposition of the envelope could form a platform that is essential for the deposition of all cuticle layers.

Workplace violence prevention policies in home health and hospice care agencies.

Science.gov (United States)

Gross, Nathan; Peek-Asa, Corinne; Nocera, Maryalice; Casteel, Carri

2013-01-31

Workplace violence in the home health industry is a growing concern, but little is known about the content of existing workplace violence prevention programs. The authors present the methods for this study that examined workplace violence prevention programs in a sample of 40 California home health and hospice agencies. Data was collected through surveys that were completed by the branch managers of participating facilities. Programs were scored in six different areas, including general workplace violence prevention components; management commitment and employee involvement; worksite analysis; hazard prevention and control; safety and health training; and recordkeeping and program evaluation. The results and discussion sections consider these six areas and the important gaps that were found in existing programs. For example, although most agencies offered workplace violence training, not every worker performing patient care was required to receive the training. Similarly, not all programs were written or reviewed and updated regularly. Few program differences were observed between agency characteristics, but nonetheless several striking gaps were found.

Gene expression programming for prediction of scour depth downstream of sills

Science.gov (United States)

Azamathulla, H. Md.

2012-08-01

SummaryLocal scour is crucial in the degradation of river bed and the stability of grade control structures, stilling basins, aprons, ski-jump bucket spillways, bed sills, weirs, check dams, etc. This short communication presents gene-expression programming (GEP), which is an extension to genetic programming (GP), as an alternative approach to predict scour depth downstream of sills. Published data were compiled from the literature for the scour depth downstream of sills. The proposed GEP approach gives satisfactory results (R2 = 0.967 and RMSE = 0.088) compared to the existing predictors (Chinnarasri and Kositgittiwong, 2008) with R2 = 0.87 and RMSE = 2.452 for relative scour depth.

French local agencies of energy control; Agences locales francaise de maitrise de l'energie

Energy Technology Data Exchange (ETDEWEB)

NONE

2000-07-01

In the framework of the SAVE program, the European Commission brings financial assistance to the creation of local or regional agencies of energy control in municipalities and regions. The main criteria are the impacts on the energy demand, the reinforcement of the economic and social cohesion, the environmental quality and the contribution to the economic development and the employment creation. In this document, realized by Energie-Cites, the Ademe objective is to present a state of the art of french local agencies. Ten agencies are presented as case study. Each case deals with the following topics: the main context of the action which details the energy and the environmental policy of the municipality, the creation and the description of the agency, the implemented actions and the perspectives. (A.L.B.)

77 FR 36010 - Agency Information Collection Activities; Agency Information Collection Activities; Proposed...

Science.gov (United States)

2012-06-15

... Respondents, Local Jails and State Prisons ACTION: 60-day notice. The Department of Justice (DOJ), Office of..., students, the media, others interested in criminal justice statistics, and the general public. (5) An... DEPARTMENT OF JUSTICE Office of Justice Programs [OMB No. 1121-0249] Agency Information Collection...

77 FR 13530 - Funding for the Conservation Loan Program; Farm Loan Programs

Science.gov (United States)

2012-03-07

... DEPARTMENT OF AGRICULTURE Farm Service Agency Funding for the Conservation Loan Program; Farm Loan... Service Agency (FSA) now has funding for and is accepting guaranteed loan applications for the Conservation Loan (CL) Program. Due to a lack of program funding for direct CLs, direct loan applications are...

41 CFR 102-75.760 - Who must the Office of Justice Programs (OJP) and the Federal Emergency Management Agency (FEMA...

Science.gov (United States)

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Who must the Office of Justice Programs (OJP) and the Federal Emergency Management Agency (FEMA) notify that surplus real property is available for correctional facility, law enforcement, or emergency management response purposes? 102-75.760 Section 102-75.760 Public...

25 CFR 700.509 - Duties of the designated agency ethics official.

Science.gov (United States)

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false Duties of the designated agency ethics official. 700.509... RELOCATION PROCEDURES Employee Responsibility and Conduct § 700.509 Duties of the designated agency ethics official. The Designated Agency Ethics Official shall coordinate and manage the agency's ethics program...

The International Atomic Energy Agency (IAEA) research program to improve safety assessment methodologies for near-surface radioactive waste disposal facilities (ISAM)

International Nuclear Information System (INIS)

Torres-Vidal, C.; Kozak, M.W.

2000-01-01

The International Atomic Energy Agency (IAEA) launched a Coordinated Research Program in November 1997 on Improvement of Safety Assessment Methodologies for Near Surface Radioactive Waste Disposal Facilities (ISAM). The purpose of this paper is to describe the program and its goals, and to describe achievements of the program to date. The main objectives of the ISAM program are outlined. The primary focus of ISAM is on the practical application of safety assessment methodologies. Three kinds of practical situations are being addressed in the program: safety assessments for large vaults typical of those in Western Europe and North America, smaller vaults for medium and industrial wastes typical in eastern Europe and the former Soviet Union, and a proposed borehole technology for disposal of spent sources in low-technology conditions. (author)

INVESTIGATION OF THE TOTAL ORGANIC HALOGEN ANALYTICAL METHOD AT THE WASTE SAMPLING CHARACTERIZATION FACILITY (WSCF)

International Nuclear Information System (INIS)

DOUGLAS JG; MEZNARICH HD, PHD; OLSEN JR; ROSS GA; STAUFFER M

2008-01-01

Total organic halogen (TOX) is used as a parameter to screen groundwater samples at the Hanford Site. Trending is done for each groundwater well, and changes in TOX and other screening parameters can lead to costly changes in the monitoring protocol. The Waste Sampling and Characterization Facility (WSCF) analyzes groundwater samples for TOX using the United States Environmental Protection Agency (EPA) SW-846 method 9020B (EPA 1996a). Samples from the Soil and Groundwater Remediation Project (S and GRP) are submitted to the WSCF for analysis without information regarding the source of the sample; each sample is in essence a 'blind' sample to the laboratory. Feedback from the S and GRP indicated that some of the WSCF-generated TOX data from groundwater wells had a number of outlier values based on the historical trends (Anastos 2008a). Additionally, analysts at WSCF observed inconsistent TOX results among field sample replicates. Therefore, the WSCF lab performed an investigation of the TOX analysis to determine the cause of the outlier data points. Two causes were found that contributed to generating out-of-trend TOX data: (1) The presence of inorganic chloride in the groundwater samples: at inorganic chloride concentrations greater than about 10 parts per million (ppm), apparent TOX values increase with increasing chloride concentration. A parallel observation is the increase in apparent breakthrough of TOX from the first to the second activated-carbon adsorption tubes with increasing inorganic chloride concentration. (2) During the sample preparation step, excessive purging of the adsorption tubes with oxygen pressurization gas after sample loading may cause channeling in the activated-carbon bed. This channeling leads to poor removal of inorganic chloride during the subsequent wash step with aqueous potassium nitrate. The presence of this residual inorganic chloride then produces erroneously high TOX values. Changes in sample preparation were studied to more

Collaborative development of predictive toxicology applications

Directory of Open Access Journals (Sweden)

Hardy Barry

2010-08-01

Full Text Available Abstract OpenTox provides an interoperable, standards-based Framework for the support of predictive toxicology data management, algorithms, modelling, validation and reporting. It is relevant to satisfying the chemical safety assessment requirements of the REACH legislation as it supports access to experimental data, (Quantitative Structure-Activity Relationship models, and toxicological information through an integrating platform that adheres to regulatory requirements and OECD validation principles. Initial research defined the essential components of the Framework including the approach to data access, schema and management, use of controlled vocabularies and ontologies, architecture, web service and communications protocols, and selection and integration of algorithms for predictive modelling. OpenTox provides end-user oriented tools to non-computational specialists, risk assessors, and toxicological experts in addition to Application Programming Interfaces (APIs for developers of new applications. OpenTox actively supports public standards for data representation, interfaces, vocabularies and ontologies, Open Source approaches to core platform components, and community-based collaboration approaches, so as to progress system interoperability goals. The OpenTox Framework includes APIs and services for compounds, datasets, features, algorithms, models, ontologies, tasks, validation, and reporting which may be combined into multiple applications satisfying a variety of different user needs. OpenTox applications are based on a set of distributed, interoperable OpenTox API-compliant REST web services. The OpenTox approach to ontology allows for efficient mapping of complementary data coming from different datasets into a unifying structure having a shared terminology and representation. Two initial OpenTox applications are presented as an illustration of the potential impact of OpenTox for high-quality and consistent structure

Genome-Based Comparison of Clostridioides difficile: Average Amino Acid Identity Analysis of Core Genomes.

Science.gov (United States)

Cabal, Adriana; Jun, Se-Ran; Jenjaroenpun, Piroon; Wanchai, Visanu; Nookaew, Intawat; Wongsurawat, Thidathip; Burgess, Mary J; Kothari, Atul; Wassenaar, Trudy M; Ussery, David W

2018-02-14

Infections due to Clostridioides difficile (previously known as Clostridium difficile) are a major problem in hospitals, where cases can be caused by community-acquired strains as well as by nosocomial spread. Whole genome sequences from clinical samples contain a lot of information but that needs to be analyzed and compared in such a way that the outcome is useful for clinicians or epidemiologists. Here, we compare 663 public available complete genome sequences of C. difficile using average amino acid identity (AAI) scores. This analysis revealed that most of these genomes (640, 96.5%) clearly belong to the same species, while the remaining 23 genomes produce four distinct clusters within the Clostridioides genus. The main C. difficile cluster can be further divided into sub-clusters, depending on the chosen cutoff. We demonstrate that MLST, either based on partial or full gene-length, results in biased estimates of genetic differences and does not capture the true degree of similarity or differences of complete genomes. Presence of genes coding for C. difficile toxins A and B (ToxA/B), as well as the binary C. difficile toxin (CDT), was deduced from their unique PfamA domain architectures. Out of the 663 C. difficile genomes, 535 (80.7%) contained at least one copy of ToxA or ToxB, while these genes were missing from 128 genomes. Although some clusters were enriched for toxin presence, these genes are variably present in a given genetic background. The CDT genes were found in 191 genomes, which were restricted to a few clusters only, and only one cluster lacked the toxin A/B genes consistently. A total of 310 genomes contained ToxA/B without CDT (47%). Further, published metagenomic data from stools were used to assess the presence of C. difficile sequences in blinded cases of C. difficile infection (CDI) and controls, to test if metagenomic analysis is sensitive enough to detect the pathogen, and to establish strain relationships between cases from the same

SURVEY ON V. CHOLERAE, V. VULNIFICUS AND V. PARAHAEMOLYTICUS IN BIVALVE MOLLUSCS OF THE ADRIATIC SEA AND PROPOSAL OF AN ANALYTICAL PROTOCOL

Directory of Open Access Journals (Sweden)

M.L. Valeri

2009-06-01

Full Text Available Bivalve molluscs from Adriatic sea were analyzed for V. parahaemolyticus, V. cholerae e V. vulnificus presence. The isolates on TCBS Agar and m-CPC Agar were selected on the basis of a new biochemical screening, that showed a good performance, because among 2344 strains from primary culture only 237 (10% were presumptively assigned to the species of interest. The PCR analyses was performed for the target genes toxR hlyA, ctxA, tcpI (V. cholerae, toxR, tl, tdh, trh (V. parahaemolyticus, vvhA and viuB (V. vulnificus. Among the 9 strains confirmed to belong to V. parahaemolyticus specie, 6 were sucrose positive. On 215 samples of molluscs only 5 resulted positive for V. parahaemolyticus being toxR+, tl+, although non pathogenic (tdh-, trh-, and none for V. cholerae e V. vulnificus.

Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs.

Science.gov (United States)

Spiegel, Ivo; Mardinly, Alan R; Gabel, Harrison W; Bazinet, Jeremy E; Couch, Cameron H; Tzeng, Christopher P; Harmin, David A; Greenberg, Michael E

2014-05-22

The nervous system adapts to experience by inducing a transcriptional program that controls important aspects of synaptic plasticity. Although the molecular mechanisms of experience-dependent plasticity are well characterized in excitatory neurons, the mechanisms that regulate this process in inhibitory neurons are only poorly understood. Here, we describe a transcriptional program that is induced by neuronal activity in inhibitory neurons. We find that, while neuronal activity induces expression of early-response transcription factors such as Npas4 in both excitatory and inhibitory neurons, Npas4 activates distinct programs of late-response genes in inhibitory and excitatory neurons. These late-response genes differentially regulate synaptic input to these two types of neurons, promoting inhibition onto excitatory neurons while inducing excitation onto inhibitory neurons. These findings suggest that the functional outcomes of activity-induced transcriptional responses are adapted in a cell-type-specific manner to achieve a circuit-wide homeostatic response. Copyright © 2014 Elsevier Inc. All rights reserved.

Early results of sarcomeric gene screening from the Egyptian National BA-HCM Program.

Science.gov (United States)

Kassem, Heba Sh; Azer, Remon S; Saber-Ayad, Maha; Ayad, Maha S; Moharem-Elgamal, Sarah; Magdy, Gehan; Elguindy, Ahmed; Cecchi, Franco; Olivotto, Iacopo; Yacoub, Magdi H

2013-02-01

The present study comprised sarcomeric genotyping of the three most commonly involved sarcomeric genes: MYBPC3, MYH7, and TNNT2 in 192 unrelated Egyptian hypertrophic cardiomyopathy (HCM) index patients. Mutations were detected in 40 % of cases. Presence of positive family history was significantly (p=0.002) associated with a higher genetic positive yield (49/78, 62.8 %). The majority of the detected mutations in the three sarcomeric genes were novel (40/62, 65 %) and mostly private (47/62, 77 %). Single nucleotide substitution was the most frequently detected mutation type (51/62, 82 %). Over three quarters of these substitutions (21/27, 78 %) involved CpG dinucleotide sites and resulted from C>T or G>A transition in the three analyzed genes, highlighting the significance of CpG high mutability within the sarcomeric genes examined. This study could aid in global comparative studies in different ethnic populations and constitutes an important step in the evolution of the integrated clinical, translational, and basic science HCM program.

