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Sample records for highlights ntp bioassay

  1. Investigation of independence in inter-animal tumor-type occurrences within the NTP rodent-bioassay database

    SciTech Connect

    Bogen, K.T.; Seilkop, S.

    1993-05-01

    Statistically significant elevation in tumor incidence at multiple histologically distinct sites is occasionally observed among rodent bioassays of chemically induced carcinogenesis. If such data are to be relied on (as they have, e.g., by the US EPA) for quantitative cancer potency assessment, their proper analysis requires a knowledge of the extent to which multiple tumor-type occurrences are independent or uncorrelated within individual bioassay animals. Although difficult to assess in a statistically rigorous fashion, a few significant associations among tumor-type occurrences in rodent bioassays have been reported. However, no comprehensive studies of animal-specific tumor-type occurrences at death or sacrifice have been conducted using the extensive set of available NTP rodent-bioassay data, on which most cancer-potency assessment for environmental chemicals is currently based. This report presents the results of such an analysis conducted on behalf of the National Research Council`s Committee on Risk Assessment for Hazardous Air Pollutants. Tumor-type associations among individual animals were examined for {approximately}2500 to 3000 control and {approximately}200 to 600 treated animals using pathology data from 62 B6C3F1 mouse studies and 61 F/344N rat studies obtained from a readily available subset of the NTP carcinogenesis bioassay database. No evidence was found for any large correlation in either the onset probability or the prevalence-at-death or sacrifice of any tumor-type pair investigated in control and treated rats and niece, although a few of the small correlations present were statistically significant. Tumor-type occurrences were in most cases nearly independent, and departures from independence, where they did occur, were small. This finding is qualified in that tumor-type onset correlations were measured only indirectly, given the limited nature of the data analyzed.

  2. NTP Carcinogenesis Bioassay of Diallyl Phthalate (CAS No. 131-17-9) in B6C3F1 Mice (Gavage Study).

    PubMed

    1983-04-01

    Diallyl phthalate is a widely used crosslinking agent for unsaturated polyesters. Diallyl phthalate or diallyl phthalate polyester blends are used primarily as plasticizers and carriers for adding catalysts and pigments to polyesters and in molding, electrical parts, laminating compounds, and impregnation of metal castings. Rubber compounds, epoxy formulations, and polyurethane foams may also contain diallyl phthalate. Annual production of diallyl phthalate in the United States exceeds 5,000 pounds; precise figures are not available. A NTP Carcinogenesis bioassay of diallyl phthalate (99% pure) was conducted by administering 0 (vehicle control), 150, or 300 mg/kg diallyl phthalate in corn oil by gavage, 5 days per week for 103 weeks, to groups of 50 male and 50 female B6C3F1 mice. Survival rates and mean body weights of dosed mice were not different from those of the controls, and pathological lesions unrelated to proliferative changes were not observed. Therefore, a maximally tolerated dose for the purposes of carcinogenicity testing may not have been achieved. The incidences of lymphoma and either lymphoma or leukemia in dosed male mice were no significantly greater than those in the controls according to pairwise comparisons (P=0.051 to P=0.096), but the trend tests were statistically significant by either life table or incidental tumor analysis (P=0.031 to P=0.045). The incidence of lymphomas in the high-dose male mice was 12/50 (24%) in comparison with 6/50 (12%) in the controls. Recent historical incidences at the performing laboratory and in the NTP Bioassay Program were 18/120 (15%) and 71/661 (11%), respectively. Since the incidence of high-dose male mice with leukemia was not significantly greater than that of concurrent or historical controls at the performing laboratory by pairwise comparisons, this marginal increase was considered only to be equivocally related to diallyl phthalate administration. Increased incidences of squamous cell papillomas

  3. NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study).

    PubMed

    1982-12-01

    Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the

  4. NTP Carcinogenesis Bioassay of L-Ascorbic Acid (Vitamin C) (CAS No. 50-81-7) in F344/N Rats and B6C3F1 Mice (Feed Study).

    PubMed

    1983-03-01

    L-Ascorbic acid is essential for many physiologic functions in animals and humans, mostly biochemical reactions involving oxidation. L-Ascorbic acid is approved for use as a dietary supplement and chemical preservative by the U.S. Food and Drug Administration and is on the FDA's list of substances generally recognized as safe. L-Ascorbic acid may be used in soft drinks as an antioxidant for flavor ingredients, in meat and meat-containing products, for curing and pickling, in flour to improve baking quality, in beer as a stabilizer, in fats and oils as an antioxidant, and in a wide variety of foods for vitamin C enrichment. L-Ascorbic acid may also find use in stain removers, hair waving preparations; plastics manufacture, photography, and water treatment. A NTP Carcinogenesis bioassay of L-ascorbic acid (>97% pure) was conducted by administering diets containing 25,000 or 50,000 ppm L-ascorbic acid to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Controls consisted of 50 untreated rats and untreated mice of each sex. Fifty-thousand ppm is the highest dose recommended for chronic studies. Survival of dosed and control female rats and of dosed and control female mice were comparable. Survival of high-dose male rats was slightly greater than that of the controls (P=0.087). Survival of high-dose male mice was significantly greater (P=0.009) than that of the controls. Throughout most of the study, mean body weights of dosed female rats and dosed female mice were lower than those of the controls. Final body weights were comparable among groups, except for the high-dose female rats (<13%); marginal differences (<8%) were observed for low-dose female rats and for dosed female mice (8%-11%). Food consumption was equivalent among groups. Most observational differences were confined to the female rat. The incidence of low-dose female rats with undifferentiated (mononuclear-cell) leukemias (control, 6/50, 12%; low-dose, 17/50, 34%; high-dose, 12/50, 24

  5. Nuclear Thermal Propulsion (NTP)

    NASA Video Gallery

    NASA's history with nuclear thermal propulsion (NTP) technology goes back to the earliest days of the Agency. The Manned Lunar Rover Vehicle and the Nuclear Engine for Rocket Vehicle Applications p...

  6. NTP comparison process

    NASA Technical Reports Server (NTRS)

    Corban, Robert

    1993-01-01

    The systems engineering process for the concept definition phase of the program involves requirements definition, system definition, and consistent concept definition. The requirements definition process involves obtaining a complete understanding of the system requirements based on customer needs, mission scenarios, and nuclear thermal propulsion (NTP) operating characteristics. A system functional analysis is performed to provide a comprehensive traceability and verification of top-level requirements down to detailed system specifications and provides significant insight into the measures of system effectiveness to be utilized in system evaluation. The second key element in the process is the definition of system concepts to meet the requirements. This part of the process involves engine system and reactor contractor teams to develop alternative NTP system concepts that can be evaluated against specific attributes, as well as a reference configuration against which to compare system benefits and merits. Quality function deployment (QFD), as an excellent tool within Total Quality Management (TQM) techniques, can provide the required structure and provide a link to the voice of the customer in establishing critical system qualities and their relationships. The third element of the process is the consistent performance comparison. The comparison process involves validating developed concept data and quantifying system merits through analysis, computer modeling, simulation, and rapid prototyping of the proposed high risk NTP subsystems. The maximum amount possible of quantitative data will be developed and/or validated to be utilized in the QFD evaluation matrix. If upon evaluation of a new concept or its associated subsystems determine to have substantial merit, those features will be incorporated into the reference configuration for subsequent system definition and comparison efforts.

  7. NATIONAL TOXICOLOGY PROGRAM (NTP) DATA

    EPA Science Inventory

    The National Toxicology Program (NTP) was established in 1978 by the Department of Health and Human Services (DHHS) to coordinate toxicological testing programs within the department, strengthen the science base in toxicology; develop and validate improved testing methods; and pr...

  8. Laser diagnostics for NTP fuel corrosion studies

    NASA Technical Reports Server (NTRS)

    Wantuck, Paul J.; Butt, D. P.; Sappey, A. D.

    1993-01-01

    Viewgraphs and explanations on laser diagnostics for nuclear thermal propulsion (NTP) fuel corrosion studies are presented. Topics covered include: NTP fuels; U-Zr-C system corrosion products; planar laser-induced fluorescence (PLIF); utilization of PLIF for corrosion product characterization of nuclear thermal rocket fuel elements under test; ZrC emission spectrum; and PLIF imaging of ZrC plume.

  9. 76 FR 71037 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ... Federal Register (76 FR 67200) and is available on the NTP Web site ( http://ntp.niehs.nih.gov/go... on the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) prior to the November 29, 2011... the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ). TTY users should contact the Federal...

  10. Aerobrake concepts for NTP systems study

    NASA Technical Reports Server (NTRS)

    Cruz, Manuel I.

    1992-01-01

    Design concepts are described for landing large spacecraft masses on the Mars surface in support of manned missions with interplanetary transportation using Nuclear Thermal Propulsion (NTP). Included are the mission and systems analyses, trade studies and sensitivity analyses, design analyses, technology assessment, and derived requirements to support this concept. The mission phases include the Mars de-orbit, entry, terminal descent, and terminal touchdown. The study focuses primarily on Mars surface delivery from orbit after Mars orbit insertion using an NTP. The requirements associated with delivery of logistical supplies, habitats, and other equipment on minimum energy Earth to Mars transfers are also addressed in a preliminary fashion.

  11. Final Report Navajo Transmission Project (NTP)

    SciTech Connect

    Bennie Hoisington; Steven Begay

    2006-09-14

    The Diné Power Authority is developing the Navajo Transmission Project (NTP) to relieve the constraints on the transmission of electricity west of the Four Corners area and to improve the operation flexibility and reliability of the extra-high-voltage transmission system in the region. The NTP creates the wholesale transmission capacity for more economical power transfers, sales, and purchases in the region. It will facilitate the development of Navajo energy resources, improve economic conditions on the Navajo Nation as well as allow DPA to participate in the western electrical utility industry.

  12. 75 FR 12244 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-15

    ...Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (BSC). The BSC is a Federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP Director and evaluates the scientific merit of the NTP's intramural and collaborative...

  13. 76 FR 8370 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-14

    ...Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (BSC). The BSC is a federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP Director and evaluates the scientific merit of the NTP's intramural and collaborative...

  14. 75 FR 64311 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-19

    ...Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (BSC). The BSC is a federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP Director and evaluates the scientific merit of the NTP's intramural and collaborative...

  15. Summary of Chemically Induced Pulmonary Lesions in the National Toxicology Program (NTP) Toxicology and Carcinogenesis Studies

    PubMed Central

    Dixon, Darlene; Herbert, Ronald A.; Kissling, Grace E.; Brix, Amy E.; Miller, Rodney A.; Maronpot, Robert R.

    2009-01-01

    The lung is the second most common target site of neoplasia of chemicals tested by the National Toxicology Program (NTP). Of all peer-reviewed NTP studies to date (N = 545), a total of sixty-four chemicals in sixty-six reports produced significant site-specific neoplasia in the lungs of rats and/or mice. Of the studies associated with lung tumor induction, approximately 35% were inhalation and 35% were gavage studies, with dosed-feed, dosed-water, topical, intraperitoneal, or in utero routes of chemical administration accounting for 18%, 6%, 3%, 1%, and 1% of the studies, respectively. The most commonly induced lung tumors were alveolar/bronchiolar (A/B) adenoma and/or carcinoma for both species. The most frequently observed nonneoplastic lesions included hyperplasia and inflammation in both species. The liver was the most common primary site of origin of metastatic lesions to the lungs of mice; however, skin was most often the primary site of origin of metastatic lesions to the lungs of rats. In summary, A/B adenoma and carcinoma were the most frequently diagnosed chemically induced tumors in the lungs of both rats and mice in the NTP toxicology and carcinogenesis bioassays, and hyperplasia and inflammation were the most common nonneoplastic changes observed. PMID:18441259

  16. 76 FR 51034 - Availability of Draft NTP Monograph on Potential Developmental Effects of Cancer Chemotherapy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... (available at http://ntp.niehs.nih.gov/go/36639 ) that will be peer reviewed by an NTP Peer Review Panel at a... available, will be posted on the NTP Web site ( http://ntp.niehs.nih.gov/go/36639 ) or may be requested in... ( http://ntp.niehs.nih.gov/go/36639 ) by October 12, 2011, to facilitate access to the NIEHS campus....

  17. Chemical-induced atrial thrombosis in NTP rodent studies.

    PubMed

    Yoshizawa, Katsuhiko; Kissling, Grace E; Johnson, Jo Anne; Clayton, Natasha P; Flagler, Norris D; Nyska, Abraham

    2005-01-01

    Cardiac thrombosis, one of the causes of sudden death throughout the world, plays a principal role in several cardiovascular diseases, such as myocardial infarction and stroke in humans. Data from studies of induction of chemical thrombosis in rodents help to identify substances in our environment that may contribute to cardiac thrombosis. Results for more than 500 chemicals tested in rodents in 2-year bioassays have been published as Technical Reports of the National Toxicology Program (NTP) http://ntp-server.niehs.nih.gov/index. We evaluated atrial thrombosis induced by these chemical exposures and compared it to similarly induced lesions reported in the literature. Spontaneous rates of cardiac thrombosis were determined for control Fischer 344 rats and B6C3F1 mice: 0% in rats and mice in 90-day studies and, in 2-year studies, 0.7% in both genders of mice, 4% in male rats, and 1% in female rats. Incidences of atrial thrombosis were increased in high-dosed groups involving 13 compounds (incidence rate: 20-100%): 2-butoxyethanol, C.I. Direct Blue 15, bis(2-chloroethoxy)methane, diazoaminobenzene, diethanolamine, 3,3'-dimethoxybenzidine dihydrochloride, hexachloroethane, isobutene, methyleugenol, oxazepam, C.I. Pigment Red 23, C.I. Acid Red 114, and 4,4'-thiobis(6-t-butyl-m-cresol). The main localization of spontaneously occurring and chemically induced thromboses occurred in the left atrium. The literature survey suggested that chemical-induced atrial thrombosis might be closely related to myocardial injury, endothelial injury, circulatory stasis, hypercoagulability, and impaired atrial mechanical activity, such as atrial fibrillation, which could cause stasis of blood within the left atrial appendage, contributing to left atrial thrombosis. Supplementary data referenced in this paper are not printed in this issue of Toxicologic Pathology. They are available as downloadable files at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. To

  18. 76 FR 8741 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... a Meeting SUMMARY: The NTP announces the availability of draft NTP Technical Reports (TRs; available... meeting. DATES: The meeting to review the draft NTP TRs will be held on April 5, 2011. The draft NTP TRs... any other correspondence on the draft TRs should be sent to Danica Andrews, NIEHS, P.O. Box 12233,...

  19. 75 FR 73085 - National Toxicology Program (NTP): Office of Liaison, Policy, and Review; Availability of Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... a Meeting. SUMMARY: The NTP announces the availability of draft NTP Technical Reports (TRs... meeting. DATES: The meeting to review the draft NTP TRs will be held on January 26, 2011. The draft NTP TRs will be available for public comment by December 8, 2010. The deadline to submit written...

  20. A Research Reactor Concept to Support NTP Development

    NASA Technical Reports Server (NTRS)

    Eades, Michael J.; Blue, T. E.; Gerrish, Harold P.; Hardin, Leroy A.

    2014-01-01

    In support of efforts for research into the design and development of man rated Nuclear Thermal Propulsion (NTP), the National Aeronautics and Space Administration (NASA), Marshall Space Flight Center (MSFC), is evaluating the potential for building a Nuclear Regulatory Commission (NRC) licensed NTP based research reactor (NTPRR). The proposed NTPRR would be licensed by NASA and operated jointly by NASA and university partners. The purpose of the NTPRR would be used to perform further research into the technologies and systems needed for a successful NTP project and promote nuclear training and education.

  1. An overview of tested and analyzed NTP concepts

    NASA Technical Reports Server (NTRS)

    Walton, James T.

    1991-01-01

    If we buy into the goals of the Space Exploration Initiative (SEI) and accept that they are worthy of the hefty investment of our tax dollars, then we must begin to evaluate the technologies which enable their attainment. The main driving technology is the propulsion systems; for interplanetary missions, the safest and most affordable is a Nuclear Thermal Propulsion (NTP) system. An overview is presented of the NTP systems which received detailed conceptual design and, for several, testing.

  2. 75 FR 66766 - National Toxicology Program (NTP); Office of Liaison, Policy and Review; Meeting of the NTP Board...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-29

    ... meeting was published on October 19, 2010, in the Federal Register (75 FR 201) and is available on the BSC meeting page ( http://ntp.niehs.nih.gov/go/165 ). The guidelines and deadlines published in this...

  3. Integrated System Modeling for Nuclear Thermal Propulsion (NTP)

    NASA Technical Reports Server (NTRS)

    Ryan, Stephen W.; Borowski, Stanley K.

    2014-01-01

    Nuclear thermal propulsion (NTP) has long been identified as a key enabling technology for space exploration beyond LEO. From Wernher Von Braun's early concepts for crewed missions to the Moon and Mars to the current Mars Design Reference Architecture (DRA) 5.0 and recent lunar and asteroid mission studies, the high thrust and specific impulse of NTP opens up possibilities such as reusability that are just not feasible with competing approaches. Although NTP technology was proven in the Rover / NERVA projects in the early days of the space program, an integrated spacecraft using NTP has never been developed. Such a spacecraft presents a challenging multidisciplinary systems integration problem. The disciplines that must come together include not only nuclear propulsion and power, but also thermal management, power, structures, orbital dynamics, etc. Some of this integration logic was incorporated into a vehicle sizing code developed at NASA's Glenn Research Center (GRC) in the early 1990s called MOMMA, and later into an Excel-based tool called SIZER. Recently, a team at GRC has developed an open source framework for solving Multidisciplinary Design, Analysis and Optimization (MDAO) problems called OpenMDAO. A modeling approach is presented that builds on previous work in NTP vehicle sizing and mission analysis by making use of the OpenMDAO framework to enable modular and reconfigurable representations of various NTP vehicle configurations and mission scenarios. This approach is currently applied to vehicle sizing, but is extensible to optimization of vehicle and mission designs. The key features of the code will be discussed and examples of NTP transfer vehicles and candidate missions will be presented.

  4. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF 2-BROMOPROPANE

    EPA Science Inventory

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in order to provide timely, unbiased, scientifically sound evaluations of human and exper...

  5. 76 FR 68461 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ...Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (BSC). The BSC is a federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP and evaluates the scientific merit of the NTP's intramural and collaborative...

  6. 77 FR 24714 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ...Pursuant to Public Law 92-463, notice is hereby given of a meeting of the NTP Board of Scientific Counselors (BSC). The BSC is a federally chartered, external advisory group composed of scientists from the public and private sectors that provides primary scientific oversight to the NTP and evaluates the scientific merit of the NTP's intramural and collaborative...

  7. NTP system definition and comparison process for SEI

    SciTech Connect

    Corban, R.R. )

    1993-01-20

    The concept definition, trade-offs, and ultimate selection of a nuclear thermal propulsion (NTP) system that will enable the Space Exploration Initiative (SEI) missions to Mars will require a rigorous systems engineering approach. A systems engineering process to provide a consistent comparison has been established to allow for evolving SEI mission requirements, level of concept definition and changing customer'' requirements, while continuing to improve the process as more data becomes available. All concepts will be evaluated against an established baseline NTP system to compare system benefits and merits. Establishing the evaluation criteria is extremely challenging and critical to the evaluation and selection process. Quality function deployment (QFD) will be utilized to provide structure and focus in obtaining the critical needs and attributes of the NTP system. System performance, cost, and risk analysis tools will be integrated into the process to provide the quantitative data required to allow for an informative decision on concept and technology decisions. This process will initiate the framework for design and development of a robust, reliable, cost effective NTP engine within NASA's philosophy for space systems to be developed faster, better, and cheaper.''

  8. Nanovehicles based Bioassay Labels

    SciTech Connect

    Liu, Guodong; Wang, Jun; Wu, Hong; Lin, Ying-Ying; Lin, Yuehe

    2007-04-01

    In this article, we review recent advances of our group in nanoparticle labels based bioassay. Apoferritin and silica nanoparticles have been used as nanovehicles to load large amount of markers for highly sensitive bioassay. Markers loaded apoferritin, apoferritin-templated metallic phosphate nanoparticles, and poly [guanine] coated silica nanoparticles have been prepared, characterized and used as labels for highly sensitive bioassay of protein and DNA. Dissociation and reconstitution characteristics at different pH as well as the special cavity structure of apoferritin nanovehicle provides a simple and convenient route to prepare versatile nanoparticle labels and avoid the complicated and tedious synthesis process of conventional nanoparticle labels. The optical and electrochemical characteristics of the prepared nanoparticle labels are easily controlled by loading different optical or electrochemical markers. Additionally, the use of apoferritin nanovehicle as template for synthesis of metallic phosphate nanoparticle labels offers fast route to prepare uniform-size metallic nanoparticle labels for electrochemical bioassay and avoids the traditional harsh dissolution conditions to dissolve metallic nanoparticle tags (that is, the strong-acid dissolution of quantum dots and gold nanoparticles) during the stripping analysis step. Silica nanoparticle has also been used as nanovehicle to carry thousands of poly [guanine] tracers, which was used to enhance the oxidation current of Ru(bpy)32+, resulting in enhanced sensitivity of electrochemical immunoassay. The new nanovehicle-based labels have been used for highly sensitive electrochemical detection of DNA and protein biomarkers, such as tumor necrosis factor-alpha (TNF-a). The high sensitivity and selectivity make these labels a useful addition to the armory of nanoparticle-based bioassay. The new nanovehicles based labels hold great promise for multiplex protein and DNA detection and for enhancing the sensitivity

  9. Nuclear Thermal Propulsion (NTP) Development Activities at the NASA Marshall Space Flight Center - 2006 Accomplishments

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2007-01-01

    In 2005-06, the Prometheus program funded a number of tasks at the NASA-Marshall Space Flight Center (MSFC) to support development of a Nuclear Thermal Propulsion (NTP) system for future manned exploration missions. These tasks include the following: 1. NTP Design Develop Test & Evaluate (DDT&E) Planning 2. NTP Mission & Systems Analysis / Stage Concepts & Engine Requirements 3. NTP Engine System Trade Space Analysis and Studies 4. NTP Engine Ground Test Facility Assessment 5. Non-Nuclear Environmental Simulator (NTREES) 6. Non-Nuclear Materials Fabrication & Evaluation 7. Multi-Physics TCA Modeling. This presentation is a overview of these tasks and their accomplishments

  10. 77 FR 1707 - National Toxicology Program (NTP) Final Process for Preparation of the Report on Carcinogens (RoC)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... October 31, 2011, the NTP released its proposed process for preparation of the RoC (76 FR 67200 and 76 FR..., and presented a revised process at the NTP Board of Scientific Counselors public meeting (76 FR 68461... available on the NTP Web site ( http://ntp.niehs.nih.gov/go/rocprocess ) or by contacting Dr. Ruth Lunn...

  11. 76 FR 61704 - Availability of Draft NTP Monograph on the Health Effects of Low-Level Lead; Request for Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... Health Effects of Low-level Lead (available at http://ntp.niehs.nih.gov/go/36639 ) that will be peer... studies on health effects associated with low blood lead levels ( http://ntp.niehs.nih.gov/go/36639 ) by... online at the NTP Web site ( http://ntp.niehs.nih.gov/go/36639 ) by November 10, 2011, to...

  12. 75 FR 21003 - National Toxicology Program (NTP); Office of Liaison, Policy and Review Meeting of the NTP Board...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-22

    ....nih.gov/go/29353 ) that was announced in the Federal Register on April 16, 2007 (72 FR 18999). On... review for the 12th RoC (69 FR 28940, 69 FR 62276, 70 FR 60548, 72 FR 26394). Publication of the RoC is... extended review process for the 12th RoC (72 FR 18999). Although the NTP initially planned to review...

  13. NTP system simulation and detailed nuclear engine modeling

    NASA Technical Reports Server (NTRS)

    Anghaie, Samim

    1993-01-01

    The topics are presented in viewgraph form and include the following: nuclear thermal propulsion (NTP) & detailed nuclear engine modeling; modeling and engineering simulation of nuclear thermal rocket systems; nuclear thermal rocket simulation system; INSPI-NTVR core axial flow profiles; INSPI-NTRV core axial flow profiles; specific impulse vs. chamber pressure; turbine pressure ratio vs. chamber pressure; NERVA core axial flow profiles; P&W XNR2000 core axial flow profiles; pump pressure rise vs. chamber pressure; streamline of jet-induced flow in cylindrical chamber; flow pattern of a jet-induced flow in a chamber; and radiative heat transfer models.

  14. Bioassay for assessing marine contamination

    SciTech Connect

    Lapota, D.; Copeland, H.; Mastny, G.; Rosenberger, D.; Duckworth, D.

    1996-03-01

    The Qwiklite bioassay, developed by the laboratory at NCCOSC, is used as a biological tool to gauge the extent of environmental contamination. Some species of marine phytoplankton produce bioluminescence. The Qwiklite bioassay determines acute response and chronic effects of a wide variety of toxicants upon bioluminescent dinotlagellates by measuring their light output after exposure.

  15. Prediction of rodent carcinogenicity bioassays from molecular structure using inductive logic programming

    SciTech Connect

    King, R.D.; Srinivasan, A.

    1996-10-01

    The machine learning program Progol was applied to the problem of forming the structure-activity relationship (SAR) for a set of compounds tested for carcinogenicity in rodent bioassays by the U.S. National Toxicology Program (NTP). Progol is the first inductive logic programming (ILP) algorithm to use a fully relational method for describing chemical structure in SARs, based on using atoms and their bond connectivities. Progol is well suited to forming SARs for carcinogenicity as it is designed to produce easily understandable rules (structural alerts) for sets of noncongeneric compounds. The Progol SAR method was tested by prediction of a set of compounds that have been widely predicted by other SAR methods (the compounds used in the NTP`s first round of carcinogenesis predictions). For these compounds no method (human or machine) was significantly more accurate than Progol. Progol was the most accurate method that did not use data from biological tests on rodents (however, the difference in accuracy is not significant). The Progol predictions were based solely on chemical structure and the results of tests for Salmonella mutagenicity. Using the full NTP database, the prediction accuracy of Progol was estimated to be 63% ({+-}3%) using 5-fold cross validation. A set of structural alerts for carcinogenesis was automatically generated and the chemical rationale for them investigated-these structural alerts are statistically independent of the Salmonella mutagenicity. Carcinogenicity is predicted for the compounds used in the NTP`s second round of carcinogenesis predictions. The results for prediction of carcinogenesis, taken together with the previous successful applications of predicting mutagenicity in nitroaromatic compounds, and inhibition of angiogenesis by suramin analogues, show that Progol has a role to play in understanding the SARs of cancer-related compounds. 29 refs., 2 figs., 4 tabs.

  16. Prediction of rodent carcinogenicity bioassays from molecular structure using inductive logic programming.

    PubMed Central

    King, R D; Srinivasan, A

    1996-01-01

    The machine learning program Progol was applied to the problem of forming the structure-activity relationship (SAR) for a set of compounds tested for carcinogenicity in rodent bioassays by the U.S. National Toxicology Program (NTP). Progol is the first inductive logic programming (ILP) algorithm to use a fully relational method for describing chemical structure in SARs, based on using atoms and their bond connectivities. Progol is well suited to forming SARs for carcinogenicity as it is designed to produce easily understandable rules (structural alerts) for sets of noncongeneric compounds. The Progol SAR method was tested by prediction of a set of compounds that have been widely predicted by other SAR methods (the compounds used in the NTP's first round of carcinogenesis predictions). For these compounds no method (human or machine) was significantly more accurate than Progol. Progol was the most accurate method that did not use data from biological tests on rodents (however, the difference in accuracy is not significant). The Progol predictions were based solely on chemical structure and the results of tests for Salmonella mutagenicity. Using the full NTP database, the prediction accuracy of Progol was estimated to be 63% (+/- 3%) using 5-fold cross validation. A set of structural alerts for carcinogenesis was automatically generated and the chemical rationale for them investigated- these structural alerts are statistically independent of the Salmonella mutagenicity. Carcinogenicity is predicted for the compounds used in the NTP's second round of carcinogenesis predictions. The results for prediction of carcinogenesis, taken together with the previous successful applications of predicting mutagenicity in nitroaromatic compounds, and inhibition of angiogenesis by suramin analogues, show that Progol has a role to play in understanding the SARs of cancer-related compounds. PMID:8933051

  17. NTP-CERHR Expert Panel Report on the reproductive and developmental toxicity of hydroxyurea

    EPA Science Inventory

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound e...

