Science.gov

Sample records for regulatory site visit

  1. 76 FR 76168 - Regulatory Site Visit Training Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... HUMAN SERVICES Food and Drug Administration Regulatory Site Visit Training Program AGENCY: Food and Drug... Training Program (RSVP). This training program is intended to give CBER regulatory review, compliance, and... INFORMATION CONTACT: Lonnie W. Henderson, Division of Manufacturers Assistance and Training, Center...

  2. 76 FR 4919 - Regulatory Site Visit Training Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... HUMAN SERVICES Food and Drug Administration Regulatory Site Visit Training Program AGENCY: Food and Drug... Training Program (RSVP). This training program is intended to give CBER regulatory review, compliance, and... INFORMATION CONTACT: Lonnie W. Henderson, Division of Manufacturers Assistance and Training, Center...

  3. 75 FR 6404 - Regulatory Site Visit Training Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... Training Program AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug... participation in its Regulatory Site Visit Training Program (RSVP). This training program is intended to give.... Henderson, Division of Manufacturers Assistance and Training, Center for Biologics Evaluation and...

  4. The CACREP Site Visit Process

    ERIC Educational Resources Information Center

    Lee, Courtland C.

    2013-01-01

    An important step in the CACREP review process is the campus site visit. The visit involves a team, usually from comparable institutions, coming to a campus for a review of the counselor training program(s). The role of the team is to be the CACREP Board's representative on campus to verify the self-study. In this article, the author reviews…

  5. 48 CFR 52.236-27 - Site Visit (Construction).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Site Visit (Construction....236-27 Site Visit (Construction). As prescribed in 36.523, insert a provision substantially the same as the following: Site Visit (Construction) (FEB 1995) (a) The clauses at 52.236-2, Differing...

  6. Prescribed Fire: The Influence of Site Visits on Citizen Attitudes

    ERIC Educational Resources Information Center

    Toman, Eric; Shindler, Bruce; Reed, Michelle

    2004-01-01

    This research employed a panel design to measure the effect of site visits on public perceptions of prescribed fire. On-site survey questions were devised to compare answers to a mail questionnaire previously completed by the same respondents. Questions were designed to examine how site visits influence public opinion and affect acceptance of…

  7. Changes in AIDS case reporting after hospital site visits.

    PubMed Central

    Fife, D; McAnaney, J; Rahman, M A

    1991-01-01

    In an effort to improve AIDS case reporting, site visits (meetings with hospital staff to encourage reporting) were made to all Philadelphia hospitals. Comparisons of hospitals visited during a 7-week period with hospitals not visited during that period indicated that the site visits were followed by a marked increase in case reports. No similar increase was observed at the comparison hospitals. The increased reporting was accompanied by an increased lag time from diagnosis to report, suggesting that the additional reports at visited hospitals were the result of the identification of previously missed cases rather than a speedup of reporting. Cases reported after the visits were more likely to have white-collar occupations or private medical insurance than were those reported before the visits. PMID:1746665

  8. Designing a Marketing Course with Field Site Visits

    ERIC Educational Resources Information Center

    Van Doren, Doris; Corrigan, Hope Bober

    2008-01-01

    A key goal of including field site visits in marketing courses is to give business students increased interaction with industry professionals and community leaders. Site visits give students a concrete idea of how different marketing disciplines work in the business world. Business students gain greater insight into a career in marketing from this…

  9. Corrections Education Evaluation System Project. Site Visit Report.

    ERIC Educational Resources Information Center

    Nelson, Orville; And Others

    Site visits to five correctional institutions in Wisconsin were conducted as part of the development of an evaluation model for the competency-based vocational education (CBVE) project for the Wisconsin Correctional System. The evaluators' perceptions of the CBVE system are presented with recommendations for improvement. Site visits were conducted…

  10. 19 CFR 10.553 - Textile and apparel site visits.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Textile and apparel site visits. 10.553 Section 10... Trade Agreement Origin Verifications and Determinations § 10.553 Textile and apparel site visits. (a... Textile Agreements (CITA), exclude from the territory of the United States textile or apparel...

  11. 19 CFR 10.553 - Textile and apparel site visits.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Textile and apparel site visits. 10.553 Section 10... Trade Agreement Origin Verifications and Determinations § 10.553 Textile and apparel site visits. (a... Textile Agreements (CITA), exclude from the territory of the United States textile or apparel...

  12. 19 CFR 10.553 - Textile and apparel site visits.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Textile and apparel site visits. 10.553 Section 10... Trade Agreement Origin Verifications and Determinations § 10.553 Textile and apparel site visits. (a... Textile Agreements (CITA), exclude from the territory of the United States textile or apparel...

  13. 19 CFR 10.553 - Textile and apparel site visits.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Textile and apparel site visits. 10.553 Section 10... Trade Agreement Origin Verifications and Determinations § 10.553 Textile and apparel site visits. (a... Textile Agreements (CITA), exclude from the territory of the United States textile or apparel...

  14. 19 CFR 10.553 - Textile and apparel site visits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Textile and apparel site visits. 10.553 Section 10... Trade Agreement Origin Verifications and Determinations § 10.553 Textile and apparel site visits. (a... Textile Agreements (CITA), exclude from the territory of the United States textile or apparel...

  15. Russian research capabilities: Findings of site visits

    SciTech Connect

    Wester, D.W.

    1994-02-01

    In June 1993, a proposal was presented to the International Environmental Institute (IEI) in Kennewick, Washington, to establish cooperation and coordination to further pursue the interests of the United States of America and the Republic of Russia in the application and promotion of environmental technology; characterization, treatment, handling, isolation, and disposal of hazardous and radioactive materials; conversion of defense sites to other purposes; and technology transfer, cooperative programs, joint technology development and contractual research. In response to this proposal, IEI and Pacific Northwest Laboratory (PNL) jointly provided funding to send Dr. Dennis W. Wester on a fact-finding mission to Novosibirsk, Moscow, and St. Petersburg, Russia. The trip covered a period of eight weeks, six of which were spent in Novosibirsk and adjoining or related cities and one of which was spent in each of Moscow and St. Petersburg. The general objectives of the trip were to establish a basis for cooperation between IEI and the Russian Academy of Sciences (RAS) for future coordination of mutual interests and objectives such as technology acquisition, development, demonstration, application, and commercialization; use of capabilities and assets developed by the U.S. Department of Energy (DOE) and the RAS; and expediting of cooperative agreements, personnel exchanges, joint ventures and other contractual relationships. The particular objectives of this trip were to evaluate the capabilities of the RAS to satisfy the technology needs associated with the cleanup of the Hanford Site and similar sites in the U.S. and to evaluate the expediency of establishing an IEI presence in Russia.