33 CFR 238.10 - Coordination with other Federal agencies.

Science.gov (United States)

2010-07-01

... abreast of the public works programs administered by other Federal agencies, such as the Environmental Protection Agency, the Department of Housing and Urban Development, Farmers Home Administration and the... help to achieve this objective (see ER 1105-2-811). ...

49 CFR 659.29 - Oversight agency safety and security reviews.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Oversight agency safety and security reviews. 659... Role of the State Oversight Agency § 659.29 Oversight agency safety and security reviews. At least... safety program plan and system security plan. Alternatively, the on-site review may be conducted in an on...

13 CFR 124.502 - How does an agency offer a procurement to SBA for award through the 8(a) BD program?

Science.gov (United States)

2010-01-01

... history, if any, of the requirement; (10) The names and addresses of any small business contractors which... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false How does an agency offer a procurement to SBA for award through the 8(a) BD program? 124.502 Section 124.502 Business Credit and...

Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

International Nuclear Information System (INIS)

Haggard, Derik E.; Noyes, Pamela D.; Waters, Katrina M.; Tanguay, Robert L.

2016-01-01

Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC 80 ) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC 80 (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC 80 causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and development in

Phenotypically anchored transcriptome profiling of developmental exposure to the antimicrobial agent, triclosan, reveals hepatotoxicity in embryonic zebrafish

Energy Technology Data Exchange (ETDEWEB)

Haggard, Derik E. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Noyes, Pamela D. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States); Office of Science Coordination and Policy (OSCP), Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Washington, DC (United States); Waters, Katrina M. [Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA (United States); Tanguay, Robert L., E-mail: Robert.Tanguay@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR (United States)

2016-10-01

Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen signaling; therefore, research examining the developmental effects of TCS is warranted. In this study, we used embryonic zebrafish to investigate the developmental toxicity and potential mechanism of action of TCS. Embryos were exposed to graded concentrations of TCS from 6 to 120 hours post-fertilization (hpf) and the concentration where 80% of the animals had mortality or morbidity at 120 hpf (EC{sub 80}) was calculated. Transcriptomic profiling was conducted on embryos exposed to the EC{sub 80} (7.37 μM). We identified a total of 922 significant differentially expressed transcripts (FDR adjusted P-value ≤ 0.05; fold change ≥ 2). Pathway and gene ontology enrichment analyses identified biological networks and transcriptional hubs involving normal liver functioning, suggesting TCS may be hepatotoxic in zebrafish. Tissue-specific gene enrichment analysis further supported the role of the liver as a target organ for TCS toxicity. We also examined the in vitro bioactivity profile of TCS reported by the ToxCast screening program. TCS had a diverse bioactivity profile and was a hit in 217 of the 385 assay endpoints we identified. We observed similarities in gene expression and hepatic steatosis assays; however, hit data for TCS were more concordant with the hypothesized CAR/PXR activity of TCS from rodent and human in vitro studies. - Highlights: • Triclosan is a common antimicrobial agent with widespread human exposure. • Exposure to the triclosan EC{sub 80} causes robust gene expression changes in zebrafish. • The liver may be a target organ of triclosan toxicity in embryonic zebrafish. • Triclosan disrupts normal liver functioning and

5 CFR 2638.203 - Duties of the designated agency ethics official.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Duties of the designated agency ethics official. 2638.203 Section 2638.203 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES Designated Agency Ethics...

5 CFR 2638.706 - Agency's written plan for annual ethics training.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Agency's written plan for annual ethics training. 2638.706 Section 2638.706 Administrative Personnel OFFICE OF GOVERNMENT ETHICS GOVERNMENT ETHICS OFFICE OF GOVERNMENT ETHICS AND EXECUTIVE AGENCY ETHICS PROGRAM RESPONSIBILITIES Executive Agency Ethics...

Rapid gene expression changes in peripheral blood lymphocytes upon practice of a comprehensive yoga program.

Directory of Open Access Journals (Sweden)

Su Qu

Full Text Available One of the most common integrative medicine (IM modalities is yoga and related practices. Previous work has shown that yoga may improve wellness in healthy people and have benefits for patients. However, the mechanisms of how yoga may positively affect the mind-body system are largely unknown. Here we have assessed possible rapid changes in global gene expression profiles in the peripheral blood mononuclear cells (PBMCs in healthy people that practiced either a comprehensive yoga program or a control regimen. The experimental sessions included gentle yoga postures, breathing exercises, and meditation (Sudarshan Kriya and Related Practices--SK&P compared with a control regimen of a nature walk and listening to relaxing music. We show that the SK&P program has a rapid and significantly greater effect on gene expression in PBMCs compared with the control regimen. These data suggest that yoga and related practices result in rapid gene expression alterations which may be the basis for their longer term cell biological and higher level health effects.

Nanotechnology applications and implications research supported by the US Environmental Protection Agency STAR grants program.

Science.gov (United States)

Savage, Nora; Thomas, Treye A; Duncan, Jeremiah S

2007-10-01

Since 2002, the US Environmental Protection Agency (EPA) has been funding research on the environmental aspects of nanotechnology through its Science to Achieve Results (STAR) grants program. In total, more than $25 million has been awarded for 86 research projects on the environmental applications and implications of nanotechnology. In the applications area, grantees have produced promising results in green manufacturing, remediation, sensors, and treatment using nanotechnology and nanomaterials. Although there are many potential benefits of nanotechnology, there has also been increasing concern about the environmental and health effects of nanomaterials, and there are significant gaps in the data needed to address these concerns. Research performed by STAR grantees is beginning to address these needs.

76 FR 161 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-01-03

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... certification maintenance program. MedTox Laboratories, Inc., 402 W. County Road D,St. Paul, MN 55112. 651-636...

Study of Risk Assessment Programs at Federal Agencies and Commercial Industry Related to the Conduct or Regulation of High Hazard Operations

International Nuclear Information System (INIS)

Bari, R.; Rosenbloom, S.; O'Brien, J.

2011-01-01

In the Department of Energy (DOE) Implementation Plan (IP) for Defense Nuclear Facilities Safety Board's Recommendation 2009-1, the DOE committed to studying the use of quantitative risk assessment methodologies at government agencies and industry. This study consisted of document reviews and interviews of senior management and risk assessment staff at six organizations. Data were collected and analyzed on risk assessment applications, risk assessment tools, and controls and infrastructure supporting the correct usage of risk assessment and risk management tools. The study found that the agencies were in different degrees of maturity in the use of risk assessment to support the analysis of high hazard operations and to support decisions related to these operations. Agencies did not share a simple, 'one size fits all' approach to tools, controls, and infrastructure needs. The agencies recognized that flexibility was warranted to allow use of risk assessment tools in a manner that is commensurate with the complexity of the application. The study also found that, even with the lack of some data, agencies application of the risk analysis structured approach could provide useful insights such as potential system vulnerabilities. This study, in combination with a companion study of risk assessment programs in the DOE Offices involved in high hazard operations, is being used to determine the nature and type of controls and infrastructure needed to support risk assessments at the DOE.

Australia and the International Atomic Energy Agency

International Nuclear Information System (INIS)

1987-01-01

Australia's support for the IAEA's safeguards program is described. Through a program of bilateral assistance to the Agency, Austrlia has developed and sponsored special programs of assistance to the IAEA's Safeguards over the period 1980 to 1986. The speech by the Minister for Foreign Affairs and Trade, Mr Bill Hayden, to the IAEA Thirtieth Anniversary Conference in Vienna on 21 September 1987 is included

77 FR 2304 - Agency Information Collection Activities: Proposed Collection; Comment Request, Application for...

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2012-01-17

... Resolution--Collateral Security; FEMA Form 090-0-2, Application for Community Disaster Loan. Abstract: The..., Application for Community Disaster Loan (CDL) Program AGENCY: Federal Emergency Management Agency, DHS. ACTION... concerning the Community Disaster Loan (CDL) Program. This collection allows the government to make loans to...

EXONSAMPLER: a computer program for genome-wide and candidate gene exon sampling for targeted next-generation sequencing.

Science.gov (United States)

Cosart, Ted; Beja-Pereira, Albano; Luikart, Gordon

2014-11-01

The computer program EXONSAMPLER automates the sampling of thousands of exon sequences from publicly available reference genome sequences and gene annotation databases. It was designed to provide exon sequences for the efficient, next-generation gene sequencing method called exon capture. The exon sequences can be sampled by a list of gene name abbreviations (e.g. IFNG, TLR1), or by sampling exons from genes spaced evenly across chromosomes. It provides a list of genomic coordinates (a bed file), as well as a set of sequences in fasta format. User-adjustable parameters for collecting exon sequences include a minimum and maximum acceptable exon length, maximum number of exonic base pairs (bp) to sample per gene, and maximum total bp for the entire collection. It allows for partial sampling of very large exons. It can preferentially sample upstream (5 prime) exons, downstream (3 prime) exons, both external exons, or all internal exons. It is written in the Python programming language using its free libraries. We describe the use of EXONSAMPLER to collect exon sequences from the domestic cow (Bos taurus) genome for the design of an exon-capture microarray to sequence exons from related species, including the zebu cow and wild bison. We collected ~10% of the exome (~3 million bp), including 155 candidate genes, and ~16,000 exons evenly spaced genomewide. We prioritized the collection of 5 prime exons to facilitate discovery and genotyping of SNPs near upstream gene regulatory DNA sequences, which control gene expression and are often under natural selection. © 2014 John Wiley & Sons Ltd.

Co-ordinate regulation of Salmonella typhimurium invasion genes by environmental and regulatory factors is mediated by control of hilA expression.

Science.gov (United States)

Bajaj, V; Lucas, R L; Hwang, C; Lee, C A

1996-11-01

During infection of their hosts, salmonellae enter intestinal epithelial cells. It has been proposed that when Salmonella typhimurium is present in the intestinal lumen, several environmental and regulatory conditions modulate the expression of invasion factors required for bacterial entry into host cells. We report here that the expression of six different S. typhimurium invasion genes encoded on SPI1 (Salmonella pathogenicity island 1) is co-ordinately regulated by oxygen, osmolarity, pH, PhoPQ, and HilA. HilA is a transcriptional activator of the OmpR/ToxR family that is also encoded on SPI1. We have found that HilA plays a central role in the co-ordinated regulation of invasion genes by environmental and regulatory conditions. HilA can activate the expression of two invasion gene-lacZY fusions on reporter plasmids in Escherichia coll, suggesting that HilA acts directly at invasion-gene promoters in S. typhimurium. We have found that the regulation of invasion genes by oxygen, osmolarity, pH, and PhoPQ is indirect and is mediated by regulation of hilA expression by these environmental and regulatory factors. We hypothesize that the complex and co-ordinate regulation of Invasion genes by HilA is an important feature of salmonella pathogenesis and allows salmonellae to enter intestinal epithelial cells.

Defense Threat Reduction Agency > Careers > Onboarding > Special Programs

Science.gov (United States)

Development Work/Life Programs Onboarding Onboarding Overview Before You Report Sponsor Program Getting Here , programs, and practices to help our employees and Service members balance work and family responsibilities . We have put in place family-friendly Work/Life programs and policies designed to create a more

Gene selection for the reconstruction of stem cell differentiation trees: a linear programming approach.

Science.gov (United States)

Ghadie, Mohamed A; Japkowicz, Nathalie; Perkins, Theodore J

2015-08-15

Stem cell differentiation is largely guided by master transcriptional regulators, but it also depends on the expression of other types of genes, such as cell cycle genes, signaling genes, metabolic genes, trafficking genes, etc. Traditional approaches to understanding gene expression patterns across multiple conditions, such as principal components analysis or K-means clustering, can group cell types based on gene expression, but they do so without knowledge of the differentiation hierarchy. Hierarchical clustering can organize cell types into a tree, but in general this tree is different from the differentiation hierarchy itself. Given the differentiation hierarchy and gene expression data at each node, we construct a weighted Euclidean distance metric such that the minimum spanning tree with respect to that metric is precisely the given differentiation hierarchy. We provide a set of linear constraints that are provably sufficient for the desired construction and a linear programming approach to identify sparse sets of weights, effectively identifying genes that are most relevant for discriminating different parts of the tree. We apply our method to microarray gene expression data describing 38 cell types in the hematopoiesis hierarchy, constructing a weighted Euclidean metric that uses just 175 genes. However, we find that there are many alternative sets of weights that satisfy the linear constraints. Thus, in the style of random-forest training, we also construct metrics based on random subsets of the genes and compare them to the metric of 175 genes. We then report on the selected genes and their biological functions. Our approach offers a new way to identify genes that may have important roles in stem cell differentiation. tperkins@ohri.ca Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Relationship of the Interaction Between Two Quantitative Trait Loci with γ-Globin Expression in β-Thalassemia Intermedia Patients.

Science.gov (United States)

NickAria, Shiva; Haghpanah, Sezaneh; Ramzi, Mani; Karimi, Mehran

2018-05-10

Globin switching is a significant factor on blood hemoglobin (Hb) level but its molecular mechanisms have not yet been identified, however, several quantitative trait loci (QTL) and polymorphisms involved regions on chromosomes 2p, 6q, 8q and X account for variation in the γ-globin expression level. We studied the effect of interaction between a region on intron six of the TOX gene, chromosome 8q (chr8q) and XmnI locus on the γ-globin promoter, chr11p on γ-globin expression in 150 β-thalassemia intermedia (β-TI) patients, evaluated by statistical interaction analysis. Our results showed a significant interaction between one QTL on intron six of the TOX gene (rs9693712) and XmnI locus that effect γ-globin expression. Interchromosomal interaction mediates through transcriptional machanisms to preserve true genome architectural features, chromosomes localization and DNA bending. This interaction can be a part of the unknown molecular mechanism of globin switching and regulation of gene expression.