  18. 76 FR 77832 - Availability of Draft NTP Technical Reports; Request for Comments; Announcement of a Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-14

    ... announces the availability of seven draft NTP Technical Reports (TRs) tentatively scheduled for peer review... meeting. DATES: The meeting will be held on February 8-9, 2012. The draft NTP TRs should be available for... on the draft TRs should be sent to Danica Andrews, Designated Federal Official, Office of...

  19. Conceptual design of the french MAPS NTP cargo shuttle based on a particle bed reactor

    SciTech Connect

    Lenain, R.; Linet, F.L.; Poitevin, Y.; Proust, E.; Raepsaet, X.; Bernard, S.; Duchesne, A.

    1996-03-01

    MAPS, a 3-years study program on NTP has been launched at CEA in 1994 following the conclusions of a preliminary scoping study of an NTP system for earth to moon orbit cargo shuttle missions. This paper presents the main results obtained after one year of studies, and gives an outline of the future work. {copyright} {ital 1996 American Institute of Physics.}

  20. 75 FR 76995 - National Toxicology Program (NTP); Center for the Evaluation of Risks to Human Reproduction...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-10

    ... established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in 1998 (63 FR 68782) to... Reproduction (CERHR); NTP Workshop: Role of Environmental Chemicals in the Development of Diabetes and Obesity... (collectively referred to as ``substances'') cause adverse effects on reproduction and development and...

  1. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A

    EPA Science Inventory

    The National Toxicology Program (NTP)1 established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the CERHR is to provide timely, unbiased, scientifically sound evaluations of the potential for adverse effects on reproduction...

  2. 48 CFR 1516.603-2 - What are the requirements for use of an NTP?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... for use of an NTP? 1516.603-2 Section 1516.603-2 Federal Acquisition Regulations System ENVIRONMENTAL..., and Letter Contracts 1516.603-2 What are the requirements for use of an NTP? (a) An EPA FCS 1102....S.C. 9604(a)(1), and the National Oil and Hazardous Substances Pollution Contingency Plan (40...

  3. 48 CFR 1516.603-2 - What are the requirements for use of an NTP?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for use of an NTP? 1516.603-2 Section 1516.603-2 Federal Acquisition Regulations System ENVIRONMENTAL..., and Letter Contracts 1516.603-2 What are the requirements for use of an NTP? (a) An EPA FCS 1102....S.C. 9604(a)(1), and the National Oil and Hazardous Substances Pollution Contingency Plan (40...

  4. 48 CFR 1516.603-2 - What are the requirements for use of an NTP?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... for use of an NTP? 1516.603-2 Section 1516.603-2 Federal Acquisition Regulations System ENVIRONMENTAL..., and Letter Contracts 1516.603-2 What are the requirements for use of an NTP? (a) An EPA FCS 1102....S.C. 9604(a)(1), and the National Oil and Hazardous Substances Pollution Contingency Plan (40...

  5. BIOASSAY VESSEL FAILURE ANALYSIS

    SciTech Connect

    Vormelker, P

    2008-09-22

    Two high-pressure bioassay vessels failed at the Savannah River Site during a microwave heating process for biosample testing. Improper installation of the thermal shield in the first failure caused the vessel to burst during microwave heating. The second vessel failure is attributed to overpressurization during a test run. Vessel failure appeared to initiate in the mold parting line, the thinnest cross-section of the octagonal vessel. No material flaws were found in the vessel that would impair its structural performance. Content weight should be minimized to reduce operating temperature and pressure. Outer vessel life is dependent on actual temperature exposure. Since thermal aging of the vessels can be detrimental to their performance, it was recommended that the vessels be used for a limited number of cycles to be determined by additional testing.

  6. Impact of Environmental Enrichment Devices on NTP In Vivo Studies.

    PubMed

    Churchill, Sheba R; Morgan, Daniel L; Kissling, Grace E; Travlos, Gregory S; King-Herbert, Angela P

    2016-02-01

    The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices. PMID:26873679

  7. Pulse-based non-thermal plasma (NTP) disrupts the structural characteristics of bacterial biofilms.

    PubMed

    Ferrell, James R; Shen, Fan; Grey, Scott F; Woolverton, Christopher J

    2013-01-01

    Bacterial biofilms were constructed in vitro with two pathogenic strains of Pseudomonas aeruginosa and Staphylococcus aureus using a modified, novel sequential bioreactor system. The structure and stability of bacterial biofilms were evaluated following exposure to non-thermal plasma (NTP) discharge. Mathematical software was used to determine structural changes as biofilms grew over the course of 7 days. Statistical modeling was also performed to assess the ability of NTP to affect the development of the biofilms over different periods of time. Several structural characteristics were significantly affected by NTP discharge whereas others were unaffected. Changes in the three-dimensional structure of the biofilm following introduction of NTP was not limited to one period of development. The mechanism for this phenomenon is not understood but is likely to be a dual, synergistic effect due to the composition of the reactive species and other plasma-associated molecules isolated previously in the NTP discharge used in this study. PMID:23682750

  8. 76 FR 36923 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-23

    ...: The NTP BSC meeting, scheduled for July 21, 2011, and announced in the Federal Register (76 FR 28785... HUMAN SERVICES Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors (BSC): Notice of Cancellation AGENCY: National Toxicology Program (NTP), National Institute of...

  9. Raising Nuclear Thermal Propulsion (NTP) Technology Readiness Above 3

    NASA Technical Reports Server (NTRS)

    Gerrish, Harold P., Jr.

    2014-01-01

    NTP development is currently supported by the NASA program office "Advanced Exploration Systems". The concept is a main propulsion option being considered for human missions to Mars in the 2030's. Major NTP development took place in the 1960's and 1970's under the Rover/NERVA program. The technology had matured to TRL 6 and was preparing to go to TRL 7 with a prototype flight engine before the program was cancelled. Over the last 40 years, a variety of continuations started, but only lasted a few years each. The Rover/NERVA infrastructure is almost all gone. The only remains are a few pieces of hardware, final reports and a few who worked the Rover/NERVA. Two types of nuclear fuel are being investigated to meet the current engine design specific impulse of 900 seconds compared to approximately 850 seconds demonstrated during Rover/NERVA. One is a continuation of composite fuel with new coatings to better control mid-band corrosion. The other type is a CERMET fuel made of Tungsten and UO2. Both fuels are being made from Rover/NERVA lessons learned, but with slightly different recipes to increase fuel endurance at higher operating temperatures. The technology readiness level (TRL) of these current modified reactor fuels is approximately TRL 3. To keep the development cost low and help mature the TRL level past 4 quickly, a few special non-nuclear test facilities have been made to test surrogate fuel, with depleted uranium, as coupons and full length elements. Both facilities utilize inductive heating and are licensed to handle depleted uranium. TRL 5 requires exposing the fuel to a nuclear environment and TRL 6 requires a prototype ground or flight engine system test. Currently, three different NTP ground test facility options are being investigated: exhaust scrubber, bore hole, and total exhaust containment. In parallel, a prototype flight demonstration test is also being studied. The first human mission to Mars in the 2030's is currently 2033. For an advanced

  10. Prostaglandins, bioassay and inflammation

    PubMed Central

    Flower, R J

    2006-01-01

    The formation of the British Pharmacological Society coincided almost exactly with a series of ground-breaking studies that ushered in an entirely new field of research – that of lipid mediator pharmacology. For many years following their chemical characterisation, lipids were considered only to be of dietary or structural importance. From the 1930s, all this changed – slowly at first and then more dramatically in the 1970s and 1980s with the emergence of the prostaglandins (PGs), the first intercellular mediators to be clearly derived from lipids, in a dynamic on-demand system. The PGs exhibit a wide range of biological activities that are still being evaluated and their properties underlie the action of one of the world's all-time favourite medicines, aspirin, as well as its more modern congeners. This paper traces the development of the PG field, with particular emphasis on the skilful utilisation of the twin techniques of bioassay and analytical chemistry by U.K. and Swedish scientists, and the intellectual interplay between them that led to the award of a joint Nobel Prize to the principal researchers in the PG field, half a century after the first discovery of these astonishingly versatile mediators. PMID:16402103

  11. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    NASA Astrophysics Data System (ADS)

    Ballard, Richard O.

    2008-01-01

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP turbomachinery; and low-boiloff propellant management, and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be shown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  12. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    NASA Technical Reports Server (NTRS)

    Ballard, Richard O.

    2008-01-01

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP. turbomachinery; and low-boiloff propellant management; and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be $hown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  13. Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes

    PubMed Central

    Zhang, Lu; Silva, Daniel-Adriano; Pardo-Avila, Fátima; Wang, Dong; Huang, Xuhui

    2015-01-01

    The RNA polymerase II (Pol II) is a eukaryotic enzyme that catalyzes the synthesis of the messenger RNA using a DNA template. Despite numerous biochemical and biophysical studies, it remains elusive whether the “secondary channel” is the only route for NTP to reach the active site of the enzyme or if the “main channel” could be an alternative. On this regard, crystallographic structures of Pol II have been extremely useful to understand the structural basis of transcription, however, the conformation of the unpaired non-template DNA part of the full transcription bubble (TB) is still unknown. Since diffusion routes of the nucleoside triphosphate (NTP) substrate through the main channel might overlap with the TB region, gaining structural information of the full TB is critical for a complete understanding of Pol II transcription process. In this study, we have built a structural model of Pol II with a complete transcription bubble based on multiple sources of existing structural data and used Molecular Dynamics (MD) simulations together with structural analysis to shed light on NTP entry pathways. Interestingly, we found that although both channels have enough space to allow NTP loading, the percentage of MD conformations containing enough space for NTP loading through the secondary channel is twice higher than that of the main channel. Further energetic study based on MD simulations with NTP loaded in the channels has revealed that the diffusion of the NTP through the main channel is greatly disfavored by electrostatic repulsion between the NTP and the highly negatively charged backbones of nucleotides in the non-template DNA strand. Taken together, our results suggest that the secondary channel is the major route for NTP entry during Pol II transcription. PMID:26134169

  14. Future NTP Development Synergy Leveraged from Current J-2X Engine Development

    SciTech Connect

    Ballard, Richard O.

    2008-01-21

    This paper is a discussion of how the many long-lead development elements required for the realization of a future nuclear thermal propulsion (NTP) system can be effectively leveraged from the ongoing work being conducted on the J-2X engine program for the Constellation Program. Development studies conducted to date for NTP forward planning have identified a number of technical areas that will require advancement to acceptable technology readiness levels (TRLs) before they can be utilized in NTP system development. These include high-temperature, high-area ratio nozzle extension; long-life, low-NPSP turbomachinery; and low-boiloff propellant management, and a qualified nuclear fuel element. The current J-2X program is working many of these areas that can be leveraged to support NTP development in a highly compatible and synergistic fashion. In addition to supporting technical development, there are other programmatic issues being worked in the J-2X program that can be leveraged by a future NTP development program. These include compliance with recently-evolved space system requirements such as human-rating, fault tolerance and fracture control. These and other similar mandatory system requirements have been adopted by NASA and can result in a significant technical impact beyond elevation of the root technologies required by NTP. Finally, the exploitation of experience, methodologies, and procedures developed by the J-2X program in the areas of verification, qualification, certification, altitude simulation testing, and facility definition will be especially applicable to a future NTP system. The similarities in system mission (in-space propulsion) and operational environment (vacuum, zero-gee) between J-2X and NTP make this highly synergistic. Thus, it can be shown that the collective benefit of leveraging experience and technologies developed during the J-2X program can result in significant savings in development cost and schedule for NTP.

  15. Sensitive bioassay for detection of biologically active ricin in food

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The potential use of ricin as an agent of biological warfare highlights the need to develop fast and effective methods to detect biologically active ricin. The current “gold standard” for ricin detection is an in vivo mouse bioassay; however, this method is not practical to test on a large number of...

  16. Research Highlights

    ERIC Educational Resources Information Center

    Australian Council for Educational Research, 2004

    2004-01-01

    This document is an annual publication documenting developments in the Australian Council for Educational Research (ACER)'s research programs for the previous year. The 2004 edition highlights research on the following themes: (1) Helping international schools measure achievement; (2) Evaluating Australian teachers; (3) Tests of reading…

  17. 76 FR 67200 - Proposed National Toxicology Program (NTP) Review Process for the Report on Carcinogens: Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-31

    ... HUMAN SERVICES National Institutes of Health Proposed National Toxicology Program (NTP) Review Process... the National Toxicology Program (DNTP), National Institute of Environmental Health Sciences (NIEHS... Toxicology Program. BILLING CODE 4140-01-P...

  18. 77 FR 48995 - Draft National Toxicology Program (NTP) Monograph on Developmental Effects and Pregnancy Outcomes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-15

    ... Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy; Request... Pregnancy Outcomes Associated with Cancer Chemotherapy Use during Pregnancy (available by August 14, 2012... NTP Monograph on Developmental Effects and Pregnancy Outcomes Associated with Cancer Chemotherapy...

  19. 76 FR 28785 - Meeting of the National Toxicology Program (NTP) Board of Scientific Counselors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ...: National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National... of Environmental Chemicals in the Development of Diabetes and Obesity Collaborative Transgenerational... from recognized authorities knowledgeable in fields such as toxicology, pharmacology,...

  20. Current Ground Test Options for Nuclear Thermal Propulsion (NTP)

    NASA Technical Reports Server (NTRS)

    Gerrish, Harold P., Jr.

    2014-01-01

    About 20 different NTP engines/ reactors were tested from 1959 to 1972 as part of the Rover and Nuclear Engine for Rocket Vehicle Application (NERVA) program. Most were tested in open air at test cell A or test cell C, at the Nevada Test Site (NTS). Even after serious engine breakdowns of the reactor (e.g., Phoebus 1A), the test cells were cleaned up for other engine tests. The engine test stand (ETS) was made for high altitude (approximately 1 psia) testing of an NTP engine with a flight configuration, but still had the exhaust released to open air. The Rover/NERVA program became aware of new environmental regulations which would prohibit the release of any significant quantity of radioactive particulates and noble gases into the open air. The nuclear furnace (NF-1) was the last reactor tested before the program was cancelled in 1973, but successfully demonstrated a scrubber concept on how to filter the NTP exhaust. The NF-1 was demonstrated in the summer of 1972. The NF-1 used a 44MW reactor and operated each run for approximately 90 minutes. The system cooled the hot hydrogen exhaust from the engine with a water spray before entering a particle filter. The exhaust then passed through a series of heat exchangers and water separators to help remove water from the exhaust and further reduce the exhaust temperatures. The exhaust was next prepared for the charcoal trap by passing through a dryer and effluent cooler to bring exhaust temperatures close to liquid nitrogen. At those low temperatures, most of the noble gases (e.g., Xe and Kr made from fission products) get captured in the charcoal trap. The filtered hydrogen is finally passed through a flare stack and released to the air. The concept was overall successful but did show a La plating on some surfaces and had multiple recommendations for improvement. The most recent detailed study on the NTP scrubber concept was performed by the ARES Corporation in 2006. The concept is based on a 50,000 lbf thrust engine

  1. A particle bed reactor based NTP in the 112,500 N thrust class

    SciTech Connect

    Ludewig, H.; Powell, J.R.; Lazareth, O.W. Jr.; Todosow, M.

    1993-04-01

    This paper discusses the application of a Particle bed Reactor (PBR) to a 112,500 N thrust Nuclear Thermal Propulsion (NTP) Engine. The method of analysis is described, followed by a presentation of the results. It is concluded that the PBR would result in a very competitive NTP engine. In addition, due to the high power densities possible with a PBR, high thrust/weight ratios are possible. This conclusion can be used to satisfy a variety of mission goals.

  2. A particle bed reactor based NTP in the 112,500 N thrust class

    SciTech Connect

    Ludewig, H.; Powell, J.R.; Lazareth, O.W. Jr.; Todosow, M. )

    1993-01-20

    This paper discusses the application of a Particle Bed Reactor (PBR) to a 112,500 N thrust Nuclear Thermal Propulsion (NTP) Engine. The method of analysis is described, followed by a presentation of the results. It is concluded that the PBR would result in a very competitive NTP engine. In addition, due to the high power densities possible with a PBR, high thrust/weight ratios are possible. This conclusion can be used to satisfy a variety of mission goals.

  3. Operational mode analysis of the maps NTP system

    SciTech Connect

    Linet, F.L.; Bernard, S.; Carruge, D.; Poitevin, Y.; Raepsaet, X.

    1996-03-01

    Within the framework of the french NTP program MAPS, the analysis of the (start-up/shut-down) transient sequences whose negative impact on the specific impulsion Isp is important, requires the evaluation of the hydrogen system performance and consequently the development of a simulation computer program. This work induces a preliminary evaluation of the hydrogen system performance under nominal operating conditions. A first approach of the transient operating mode has been simultaneously performed; more specifically the evolution of the core during a shut-down sequence has been studied in order to improve the residual power evacuation and optimize necessary hydrogen amounts for cooling. Furthermore the {open_quote}{open_quote}SIMAPS{close_quote}{close_quote} computer program based on the 3D thermohydraulic code {open_quote}{open_quote}FLICA 4{close_quote}{close_quote} is being developed to analyze transient process and its benchmarking under nominal conditions is under way. Its summary presentation is given in conclusion. {copyright} {ital 1996 American Institute of Physics.}

  4. Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

    PubMed Central

    Elcombe, Clifford R; Odum, Jenny; Foster, John R; Stone, Susan; Hasmall, Susan; Soames, Anthony R; Kimber, Ian; Ashby, John

    2002-01-01

    We studied nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), to determine their ability to induce acute or subacute biochemical and tissue changes that may act as useful predictors of nongenotoxic rodent carcinogenesis. The chemicals selected included six liver carcinogens (two of which are peroxisome proliferators), three thyroid gland carcinogens, and four kidney carcinogens. We administered the chemicals (diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene to the same strains of mice and rats used in the original NTP bioassays (nine chemicals to rats and seven to mice). Selected tissues (liver, thyroid gland, and kidney) were collected from groups of animals at 7, 28, and 90 days for evaluation. Tissue changes selected for study were monitored for all of the test groups, irrespective of the specificity of the carcinogenic responses observed in those tissues. This allowed us to assess both the carcinogen specificity and the carcinogen sensitivity of the events being monitored. We studied relative weight, cell labeling indices, and pathologic changes such as hypertrophy in all tissues; a range of cytochrome P450 enzymes and palmitoyl coenzyme A oxidase in the liver; changes in the levels of plasma total triiodothyronine, total thyroxine, and thyroid-stimulating hormone (TSH) as markers of thyroid gland function; and hyaline droplet formation, tubular basophilia, and the formation of granular casts in the kidney. There were no single measurements that alerted specifically to the carcinogenicity of the agents to the rodent liver, thyroid gland, or kidney. However, in the majority of cases, the chemical induction of cancer in a tissue was preceded by a range of biochemical/morphologic changes, most of which were moderately specific for a carcinogenic outcome, and some of which were highly specific for

  5. Sediment bioassays with oyster larvae

    SciTech Connect

    Chapman, P.M.; Morgan, J.D.

    1983-10-01

    Tests with naturally-occurring sediments are rare and sediment testing methodology is not standardized. The authors present a simple methodology for undertaking sediment bioassays with oyster larvae, and present data from a recent study to prove the utility of this method.

  6. UNIFYING SCALER FOR BIOASSAY TESTS

    EPA Science Inventory

    An extensive set of interlaboratory root bioassay data was unified using centroids of individual tests as scalers. It is shown that the dose response obeys a first order differential equation with the constant of the equation related to the sensitivity of the dose response relati...

  7. Proceedings of the 2013 Joint JSTP/NTP Satellite Symposium

    PubMed Central

    Elmore, Susan A.; Hoenerhoff, Mark; Katsuta, Osamu; Kokoshima, Hiroko; Maronpot, Robert; Nagai, Hiroaki; Satoh, Hiroshi; Tanaka, Yasuhiro; Tochitani, Tomoaki; Tsuchiya, Seiichiro; Yoshizawa, Katsuhiko

    2013-01-01

    The first joint Japanese Society of Toxicologic Pathology (JSTP) and National Toxicology Program (NTP) Satellite Symposium, entitled “Pathology Potpourri,” was held on January 29th at Okura Frontier Hotel in Tsukuba, Ibaraki, Japan, in advance of the JSTP’s 29th Annual Meeting. The goal of this Symposium was to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers’ presentations, including diagnostic or nomenclature issues that were presented, select images that were used for audience voting or discussion, and the voting results. Some lesions and topics covered during the symposium include: treatment-related atypical hepatocellular foci of cellular alteration in B6C3F1 mice; purulent ventriculoencephalitis in a young BALB/c mouse; a subcutaneous malignant schwannoma in a RccHan:WIST rat; spontaneous nasal septum hyalinosis/eosinophilic substance in B6C3F1 mice; a rare pancreatic ductal cell adenoma in a young Lewis rat; eosinophilic crystalline pneumonia in a transgenic mouse model; hyaline glomerulopathy in two female ddY mice; treatment-related intrahepatic erythrocytes in B6C3F1 mice; treatment-related subendothelial hepatocytes in B6C3F1 mice; spontaneous thyroid follicular cell vacuolar degeneration in a cynomolgus monkey; congenital hepatic fibrosis in a 1-year-old cat; a spontaneous adenocarcinoma of the middle ear in a young Crl:CD(SD) rat; and finally a series of cases illustrating some differences between cholangiofibrosis and cholangiocarcinoma in Sprague Dawley and F344 rats. PMID:23914068

  8. Environmental monitoring using genetic bioassays

    SciTech Connect

    Lewtas, J.

    1989-01-01

    Environmental monitoring has evolved over the last ten years toward providing data more useful for exposure and risk assessment. The objective of many monitoring studies in the 1960s and 1970s was to monitor concentrations of pollutants including environmental mutagens at ambient locations, such as roof tops and in large bodies of water, where the pollutants would be well mixed and represent a homogeneous sample. In the 1980s, a number of studies focused on assessing the emission of mutagens from various sources. Now the emphasis has shifted to monitoring human exposure to environmental mutagens and to understanding which sources and factors lead to increased exposure and potential cancer risk. The chapter briefly reviews advances in genetic bioassay methods for environmental monitoring and focuses on approaches to integrating genetic bioassay methods with environmental-monitoring studies.

  9. NTP-CERHR monograph on the potential human reproductive and developmental effects of bisphenol A.

    PubMed

    Shelby, Michael D

    2008-09-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for bisphenol A to cause adverse effects on reproduction and development in humans. The CERHR Expert Panel on Bisphenol A completed its evaluation in August 2007. CERHR selected bisphenol A for evaluation because of the: widespread human exposure; public concern for possible health effects from human exposures; high production volume; evidence of reproductive and developmental toxicity in laboratory animal studies Bisphenol A (CAS RN: 80-05-7) is a high production volume chemical used primarily in the production of polycarbonate plastics and epoxy resins. Polycarbonate plastics are used in some food and drink containers; the resins are used as lacquers to coat metal products such as food cans, bottle tops, and water supply pipes. To a lesser extent bisphenol A is used in the production of polyester resins, polysulfone resins, polyacrylate resins, and flame retardants. In addition, bisphenol A is used in the processing of polyvinyl chloride plastic and in the recycling of thermal paper. Some polymers used in dental sealants and tooth coatings contain bisphenol A. The primary source of exposure to bisphenol A for most people is assumed to occur through the diet. While air, dust, and water (including skin contact during bathing and swimming) are other possible sources of exposure, bisphenol A in food and beverages accounts for the majority of daily human exposure. The highest estimated daily intakes of bisphenol A in the general population occur in infants and children. The results of this bisphenol A evaluation are published in an NTP-CERHR Monograph that includes the (1) NTP Brief and (2) Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A. Additional information related to the evaluation process, including the peer review report for the NTP Brief and public comments received on the draft NTP

  10. NTP-CERHR monograph on the potential human reproductive and developmental effects of methylphenidate.

    PubMed

    2005-08-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for methylphenidate to cause adverse effects on reproduction and development in humans. Methylphenidate was selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. Methylphenidate is a central nervous system stimulant approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons 6 years of age and older and for narcolepsy. The results of this evaluation on methylphenidate are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is negligible concern for methylphenidate-induced tics and movement disorders. This conclusion is based on studies showing that children treated with therapeutic doses of methylphenidate have no evidence of movement disorders or tics due to the medication. Second, there is minimal concern for methylphenidate-induced growth restriction. This conclusion is based on growth restriction being observed in animal studies only at high doses of methylphenidate using a non-therapeutic route of exposure. The effect on growth was reversible. Finally, there are insufficient data to draw conclusions on 1) an association between methylphenidate therapy in pregnant women and pregnancy loss and 2) possible reproductive effects of methylphenidate in humans. NTP-CERHR monographs are transmitted to federal and state agencies, interested

  11. A review comparing deoxyribonucleoside triphosphate (dNTP) concentrations in the mitochondrial and cytoplasmic compartments of normal and transformed cells

    PubMed Central

    Gandhi, Vishal V.; Samuels, David C.

    2011-01-01

    The deoxyribonucleoside triphosphate (dNTP) pools that support the replication of mitochondrial DNA are physically separated from the rest of the cell by the double membrane of the mitochondria. Perturbed homeostasis of mitochondrial dNTP pools is associated with a set of severe diseases collectively termed mitochondrial DNA depletion syndromes. The degree of interaction of the mitochondrial dNTP pools with the corresponding dNTP pools in the cytoplasm is currently not clear. We reviewed the literature on previously reported simultaneous measurements of mitochondrial and cytoplasmic deoxyribonucleoside triphosphate pools to investigate and quantify the extent of the influence of the cytoplasmic nucleotide metabolism on mitochondrial dNTP pools. We converted the reported measurements to concentrations creating a catalog of paired mitochondrial and cytoplasmic dNTP concentration measurements. Over experiments from multiple laboratories, dNTP concentrations in the mitochondria are highly correlated with dNTP concentrations in the cytoplasm in normal cells in culture (Pearson R = 0.79, p = 3 × 10-7) but not in transformed cells. For dTTP and dATP there was a strong linear relationship between the cytoplasmic and mitochondrial concentrations in normal cells. From this linear model we hypothesize that the salvage pathway within the mitochondrion is only capable of forming a concentration of approximately 2 μM of dTTP and dATP, and that higher concentrations require transport of deoxyribonucleotides from the cytoplasm. PMID:21774628

  12. A review of whole animal bioassays of the carcinogenic potential of naphthalene.

    PubMed

    North, D Warner; Abdo, Kamal M; Benson, Janet M; Dahl, Alan R; Morris, John B; Renne, Roger; Witschi, Hanspeter

    2008-07-01

    This report provides a summary of deliberations conducted under the charge for members of Module A participating in the Naphthalene State-of-the-Science Symposium (NS3), Monterey, CA, October 9-12, 2006. Whole animal bioassays have been performed by the National Toxicology Program in mice and rats to ascertain the carcinogenic potential of naphthalene by inhalation exposure. A statistically significant increased incidence of pulmonary alveolar/bronchiolar adenoma (a benign lesion), was observed among female mice; an observed increase among the males did not reach statistical significance. No nasal tumors were observed in either sex. A tumorigenic response was observed in both sexes of rats, in males an increased incidence of nasal respiratory epithelium adenoma (a benign rather than malignant lesion) and in females, olfactory epithelial neuroblastoma. Interpretations of these studies vary. On the one hand, evidence of extensive non-neoplastic response in both sexes of both species indicates cytotoxicity occurred at all doses, and strongly suggests that cytotoxicity played a significant role in the tumor responses observed in the target tissues. On the other hand, olfactory epithelial neuroblastoma has rarely been observed in NTP bioassays. This review seeks to develop a consensus understanding of the scientific evidence provided by these studies, taking into account that they have been used as the basis for quantitative human cancer risk assessment, and suggests scientific studies that, if performed, could resolve scientific uncertainties. PMID:18364246

  13. Nanomaterial-Based Electrochemical Biosensors and Bioassays

    SciTech Connect

    Liu, Guodong; Mao, Xun; Gurung, Anant; Baloda, Meenu; Lin, Yuehe; He, Yuqing

    2010-08-31

    This book chapter summarizes the recent advance in nanomaterials for electrochemical biosensors and bioassays. Biofunctionalization of nanomaterials for biosensors fabrication and their biomedical applications are discussed.