  16. Site Visit to Calvert County, Maryland ARC Family Support Services.

    ERIC Educational Resources Information Center

    Bersani, Hank A., Jr.

    The site visit report describes the Family Support Services program run by the Calvert County (Maryland) Association for Retarded Citizens. The program's goal is to prevent any person 21 years of age or younger from being institutionalized. It provides respite care services, specialized family support, and integrated day care for approximately 50…

  17. Site Visit Report: Seven Counties Services, Louisville, Kentucky.

    ERIC Educational Resources Information Center

    Racino, Julie Ann

    The report describes a site visit to the Seven Counties Services Region in Kentucky to identify and document promising practices for serving people with severe disabilities in integrated community-based services. The regional agency serves Jefferson, Oldham, Henry, Trimble, Spencer, Bullitt and Shelby Counties. Regional service priorities have…

  18. Hanford/Tomsk reciprocal site visit: Plutonium agreement compliance talks

    SciTech Connect

    Libby, R.A.; Sorenson, R.; Six, D.; Schiegel, S.C.

    1994-11-01

    The objective of the visit to Hanford Site was to: demonstrate equipment, technology, and methods for calculating Pu production, measuring integrated reactor power, and storing and safeguarding PuO{sub 2}; demonstrate the shutdown of Hanford production reactors; and foster openness and transparency of Hanford operations. The first day`s visit was an introduction to Hanford and a review of the history of the reactors. The second day consisted of discussions on the production reactors, reprocessing operations, and PuO{sub 2} storage. The group divided on the third day to tour facilities. Group A toured the N reactor, K-West reactor, K-West Basins, B reactor, and participated in a demonstration and discussion of reactor modeling computer codes. Group B toured the Hanford Pu Storage Facility, 200-East Area, N-cell (oxide loadout station), the Automated Storage Facility, and the Nondestructive Assay Measurement System. Group discussions were held during the last day of the visit, which included scheduling of a US visit to Russia.

  19. 76 FR 38383 - Albany Engineering Corporation, Town of Stuyvesant, NY; Notice of Site Visit and Technical Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Albany Engineering Corporation, Town of Stuyvesant, NY; Notice of Site Visit and Technical Meeting On July 12, 2011, Office of Energy Projects staff will participate in a...

  20. 76 FR 51022 - Juneau Hydropower, Inc.; Notice of Scoping Meeting and Site Visit and Soliciting Scoping Comments...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... Energy Regulatory Commission Juneau Hydropower, Inc.; Notice of Scoping Meeting and Site Visit and.... Applicant: Juneau Hydropower, Inc. d. Name of Project: Sweetheart Lake Hydroelectric Project. e. Location.... 791(a)-825(r). g. Applicant Contact: Duff Mitchell, Business Manager, Juneau Hydropower, Inc.,...

  1. Remotely operated excavator needs assessment/site visit summary

    SciTech Connect

    Straub, J.; Haller, S.; Worsley, R.; King, M.

    1992-12-02

    The Uranium in Soils Integrated Demonstration requested an assessment of soil excavation needs relative to soil remediation. The following list identifies the DOE sites assessed: Mound Laboratory, Paducah Gaseous Diffusion Plant, Portsmouth Gaseous Diffusion Plant, Nevada Test Site, Lawrence Livermore National Laboratory, Rocky Flats Plant, Los Alamos National Laboratory, Sandia National Laboratory, Idaho National Engineering Laboratory, Hanford Site, and Fernald Site. The reviewed sites fall into one or more of the following three categories: production, EPA National Priorities List, or CERCLA (superfund) designation. Only three of the sites appear to have the need for a remotely operated excavator rope. Hanford and Idaho Falls have areas of high-level radioactive contamination either buried or in/under buildings. The Fernald site has a need for remote operated equipment of different types. It is their feeling that remote equipment can be used to remove the health dangers to humans by removing them from the area. Most interviewees stated that characterization technologies needs are more immediate concern over excavation. In addition, the sites do not have similar geographic conditions which would aid in the development of a generic precision excavator. The sites visited were not ready to utilize or provide the required design information necessary to draft a performance specification. This creates a strong case against the development of one type of ROPE for use at these sites. Assuming soil characterization technology/methodology is improved sufficiently to allow accurate and real time field characterization then development of a precision excavator might be pursued based on FEMP needs, since the FEMP`s sole scope of work is remediation. The excavator could then be used/tested and then later modified for other sites as warranted.

  2. 48 CFR 1352.270-71 - Pre-bid/pre-proposal conference and site visit.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Clauses 1352.270-71 Pre-bid/pre-proposal conference and site visit. As prescribed in 48 CFR 1370.102, insert the following provision: Pre-Bid/Pre-Proposal Conference and Site Visit (APR 2010) (a) The... conference and site visit. 1352.270-71 Section 1352.270-71 Federal Acquisition Regulations System...

  3. 48 CFR 1352.270-71 - Pre-bid/pre-proposal conference and site visit.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Clauses 1352.270-71 Pre-bid/pre-proposal conference and site visit. As prescribed in 48 CFR 1370.102, insert the following provision: Pre-Bid/Pre-Proposal Conference and Site Visit (APR 2010) (a) The... conference and site visit. 1352.270-71 Section 1352.270-71 Federal Acquisition Regulations System...

  4. 48 CFR 1352.270-71 - Pre-bid/pre-proposal conference and site visit.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Clauses 1352.270-71 Pre-bid/pre-proposal conference and site visit. As prescribed in 48 CFR 1370.102, insert the following provision: Pre-Bid/Pre-Proposal Conference and Site Visit (APR 2010) (a) The... conference and site visit. 1352.270-71 Section 1352.270-71 Federal Acquisition Regulations System...

  5. 48 CFR 1352.270-71 - Pre-bid/pre-proposal conference and site visit.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Clauses 1352.270-71 Pre-bid/pre-proposal conference and site visit. As prescribed in 48 CFR 1370.102, insert the following provision: Pre-Bid/Pre-Proposal Conference and Site Visit (APR 2010) (a) The... conference and site visit. 1352.270-71 Section 1352.270-71 Federal Acquisition Regulations System...

  6. 48 CFR 1352.270-71 - Pre-bid/pre-proposal conference and site visit.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Clauses 1352.270-71 Pre-bid/pre-proposal conference and site visit. As prescribed in 48 CFR 1370.102, insert the following provision: Pre-Bid/Pre-Proposal Conference and Site Visit (APR 2010) (a) The... conference and site visit. 1352.270-71 Section 1352.270-71 Federal Acquisition Regulations System...

  7. Number of distinct sites visited by N random walkers

    NASA Astrophysics Data System (ADS)

    Larralde, Hernan; Trunfio, Paul; Havlin, Shlomo; Stanley, H. Eugene; Weiss, George H.