Broodyear Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Data is collected by broodyear on % survival to adult, % maturity as two...

WellReader: a MATLAB program for the analysis of fluorescence and luminescence reporter gene data.

Science.gov (United States)

Boyer, Frédéric; Besson, Bruno; Baptist, Guillaume; Izard, Jérôme; Pinel, Corinne; Ropers, Delphine; Geiselmann, Johannes; de Jong, Hidde

2010-05-01

Fluorescent and luminescent reporter gene systems in combination with automated microplate readers allow real-time monitoring of gene expression on the population level at high precision and sampling density. This generates large amounts of data for the analysis of which computer tools are missing to date. We have developed WellReader, a MATLAB program for the analysis of fluorescent and luminescent reporter gene data. WellReader allows the user to load the output files of microplate readers, remove outliers, correct for background effects and smooth and fit the data. Moreover, it computes biologically relevant quantities from the measured signals, notably promoter activities and protein concentrations, and compares the resulting expression profiles of different genes under different conditions. WellReader is available under a LGPL licence at http://prabi1.inrialpes.fr/trac/wellreader.

75 FR 9918 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-0006...

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2010-03-04

... Insurance Program Policy Forms AGENCY: Federal Emergency Management Agency, DHS. ACTION: Notice; 60-day... Endorsement; FEMA Form 086-0-5, Flood Insurance Preferred Risk Policy Application; FEMA Form 086-0-4, V-Zone... Program Policy Forms. Type of Information Collection: Extension, without change, of a currently approved...

Bibliography of publications prepared by US Geological Survey personnel under cooperative programs with the US Department of Energy and predecessor agencies, 1957--1991, with emphasis on nuclear testing programs

International Nuclear Information System (INIS)

Glanzman, V.M.

1992-01-01

The US Geological Survey has participated in continuing studies related to nuclear energy in cooperation with the US Department of Energy and predecessor agencies since the 1940's. Geologic, geophysical and hydrologic studies have been conducted to aid in mineral exploration; in support of the nuclear weapons testing programs at the Nevada Test Site and several other locations; in support of the Plowshare Program for peaceful uses of nuclear explosions; and in the search for potential radioactive waste disposal sites. This bibliography contains alphabetical listings of 850 publications and 95 additional abstracts related to these investigations from 1957 through 1991, and contains an extensive index based on title-subject keywords

Suppression of Virulence of Toxigenic Vibrio cholerae by Anethole through the Cyclic AMP (cAMP-cAMP Receptor Protein Signaling System.

Directory of Open Access Journals (Sweden)

M Shamim Hasan Zahid

Full Text Available Use of natural compounds as antivirulence drugs could be an alternative therapeutic approach to modify the outcome of bacterial infections, particularly in view of growing resistance to available antimicrobials. Here, we show that sub-bactericidal concentration of anethole, a component of sweet fennel seed, could suppress virulence potential in O1 El Tor biotype strains of toxigenic Vibrio cholerae, the causative agent of the ongoing 7th cholera pandemic. The expression of cholera toxin (CT and toxin coregulated pilus (TCP, the major virulence factors of V. cholerae, is controlled through a regulatory cascade involving activation of ToxT with synergistic coupling interaction of ToxR/ToxS with TcpP/TcpH. We present evidence that anethole inhibits in vitro expression of CT and TCP in a toxT-dependent but toxR/toxS-independent manner and through repression of tcpP/tcpH, by using bead-ELISA, western blotting and quantitative real-time RT-PCR assays. The cyclic AMP (cAMP-cAMP receptor protein (CRP is a well-studied global signaling system in bacterial pathogens, and this complex is known to suppress expression of tcpP/tcpH in V. cholerae. We find that anethole influences the virulence regulatory cascade by over-expressing cyaA and crp genes. Moreover, suppression of toxigenic V. cholerae-mediated fluid accumulation in ligated ileum of rabbit by anethole demonstrates its potentiality as an antivirulence drug candidate against the diseases caused by toxigenic V. cholerae. Taken altogether, these results revealing a mechanism of virulence inhibition in V. cholerae by the natural compound anethole, may have relevance in designing antivirulence compounds, particularly against multiple antibiotic resistant bacterial pathogens.

Suppression of Virulence of Toxigenic Vibrio cholerae by Anethole through the Cyclic AMP (cAMP)-cAMP Receptor Protein Signaling System.

Science.gov (United States)

Zahid, M Shamim Hasan; Awasthi, Sharda Prasad; Asakura, Masahiro; Chatterjee, Shruti; Hinenoya, Atsushi; Faruque, Shah M; Yamasaki, Shinji

2015-01-01

Use of natural compounds as antivirulence drugs could be an alternative therapeutic approach to modify the outcome of bacterial infections, particularly in view of growing resistance to available antimicrobials. Here, we show that sub-bactericidal concentration of anethole, a component of sweet fennel seed, could suppress virulence potential in O1 El Tor biotype strains of toxigenic Vibrio cholerae, the causative agent of the ongoing 7th cholera pandemic. The expression of cholera toxin (CT) and toxin coregulated pilus (TCP), the major virulence factors of V. cholerae, is controlled through a regulatory cascade involving activation of ToxT with synergistic coupling interaction of ToxR/ToxS with TcpP/TcpH. We present evidence that anethole inhibits in vitro expression of CT and TCP in a toxT-dependent but toxR/toxS-independent manner and through repression of tcpP/tcpH, by using bead-ELISA, western blotting and quantitative real-time RT-PCR assays. The cyclic AMP (cAMP)-cAMP receptor protein (CRP) is a well-studied global signaling system in bacterial pathogens, and this complex is known to suppress expression of tcpP/tcpH in V. cholerae. We find that anethole influences the virulence regulatory cascade by over-expressing cyaA and crp genes. Moreover, suppression of toxigenic V. cholerae-mediated fluid accumulation in ligated ileum of rabbit by anethole demonstrates its potentiality as an antivirulence drug candidate against the diseases caused by toxigenic V. cholerae. Taken altogether, these results revealing a mechanism of virulence inhibition in V. cholerae by the natural compound anethole, may have relevance in designing antivirulence compounds, particularly against multiple antibiotic resistant bacterial pathogens.

75 FR 56501 - Information Collection; Land Management Agency Volunteer Surveys

Science.gov (United States)

2010-09-16

... Information Collection; Land Management Agency Volunteer Surveys AGENCY: Forest Service, USDA. ACTION: Notice... and test models of volunteer management; supply information to LMA program managers and other... is seeking comments from all interested individuals and organizations on the new information...

Predicting_Systemic_Toxicity_Effects_ArchTox_2017_Data

Data.gov (United States)

U.S. Environmental Protection Agency — In an effort to address a major challenge in chemical safety assessment, alternative approaches for characterizing systemic effect levels, a predictive model was...

7 CFR 249.13 - Program income.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Program income. 249.13 Section 249.13 Agriculture....13 Program income. Program income means gross income the State agency earns from grant supported... property. The State agency must retain Program income earned during the agreement period and use it for...

Growth Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. The fork length to the nearest mm and weight to the nearest gram of a...

Activity profiles of 309 ToxCastTM chemicals evaluated across 292 biochemical targets

International Nuclear Information System (INIS)

Knudsen, Thomas B.; Houck, Keith A.; Sipes, Nisha S.; Singh, Amar V.; Judson, Richard S.; Martin, Matthew T.; Weissman, Arthur; Kleinstreuer, Nicole C.; Mortensen, Holly M.; Reif, David M.; Rabinowitz, James R.; Setzer, R. Woodrow; Richard, Ann M.; Dix, David J.; Kavlock, Robert J.

2011-01-01

Understanding the potential health risks posed by environmental chemicals is a significant challenge elevated by the large number of diverse chemicals with generally uncharacterized exposures, mechanisms, and toxicities. The present study is a performance evaluation and critical analysis of assay results for an array of 292 high-throughput cell-free assays aimed at preliminary toxicity evaluation of 320 environmental chemicals in EPA's ToxCast TM project (Phase I). The chemicals (309 unique, 11 replicates) were mainly precursors or the active agent of commercial pesticides, for which a wealth of in vivo toxicity data is available. Biochemical HTS (high-throughput screening) profiled cell and tissue extracts using semi-automated biochemical and pharmacological methodologies to evaluate a subset of G-protein coupled receptors (GPCRs), CYP450 enzymes (CYPs), kinases, phosphatases, proteases, HDACs, nuclear receptors, ion channels, and transporters. The primary screen tested all chemicals at a relatively high concentration 25 μM concentration (or 10 μM for CYP assays), and a secondary screen re-tested 9132 chemical-assay pairs in 8-point concentration series from 0.023 to 50 μM (or 0.009-20 μM for CYPs). Mapping relationships across 93,440 chemical-assay pairs based on half-maximal activity concentration (AC50) revealed both known and novel targets in signaling and metabolic pathways. The primary dataset, summary data and details on quality control checks are available for download at (http://www.epa.gov/ncct/toxcast/).

42 CFR 431.18 - Availability of agency program manuals.

Science.gov (United States)

2010-10-01

... its current rules and policies to— (1) Public and university libraries; (2) The local or district... rules and policies by individuals outside the State Medicaid agency. (b) State plan requirements. A..., copies of its current rules and policies that affect the public, including those that govern eligibility...

7 CFR 246.6 - Agreements with local agencies.

Science.gov (United States)

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Agreements with local agencies. 246.6 Section 246.6 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS AND CHILDREN...

Maine Migrant Program: 1997-1998 Program Evaluation.

Science.gov (United States)

Bazinet, Suzanne C., Ed.

The Maine Department of Education contracts with local educational agencies to administer the Maine Migrant Education Program. The program's overall mission is to provide the support necessary for migrant children to achieve Maine's academic standards. In 1997-98, 73 local migrant programs served 9,838 students, and 63 summer programs served 1,769…

Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

Directory of Open Access Journals (Sweden)

Xin Sun

2018-01-01

Full Text Available How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3 encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD. In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.

Creating Spaces for Children's Agency: "I Wonder…" Formulations in Teacher-Child Interactions

Science.gov (United States)

Houen, Sandy; Danby, Susan; Farrell, Ann; Thorpe, Karen

2016-01-01

Affording children's agency is an important pedagogical underpinning of a high-quality early childhood program. Yet little is known about how teachers' interactions create spaces for children's agency. From the perspectives of ethnomethodology and conversation analysis, this paper investigates how teachers and children navigate agency through…

78 FR 9711 - Agency Information Collection Activities; Submission for OMB Review; Comment Request: Crisis...

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2013-02-11

... Request: Crisis Counseling Assistance and Training Program AGENCY: Federal Emergency Management Agency.... FEMA has codified Section 416 of the Stafford Act at section 44 CFR 206.171 entitled Crisis Counseling... coordinate with FEMA in administering the Crisis Counseling Assistance and Training Program (CCP). FEMA and...

77 FR 19303 - Agency Information Collection Activities: Submission for OMB Review; Comment Request, Application...

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2012-03-30

...--Collateral Security, FEMA Form 085-0-1, 10 hours; Application for Community Disaster Loan, FEMA Form 090-0-2... Request, Application for Community Disaster Loan (CDL) Program AGENCY: Federal Emergency Management Agency... Title: Application for Community Disaster Loan (CDL) Program. Type of information collection: Extension...

Sex-specific mouse liver gene expression: genome-wide analysis of developmental changes from pre-pubertal period to young adulthood

Directory of Open Access Journals (Sweden)

Conforto Tara L

2012-04-01

Full Text Available Abstract Background Early liver development and the transcriptional transitions during hepatogenesis are well characterized. However, gene expression changes during the late postnatal/pre-pubertal to young adulthood period are less well understood, especially with regards to sex-specific gene expression. Methods Microarray analysis of male and female mouse liver was carried out at 3, 4, and 8 wk of age to elucidate developmental changes in gene expression from the late postnatal/pre-pubertal period to young adulthood. Results A large number of sex-biased and sex-independent genes showed significant changes during this developmental period. Notably, sex-independent genes involved in cell cycle, chromosome condensation, and DNA replication were down regulated from 3 wk to 8 wk, while genes associated with metal ion binding, ion transport and kinase activity were up regulated. A majority of genes showing sex differential expression in adult liver did not display sex differences prior to puberty, at which time extensive changes in sex-specific gene expression were seen, primarily in males. Thus, in male liver, 76% of male-specific genes were up regulated and 47% of female-specific genes were down regulated from 3 to 8 wk of age, whereas in female liver 67% of sex-specific genes showed no significant change in expression. In both sexes, genes up regulated from 3 to 8 wk were significantly enriched (p p Ihh; female-specific Cdx4, Cux2, Tox, and Trim24 and may contribute to the developmental changes that lead to global acquisition of liver sex-specificity by 8 wk of age. Conclusions Overall, the observed changes in gene expression during postnatal liver development reflect the deceleration of liver growth and the induction of specialized liver functions, with widespread changes in sex-specific gene expression primarily occurring in male liver.

Inspector General, DoD, Oversight of the Army Audit Agency Audit of the U.S. Army Corps of Engineers, Civil Works Program, FY 1996 Financial Statements

National Research Council Canada - National Science Library

Lane, F

1997-01-01

The audit objective was to determine the accuracy and completeness of the audit of the U.S. Army Corps of Engineers, Civil Works Program, FY 1996, financial statements conducted by the Army Audit Agency...

Comparing the Medicaid Retrospective Drug Utilization Review Program Cost-Savings Methods Used by State Agencies.