  14. NTP-CERHR EXPERT PANEL REPORT ON REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF METHYLPHENIDATE.

    EPA Science Inventory

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on...

  15. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AMPHETAMINE AND METHAMPHETAMINE.

    EPA Science Inventory

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects ...

  16. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF ACRYLAMIDE

    EPA Science Inventory

    The National Toxicology Program Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) convened an expert panel in May 2004 to evaluate acrylamide. The report of the expert panel, prepared in accordance with CERHR Guidelines, provides a detailed summary of all publi...

  17. Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism.

    PubMed

    Nikkanen, Joni; Forsström, Saara; Euro, Liliya; Paetau, Ilse; Kohnz, Rebecca A; Wang, Liya; Chilov, Dmitri; Viinamäki, Jenni; Roivainen, Anne; Marjamäki, Päivi; Liljenbäck, Heidi; Ahola, Sofia; Buzkova, Jana; Terzioglu, Mügen; Khan, Nahid A; Pirnes-Karhu, Sini; Paetau, Anders; Lönnqvist, Tuula; Sajantila, Antti; Isohanni, Pirjo; Tyynismaa, Henna; Nomura, Daniel K; Battersby, Brendan J; Velagapudi, Vidya; Carroll, Christopher J; Suomalainen, Anu

    2016-04-12

    Mitochondrial dysfunction affects cellular energy metabolism, but less is known about the consequences for cytoplasmic biosynthetic reactions. We report that mtDNA replication disorders caused by TWINKLE mutations-mitochondrial myopathy (MM) and infantile onset spinocerebellar ataxia (IOSCA)-remodel cellular dNTP pools in mice. MM muscle shows tissue-specific induction of the mitochondrial folate cycle, purine metabolism, and imbalanced and increased dNTP pools, consistent with progressive mtDNA mutagenesis. IOSCA-TWINKLE is predicted to hydrolyze dNTPs, consistent with low dNTP pools and mtDNA depletion in the disease. MM muscle also modifies the cytoplasmic one-carbon cycle, transsulfuration, and methylation, as well as increases glucose uptake and its utilization for de novo serine and glutathione biosynthesis. Our evidence indicates that the mitochondrial replication machinery communicates with cytoplasmic dNTP pools and that upregulation of glutathione synthesis through glucose-driven de novo serine biosynthesis contributes to the metabolic stress response. These results are important for disorders with primary or secondary mtDNA instability and offer targets for metabolic therapy. PMID:26924217

  18. 77 FR 22321 - National Toxicology Program (NTP) Interagency Center for the Evaluation of Alternative...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ...\\ NIEHS/NTP,\\2\\ U.S. Environmental Protection Agency (EPA),\\3\\ and U.S. Food and Drug Administration (FDA....niehs.nih.gov/go/28213 . \\3\\ http://www.epa.gov/ncct/Tox21/ . \\4\\ http://www.fda.gov/ . The Tox21 HTS... efficient, high throughput in vitro assays. Tox21 also aims to expand the ability to screen...

  19. dNTP-dependent Conformational Transitions in the Fingers Subdomain of Klentaq1 DNA Polymerase

    PubMed Central

    Rothwell, Paul J.; Allen, William J.; Sisamakis, Evangelos; Kalinin, Stanislav; Felekyan, Suren; Widengren, Jerker; Waksman, Gabriel; Seidel, Claus A. M.

    2013-01-01

    DNA polymerases are responsible for the accurate replication of DNA. Kinetic, single-molecule, and x-ray studies show that multiple conformational states are important for DNA polymerase fidelity. Using high precision FRET measurements, we show that Klentaq1 (the Klenow fragment of Thermus aquaticus DNA polymerase 1) is in equilibrium between three structurally distinct states. In the absence of nucleotide, the enzyme is mostly open, whereas in the presence of DNA and a correctly base-pairing dNTP, it re-equilibrates to a closed state. In the presence of a dNTP alone, with DNA and an incorrect dNTP, or in elevated MgCl2 concentrations, an intermediate state termed the “nucleotide-binding” state predominates. Photon distribution and hidden Markov modeling revealed fast dynamic and slow conformational processes occurring between all three states in a complex energy landscape suggesting a mechanism in which dNTP delivery is mediated by the nucleotide-binding state. After nucleotide binding, correct dNTPs are transported to the closed state, whereas incorrect dNTPs are delivered to the open state. PMID:23525110

  20. Nanoparticle-Based Biosensors and Bioassays

    SciTech Connect

    Liu, Guodong; Wang, Jun; Lin, Yuehe; Wang, Joseph

    2007-10-11

    In this book chapter, we review the recent advances in nanoparticles based bioassay. The nanoparticles include quantum dots, silica nanoparticles and apoferritin nanoparticles. The new nanoparticles-based labels hold great promise for multiplex protein and DNA detection and for enhancing the sensitivity of other bioassays.

  1. The legacy of the F344 rat as a cancer bioassay model (a retrospective summary of three common F344 rat neoplasms).

    PubMed

    Maronpot, Robert R; Nyska, Abraham; Foreman, Jennifer E; Ramot, Yuval

    2016-09-01

    The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat. We show that due to the highly variable background incidence of F344 MNCL, more reliance on historical control data than is usual for most tumor responses is warranted to evaluate potential effect of any chemical treatment in this rat strain. The high spontaneous incidence of LCTs in the testes of male F344 rats has made this tumor endpoint of little practical use in identifying potential testicular carcinogenic responses. TVM responses in F344 rats have a biological plausible relationship to LCTs unlike TVM in humans. Given their high spontaneous background incidence and species-specific biology, we contend that MNCL and LCT, along with TVM responses, in F344 rat carcinogenicity studies are inappropriate tumor types for human health risk assessment and lack relevance in predicting human carcinogenicity. PMID:27278595

  2. Regulatory Forum Opinion Piece*: New testing paradigms for reproductive and developmental toxicity - The NTP Modified One generation study and OECD 443

    PubMed Central

    Foster, Paul M.D.

    2014-01-01

    The NTP has developed a new flexible study design, termed the modified one generation reproduction (MOG) study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity which is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new OECD 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F1 animals, the generation of adequately powered, robust datasets which include both pre-and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R’s. PMID:24862797

  3. Regulatory Forum opinion piece: New testing paradigms for reproductive and developmental toxicity--the NTP modified one generation study and OECD 443.

    PubMed

    Foster, Paul M D

    2014-12-01

    The National Toxicology Program (NTP) has developed a new flexible study design, termed the modified one generation (MOG) reproduction study. The MOG study will encompass measurements of developmental and reproductive toxicity parameters as well as enable the setting of appropriate dose levels for a cancer bioassay through evaluation of target organ toxicity that is based on test article exposure that starts during gestation. This study design is compared and contrasted with the new Organization for Economic Co-operation and Development (OECD) 443 test guideline, the extended one generation reproduction study. The MOG study has a number of advantages, with a focus on F 1 animals, the generation of adequately powered, robust data sets that include both pre and postnatal developmental toxicity information, and the measurement of effects on reproductive structure and function in the same animals. This new study design does not employ the use of internal triggers in the design structure for the use of animals already on test and is also consistent with the principles of the 3R's. PMID:24862797

  4. Bioassays Based on Molecular Nanomechanics

    DOE PAGESBeta

    Majumdar, Arun

    2002-01-01

    Recent experiments have shown that when specific biomolecular interactions are confined to one surface of a microcantilever beam, changes in intermolecular nanomechanical forces provide sufficient differential torque to bend the cantilever beam. This has been used to detect single base pair mismatches during DNA hybridization, as well as prostate specific antigen (PSA) at concentrations and conditions that are clinically relevant for prostate cancer diagnosis. Since cantilever motion originates from free energy change induced by specific biomolecular binding, this technique is now offering a common platform for label-free quantitative analysis of protein-protein binding, DNA hybridization DNA-protein interactions, and in general receptor-ligandmore » interactions. Current work is focused on developing “universal microarrays” of microcantilever beams for high-throughput multiplexed bioassays.« less

  5. NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Fluoxetine.

    PubMed

    2004-11-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for fluoxetine to cause adverse effects on reproduction and development in humans. Fluoxetine (Prozac(R); Serafemtrade mark) was selected for evaluation because of 1) sufficient reproductive and developmental studies, 2) human exposure information, 3) changing prescription patterns, and 4) public concern about potential reproductive and/or developmental hazards associated with exposure. Fluoxetine, an antidepressant, is also prescribed to treat premenstrual dysphoric disorder and has recently been approved for use in 7-17 year-olds. The results of this evaluation on fluoxetine are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Fluoxetine, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to fluoxetine on human development and reproduction. First, there is some concern for developmental effects, specifically shortened gestation and poor neonatal adaptation at therapeutic doses (20-80 mg/day). This conclusion is based on evidence from human studies that fluoxetine produces an increased rate of poor neonatal adaptation and that fluoxetine exposure during pregnancy can result in a shortened gestation and reduced birth weight at term. Second, there is minimal concern for adverse reproductive effects in fluoxetine-exposed adults. Evidence from human studies show that therapeutic doses of fluoxetine may, in both men and women, result in reversible, impaired sexual function, specifically a delay in or an inability to achieve orgasm. Finally, there are insufficient data to draw conclusions on 1) an association between fluoxetine therapy in pregnant women and pregnancy loss; and 2) on how breast milk or therapeutic

  6. NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

    PubMed

    2005-07-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based

  7. A bioaccumulation bioassay for freshwater sediments

    USGS Publications Warehouse

    Mac, Michael J.; Noguchi, George E.; Hesselberg, Robert J.; Edsall, Carol C.; Shoesmith, John A.; Bowker, James D.

    1990-01-01

    A laboratory bioassay is described for determining the bioavailability of contaminants from freshwater sediments. The bioassay consists of 10-d exposures to whole sediments under flow-through conditions. After testing five species, the fathead minnow (Pimephales promelas) and the earthworm (Lubricus terrestris) were recommended for use in the test. When the availability of polychlorinated biphenyls (PCBs), Hg and Zn from Great Lakes sediments was examined in laboratory exposures, only the PCBs were accumulated. A field validation study demonstrated that the magnitude of accumulation in laboratory exposures was similar to that in organisms caged in the field. A protocol is recommended for using the test as a standardized bioaccumulation bioassay.

  8. Subscale Validation of the Subsurface Active Filtration of Exhaust (SAFE) Approach to the NTP Ground Testing

    NASA Technical Reports Server (NTRS)

    Marshall, William M.; Borowski, Stanley K.; Bulman, Mel; Joyner, Russell; Martin, Charles R.

    2015-01-01

    Nuclear thermal propulsion (NTP) has been recognized as an enabling technology for missions to Mars and beyond. However, one of the key challenges of developing a nuclear thermal rocket is conducting verification and development tests on the ground. A number of ground test options are presented, with the Sub-surface Active Filtration of Exhaust (SAFE) method identified as a preferred path forward for the NTP program. The SAFE concept utilizes the natural soil characteristics present at the Nevada National Security Site to provide a natural filter for nuclear rocket exhaust during ground testing. A validation method of the SAFE concept is presented, utilizing a non-nuclear sub-scale hydrogen/oxygen rocket seeded with detectible radioisotopes. Additionally, some alternative ground test concepts, based upon the SAFE concept, are presented. Finally, an overview of the ongoing discussions of developing a ground test campaign are presented.

  9. Multidisciplinary Simulation of Graphite-Composite and Cermet Fuel Elements for NTP Point of Departure Designs

    NASA Technical Reports Server (NTRS)

    Stewart, Mark E.; Schnitzler, Bruce G.

    2015-01-01

    This paper compares the expected performance of two Nuclear Thermal Propulsion fuel types. High fidelity, fluid/thermal/structural + neutronic simulations help predict the performance of graphite-composite and cermet fuel types from point of departure engine designs from the Nuclear Thermal Propulsion project. Materials and nuclear reactivity issues are reviewed for each fuel type. Thermal/structural simulations predict thermal stresses in the fuel and thermal expansion mis-match stresses in the coatings. Fluid/thermal/structural/neutronic simulations provide predictions for full fuel elements. Although NTP engines will utilize many existing chemical engine components and technologies, nuclear fuel elements are a less developed engine component and introduce design uncertainty. Consequently, these fuel element simulations provide important insights into NTP engine performance.

  10. Design Evolutuion of Hot Isotatic Press Cans for NTP Cermet Fuel Fabrication

    NASA Technical Reports Server (NTRS)

    Mireles, O. R.; Broadway, J.; Hickman, R.

    2014-01-01

    Nuclear Thermal Propulsion (NTP) is under consideration for potential use in deep space exploration missions due to desirable performance properties such as a high specific impulse (> 850 seconds). Tungsten (W)-60vol%UO2 cermet fuel elements are under development, with efforts emphasizing fabrication, performance testing and process optimization to meet NTP service life requirements [1]. Fuel elements incorporate design features that provide redundant protection from crack initiation, crack propagation potentially resulting in hot hydrogen (H2) reduction of UO2 kernels. Fuel erosion and fission product retention barriers include W coated UO2 fuel kernels, W clad internal flow channels and fuel element external W clad resulting in a fully encapsulated fuel element design as shown.

  11. Characterization of purple acid phosphatases involved in extracellular dNTP utilization in Stylosanthes.

    PubMed

    Liu, Pan-Dao; Xue, Ying-Bin; Chen, Zhi-Jian; Liu, Guo-Dao; Tian, Jiang

    2016-07-01

    Stylo (Stylosanthes spp.) is a pasture legume predominant in tropical and subtropical areas, where low phosphorus (P) availability is a major constraint for plant growth. Therefore, stylo might exhibit superior utilization of the P pool on acid soils, particularly organic P. However, little is known about mechanisms of inorganic phosphate (Pi) acquisition employed by stylo. In this study, the utilization of extracellular deoxy-ribonucleotide triphosphate (dNTP) and the underlying physiological and molecular mechanisms were examined for two stylo genotypes with contrasting P efficiency. Results showed that the P-efficient genotype, TPRC2001-1, was superior to the P-inefficient genotype, Fine-stem, when using dNTP as the sole P source. This was reflected by a higher dry weight and total P content for TPRC2001-1 than for Fine-stem, which was correlated with higher root-associated acid phosphatase (APase) activities in TPRC2001-1 under low P conditions. Subsequently, three PAP members were cloned from TPRC2001-1: SgPAP7, SgPAP10, and SgPAP26 Expression levels of these three SgPAPs were up-regulated by Pi starvation in stylo roots. Furthermore, there was a higher abundance of transcripts of SgPAP7 and SgPAP10 in TPRC2001-1 than in Fine-stem. Subcellular localization analysis demonstrated that these three SgPAPs were localized on the plasma membrane. Overexpression of these three SgPAPs could result in significantly increased root-associated APase activities, and thus extracellular dNTP utilization in bean hairy roots. Taken together, the results herein suggest that SgPAP7, SgPAP10, and SgPAP26 may differentially contribute to root-associated APase activities, and thus control extracellular dNTP utilization in stylo. PMID:27194738

  12. Suppression of the E. coli SOS response by dNTP pool changes.

    PubMed

    Maslowska, Katarzyna H; Makiela-Dzbenska, Karolina; Fijalkowska, Iwona J; Schaaper, Roel M

    2015-04-30

    The Escherichia coli SOS system is a well-established model for the cellular response to DNA damage. Control of SOS depends largely on the RecA protein. When RecA is activated by single-stranded DNA in the presence of a nucleotide triphosphate cofactor, it mediates cleavage of the LexA repressor, leading to expression of the 30(+)-member SOS regulon. RecA activation generally requires the introduction of DNA damage. However, certain recA mutants, like recA730, bypass this requirement and display constitutive SOS expression as well as a spontaneous (SOS) mutator effect. Presently, we investigated the possible interaction between SOS and the cellular deoxynucleoside triphosphate (dNTP) pools. We found that dNTP pool changes caused by deficiencies in the ndk or dcd genes, encoding nucleoside diphosphate kinase and dCTP deaminase, respectively, had a strongly suppressive effect on constitutive SOS expression in recA730 strains. The suppression of the recA730 mutator effect was alleviated in a lexA-deficient background. Overall, the findings suggest a model in which the dNTP alterations in the ndk and dcd strains interfere with the activation of RecA, thereby preventing LexA cleavage and SOS induction. PMID:25824947

  13. Two-generation saccharin bioassays.

    PubMed

    Arnold, D L

    1983-04-01

    The controversy regarding the safety of saccharin for human consumption started shortly after its discovery over 100 years ago and has yet to subside appreciably. The consumption of saccharin, particularly in North America, began to escalate when the U.S. Food and Drug Administration set new standards of identity which allowed foods containing artificial sweeteners to be promoted as "nonnutritive" or "noncaloric" sweeteners for use by the general public. In 1969, when cyclamates were banned, at least 10 single-generation feeding studies were undertaken with saccharin to more accurately assess the potential toxicological consequences resulting from the anticipated increase in its consumption. None of these studies resulted in any overt regulatory action. Subsequently, the introduction of the two-generation chronic toxicity/carcinogenicity bioassay added a new tool to the toxicologist's arsenal. Three two-generation studies using saccharin have since been conducted. The results from these studies clearly show that when rats were exposed to diets containing 5 or 7.5% sodium saccharin from the time of conception to death, an increased frequency of urinary bladder cancers was found, predominantly in the males. While some study results suggested that impurities in commercial saccharin or the presence of urinary tract calculi may have been responsible for the observed bladder tumors, it now appears that these possibilities are highly unlikely. The mechanism by which saccharin elicited the bladder tumors using the two-generation experiment has not been ascertained. PMID:6347682

  14. Bioassays for Monitoring Insecticide Resistance

    PubMed Central

    Miller, Audra L.E.; Tindall, Kelly; Leonard, B. Rogers

    2010-01-01

    Pest resistance to pesticides is an increasing problem because pesticides are an integral part of high-yielding production agriculture. When few products are labeled for an individual pest within a particular crop system, chemical control options are limited. Therefore, the same product(s) are used repeatedly and continual selection pressure is placed on the target pest. There are both financial and environmental costs associated with the development of resistant populations. The cost of pesticide resistance has been estimated at approximately $ 1.5 billion annually in the United States. This paper will describe protocols, currently used to monitor arthropod (specifically insects) populations for the development of resistance. The adult vial test is used to measure the toxicity to contact insecticides and a modification of this test is used for plant-systemic insecticides. In these bioassays, insects are exposed to technical grade insecticide and responses (mortality) recorded at a specific post-exposure interval. The mortality data are subjected to Log Dose probit analysis to generate estimates of a lethal concentration that provides mortality to 50% (LC50) of the target populations and a series of confidence limits (CL's) as estimates of data variability. When these data are collected for a range of insecticide-susceptible populations, the LC50 can be used as baseline data for future monitoring purposes. After populations have been exposed to products, the results can be compared to a previously determined LC50 using the same methodology. PMID:21248689

  15. PHOXOCEPHALID AMPHIPOD BIOASSAY FOR MARINE SEDIMENT TOXICITY

    EPA Science Inventory

    The relative toxicity of marine sediment can be accurately determined through acute, static bioassays with the phoxocepalid amphipod Repoxynius abronius. Mortality and sublethal effects on emergence from sediment and reburial behavior are determined after ten day exposure in 1-L ...

  16. Bioassay criteria for environmental restoration workers

    SciTech Connect

    Carbaugh, E.H.; Bihl, D.E.

    1993-01-01

    Environmental restoration (ER) work at the U. S. Department of Energy Hanford Site posed questions concerning when to perform bioassay monitoring of workers for potential intakes of radioactivity. Application of criteria originally developed for use inside radionuclide processing facilities to ER work resulted in overly restrictive bioassay requirements. ER work typically involves site characterization or, excavating large quantities of potentially contaminated soil, rather than working with concentrated quantities of radioactivity as in a processing facility. An improved approach, tailored to ER work, provided soil contamination concentrations above which worker bioassay would be required. Soil concentrations were derived assuming acute or chronic intakes of 2% of an Annual Limit on Intake (ALI), or a potential committed effective dose equivalent of 100 mrem, and conservative dust loading of air from the work. When planning ER work, the anticipated soil concentration and corresponding need for bioassay could be estimated from work-site historical records. Once site work commenced, soil sampling and work-place surveys could be used to determine bioassay needs. This approach substantially reduced the required number of bioassay samples with corresponding reductions in analytical costs, schedules, and more flexible work-force management. (Work supported by the US Department of Energy under contract DOE-AC06-76RLO 1830.)

  17. A Colorimetric Bioassay for Perchlorate

    NASA Astrophysics Data System (ADS)

    Heinnickel, M. L.; Smith, S.; Coates, J. D.

    2007-12-01

    Recognition of perchlorate (ClO4-) as a widespread contaminant across the United States and its potential adverse affects towards human health has motivated the EPA to place ClO4- on its contaminant candidate list for drinking water supplies. While a federal MCL has not yet been set, a recommended public health goal of 1 ppb (μg.L-1) was established by the US EPA in 2002. To date, methods of detection require use of sensitive ion chromatographic equipment that are expensive, time consuming, and require highly trained personnel for use. Our studies are focused on the development of a highly sensitive, simple, and robust colorimetric bioassay based on the primary enzyme involved in microbial ClO4- reduction, the perchlorate reductase (Pcr). A previously published assay used reduced methyl viologen (MV, the dye is reduced with sodium hydrosulfite) as an electron donor to demonstrate Pcr activity. The assay directly correlates the amount of MV oxidized with the amount of ClO4- reduced by assuming a transfer of four electrons. To test this assumption, we compared actual concentrations of MV oxidized to ClO4- reduced in this assay. ClO4- concentrations were determined using a Dionex ICS-500 ion chromatography system, while MV concentrations were determined using a standard curve generated at 578 nm. Comparisons between the two revealed that twelve molecules of MV were oxidized for each molecule of ClO4- reduced. The oxidation of these additional eight MV molecules is explained by the interaction of the dye with chlorite (the product of the Pcr reaction) and other contaminants that could be present in the enzyme prep. This unsettling result indicated this assay would be problematic for the detection of ClO4- in soil, which has many chemicals that could react with MV. To improve upon this assay, we have tried to reduce ClO4- using less reactive dyes and reductants. The reductants ascorbic acid, NADH, and dithiothreitol drive Pcr catalyzed ClO4- reduction, however, they

  18. Experiences with Non-traditional Bioassay Methods in a Plutonium Processing Line

    SciTech Connect

    La Bone, T.R.

    2003-10-17

    An incident in an Savannah River Site (SRS) plutonium processing line (FB-Line) in 1999 highlighted the fact insoluble forms of plutonium exist at SRS that may not be readily monitored with the routine bioassay programs traditionally used at this site. To address this issue, a study was conducted in FB-Line with 21 participants for a year ending in July 2002. The purpose of the study was to examine the use of three non-traditional monitoring methods and, based on this experience, recommend a routine bioassay program that is capable of monitoring workers potentially exposed to insoluble plutonium. These non-traditional monitoring methods are personal air sampling (PAS), thermal ionization mass spectrometry (TIMS) of urine samples, and routine fecal bioassay. The main conclusions and recommendations of the study are: (1) A routine TIMS urine bioassay program, which is called the enhanced bioassay program (EBP), is recommended for workers in SRS facilities that have a reasonable potential for exposure to insoluble forms of plutonium. (2) Under certain conditions the EBP could result in onerous work restrictions. A contingency plan involving the use of PAS is recommended in this case. PAS is also recommended for workers who have had historic intakes of plutonium that interfere with the detection and interpretation of future intakes of insoluble plutonium. (3) For the EBP to be successful it must be used only for those workers who have a reasonable potential for exposure to insoluble plutonium, and these workers must take all necessary precautions to avoid cross-contamination of the urine (and follow-up fecal) samples. (4) Fecal bioassay is an important tool for follow-up to abnormal events, but routine fecal bioassay is not recommended. (5) The PAS data clearly shows that workers are exposed to low levels of airborne plutonium, but the participants appear to be unlikely to exceed a committed effective dose equivalent of 100 mrem from these exposures.

  19. Low dNTP levels are necessary but may not be sufficient for lentiviral restriction by SAMHD1.

    PubMed

    Welbourn, Sarah; Strebel, Klaus

    2016-01-15

    SAMHD1 is a cellular dNTPase that restricts lentiviral infection presumably by lowering cellular dNTP levels to below a critical threshold required for reverse transcription; however, lowering cellular dNTP levels may not be the sole mechanism of restriction. In particular, an exonuclease activity of SAMHD1 was reported to contribute to virus restriction. We further investigated the requirements for SAMHD1 restriction activity in both differentiated U937 and cycling HeLa cells. Using hydroxyurea treatment to lower baseline dNTP levels in HeLa cells, we were able to document efficient SAMHD1 restriction without significant further reduction in dNTP levels by SAMHD1. These results argue against a requirement for additional myeloid-specific host factors for SAMHD1 function but further support the notion that SAMHD1 possesses an additional dNTP-independent function contributing to lentiviral restriction. However, our own experiments failed to associate this presumed additional SAMHD1 antiviral activity with a reported nuclease activity. PMID:26655245

  20. Tunneling characteristics of Au-alkanedithiol-Au junctions formed via nanotransfer printing (nTP).

    PubMed

    Niskala, Jeremy R; Rice, William C; Bruce, Robert C; Merkel, Timothy J; Tsui, Frank; You, Wei

    2012-07-25

    Construction of permanent metal-molecule-metal (MMM) junctions, though technically challenging, is desirable for both fundamental investigations and applications of molecule-based electronics. In this study, we employed the nanotransfer printing (nTP) technique using perfluoropolyether (PFPE) stamps to print Au thin films onto self-assembled monolayers (SAMs) of alkanedithiol formed on Au thin films. We show that the resulting MMM junctions form permanent and symmetrical tunnel junctions, without the need for an additional protection layer between the top metal electrode and the molecular layer. This type of junction makes it possible for direct investigations into the electrical properties of the molecules and the metal-molecule interfaces. Dependence of transport properties on the length of the alkane molecules and the area of the printed Au electrodes has been examined systematically. From the analysis of the current-voltage (I-V) curves using the Simmons model, the height of tunneling barrier associated with the molecule (alkane) has been determined to be 3.5 ± 0.2 eV, while the analysis yielded an upper bound of 2.4 eV for the counterpart at the interface (thiol). The former is consistent with the theoretical value of ~3.5-5.0 eV. The measured I-V curves show scaling with respect to the printed Au electrode area with lateral dimensions ranging from 80 nm to 7 μm. These results demonstrate that PFPE-assisted nTP is a promising technique for producing potentially scalable and permanent MMM junctions. They also demonstrate that MMM structures (produced by the unique PFPE-assisted nTP) constitute a reliable test bed for exploring molecule-based electronics. PMID:22720785

  1. Affordable Development and Optimization of CERMET Fuels for NTP Ground Testing

    NASA Technical Reports Server (NTRS)

    Hickman, Robert R.; Broadway, Jeramie W.; Mireles, Omar R.