    1992-05-01

    We study the number of distinct sites visited by N random walkers after t steps SN(t) under the condition that all the walkers are initially at the origin. We derive asymptotic expressions for the mean number of distinct sites in one, two, and three dimensions. We find that passes through several growth regimes; at short times ~td (regime I), for tx<~(t ln[N S1(t)/td/2])d/2 (regime II), and for t>>tx', ~NS1(t) (regime III). The crossover times are tx~ln N for all dimensions, and tx'~∞, exp N, and N2 for one, two, and three dimensions, respectively. We show that in regimes II and III satisfies a scaling relation of the form ~td/2f(x), with x≡N/td/2. We also obtain asymptotic results for the complete probability distribution of SN(t) for the one-dimensional case in the limit of large N and t.

  8. The value of crime scene and site visitation by forensic psychologists and psychiatrists.

    PubMed

    Mohandie, Kris; Meloy, J Reid

    2013-05-01

    Site visits and crime scene visitation by forensic psychologists and psychiatrists may enhance the accuracy and credibility of their forensic work in criminal, civil, and other important contexts. This ethically sound technique of after-the-fact data collection and verification offers numerous potential benefits to the forensic mental health professional: clarifying the subject's actions, assessing the reliability of witness reports, identifying contextual determinants of behavior, and more fully illuminating subject motivation and decision-making. Limitations and suggested guidelines for conducting site visits are offered. Guidelines include preplanning, arranging for an informed guide to accompany and narrate the visit, and conducting the site visit prior to forensic examinations. PMID:23550941

  9. The impacts of human visitation on mussel bed communities along the California coast: are regulatory marine reserves effective in protecting these communities?

    PubMed

    Smith, Jayson R; Fong, Peggy; Ambrose, Richard F

    2008-04-01

    Rocky intertidal habitats frequently are used by humans for recreational, educational, and subsistence-harvesting purposes, with intertidal populations damaged by visitation activities such as extraction, trampling, and handling. California Marine Managed Areas, particularly regulatory marine reserves (MRs), were established to provide legal protection and enhancement of coastal resources and include prohibitions on harvesting intertidal populations. However, the effectiveness of MRs is unclear as enforcement of no-take laws is weak and no regulations protect intertidal species from other detrimental visitor impacts such as trampling. The goal of this study was two-fold: (1) to determine impacts from human visitation on California mussel populations (Mytilus californianus) and mussel bed community diversity; and (2) to investigate the effectiveness of regulatory MRs in reducing visitor impacts on these populations. Surveys of mussel populations and bed-associated diversity were compared: (1) at sites subjected to either high or low levels of human use, and (2) at sites either unprotected or with regulatory protection banning collecting. At sites subjected to higher levels of human visitation, mussel populations were significantly lower than low-use sites. Comparisons of mussel populations inside and outside of regulatory MRs revealed no consistent pattern suggesting that California no-take regulatory reserves may have limited effectiveness in protecting mussel communities. In areas where many people visit intertidal habitats for purposes other than collecting, many organisms will be affected by trampling, turning of rocks, and handling. In these cases, effective protection of rocky intertidal communities requires an approach that goes beyond the singular focus on collecting to reduce the full suite of impacts. PMID:18185953

  10. Study of New Youth Initiatives in Apprenticeship. Interim Report. Volume 2: Site Visit Reports.

    ERIC Educational Resources Information Center

    CSR, Inc., Washington, DC.

    This second volume of the interim report provides detailed case study reports on each of the eight Youth Apprenticeship Projects. (Volume 1, an overview of data from the site visits, is available separately as CE 032 791.) Discussion areas covered in each site visit report are local context/operational environment, administrative information,…

  11. 77 FR 44675 - Agency Information Collection Activities; Submission for OMB Review; Comment Request: Site Visit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-30

    ... Register on April 20, 2012 (77 FR 23764). Interested parties are encouraged to send comments to the OMB...: Site Visit Data Collection Request for American Recovery and Reinvestment Act Funded Grants; Job..., ``Site Visit Data Collection Request for American Recovery and Reinvestment Act funded Grants;...

  12. Visiting the Site of Death: Experiences of the Bereaved after the 2004 Southeast Asian Tsunami

    ERIC Educational Resources Information Center

    Kristensen, Pal; Tonnessen, Arnfinn; Weisaeth, Lars; Heir, Trond

    2012-01-01

    The authors examined how many bereaved relatives of Norwegian tourists who perished in the 2004 Southeast Asian Tsunami had visited the site of death and the most important outcome from the visit. We conducted in-depth interviews (n = 110) and used self-report questionnaires (Impact of Event Scale--Revised, Inventory of Complicated Grief, and…

  13. Historical Visit to the Site of the Canard River Skirmishes.

    ERIC Educational Resources Information Center

    Sutter, David S.

    1993-01-01

    Reports on a field trip by secondary school history students to Fort Malden National Historic Site in Canada. Describes the use of primary sources and battlefield sites to help students understand historical perspective and interpretation. Includes discussion questions for students and recommendations for implementation. (CFR)

  14. Visiting the site of death: experiences of the bereaved after the 2004 Southeast Asian Tsunami.

    PubMed

    Kristensen, Pål; Tønnessen, Arnfinn; Weisaeth, Lars; Heir, Trond

    2012-01-01

    The authors examined how many bereaved relatives of Norwegian tourists who perished in the 2004 Southeast Asian Tsunami had visited the site of death and the most important outcome from the visit. We conducted in-depth interviews (n = 110) and used self-report questionnaires (Impact of Event Scale-Revised, Inventory of Complicated Grief and General Health Questionnaire) in a total of 130 first-degree family members 2 years post-disaster. Results showed that the majority of participants (n = 113; 87%) had visited the site of death. The most important outcome was gaining an increased understanding of what occurred (61%) and a feeling of closeness to the deceased (27%). Those who had visited the site of death reported lower avoidance behavior and higher degree of acceptance of the loss than non-visitors. Although this could be a cause as well as a consequence of the visit, visiting the site of death may be an important part of the support offered to bereaved families after experiencing a disaster loss. PMID:24567999

  15. Understanding the Experience of CACREP On-Site Visiting Review Team Chairpersons

    ERIC Educational Resources Information Center

    Minor, Amanda J.