Science.gov (United States)

Prada, Sergio I

2017-12-01

The Medicaid Drug Utilization Review (DUR) program is a 2-phase process conducted by Medicaid state agencies. The first phase is a prospective DUR and involves electronically monitoring prescription drug claims to identify prescription-related problems, such as therapeutic duplication, contraindications, incorrect dosage, or duration of treatment. The second phase is a retrospective DUR and involves ongoing and periodic examinations of claims data to identify patterns of fraud, abuse, underutilization, drug-drug interaction, or medically unnecessary care, implementing corrective actions when needed. The Centers for Medicare & Medicaid Services requires each state to measure prescription drug cost-savings generated from its DUR programs on an annual basis, but it provides no guidance or unified methodology for doing so. To describe and synthesize the methodologies used by states to measure cost-savings using their Medicaid retrospective DUR program in federal fiscal years 2014 and 2015. For each state, the cost-savings methodologies included in the Medicaid DUR 2014 and 2015 reports were downloaded from Medicaid's website. The reports were then reviewed and synthesized. Methods described by the states were classified according to research designs often described in evaluation textbooks. In 2014, the most often used prescription drugs cost-savings estimation methodology for the Medicaid retrospective DUR program was a simple pre-post intervention method, without a comparison group (ie, 12 states). In 2015, the most common methodology used was a pre-post intervention method, with a comparison group (ie, 14 states). Comparisons of savings attributed to the program among states are still unreliable, because of a lack of a common methodology available for measuring cost-savings. There is great variation among states in the methods used to measure prescription drug utilization cost-savings. This analysis suggests that there is still room for improvement in terms of

Fish Culture Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. Raw data on rearing density, loading density, water temperature, ration,...

78 FR 26033 - Agency Forms Undergoing Paperwork Reduction Act Review

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2013-05-03

... precision requirements or power calculations that justify the proposed sample size, the expected response... Collection of Qualitative Feedback on Agency Service Delivery--NEW--Epidemiology and Analysis Program Office... Clearance for the Collection of Qualitative Feedback on Agency Service Delivery'' to OMB for approval under...

45 CFR 2523.110 - Can Federal agencies submit multiple applications?

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2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Can Federal agencies submit multiple applications? 2523.110 Section 2523.110 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION... AMERICORPS PROGRAM ASSISTANCE § 2523.110 Can Federal agencies submit multiple applications? No. The...

National Association of Area Agencies on Aging

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National Association of Area Agencies on Aging Search Member Login Forgot Password? Menu ABOUT n4a Mission, Vision & Work AAAs & Title VI Aging Programs Membership Board of Directors Staff Contact ...

Comparative transcriptional profiling of the axolotl limb identifies a tripartite regeneration-specific gene program.

Directory of Open Access Journals (Sweden)

Dunja Knapp

Full Text Available Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression - early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation.

RESTORATION PLUS: A COLLABORATIVE ENVIRONMENTAL PROTECTION AGENCY RESEARCH PROGRAM TO DEVELOP AND EVALUATE ECOSYSTEM RESTORATION AND MANAGEMENT OPTIONS TO ACHIEVE ECOLOGICALLY AND ECONOMICALLY SUSTAINABLE SOLUTIONS

Science.gov (United States)

The U.S. Environmental Protection Agency (U.S. EPA) is evaluating ecosystem restoration and management techniques to ensure they create sustainable solutions for degraded watersheds. The ORD/NRMRL initiated the Restoration Plus (RePlus) program in 2002, which emphasizes collabora...

5 CFR 362.206 - Movement between departments or agencies.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Movement between departments or agencies. 362.206 Section 362.206 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PRESIDENTIAL MANAGEMENT FELLOWS PROGRAM Program Administration § 362.206 Movement between...

Multiscale Systems Modeling of Male Reproductive Tract Defects: from Genes to Populations (SOT)

Science.gov (United States)

The reproductive tract is a complex, integrated organ system with diverse embryology and unique sensitivity to prenatal environmental exposures that disrupt morphoregulatory processes and endocrine signaling. U.S. EPA’s in vitro high-throughput screening (HTS) database (ToxCastDB...

Exploring the effect of organizational culture on consumer perceptions of agency support for mental health recovery.

Science.gov (United States)

Clossey, Laurene; Rheinheimer, David

2014-05-01

This research explores the impact of mental health agency culture on consumers' perceptions of agency support for their recovery. This study hypothesized that a constructive organizational culture must be present for consumers to perceive agency support for recovery. A sample of 12 mental health agencies in rural Pennsylvania participated in the research. Agency administrators completed an instrument called the recovery oriented service environment, which measured the number of recovery model program components offered by the agency. Consumers completed the recovery oriented services indicators, which taps into their perception of agency support for recovery. Direct service staff completed the organizational social context, which measured their agency's culture. Results showed that in this sample stronger consumer perceptions of agency support for recovery were correlated with higher ratings of agency constructive culture. The results suggest that agency culture is an important variable to target when implementing recovery model programming.

77 FR 3837 - Proposed Agency Information Collection Activities; Comment Request

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2012-01-25

... agency adequate time to digest public comments before it renders a decision. 60 FR 44983, Aug. 29, 1995... Rehabilitation and Improvement Financing Program. OMB Control Number: 2130-0548. Type of Request: Revision of a... Railroad Rehabilitation and Improvement Financing (``RRIF Program''). Under the RRIF program, direct loans...

Identification of Chemical Features Linked to Thyroperoxidase Inhibition (SOT)

Science.gov (United States)

Disruption of maternal serum thyroid hormone (TH) adversely affects fetal neurodevelopment. Therefore, assay development within the US EPA ToxCast program is ongoing to enable screening for chemicals that may disrupt TH, in support of the Endocrine Disruption Screening Program (E...

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

Science.gov (United States)

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits. PMID:22536398

Effects of Metabolic Programming on Juvenile Play Behavior and Gene Expression in the Prefrontal Cortex of Rats.

Science.gov (United States)

Hehar, Harleen; Ma, Irene; Mychasiuk, Richelle

2016-01-01

Early developmental processes, such as metabolic programming, can provide cues to an organism, which allow it to make modifications that are predicted to be beneficial for survival. Similarly, social play has a multifaceted role in promoting survival and fitness of animals. Play is a complex behavior that is greatly influenced by motivational and reward circuits, as well as the energy reserves and metabolism of an organism. This study examined the association between metabolic programming and juvenile play behavior in an effort to further elucidate insight into the consequences that early adaptions have on developmental trajectories. The study also examined changes in expression of four genes (Drd2, IGF1, Opa1, and OxyR) in the prefrontal cortex known to play significant roles in reward, bioenergetics, and social-emotional functioning. Using four distinct variations in developmental programming (high-fat diet, caloric restriction, exercise, or high-fat diet combined with exercise), we found that dietary programming (high-fat diet vs. caloric restriction) had the greatest impact on play behavior and gene expression. However, exercise also induced changes in both measures. This study demonstrates that metabolic programming can alter neural circuits and bioenergetics involved in play behavior, thus providing new insights into mechanisms that allow programming to influence the evolutionary success of an organism. © 2016 S. Karger AG, Basel.

75 FR 32199 - Agency Information Collection Activities: Submission for OMB Review; Comment Request, OMB No...

Science.gov (United States)

2010-06-07

...; National Flood Insurance Program Policy Forms AGENCY: Federal Emergency Management Agency, DHS. ACTION... Change Endorsement; FEMA Form 086-0-5, Flood Insurance Preferred Risk Policy Application; FEMA Form 086-0...: Collection of Information Title: National Flood Insurance Program Policy Forms. Type of information...

Genetic Toxicology in the 21st Century: Reflections and Future Directions

Science.gov (United States)

Mahadevan, Brinda; Snyder, Ronald D.; Waters, Michael D.; Benz, R. Daniel; Kemper, Raymond A.; Tice, Raymond R.; Richard, Ann M.

2011-01-01

A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24–28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U.S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast™, a related research program of the U.S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. PMID:21538556

Fish Health Data - Captive Broodstock Gene Rescue Program for Odd Year Class Elwha River Pink Salmon

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Conduct captive brood stock gene rescue program for Elwha River odd-year class pink salmon. All fresh mortalities larger than 100 mm are sent to Fish Health for...

75 FR 43944 - Membership of the Defense Logistics Agency (DLA) Senior Executive Service (SES) Performance...

Science.gov (United States)

2010-07-27

... CONTACT: Ms. Lisa Novajosky, SES Program Manager, DLA Human Resources (J-14), Defense Logistics Agency... DEPARTMENT OF DEFENSE Defense Logistics Agency Membership of the Defense Logistics Agency (DLA... management of the SES cadre. DATES: Effective Date: September 16, 2010. ADDRESSES: Defense Logistics Agency...

Court-agency interaction in environmental policymaking: the cases of the Nuclear Regulatory Commission and the Environmental Protection Agency

International Nuclear Information System (INIS)

Thomas, L.W.

1981-01-01

This study examines the increasingly active participation of courts in the administrative process as well as agency responses to court-imposed policy shifts. More specifically, it is an investigation of the interaction between the federal courts, primarily the Supreme Court and the District of Columbia Court of Appeals, and two federal regulatory agencies, the Nuclar Regulatory Commission and the Environmental Protection Agency. There are five objectives to the study. The first is to examine the natura of court-agency interaction and to determine the extent to which patterns of judicial review of administrative actions can be discerned. The second is to examine the effect of court orders on agency programs and policies. The third is to assess the anticipatory dimension of court-agency relations. The fourth is to inquire into the recurring dimension of court-agency interaction and to determine its effect on subsequent court decisions. The last is to assess the institutional capacity of courts to deal with scientific and technological issues. This study indicates that judicial review has a substantial effect on the NRC's and the EPA's decision-making activities. Few, if any, recent major policy decisions of the two agencies have not been scrutinized closely by federal appellate courts. During the past decade, the courts have blocked policy initiative on numerous occasions and have been the primary source of change in others. In addition, the mere anticipation of judicial review was found to be a factor motivating the two agencies to make reasoned decisions

The combined SPE:ToxY-PAM phytotoxicity assay; application and appraisal of a novel biomonitoring tool for the aquatic environment.

Science.gov (United States)

Bengtson Nash, S M; Schreiber, U; Ralph, P J; Müller, J F

2005-01-15

Mounting concerns regarding the environmental impact of herbicides has meant a growing requirement for accurate, timely information regarding herbicide residue contamination of, in particular, aquatic systems. Conventional methods of detection remain limited in terms of practicality due to high costs of operation and the specialised information that analysis provides. A new phytotoxicity bioassay was trialled for the detection of herbicide residues in filter-purified (Milli-Q) as well as natural waters. The performance of the system, which combines solid-phase extraction (SPE) with the ToxY-PAM dual-channel yield analyser (Heinz Walz GmbH), was tested alongside the traditional method of liquid chromatography-mass spectrometry (LC-MS). The assay methodology was found to be highly sensitive (LOD 0.1 ng L(-1) diuron) with good reproducibility. The study showed that the assay protocol is time effective and can be employed for the aquatic screening of herbicide residues in purified as well as natural waters.

Induction of a program gene expression during osteoblast differentiation with strontium ranelate

International Nuclear Information System (INIS)

Zhu Lingling; Zaidi, Samir; Peng Yuanzhen; Zhou Hang; Moonga, Baljit S.; Blesius, Alexia; Dupin-Roger, Isabelle; Zaidi, Mone; Sun Li

2007-01-01

Strontium ranelate, a new agent for the treatment of osteoporosis, has been shown stimulate bone formation in various experimental models. This study examines the effect of strontium ranelate on gene expression in osteoblasts, as well as the formation of mineralized (von Kossa-positive) colony-forming unit-osteoblasts (CFU-obs). Bone marrow-derived stromal cells cultured for 21 days under differentiating conditions, when exposed to strontium ranelate, displayed a significant time- and concentration-dependent increase in the expression of the master gene, Runx2, as well as bone sialoprotein (BSP), but interestingly without effects on osteocalcin. This was associated with a significant increase in the formation of CFU-obs at day 21 of culture. In U-33 pre-osteoblastic cells, strontium ranelate significantly enhanced the expression of Runx2 and osteocalcin, but not BSP. Late, more mature osteoblastic OB-6 cells showed significant elevations in BSP and osteocalcin, but with only minimal effects on Runx2. In conclusion, strontium ranelate stimulates osteoblast differentiation, but the induction of the program of gene expression appears to be cell type-specific. The increased osteoblastic differentiation is the likely basis underlying the therapeutic bone-forming actions of strontium ranelate

Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

DEFF Research Database (Denmark)

Hakim-Weber, Robab; Krogsdam, Anne-M; Jørgensen, Claus

2011-01-01

Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate...... this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs...... of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis...

75 FR 34093 - Information Collection; General Program Administration

Science.gov (United States)

2010-06-16

... Administration AGENCY: Farm Service Agency, USDA. ACTION: Notice; request for comments. SUMMARY: In accordance... supports Farm Loan Programs (FLP) for the General Program Administration. DATES: We will consider comments.... SUPPLEMENTARY INFORMATION: Title: Farm Loan Programs--General Program Administration (7 CFR part 761). OMB...