    2014-01-01

    CERMET fuel materials for Nuclear Thermal Propulsion (NTP) are currently being developed at NASA's Marshall Space Flight Center. The work is part of NASA's Advanced Space Exploration Systems Nuclear Cryogenic Propulsion Stage (NCPS) Project. The goal of the FY12-14 project is to address critical NTP technology challenges and programmatic issues to establish confidence in the affordability and viability of an NTP system. A key enabling technology for an NCPS system is the fabrication of a stable high temperature nuclear fuel form. Although much of the technology was demonstrated during previous programs, there are currently no qualified fuel materials or processes. The work at MSFC is focused on developing critical materials and process technologies for manufacturing robust, full-scale CERMET fuels. Prototypical samples are being fabricated and tested in flowing hot hydrogen to understand processing and performance relationships. As part of this initial demonstration task, a final full scale element test will be performed to validate robust designs. The next phase of the project will focus on continued development and optimization of the fuel materials to enable future ground testing. The purpose of this paper is to provide a detailed overview of the CERMET fuel materials development plan. The overall CERMET fuel development path is shown in Figure 2. The activities begin prior to ATP for a ground reactor or engine system test and include materials and process optimization, hot hydrogen screening, material property testing, and irradiation testing. The goal of the development is to increase the maturity of the fuel form and reduce risk. One of the main accomplishmens of the current AES FY12-14 project was to develop dedicated laboratories at MSFC for the fabrication and testing of full length fuel elements. This capability will enable affordable, near term development and optimization of the CERMET fuels for future ground testing. Figure 2 provides a timeline of the

  2. Susceptibility of Bagrada hilaris (Hemiptera: Pentatomidae) to Insecticides in Laboratory and Greenhouse Bioassays.

    PubMed

    Palumbo, John C; Prabhaker, Nilima; Reed, Darcy A; Perring, Thomas M; Castle, Steven J; Huang, Ta-I

    2015-04-01

    Field-collected nymphs and adults of Bagrada hilaris (Burmeister) (Hemiptera: Penatatomidae) from three locations were evaluated for susceptibility to insecticides representing 10 classes of insecticide chemistry. Although relative susceptibilities differed between leaf-spray and leaf-dip Petri dish bioassays, consistently low LC50 values were determined for chlorpyrifos, bifenthrin, and lambda-cyhalothrin. Fenpropathrin and methomyl had intermediate values. Susceptibility to dinotefuran varied depending on the bioassay, possibly owing to leaf substrates used in the two bioassays. In soil systemic bioassays, the LC50 value of dinotefuran was significantly greater than that of two other neonicotinoids, imidacloprid and thiamethoxam, and the anthranilic diamide, cyantraniliprole. Mortality and feeding damage of B. hilaris and plant growth on insecticide-treated plants in greenhouse trials were consistent with the laboratory bioassays; the best results were seen with bifenthrin, methomyl, and chlorpyrifos. Mortality to the neonicotinoids was not evident; however, feeding damage and plant growth responses on dinotefuran-treated plants damage were similar to the noninfested control. This highlights the apparent antifeedant properties of dinotefuran that may have prevented adults from injuring broccoli plants after exposure to foliar spray residues. Data presented serve as baseline susceptibilities that can be used to monitor for resistance development in field populations of B. hilaris. PMID:26470178

  3. Effects of metals in in vitro bioassays.

    PubMed Central

    Sirover, M A

    1981-01-01

    The capacity of in vitro bioassays to detect the potential carcinogenicity of metal compounds is reviewed. The in vitro bioassays discussed include: bacterial reversion analysis to determine the capacity of metal salts to revert Salmonella typhimurium histidine auxotrophs or to revert Escherichia coli WP 2 tryp- to tryptophan prototrophy; examination of the ability of metal salts to preferentially inhibit cell growth in Bacillus subtilis cells deficient in DNA repair pathways; determination of the ability of metal salts to induce resistance to base analogs in mammalian cells; the capacity of metal salts to enhance viral transformation of mammalian cells or to transform cells in the absence of virus; and the ability of metal salts to induce chromosomal aberrations in mammalian cells. Using each of these in vitro bioassays, diverse metal compounds have been identified as potential carcinogens. Furthermore, the use of different compounds of a specific metal may allow a determination of the valence which may be required for carcinogenesis. PMID:7023930

  4. Poultry litter toxicity comparison from various bioassays

    SciTech Connect

    Gupta, G.; Kelly, P. )

    1992-01-01

    Poultry litter contains many toxic chemicals including Cu, As, Pb, Cd, Hg, Se and PCBs. Poultry litter leachate has been shown to be more toxic to marine luminescent organisms (Photobacterium phosphoreum) than other farm animal manures. A comparison of toxicity of the poultry litter leachate was undertaken using various bioassays. The EC{sub 50} (or LC{sub 50}) value for the leachate with the Microtox and Daphnia bioassays was 2.9 g/L/ Nitrobacter and Pseudomonas bioassays were not useful in determining the leachate toxicity because of the nutritional properties of the litter. Poultry litter leachate was found to be mutagenic to strains TA 97, TA 98, TA 100 and TA 102 using the Ames Test.

  5. RECOMMENDATIONS FOR UO3 PLANT BIOASSAY

    SciTech Connect

    Carbaugh, Eugene H.

    2010-07-12

    Alternative urine bioassay programs are described for application with decontamination and decommissioning activities at the Hanford UO3 Plant. The alternatives are based on quarterly or monthly urine bioassay for recycled uranium, assuming multiple acute inhalation intakes of recycled uranium occurring over a year. The inhalations are assumed to be 5µm AMAD particles of 80% absorption type F and 20% absorption type M. Screening levels, expressed as daily uranium mass excretion rates in urine, and the actions associated with these levels are provided for both quarterly and monthly sampling frequencies.

  6. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI(2-ETHYLHEXYL) PHTHALATE

    EPA Science Inventory

    Kavlock et al.; "NTP Center for the Evaluation....

    Abstract

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk...

  7. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI-ISONONYL PHTHALATE

    EPA Science Inventory

    Kavlock et al.; "NTP Center for the Evaluation....

    Abstract

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk...

  8. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI-ISODECYL PHTHALATE

    EPA Science Inventory

    Kavlock et al.; "NTP Center for the Evaluation....

    Abstract

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk...

  9. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI-N-OCTYL PHTHALATE

    EPA Science Inventory

    Kavlock et al.; "NTP Center for the Evaluation....

    Abstract

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk...

  10. NTP-CERHR expert panel report on the reproductive anddevelopmental toxicity of hydroxyurea

    SciTech Connect

    Liebelt, E.L.; Balk, S.J.; Faber, W.; Fisher, J.W.; Hughes, C.L.; Lanzkron, S.M.; Lewis, K.M.; Marchetti, F.; Mehendale, H.M.; Rogers,J.M.; Shad, A.T.; Skalko, R.G.; Stanek, E.J.

    2007-01-01

    The National Toxicology Program (NTP) and the National Institute of Environmental Health Sciences (NIEHS) established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed. Hydroxyurea was selected for evaluation by a CERHR expert panel because of (1) its increasing use in the treatment of sickle cell disease in children and adults, (2) knowledge that it inhibits DNA synthesis and is cytotoxic, and (3) published evidence of its reproductive and developmental toxicity in rodents. Hydroxyurea is FDA-approved for reducing the frequency of painful crises and the need for blood transfusions in adults with sickle cell anemia who experience recurrent moderate-to-severe crises. Hydroxyurea is used in the treatment of cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease aside from blood transfusion used in children. Hydroxyurea may be used in the treatment of children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea may be associated with cytotoxic and myelosuppressive effects, and hydroxyurea is mutagenic.

  11. BIOASSAY-DIRECTED CHEMICAL ANALYSIS IN ENVIRONMENTAL RESEARCH

    EPA Science Inventory

    The use of short-term bioassay tests in conjunction with analytical measurements, constitute a powerful tool for identifying important environmental contaminants. The authors have coined the terminology 'bioassay directed chemical analysis' to best describe this marriage of analy...

  12. Micro-organism distribution sampling for bioassays

    NASA Technical Reports Server (NTRS)

    Nelson, B. A.

    1975-01-01

    Purpose of sampling distribution is to characterize sample-to-sample variation so statistical tests may be applied, to estimate error due to sampling (confidence limits) and to evaluate observed differences between samples. Distribution could be used for bioassays taken in hospitals, breweries, food-processing plants, and pharmaceutical plants.

  13. EDC BIOASSAYS FOR RISK MANAGEMENT PROJECTS

    EPA Science Inventory

    Overall goal for this research is to develop 3 bioassays for use in EDC projects across NRMRL (estrogenic, androgenic and thyroid assays). Currently, research is focused on estrogenic assays. A literature search was conducted to identify potential assays. The Yeast Estrogen Sc...

  14. Brine Shrimp Bioassays: A Useful Technique in Biological Investigations

    ERIC Educational Resources Information Center

    Rice, Stanley A.; Maness, Ian B.

    2004-01-01

    A technique to measure the potency of leaf compounds against herbivores with the use of a bioassay is described. Bioassays are useful in classes where students have career plans like medicine in which bioassays can be used as tools for screening plants for possible medicinal potency.

  15. BIOASSAY-DIRECTED FRACTIONATION OF ORGANIC CONTAMINANTS IN AN ESTUARINE SEDIMENT USING THE NEW MUTAGENIC BIOASSAY, MUTATOX

    EPA Science Inventory

    Bioassay-directed fractionation of organic compounds was performed on an organic solvent extract of a contaminated estuarine sediment from Black Rock Harbor, Connecticut, using the new mutagenic bioassay, Mutatox-. hemical fractionation methods of the sediment extract included si...

  16. In vitro bioassays to evaluate complex chemical mixtures in recycled water

    PubMed Central

    Jia, Ai; Escher, Beate I.; Leusch, Frederic D.L.; Tang, Janet Y.M.; Prochazka, Erik; Dong, Bingfeng; Snyder, Erin M.; Snyder, Shane A.

    2016-01-01

    With burgeoning population and diminishing availability of freshwater resources, the world continues to expand the use of alternative water resources for drinking, and the quality of these sources has been a great concern for the public as well as public health professionals. In vitro bioassays are increasingly being used to enable rapid, relatively inexpensive toxicity screening that can be used in conjunction with analytical chemistry data to evaluate water quality and the effectiveness of water treatment. In this study, a comprehensive bioassay battery consisting of 36 bioassays covering 18 biological endpoints was applied to screen the bioactivity of waters of varying qualities with parallel treatments. Samples include wastewater effluent, ultraviolet light (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and infiltrated recycled groundwater. Based on assay sensitivity and detection frequency in the samples, several endpoints were highlighted in the battery, including assays for genotoxicity, mutagenicity, estrogenic activity, glucocorticoid activity, aryl hydrocarbon receptor activity, oxidative stress response, and cytotoxicity. Attenuation of bioactivity was found to be dependent on the treatment process and bioassay endpoint. For instance, ozone technology significantly removed oxidative stress activity, while UV based technologies were most efficient for the attenuation of glucocorticoid activity. Chlorination partially attenuated genotoxicity and greatly decreased herbicidal activity, while groundwater infiltration efficiently attenuated most of the evaluated bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g., mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following water treatment, indicating that transformation products of water treatment may be a concern. Furthermore, several types of bioassays with the same endpoint were compared in this study, which could help guide the selection

  17. In vitro bioassays to evaluate complex chemical mixtures in recycled water.

    PubMed

    Jia, Ai; Escher, Beate I; Leusch, Frederic D L; Tang, Janet Y M; Prochazka, Erik; Dong, Bingfeng; Snyder, Erin M; Snyder, Shane A

    2015-09-01

    With burgeoning population and diminishing availability of freshwater resources, the world continues to expand the use of alternative water resources for drinking, and the quality of these sources has been a great concern for the public as well as public health professionals. In vitro bioassays are increasingly being used to enable rapid, relatively inexpensive toxicity screening that can be used in conjunction with analytical chemistry data to evaluate water quality and the effectiveness of water treatment. In this study, a comprehensive bioassay battery consisting of 36 bioassays covering 18 biological endpoints was applied to screen the bioactivity of waters of varying qualities with parallel treatments. Samples include wastewater effluent, ultraviolet light (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and infiltrated recycled groundwater. Based on assay sensitivity and detection frequency in the samples, several endpoints were highlighted in the battery, including assays for genotoxicity, mutagenicity, estrogenic activity, glucocorticoid activity, arylhydrocarbon receptor activity, oxidative stress response, and cytotoxicity. Attenuation of bioactivity was found to be dependent on the treatment process and bioassay endpoint. For instance, ozone technology significantly removed oxidative stress activity, while UV based technologies were most efficient for the attenuation of glucocorticoid activity. Chlorination partially attenuated genotoxicity and greatly decreased herbicidal activity, while groundwater infiltration efficiently attenuated most of the evaluated bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g., mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following water treatment, indicating that transformation products of water treatment may be a concern. Furthermore, several types of bioassays with the same endpoint were compared in this study, which could help guide the selection

  18. Cyclin D3-dependent control of the dNTP pool and HIV-1 replication in human macrophages.

    PubMed

    Ruiz, Alba; Pauls, Eduardo; Badia, Roger; Torres-Torronteras, Javier; Riveira-Muñoz, Eva; Clotet, Bonaventura; Martí, Ramon; Ballana, Ester; Esté, José A

    2015-01-01

    Cyclins control the activation of cyclin-dependent kinases (CDK), which in turn, control the cell cycle and cell division. Intracellular availability of deoxynucleotides (dNTP) plays a fundamental role in cell cycle progression. SAM domain and HD domain-containing protein 1 (SAMHD1) degrades nucleotide triphosphates and controls the size of the dNTP pool. SAMHD1 activity appears to be controlled by CDK. Here, we show that knockdown of cyclin D3 a partner of CDK6 and E2 a partner of CDK2 had a major impact in SAMHD1 phosphorylation and inactivation and led to decreased dNTP levels and inhibition of HIV-1 at the reverse transcription step in primary human macrophages. The effect of cyclin D3 RNA interference was lost after degradation of SAMHD1 by HIV-2 Vpx, demonstrating the specificity of the mechanism. Cyclin D3 inhibition correlated with decreased activation of CDK2. Our results confirm the fundamental role of the CDK6-cyclin D3 pair in controlling CDK2-dependent SAMHD1 phosphorylation and dNTP pool in primary macrophages. PMID:25927932

  19. Genetic evidence that both dNTP-stabilized and strand slippage mechanisms may dictate DNA polymerase errors within mononucleotide microsatellites.

    PubMed

    Baptiste, Beverly A; Jacob, Kimberly D; Eckert, Kristin A

    2015-05-01

    Mononucleotide microsatellites are tandem repeats of a single base pair, abundant within coding exons and frequent sites of mutation in the human genome. Because the repeated unit is one base pair, multiple mechanisms of insertion/deletion (indel) mutagenesis are possible, including strand-slippage, dNTP-stabilized, and misincorportion-misalignment. Here, we examine the effects of polymerase identity (mammalian Pols α, β, κ, and η), template sequence, dNTP pool size, and reaction temperature on indel errors during in vitro synthesis of mononucleotide microsatellites. We utilized the ratio of insertion to deletion errors as a genetic indicator of mechanism. Strikingly, we observed a statistically significant bias toward deletion errors within mononucleotide repeats for the majority of the 28 DNA template and polymerase combinations examined, with notable exceptions based on sequence and polymerase identity. Using mutator forms of Pol β did not substantially alter the error specificity, suggesting that mispairing-misalignment mechanism is not a primary mechanism. Based on our results for mammalian DNA polymerases representing three structurally distinct families, we suggest that dNTP-stabilized mutagenesis may be an alternative mechanism for mononucleotide microsatellite indel mutation. The change from a predominantly dNTP-stabilized mechanism to a strand-slippage mechanism with increasing microsatellite length may account for the differential rates of tandem repeat mutation that are observed genome-wide. PMID:25758780

  20. Mismatched dNTP incorporation by DNA polymerase [beta] does not proceed via globally different conformational pathways

    SciTech Connect

    Tang, Kuo-Hsiang; Niebuhr, Marc; Tung, Chang-Shung; Chan, Hsiu-chien; Chou, Chia-Cheng; Tsai, Ming-Daw

    2008-07-07

    Understanding how DNA polymerases control fidelity requires elucidation of the mechanisms of matched and mismatched dNTP incorporations. Little is known about the latter because mismatched complexes do not crystallize readily. In this report, we employed small-angle X-ray scattering (SAXS) and structural modeling to probe the conformations of different intermediate states of mammalian DNA polymerase {beta} (Pol {beta}) in its wild-type and an error-prone variant, I260Q. Our structural results indicate that the mismatched ternary complex lies in-between the open and the closed forms, but more closely resembles the open form for WT and the closed form for I260Q. On the basis of molecular modeling, this over-stabilization of mismatched ternary complex of I260Q is likely caused by formation of a hydrogen bonding network between the side chains of Gln{sup 260}, Tyr{sup 296}, Glu{sup 295} and Arg{sup 258}, freeing up Asp{sup 192} to coordinate MgdNTP. These results argue against recent reports suggesting that mismatched dNTP incorporations follow a conformational path distinctly different from that of matched dNTP incorporation, or that its conformational closing is a major contributor to fidelity.

  1. Genetic Evidence That Both dNTP-Stabilized and Strand Slippage Mechanisms May Dictate DNA Polymerase Errors Within Mononucleotide Microsatellites

    PubMed Central

    Baptiste, Beverly A.; Jacob, Kimberly D.; Eckert, Kristin A.

    2015-01-01

    Mononucleotide microsatellites are tandem repeats of a single base pair, abundant within coding exons and frequent sites of mutation in the human genome. Because the repeated unit is one base pair, multiple mechanisms of insertion/deletion (indel) mutagenesis are possible, including strand-slippage, dNTP-stabilized, and misincorportion-misalignment. Here, we examine the effects of polymerase identity (mammalian Pols α, β, κ, and η), template sequence, dNTP pool size, and reaction temperature on indel errors during in vitro synthesis of mononucleotide microsatellites. We utilized the ratio of insertion to deletion errors as a genetic indicator of mechanism. Strikingly, we observed a statistically significant bias towards deletion errors within mononucleotide repeats for the majority of the 28 DNA template and polymerase combinations examined, with notable exceptions based on sequence and polymerase identity. Using mutator forms of Pol β did not substantially alter the error specificity, suggesting that mispairing-misalignment mechanism is not a primary mechanism. Based on our results for mammalian DNA polymerases representing three structurally distinct families, we suggest that dNTP-stabilized mutagenesis may be an alternative mechanism for mononucleotide microsatellite indel mutation. The change from a predominantly dNTP-stabilized mechanism to a strand-slippage mechanism with increasing microsatellite length may account for the differential rates of tandem repeat mutation that are observed genome-wide. PMID:25758780

  2. Combination of NTP with cetuximab inhibited invasion/migration of cetuximab-resistant OSCC cells: Involvement of NF-κB signaling.

    PubMed

    Chang, Jae Won; Kang, Sung Un; Shin, Yoo Seob; Seo, Seong Jin; Kim, Yeon Soo; Yang, Sang Sik; Lee, Jong-Soo; Moon, Eunpyo; Lee, Keunho; Kim, Chul-Ho

    2015-01-01

    Although the epidermal growth factor receptor (EGFR) is an established target in head-and-neck cancer (HNC), resistance to EGFR-targeted therapy mediated by various mechanisms has been reported. Therefore, a combination strategy to overcome resistance to EGFR mono-targeted therapy is clinically required. We have previously demonstrated that non-thermal atmospheric pressure plasma (NTP) induces death of various cancer cells, including oral squamous cancer (OSCC) cells. In this study, we report for the first time that combining NTP treatment with cetuximab led to inhibition of migration and invasion in cetuximab-resistant OSCC cells, which could be a promising strategy to overcome resistance to anti-EGFR therapy. NTP induced deactivation of NF-κB in SCCQLL1 cells, but not in MSKQLL1 cells. In addition, NTP increased the expression level of E-cadherin, and decreased those of vimentin, Slug, Snail, matrix metalloproteinase (MMP)-2, -9, and activities of MMPs. Moreover, NF-κB upregulation using cDNA diminished the combination effect of NTP on invasion, migration and related signals. Taken together, these results indicate that the combination of NTP with cetuximab can decrease invasiveness in cetuximab-resistant OSCCs through a novel mechanism involving the NF-κB pathway. These findings show the therapeutic potential of treatment that combines NTP and cetuximab in OSCC. PMID:26655729

  3. Combination of NTP with cetuximab inhibited invasion/migration of cetuximab-resistant OSCC cells: Involvement of NF-κB signaling

    PubMed Central

    Chang, Jae Won; Kang, Sung Un; Shin, Yoo Seob; Seo, Seong Jin; Kim, Yeon Soo; Yang, Sang Sik; Lee, Jong-Soo; Moon, Eunpyo; Lee, Keunho; Kim, Chul-Ho

    2015-01-01

    Although the epidermal growth factor receptor (EGFR) is an established target in head-and-neck cancer (HNC), resistance to EGFR-targeted therapy mediated by various mechanisms has been reported. Therefore, a combination strategy to overcome resistance to EGFR mono-targeted therapy is clinically required. We have previously demonstrated that non-thermal atmospheric pressure plasma (NTP) induces death of various cancer cells, including oral squamous cancer (OSCC) cells. In this study, we report for the first time that combining NTP treatment with cetuximab led to inhibition of migration and invasion in cetuximab-resistant OSCC cells, which could be a promising strategy to overcome resistance to anti-EGFR therapy. NTP induced deactivation of NF-κB in SCCQLL1 cells, but not in MSKQLL1 cells. In addition, NTP increased the expression level of E-cadherin, and decreased those of vimentin, Slug, Snail, matrix metalloproteinase (MMP)-2, -9, and activities of MMPs. Moreover, NF-κB upregulation using cDNA diminished the combination effect of NTP on invasion, migration and related signals. Taken together, these results indicate that the combination of NTP with cetuximab can decrease invasiveness in cetuximab-resistant OSCCs through a novel mechanism involving the NF-κB pathway. These findings show the therapeutic potential of treatment that combines NTP and cetuximab in OSCC. PMID:26655729

  4. The impact of molecular manipulation in residue 114 of Human Immunodeficiency Virus Type-1 reverse transcriptase on dNTP substrate binding and viral replication

    PubMed Central

    Van Cor-Hosmer, Sarah K.; Daddacha, Waaqo; Kelly, Z; Tsurumi, Amy; Kennedy, Edward M.; Kim, Baek

    2013-01-01

    Human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) has a unique tight binding to dNTP substrates. Structural modeling of Ala-114 of HIV-1 RT suggests that longer side chains at this residue can reduce the space normally occupied by the sugar moiety of an incoming dNTP. Indeed, mutations at Ala-114 decrease the ability of RT to synthesize DNA at low dNTP concentrations and reduce the dNTP-binding affinity (Kd) of RT. However, the Kd values of WT and A114C RT remained equivalent with an acylic dNTP substrate. Finally, mutant A114 RT HIV-1 vectors displayed a greatly reduced transduction in nondividing human lung fibroblasts (HLFs), while WT HIV-1 vector efficiently transduced both dividing and nondividing HLFs. Together these data support that the A114 residue of HIV-1 RT plays a key mechanistic role in the dNTP binding of HIV-1 RT and the unique viral infectivity of target cell types with low dNTP pools. PMID:22153297

  5. A Comparison of Materials Issues for Cermet and Graphite-Based NTP Fuels

    NASA Technical Reports Server (NTRS)

    Stewart, Mark E.; Schnitzler, Bruce G.

    2013-01-01

    This paper compares material issues for cermet and graphite fuel elements. In particular, two issues in NTP fuel element performance are considered here: ductile to brittle transition in relation to crack propagation, and orificing individual coolant channels in fuel elements. Their relevance to fuel element performance is supported by considering material properties, experimental data, and results from multidisciplinary fluid/thermal/structural simulations. Ductile to brittle transition results in a fuel element region prone to brittle fracture under stress, while outside this region, stresses lead to deformation and resilience under stress. Poor coolant distribution between fuel element channels can increase stresses in certain channels. NERVA fuel element experimental results are consistent with this interpretation. An understanding of these mechanisms will help interpret fuel element testing results.

  6. Controlador para un Reloj GPS de Referencia en el Protocolo NTP

    NASA Astrophysics Data System (ADS)

    Hauscarriaga, F.; Bareilles, F. A.

    The synchronization between computers in a local network plays a very important role on enviroments similar to IAR. Calculations for exact time are needed before, during and after an observation. For this purpose the IAR's GNU/Linux Software Development Team implemented a driver inside NTP protocol (an internet standard for time synchronization of computers) for a GPS receiver acquired a few years ago by IAR, which did not have support in such protocol. Today our Institute has a stable and reliable time base synchronized to atomic clocks on board GPS Satellites according to computers's synchronization standard, offering precise time services to all scientific community and particularly to the University of La Plata. FULL TEXT IN SPANISH

  7. Bioassaying for ozone with pollen systems

    SciTech Connect

    Feder, W.A.

    1981-01-01

    Sensitivity to ozone of pollen germinating in vitro is closely correlated with ozone sensitivity of the pollen parent. Ozone-sensitive and tolerant pollen populations have been identified in tobacco, petunia, and tomato cultivars. The rate of tube elongation can be reversibly slowed or stopped by exposure to low concentrations of ozone. The performance of selected pollen populations can then be used to bioassay ozone in ambient air by introducing the air sample into a growth chamber where ozone-sensitive pollen in growing. Year-round pollen producion can be achieved in the greenhouse. Harvested pollen can be tested, packaged, and transported to user facilities without loss of vigor. Pollen populations are inexpensive to produce, respond reliably, and are simple to use as a bioassay for air quality.

  8. Bioassay Labels Based on Apoferritin Nanovehicles

    SciTech Connect

    Liu, Guodong; Wang, Jun; Lea, Alan S.; Lin, Yuehe

    2006-09-04

    Here we report a nanoparticle label based on apoferritin nanovehicle loaded internally with markers for sensitive electrochemical DNA detection. The central cavity structure, the dissociation and reconstitute properties at different pHs of apoferritin provide a facile method to load and release markers. Hexacynoferrate(III) was used as model marker to load into the cavity of apoferritin protein cage. The loaded nanoparticle surface was functionalized with amino-modified DNA probe. Electrochemical DNA hybridization assay based on the hexacynoferrate loaded apoferritin nanovehicle could detect 23 atmol DNA targets in 50 ul sample solution. The concept could be readily extended to load other redox and fluorescence markers for bioassay applications. The new nanoparticle labels hold great promise for multi-target detection (in connection to nanoparticles loaded with different markers) and for enhancing the sensitivity of other bioassays.

  9. Disruption of the mevalonate pathway induces dNTP depletion and DNA damage.

    PubMed

    Martín Sánchez, Covadonga; Pérez Martín, José Manuel; Jin, Jong-Sik; Dávalos, Alberto; Zhang, Wei; de la Peña, Gema; Martínez-Botas, Javier; Rodríguez-Acebes, Sara; Suárez, Yajaira; Hazen, María José; Gómez-Coronado, Diego; Busto, Rebeca; Cheng, Yung-Chi; Lasunción, Miguel A

    2015-09-01

    The mevalonate pathway is tightly linked to cell division. Mevalonate derived non-sterol isoprenoids and cholesterol are essential for cell cycle progression and mitosis completion respectively. In the present work, we studied the effects of fluoromevalonate, a competitive inhibitor of mevalonate diphosphate decarboxylase, on cell proliferation and cell cycle progression in both HL-60 and MOLT-4 cells. This enzyme catalyzes the synthesis of isopentenyl diphosphate, the first isoprenoid in the cholesterol biosynthesis pathway, consuming ATP at the same time. Inhibition of mevalonate diphosphate decarboxylase was followed by a rapid accumulation of mevalonate diphosphate and the reduction of ATP concentrations, while the cell content of cholesterol was barely affected. Strikingly, mevalonate diphosphate decarboxylase inhibition also resulted in the depletion of dNTP pools, which has never been reported before. These effects were accompanied by inhibition of cell proliferation and cell cycle arrest at S phase, together with the appearance of γ-H2AX foci and Chk1 activation. Inhibition of Chk1 in cells treated with fluoromevalonate resulted in premature entry into mitosis and massive cell death, indicating that the inhibition of mevalonate diphosphate decarboxylase triggered a DNA damage response. Notably, the supply of exogenously deoxyribonucleosides abolished γ-H2AX formation and prevented the effects of mevalonate diphosphate decarboxylase inhibition on DNA replication and cell growth. The results indicate that dNTP pool depletion caused by mevalonate diphosphate decarboxylase inhibition hampered DNA replication with subsequent DNA damage, which may have important consequences for replication stress and genomic instability. PMID:26055626

  10. Perspectives in avoidance-preference bioassays

    SciTech Connect

    Steele, C.W.; Taylor, D.H.; Strickler-Shaw, S.