    2012-01-01

    Understanding the experience of CACREP on-site review team members provides insight into the phenomenon of four counselor educators who have each served as a CACREP on-site visiting review team chairperson a minimum of three times. In total, the participants had been within the counselor education field for approximately 95 years and active within…

  16. Pharmacy Student and Preceptor Impressions of Faculty Liaison Visits to Experiential Training Sites

    PubMed Central

    Paiva, Maria; Black, Emily

    2015-01-01

    Objective. To characterize preceptor and student views about and experiences with faculty liaison visits to practice sites during clinical internships. Methods. A survey was administered at the conclusion of each of the first 3 academic years of a new postbaccalaureate doctor of pharmacy (PharmD) program. Results. Preceptors were satisfied overall with faculty liaison visits, while students initially were not; however, their perception increased in subsequent years. Students felt development of their patient care skills benefited, but less so their interpersonal communication skills. Each year, almost all preceptors indicated faculty liaison visits were helpful in developing and refining their mentorship skills. Conclusion. Faculty liaison visits provided a valuable opportunity to interact and support preceptors and students during advanced pharmacy internships in a nascent PharmD program. PMID:26839424

  17. School Site Visits for Community-Based Participatory Research on Healthy Eating

    PubMed Central

    Patel, Anisha I.; Bogart, Laura M.; Uyeda, Kimberly E.; Martinez, Homero; Knizewski, Ritamarie; Ryan, Gery W.; Schuster, Mark A.

    2010-01-01

    Background School nutrition policies are gaining support as a means of addressing childhood obesity. Community-based participatory research (CBPR) offers an approach for academic and community partners to collaborate to translate obesity-related school policies into practice. Site visits, in which trained observers visit settings to collect multilevel data (e.g., observation, qualitative interviews), may complement other methods that inform health promotion efforts. This paper demonstrates the utility of site visits in the development of an intervention to implement obesity-related policies in Los Angeles Unified School District (LAUSD) middle schools. Methods In 2006, trained observers visited four LAUSD middle schools. Observers mapped cafeteria layout; observed food/beverage offerings, student consumption, waste patterns, and duration of cafeteria lines; spoke with school staff and students; and collected relevant documents. Data were examined for common themes and patterns. Results Food and beverages sold in study schools met LAUSD nutritional guidelines, and nearly all observed students had time to eat most or all of their meal. Some LAUSD policies were not implemented, including posting nutritional information for cafeteria food, marketing school meals to improve student participation in the National School Lunch Program, and serving a variety of fruits and vegetables. Cafeteria understaffing and cost were obstacles to policy implementation. Conclusions Site visits were a valuable methodology for evaluating the implementation of school district obesity-related policies and contributed to the development of a CBPR intervention to translate school food policies into practice. Future CBPR studies may consider site visits in their toolbox of formative research methods. PMID:19896033

  18. White-tailed Deer Visitation Rates at Medicated Bait Sites in Southern Texas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cattle fever tick, Rhipicephalus (Boophilus) microplus, has been found on white-tailed deer (Odocoileus virginianus) complicating eradication efforts of the USDA’s Cattle Fever Tick Eradication Program. Our objective was to assess patterns of deer visitation to medicated bait sites used to treat...

  19. Appendix B: Site Visit Reports. Assessment of Research Needs for Coal Utilization

    SciTech Connect

    Penner, S.S.

    1983-05-01

    This section contains edited copies of site-visit and other reports prepared by CCAWG members. Some of the hand-out materials prepared by DOE contractors and others are included (without explication) to permit readers the construction of a coherent picture of work in progress.

  20. Female Faculty Members in University Chemistry Departments: Observations and Conclusions Based on Site Visits

    ERIC Educational Resources Information Center

    Chapman, Sally; Dixon, Felicia F.; Foster, Natalie; Kuck, Valerie J.; McCarthy, Deborah A.; Tooney, Nancy M.; Buckner, Janine P.; Nolan, Susan A.; Marzabadi, Cecilia H.

    2011-01-01

    Oral interviews in focus groups and written surveys were conducted with 877 men and women, including administrators, faculty members, postdoctoral associates, and graduate students, during one-day site visits to chemistry and chemical engineering departments at 28 Ph.D.-granting institutions. This report is a preliminary review of the perceptions…

  1. Preparing for a Successful Psychiatry Residency Review Committee Site Visit: A Guide for New Training Directors

    ERIC Educational Resources Information Center

    Bhatia, Shashi K.; Bhatia, Subhash C.

    2005-01-01

    Objective: New residency training directors are often faced with multiple competing tasks such as meeting Accreditation Council for Graduate Medical Education (ACGME) Psychiatry Program Requirements and achieving successful completion of residency review committee (RRC) site visits. For many years, the authors have presented workshops on this…

  2. The impact of national cultural distance on the number of foreign Web site visits by U.S. households.

    PubMed

    Beugelsdijk, Sjoerd; Slangen, Arjen

    2010-04-01

    We investigate how national cultural distance, defined as the extent to which the shared values and norms in one country differ from those in another, affect the number of Web site visits. Based on a sample of 2,654 U.S. households visiting Web sites in 38 countries over 25 different Web site categories, we find that cultural distance has a negative and significant effect on the number of taste-related foreign Web site visits. In the case of Web sites containing sexually explicit material, we obtain a significantly positive effect of cultural distance. Our findings suggest that cultural distance can be both a source of attraction and a source of repulsion in explaining the number of Web site visits depending on the nature of the Web site. PMID:20528279

  3. DISSS/PSDB - Personnel Security Database Modernization Project: Compilation of data gathered from DOE Operations Office`s site visits

    SciTech Connect

    Carpenter, R.; Sweeney, D.

    1995-03-15

    This document is a compilation of the information gathered from visits to the DOE Operations Offices. The purpose of these visits was to gather requirements for the modernization of the personnel security database. The initial phase of visits were to sites which had known local systems to augment CPCI. They were; Rocky Flats, Richland, Las Vegas, Savannah River, Oak Ridge, and Oakland. The second phase of site visits were to; Headquarters, Schenectady, Pittsburgh, Idaho Falls, Chicago, and Albuquerque. We also visited the NRC. At each site we reviewed the current clearance process in use at the field office. If the site had a local personnel security database (PSDB), we also reviewed the current PSDB processing. Each meeting was began with the a discussion on the purpose of the meeting and the background of the redesign effort.

  4. A delay differential equation model for dengue transmission with regular visits to a mosquito breeding site

    NASA Astrophysics Data System (ADS)

    Yaacob, Y.; Yeak, S. H.; Lim, R. S.; Soewono, E.

    2015-03-01

    Dengue disease has been known as one of widely transmitted vector-borne diseases which potentially affects millions of people throughout the world especially in tropical and sub-tropical countries. One of the main factors contributing in the complication of the transmission process is the mobility of people in which people may get infection in the places far from their home. Here we construct a delay differential equation model for dengue transmission in a closed population where regular visits of people to a mosquito breeding site out of their residency such as traditional market take place daily. Basic reproductive ratio of the system is obtained and depends on the ratio between the outgoing rates of susceptible human and infective human. It is shown that the increase of mobility with different variation of mobility rates may contribute to different level of basic reproductive ratio as well as different level of outbreaks.

  5. Go ahead, visit those web sites, you can`t get hurt, can you?

    SciTech Connect

    Rothfuss, J.S.; Parrett, J.W.