Clinical significance of combined detection of multiple serum antibodies (AsAb, EmAb, AcAb, AoAb, ToxAb) in infertile women

International Nuclear Information System (INIS)

Chen Jing; Jiang Li; Lu Ya

2005-01-01

Objective: To determine the clinical significance of combined detection of multiple serum antibodies in infertile women. Methods; Serum multiple antibodies were examined in 120 infertile women, including 88 failed to get pregnancy and 32 with repeated spontaneous abortion. The antibodies tested were: (1) anti-sperm antibody (AsAb) (2) endometrial antibody (EmAb) (3) anti-cardiophospholipid antibody (AcAb) (4) Anti-ovarian antibody (AoAb) and Toxoplasmosis antibody (ToxAb). Results: In 48 of the infertile women, none of the five antibodies were positive (40% of 120). The rest were: one antibody positive--38/120 or 31.6%; two antibodies positive--31/120 or 25.83%, three and four antibodies positive--4/120 or 3.33%. None of the women were positive with all five antibodies. Conclusion: Immune factor was the chief cause of infertility in women. (authors)

75 FR 58468 - Terrorism Risk Insurance Program; Program Loss Reporting

Science.gov (United States)

2010-09-24

... DEPARTMENT OF THE TREASURY Terrorism Risk Insurance Program; Program Loss Reporting AGENCY: Departmental Offices, Terrorism Risk Insurance Program Office, Treasury. ACTION: Notice and request for... 1995, Public Law 104-13 (44 U.S.C. 3506(c)(2)(A)). Currently, the Terrorism Risk Insurance Program...

The immediate early gene product EGR1 and polycomb group proteins interact in epigenetic programming during chondrogenesis.

Directory of Open Access Journals (Sweden)

Frank Spaapen

Full Text Available Initiation of and progression through chondrogenesis is driven by changes in the cellular microenvironment. At the onset of chondrogenesis, resting mesenchymal stem cells are mobilized in vivo and a complex, step-wise chondrogenic differentiation program is initiated. Differentiation requires coordinated transcriptomic reprogramming and increased progenitor proliferation; both processes require chromatin remodeling. The nature of early molecular responses that relay differentiation signals to chromatin is poorly understood. We here show that immediate early genes are rapidly and transiently induced in response to differentiation stimuli in vitro. Functional ablation of the immediate early factor EGR1 severely deregulates expression of key chondrogenic control genes at the onset of differentiation. In addition, differentiating cells accumulate DNA damage, activate a DNA damage response and undergo a cell cycle arrest and prevent differentiation associated hyper-proliferation. Failed differentiation in the absence of EGR1 affects global acetylation and terminates in overall histone hypermethylation. We report novel molecular connections between EGR1 and Polycomb Group function: Polycomb associated histone H3 lysine27 trimethylation (H3K27me3 blocks chromatin access of EGR1. In addition, EGR1 ablation results in abnormal Ezh2 and Bmi1 expression. Consistent with this functional interaction, we identify a number of co-regulated targets genes in a chondrogenic gene network. We here describe an important role for EGR1 in early chondrogenic epigenetic programming to accommodate early gene-environment interactions in chondrogenesis.

Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization

Directory of Open Access Journals (Sweden)

McDonald Karen

2011-08-01

Full Text Available Abstract Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.

Myeloid translocation genes differentially regulate colorectal cancer programs

Science.gov (United States)

Parang, Bobak; Bradley, Amber M.; Mittal, Mukul K.; Short, Sarah P.; Thompson, Joshua J.; Barrett, Caitlyn W.; Naik, Rishi D.; Bilotta, Anthony J.; Washington, Mary K.; Revetta, Frank L.; Smith, Jesse J.; Chen, Xi; Wilson, Keith T.; Hiebert, Scott W.; Williams, Christopher S.

2016-01-01

Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1−/− mice have progressive depletion of all intestinal secretory cells, and Mtg16−/− mice have a decrease in goblet cells. Furthermore, both Mtgr1−/− and Mtg16−/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1−/− mice, but not Mtg16−/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1−/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis. PMID:27270437

StrateGene: object-oriented programming in molecular biology.

Science.gov (United States)

Carhart, R E; Cash, H D; Moore, J F

1988-03-01

This paper describes some of the ways that object-oriented programming methodologies have been used to represent and manipulate biological information in a working application. When running on a Xerox 1100 series computer, StrateGene functions as a genetic engineering workstation for the management of information about cloning experiments. It represents biological molecules, enzymes, fragments, and methods as classes, subclasses, and members in a hierarchy of objects. These objects may have various attributes, which themselves can be defined and classified. The attributes and their values can be passed from the classes of objects down to the subclasses and members. The user can modify the objects and their attributes while using them. New knowledge and changes to the system can be incorporated relatively easily. The operations on the biological objects are associated with the objects themselves. This makes it easier to invoke them correctly and allows generic operations to be customized for the particular object.

36 CFR 1226.20 - How do agencies temporarily extend retention periods?

Science.gov (United States)

2010-07-01

... AND RECORDS ADMINISTRATION RECORDS MANAGEMENT IMPLEMENTING DISPOSITION § 1226.20 How do agencies... Records Administration, Modern Records Programs (NWM), 8601 Adelphi Road, College Park, MD 20740-6001... of time that the records will be required; and (4) For records in the agency's custody, a statement...

43 CFR 20.202 - Ethics program responsibilities.

Science.gov (United States)

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Ethics program responsibilities. 20.202... AND CONDUCT Department Ethics Program § 20.202 Ethics program responsibilities. (a) The Designated Agency Ethics Official (or the alternate agency ethics official in his or her absence) shall coordinate...

Parallelizing Gene Expression Programming Algorithm in Enabling Large-Scale Classification

Directory of Open Access Journals (Sweden)

Lixiong Xu

2017-01-01

Full Text Available As one of the most effective function mining algorithms, Gene Expression Programming (GEP algorithm has been widely used in classification, pattern recognition, prediction, and other research fields. Based on the self-evolution, GEP is able to mine an optimal function for dealing with further complicated tasks. However, in big data researches, GEP encounters low efficiency issue due to its long time mining processes. To improve the efficiency of GEP in big data researches especially for processing large-scale classification tasks, this paper presents a parallelized GEP algorithm using MapReduce computing model. The experimental results show that the presented algorithm is scalable and efficient for processing large-scale classification tasks.

77 FR 50718 - Agency Information Collection Activities: Proposed Collection; Comments Requested: Accounting...

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2012-08-22

... DEPARTMENT OF JUSTICE Office of Justice Programs [OMB Number 1121-0021] Agency Information Collection Activities: Proposed Collection; Comments Requested: Accounting System and Financial Capability...: Accounting System and Financial Capability Questionnaire. (3) Agency form number 7120/1. Component Sponsoring...

78 FR 47676 - Agency Information Collection Activities; Comment Request; National Professional Development...

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2013-08-06

... DEPARTMENT OF EDUCATION [Docket No. ED-2013-ICCD-0100] Agency Information Collection Activities; Comment Request; National Professional Development Program: Grantee Performance Report AGENCY: Office of English Language Acquisition (OLEA), Department of Education (ED). ACTION: Notice. SUMMARY: In accordance...

76 FR 51970 - Agency Information Collection Activities; Proposed Collection; Comment Request; Underground...

Science.gov (United States)

2011-08-19

... Underground Injection Control (UIC) Program under the Safe Drinking Water Act established a Federal and State... Activities; Proposed Collection; Comment Request; Underground Injection Control (UIC) Program AGENCY... Water Protection Division/Underground Injection Control Program, Mailcode: 4606M, Environmental...

Flate-plate photovoltaic power systems handbook for Federal agencies

Science.gov (United States)

Cochrane, E. H.; Lawson, A. C.; Savage, C. H.

1984-01-01

The primary purpose is to provide a tool for personnel in Federal agencies to evaluate the viability of potential photovoltaic applications. A second objective is to provide descriptions of various photovoltaic systems installed by different Federal agencies under the Federal Photovoltaic Utilization Program so that other agencies may consider similar applications. A third objective is to share lessons learned to enable more effective procurement, design, installation, and operation of future photovoltaic systems. The intent is not to provide a complete handbook, but rather to provide a guide for Federal agency personnel with additional information incorporated by references. The steps to be followed in selecting, procuring, and installing a photovoltaic application are given.

42 CFR 1002.3 - Disclosure by providers and State Medicaid agencies.

Science.gov (United States)

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Disclosure by providers and State Medicaid agencies... HUMAN SERVICES OIG AUTHORITIES PROGRAM INTEGRITY-STATE-INITIATED EXCLUSIONS FROM MEDICAID General Provisions § 1002.3 Disclosure by providers and State Medicaid agencies. (a) Information that must be...

A High-Throughput Screening Assay to Detect Thyroperoxidase Inhibitors (Teratology Society)

Science.gov (United States)

In support of the Endocrine Disruption Screening Program (EDSP21), the US EPA ToxCast program is developing assays to enable screening for chemicals that may disrupt thyroid hormone synthesis. Thyroperoxidase (TPO) is critical for TH synthesis and is a known target of thyroid-dis...

75 FR 66116 - Agency Information Collection Activities: Proposed Collection; Comment Request, OMB No. 1660-NEW...

Science.gov (United States)

2010-10-27

...; Logistics Capability Assessment Tool (LCAT) AGENCY: Federal Emergency Management Agency, DHS. ACTION: Notice... FURTHER INFORMATION CONTACT: Nicole Kelsey, Program Analyst, Logistics Management Directorate, Logistics... DEPARTMENT OF HOMELAND SECURITY Federal Emergency Management Agency [Docket ID: FEMA-2010-0061...

Liver steatosis study_PFAA treated mouse gene array data

Data.gov (United States)

U.S. Environmental Protection Agency — This file contains a link for Gene Expression Omnibus and the GSE designations for the publicly available gene expression data used in the study and reflected in...

Accelerating Adverse Outcome Pathway (AOP) development ...

Science.gov (United States)

The Adverse Outcome Pathway (AOP) framework is increasingly being adopted as a tool for organizing and summarizing the mechanistic information connecting molecular perturbations by environmental stressors with adverse outcomes relevant for ecological and human health outcomes. However, the conventional process for assembly of these AOPs is time and resource intensive, and has been a rate limiting step for AOP use and development. Therefore computational approaches to accelerate the process need to be developed. We previously developed a method for generating computationally predicted AOPs (cpAOPs) by association mining and integration of data from publicly available databases. In this work, a cpAOP network of ~21,000 associations was established between 105 phenotypes from TG-GATEs rat liver data from different time points (including microarray, pathological effects and clinical chemistry data), 994 REACTOME pathways, 688 High-throughput assays from ToxCast and 194 chemicals. A second network of 128,536 associations was generated by connecting 255 biological target genes from ToxCast to 4,980 diseases from CTD using either HT screening activity from ToxCast for 286 chemicals or CTD gene expression changes in response to 2,330 chemicals. Both networks were separately evaluated through manual extraction of disease-specific cpAOPs and comparison with expert curation of the relevant literature. By employing data integration strategies that involve the weighting of n

Mercury and Your Health

Science.gov (United States)

... the Risk of Exposure to Mercury Learn About Mercury What is Mercury What is Metallic mercury? Toxicological Profile ToxFAQs Mercury Resources CDC’s National Biomonitoring Program Factsheet on Mercury ...

7 CFR 249.14 - Distribution of funds to State agencies.

Science.gov (United States)

2010-01-01

... Section 249.14 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS SENIOR FARMERS' MARKET NUTRITION PROGRAM... funds it receives. (h) Recovery of unused funds. State agencies must return to FNS any unexpended funds...

75 FR 81327 - Agency Information Collection Activity Under OMB Review

Science.gov (United States)

2010-12-27

... developing transportation plans and programs to serve the transportation needs of urbanized areas over 50,000... activities involved in developing the Unified Planning Work Program (UPWP), the Metropolitan Transportation... DEPARTMENT OF TRANSPORTATION Federal Transit Administration [FTA Docket No. FTA-2010-0048] Agency...

78 FR 40084 - Proposed Requirement-Migrant Education Program Consortium Incentive Grant Program

Science.gov (United States)

2013-07-03

... DEPARTMENT OF EDUCATION 34 CFR Chapter II Proposed Requirement--Migrant Education Program... educational agencies (SEAs) under the Migrant Education Program (MEP) Consortium Incentive Grant (CIG) Program... the interstate or intrastate coordination of migrant education programs by addressing key needs of...

Mechanism Profiling of Hepatotoxicity Caused by Oxidative Stress Using Antioxidant Response Element Reporter Gene Assay Models and Big Data.

Science.gov (United States)

Kim, Marlene Thai; Huang, Ruili; Sedykh, Alexander; Wang, Wenyi; Xia, Menghang; Zhu, Hao

2016-05-01

Hepatotoxicity accounts for a substantial number of drugs being withdrawn from the market. Using traditional animal models to detect hepatotoxicity is expensive and time-consuming. Alternative in vitro methods, in particular cell-based high-throughput screening (HTS) studies, have provided the research community with a large amount of data from toxicity assays. Among the various assays used to screen potential toxicants is the antioxidant response element beta lactamase reporter gene assay (ARE-bla), which identifies chemicals that have the potential to induce oxidative stress and was used to test > 10,000 compounds from the Tox21 program. The ARE-bla computational model and HTS data from a big data source (PubChem) were used to profile environmental and pharmaceutical compounds with hepatotoxicity data. Quantitative structure-activity relationship (QSAR) models were developed based on ARE-bla data. The models predicted the potential oxidative stress response for known liver toxicants when no ARE-bla data were available. Liver toxicants were used as probe compounds to search PubChem Bioassay and generate a response profile, which contained thousands of bioassays (> 10 million data points). By ranking the in vitro-in vivo correlations (IVIVCs), the most relevant bioassay(s) related to hepatotoxicity were identified. The liver toxicants profile contained the ARE-bla and relevant PubChem assays. Potential toxicophores for well-known toxicants were created by identifying chemical features that existed only in compounds with high IVIVCs. Profiling chemical IVIVCs created an opportunity to fully explore the source-to-outcome continuum of modern experimental toxicology using cheminformatics approaches and big data sources. Kim MT, Huang R, Sedykh A, Wang W, Xia M, Zhu H. 2016. Mechanism profiling of hepatotoxicity caused by oxidative stress using antioxidant response element reporter gene assay models and big data. Environ Health Perspect 124:634-641;�

Quality management as knowledge sharing: experiences of the Napa County Health and Human Services Agency.