    1996-12-31

    Although behavioral endpoints are used in hazard assessment, establishment of water quality criteria and assessment of a contaminant`s hazard to aquatic life rely primarily on standard acute and chronic toxicity tests. Sublethal effects of pollutants should, however, be of major concern because more organisms experience sublethal rather than acutely or chronically lethal exposures of contaminants. The avoidance-preference approach to behavioral bioassays is very useful in screening pollutants for which the mechanisms of perception or response are largely unknown. The underlying philosophy of these studies is that an animal which perceives a chemical can be attracted or repulsed by it. No response is frequently assumed to indicate lack of perception. All three responses have broad ecological implications. The authors discuss the conditions required for performing avoidance-preference bioassays, as well as their sensitivities, advantages, and limitations. In this regard, a comparative approach is used in examining the results of avoidance-preference bioassays with zebrafish in two different apparatuses. Finally, they compare the results of avoidance-preference studies with other measures of the behavioral toxicity of lead to tadpoles.

  11. APPA 2011 Conference Highlights

    ERIC Educational Resources Information Center

    Facilities Manager, 2011

    2011-01-01

    This article presents highlights of APPA conference that was held on July 16-18, 2011. The highlights feature photos of 2011-2012 board of directors, outgoing senior regional representatives to the board, meritorious service award, APPA fellow, president's recognition and gavel exchange, and diamond business partner award.

  12. Research Highlights, 2003

    ERIC Educational Resources Information Center

    ACER Press (Australian Council for Educational Research), 2003

    2003-01-01

    "Research Highlights" is an annual publication documenting developments in the Australian Council for Educational Research's (ACER's) research programs for the previous year. The 2003 edition highlights research on the following themes: (1) Australian students excel in international study; (2) Assessing the moral and ethical outcomes of schooling;…

  13. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  14. Highlights from Fermilab

    SciTech Connect

    Parke, Stephen J.; /Fermilab

    2009-12-01

    In these two lectures I will chose some highlights from the Tevatron experiments (CDF/D0) and the Neutrino experiments and then discuss the future direction of physics at Fermilab after the Tevatron collider era.

  15. NSI organization and highlights

    NASA Technical Reports Server (NTRS)

    Rounds, Fred

    1991-01-01

    The agenda of the NASA Science Internet (NSI) Users Working Group is given. The NSI project organization is laid out in view graph format. Also given are NSI highlights which are divided into three areas: administration, engineering, and operations.

  16. Langley test highlights, 1981

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Significant aircraft tests which were performed are highlighted. The broad range of the research and technology activities. The conributions of this work toward maintaining United States leadership in aeronautics and space research are illustrated.

  17. Highlights from Fermilab

    NASA Astrophysics Data System (ADS)

    Oddone, P. J.

    2010-12-01

    DISCUSSION by CHAIRMAN: P.J. ODDONE, Scientific Secretaries: W. Fisher, A. Holzner Note from Publisher: The Slides of the Lecture: "Highlights from Fermilab" can be found at http://www.ccsem.infn.it/issp2007/

  18. In-situ bioassays using caged bivalves

    SciTech Connect

    Salazar, M.H.; Salazar, S.M.

    1995-12-31

    It is important to make the distinction between chemical measurements to assess bioaccumulation potential versus biological measurements to assess potential bioeffects because bioaccumulation is not a bioeffect. Caging provides a unique opportunity to make synoptic measurements of each and facilitates making these measurements over space and time. Measuring bioaccumulation in resident and transplanted bivalves has probably been the most frequently used form of an in-situ bioassay because bivalves concentrate chemicals in their tissues. They are also easy to collect, cage, and measure. The authors have refined bivalve bioassay methods by minimizing the size range of test animals, making repetitive measurements of the same individuals, and standardizing test protocols for a variety of applications. They are now attempting to standardize criteria for accepting and interpreting data in the same way that laboratory bioassays have been standardized. Growth measurements can serve two purposes in this assessment strategy: (1) An integrated biological response endpoint that is easily quantifiable and with significance to the population, and (2) A means of calibrating bioaccumulation by assessing the relative health and physiological state of tissues that have accumulated the chemicals. In general, the authors have found the highest bioconcentration factors associated with the highest growth rates, the highest concentrations ({micro}g/g) of chemicals in juvenile mussels, and the highest chemical content ({micro}g/animal) in adult mussels. Without accounting for possible dilution of chemical concentrations by tissue growth or magnification through degrowth, contaminant concentrations can be misleading. Examples are provided for the Sudbury River in Massachusetts (Elliptio complanata), San Diego Bay (Mytilus galloprovincialis), and the Harbor Island Superfund Site in Puget Sound (Mytilus trossulus).

  19. A Multichannel Bioluminescence Determination Platform for Bioassays.

    PubMed

    Kim, Sung-Bae; Naganawa, Ryuichi

    2016-01-01

    The present protocol introduces a multichannel bioluminescence determination platform allowing a high sample throughput determination of weak bioluminescence with reduced standard deviations. The platform is designed to carry a multichannel conveyer, an optical filter, and a mirror cap. The platform enables us to near-simultaneously determine ligands in multiple samples without the replacement of the sample tubes. Furthermore, the optical filters beneath the multichannel conveyer are designed to easily discriminate colors during assays. This optical system provides excellent time- and labor-efficiency to users during bioassays. PMID:27424912

  20. Nuclear Thermal Propulsion (NTP): A Proven Growth Technology for Human NEO/Mars Exploration Missions

    NASA Technical Reports Server (NTRS)

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2012-01-01

    The nuclear thermal rocket (NTR) represents the next "evolutionary step" in high performance rocket propulsion. Unlike conventional chemical rockets that produce their energy through combustion, the NTR derives its energy from fission of Uranium-235 atoms contained within fuel elements that comprise the engine s reactor core. Using an "expander" cycle for turbopump drive power, hydrogen propellant is raised to a high pressure and pumped through coolant channels in the fuel elements where it is superheated then expanded out a supersonic nozzle to generate high thrust. By using hydrogen for both the reactor coolant and propellant, the NTR can achieve specific impulse (Isp) values of 900 seconds (s) or more - twice that of today s best chemical rockets. From 1955 - 1972, twenty rocket reactors were designed, built and ground tested in the Rover and NERVA (Nuclear Engine for Rocket Vehicle Applications) programs. These programs demonstrated: (1) high temperature carbide-based nuclear fuels; (2) a wide range of thrust levels; (3) sustained engine operation; (4) accumulated lifetime at full power; and (5) restart capability - all the requirements needed for a human Mars mission. Ceramic metal "cermet" fuel was pursued as well, as a backup option. The NTR also has significant "evolution and growth" capability. Configured as a "bimodal" system, it can generate its own electrical power to support spacecraft operational needs. Adding an oxygen "afterburner" nozzle introduces a variable thrust and Isp capability and allows bipropellant operation. In NASA s recent Mars Design Reference Architecture (DRA) 5.0 study, the NTR was selected as the preferred propulsion option because of its proven technology, higher performance, lower launch mass, versatile vehicle design, simple assembly, and growth potential. In contrast to other advanced propulsion options, no large technology scale-ups are required for NTP either. In fact, the smallest engine tested during the Rover program

  1. The Numerical Tokamak Project (NTP) simulation of turbulent transport in the core plasma: A grand challenge in plasma physics

    SciTech Connect

    Not Available

    1993-12-01

    The long-range goal of the Numerical Tokamak Project (NTP) is the reliable prediction of tokamak performance using physics-based numerical tools describing tokamak physics. The NTP is accomplishing the development of the most advanced particle and extended fluid model`s on massively parallel processing (MPP) environments as part of a multi-institutional, multi-disciplinary numerical study of tokamak core fluctuations. The NTP is a continuing focus of the Office of Fusion Energy`s theory and computation program. Near-term HPCC work concentrates on developing a predictive numerical description of the core plasma transport in tokamaks driven by low-frequency collective fluctuations. This work addresses one of the greatest intellectual challenges to our understanding of the physics of tokamak performance and needs the most advanced computational resources to progress. We are conducting detailed comparisons of kinetic and fluid numerical models of tokamak turbulence. These comparisons are stimulating the improvement of each and the development of hybrid models which embody aspects of both. The combination of emerging massively parallel processing hardware and algorithmic improvements will result in an estimated 10**2--10**6 performance increase. Development of information processing and visualization tools is accelerating our comparison of computational models to one another, to experimental data, and to analytical theory, providing a bootstrap effect in our understanding of the target physics. The measure of success is the degree to which the experimentally observed scaling of fluctuation-driven transport may be predicted numerically. The NTP is advancing the HPCC Initiative through its state-of-the-art computational work. We are pushing the capability of high performance computing through our efforts which are strongly leveraged by OFE support.

  2. The Manufacture of W-UO2 Fuel Elements for NTP Using the Hot Isostatic Pressing Consolidation Process

    NASA Technical Reports Server (NTRS)

    Broadway, Jeramie; Hickman, Robert; Mireles, Omar

    2012-01-01

    NTP is attractive for space exploration because: (1) Higher Isp than traditional chemical rockets (2)Shorter trip times (3) Reduced propellant mass (4) Increased payload. Lack of qualified fuel material is a key risk (cost, schedule, and performance). Development of stable fuel form is a critical path, long lead activity. Goals of this project are: Mature CERMET and Graphite based fuel materials and Develop and demonstrate critical technologies and capabilities.

  3. Urine sample collection protocols for bioassay samples

    SciTech Connect

    MacLellan, J.A.; McFadden, K.M.

    1992-11-01

    In vitro radiobioassay analyses are used to measure the amount of radioactive material excreted by personnel exposed to the potential intake of radioactive material. The analytical results are then used with various metabolic models to estimate the amount of radioactive material in the subject`s body and the original intake of radioactive material. Proper application of these metabolic models requires knowledge of the excretion period. It is normal practice to design the bioassay program based on a 24-hour excretion sample. The Hanford bioassay program simulates a total 24-hour urine excretion sample with urine collection periods lasting from one-half hour before retiring to one-half hour after rising on two consecutive days. Urine passed during the specified periods is collected in three 1-L bottles. Because the daily excretion volume given in Publication 23 of the International Commission on Radiological Protection (ICRP 1975, p. 354) for Reference Man is 1.4 L, it was proposed to use only two 1-L bottles as a cost-saving measure. This raised the broader question of what should be the design capacity of a 24-hour urine sample kit.

  4. Urine sample collection protocols for bioassay samples

    SciTech Connect

    MacLellan, J.A.; McFadden, K.M.

    1992-11-01

    In vitro radiobioassay analyses are used to measure the amount of radioactive material excreted by personnel exposed to the potential intake of radioactive material. The analytical results are then used with various metabolic models to estimate the amount of radioactive material in the subject's body and the original intake of radioactive material. Proper application of these metabolic models requires knowledge of the excretion period. It is normal practice to design the bioassay program based on a 24-hour excretion sample. The Hanford bioassay program simulates a total 24-hour urine excretion sample with urine collection periods lasting from one-half hour before retiring to one-half hour after rising on two consecutive days. Urine passed during the specified periods is collected in three 1-L bottles. Because the daily excretion volume given in Publication 23 of the International Commission on Radiological Protection (ICRP 1975, p. 354) for Reference Man is 1.4 L, it was proposed to use only two 1-L bottles as a cost-saving measure. This raised the broader question of what should be the design capacity of a 24-hour urine sample kit.

  5. NASA Langley Highlights, 1997

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Langley's mission is accomplished by performing innovative research relevant to national needs and Agency goals, transferring technology to users in a timely manner, and providing development support to other United States Government Agencies, industry, other NASA Centers, the educational community, and the local community. This report contains highlights of some of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate the broad range of research and technology activities carried out by NASA Langley Research Center and the contributions of this work toward maintaining United States' leadership in aeronautics and space research.

  6. Subscale Validation of the Subsurface Active Filtration of Exhaust (SAFE) Approach to NTP Ground Testing

    NASA Technical Reports Server (NTRS)

    Marshall, William M.; Borowski, Stanley K.; Bulman, Mel; Joyner, Russell; Martin, Charles R.

    2015-01-01

    Brief History of NTP: Project Rover Began in 1950s by Los Alamos Scientific Labs (now Los Alamos National Labs) and ran until 1970s Tested a series of nuclear reactor engines of varying size at Nevada Test Site (now Nevada National Security Site) Ranged in scale from 111 kN (25 klbf) to 1.1 MN (250 klbf) Included Nuclear Furnace-1 tests Demonstrated the viability and capability of a nuclear rocket engine test program One of Kennedys 4 goals during famous moon speech to Congress Nuclear Engines for Rocket Vehicle Applications (NERVA) Atomic Energy Commission and NASA joint venture started in 1964 Parallel effort to Project Rover was focused on technology demonstration Tested XE engine, a 245-kN (55-klbf) engine to demonstrate startup shutdown sequencing. Hot-hydrogen stream is passed directly through fuel elements potential for radioactive material to be eroded into gaseous fuel flow as identified in previous programs NERVA and Project Rover (1950s-70s) were able to test in open atmosphere similar to conventional rocket engine test stands today Nuclear Furance-1 tests employed a full scrubber system Increased government and environmental regulations prohibit the modern testing in open atmosphere. Since the 1960s, there has been an increasing cessation on open air testing of nuclear material Political and national security concerns further compound the regulatory environment

  7. Appplication of a general fluid mechanics program to NTP system modeling

    NASA Astrophysics Data System (ADS)

    Lee, Stacey K.

    1993-01-01

    An effort is currently underway at NASA and the Department of Energy (DOE) to develop an accurate model for predicting nuclear thermal propulsion (NTP) system performance. The objective of the effort is to develop several levels of computer programs which vary in detail and complexity according to user's needs. The current focus is on the Level 1 steady-state, parametric system model. This system model will combine a general fluid mechanics program, SAFSIM, with the ability to analyze turbines, pumps, nozzles, and reactor physics. SAFSIM (System Analysis Flow SIMulator) is a FORTRAN computer program that simulates integrated performance of systems involving fluid mechanics, heat transfer, and reactor dynamics. SAFSIM has the versatility to allow simulation of almost any system, including a nuclear reactor system. The focus of this paper is the validation of SAFSIM's capabilities as a base computational engine for a nuclear thermal propulsion system model. Validation is being accomplished by modeling of a nuclear engine test using SAFSIM and comparing the results to known experimental data. For this study, the NRX/EST test was chosen; it was the first of the tests to demonstrate the integration of all system components (including the turbopump) and it utilized the hot bleed cycle. This paper present a comparison of analytical results with experimental system performance in terms of state points, mass flow rates, wall temperatures, and specific impulse. In addition, the methodology used in the validation efforts will be discussed.

  8. Stopped-flow DNA polymerase assay by continuous monitoring of dNTP incorporation by fluorescence.

    PubMed

    Montgomery, Jesse L; Rejali, Nick; Wittwer, Carl T

    2013-10-15

    DNA polymerase activity was measured by a stopped-flow assay that monitors polymerase extension using an intercalating dye. Double-stranded DNA formation during extension of a hairpin substrate was monitored at 75°C for 2 min. Rates were determined in nucleotides per second per molecule of polymerase (nt/s) and were linear with time and polymerase concentration from 1 to 50 nM. The concentrations of 15 available polymerases were quantified and their extension rates determined in 50 mM Tris, pH 8.3, 0.5 mg/ml BSA, 2 mM MgCl₂, and 200 μM each dNTP as well as their commercially recommended buffers. Native Taq polymerases had similar extension rates of 10-45 nt/s. Three alternative polymerases showed faster speeds, including KOD (76 nt/s), Klentaq I (101 nt/s), and KAPA2G (155 nt/s). Fusion polymerases including Herculase II and Phusion were relatively slow (3-13 nt/s). The pH optimum for Klentaq extension was between 8.5 and 8.7 with no effect of Tris concentration. Activity was directly correlated to the MgCl2 concentration and inversely correlated to the KCl concentration. This continuous assay is relevant to PCR and provides accurate measurement of polymerase activity using a defined template without the need of radiolabeled substrates. PMID:23872003

  9. Extreme dNTP pool changes and hypermutability in dcd ndk strains.

    PubMed

    Tse, Lawrence; Kang, Tina Manzhu; Yuan, Jessica; Mihora, Danielle; Becket, Elinne; Maslowska, Katarzyna H; Schaaper, Roel M; Miller, Jeffrey H

    2016-01-01

    Cells lacking deoxycytidine deaminase (DCD) have been shown to have imbalances in the normal dNTP pools that lead to multiple phenotypes, including increased mutagenesis, increased sensitivity to oxidizing agents, and to a number of antibiotics. In particular, there is an increased dCTP pool, often accompanied by a decreased dTTP pool. In the work presented here, we show that double mutants of Escherichia coli lacking both DCD and NDK (nucleoside diphosphate kinase) have even more extreme imbalances of dNTPs than mutants lacking only one or the other of these enzymes. In particular, the dCTP pool rises to very high levels, exceeding even the cellular ATP level by several-fold. This increased level of dCTP, coupled with more modest changes in other dNTPs, results in exceptionally high mutation levels. The high mutation levels are attenuated by the addition of thymidine. The results corroborate the critical importance of controlling DNA precursor levels for promoting genome stability. We also show that the addition of certain exogenous nucleosides can influence replication errors in DCD-proficient strains that are deficient in mismatch repair. PMID:26789486

  10. Recent Highlights from VERITAS

    NASA Astrophysics Data System (ADS)

    Wakely, Scott

    VERITAS, an array of atmospheric Cherenkov TeV gamma-ray telescopes, has been in opera-tion since 2007. We will present some highlights from the first few years of observations, with an emphasis on those results most relevant to galactic cosmic-ray astrophysics.

  11. Collegiate Athletics Highlights.

    ERIC Educational Resources Information Center

    St. John, Eric

    1999-01-01

    Highlights 15 trends/events in black college athletics, including championship coaches, Black Coaches Association, eligibility issues, disclosure of athlete graduation rates, athletics resource allocation, early adoption of professional athlete status, success of the Women's National Basketball Association, lack of black access to certain sports,…

  12. E News: Report highlights

    SciTech Connect

    1995-01-01

    Three technologies are highlighted in this issue: a rooftop ice storage system for small commercial loads; chlorofluorocarbon-free electric chillers and their expected market; and the FlashBake oven, a commercial-sized oven that uses high intensity quartz lamps to cook food quickly. Regular columns on Member News and Work in Progress are included.

  13. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  14. NASA highlights, 1986 - 1988

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Highlights of NASA research from 1986 to 1988 are discussed. Topics covered include Space Shuttle flights, understanding the Universe and its origins, understanding the Earth and its environment, air and space transportation, using space to make America more competitive, using space technology an Earth, strengthening America's education in science and technology, the space station, and human exploration of the solar system.

  15. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  16. Bioassay vs. Air Sampling: Practical Guidance and Experience at Hanford

    SciTech Connect

    Carbaugh, Eugene H.; Carlson, Eric W.; Hill, Robin L.

    2004-02-08

    The Hanford Site has implemented a policy to guide in determining whether air sampling data or special fecal bioassay data are more appropriate for determining doses of record for low-level plutonium exposures. The basis for the policy and four years of experience in comparing DAC-hours exposure with bioassay-based dosimetry is discussed.

  17. Aspirator Gun for High-Throughput Mosquito Bioassays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We describe an innovative aspirator gun designed to transfer anaesthetized mosquitoes directly into glass bioassay tubes. The gun has been used for thousands of transfers with extremely low associated mortality and is the central component of a high-throughput bioassay system. The gun is constructed...

  18. COLLECTION, CHEMICAL FRACTIONATION, AND MUTAGENICITY BIOASSAY OF AMBIENT AIR PARTICULATE

    EPA Science Inventory

    The influence of industrialization and consequent increased concentration of urban particulate matter on the incidence of cancer has long been a concern. The first bioassays used to evaluate complex ambient air samples were whole-animal carcinogenesis bioassays. In these studies,...

  19. Aspirator gun for high-throughput mosquito bioassays.

    PubMed

    Aldridge, Robert L; Wynn, W Wayne; Britch, Seth C; Linthicum, Kenneth J

    2012-03-01

    We describe an innovative aspirator gun designed to transfer individual anesthetized mosquitoes directly into glass bioassay tubes. The gun has been used for thousands of transfers with extremely low associated mortality and is the central component of a high-throughput bioassay system. The gun is constructed using readily obtainable materials and can be modified for a range of insects. PMID:22533090

  20. Signal Amplification of Bioassay Using Zinc Nanomaterials

    NASA Astrophysics Data System (ADS)

    Cowles, Chad L.

    An emerging trend in the analytical detection sciences is the employment of nanomaterials for bioassay signal transduction to identify analytes critical to public health. These nanomaterials have been specifically investigated for applications which require identification of trace levels of cells, proteins, or other molecules that can have broad ranging impacts to human health in fields such as clinical diagnostics, environmental monitoring, food and drink control, and the prevention of bioterrorism. Oftentimes these nanoparticle-based signal transduction or amplification approaches offer distinct advantages over conventional methods such as increased sensitivity, rapidity, or stability. The biological application of nanoparticles however, does suffer from drawbacks that have limited more widespread adoption of these techniques. Some of these drawbacks are, high cost and toxicity, arduous synthesis methods, functionalization and bioconjugation challenges, and laboratory disposal and environmental hazard issues, all of which have impeded the progression of this technology in some way or another. This work aims at developing novel techniques that offer solutions to a number of these hurdles through the development of new nanoparticle-based signal transduction approaches and the description of a previously undescribed nanomaterial. Zinc-based nanomaterials offer the opportunity to overcome some of the limitations that are encountered when other nanomaterials are employed for bioassay signal transduction. On the other hand, the biological application of zinc nanomaterials has been difficult because in general their fluorescence is in the blue range and the reported quantum yields are usually too low for highly sensitive applications. The advantages of using zinc nanomaterials for biological applications, such as reduced toxicity, simple synthesis, low cost, and straightforward functionalization strategies contribute to the research interest in their application as

  1. NASA Langley Highlights, 1998

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Langley's mission is accomplished by performing innovative research relevant to national needs and Agency goals, transferring technology to users in a timely manner, and providing development support to other United States Government Agencies, industry, other NASA Centers, the educational community, and the local community. This report contains highlights of some of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate the broad range of research and technology activities carried out by NASA Langley Research Center and the contributions of this work toward maintaining United States' leadership in aeronautics and space research. A color electronic version of this report is available at URL http://larcpubs.larc.nasa.gov/randt/1998/.

  2. 1999 Digital Avionics Highlights

    NASA Technical Reports Server (NTRS)

    Polites, Michael E.

    1999-01-01

    This article summarizes the highlights of recent events and developments in guidance, navigation, and control in space, aircraft, and weapons. This article is about 1,200 words long. Information for the article was collected from other NASA Centers, DoD, and industry. All information was previously cleared by the originating organizations. Information for the article was also gathered from Aviation Week and Space Technology, and similar sources.

  3. Circular Bioassay Platforms for Applications in Microwave-Accelerated Techniques

    PubMed Central

    Mohammed, Muzaffer; Clement, Travis C.; Aslan, Kadir

    2014-01-01

    In this paper, we present the design of four different circular bioassay platforms, which are suitable for homogeneous microwave heating, using theoretical calculations (i.e., COMSOL™ multiphysics software). Circular bioassay platforms are constructed from poly(methyl methacrylate) (PMMA) for optical transparency between 400–800 nm, has multiple sample capacity (12, 16, 19 and 21 wells) and modified with silver nanoparticle films (SNFs) to be used in microwave-accelerated bioassays (MABs). In addition, a small monomode microwave cavity, which can be operated with an external microwave generator (100 W), for use with the bioassay platforms in MABs is also developed. Our design parameters for the circular bioassay platforms and monomode microwave cavity during microwave heating were: (i) temperature profiles, (ii) electric field distributions, (iii) location of the circular bioassay platforms inside the microwave cavity, and (iv) design and number of wells on the circular bioassay platforms. We have also carried out additional simulations to assess the use of circular bioassay platforms in a conventional kitchen microwave oven (e.g., 900 W). Our results show that the location of the circular bioassay platforms in the microwave cavity was predicted to have a significant effect on the homogeneous heating of these platforms. The 21-well circular bioassay platform design in our monomode microwave cavity was predicted to offer a homogeneous heating pattern, where inter-well temperature was observed to be in between 23.72–24.13°C and intra-well temperature difference was less than 0.21°C for 60 seconds of microwave heating, which was also verified experimentally. PMID:25568813

  4. Modelling larval movement data from individual bioassays.

    PubMed

    McLellan, Chris R; Worton, Bruce J; Deasy, William; Birch, A Nicholas E

    2015-05-01

    We consider modelling the movements of larvae using individual bioassays in which data are collected at a high-frequency rate of five observations per second. The aim is to characterize the behaviour of the larvae when exposed to attractant and repellent compounds. Mixtures of diffusion processes, as well as Hidden Markov models, are proposed as models of larval movement. These models account for directed and localized movements, and successfully distinguish between the behaviour of larvae exposed to attractant and repellent compounds. A simulation study illustrates the advantage of using a Hidden Markov model rather than a simpler mixture model. Practical aspects of model estimation and inference are considered on extensive data collected in a study of novel approaches for the management of cabbage root fly. PMID:25764283

  5. Cell-based bioassays in microfluidic systems

    NASA Astrophysics Data System (ADS)

    Itle, Laura J.; Zguris, Jeanna C.; Pishko, Michael V.

    2004-12-01

    The development of cell-based bioassays for high throughput drug screening or the sensing of biotoxins is contingent on the development of whole cell sensors for specific changes in intracellular conditions and the integration of those systems into sample delivery devices. Here we show the feasibility of using a 5-(and-6)-carboxy SNARF-1, acetoxymethyl ester, acetate, a fluorescent dye capable of responding to changes in intracellular pH, as a detection method for the bacterial endotoxin, lipopolysaccharide. We used photolithography to entrap cells with this dye within poly(ethylene) glyocol diacrylate hydrogels in microfluidic channels. After 18 hours of exposure to lipopolysaccharide, we were able to see visible changes in the fluorescent pattern. This work shows the feasibility of using whole cell based biosensors within microfluidic networks to detect cellular changes in response to exogenous agents.

  6. Plasmonically amplified fluorescence bioassay with microarray format

    NASA Astrophysics Data System (ADS)

    Gogalic, S.; Hageneder, S.; Ctortecka, C.; Bauch, M.; Khan, I.; Preininger, Claudia; Sauer, U.; Dostalek, J.

    2015-05-01

    Plasmonic amplification of fluorescence signal in bioassays with microarray detection format is reported. A crossed relief diffraction grating was designed to couple an excitation laser beam to surface plasmons at the wavelength overlapping with the absorption and emission bands of fluorophore Dy647 that was used as a label. The surface of periodically corrugated sensor chip was coated with surface plasmon-supporting gold layer and a thin SU8 polymer film carrying epoxy groups. These groups were employed for the covalent immobilization of capture antibodies at arrays of spots. The plasmonic amplification of fluorescence signal on the developed microarray chip was tested by using interleukin 8 sandwich immunoassay. The readout was performed ex situ after drying the chip by using a commercial scanner with high numerical aperture collecting lens. Obtained results reveal the enhancement of fluorescence signal by a factor of 5 when compared to a regular glass chip.

  7. Superluminescent variants of marine luciferases for bioassays.

    PubMed

    Kim, Sung Bae; Suzuki, Hideyuki; Sato, Moritoshi; Tao, Hiroaki

    2011-11-15

    In this study, a rational synthesis of superluminescent variants from marine luciferases with prolonged bioluminescence has been demonstrated. A putative active site of a model marine luciferase, Gaussia princeps Luciferase (GLuc), was assigned and modified by a site-directed mutagenesis. The potent variants were found to generate up to 10 times stronger bioluminescence, emitting red shifts of up to 33 nm with natural coelenterazine than native GLuc, rendering an efficient optical signature in bioassays. The advantageous properties were demonstrated with mammalian two-hybrid assays, single-chain probes, and metastases of murine B16 melanoma in BALB/c nude mice. The unique ideas for engineering GLuc are proved to be valid even for other marine luciferases. PMID:21951281

  8. Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

    PubMed Central

    Eom, Kilho; Yang, Jaemoon; Park, Jinsung; Yoon, Gwonchan; Soo Sohn, Young; Park, Shinsuk; Yoon, Dae Sung; Na, Sungsoo; Kwon, Taeyun

    2009-01-01

    Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM) have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins. PMID:19865530

  9. Mini-MITEE: Ultra Small, Ultra Light NTP Engines for Robotic Science and Manned Exploration Missions

    SciTech Connect

    Powell, James; Maise, George; Paniagua, John

    2006-01-20

    A compact, ultra lightweight Nuclear Thermal Propulsion (NTP) engine design is described with the capability to carry out a wide range of unique and important robotic science missions that are not possible using chemical or Nuclear Electric Propulsion (NEP). The MITEE (MInature ReacTor EnginE) reactor uses hydrogeneous moderator, such as solid lithium-7 hydride, and high temperature cermet tungsten/UO2 nuclear fuel. The reactor is configured as a modular pressure tube assembly, with each pressure tube containing an outer annual shell of moderator with an inner annular region of W/UO2 cermet fuel sheets. H2 propellant flows radially inwards through the moderator and fuel regions, exiting at {approx}3000 K into a central channel that leads to a nozzle at the end of the pressure tube. Power density in the fuel region is 10 to 20 megawatts per liter, depending on design, producing a thrust output on the order of 15,000 Newtons and an Isp of {approx}1000 seconds. 3D Monte Carlo neutronic analyses are described for MITEE reactors utilizing various fissile fuel options (U-235, U-233, and Am242m) and moderators (7LiH and BeH2). Reactor mass ranges from a maximum of 100 kg for the 7LiH/U-235 option to a minimum of 28 kg for the BeH2/Am-242 m option. Pure thrust only and bi-modal (thrust plus electric power generation) MITEE designs are described. Potential unique robotic science missions enabled by the MITEE engine are described, including landing on Europa and exploring the ice sheet interior with return of samples to Earth, hopping to and exploring multiple sites on Mars, unlimited ramjet flight in the atmospheres of Jupiter, Saturn, Uranus, and Neptune and landing on, and sample return from Pluto.