    1997-02-01

    Browsing (surfing) the World Wide Web (the web) has exploded onto the Internet with an unprecedented popularity. Fueled by massive acceptance, the web client/server technology is leaping forward with a speed that competes with no other software technology. The primary force behind this phenomenon is the simplicity of the web browsing experience. People who have never touched a computer before can now perform sophisticated network tasks with a simple point-and-click. Unfortunately, this simplicity gives many, if not most, web wanderers the impression that the web browser is risk free, nothing more than a high powered television. This misconception is dangerous by creating the myth that a user visiting a web site is immune from subversive or malicious intent. While many want you to believe that surfing the web is as simple as using any other household appliance, it is not like surfing television channels, it is bi-directional. You can learn a lot of useful information from web sites. But, either directly or indirectly, others can also learn quite a bit about you. Of even more concern is a web sites` potential ability to exert control over the local computer. This paper tries to consolidate some of the current concerns that you should consider as you jump into the surf.

  6. Visiting Holocaust-Related Sites with Medical Students as an Aid in Teaching Medical Ethics.

    PubMed

    González-López, Esteban; Ríos-Cortés, Rosa

    2016-05-01

    During the Nazi period numerous doctors and nurses played a nefarious role. In Germany they were responsible for the sterilization and killing of disabled persons. Furthermore, the Nazi doctors used concentration camp inmates as guinea pigs in medical experiments for military or racial purposes. A study of the collaboration of doctors with National Socialism exemplifies behavior that must be avoided. Combining medical teaching with lessons from the Holocaust could be a way to transmit Medical Ethics to doctors, nurses and students. The authors describe a study tour with medical students to Poland, to the largest Nazi extermination camp, Auschwitz, and to the city of Krakow. The tour is the final component of a formal course entitled: "The Holocaust, a Reflection from Medicine" at the Autónoma University of Madrid, Spain. Visiting sites related to the Holocaust, the killing centers and the sites where medical experiments were conducted has a singular meaning for medical students. Tolerance, non-discrimination, and the value of human life can be both learnt and taught at the very place where such values were utterly absent. PMID:27430079

  7. Geomorphic stability field reconnaissance site visit, Canonsburg, Pennsylvania, December 1992. Final report

    SciTech Connect

    1993-05-01

    To license the Canonsburg site, the US Nuclear Regulatory Commission (NRC) has required that geomorphic stability be demonstrated for the stream banks and slopes around the perimeter of the site for 200 years. Based on a study of the stream channel and slopes, it has been determined that due to recent human intervention, the required geomorphic stability cannot now be achieved without installation of erosion protection works and continued monitoring of the site. The Pittsburgh District Corps of Engineers has plans to channelize Chartiers Creek and install erosion protection rock within the next 5 or 6 years, if local government agencies raise the necessary matching funds. Much of the stream bank and slope adjacent to the ``fenced in`` western area of the site is anticipated to remain geomorphically stable for more than 20 years, but less than 200 years without human intervention. Therefore in much of this area, the Corps of Engineers will have adequate time to perform its work without jeopardizing the integrity of the controlled area. In contrast, two approximately 200-foot (ft) (60-meter [m]) long portions of the stream channel located north-northwest of the encapsulation area are subject to active stream erosion that threatens the integrity of the controlled area. These areas should be fixed by installation of erosion protection rock within the next 2 years.

  8. Hazardous waste site remediation and community acceptance: Beyond regulatory compliance

    SciTech Connect

    Howard, M.A.; Moreau, J.P.

    1998-12-31

    Community acceptance is an important criteria in securing regulatory approval of remediation alternatives, and yet the legal requirements for public consultation during the preparation of site investigation and feasibility study reports are minimal. Usually the only provision for formal public input on remedial plans is at the final stages of preparation through the formalistic constraints of a public meeting and limited comment period. This is often too late for meaningful public input and precludes constructive dialogue between responsible parties, local citizens, and regulatory representatives. Often the public opposes proposed remediation alternatives because of insufficient information leading to mistrust and irreconcilable differences. This paper suggests that responsible parties run the risk of community rejection of remediation plans, and costly project delays, if they follow the minimum regulatory requirements for public involvement. Through the use of active and meaningful citizen participation throughout project planning, success in securing community acceptance for preferred remedial alternatives in potentially controversial remediation projects is greatly enhanced.

  9. Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site Visits

    PubMed Central

    Dahm, Matthew M.; Schubauer-Berigan, Mary K.; Evans, Douglas E.; Birch, M. Eileen; Fernback, Joseph E.; Deddens, James A.

    2015-01-01

    Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 µg m−3 as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 µg m−3 with a geometric mean (GM) of 0.34 µg m−3 and an 8-h TWA of 0.16 µg m−3. PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 µg m−3 with a GM of 1.21 µg m−3. PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm3 with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2–5 µm range as well as agglomerates >5 µm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman ρ = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 μg m−3 at the respirable size fraction), while 30% of the inhalable PBZ EC

  10. Carbon Nanotube and Nanofiber Exposure Assessments: An Analysis of 14 Site Visits.

    PubMed

    Dahm, Matthew M; Schubauer-Berigan, Mary K; Evans, Douglas E; Birch, M Eileen; Fernback, Joseph E; Deddens, James A

    2015-07-01

    Recent evidence has suggested the potential for wide-ranging health effects that could result from exposure to carbon nanotubes (CNT) and carbon nanofibers (CNF). In response, the National Institute for Occupational Safety and Health (NIOSH) set a recommended exposure limit (REL) for CNT and CNF: 1 µg m(-3) as an 8-h time weighted average (TWA) of elemental carbon (EC) for the respirable size fraction. The purpose of this study was to conduct an industrywide exposure assessment among US CNT and CNF manufacturers and users. Fourteen total sites were visited to assess exposures to CNT (13 sites) and CNF (1 site). Personal breathing zone (PBZ) and area samples were collected for both the inhalable and respirable mass concentration of EC, using NIOSH Method 5040. Inhalable PBZ samples were collected at nine sites while at the remaining five sites both respirable and inhalable PBZ samples were collected side-by-side. Transmission electron microscopy (TEM) PBZ and area samples were also collected at the inhalable size fraction and analyzed to quantify and size CNT and CNF agglomerate and fibrous exposures. Respirable EC PBZ concentrations ranged from 0.02 to 2.94 µg m(-3) with a geometric mean (GM) of 0.34 µg m(-3) and an 8-h TWA of 0.16 µg m(-3). PBZ samples at the inhalable size fraction for EC ranged from 0.01 to 79.57 µg m(-3) with a GM of 1.21 µg m(-3). PBZ samples analyzed by TEM showed concentrations ranging from 0.0001 to 1.613 CNT or CNF-structures per cm(3) with a GM of 0.008 and an 8-h TWA concentration of 0.003. The most common CNT structure sizes were found to be larger agglomerates in the 2-5 µm range as well as agglomerates >5 µm. A statistically significant correlation was observed between the inhalable samples for the mass of EC and structure counts by TEM (Spearman ρ = 0.39, P < 0.0001). Overall, EC PBZ and area TWA samples were below the NIOSH REL (96% were <1 μg m(-3) at the respirable size fraction), while 30% of the inhalable PBZ EC

  11. Utility siting of WECS: A preliminary legal/regulatory assessment

    NASA Astrophysics Data System (ADS)

    Noun, R. J.; Lotker, M.; Frieseman, H. P.