Science.gov (United States)

Harrison, Lindsay

2012-01-01

Lacking a coordinated effort in utilizing data and tracking program outcomes, one agency developed a Quality Management (QM) division to facilitate and manage more effective data use. To support this process, the agency sought to develop a collective, agency-wide understanding and investment in improving and measuring client outcomes. Similarly, the agency also focused efforts on creating a culture of transparency and accountability, with goals of improving service, increasing agency integrity, meeting regulatory compliance, and engaging in effective risk management. Operationalizing the QM initiative involved developing procedures, systems, and guidelines that would facilitate the generation of reliable and accurate data that could be used to inform program change and decision-making. This case study describes this agency's experience in successfully creating and implementing a QM initiative aimed at engaging in greater knowledge sharing. Copyright © Taylor & Francis Group, LLC

International Geoscience Workforce Trends: More Challenges for Federal Agencies

Science.gov (United States)

Groat, C. G.

2005-12-01

Concern about the decreasing number of students entering undergraduate geoscience programs has been chronic and, at times, acute over the past three decades. Despite dwindling populations of undergraduate majors, graduate programs have remained relatively robust, bolstered by international students. With Increasing competition for graduate students by universities in Europe, Japan, Australia, and some developing countries, and with procedural challenges faced by international students seeking entry into the United States and its universities, this supply source is threatened. For corporations operating on a global scale, the opportunity to employ students from and trained in the regions in which they operate is generally a plus. For U.S. universities that have traditionally supplied this workforce, the changing situation poses challenges, but also opportunities for creative international partnerships. Federal government science agencies face more challenges than opportunities in meeting workforce needs under both present and changing education conditions. Restrictions on hiring non-U.S. citizens into the permanent workforce have been a long-standing issue for federal agencies. Exceptions are granted only where they can document the absence of eligible U.S.-citizen candidates. The U.S. Geological Survey has been successful in doing this in its Mendenhall Postdoctoral Research Fellowship Program, but there has been no solution to the broader limitation. Under current and forecast workforce recruitment conditions, creativity, such as that evidenced by the Mendenhall program,will be necessary if federal agencies are to draw from the increasingly international geoscience talent pool. With fewer U.S. citizens in U.S. geoscience graduate programs and a growing number of advanced-degreed scientists coming from universities outside the U.S., the need for changes in federal hiring policies is heightened. The near-term liklihood of this is low and combined with the decline in

Identification of reference genes for RT-qPCR in ovine mammary tissue during late pregnancy and lactation and in response to maternal nutritional programming.

Science.gov (United States)

Paten, A M; Pain, S J; Peterson, S W; Blair, H T; Kenyon, P R; Dearden, P K; Duncan, E J

2014-08-01

The mammary gland is a complex tissue consisting of multiple cell types which, over the lifetime of an animal, go through repeated cycles of development associated with pregnancy, lactation and involution. The mammary gland is also known to be sensitive to maternal programming by environmental stimuli such as nutrition. The molecular basis of these adaptations is of significant interest, but requires robust methods to measure gene expression. Reverse-transcription quantitative PCR (RT-qPCR) is commonly used to measure gene expression, and is currently the method of choice for validating genome-wide expression studies. RT-qPCR requires the selection of reference genes that are stably expressed over physiological states and treatments. In this study we identify suitable reference genes to normalize RT-qPCR data for the ovine mammary gland in two physiological states; late pregnancy and lactation. Biopsies were collected from offspring of ewes that had been subjected to different nutritional paradigms during pregnancy to examine effects of maternal programming on the mammary gland of the offspring. We evaluated eight candidate reference genes and found that two reference genes (PRPF3 and CUL1) are required for normalising RT-qPCR data from pooled RNA samples, but five reference genes are required for analyzing gene expression in individual animals (SENP2, EIF6, MRPL39, ATP1A1, CUL1). Using these stable reference genes, we showed that TET1, a key regulator of DNA methylation, is responsive to maternal programming and physiological state. The identification of these novel reference genes will be of utility to future studies of gene expression in the ovine mammary gland. Copyright © 2014 the American Physiological Society.

75 FR 6671 - Agency Forms Undergoing Paperwork Reduction Act Review

Science.gov (United States)

2010-02-10

... programs implemented a new consent form. This form asked participants for permission for CDC to contact...] Agency Forms Undergoing Paperwork Reduction Act Review The Centers for Disease Control and Prevention... prevention behaviors, CDC will conduct telephone interviews of 425 Matter of Balance program participants six...

Genome-Wide Comparative Gene Family Classification

Science.gov (United States)

Frech, Christian; Chen, Nansheng

2010-01-01

Correct classification of genes into gene families is important for understanding gene function and evolution. Although gene families of many species have been resolved both computationally and experimentally with high accuracy, gene family classification in most newly sequenced genomes has not been done with the same high standard. This project has been designed to develop a strategy to effectively and accurately classify gene families across genomes. We first examine and compare the performance of computer programs developed for automated gene family classification. We demonstrate that some programs, including the hierarchical average-linkage clustering algorithm MC-UPGMA and the popular Markov clustering algorithm TRIBE-MCL, can reconstruct manual curation of gene families accurately. However, their performance is highly sensitive to parameter setting, i.e. different gene families require different program parameters for correct resolution. To circumvent the problem of parameterization, we have developed a comparative strategy for gene family classification. This strategy takes advantage of existing curated gene families of reference species to find suitable parameters for classifying genes in related genomes. To demonstrate the effectiveness of this novel strategy, we use TRIBE-MCL to classify chemosensory and ABC transporter gene families in C. elegans and its four sister species. We conclude that fully automated programs can establish biologically accurate gene families if parameterized accordingly. Comparative gene family classification finds optimal parameters automatically, thus allowing rapid insights into gene families of newly sequenced species. PMID:20976221

76 FR 16598 - Agency Information Collection Activities: Proposed Collection; Comment Request-Supplemental...

Science.gov (United States)

2011-03-24

... States have reported as disqualified. One of the factors used by a State agency to determine the...: Proposed Collection; Comment Request--Supplemental Nutrition Assistance Program Repayment Demand and... Assistance Program Repayment Demand and Program Disqualification. OMB Number: 0584-0492. Form Number: None...

78 FR 54862 - Information Collection; General Program Administration

Science.gov (United States)

2013-09-06

... Administration AGENCY: Farm Service Agency, USDA. ACTION: Notice; request for comments. SUMMARY: In accordance... associated with FSA's Farm Loan Programs (FLP) General Program Administration. The information collected is... Program Administration. OMB Control Number: 0560-0238. Expiration Date of Approval: 02/28/2014. Type of...

General Conformity Training Module 2.5: Proactive Role for Federal Agencies

Science.gov (United States)

Module 2.5 explains how taking a proactive role will allow a federal agency to more effectively participate in newly promulgated programs under the General Conformity Regulations, such as the emission reduction credits and the emission budgets programs.

Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients

DEFF Research Database (Denmark)

Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan

2014-01-01

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients....

Radiation processing program at the Malaysian Nuclear Agency

International Nuclear Information System (INIS)

Khairul Zaman

2007-01-01

Radiation processing technology has been proven to enhance industrial efficiency and productivity, improve product quality and competitiveness. For many years, variety of radiation crosslinkable materials based on synthetic polymers have been studied at the Malaysian Nuclear Agency either in the form of thermoplastic resins, polymer blends or composites. At present, effort is focused towards developing new materials based on natural polymers such as natural rubber and rubber based products, palm oil and palm oil based products and polysaccharide. In this respect, the most challenging issues are to develop new materials/products that have commercial value and to bring the products from laboratory to market. (author)

75 FR 67751 - Medicare Program: Community-Based Care Transitions Program (CCTP) Meeting

Science.gov (United States)

2010-11-03

...] Medicare Program: Community-Based Care Transitions Program (CCTP) Meeting AGENCY: Centers for Medicare... guidance and ask questions about the upcoming Community-based Care Transitions Program. The meeting is open... conference will also provide an overview of the Community-based Care Transitions Program (CCTP) and provide...

77 FR 71605 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-12-03

... Hersh, Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville... Analytics Inc., NOVAMANN (Ontario), Inc.) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN...

77 FR 32653 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-06-01

... Hersh, Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville... Analytics Inc., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN...

40 CFR 255.32 - Coordination with other programs.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Coordination with other programs. 255.32 Section 255.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... Relationship to Other Programs § 255.32 Coordination with other programs. The region and agency identification...

41 CFR 102-118.60 - To what extent must my agency use electronic commerce?

Science.gov (United States)

2010-07-01

... agency use electronic commerce? 102-118.60 Section 102-118.60 Public Contracts and Property Management... Services § 102-118.60 To what extent must my agency use electronic commerce? Your agency must use electronic commerce in all areas of your transportation program. This includes the use of electronic systems...

Focus on Nutrition. MCH Program Interchange.

Science.gov (United States)

National Center for Education in Maternal and Child Health, Washington, DC.

This issue of the "MCH Program Interchange" describes selected materials and publications in maternal and child health (MCH) nutrition services and programs. The materials were developed by or are available from federal agencies, state and local public health agencies, and voluntary and professional organizations. The information is intended to…

Artificial Neural Networks and Gene Expression Programing based age estimation using facial features

Directory of Open Access Journals (Sweden)

Baddrud Z. Laskar

2015-10-01

Full Text Available This work is about estimating human age automatically through analysis of facial images. It has got a lot of real-world applications. Due to prompt advances in the fields of machine vision, facial image processing, and computer graphics, automatic age estimation via faces in computer is one of the dominant topics these days. This is due to widespread real-world applications, in areas of biometrics, security, surveillance, control, forensic art, entertainment, online customer management and support, along with cosmetology. As it is difficult to estimate the exact age, this system is to estimate a certain range of ages. Four sets of classifications have been used to differentiate a person’s data into one of the different age groups. The uniqueness about this study is the usage of two technologies i.e., Artificial Neural Networks (ANN and Gene Expression Programing (GEP to estimate the age and then compare the results. New methodologies like Gene Expression Programing (GEP have been explored here and significant results were found. The dataset has been developed to provide more efficient results by superior preprocessing methods. This proposed approach has been developed, tested and trained using both the methods. A public data set was used to test the system, FG-NET. The quality of the proposed system for age estimation using facial features is shown by broad experiments on the available database of FG-NET.

Analysis of the Education Program Approval Process: A Program Evaluation.

Science.gov (United States)

Fountaine, Charles A.; And Others

A study of the education program approval process involving the Veterans Administration (VA) and the State Approving Agencies (SAAs) had the following objectives: to describe the present education program approval process; to determine time and costs associated with the education program approval process; to describe the approval process at…

78 FR 77095 - Agency Information Collection Activities: Proposed Collection; Comment Request-Form FNS-648, WIC...

Science.gov (United States)

2013-12-20

... DEPARTMENT OF AGRICULTURE Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--Form FNS-648, WIC Local Agency Directory Report AGENCY: Food and... continuity of program services to migrant and other transient participants. It is also used as a mailing list...

41 CFR 102-192.125 - What is the appropriate managerial level for an agency mail manager?

Science.gov (United States)

2010-07-01

... managerial level for an agency mail manager? 102-192.125 Section 102-192.125 Public Contracts and Property... ADMINISTRATIVE PROGRAMS 192-MAIL MANAGEMENT Agency Mail Manager Requirements § 102-192.125 What is the appropriate managerial level for an agency mail manager? The agency mail manager should be at a managerial...

Consequences of increased extraction of forest fuel - A synthesis from the Energy Agency fuel program 2007-2011 Summary of the Synthesis Report; Konsekvenser av ett oekat uttag av skogsbraensle - En syntes fraan Energimyndighetens braensleprogram 2007-2011 Sammanfattning av syntesrapporten

Energy Technology Data Exchange (ETDEWEB)

NONE

2013-07-01

This report summarizes the findings of a research synthesis of forest fuels. The full report (de Jong et al 2012) can be ordered from the Swedish Energy Agency (report number: ER 2012:08), or downloaded from www.energimyndigheten.se. The Energy Agency's research program 'Sustainable supply and refining of biofuels', also known as 'Fuel program', ran from 2007-01-01 to 2011-06-30. The results of the program are reported in synthesis reports for various program areas. The purpose of the synthesis reports is to compile the knowledge in various areas, to identify knowledge gaps that need to be elucidated further, and to place and discuss the aggregated research results in a larger energy- and societal perspective, including relations to environmental quality and forest policy environmental- and production goals. This report covers sub-project 'Forest fuel and environmental impacts', conducted during the years 2007-2011. The report covers projects within the program 'Sustainable supply and refining of biofuels', adjacent individual projects funded by the Energy Agency and certain other national related activities.

78 FR 17646 - Agency Information Collection Activities; Comment Request; Ronald E. McNair Postbaccalaureate...

Science.gov (United States)

2013-03-22

...; Comment Request; Ronald E. McNair Postbaccalaureate Achievement Program Annual Performance Report AGENCY... of Collection: Ronald E. McNair Postbaccalaureate Achievement Program Annual Performance Report. OMB...: Ronald E. McNair Postbaccalaureate Achievement (McNair) Program Annual Performance Report Program...

An Integrative data mining approach to identifying Adverse ...