  10. Mini-MITEE: Ultra Small, Ultra Light NTP Engines for Robotic Science and Manned Exploration Missions

    NASA Astrophysics Data System (ADS)

    Powell, James; Maise, George; Paniagua, John

    2006-01-01

    A compact, ultra lightweight Nuclear Thermal Propulsion (NTP) engine design is described with the capability to carry out a wide range of unique and important robotic science missions that are not possible using chemical or Nuclear Electric Propulsion (NEP). The MITEE (MInature ReacTor EnginE) reactor uses hydrogeneous moderator, such as solid lithium-7 hydride, and high temperature cermet tungsten/UO2 nuclear fuel. The reactor is configured as a modular pressure tube assembly, with each pressure tube containing an outer annual shell of moderator with an inner annular region of W/UO2 cermet fuel sheets. H2 propellant flows radially inwards through the moderator and fuel regions, exiting at ~3000 K into a central channel that leads to a nozzle at the end of the pressure tube. Power density in the fuel region is 10 to 20 megawatts per liter, depending on design, producing a thrust output on the order of 15,000 Newtons and an Isp of ~1000 seconds. 3D Monte Carlo neutronic analyses are described for MITEE reactors utilizing various fissile fuel options (U-235, U-233, and Am242m) and moderators (7LiH and BeH2). Reactor mass ranges from a maximum of 100 kg for the 7LiH/U-235 option to a minimum of 28 kg for the BeH2/Am-242 m option. Pure thrust only and bi-modal (thrust plus electric power generation) MITEE designs are described. Potential unique robotic science missions enabled by the MITEE engine are described, including landing on Europa and exploring the ice sheet interior with return of samples to Earth, hopping to and exploring multiple sites on Mars, unlimited ramjet flight in the atmospheres of Jupiter, Saturn, Uranus, and Neptune and landing on, and sample return from Pluto.

  11. Stabilization of Poliovirus Polymerase by NTP Binding and Fingers-Thumb Interactions

    PubMed Central

    Thompson, Aaron A.; Albertini, Rebecca A.; Peersen, Olve B.

    2007-01-01

    The viral RNA-dependent RNA polymerases show a conserved structure where the fingers domain interacts with the top of the thumb domain to create a tunnel through which nucleotide triphosphates reach the active site. We have solved the crystal structures of poliovirus polymerase (3Dpol) in complex with all four NTPs, showing that they all bind in a common preinsertion site where the phosphates are not yet positioned over the active site. The NTPs interact with both the fingers and palm domains, forming bridging interactions that explain the increased thermal stability of 3Dpol in the presence of NTPs. We have also examined the importance of the fingers-thumb domain interaction for the function and structural stability of 3Dpol. Results from thermal denaturation experiments using circular dichroism and 2-aniliino-6-napthaline-sulfonate (ANS) fluorescence show that 3Dpol has a melting temperature of only ∼40°C. NTP binding stabilizes the protein and increases the melting by 5-6 °C while mutations in the fingers-thumb domain interface destabilize the protein and reduce the melting point by as much as 6 °C. In particular, the burial of Phe30 and Phe34 from the tip of the index finger into a pocket at the top of the thumb and the presence of Trp403 on the thumb domain are key interactions required to maintain the structural integrity of the polymerase. The data suggest the fingers domain has significant conformational flexibility and exists in a highly dynamic molten globule state at physiological temperature. The role of the enclosed active site motif as a structural scaffold for constraining the fingers domain and accommodating conformational changes in 3Dpol and other viral polymerases during the catalytic cycle is discussed. PMID:17223130

  12. PubChem BioAssay: 2014 update.

    PubMed

    Wang, Yanli; Suzek, Tugba; Zhang, Jian; Wang, Jiyao; He, Siqian; Cheng, Tiejun; Shoemaker, Benjamin A; Gindulyte, Asta; Bryant, Stephen H

    2014-01-01

    PubChem's BioAssay database (http://pubchem.ncbi.nlm.nih.gov) is a public repository for archiving biological tests of small molecules generated through high-throughput screening experiments, medicinal chemistry studies, chemical biology research and drug discovery programs. In addition, the BioAssay database contains data from high-throughput RNA interference screening aimed at identifying critical genes responsible for a biological process or disease condition. The mission of PubChem is to serve the community by providing free and easy access to all deposited data. To this end, PubChem BioAssay is integrated into the National Center for Biotechnology Information retrieval system, making them searchable by Entrez queries and cross-linked to other biomedical information archived at National Center for Biotechnology Information. Moreover, PubChem BioAssay provides web-based and programmatic tools allowing users to search, access and analyze bioassay test results and metadata. In this work, we provide an update for the PubChem BioAssay resource, such as information content growth, new developments supporting data integration and search, and the recently deployed PubChem Upload to streamline chemical structure and bioassay submissions. PMID:24198245

  13. PubChem BioAssay: 2014 update

    PubMed Central

    Wang, Yanli; Suzek, Tugba; Zhang, Jian; Wang, Jiyao; He, Siqian; Cheng, Tiejun; Shoemaker, Benjamin A.; Gindulyte, Asta; Bryant, Stephen H.

    2014-01-01

    PubChem’s BioAssay database (http://pubchem.ncbi.nlm.nih.gov) is a public repository for archiving biological tests of small molecules generated through high-throughput screening experiments, medicinal chemistry studies, chemical biology research and drug discovery programs. In addition, the BioAssay database contains data from high-throughput RNA interference screening aimed at identifying critical genes responsible for a biological process or disease condition. The mission of PubChem is to serve the community by providing free and easy access to all deposited data. To this end, PubChem BioAssay is integrated into the National Center for Biotechnology Information retrieval system, making them searchable by Entrez queries and cross-linked to other biomedical information archived at National Center for Biotechnology Information. Moreover, PubChem BioAssay provides web-based and programmatic tools allowing users to search, access and analyze bioassay test results and metadata. In this work, we provide an update for the PubChem BioAssay resource, such as information content growth, new developments supporting data integration and search, and the recently deployed PubChem Upload to streamline chemical structure and bioassay submissions. PMID:24198245

  14. NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP).

    PubMed

    Shelby, Michael D

    2006-11-01

    The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to cause adverse effects on reproduction and development in humans. The first CERHR expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread human exposure, (2) public and government interest in adverse health effects, (3) recently available human exposure studies, and (4) the large number of relevant toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7) is a high production volume chemical used as a plasticizer of polyvinyl chloride in the manufacture of a wide variety of consumer goods, such as building products, car products, clothing, food packaging, children's products (but not in toys intended for mouthing), and in medical devices made of polyvinyl chloride. The public can be exposed to DEHP by ingesting food, drink or dust that has been in contact with DEHP-containing materials, by inhaling contaminated air or dust, or by undergoing a medical procedure that uses polyvinyl chloride medical tubing or storage bags. It is estimated that the general population of the United States is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per kilogram body weight per day). The results of this DEHP update evaluation are published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and (3) public comments on the expert panel report. The NTP reached the following conclusions on the possible effects of exposure to DEHP on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. There is serious concern that certain intensive medical treatments of

  15. Nucleotide binding interactions modulate dNTP selectivity and facilitate 8-oxo-dGTP incorporation by DNA polymerase lambda

    PubMed Central

    Burak, Matthew J.; Guja, Kip E.; Garcia-Diaz, Miguel

    2015-01-01

    8-Oxo-7,8,-dihydro-2′-deoxyguanosine triphosphate (8-oxo-dGTP) is a major product of oxidative damage in the nucleotide pool. It is capable of mispairing with adenosine (dA), resulting in futile, mutagenic cycles of base excision repair. Therefore, it is critical that DNA polymerases discriminate against 8-oxo-dGTP at the insertion step. Because of its roles in oxidative DNA damage repair and non-homologous end joining, DNA polymerase lambda (Pol λ) may frequently encounter 8-oxo-dGTP. Here, we have studied the mechanisms of 8-oxo-dGMP incorporation and discrimination by Pol λ. We have solved high resolution crystal structures showing how Pol λ accommodates 8-oxo-dGTP in its active site. The structures indicate that when mispaired with dA, the oxidized nucleotide assumes the mutagenic syn-conformation, and is stabilized by multiple interactions. Steady-state kinetics reveal that two residues lining the dNTP binding pocket, Ala510 and Asn513, play differential roles in dNTP selectivity. Specifically, Ala510 and Asn513 facilitate incorporation of 8-oxo-dGMP opposite dA and dC, respectively. These residues also modulate the balance between purine and pyrimidine incorporation. Our results shed light on the mechanisms controlling 8-oxo-dGMP incorporation in Pol λ and on the importance of interactions with the incoming dNTP to determine selectivity in family X DNA polymerases. PMID:26220180

  16. Collection and control of tritium bioassay samples at Pantex

    SciTech Connect

    Fairrow, N.L.; Ivie, W.E.

    1992-01-01

    Pantex is the final assembly/disassembly point for US nuclear weapons. The Pantex internal dosimetry section monitors radiation workers once a month for tritium exposure. In order to manage collection and control of the bioassay specimens efficiently, a bar code system for collection of samples was developed and implemented to speed up the process and decrease the number of errors probable when transferring data. In the past, all the bioassay data from samples were entered manually into a computer database. Transferring the bioassay data from the liquid scintillation counter to each individual's dosimetry record required as much as two weeks of concentrated effort.

  17. Collection and control of tritium bioassay samples at Pantex

    SciTech Connect

    Fairrow, N.L.; Ivie, W.E.

    1992-12-31

    Pantex is the final assembly/disassembly point for US nuclear weapons. The Pantex internal dosimetry section monitors radiation workers once a month for tritium exposure. In order to manage collection and control of the bioassay specimens efficiently, a bar code system for collection of samples was developed and implemented to speed up the process and decrease the number of errors probable when transferring data. In the past, all the bioassay data from samples were entered manually into a computer database. Transferring the bioassay data from the liquid scintillation counter to each individual`s dosimetry record required as much as two weeks of concentrated effort.

  18. Estrogen Receptor Agonists and Antagonists in the Yeast Estrogen Bioassay.

    PubMed

    Wang, Si; Bovee, Toine F H

    2016-01-01

    Cell-based bioassays can be used to predict the eventual biological activity of a substance on a living organism. In vitro reporter gene bioassays are based on recombinant vertebrate cell lines or yeast strains and especially the latter are easy-to-handle, cheap, and fast. Moreover, yeast cells do not express estrogen, androgen, progesterone or glucocorticoid receptors, and are thus powerful tools in the development of specific reporter gene systems that are devoid of crosstalk from other hormone pathways. This chapter describes our experience with an in-house developed RIKILT yeast estrogen bioassay for testing estrogen receptor agonists and antagonists, focusing on the applicability of the latter. PMID:26585147

  19. Evaporation-Driven Bioassays in Suspended Droplets.

    PubMed

    Hernandez-Perez, Ruth; Fan, Z Hugh; Garcia-Cordero, Jose L

    2016-07-19

    The microtiter plate has been an essential tool for diagnostics, high-throughput screening, and biological assays. We present an alternative platform to perform bioassays in a microplate format that exploits evaporation to drive assay reactions. Our method consists of droplets suspended on plastic pillars; reactions occur in these droplets instead of the wells. The pillars are fabricated by milling, and the rough surface created by this fabrication method pins the droplet to a constant contact line during the assay and also acts as a hydrophobic surface. Upon evaporation, natural convection arising from Marangoni currents mixes solutions in the droplet, which speeds up assay reactions, decreases assay times, and increases limits of detection. As a proof of concept we implemented two colorimetric assays to detect glucose and proteins in only 1.5 μL, without any external devices for mixing and with a digital microscope as a readout mechanism. Our platform is an ideal alternative to the microtiter plate, works with different volumes, is compatible with commercially available reagent dispensers and plate-readers, and could have broad applications in diagnostics and high-throughput screening. PMID:27331825

  20. Annotating Human P-Glycoprotein Bioassay Data

    PubMed Central

    Zdrazil, Barbara; Pinto, Marta; Vasanthanathan, Poongavanam; Williams, Antony J; Balderud, Linda Zander; Engkvist, Ola; Chichester, Christine; Hersey, Anne; Overington, John P; Ecker, Gerhard F

    2012-01-01

    Abstract Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are represented in the ChEMBL and TP-search open source databases. Furthermore, the ability of data, determined in different assays, to be combined with each other is explored. As a result of this study, it is suggested that for inhibitors of human P-glycoprotein it is possible to combine data coming from the same assay type, if the cell lines used are also identical and the fluorescent or radiolabeled substrate have overlapping binding sites. In addition, it demonstrates that there is a need for larger chemical diverse datasets that have been measured in a panel of different assays. This would certainly alleviate the search for other inter-correlations between bioactivity data yielded by different assay setups. PMID:23293680

  1. Voyager: Neptune Encounter Highlights

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Voyager encounter data are presented in computer animation (CA) and real (R) animation. The highlights include a view of 2 full rotations of Neptune. It shows spacecraft trajectory 'diving' over Neptune and intercepting Triton's orbit, depicting radiation and occulation zones. Also shown are a renegade orbit of Triton and Voyager's encounter with Neptune's Magnetopause. A model of the spacecraft's complex maneuvers during close encounters of Neptune and Triton is presented. A view from Earth of Neptune's occulation experiment is is shown as well as a recreation of Voyager's final pass. There is detail of Voyager's Image Compensation technique which produces Voyager images. Eighteen images were produced on June 22 - 23, 1989, from 57 million miles away. A 68 day sequence which provides a stroboscopic view - colorization approximates what is seen by the human eye. Real time images recorded live from Voyager on 8/24/89 are presented. Photoclinometry produced the topography of Triton. Three images are used to create a sequence of Neptune's rings. The globe of Neptune and 2 views of the south pole are shown as well as Neptune rotating. The rotation of a scooter is frozen in images showing differential motion. There is a view of rotation of the Great Dark Spot about its own axis. Photoclinometry provides a 3-dimensional perspective using a color mosaic of Triton images. The globe is used to indicate the orientation of Neptune's crescent. The east and west plumes on Triton are shown.

  2. 1999 NCCS Highlights

    NASA Technical Reports Server (NTRS)

    Bennett, Jerome (Technical Monitor)

    2002-01-01

    The NASA Center for Computational Sciences (NCCS) is a high-performance scientific computing facility operated, maintained and managed by the Earth and Space Data Computing Division (ESDCD) of NASA Goddard Space Flight Center's (GSFC) Earth Sciences Directorate. The mission of the NCCS is to advance leading-edge science by providing the best people, computers, and data storage systems to NASA's Earth and space sciences programs and those of other U.S. Government agencies, universities, and private institutions. Among the many computationally demanding Earth science research efforts supported by the NCCS in Fiscal Year 1999 (FY99) are the NASA Seasonal-to-Interannual Prediction Project, the NASA Search and Rescue Mission, Earth gravitational model development efforts, the National Weather Service's North American Observing System program, Data Assimilation Office studies, a NASA-sponsored project at the Center for Ocean-Land-Atmosphere Studies, a NASA-sponsored microgravity project conducted by researchers at the City University of New York and the University of Pennsylvania, the completion of a satellite-derived global climate data set, simulations of a new geodynamo model, and studies of Earth's torque. This document presents highlights of these research efforts and an overview of the NCCS, its facilities, and its people.

  3. FY 1986 budget highlights

    SciTech Connect

    Not Available

    1985-02-01

    The FY 1986 budget request for DOE supports the energy, general science and defense missions of the Department in a comprehensive manner, while being responsive to the President's directive to all Federal agencies to freeze or reduce Government spending wherever possible to reduce the Federal deficit. The discussion displays the budget in a format designed to emphasize the varied activities of DOE. ''Research and Development'' describes the nature of the scientific and technical effort which underlies the Department's programs in a number of areas, such as energy, general science, and weapons research, which previously appeared in three distinct sections of our budget presentation. ''Defense Production and Support'' highlights a significant element of our defense activities which have production, whether of weapons or materials, as a common thread. ''Waste Activities'' combines programs from the civilian and defense areas to bring attention to a major effort of DOE ''Business Enterprises'' focuses attention on the fact that a number of the Department's activities are operated like businesses, marketing products and generating revenues. ''Grants and Other Energy Functions'' is how we group non-research and development grant programs and such essential activities as energy information and regulation. Finally, ''Department Management'' includes the various ''overhead'' organizations which keep the Department functioning at headquarters and in the field.

  4. Bioassay Phantoms Using Medical Images and Computer Aided Manufacturing

    SciTech Connect

    Dr. X. Geroge Xu

    2011-01-28

    A radiation bioassay program relies on a set of standard human phantoms to calibrate and assess radioactivity levels inside a human body for radiation protection and nuclear medicine imaging purposes. However, the methodologies in the development and application of anthropomorphic phantoms, both physical and computational, had mostly remained the same for the past 40 years. We herein propose a 3-year research project to develop medical image-based physical and computational phantoms specifically for radiation bioassay applications involving internally deposited radionuclides. The broad, long-term objective of this research was to set the foundation for a systematic paradigm shift away from the anatomically crude phantoms in existence today to realistic and ultimately individual-specific bioassay methodologies. This long-term objective is expected to impact all areas of radiation bioassay involving nuclear power plants, U.S. DOE laboratories, and nuclear medicine clinics.

  5. A CONTROLLED BIOASSAY SYSTEM FOR MEASURING TOXICITY OF HEAVY METALS

    EPA Science Inventory

    Biological availability of metal micronutrients and metal toxicity are believed to be dependent on metal oxidation state, complexation, and solubility as well as the physicochemical characteristics of the aqueous phase. Basic design criteria for fish bioassays which are capable o...

  6. Bioassay-Directed Fractionation of Diesel and Biodiesel Emissions

    EPA Science Inventory

    Biofuels are being developed as alternatives to petroleum-derived products, but published research is contradictory regarding the mutagenic activity of such emissions relative to those from petroleum diesel. We performed bioassay-directed fractionation and analyzed the polycyclic...

  7. A wind tunnel bioassay system for screening mosquito repellents.

    PubMed

    Sharpington, P J; Healy, T P; Copland, M J

    2000-09-01

    A wind tunnel bioassay system to screen mosquito repellents is described. A wind tunnel is utilized to exploit the upwind flight response of host-seeking mosquitoes. Mosquitoes within the wind tunnel are activated with human breath, fly upwind, and land on heated chick skins. This behavioral sequence results in a consistently high percentage of the test population approaching repellent or control stimuli. The bioassay system is calibrated with diethyl methylbenzamide against Aedes aegypti and demonstrates a reproducible dose-response relationship. The persistence of diethyl methyl benzamide after a 1-h period is also recorded. The design of the bioassay system permits simultaneous, independent testing of 3 candidate repellents. The wind tunnel bioassay system is compared to other techniques for evaluating mosquito repellents. PMID:11081652

  8. K65R and K65A substitutions in HIV-1 reverse transcriptase enhance polymerase fidelity by decreasing both dNTP misinsertion and mispaired primer extension efficiencies

    PubMed Central

    Garforth, Scott J.; Domaoal, Robert A.; Lwatula, Chisanga; Landau, Mark J.; Meyer, Amanda J.; Anderson, Karen S.; Prasad, Vinayaka R.

    2010-01-01

    The Lys65 residue, in the fingers domain of HIV reverse transcriptase (RT), interacts in a sequence independent fashion with the incoming dNTP. Previously, we showed that a 5 amino acid deletion spanning Lys65 and a K65A substitution both enhanced the fidelity of dNTP insertion. We hypothesized that the Lys65 residue enhances dNTP misinsertion via interactions with the γ-phosphate of the incoming dNTP. We now examine this hypothesis in pre-steady state kinetic studies using wild type HIV-1 RT and two substitution mutants: K65A and K65R. The K65R mutation did not greatly increase misinsertion fidelity, but the K65A mutation led to higher incorporation fidelity. For a misinsertion to become a permanent error, it needs to be accompanied by the extension of the mispaired terminus thus formed. Both mutants, and the wild-type enzyme, discriminated against the mismatched primer at the catalytic step (kpol). Additionally, K65A and K65R mutants displayed a further decrease in mismatch extension efficiency, primarily at the level of dNTP binding. We employed hydroxyl radical footprinting to determine the position of the RT on the primer-template. The wild-type and Lys65 substituted enzymes occupied the same position at the primer terminus; the presence of a mismatched primer terminus caused all three enzymes to be displaced to a −2 position relative to the primer 3’ end. In the context of an efficiently extended mismatched terminus, the presence of the next complementary nucleotide overcame the displacement, resulting in a complex resembling the matched terminus. The results are consistent with the observed reduction in kpol in mispaired primer extension being due to the position of the enzyme at a mismatched terminus. Our work shows the influence of stabilizing interactions of Lys65 with the incoming dNTP in affecting two different aspects of polymerase fidelity. PMID:20538005

  9. STS-70 mission highlights

    NASA Astrophysics Data System (ADS)

    1995-09-01

    The highlights of the STS-70 mission are presented in this video. The flight crew consisted of Cmdr. John Hendricks, Pilot Kevin Kregel, Flight Engineer Nancy Curie, and Mission Specialists Dr. Don Thomas and Dr. Mary Ellen Weber. The mission's primary objective was the deployment of the 7th Tracking Data and Relay Satellite (TDRS), which will provide a communication, tracking, telemetry, data acquisition, and command services space-based network system essential to low Earth orbital spacecraft. Secondary mission objectives included activating and studying the Physiological and Anatomical Rodent Experiment/National Institutes of Health-Rodents (PARE/NIH-R), The Bioreactor Demonstration System (BDS), the Commercial Protein Crystal Growth (CPCG) studies, the Space Tissue Loss/National Institutes of Health-Cells (STL/NIH-C) experiment, the Biological Research in Canisters (BRIC) experiment, Shuttle Amateur Radio Experiment-2 (SAREX-2), the Visual Function Tester-4 (VFT-4), the Hand-Held, Earth Oriented, Real-Time, Cooperative, User-Friendly, Location-Targeting and Environmental System (HERCULES), the Microcapsules in Space-B (MIS-B) experiment, the Windows Experiment (WINDEX), the Radiation Monitoring Equipment-3 (RME-3), and the Military Applications of Ship Tracks (MAST) experiment. There was an in-orbit dedication ceremony by the spacecrew and the newly Integrated Mission Control Center to commemorate the Center's integration. The STS-70 mission was the first mission monitored by this new control center. Earth views included the Earth's atmosphere, a sunrise over the Earth's horizon, several views of various land masses, some B/W lightning shots, some cloud cover, and a tropical storm.

  10. Comparison of laboratory batch and flow-through microcosm bioassays.

    PubMed

    Clément, Bernard J P; Delhaye, Hélène L; Triffault-Bouchet, Gaëlle G

    2014-10-01

    Since 1997, we have been developing a protocol for ecotoxicological bioassays in 2-L laboratory microcosms and have applied it to the study of various pollutants and ecotoxicological risk assessment scenarios in the area of urban facilities and transport infrastructures. The effects on five different organisms (micro-algae, duckweeds, daphnids, amphipods, chironomids) are assessed using biological responses such as growth, emergence (chironomids), reproduction (daphnids) and survival, with a duration of exposure of 3 weeks. This bioassay has mainly been used as a batch bioassay, i.e., the water was not renewed during the test. A flow-through microcosm bioassay has been developed recently, with the assumption that conditions for the biota should be improved, variability reduced, and the range of exposure patterns enlarged (e.g., the possibility of maintaining constant exposure in the water column). This paper compares the results obtained in batch and flow-through microcosm bioassays, using cadmium as a model toxicant. As expected, the stabilization of physico-chemical parameters, increased organism fitness and reduced variability were observed in the flow-through microcosm bioassay. PMID:25086825

  11. Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution

    PubMed Central

    Hwang, Candy S.; Xu, Liang; Wang, Wei; Ulrich, Sébastien; Zhang, Lu; Chong, Jenny; Shin, Ji Hyun; Huang, Xuhui; Kool, Eric T.; McKenna, Charles E.; Wang, Dong

    2016-01-01

    RNA polymerase II (pol II) utilizes a complex interaction network to select and incorporate correct nucleoside triphosphate (NTP) substrates with high efficiency and fidelity. Our previous ‘synthetic nucleic acid substitution’ strategy has been successfully applied in dissecting the function of nucleic acid moieties in pol II transcription. However, how the triphosphate moiety of substrate influences the rate of P-O bond cleavage and formation during nucleotide incorporation is still unclear. Here, by employing β,γ-bridging atom-‘substituted’ NTPs, we elucidate how the methylene substitution in the pyrophosphate leaving group affects cognate and non-cognate nucleotide incorporation. Intriguingly, the effect of the β,γ-methylene substitution on the non-cognate UTP/dT scaffold (∼3-fold decrease in kpol) is significantly different from that of the cognate ATP/dT scaffold (∼130-fold decrease in kpol). Removal of the wobble hydrogen bonds in U:dT recovers a strong response to methylene substitution of UTP. Our kinetic and modeling studies are consistent with a unique altered transition state for bond formation and cleavage for UTP/dT incorporation compared with ATP/dT incorporation. Collectively, our data reveals the functional interplay between NTP triphosphate moiety and base pair hydrogen bonding recognition during nucleotide incorporation. PMID:27060150

  12. Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study.