    1981-05-01

    The early experiences of several utilities in dealing with the legal and regulatory issues that were raised in the process of siting wing energy installations were examined. Recommendations are made as to how utilities can begin to address many of the identified issues. Two issues associated with utility siting of wind machines are cited: (1) land acquisition and use and (2) aesthetic controls. Land use control regulations dealing with incompatible uses, nuisance factors, building scale limitations, and on site environmental impacts many constrain wind machine siting by utilities. The siting issue of greatest concern is how the public will react to the hard reality of wind power development. Little public opposition to wind energy projects is raised to date, yet it is possible that local attitudes will change as the novelty of the early single unit machines wears off. It is concluded that potentially adverse impacts based on local aesthetic concerns can be minimized by careful planning, siting, and design by utility developers and by close coordination with local planning and regulatory officials.

  12. A Study of Program Management Procedures in the Campus-Based and Basic Grant Programs. Site Visit Report.

    ERIC Educational Resources Information Center

    Ellis, Richard, Ed.; Puma, Michael, Ed.

    Site visits to a sample of 173 colleges, universities, vocational-technical schools, and other postsecondary institutions--conducted to examine the procedures used to manage federal Basic Educational Opportunity Grant (BEOG) and campus-based student financial assistance programs--are summarized. This report deals only with the conduct of the…

  13. SUMMARY REPORT FOR THE NATIONAL ATMOSPHERIC DEPOSITION PROGRAM/NATIONAL TRENDS NETWORK (NADP/NTN) SITE VISITATION PROGRAM FOR THE PERIOD OCTOBER 1987 THROUGH SEPTEMBER 1988

    EPA Science Inventory

    The U.S Environmental Protection Agency (EPA) provides technical assistance to the NADP/NTN network through a site visitation program. esearch Triangle Institute, as contractor to EPA, conducts these visits. f deficiencies or nonstandard procedures are noted, the site operator an...

  14. Reaching Site Closure for Groundwater under Multiple Regulatory Agencies

    SciTech Connect

    Glucksberg, N.; Shephard, Gene; Peters, Jay; Couture, B.

    2008-01-15

    Groundwater at the Connecticut Yankee Atomic Power Company (CYAPCO) Haddam Neck Plant (HNP) requires investigation of both radionuclides and chemical constituents in order to achieve closure. Cleanup criteria for groundwater are regulated both by federal and state agencies. These requirements vary in both numerical values as well as the duration of post remediation monitoring. The only consistent requirement is the development of a site conceptual model and an understanding of the hydrogeologic conditions that will govern contaminant transport and identify potential receptors. To successfully reach closure under each agency, it is paramount to understand the different requirements during the planning stages of the investigation. Therefore, the conceptual site model, groundwater transport mechanisms, and potential receptors must be defined. Once the hydrogeology is understood, a long term groundwater program can then be coordinated to meet each regulatory agency requirement to both terminate the NRC license and reach site closure under RCRA. Based on the different criteria, the CTDEP-LR (or RSR criteria) are not only bounding, but also requires the longest duration. As with most decommissioning efforts, regulatory attention is focused on the NRC, however, with the recent industry initiatives based on concern of tritium releases to groundwater at other plants, it is likely that the USEPA and state agencies may continue to drive site investigations. By recognizing these differences, data quality objectives can include all agency requirements, thus minimizing rework or duplicative efforts. CYAPCO intends to complete groundwater monitoring for the NRC and CTDEP-RD by July 2007. However, because shallow remediations are still being conducted, site closure under USEPA and CTDEP-LR is projected to be late 2011.

  15. Mineral licks: motivational factors for visitation and accompanying disease risk at communal use sites of elk and deer.

    PubMed

    Lavelle, Michael J; Phillips, Gregory E; Fischer, Justin W; Burke, Patrick W; Seward, Nathan W; Stahl, Randal S; Nichols, Tracy A; Wunder, Bruce A; VerCauteren, Kurt C

    2014-12-01

    Free-ranging cervids acquire most of their essential minerals through forage consumption, though occasionally seek other sources to account for seasonal mineral deficiencies. Mineral sources occur as natural geological deposits (i.e., licks) or as anthropogenic mineral supplements. In both scenarios, these sources commonly serve as focal sites for visitation. We monitored 11 licks in Rocky Mountain National Park, north-central Colorado, using trail cameras to quantify daily visitation indices (DVI) and soil consumption indices (SCI) for Rocky Mountain elk (Cervus elaphus) and mule deer (Odocoileus hemionus) during summer 2006 and documented elk, mule deer, and moose (Alces alces) visiting licks. Additionally, soil samples were collected, and mineral concentrations were compared to discern levels that explain rates of visitation. Relationships between response variables; DVI and SCI, and explanatory variables; elevation class, moisture class, period of study, and concentrations of minerals were examined. We found that DVI and SCI were greatest at two wet, low-elevation licks exhibiting relatively high concentrations of manganese and sodium. Because cervids are known to seek Na from soils, we suggest our observed association of Mn with DVI and SCI was a likely consequence of deer and elk seeking supplemental dietary Na. Additionally, highly utilized licks such as these provide an area of concentrated cervid occupation and interaction, thus increasing risk for environmental transmission of infectious pathogens such as chronic wasting disease, which has been shown to be shed in the saliva, urine, and feces of infected cervids. PMID:24711146

  16. Records for the number of distinct sites visited by a random walk on the fully connected lattice

    NASA Astrophysics Data System (ADS)

    Turban, Loïc

    2015-11-01

    We consider a random walk on the fully connected lattice with N sites and study the time evolution of the number of distinct sites s visited by the walker on a subset with n sites. A record value v is obtained for s at a record time t when the walker visits a site of the subset for the first time. The record time t is a partial covering time when v\\lt n and a total covering time when v = n. The probability distributions for the number of records s, the record value v and the record (covering) time t, involving r-Stirling numbers, are obtained using generating function techniques. The mean values, variances and skewnesses are deduced from the generating functions. In the scaling limit the probability distributions for s and v lead to the same Gaussian density. The fluctuations of the record time t are also Gaussian at partial covering, when n-v={{O}}(n). They are distributed according to the type-I Gumbel extreme-value distribution at total covering, when v = n. A discrete sequence of generalized Gumbel distributions, indexed by n-v, is obtained at almost total covering, when n-v={{O}}(1). These generalized Gumbel distributions are crossing over to the Gaussian distribution when n - v increases.