Science.gov (United States)

The Adverse Outcome Pathway (AOP) framework is a tool for making biological connections and summarizing key information across different levels of biological organization to connect biological perturbations at the molecular level to adverse outcomes for an individual or population. Computational approaches to explore and determine these connections can accelerate the assembly of AOPs. By leveraging the wealth of publicly available data covering chemical effects on biological systems, computationally-predicted AOPs (cpAOPs) were assembled via data mining of high-throughput screening (HTS) in vitro data, in vivo data and other disease phenotype information. Frequent Itemset Mining (FIM) was used to find associations between the gene targets of ToxCast HTS assays and disease data from Comparative Toxicogenomics Database (CTD) by using the chemicals as the common aggregators between datasets. The method was also used to map gene expression data to disease data from CTD. A cpAOP network was defined by considering genes and diseases as nodes and FIM associations as edges. This network contained 18,283 gene to disease associations for the ToxCast data and 110,253 for CTD gene expression. Two case studies show the value of the cpAOP network by extracting subnetworks focused either on fatty liver disease or the Aryl Hydrocarbon Receptor (AHR). The subnetwork surrounding fatty liver disease included many genes known to play a role in this disease. When querying the cpAOP

78 FR 61324 - Agency Information Collection Activities: Proposed Collection; Comment Request-Special Nutrition...

Science.gov (United States)

2013-10-03

..., Social Science Research Analyst, Office of Policy Support, Food and Nutrition Service, USDA, 3101 Park... DEPARTMENT OF AGRICULTURE Food and Nutrition Service Agency Information Collection Activities: Proposed Collection; Comment Request--Special Nutrition Program Operations Study (SNPOS) AGENCY: Food and...

The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Bowen Xu

2018-03-01

Full Text Available Summary: Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF, a component of the nucleosome remodeling factor (NURF chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs, including long-term hematopoietic stem cells (HSCs. Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2 required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC “stemness” genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of “stemness” gene-expression programs and proper function of adult HSCs. : Wang and colleagues show that a chromatin remodeler, BPTF, sustains appropriate functions of hematopoietic stem/progenitor cells (HSPCs. BPTF loss causes bone marrow failure and anemia. The authors further define a BPTF-dependent gene-expression program in HSPCs, which contains key HSC stemness factors. These results demonstrate an essential requirement of the BPTF-associated chromatin remodelers for HSC functionality and adult hematopoiesis. Keywords: Bptf, hematopoietic stem cells, chromatin remodeler, Meis1, Pbx1, Mn1, DNA accessibility, NURF, AP1 complex

76 FR 29720 - Information Collection: Volunteer Programs

Science.gov (United States)

2011-05-23

... designed to provide educationally related work assignments for students in non-pay status. The volunteer... DEPARTMENT OF AGRICULTURE Farm Service Agency Information Collection: Volunteer Programs AGENCY... the Volunteer Programs. DATES: We will consider comment that we received by July 22, 2011. ADDRESSES...

Combining gene prediction methods to improve metagenomic gene annotation

Directory of Open Access Journals (Sweden)

Rosen Gail L

2011-01-01

Full Text Available Abstract Background Traditional gene annotation methods rely on characteristics that may not be available in short reads generated from next generation technology, resulting in suboptimal performance for metagenomic (environmental samples. Therefore, in recent years, new programs have been developed that optimize performance on short reads. In this work, we benchmark three metagenomic gene prediction programs and combine their predictions to improve metagenomic read gene annotation. Results We not only analyze the programs' performance at different read-lengths like similar studies, but also separate different types of reads, including intra- and intergenic regions, for analysis. The main deficiencies are in the algorithms' ability to predict non-coding regions and gene edges, resulting in more false-positives and false-negatives than desired. In fact, the specificities of the algorithms are notably worse than the sensitivities. By combining the programs' predictions, we show significant improvement in specificity at minimal cost to sensitivity, resulting in 4% improvement in accuracy for 100 bp reads with ~1% improvement in accuracy for 200 bp reads and above. To correctly annotate the start and stop of the genes, we find that a consensus of all the predictors performs best for shorter read lengths while a unanimous agreement is better for longer read lengths, boosting annotation accuracy by 1-8%. We also demonstrate use of the classifier combinations on a real dataset. Conclusions To optimize the performance for both prediction and annotation accuracies, we conclude that the consensus of all methods (or a majority vote is the best for reads 400 bp and shorter, while using the intersection of GeneMark and Orphelia predictions is the best for reads 500 bp and longer. We demonstrate that most methods predict over 80% coding (including partially coding reads on a real human gut sample sequenced by Illumina technology.

Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

Directory of Open Access Journals (Sweden)

Christopher Terranova

Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

75 FR 27786 - Agency Information Collection Activities: Proposed Collection: Comment Request

Science.gov (United States)

2010-05-18

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Agency... performance-related criteria, including program design and purpose, strategic planning, program management... States Code, as amended by the Paperwork Reduction Act of 1995, Pub. L. 104-13), the Health Resources and...

76 FR 33272 - Agency Information Collection Activities OMB Responses

Science.gov (United States)

2011-06-08

... INFORMATION: OMB Responses to Agency Clearance Requests OMB Approvals EPA ICR Number 2409.01; Production... 2261.02; Safer Detergent Stewardship Initiative (SDSI) Program; was approved on 05/31/2011; OMB Number...

The Agency's technical co-operation activities in 1992

International Nuclear Information System (INIS)

1993-08-01

This report on the International Atomic Energy Agency's Technical Co-operation Activities in 1992 contains an overview of the general issues involved, including both in-house and external developments, resources and delivery, and evaluation of programs; an overview by field of activity and by division within the Agency; an overview by geographic area, distinguishing (i) Africa, (ii) Asia and the Pacific, (iii) Latin America, (iv) and the Middle East and Europe; an overview by component (i.e., experts, equipment, fellowships, training courses, sub-contracts and miscellaneous); and an overview by fund technical assistance and co-operation fund, extrabudgetary resources, United Nations Development Program (UNDP), assistance in kind. It also contains a profile on technical co-operation activities in Latin America. Projects concluded during 1992 are listed together with a description of their achievements. It concludes with implementation summaries. 10 figs, 9 tabs

DETEKSI GEN-GEN PENYANDI FAKTOR VIRULENSI PADA BAKTERI VIBRIO

Directory of Open Access Journals (Sweden)

Ince Ayu Khairani Kadriah

2011-04-01

menggunakan isolat bakteri yang diisolasi dari budidaya udang windu di berbagai daerah di Sulawesi Selatan dan Jawa. Pada penelitian ini digunakan primer spesifik untuk mendeteksi gen-gen virulen toxR gene, hemolysin (vvh gene, dan GyrB gene dengan metode PCR. Dari 35 isolat yang diisolasi, 20 isolat terdeteksi memiliki gen virulensi dan 8 di antaranya memiliki dua gen virulen. Spesies bakteri yang memiliki gen virulen adalah: V.harveyi, V. parahaemolyticus, V. mimicus, dan V. campbelli

76 FR 40924 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-07-12

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

76 FR 31969 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-06-02

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

77 FR 26022 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-05-02

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

77 FR 5037 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-02-01

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.); MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

77 FR 20832 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-04-06

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

77 FR 54597 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-09-05

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857...., NOVAMANN (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636...

Antimicrobial Effects of Blueberry, Raspberry, and Strawberry Aqueous Extracts and their Effects on Virulence Gene Expression in Vibrio cholerae.

Science.gov (United States)

Khalifa, Hazim O; Kamimoto, Maki; Shimamoto, Toshi; Shimamoto, Tadashi

2015-11-01

The antimicrobial effects of aqueous extracts of blueberry, raspberry, and strawberry on 13 pathogenic bacteria were evaluated. The minimum inhibitory concentrations and minimum bactericidal concentrations of the extracts were determined before and after neutralization to pH 7.03 ± 0.15. Both Gram-positive and Gram-negative pathogenic bacteria were selectively inhibited by the non-neutralized berries. Blueberry was the best inhibitor, and Vibrio and Listeria were the most sensitive bacteria. After neutralization, blueberry affected only Vibrio and Listeria, whereas the antimicrobial activities of raspberry and strawberry were abolished. The total contents of phenolics, flavonoids, and proanthocyanidins in the extracts were measured with colorimetric methods and were highest in strawberry, followed by raspberry, and then blueberry. We also studied the effects of sub-bactericidal concentrations of the three berry extracts on virulence gene expression in Vibrio cholerae. Real-time quantitative reverse transcription-polymerase chain reaction revealed that the three berry extracts effectively repressed the transcription of the tcpA gene. Raspberry also repressed the transcription of the ctxA gene, whereas blueberry and strawberry did not. However, the three berry extracts did not affect the transcription of toxT. These results suggest that the three berry extracts exert potent antimicrobial effects and inhibit the expression of the virulence factors of V. cholerae. Copyright © 2015 John Wiley & Sons, Ltd.

Factors influencing law enforcement decisions to adopt an evidence-based robbery prevention program.

Science.gov (United States)

Cabell, A; Casteel, C; Chronister, T; Nocera, M; Vladutiu, C J; Peek-Asa, C

2013-12-01

Homicide is the leading cause of workplace death among small retail and service businesses in the United States. Evidence-based programs have been shown to reduce robbery and robbery-related crimes in small retail businesses; however, reaching small businesses with programs has been difficult. As small businesses typically have no corporate backing or trade affiliation, police departments have been identified as potential vehicles for program dissemination. A national sample of 300 law enforcement agencies was surveyed to identify facilitators and barriers to adoption and sustainability of an evidence-based program. The questionnaire was developed using behavioral theory concepts and administered via telephone. Preliminary findings suggest the primary facilitators to program adoption included organizational capacity factors such as staff buy-in, dedicated personnel and financial support. Competing responsibilities was the primary barrier identified by agencies. Agency size and program complexity were identified as potential predictors of program adoption. Identifying agency and program-specific characteristics that influence program adoption by law enforcement agencies will be valuable for marketing programs to agencies that have the infrastructure to support and sustain program dissemination. Understanding these factors will optimize the reach of evidence-based strategies to small businesses.

Southern state radiological emergency preparedness and response agencies

International Nuclear Information System (INIS)

1988-11-01

This Report provides information on the state agencies assigned to radioactive materials transportation incidents in 16 Southern States Energy Board member states. For each, the report lists the agencies with primary authority for preparedness and response, their responsibilities and personnel within the agencies who can offer additional information on their radioactive materials transportation programs. The report also lists each state's emergency team members and its laboratory and analytical capabilities. Finally, the governor's designee for receiving advance notification of high-level radioactive materials and spent fuel shipments under 10 CFR Parts 71 and 73 of the US Nuclear Regulatory Commission's regulations is listed for each state. Part 71 requires prenotification for large quantity radioactive waste shipments. Part 73 addresses prenotification for spent nuclear reactor fuel shipments

78 FR 24293 - Pilot Program on NAFTA Trucking Provisions

Science.gov (United States)

2013-04-24

...-0097] Pilot Program on NAFTA Trucking Provisions AGENCY: Federal Motor Carrier Safety Administration... in the Agency's long-haul pilot program to test and demonstrate the ability of Mexico- domiciled... cross-border long-haul trucking pilot program to test and demonstrate the ability of Mexico-domiciled...

77 FR 70422 - Agency Information Collection Activities; Comment Request; Mathematics and Science Partnerships...

Science.gov (United States)

2012-11-26

...; Comment Request; Mathematics and Science Partnerships Program: Annual Performance Report AGENCY: Office of... notice will be considered public records. Title of Collection: Mathematics and Science Partnerships... Mathematics and Science Partnerships (MSP) program is a formula grant program to the States in which states...

29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

Science.gov (United States)

2010-07-01

... safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other Federal agency standards affecting occupational safety and health. (a) Where employees of different agencies...

75 FR 66699 - Farm Loan Programs Loan Making Activities; Correction

Science.gov (United States)

2010-10-29

... Loan Programs Loan Making Activities; Correction AGENCY: Farm Service Agency, USDA. ACTION: Proposed rule; correction. SUMMARY: This document contains a correction to the proposed rule titled ``Farm Loan Programs Loan Making Activities'' that was published September 23, 2010. The Farm Service Agency (FSA) is...

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations.

Science.gov (United States)

Jara, Lilian; Morales, Sebastian; de Mayo, Tomas; Gonzalez-Hormazabal, Patricio; Carrasco, Valentina; Godoy, Raul

2017-10-06

Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate- and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

Gene Locater

DEFF Research Database (Denmark)

Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

2012-01-01

software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...... of flexibility in calculating genetic linkage and displaying linkage group. Among other features, this software enables user to identify linkage groups with output visualized graphically. The program calculates interference and coefficient of coincidence with elevated accuracy in sample datasets. AVAILABILITY...

48 CFR 619.804-2 - Agency offering.

Science.gov (United States)

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Agency offering. 619.804-2 Section 619.804-2 Federal Acquisition Regulations System DEPARTMENT OF STATE SOCIOECONOMIC PROGRAMS SMALL... offering. (a) When applicable, this notification shall identify that the offering is in accordance with the...

LOADING SIMULATION PROGRAM C

Data.gov (United States)

U.S. Environmental Protection Agency — LSPC is the Loading Simulation Program in C++, a watershed modeling system that includes streamlined Hydrologic Simulation Program Fortran (HSPF) algorithms for...

U.S. Geological Survey; North Carolina's water resources; a partnership with State, Federal and local agencies

Science.gov (United States)

Winner, M.D.

1993-01-01

For more than 80 years, the Federal-State Cooperative Program in North Carolina has been an effective partnership that provides timely water information for all levels of government. The cooperative program has raised awareness of State and local water problems and issues and has enhanced transfer and exchange of scientific information. The U.S. Geological Survey (USGS) conducts statewide water-resources investigations in North Carolina that include hydrologic data collection, applied research studies, and other interpretive studies. These programs are funded through cooperative agreements with the North Carolina Departments of Environment, Health, and Natural Resources; Human Resources; and Transportation, as well as more than a dozen city and county governmental agencies. The USGS also conducts special studies and data-collection programs for Federal agencies, including the Department of Defense, the U.S. Soil Conservation Service, the Tennessee Valley Authority, and the U.S. Environmental Protection Agency that contribute to North Carolina's water information data base. Highlights of selected programs are presented to show the scope of USGS activities in North Carolina and their usefulness in addressing water-resource problems. The reviewed programs include the statewide data-collection program, estuarine studies, the National Water-Quality Assessment program, military installation restoration program, and groundwater flow model-development program in the Coastal Plain and Piedmont provinces.