    PubMed

    Hoane, Jessica S; Johnson, Crystal L; Morrison, James P; Elmore, Susan A

    2016-07-01

    Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. PMID:27000376

  13. UV induced ubiquitination of the yeast Rad4-Rad23 complex promotes survival by regulating cellular dNTP pools.

    PubMed

    Zhou, Zheng; Humphryes, Neil; van Eijk, Patrick; Waters, Raymond; Yu, Shirong; Kraehenbuehl, Rolf; Hartsuiker, Edgar; Reed, Simon H

    2015-09-01

    Regulating gene expression programmes is a central facet of the DNA damage response. The Dun1 kinase protein controls expression of many DNA damage induced genes, including the ribonucleotide reductase genes, which regulate cellular dNTP pools. Using a combination of gene expression profiling and chromatin immunoprecipitation, we demonstrate that in the absence of DNA damage the yeast Rad4-Rad23 nucleotide excision repair complex binds to the promoters of certain DNA damage response genes including DUN1, inhibiting their expression. UV radiation promotes the loss of occupancy of the Rad4-Rad23 complex from the regulatory regions of these genes, enabling their induction and thereby controlling the production of dNTPs. We demonstrate that this regulatory mechanism, which is dependent on the ubiquitination of Rad4 by the GG-NER E3 ligase, promotes UV survival in yeast cells. These results support an unanticipated regulatory mechanism that integrates ubiquitination of NER DNA repair factors with the regulation of the transcriptional response controlling dNTP production and cellular survival after UV damage. PMID:26150418

  14. Highlights of Astronomy

    NASA Astrophysics Data System (ADS)

    van der Hucht, Karel

    2008-02-01

    Preface Karel A. van der Hucht; Part I. Invited Discourses: Part II. Joint Discussions: 1. Particle acceleration - from Solar System to AGN Marian Karlicky and John C. Brown; 2. Pulsar emission and related phenomena Werner Becker, Janusz A. Gil and Bronislaw Rudak; 3. Solar activity regions and magnetic structure Debi Prasad Choudhary and Michal Sobotka; 4. The ultraviolet universe: Stars from birth to death Ana I. Gomez de Castro and Martin A. Barstow; 5. Calibrating the top of the stellar M-L relationship Claus Leitherer, Anthony F. J. Moat and Joachim Puls; 6. Neutron stars and black holes in star clusters Frederic A. Rasio; 7. The Universe at z > 6 Daniel Schaerer and Andrea Ferrara; 8. Solar and stellar activity cycles Klaus G. Strassmeier and Alexander Kosovichev; 9. Supernovae: One millennium after SN 1006 P. Frank Winkler, Wolfgang Hillebrandt and Brian P. Schmidt; 10. Progress in planetary exploration missions Guy J. Consolmagno; 11. Pre-solar grains as astrophysical tools Anja C. Andersen and John C. Lattanzio; 12. Long wavelength astrophysics T. Joseph W. Lazio and Namir E. Kassim; 13. Exploiting large surveys for galactic astronomy Christopher J. Corbally, Coryn A. L. Bailer-Jones, Sunetra Giridhar and Thomas H. Lloyd Evans; 14. Modeling dense stellar systems Alison I. Sills, Ladislav Subr and Simon F. Portegies Zwart; 15. New cosmology results from the Spitzer Space Telescope George Helou and David T. Frayer; 16. Nomenclature, precession and new models in fundamental astronomy Nicole Capitaine, Jan Vondrak & James L. Hilton; 17. Highlights of recent progress in seismology of the Sun and Sun-like stars John W. Leibacher and Michael J. Thompson; Part III. Special Sessions: SpS 1. Large astronomical facilities of the next decade Gerard F. Gilmore and Richard T. Schilizzi; SpS 2. Innovation in teaching and learning astronomy methods Rosa M. Ros and Jay M. Pasachoff; SpS 3. The Virtual Observatory in action: New science, new technology and next

  15. ESO Highlights in 2008

    NASA Astrophysics Data System (ADS)

    2009-01-01

    As is now the tradition, the European Southern Observatory looks back at the exciting moments of last year. 2008 was in several aspects an exceptionally good year. Over the year, ESO's telescopes provided data for more than 700 scientific publications in refereed journals, making ESO the most productive ground-based observatory in the world. ESO PR Highlights 2008 ESO PR Photo 01a/09 The image above is a clickable map. These are only some of the press releases issued by ESO in 2008. For a full listing, please go to ESO 2008 page. Austria signed the agreement to join the other 13 ESO member states (ESO 11/08 and 20/08), while the year marked the 10th anniversary of first light for ESO's "perfect science machine", the Very Large Telescope (ESO 16/08 and 17/08). The ALMA project, for which ESO is the European partner, had a major milestone in December, as the observatory was equipped with its first antenna (ESO 49/08). Also the Atacama Pathfinder Experiment (APEX) telescope impressed this year with some very impressive and publicly visible results. Highlights came in many fields: Astronomers for instance used the Very Large Telescope (VLT) to discover and image a probable giant planet long sought around the star Beta Pictoris (ESO 42/08). This is now the eighth extrasolar planet to have been imaged since the VLT imaged the first extrasolar planet in 2004 (three of eight were imaged with VLT). The VLT also enabled three students to confirm the nature of a unique planet (ESO 45/08). This extraordinary find, which turned up during their research project, is a planet about five times as massive as Jupiter. This is the first planet discovered orbiting a fast-rotating hot star. The world's foremost planet-hunting instrument, HARPS, located at ESO's La Silla observatory, scored a new first, finding a system of three super-Earths around a star (ESO 19/08). Based on the complete HARPS sample, astronomers now think that one Sun-like star out of three harbours short orbit, low

  16. ESO Highlights in 2008

    NASA Astrophysics Data System (ADS)

    2009-01-01

    As is now the tradition, the European Southern Observatory looks back at the exciting moments of last year. 2008 was in several aspects an exceptionally good year. Over the year, ESO's telescopes provided data for more than 700 scientific publications in refereed journals, making ESO the most productive ground-based observatory in the world. ESO PR Highlights 2008 ESO PR Photo 01a/09 The image above is a clickable map. These are only some of the press releases issued by ESO in 2008. For a full listing, please go to ESO 2008 page. Austria signed the agreement to join the other 13 ESO member states (ESO 11/08 and 20/08), while the year marked the 10th anniversary of first light for ESO's "perfect science machine", the Very Large Telescope (ESO 16/08 and 17/08). The ALMA project, for which ESO is the European partner, had a major milestone in December, as the observatory was equipped with its first antenna (ESO 49/08). Also the Atacama Pathfinder Experiment (APEX) telescope impressed this year with some very impressive and publicly visible results. Highlights came in many fields: Astronomers for instance used the Very Large Telescope (VLT) to discover and image a probable giant planet long sought around the star Beta Pictoris (ESO 42/08). This is now the eighth extrasolar planet to have been imaged since the VLT imaged the first extrasolar planet in 2004 (three of eight were imaged with VLT). The VLT also enabled three students to confirm the nature of a unique planet (ESO 45/08). This extraordinary find, which turned up during their research project, is a planet about five times as massive as Jupiter. This is the first planet discovered orbiting a fast-rotating hot star. The world's foremost planet-hunting instrument, HARPS, located at ESO's La Silla observatory, scored a new first, finding a system of three super-Earths around a star (ESO 19/08). Based on the complete HARPS sample, astronomers now think that one Sun-like star out of three harbours short orbit, low

  17. Acarine attractants: Chemoreception, bioassay, chemistry and control.

    PubMed

    Carr, Ann L; Roe, Michael

    2016-07-01

    The Acari are of significant economic importance in crop production and human and animal health. Acaricides are essential for the control of these pests, but at the same time, the number of available pesticides is limited, especially for applications in animal production. The Acari consist of two major groups, the mites that demonstrate a wide variety of life strategies, i.e., herbivory, predation and ectoparasitism, and ticks which have evolved obligatory hematophagy. The major sites of chemoreception in the acarines are the chelicerae, palps and tarsi on the forelegs. A unifying name, the "foretarsal sensory organ" (FSO), is proposed for the first time in this review for the sensory site on the forelegs of all acarines. The FSO has multiple sensory functions including olfaction, gustation, and heat detection. Preliminary transcriptomic data in ticks suggest that chemoreception in the FSO is achieved by a different mechanism from insects. There are a variety of laboratory and field bioassay methods that have been developed for the identification and characterization of attractants but minimal techniques for electrophysiology studies. Over the past three to four decades, significant progress has been made in the chemistry and analysis of function for acarine attractants in mites and ticks. In mites, attractants include aggregation, immature female, female sex and alarm pheromones; in ticks, the attraction-aggregation-attachment, assembly and sex pheromones; in mites and ticks host kairomones and plant allomones; and in mites, fungal allomones. There are still large gaps in our knowledge of chemical communication in the acarines compared to insects, especially relative to acarine pheromones, and more so for mites than ticks. However, the use of lure-and-kill and lure-enhanced biocontrol strategies has been investigated for tick and mite control, respectively, with significant environmental advantages which warrant further study. PMID:27265828

  18. Nuclear Thermal Propulsion (NTP): A Proven, Growth Technology for Fast Transit Human Missions to Mars

    NASA Technical Reports Server (NTRS)

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2014-01-01

    The "fast conjunction" long surface stay mission option was selected for NASA's recent Mars Design Reference Architecture (DRA) 5.0 study because it provided adequate time at Mars (approx. 540 days) for the crew to explore the planet's geological diversity while also reducing the "1-way" transit times to and from Mars to approx. 6 months. Short transit times are desirable in order to reduce the debilitating physiological effects on the human body that can result from prolonged exposure to the zero-gravity (0-gE) and radiation environments of space. Recent measurements from the RAD detector attached to the Curiosity rover indicate that astronauts would receive a radiation dose of approx. 0.66 Sv (approx. 66 rem)-the limiting value established by NASA-during their 1-year journey in deep space. Proven nuclear thermal rocket (NTR) technology, with its high thrust and high specific impulse (Isp approx. 900 s), can cut 1-way transit times by as much as 50 percent by increasing the propellant capacity of the Mars transfer vehicle (MTV). No large technology scale-ups in engine size are required for these short transit missions either since the smallest engine tested during the Rover program-the 25 klbf "Pewee" engine is sufficient when used in a clustered arrangement of three to four engines. The "Copernicus" crewed MTV developed for DRA 5.0 is a 0-gE design consisting of three basic components: (1) the NTP stage (NTPS); (2) the crewed payload element; and (3) an integrated "saddle truss" and LH2 propellant drop tank assembly that connects the two elements. With a propellant capacity of approx. 190 t, Copernicus can support 1-way transit times ranging from approx. 150 to 220 days over the 15-year synodic cycle. The paper examines the impact on vehicle design of decreasing transit times for the 2033 mission opportunity. With a fourth "upgraded" SLS/HLV launch, an "in-line" LH2 tank element can be added to Copernicus allowing 1-way transit times of 130 days. To achieve 100

  19. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF DI-N-HEXYL PHTHALATE

    EPA Science Inventory

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk to Human Reproduction (CERHR) convened an expert panel charged with examini...

  20. NTP CENTER FOR THE EVALUATION OF RISKS TO HUMAN REPRODUCTION: PHTHALATES EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF BUTYL BENZYL PHTHALATE

    EPA Science Inventory

    The phthalates are a family of environmentally important compounds with diverse uses. Reproductive toxicity has been demonstrated for some members of this family. The NTP Center for the Evaluation of Risk to Human Reproduction (CERHR) convened an expert panel charged with examini...

  1. A security analysis of version 2 of the Network Time Protocol (NTP): A report to the privacy and security research group

    NASA Technical Reports Server (NTRS)

    Bishop, Matt

    1991-01-01

    The Network Time Protocol is being used throughout the Internet to provide an accurate time service. The security requirements are examined of such a service, version 2 of the NTP protocol is analyzed to determine how well it meets these requirements, and improvements are suggested where appropriate.

  2. Primary Bioassay of Human Myeloma Stem Cells

    PubMed Central

    Hamburger, Anne; Salmon, Sydney E.

    1977-01-01

    The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105-106 and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B

  3. A novel laboratory screening bioassay for crop seedling allelopathy.

    PubMed

    Belz, Regina G; Hurle, Karl

    2004-01-01

    Crops that control weeds by root exudation of allelochemicals are receiving increased attention, and there are efforts to breed allelopathic cultivars in several crops. The genetic improvement of allelopathic traits is based upon parental germ plasm with high allelopathic activity. Identification of allelopathic germplasm is done in laboratory screening bioassays, but experimental protocols are limited. We developed a fast and reliable laboratory screening bioassay for grain crops that includes dose-response considerations as an integral part of the experimental design. The bioassay was conducted in hydroponic culture, and a range of experiments with 2-(3H)-benzoxazolinone (BOA), an allelochemical of several grain crops, was carried out to define the basic protocol. Because of its sensitivity to BOA, Sinapis alba L. was selected as the receiver species. BOA affected growth (fresh weight and length of shoot and root), enzyme activities (ascorbate peroxidase, catalase, glutathione S-transferase, peroxidase, phenylalanine ammonia-lyase), and chlorophyll fluorescence, whereby root length was the most reliable response parameter. BOA sensitivity was dependent on nutrients for all parameters measured, and, thus, no nutrients were added. A set of experiments with Secale cereale L. and Triticum aestivum L. as donor species was carried out to optimize the protocol. Light and pH were eliminated as primary causes for the observed inhibition. The proposed bioassay has several methodological advantages over current bioassays. PMID:15074665

  4. Soil bioassays and the {sup 129}I problem

    SciTech Connect

    Sheppard, S.C.

    1995-12-31

    Iodine-129 is a very long-lived radionuclide associated with spent nuclear fuel. Because {sup 129}I has a 10{sup 7}-year half-life, is very mobile in the environment and is a biologically essential element, it is the most limiting radionuclide affecting disposal of spent fuel. Traditionally, the potential impacts of {sup 129}I have been estimated for human receptors, with the implicit assumption that all other organisms are less at risk. Risk is the operative word, the objective for protection of humans is to protect individuals, whereas the objective for other biota is usually to protect populations. Here, {sup 129}I poses an interesting problem: the half-life is so long it is barely radioactive. Thus, the chemical toxicity may be more limiting than the radiological impact. A series of soil bioassays were employed, including a life-cycle plant (Brassica rapa) bioassay, a modified earthworm survival bioassay, a microarthropod colonization/survival bioassay, and a series of more common soil and aquatic bioassays. Chemical toxicity was indicated at soil concentrations as low as 5 mg kg{sup {minus}1}. At these levels, radiological impact on non-human biota would not be expected, and therefore the chemical toxicity effects are more critical. However, human food-chain model estimates show these levels, as pure {sup 129}I, would be unacceptable for human radiological exposure, so that for {sup 129}I, protection of the human environment should also be protective of non-human biota.

  5. [Investigation on pattern and methods of quality control for Chinese materia medica based on dao-di herbs and bioassay - bioassay for Coptis chinensis].

    PubMed

    Yan, Dan; Xiao, Xiao-he

    2011-05-01

    Establishment of bioassay methods is the technical issues to be faced with in the bioassay of Chinese materia medica. Taking the bioassay of Coptis chinensis Franch. as an example, the establishment process and application of the bioassay methods (including bio-potency and bio-activity fingerprint) were explained from the aspects of methodology, principle of selection, experimental design, method confirmation and data analysis. The common technologies were extracted and formed with the above aspects, so as to provide technical support for constructing pattern and method of the quality control for Chinese materia medica based on the dao-di herbs and bioassay. PMID:21800546

  6. Comparative activity of human carcinogens and NTP rodent carcinogens in the mouse bone marrow micronucleus assay: an integrative approach to genetic toxicity data assessment.

    PubMed Central

    Tinwell, H; Ashby, J

    1994-01-01

    The mouse bone marrow micronucleus (MN) assay holds a key position in all schemes for detecting potential human carcinogens and mutagens. It was therefore of concern when Shelby et al. reported that only 5 of 25 rodent carcinogens defined by the U.S. NTP were positive in the assay. Further, each of these positive responses was weak and indistinguishable from the 4 positive responses observed among the 24 NTP noncarcinogens tested. To focus these findings, the activity in the MN assay of 26 human carcinogens, 6 reference rodent genotoxins, and the 9 NTP chemicals positive in the MN assay have been displayed in a common format. This involved plotting the minimum positive dose level (expressed as mumole/kilogram) and the maximum fold-increase in micronucleated polychromatic erythrocytes frequency observed at any dose level. By displaying the high sensitivity of the micronucleus assay to the reference human and rodent genotoxins, this analysis emphasizes the weakness in the MN assay responses given by the NTP carcinogens reported by Shelby et al. This, in turn, poses questions about the intrinsic hazard of this selection of NTP rodent carcinogens. Using fotemustine and vitamin C as models of a toxic and a nontoxic chemical known to be active in the MN assay, this analysis describes a method by which their relative potential human hazard can be distinguished (a synthetic, as opposed to an analytical approach to data assessment). The possibility that some weak responses observed in the MN assay at elevated dose levels may be stress induced is considered. Images p758-a Figure 1. PMID:9657707

  7. GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state

    PubMed Central

    Hansen, Erik C.; Seamon, Kyle J.; Cravens, Shannen L.; Stivers, James T.

    2014-01-01

    The HIV-1 restriction factor sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) is a tetrameric protein that catalyzes the hydrolysis of all dNTPs to the deoxynucleoside and tripolyphosphate, which effectively depletes the dNTP substrates of HIV reverse transcriptase. Here, we establish that SAMHD1 is activated by GTP binding to guanine-specific activator sites (A1) as well as coactivation by substrate dNTP binding to a distinct set of nonspecific activator sites (A2). Combined activation by GTP and dNTPs results in a long-lived tetrameric form of SAMHD1 that persists for hours, even after activating nucleotides are withdrawn from the solution. These results reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer forms, where GTP binding to the A1 sites generates dimer and dNTP binding to the A2 and catalytic sites generates active tetramer. Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the levels of all dNTPs and the generation of a persistent tetramer that is not in equilibrium with free activators. The significance of the long-lived activated state is that SAMHD1 can remain active long after dNTP pools have been reduced to a level that would lead to inactivation. This property would be important in resting CD4+ T cells, where dNTP pools are reduced to nanomolar levels to restrict infection by HIV-1. PMID:24753578

  8. Addressing the recovery of feeding rates in post-exposure feeding bioassays: Cyathura carinata as a case study

    SciTech Connect

    Pais-Costa, Antonia Juliana; Acevedo, Pelayo; Marques, João Carlos; Martinez-Haro, Mónica

    2015-02-15

    Post-exposure bioassays are used in environmental assessment as a cost-effective tool, but the effects of organism's recovery after exposure to pollutant has not yet been addressed in detail. The recoveries of post-exposure feeding rates after being exposed to two sublethal concentrations of cadmium during two different exposure periods (48 h and 96 h) were evaluated under laboratory conditions using the estuarine isopod Cyathura carinata. Results showed that feeding depression was a stable endpoint up to 24 h after cadmium exposure, which is useful for ecotoxicological bioassays. - Highlights: • We studied recovery of post-exposure feeding rates 48–96 h after cadmium exposure. • The assay is based on the isopod Cyathura carinata. • Post-exposure feeding inhibition is a stable sublethal endpoint.

  9. Environmental effects of dredging. A chronic sublethal sediment bioassay with the marine polychaete nereis (Neanthes) arenaceodentata

    SciTech Connect

    Dillon, T.M.; Moore, D.W.; Bridges, T.S.

    1995-01-01

    This note provides a general overview of a new 28-day chronic sublethal sediment bioassay designed for the regulatory evaluation of dredged material. The bioassay uses survival and growth rate endpoints with the polychaete Nereis (Neanthes) arenaceodentata. The primary technical reference for this new bioassay is Dillon, Moore, and Reish (in press), upon which this overview is based. Sediment bioassays are used to assess the aggregate toxicity of sediment associated anthropogenic chemicals. Historically, these bioassays have measured survival of highly sensitive species following acute exposures (10 days). A new generation of sediment bioassays is being developed in which the subtle, sublethal response of test species is measured following chronic sediment exposures (Dillon 1993).

  10. Internal dosimetry performing dose assessments via bioassay measurements

    SciTech Connect

    Bailey, K.M.

    1993-05-11

    The Internal Dosimetry Department at the Y-12 Plant maintains a state-of-the-art bioassay program managed under the guidance and regulations of the Department of Energy. The two major bioassay techniques currently used at Y-12 are the in vitro (urinalysis) and in vivo (lung counting) programs. Fecal analysis (as part of the in vitro program) is another alternative; however, since both urine and fecal analysis provide essentially the same capabilities for detecting exposures to uranium, the urinalysis is the main choice primarily for aesthetic reasons. The bioassay frequency is based on meeting NCRP 87 objectives which are to monitor the accumulation of radioactive material in exposed individuals, and to ensure that significant depositions are detected.

  11. Carbon-14 Bioassay for Decommissioning of Hanford Reactors

    SciTech Connect

    Carbaugh, Eugene H.; Watson, David J.

    2012-05-01

    The old production reactors at the US Department of Energy Hanford Site used large graphite piles as the moderator. As part of long-term decommissioning plans, the potential need for 14C radiobioassay of workers was identified. Technical issues associated with 14C bioassay and worker monitoring were investigated, including anticipated graphite characterization, potential intake scenarios, and the bioassay capabilities that may be required to support the decommissioning of the graphite piles. A combination of urine and feces sampling would likely be required for the absorption type S 14C anticipated to be encountered. However the concentrations in the graphite piles appear to be sufficiently low that dosimetrically significant intakes of 14C are not credible, thus rendering moot the need for such bioassay.

  12. Method comparison for 241Am emergency urine bioassay.

    PubMed

    Li, Chunsheng; Sadi, Baki; Benkhedda, Karima; St-Amant, Nadereh; Moodie, Gerry; Ko, Raymond; Dinardo, Anthony; Kramer, Gary

    2010-10-01

    241Am is one of the high-risk radionuclides that might be used in a terrorist attack. 241Am in urine bioassay can identify the contaminated individuals who need immediate medical intervention and decontamination. This paper compares three methods for the measurement of 241Am in urine, namely liquid scintillation counting (LSC), inductively coupled plasma mass spectrometry (ICP-MS) and gamma spectrometry (GS), at two levels, 20 and 2 Bq l(-1). All three methods satisfied the ANSI N13.30 radio-bioassay criteria for accuracy and repeatability. ICP-MS offered the best sensitivity and fastest sample turnaround; however, the ICP-MS system used in this work may not be available in many bioassay laboratories. LSC and GS are more commonly available instruments. GS requires minimal or no sample preparation, which makes it a good candidate method. Moreover, the sample throughput can be significantly improved if the GS and LSC methods are automated. PMID:20573683

  13. The effect of pesticide residue on caged mosquito bioassays.

    PubMed

    Barber, J A S; Greer, Mike; Coughlin, Jamie

    2006-09-01

    Wind tunnel experiments showed that secondary pickup of insecticide residue by mosquitoes in cage bioassays had a significant effect on mortality. Cage bioassays using adult Ochlerotatus taeniorhynchus (Wiedemann) investigated the effect of exposure time to a contaminated surface. Cages were dosed in a wind tunnel using the LC50 for naled (0.124 mg a.i./ml) and an LC25 (0.0772 mg a.i./ml) for naled. Half of the bioassay mosquitoes were moved directly into clean cages with the other half remaining in the sprayed, hence contaminated, cage. Treatment mortality was assessed at 8, 15, 30, 60, 120, 240, and 1,440 min postapplication. Cage contamination had a significant effect on mosquito mortality for both the LC25 and LC50 between 15 and 30 min postapplication. PMID:17067048

  14. Bioassay-directed chemical analysis in environmental research

    SciTech Connect

    Schuetzle, D.; Lewtas, J.

    1986-01-01

    The use of short-term bioassay tests in conjunction with analytical measurements, constitute a powerful tool for identifying important environmental contaminants. The authors have coined the terminology bioassay directed chemical analysis to best describe this marriage of analytical chemistry and biology. The objective of this methodology is to identify key compounds in various types of air-pollutant samples. Once that task is completed, studies on metabolism, sources, environmental exposure and atmospheric chemistry can be undertaken. The principles and methodologies for bioassay directed chemical analysis are presented and illustrated in this paper. Most of this work has been directed toward the characterization of ambient air and diesel particulates, which are used as examples in this report to illustrate the analytical logic used for identifying the bio-active components of complex mixtures.

  15. Do we really need in-situ bioassays?

    SciTech Connect

    Salazar, M.H.; Salazar, S.M.

    1995-12-31

    In-situ bioassays are needed to validate the results from laboratory testing and to understand biological interactions. Standard laboratory protocols provide reproducible test results, and the precision of those tests can be mathematically defined. Significant correlations between toxic substances and levels of response (bioaccumulation and bioeffects) have also been demonstrated with natural field populations and suggest that the laboratory results can accurately predict field responses. An equal number of studies have shown a lack of correlation between laboratory bioassay results and responses of natural field populations. The best way to validate laboratory results is with manipulative field testing; i.e., in-situ bioassays with caged organisms. Bioaccumulation in transplanted bivalves has probably been the most frequently used form of an in-situ bioassay. The authors have refined those methods to include synoptic measurements of bioaccumulation and growth. Growth provides an easily-measured bioeffects endpoint and a means of calibrating bioaccumulation. Emphasis has been on minimizing the size range of test animals, repetitive measurements of individuals and standardization of test protocols for a variety of applications. They are now attempting to standardize criteria for accepting and interpreting data in the same way that laboratory bioassays have been standardized. Others have developed methods for in-situ bioassays using eggs, larvae, unicellular organisms, crustaceans, benthic invertebrates, bivalves, and fish. In the final analysis, the in-situ approach could be considered as an exposure system where any clinical measurements are possible. The most powerful approach would be to use the same species in laboratory and field experiments with the same endpoints.

  16. Highlights

    ERIC Educational Resources Information Center

    Mathematical Gazette, 1971

    1971-01-01

    Reprinted are "The Teaching of Euclid" by Bertrand Russell, an article on integrals by G. H. Hardy, "An Address on Relativity" by A. S. Eddington, "The Food of the Gods" by Prof. E. H. Neville, and "Simplicity and Truthfulness in Arithmetic" by W. Hope-Jones. (CT)

  17. Assessment of the environmental quality of coastal sediments by using a combination of in vitro bioassays.

    PubMed

    Pérez-Albaladejo, Elisabet; Rizzi, Juliane; Fernandes, Denise; Lille-Langøy, Roger; Karlsen, Odd André; Goksøyr, Anders; Oros, Andra; Spagnoli, Federico; Porte, Cinta

    2016-07-15

    The environmental quality of marine sediments collected in the area of influence of the Po and Danube Rivers was assessed by using a battery of bioassays based on the use of PLHC-1 cells, zebrafish-Pxr-transfected COS-7 cells, and sea bass ovarian subcellular fractions. This allowed the determination of multiple endpoints, namely, cytotoxicity, oxidative stress, induction of CYP1A, activation of zebrafish Pxr and inhibition of ovarian aromatase. Organic extracts of sediments influenced by the Danube River and collected near harbors and urban discharges showed significant cytotoxicity, CYP1A induction and inhibition of aromatase activity. An analogous response of CYP1A induction and zfPxr activation was observed, which suggests the existence of common ligands of AhR and PXR in the sediment extracts. The study highlights the usefulness of the selected bioassays to identify those sediments that could pose a risk to aquatic organisms and that require further action in order to improve their environmental quality. PMID:27207027

  18. A statistical treatment of bioassay pour fractions

    NASA Astrophysics Data System (ADS)

    Barengoltz, Jack; Hughes, David

    A bioassay is a method for estimating the number of bacterial spores on a spacecraft surface for the purpose of demonstrating compliance with planetary protection (PP) requirements (Ref. 1). The details of the process may be seen in the appropriate PP document (e.g., for NASA, Ref. 2). In general, the surface is mechanically sampled with a damp sterile swab or wipe. The completion of the process is colony formation in a growth medium in a plate (Petri dish); the colonies are counted. Consider a set of samples from randomly selected, known areas of one spacecraft surface, for simplicity. One may calculate the mean and standard deviation of the bioburden density, which is the ratio of counts to area sampled. The standard deviation represents an estimate of the variation from place to place of the true bioburden density commingled with the precision of the individual sample counts. The accuracy of individual sample results depends on the equipment used, the collection method, and the culturing method. One aspect that greatly influences the result is the pour fraction, which is the quantity of fluid added to the plates divided by the total fluid used in extracting spores from the sampling equipment. In an analysis of a single sample’s counts due to the pour fraction, one seeks to answer the question: What is the probability that if a certain number of spores are counted with a known pour fraction, that there are an additional number of spores in the part of the rinse not poured. This is given for specific values by the binomial distribution density, where detection (of culturable spores) is success and the probability of success is the pour fraction. A special summation over the binomial distribution, equivalent to adding for all possible values of the true total number of spores, is performed. This distribution when normalized will almost yield the desired quantity. It is the probability that the additional number of spores does not exceed a certain value. Of course

  19. A statistical treatment of bioassay pour fractions

    NASA Astrophysics Data System (ADS)

    Barengoltz, Jack; Hughes, David

    A bioassay is a method for estimating the number of bacterial spores on a spacecraft surface for the purpose of demonstrating compliance with planetary protection (PP) requirements (Ref. 1). The details of the process may be seen in the appropriate PP document (e.g., for NASA, Ref. 2). In general, the surface is mechanically sampled with a damp sterile swab or wipe. The completion of the process is colony formation in a growth medium in a plate (Petri dish); the colonies are counted. Consider a set of samples from randomly selected, known areas of one spacecraft surface, for simplicity. One may calculate the mean and standard deviation of the bioburden density, which is the ratio of counts to area sampled. The standard deviation represents an estimate of the variation from place to place of the true bioburden density commingled with the precision of the individual sample counts. The accuracy of individual sample results depends on the equipment used, the collection method, and the culturing method. One aspect that greatly influences the result is the pour fraction, which is the quantity of fluid added to the plates divided by the total fluid used in extracting spores from the sampling equipment. In an analysis of a single sample’s counts due to the pour fraction, one seeks to answer the question: What is the probability that if a certain number of spores are counted with a known pour fraction, that there are an additional number of spores in the part of the rinse not poured. This is given for specific values by the binomial distribution density, where detection (of culturable spores) is success and the probability of success is the pour fraction. A special summation over the binomial distribution, equivalent to adding for all possible values of the true total number of spores, is performed. This distribution when normalized will almost yield the desired quantity. It is the probability that the additional number of spores does not exceed a certain value. Of course

  20. US Army Radiological Bioassay and Dosimetry: The RBD software package

    SciTech Connect

    Eckerman, K. F.; Ward, R. C.; Maddox, L. B.