  17. Regulatory site of inorganic pyrophosphatase. Interaction with substrate analogs

    SciTech Connect

    Baikov, A.A.; Pavlov, A.R.; Avaeva, S.M.

    1986-08-10

    The effect of four PP/sub 1/ analogs with the structure PXP (X = N, C), phosphate, and the complex Cr(H/sub 2/O)/sub 4/PP/sub 1/ on the activity of inorganic pyrophosphatase from baker's yeast was studied over a wide range of substrate (Mg-PP/sub 1/) concentrations (lower limit 0.5 ..mu..M). The enzyme activity decreased in the presence of imidodiphosphate, hydroxymethane diphosphonate (PC(OH)P), and P/sub 1/, and a double reciprocal plot of the rate of hydrolysis of Mg-PP/sub 1/ versus its concentration became linear. Small amounts of methane diphosphonate (PCP), ethane-1-hydroxy-1,1-diphosphonate (0.1-1..mu..M), and Cr(H/sub 2/O)/sub 4/PP/sub 1/ (10 ..mu..M) activated the enzyme almost 2-fold by a competitive mechanism. The activation was due to an increase in the affinity of the protein for the activating Mg/sup 2 +/ ion. Ultrafiltration showed that the pyrophosphatase molecule has 2.1 and 3.1 binding sites for PCP and PC(OHP)P, respectively. These results confirm the hypothesis that the enzyme contains a regulatory site whose occupation by PP/sub 1/, P/sub 1/, and substrate analogs increases the affinity of the protein for the activating metal.

  18. Heavy vehicle industry site visits: comments from companies and conclusions from technical committee

    SciTech Connect

    McCallen, R.

    1998-02-01

    This report documents the results of several visits with industry as part of the Department of Energy (DOE), office of Transportation Technology, Office of Heavy Vehicle Technology, supported Heavy Vehicle Aerodynamics Project. The purpose of the DOE Heavy Vehicle Aerodynamics Project is to use government resources to bring the aerodynamic expertise available in government organizations and academia to bear in assisting the heavy vehicle industry to reduce aerodynamic drag on trucks. The obvious payback from this investment is the reduction in fuel usage and derivative reduction in the US's dependence on foreign oil imports. This report covers 2 projects: (1) The stated purpose of Project 1 was to provide near-term impact through emphasis on existing tools and capabilities and to focus on the trailer drag problem. (2) The stated purpose of Project 2 was to provide the tools necessary to accomplish the longer term goal of a fully-integrated, aerodynamic tractor-trailer combination.

  19. Summary report for the National Atmospheric Deposition Program/National Trends Network (NADP/NTN) site visitation program for the period October 1987 through September 1988

    SciTech Connect

    Eaton, W.C.; Moore, C.E.; Murdoch, R.W.; Shores, R.C.; Ward, D.A.

    1990-04-01

    The U.S. Environmental Protection Agency (EPA) provides technical assistance to the NADP/NTN network through a site visitation program. Research Triangle Institute, as contractor to EPA, conducts these visits. If deficiencies or nonstandard procedures are noted, the site operator and supervisor are notified. Brief reports are sent to the EPA Project Officer, the NADP/NTN Quality Assurance Manager, and others. In this way, necessary changes can be made promptly. All NADP.NTN sites were visited in 1985-1986. A second round of visits began in October 1986, with the goal of visiting approximately one-third of the 200 sites each year over the next three years. The document is a summary report of the findings from the 1987-1988 (Fiscal Year 1988) site visitation program to 57 of the sites of the NADP/NTN network. In its present configuration, the network's research and monitoring programs are supported and operated by the U.S. Geological Survey; State Agricultural Experiment Stations; the Departments of Agriculture, the Interior, Commerce, and Energy; and EPA. Additional support is provided by state agencies, public utilities, and industries.

  20. Summary report for the National Atmospheric Deposition Program/National Trends Network (NADP/NTN) site-visitation program. Rept. for Oct 88-Sep 89

    SciTech Connect

    Eaton, W.C.; Moore, C.E.; Murdoch, R.W.; Shores, R.C.; Ward, D.A.

    1991-12-01

    The proper collection of precipitation and the accurate measurement of its constituents are important steps in attaining a better understanding of the distribution and effects of acid rain in the United States. One of NAPAP Task Group IV's major programs concerns wet deposition monitoring. One of that program's project, 4A-15, 'Quality Assurance Support for Wet Deposition Monitoring,' is sponsored by the U.S. Environmental Protection Agency (EPA) to evaluate the sample collection process and provide technical assistance to the NADP/NTN network through a site visitation program. Research Triangle Institute, as contractor to EPA, conducts these visits. If deficiencies or nonstandard procedures are noted, the site operator and supervisor are notified. Brief reports are sent to the EPA Project Officer, the NADP/NTN Quality Assurance Manager, and others. In this way, necessary changes can be made promptly. All NADP/NTN sites were visited in 1985-1986. A second round of visits began in October 1986, with the goal of visiting approximately one-third of the 200 sites each year over the next three years. The document is a summary report of the findings from the 1988-1989 (Fiscal Year 1989) site visitation program to 72 of the sites of the NADP/NTN network.

  1. Understanding Patterns of User Visits to Web Sites: Interactive Starfield Visualizations of WWW Log Data.

    ERIC Educational Resources Information Center

    Hochheiser, Harry; Shneiderman, Ben

    1999-01-01

    Describes the use of Spotfire, a starfield visualization tool, to generate interactive visualizations of log data, ranging from aggregate views of all Web site hits in a time interval to close-ups that approximate the path of a user through a site. Highlights current efforts and provides examples of the visualizations created in Spotfire.…

  2. Protecting the Lunar Heritage Sites from the Effects of Visiting Spacecraft

    NASA Technical Reports Server (NTRS)

    Metzger, Philip; Lane, John E.

    2012-01-01

    The Problem: Rocket exhaust blows soil and rocks over vast distances at velocities upwards of 1 to 3 km/s, and this will be highly abrasive and damaging if it impacts the valuable lunar heritage sites.

  3. 12 CFR 1010.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... provisions of 12 CFR 1010.4(b) and (c) and the sales practices and standards in §§ 1011.10 through 1011.28... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Regulatory exemption-multiple site subdivision... REGISTRATION (REGULATION J) General Requirements § 1010.15 Regulatory exemption—multiple site...