Glucocorticoid effects on the programming of AT1b angiotensin receptor gene methylation and expression in the rat.

Directory of Open Access Journals (Sweden)

Irina Bogdarina

2010-02-01

Full Text Available Adverse events in pregnancy may 'programme' offspring for the later development of cardiovascular disease and hypertension. Previously, using a rodent model of programmed hypertension we have demonstrated the role of the renin-angiotensin system in this process. More recently we showed that a maternal low protein diet resulted in undermethylation of the At1b angiotensin receptor promoter and the early overexpression of this gene in the adrenal of offspring. Here, we investigate the hypothesis that maternal glucocorticoid modulates this effect on fetal DNA methylation and gene expression. We investigated whether treatment of rat dams with the 11beta-hydroxylase inhibitor metyrapone, could prevent the epigenetic and gene expression changes we observed. Offspring of mothers subjected to a low protein diet in pregnancy showed reduced adrenal Agtr1b methylation and increased adrenal gene expression as we observed previously. Treatment of mothers with metyrapone for the first 14 days of pregnancy reversed these changes and prevented the appearance of hypertension in the offspring at 4 weeks of age. As a control for non-specific effects of programmed hypertension we studied offspring of mothers treated with dexamethasone from day 15 of pregnancy and showed that, whilst they had raised blood pressure, they failed to show any evidence of Agtr1b methylation or increase in gene expression. We conclude that maternal glucocorticoid in early pregnancy may induce changes in methylation and expression of the Agtr1b gene as these are clearly reversed by an 11 beta-hydroxylase inhibitor. However in later pregnancy a converse effect with dexamethasone could not be demonstrated and this may reflect either an alternative mechanism of this glucocorticoid or a stage-specific influence.

Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation.

Science.gov (United States)

Savic, Daniel; Ramaker, Ryne C; Roberts, Brian S; Dean, Emma C; Burwell, Todd C; Meadows, Sarah K; Cooper, Sara J; Garabedian, Michael J; Gertz, Jason; Myers, Richard M

2016-07-11

The liver X receptors (LXRs, NR1H2 and NR1H3) and peroxisome proliferator-activated receptor gamma (PPARG, NR1C3) nuclear receptor transcription factors (TFs) are master regulators of energy homeostasis. Intriguingly, recent studies suggest that these metabolic regulators also impact tumor cell proliferation. However, a comprehensive temporal molecular characterization of the LXR and PPARG gene regulatory responses in tumor cells is still lacking. To better define the underlying molecular processes governing the genetic control of cellular growth in response to extracellular metabolic signals, we performed a comprehensive, genome-wide characterization of the temporal regulatory cascades mediated by LXR and PPARG signaling in HT29 colorectal cancer cells. For this analysis, we applied a multi-tiered approach that incorporated cellular phenotypic assays, gene expression profiles, chromatin state dynamics, and nuclear receptor binding patterns. Our results illustrate that the activation of both nuclear receptors inhibited cell proliferation and further decreased glutathione levels, consistent with increased cellular oxidative stress. Despite a common metabolic reprogramming, the gene regulatory network programs initiated by these nuclear receptors were widely distinct. PPARG generated a rapid and short-term response while maintaining a gene activator role. By contrast, LXR signaling was prolonged, with initial, predominantly activating functions that transitioned to repressive gene regulatory activities at late time points. Through the use of a multi-tiered strategy that integrated various genomic datasets, our data illustrate that distinct gene regulatory programs elicit common phenotypic effects, highlighting the complexity of the genome. These results further provide a detailed molecular map of metabolic reprogramming in cancer cells through LXR and PPARG activation. As ligand-inducible TFs, these nuclear receptors can potentially serve as attractive therapeutic

75 FR 30113 - Rural Microentrepreneur Assistance Program

Science.gov (United States)

2010-05-28

...)); Removing ``socially-disadvantaged'' and clarifying that the percentage of rural entrepreneurs that received... entrepreneurs that have not received a microloan from an MDO under this program would not be able to receive... the Agency is easier to implement and consistent with other program regulations. The Agency, therefore...

76 FR 75889 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-12-05

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... (Ontario), Inc.). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, (651) 636-7466/(800...

78 FR 14100 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2013-03-04

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... Laboratory Services, a Division of LabOne, Inc.,) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul...

77 FR 126 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-01-03

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857....). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, (651) 636-7466/(800) 832-3244...

77 FR 12356 - Pilot Program on NAFTA Trucking Provisions

Science.gov (United States)

2012-02-29

...-0097] Pilot Program on NAFTA Trucking Provisions AGENCY: Federal Motor Carrier Safety Administration... that applied to participate in the Agency's long-haul pilot program to test and demonstrate the ability... cross-border long-haul trucking pilot program to test and demonstrate the ability of Mexico-domiciled...

78 FR 25525 - Pilot Program on NAFTA Trucking Provisions

Science.gov (United States)

2013-05-01

...-0097] Pilot Program on NAFTA Trucking Provisions AGENCY: Federal Motor Carrier Safety Administration..., which applied to participate in the Agency's long-haul pilot program to test and demonstrate the ability... long-haul trucking pilot program to test and demonstrate the ability of Mexico-domiciled motor carriers...

The Chromatin Remodeler BPTF Activates a Stemness Gene-Expression Program Essential for the Maintenance of Adult Hematopoietic Stem Cells.

Science.gov (United States)

Xu, Bowen; Cai, Ling; Butler, Jason M; Chen, Dongliang; Lu, Xiongdong; Allison, David F; Lu, Rui; Rafii, Shahin; Parker, Joel S; Zheng, Deyou; Wang, Gang Greg

2018-03-13

Self-renewal and differentiation of adult stem cells are tightly regulated partly through configuration of chromatin structure by chromatin remodelers. Using knockout mice, we here demonstrate that bromodomain PHD finger transcription factor (BPTF), a component of the nucleosome remodeling factor (NURF) chromatin-remodeling complex, is essential for maintaining the population size of hematopoietic stem/progenitor cells (HSPCs), including long-term hematopoietic stem cells (HSCs). Bptf-deficient HSCs are defective in reconstituted hematopoiesis, and hematopoietic-specific knockout of Bptf caused profound defects including bone marrow failure and anemia. Genome-wide transcriptome profiling revealed that BPTF loss caused downregulation of HSC-specific gene-expression programs, which contain several master transcription factors (Meis1, Pbx1, Mn1, and Lmo2) required for HSC maintenance and self-renewal. Furthermore, we show that BPTF potentiates the chromatin accessibility of key HSC "stemness" genes. These results demonstrate an essential requirement of the chromatin remodeler BPTF and NURF for activation of "stemness" gene-expression programs and proper function of adult HSCs. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

36 CFR 1235.14 - May agencies retain records for the conduct of regular agency business after they are eligible...

Science.gov (United States)

2010-07-01

... MANAGEMENT TRANSFER OF RECORDS TO THE NATIONAL ARCHIVES OF THE UNITED STATES General Transfer Requirements... Administration, Modern Records Programs (NWM), 8601 Adelphi Road, College Park, MD 20740-6001, phone number (301... time the records will be needed (if no date is provided by the agency, approved certification requests...

75 FR 68316 - Agency Information Collection Activities: Proposed Collection; Comment Request-Special Nutrition...

Science.gov (United States)

2010-11-05

...: Special Nutrition Program Operations Study. OMB Number: 0584-NEW. Expiration Date of Approval: Not yet...: General descriptive data on the Child Nutrition (CN) program characteristics to help FNS respond to... (SFAs) and State Agencies responsible for administering the CN programs. The activities to be undertaken...

Survey of international personnel radiation dosimetry programs

International Nuclear Information System (INIS)

Swaja, R.E.

1985-04-01

In September of 1983, a mail survey was conducted to determine the status of external personnel gamma and neutron radiation dosimetry programs at international agencies. A total of 130 agencies participated in this study including military, regulatory, university, hospital, laboratory, and utility facilities. Information concerning basic dosimeter types, calibration sources, calibration phantoms, corrections to dosimeter responses, evaluating agencies, dose equivalent reporting conventions, ranges of typical or expected dose equivalents, and degree of satisfaction with existing systems was obtained for the gamma and neutron personnel monitoring programs at responding agencies. Results of this survey indicate that to provide the best possible occupational radiation monitoring programs and to improve dosimetry accuracy in performance studies, facility dosimetrists, regulatory and standards agencies, and research laboratories must act within their areas of responsibility to become familiar with their radiation monitoring systems, establish common reporting guidelines and performance standards, and provide opportunities for dosimetry testing and evaluation. 14 references, 10 tables

An outline of 1961 program;IAEA program of work

Energy Technology Data Exchange (ETDEWEB)

NONE

1960-09-15

The program of work for 1961 which the International Atomic Energy Agency's Board of Governors has presented to the Agency's General Conference for final approval provides for steady amplification of its work in technical assistance to specific projects, training of scientific personnel and scientific research. These activities and certain others are of special interest to those areas of the world that are less advanced in the utilization of atomic energy. This is in accord with the Agency's Statute which requires that it bear in mind 'the special needs of the under-developed areas of the world'. At the same time, the Board indicated that the 1961 program 'provides for activities intended to create a basis for general progress in the safe utilization of atomic energy for peaceful purposes which is of concern to all Member States. Thus the delay in the advent of generally economic nuclear power is used to build up the necessary technological infrastructure in the less developed countries and to establish an international framework of norms and regulations which an orderly and safe development of widespread nuclear industries will require'. Some highlights of the 1961 program are presented

Steady-state and dynamic gene expression programs in Saccharomyces cerevisiae in response to variation in environmental nitrogen

Science.gov (United States)

Airoldi, Edoardo M.; Miller, Darach; Athanasiadou, Rodoniki; Brandt, Nathan; Abdul-Rahman, Farah; Neymotin, Benjamin; Hashimoto, Tatsu; Bahmani, Tayebeh; Gresham, David

2016-01-01

Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR

41 CFR 102-192.130 - What are your general responsibilities as an agency mail manager?

Science.gov (United States)

2010-07-01

... responsibilities as an agency mail manager? 102-192.130 Section 102-192.130 Public Contracts and Property... ADMINISTRATIVE PROGRAMS 192-MAIL MANAGEMENT Agency Mail Manager Requirements § 102-192.130 What are your general responsibilities as an agency mail manager? In addition to carrying out the responsibilities in Subparts B, C, D...

77 FR 27837 - Pilot Program on NAFTA Trucking Provisions

Science.gov (United States)

2012-05-11

...-0097] Pilot Program on NAFTA Trucking Provisions AGENCY: Federal Motor Carrier Safety Administration... carriers that applied to participate in the Agency's long- haul pilot program to test and demonstrate the... intent to proceed with the initiation of a U.S.-Mexico cross-border long-haul trucking pilot program to...

77 FR 69642 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2012-11-20

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... (Ontario), Inc.) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636-7466/800-832...

76 FR 24501 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-05-02

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... (Ontario), Inc.) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636-7466/800-832...

76 FR 6147 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-02-03

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857....) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112. 651-636-7466/800-832-3244. Metro...

78 FR 33429 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2013-06-04

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857....). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636-7466/800-832-3244. Metro...

76 FR 46309 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2011-08-02

..., Division of Workplace Programs, SAMHSA/CSAP, Room 2-1042, One Choke Cherry Road, Rockville, Maryland 20857... (Ontario), Inc.) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636-7466/800-832...

78 FR 72684 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2013-12-03

... INFORMATION CONTACT: Giselle Hersh, Division of Workplace Programs, SAMHSA/CSAP, Room 7-1051, One Choke Cherry..., a Division of LabOne, Inc.) MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651...

78 FR 59946 - Current List of Laboratories and Instrumented Initial Testing Facilities Which Meet Minimum...

Science.gov (United States)

2013-09-30

... INFORMATION CONTACT: Giselle Hersh, Division of Workplace Programs, SAMHSA/CSAP, Room 7-1051, One Choke Cherry....). MedTox Laboratories, Inc., 402 W. County Road D, St. Paul, MN 55112, 651-636-7466/800-832-3244. Metro...

5 CFR 330.705 - Order of selection in filling vacancies from outside the agency's workforce.

Science.gov (United States)

2010-01-01

... reappointment of former employees with their agency into hard-to-fill positions, the duties of which require unique skills and experience necessary to conduct a formal skills-based training program for the agency...

Learning Gene Regulatory Networks Computationally from Gene Expression Data Using Weighted Consensus

KAUST Repository

Fujii, Chisato

2015-04-16

Gene regulatory networks analyze the relationships between genes allowing us to un- derstand the gene regulatory interactions in systems biology. Gene expression data from the microarray experiments is used to obtain the gene regulatory networks. How- ever, the microarray data is discrete, noisy and non-linear which makes learning the networks a challenging problem and existing gene network inference methods do not give consistent results. Current state-of-the-art study uses the average-ranking-based consensus method to combine and average the ranked predictions from individual methods. However each individual method has an equal contribution to the consen- sus prediction. We have developed a linear programming-based consensus approach which uses learned weights from linear programming among individual methods such that the methods have di↵erent weights depending on their performance. Our result reveals that assigning di↵erent weights to individual methods rather than giving them equal weights improves the performance of the consensus. The linear programming- based consensus method is evaluated and it had the best performance on in silico and Saccharomyces cerevisiae networks, and the second best on the Escherichia coli network outperformed by Inferelator Pipeline method which gives inconsistent results across a wide range of microarray data sets.