    1993-01-01

    The RBD (Radiological Bioassay and Dosimetry) software package was developed for the U. S. Army Material Command, Arlington, Virginia, to demonstrate compliance with the radiation protection guidance 10 CFR Part 20 (ref. 1). Designed to be run interactively on an IBM-compatible personal computer, RBD consists of a data base module to manage bioassay data and a computational module that incorporates algorithms for estimating radionuclide intake from either acute or chronic exposures based on measurement of the worker's rate of excretion of the radionuclide or the retained activity in the body. In estimating the intake,RBD uses a separate file for each radionuclide containing parametric representations of the retention and excretion functions. These files also contain dose-per-unit-intake coefficients used to compute the committed dose equivalent. For a given nuclide, if measurements exist for more than one type of assay, an auxiliary module, REPORT, estimates the intake by applying weights assigned in the nuclide file for each assay. Bioassay data and computed results (estimates of intake and committed dose equivalent) are stored in separate data bases, and the bioassay measurements used to compute a given result can be identified. The REPORT module creates a file containing committed effective dose equivalent for each individual that can be combined with the individual's external exposure.

  1. Book Review: Bioassays with Arthropods: 2nd Edition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The technical book "Bioassays with Arthropods: 2nd Edition" (2007. Jacqueline L. Robertson, Robert M. Russell, Haiganoush K, Preisler and N. E. Nevin, Eds. CRC Press, Boca Raton, FL, 224 pp.) was reviewed for the scientific readership of the peer-reviewed publication Journal of Economic Entomology. ...

  2. US Army Radiological Bioassay and Dosimetry: The RBD software package

    SciTech Connect

    Eckerman, K.F.; Ward, R.C.; Maddox, L.B.

    1993-01-01

    The RBD (Radiological Bioassay and Dosimetry) software package was developed for the U. S. Army Material Command, Arlington, Virginia, to demonstrate compliance with the radiation protection guidance 10 CFR Part 20 (ref. 1). Designed to be run interactively on an IBM-compatible personal computer, RBD consists of a data base module to manage bioassay data and a computational module that incorporates algorithms for estimating radionuclide intake from either acute or chronic exposures based on measurement of the worker`s rate of excretion of the radionuclide or the retained activity in the body. In estimating the intake,RBD uses a separate file for each radionuclide containing parametric representations of the retention and excretion functions. These files also contain dose-per-unit-intake coefficients used to compute the committed dose equivalent. For a given nuclide, if measurements exist for more than one type of assay, an auxiliary module, REPORT, estimates the intake by applying weights assigned in the nuclide file for each assay. Bioassay data and computed results (estimates of intake and committed dose equivalent) are stored in separate data bases, and the bioassay measurements used to compute a given result can be identified. The REPORT module creates a file containing committed effective dose equivalent for each individual that can be combined with the individual`s external exposure.

  3. BENTHIC INVERTEBRATE BIOASSAYS WITH TOXIC SEDIMENT AND PORE WATER

    EPA Science Inventory

    The relative sensitivities of bioassays to determine the toxicity of sediments were investigated and three methods of making the sample dilutions required to generate dose-response relationships were compared. he assays studied were: (a) Microtox, a 15-min assay of Photobacterium...

  4. Shape-encoded silica microparticles for multiplexed bioassays.

    PubMed

    Kim, Lily Nari; Kim, Mira; Jung, Keumsim; Bae, Hyung Jong; Jang, Jisung; Jung, Yushin; Kim, Jiyun; Kwon, Sunghoon

    2015-08-01

    Shape-encoded silica microparticles for use in multiplexed bioassays were fabricated by using optofluidic maskless lithography (OFML) and tetraethylorthosilicate (TEOS) polymerization. These encoded silica microparticles exhibit excellent bioconjugation properties and negligible non-specific analyte adsorption. Encoded silica microparticles could be useful in a wide variety of applications, including DNA- and protein-based diagnostics. PMID:26125980

  5. HIGHLY SENSITIVE BIOASSAYS FOR EVALUATING AIRBORNE MUTAGENS INDOORS

    EPA Science Inventory

    The standard mutagenicity bioassays that are readily applied to the valuation of outdoor air samples collected by high volume samplers are not efficiently sensitive to measure the mutagenicity of low volume air samples collected indoors. wo microsuspension mutation assays using v...

  6. Filtration effects due to bioassay cage design and screen type

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of bioassay cages in the efficacy assessment of specific compounds, application techniques and technologies is a common practice. There are a number of cage designs being used that range across a variety of cage shapes and sizes and mesh types. The objective of this work was to examine a r...

  7. STRESS ETHYLENE: A BIOASSAY FOR RHIZOSPHERE-APPLIED PHYTOTOXICANTS

    EPA Science Inventory

    A bioassay for rhizosphere-applied phytotoxicants was developed and evaluated with a broad range of chemicals. Test substances were applied to the rhizosphere of whole, intact bush bean plants (Phaseolus vulgaris L. cv. Bush Blue Lake 290) grown in a solid support medium and the ...

  8. Assessment of acrylamide toxicity using a battery of standardised bioassays.

    PubMed

    Zovko, Mira; Vidaković-Cifrek, Željka; Cvetković, Želimira; Bošnir, Jasna; Šikić, Sandra

    2015-12-01

    Acrylamide is a monomer widely used as an intermediate in the production of organic chemicals, e.g. polyacrylamides (PAMs). Since PAMs are low cost chemicals with applications in various industries and waste- and drinking water treatment, a certain amount of non-polymerised acrylamide is expected to end up in waterways. PAMs are non-toxic but acrylamide induces neurotoxic effects in humans and genotoxic, reproductive, and carcinogenic effects in laboratory animals. In order to evaluate the effect of acrylamide on freshwater organisms, bioassays were conducted on four species: algae Desmodesmus subspicatus and Pseudokirchneriella subcapitata, duckweed Lemna minor and water flea Daphnia magna according to ISO (International Organization for Standardisation) standardised methods. This approach ensures the evaluation of acrylamide toxicity on organisms with different levels of organisation and the comparability of results, and it examines the value of using a battery of low-cost standardised bioassays in the monitoring of pollution and contamination of aquatic ecosystems. These results showed that EC50 values were lower for Desmodesmus subspicatus and Pseudokirchneriella subcapitata than for Daphnia magna and Lemna minor, which suggests an increased sensitivity of algae to acrylamide. According to the toxic unit approach, the values estimated by the Lemna minor and Daphnia magna bioassays, classify acrylamide as slightly toxic (TU=0-1; Class 1). The results obtained from algal bioassays (Desmodesmus subspicatus and Pseudokirchneriella subcapitata) revealed the toxic effect of acrylamide (TU=1-10; Class 2) on these organisms. PMID:26751864

  9. Artificial diets for life tables bioassays of TPB in Mississippi

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two artificial diets for mass rearing and bioassay of the tarnished plant bug, (TPB), Lygus lineolaris Palisot de Beauvois, (Hemiptera: Miridae) were modified and developed, respectively. The first diet is a modification of a semisolid artificial diet (NI diet), which permits large scale rearing of ...

  10. INFLUENCE OF SEDIMENT EXTRACT FRACTIONATION METHODS ON BIOASSAY RESULTS

    EPA Science Inventory

    Four bioassays [Microtax(tm), Mutatox(tm), sister chromatid exchange (SCE), and metabolic cooperation] were used to analyze marine sediment extracts fractionated by two different methods: silica gel column chromatography and acid-base fractionation. esults indicated that a sedime...

  11. Statistical considerations in the analysis of data from replicated bioassays

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple-dose bioassay is generally the preferred method for characterizing virulence of insect pathogens. Linear regression of probit mortality on log dose enables estimation of LD50/LC50 and slope, the latter having substantial effect on LD90/95s (doses of considerable interest in pest management)...

  12. Soil bioassays as tools for sludge compost quality assessment

    SciTech Connect

    Domene, Xavier; Sola, Laura; Ramirez, Wilson; Alcaniz, Josep M.; Andres, Pilar

    2011-03-15

    Composting is a waste management technology that is becoming more widespread as a response to the increasing production of sewage sludge and the pressure for its reuse in soil. In this study, different bioassays (plant germination, earthworm survival, biomass and reproduction, and collembolan survival and reproduction) were assessed for their usefulness in the compost quality assessment. Compost samples, from two different composting plants, were taken along the composting process, which were characterized and submitted to bioassays (plant germination and collembolan and earthworm performance). Results from our study indicate that the noxious effects of some of the compost samples observed in bioassays are related to the low organic matter stability of composts and the enhanced release of decomposition endproducts, with the exception of earthworms, which are favored. Plant germination and collembolan reproduction inhibition was generally associated with uncomposted sludge, while earthworm total biomass and reproduction were enhanced by these materials. On the other hand, earthworm and collembolan survival were unaffected by the degree of composting of the wastes. However, this pattern was clear in one of the composting procedures assessed, but less in the other, where the release of decomposition endproducts was lower due to its higher stability, indicating the sensitivity and usefulness of bioassays for the quality assessment of composts.

  13. Correction of spray concentration and bioassay cage penetration data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Field trials were conducted to demonstrate the need for correcting sampled spray concentration data for sampler collection efficiencies and estimated spray exposure levels in mosquito bioassays for cage interference effects. A large spray block was targeted with aerial spray treatments of etofenpro...

  14. 1. VIEW IN ROOM 125, BIOASSAY LABORATORY, SHOWN IS THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW IN ROOM 125, BIOASSAY LABORATORY, SHOWN IS THE FIRST STEP IN A SIX-STEP PROCESS TO ANALYZE URINE SAMPLES FOR PLUTONIUM AND URANIUM CONTAMINATION. IN THIS STEP, NITRIC ACID IS ADDED TO SAMPLE, AND THE SAMPLE IS BOILED DOWN TO A WHITE POWDER. - Rocky Flats Plant, Health Physics Laboratory, On Central Avenue between Third & Fourth Streets, Golden, Jefferson County, CO

  15. Microplate Bioassay for Determining Substrate Selectivity of "Candida rugosa" Lipase

    ERIC Educational Resources Information Center

    Wang, Shi-zhen; Fang, Bai-shan

    2012-01-01

    Substrate selectivity of "Candida rugosa" lipase was tested using "p"-nitrophenyl esters of increasing chain length (C[subscript 1], C[subscript 7], C[subscript 15]) using the high-throughput screening method. A fast and easy 96-well microplate bioassay was developed to help students learn and practice biotechnological specificity screen. The…

  16. Medium-term bioassays for carcinogenicity of chemical mixtures.

    PubMed Central

    Ito, N; Imaida, K; Hirose, M; Shirai, T

    1998-01-01

    Carcinogenic effects of chemical mixtures were examined with a medium-term liver bioassay for carcinogens or a multiorgan medium-term bioassay using male F344 rats. In the medium-term liver bioassay, rats were initially treated with diethylnitrosamine (DEN) at 200 mg/kg body weight, i.p.; after 2 weeks they received chemical mixtures such as 10 different heterocyclic amines at one-tenth or one-hundredth the dose levels used in carcinogenicity studies and the mixtures of 20 different pesticides, each at acceptable daily intake (ADI) levels or a mixture of 100 times ADI levels. All animals were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. The number and areas of glutathione S-transferase placental form (GST-P) positive foci (preneoplastic lesions in the liver) were compared between respective groups. When 10 heterocyclic amines were mixed in the diet at one-tenth dose level, clear synergism was observed, but no combined effects were evident with the one-hundredth dose levels. In the pesticide experiment, treatment of rats with the 20-pesticide mixture at the ADI dose level did not enhance GST-P-positive foci. In contrast, a mixture of 100 times the ADI significantly increased those values. In a multiorgan bioassay of 28 weeks, mixtures of 40 high-volume compounds and 20 pesticides (suspected carcinogens) added together at their respective ADI levels did not enhance carcinogenesis in any organs initiated by five different carcinogens (DEN, N-methylnitrosourea, dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)nitrosamine, and dihydroxy-di-n-propylnitrosamine) in combination. The combination effect of low dietary levels of five antioxidants, butylated hydroxyanisole, caffeic acid, sesamol, 4-methoxyphenol, and catechol, were also examined using the multiorgan bioassay. The incidence of forestomach papillomas was significantly increased only in the combination group and the results indicate that combination of the five antioxidants can

  17. Atmospheric Research 2011 Technical Highlights

    NASA Technical Reports Server (NTRS)

    2012-01-01

    The 2011 Technical Highlights describes the efforts of all members of Atmospheric Research. Their dedication to advancing Earth Science through conducting research, developing and running models, designing instruments, managing projects, running field campaigns, and numerous other activities, is highlighted in this report.

  18. Genotoxicity of leachates from a landfill using three bioassays.

    PubMed

    Cabrera, G L; Rodriguez, D M

    1999-05-19

    In the city of Queretaro, around 500 tons of solid wastes are produced everyday and are deposited in a landfill. This is the result of social and economic activities of human beings or from their normal physiological functions. As a result of rain, leachates are produced, which, if not handled and treated correctly, may pollute the underground water. Among the bioassays developed for the detection of mutagenicity in environmental pollutants, plant systems have been proven to be sensitive, cheap, and effective. The purpose of this study was to determine the presence of genotoxic agents in the leachates of the landfill of the city using three bioassays: Tradescantia-micronucleus (Trad-MCN), Tradescantia stamen hair mutations (Trad-SHM) and Allium root anaphase aberrations (AL-RAA) and make a comparison of the results in the three assays. Leachates were sampled during both the dry and rainy seasons. Plant cuttings of Tradescantia or the roots of Allium were treated by submerging them in the leachates. Three replicates of each sample were analyzed in each of the three bioassays. As expected the samples of leachates collected during the dry season showed a higher genotoxicity than those collected during the rainy season. In conclusion, there are substances present in the leachates capable of inducing genotoxicity in the plant assays. On the other hand, the plant assays showed different degrees of sensitivity: the more sensitive was the Trad-MCN bioassay and the less sensitive the Trad-SHM assay. Therefore, when analyzing environmental pollutants it is recommended to use a battery of bioassays. PMID:10350599

  19. Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays.

    PubMed

    Zeng, Qiang; Zhang, Shao-Hui; Liao, Jing; Miao, Dong-Yue; Wang, Xin-Yi; Yang, Pan; Yun, Luo-Jia; Liu, Ai-Lin; Lu, Wen-Qing

    2015-10-15

    Potential genotoxic effects of chlorinated drinking water now are of a great concern. In this study, raw water, finished water, and tap water from a water plant in Wuhan, China were collected in two different sampling times of the year (January and July). Genotoxic effects of water extracts were evaluated using a combination of three different bioassays: SOS/umu test, HGPRT gene mutation assay, and micronucleus assay, which were separately used to detect DNA damage, gene mutation, and chromosome aberration. The results of three different bioassays showed that all water samples in January and July induced at least one types of genotoxic effects, of which the DNA-damage effects were all detectable. The levels of DNA-damage effects and gene-mutation effects of finished water and tap water in January were higher than those in July. Chlorination could increase the DNA-damage effects of drinking water in January and the gene-mutation effects of drinking water in both January and July, but did not increase the chromosome-aberration effects of drinking water in both January and July. Our results highlighted the importance of using a combination of different bioassays to evaluate the genotoxicity of water samples in different seasons. PMID:25910456

  20. Kinetics of muscle contraction and actomyosin NTP hydrolysis from rabbit using a series of metal–nucleotide substrates

    PubMed Central

    Burton, Kevin; White, Howard; Sleep, John

    2005-01-01

    Mechanical properties of skinned single fibres from rabbit psoas muscle have been correlated with biochemical steps in the cross-bridge cycle using a series of metal–nucleotide (Me·NTP) substrates (Mn2+ or Ni2+ substituted for Mg2+; CTP or ITP for ATP) and inorganic phosphate. Measurements were made of the rate of force redevelopment following (1) slack tests in which force recovery followed a period of unloaded shortening, or (2) ramp shortening at low load terminated by a rapid restretch. The form and rate of force recovery were described as the sum of two exponential functions. Actomyosin-Subfragment 1 (acto-S1) Me·NTPase activity and Me·NDP release were monitored under the same conditions as the fibre experiments. Mn·ATP and Mg·CTP both supported contraction well and maintained good striation order. Relative to Mg·ATP, they increased the rates and Me·NTPase activity of cross-linked acto-S1 and the fast component of a double-exponential fit to force recovery by ∼50% and 10–35%, respectively, while shortening velocity was moderately reduced (by 20–30%). Phosphate also increased the rate of the fast component of force recovery. In contrast to Mn2+ and CTP, Ni·ATP and Mg·ITP did not support contraction well and caused striations to become disordered. The rates of force recovery and Me·NTPase activity were less than for Mg·ATP (by 40–80% and 50–85%, respectively), while shortening velocity was greatly reduced (by ∼80%). Dissociation of ADP from acto-S1 was little affected by Ni2+, suggesting that Ni·ADP dissociation does not account for the large reduction in shortening velocity. The different effects of Ni2+ and Mn2+ were also observed during brief activations elicited by photolytic release of ATP. These results confirm that at least one rate-limiting step is shared by acto-S1 ATPase activity and force development. Our results are consistent with a dual rate-limitation model in which the rate of force recovery is limited by both NTP

  1. Mechanism of NTP Hydrolysis by the Escherichia coli Primary Replicative Helicase DnaB Protein. 2. Nucleotide and Nucleic Acid Specificities†

    PubMed Central

    Roychowdhury, Anasuya; Szymanski, Michal R.; Jezewska, Maria J.; Bujalowski, Wlodzimierz

    2011-01-01

    The kinetic mechanism of NTP binding and hydrolysis by the Escherichia coli replicative helicase, the DnaB protein, in the absence and presence of the single-stranded DNA (ssDNA), has been quantitatively examined using the rapid quench-flow technique, under single-turnover conditions. In the case of both the free helicase and the enzyme–ssDNA complexes, the mechanism is independent of the type of base of the cofactor or the DNA; the bimolecular association is followed by the reversible chemical hydrolysis and subsequent conformational transition of the enzyme–product complex. The NTP hydrolysis step is significantly faster for the purine than for the pyrimidine cofactor, both in the absence and in the presence of the DNA. The temperature effect indicates that the nature of intermediates of the purine nucleotide, ATP, is different from the nature of the analogous intermediates of the pyrimidine nucleotide, CTP. Nevertheless, both types of cofactors seem to approach a similar “exit” state at the end of the reaction. The effect of ssDNA on the kinetics of NTP hydrolysis depends on the type of nucleotide cofactor and the base composition of the DNA and is centered at the hydrolysis step. Homoadenosine ssDNA oligomers are particularly effective in increasing the hydrolysis rate. The allosteric signal from the DNA, which activates the NTP hydrolysis, comes predominantly from the strong DNA-binding subsite. The role of the weak DNA-binding subsite is to modulate the allosteric effect of the strong subsite. The significance of these results for the mechanism of the free energy transduction by the DnaB helicase is discussed. PMID:19435286

  2. BioAssay Ontology (BAO): a semantic description of bioassays and high-throughput screening results

    PubMed Central

    2011-01-01

    Background High-throughput screening (HTS) is one of the main strategies to identify novel entry points for the development of small molecule chemical probes and drugs and is now commonly accessible to public sector research. Large amounts of data generated in HTS campaigns are submitted to public repositories such as PubChem, which is growing at an exponential rate. The diversity and quantity of available HTS assays and screening results pose enormous challenges to organizing, standardizing, integrating, and analyzing the datasets and thus to maximize the scientific and ultimately the public health impact of the huge investments made to implement public sector HTS capabilities. Novel approaches to organize, standardize and access HTS data are required to address these challenges. Results We developed the first ontology to describe HTS experiments and screening results using expressive description logic. The BioAssay Ontology (BAO) serves as a foundation for the standardization of HTS assays and data and as a semantic knowledge model. In this paper we show important examples of formalizing HTS domain knowledge and we point out the advantages of this approach. The ontology is available online at the NCBO bioportal http://bioportal.bioontology.org/ontologies/44531. Conclusions After a large manual curation effort, we loaded BAO-mapped data triples into a RDF database store and used a reasoner in several case studies to demonstrate the benefits of formalized domain knowledge representation in BAO. The examples illustrate semantic querying capabilities where BAO enables the retrieval of inferred search results that are relevant to a given query, but are not explicitly defined. BAO thus opens new functionality for annotating, querying, and analyzing HTS datasets and the potential for discovering new knowledge by means of inference. PMID:21702939

  3. Johnson Space Center 2012 Highlights

    NASA Video Gallery

    The year has seen many highlights at NASA’s Johnson Space Center, Houston in the realm of human spaceflight exploration, international and commercial partnerships, and research and technology dev...

  4. LAMA Preconference and Program Highlights.

    ERIC Educational Resources Information Center

    Library Administration & Management, 1988

    1988-01-01

    Highlights events of the Library Administration and Management Association 1988 conference, including presentation of awards and programs on: (1) transfer of training; (2) hiring; (3) mentoring; (4) acquisitions automation; (5) library building consultation; and (6) managing shared systems. (MES)

  5. Incorporation of deoxyribonucleotides and ribonucleotides by a dNTP-binding cleft mutated reverse transcriptase in hepatitis B virus core particles

    SciTech Connect

    Kim, Hee-Young; Kim, Hye-Young; Jung, Jaesung; Park, Sun; Shin, Ho-Joon; Kim, Kyongmin

    2008-01-05

    Our recent observation that hepatitis B virus (HBV) DNA polymerase (P) might initiate minus-strand DNA synthesis without primer [Kim et al., (2004) Virology 322, 22-30], raised a possibility that HBV P protein may have the potential to function as an RNA polymerase. Thus, we mutated Phe 436, a bulky amino acid with aromatic side chain, at the putative dNTP-binding cleft in reverse transcriptase (RT) domain of P protein to smaller amino acids (Gly or Val), and examined RNA polymerase activity. HBV core particles containing RT dNTP-binding cleft mutant P protein were able to incorporate {sup 32}P-ribonucleotides, but not HBV core particles containing wild type (wt), priming-deficient mutant, or RT-deficient mutant P proteins. Since all the experiments were conducted with core particles isolated from transfected cells, our results indicate that the HBV RT mutant core particles containing RT dNTP-binding cleft mutant P protein could incorporate both deoxyribonucleotides and ribonucleotides in replicating systems.

  6. Research and technology highlights, 1993

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This report contains highlights of the major accomplishments and applications that have been made by Langley researchers and by our university and industry colleagues during the past year. The highlights illustrate both the broad range of the research and technology activities supported by NASA Langley Research Center and the contributions of this work toward maintaining United States leadership in aeronautics and space research. This report also describes some of the Center's most important research and testing facilities.

  7. Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation.

    PubMed

    Pfister, Sophia X; Markkanen, Enni; Jiang, Yanyan; Sarkar, Sovan; Woodcock, Mick; Orlando, Giulia; Mavrommati, Ioanna; Pai, Chen-Chun; Zalmas, Lykourgos-Panagiotis; Drobnitzky, Neele; Dianov, Grigory L; Verrill, Clare; Macaulay, Valentine M; Ying, Songmin; La Thangue, Nicholas B; D'Angiolella, Vincenzo; Ryan, Anderson J; Humphrey, Timothy C

    2015-11-01

    Histone H3K36 trimethylation (H3K36me3) is frequently lost in multiple cancer types, identifying it as an important therapeutic target. Here we identify a synthetic lethal interaction in which H3K36me3-deficient cancers are acutely sensitive to WEE1 inhibition. We show that RRM2, a ribonucleotide reductase subunit, is the target of this synthetic lethal interaction. RRM2 is regulated by two pathways here: first, H3K36me3 facilitates RRM2 expression through transcription initiation factor recruitment; second, WEE1 inhibition degrades RRM2 through untimely CDK activation. Therefore, WEE1 inhibition in H3K36me3-deficient cells results in RRM2 reduction, critical dNTP depletion, S-phase arrest, and apoptosis. Accordingly, this synthetic lethality is suppressed by increasing RRM2 expression or inhibiting RRM2 degradation. Finally, we demonstrate that WEE1 inhibitor AZD1775 regresses H3K36me3-deficient tumor xenografts. PMID:26602815

  8. A Rapid and Simple Bioassay Method for Herbicide Detection

    PubMed Central

    Li, Xiu-Qing; Ng, Alan; King, Russell; Durnford, Dion G.

    2008-01-01

    Chlamydomonas reinhardtii, a unicellular green alga, has been used in bioassay detection of a variety of toxic compounds such as pesticides and toxic metals, but mainly using liquid culture systems. In this study, an algal lawn—agar system for semi-quantitative bioassay of herbicidal activities has been developed. Sixteen different herbicides belonging to 11 different categories were applied to paper disks and placed on green alga lawns in Petri dishes. Presence of herbicide activities was indicated by clearing zones around the paper disks on the lawn 2–3 days after application. The different groups of herbicides induced clearing zones of variable size that depended on the amount, mode of action, and chemical properties of the herbicides applied to the paper disks. This simple, paper-disk-algal system may be used to detect the presence of herbicides in water samples and act as a quick and inexpensive semi-quantitative screening for assessing herbicide contamination. PMID:19578512

  9. Pullulan encapsulation of labile biomolecules to give stable bioassay tablets.

    PubMed

    Jahanshahi-Anbuhi, Sana; Pennings, Kevin; Leung, Vincent; Liu, Meng; Carrasquilla, Carmen; Kannan, Balamurali; Li, Yingfu; Pelton, Robert; Brennan, John D; Filipe, Carlos D M

    2014-06-10

    A simple and inexpensive method is reported for the long-term stabilization of enzymes and other unstable reagents in premeasured quantities in water-soluble tablets (cast, not compressed) made with pullulan, a nonionic polysaccharide that forms an oxygen impermeable solid upon drying. The pullulan tablets dissolve in aqueous solutions in seconds, thereby facilitating the easy execution of bioassays at remote sites with no need for special reagent handling and liquid pipetting. This approach is modular in nature, thus allowing the creation of individual tablets for enzymes and their substrates. Proof-of-principle demonstrations include a Taq polymerase tablet for DNA amplification through PCR and a pesticide assay kit consisting of separate tablets for acetylcholinesterase and its chromogenic substrate, indoxyl acetate, both of which are highly unstable. The encapsulated reagents remain stable at room temperature for months, thus enabling the room-temperature shipping and storage of bioassay components. PMID:24764260

  10. A New Bioassay for Auxins and Cytokinins 1

    PubMed Central

    Boerjan, Wout; Genetello, Chris; Van Montagu, Marc; Inzé, Dirk

    1992-01-01

    The authors have developed a sensitive bioassay that can be used to detect auxins as well as cytokinins. The bioassay is based on the expression in transformed tobacco (Nicotiana tabacum) mesophyll protoplasts of a chimeric gene, consisting of the upstream sequences of the Agrobacterium tumefaciens gene 5, coupled to the coding sequence of the β-glucuronidase. The expression of this gene is induced by the presence of both auxin and cytokinin in the culture medium. Using this assay, indole-3-acetic acid was detected at 5 × 10−8 molar, whereas trans-zeatin could be detected at 5 × 10−11 molar. The assay can be performed in microtiter plates, allowing numerous samples to be analyzed simultaneously. Only 2.5 × 105 protoplasts are required for one individual assay in 250 microliters of culture medium and for qualitative results, the reaction is readily visualized by ultraviolet light. ImagesFigure 3Figure 4Figure 6 PMID:16668975