  4. 12 CFR 1010.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... provisions of 12 CFR 1010.4(b) and (c) and the sales practices and standards in §§ 1011.10 through 1011.28... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Regulatory exemption-multiple site subdivision... REGISTRATION (REGULATION J) General Requirements § 1010.15 Regulatory exemption—multiple site...

  5. 12 CFR 1010.15 - Regulatory exemption-multiple site subdivision-determination required.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... provisions of 12 CFR 1010.4(b) and (c) and the sales practices and standards in §§ 1011.10 through 1011.28... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Regulatory exemption-multiple site subdivision... REGISTRATION (REGULATION J) General Requirements § 1010.15 Regulatory exemption—multiple site...

  6. Reaching site closure for groundwater under multiple regulatory agencies

    SciTech Connect

    Glucksberg, N.; Couture, B.

    2007-07-01

    Groundwater at the Connecticut Yankee Atomic Power Company (CYAPCO) Haddam Neck Plant (HNP) has been impacted by both radionuclides and chemical constituents. Furthermore, the cleanup standards and closure requirements for HNP are regulated both by federal and state agencies. The only consistent requirement is the development of a site conceptual model and an understanding of the hydrogeologic conditions that will govern contaminant transport and identify potential receptors. The cleanup criteria to reach site closure for radionuclides is regulated by both the Nuclear Regulatory Commission (NRC) and the Connecticut Department of Environmental Protection (CTDEP) Bureau of Air Management, Radiological Division. For license termination under the NRC, the total effective dose equivalent (TEDE) for all media can not exceed 25 milli-Rem per year (mRem/yr) plus As Low as Reasonably Achievable (ALARA). The CTDEP has a similar requirement with the TEDE not to exceed 19 mRem/yr plus ALARA. To reach these criteria, derived concentration guideline levels (DCGLs) were developed for radiological exposures from three (3) media components; soil, existing groundwater and future groundwater from left-in place foundations or footings. Based on current conditions, the target dose contribution from existing and future groundwater is not to exceed 2 mRem/yr TEDE. After source (soil) remediation is complete, the NRC requires two (2) years of quarterly monitoring to demonstrate that groundwater quality meets the DCGLs and does not show an upward trend. CYAPCO's NRC License Termination Plan (LTP) specifies a minimum 18-month period of groundwater monitoring, as long as samples are collected during two spring/high water seasons, to verify the efficacy of remedial actions at HNP. In addition to the 19 mRem/yr criteria, the CTDEP also requires groundwater to be in compliance with the Remediation Standards Regulation (RSRs). There are no published criteria for radionuclides in the RSRs

  7. Site visits for the review of grant applications to the National Institutes of Health: Views of an applicant and a scientist administrator.

    PubMed

    Merritt, D H; Eaves, G N

    1975-02-01

    The review of applications to the National Institutes of Health for individual research projects and complex programs of research may involve a visit to the applicant institution. The site visit is a review technique that is used only when information necessary for the scientific and technical review cannot be obtained satisfactorily by other means. The agenda for the visit must be carefully planned, particularly in the case of large research programs, since adequate time must be allowed for the presentation and discussion of the more complex components of the proposed research. All of the participating investigators associated with the proposal should get together for a thorough and critical rehearsal a few days before the visit. The impressions conveyed to the site visitors are transmitted to the initial review group usually through a site-visit report. The final recommendation of the visitors, which is based on the scientific merit of the proposed research, the competence of the investigators, and the suitability of the institutional setting, results from a thorough discussion of the strengths and weaknesses of the proposed program. The initial review group, in turn, uses the information obtained at the site visit in arriving at their recommendation to the appropriate National Advisory Council. PMID:1116610

  8. Sites of Predicted Stress-Induced DNA Duplex Destabilization Occur Preferentially at Regulatory Loci

    NASA Astrophysics Data System (ADS)

    Benham, Craig J.

    1993-04-01

    This paper describes a computational method to predict the sites on a DNA molecule where imposed superhelical stresses destabilize the duplex. Several DNA sequences are analyzed in this way, including the pBR322 and ColE1 plasmids, bacteriophage f1, and the polyoma and bovine papilloma virus genomes. Superhelical destabilization in these molecules is predicted to occur at small numbers of discrete sites, most of which are within regulatory regions. The most destabilized sites include the terminator and promoter regions of specific plasmid operons, the LexA binding sites of genes under SOS control, the intergenic control region of bacteriophage f1, and the polyadenylylation sites in eukaryotic viruses. These results demonstrate the existence of close correspondences between sites of predicted superhelical duplex destabilization and specific types of regulatory regions. The use of these correspondences to supplement string-matching techniques in the search for regulatory loci is discussed.

  9. Crisis Nursery and Respite Care Programs: Site Visit Results of Staff and Family Interviews (Winter and Spring of 1991).

    ERIC Educational Resources Information Center

    Huntington, Gail S.; And Others

    Visits were made to selected respite care and crisis nursery programs in order to describe the programs and services they offered to families of young children with special needs and to learn more about the families who used the services and the staff who provided them. The visits to 10 crisis nurseries and 24 respite care programs resulted in…

  10. Program Strengths and Opportunities for Improvement Identified by Residents During ACGME Site Visits in 5 Surgical Specialties.

    PubMed

    Caniano, Donna A; Hamstra, Stanley J

    2016-05-01

    Background There is limited information about how residents in surgical specialties view program strengths and opportunities for improvement (OFIs). Objective This study aggregated surgical residents' perspectives on program strengths and OFIs to determine whether there was agreement in perspectives among residents in 5 surgical specialties. Methods Resident consensus lists of program strengths and areas for improvement were aggregated from site visits reports during 2012 and 2013 for obstetrics and gynecology, orthopaedic surgery, otolaryngology, plastic surgery, and surgery programs. Four trained individuals coded each strength or OFI in 1 of 3 categories: (1) factors common to all specialties; (2) program or institutional resources; and (3) factors unique to surgical specialties. Themes were classified as most frequent when listed by residents in more than 20% of the programs and less frequent when listed by residents in less than 20% of the programs. Results This study included a total of 359 programs, representing 27% to 49% of the Accreditation Council for Graduate Medical Education accredited programs in the 5 specialties. The most frequent strengths were progressive autonomy, collegiality, program leadership, and operative volume. Improving research and didactics, increasing faculty teaching and attendance at educational sessions, and increasing the number of nurse practitioners and physician assistants were common OFIs. Conclusions Factors identified as important by surgical residents related to their learning environment, their educational program, and program and institutional support. Across programs in the study, similar attributes were listed as both program strengths and OFIs. PMID:27168889

  11. Key findings from HSC's 2010 site visits: health care markets weather economic downturn, brace for health reform.

    PubMed

    Felland, Laurie E; Grossman, Joy M; Tu, Ha T

    2011-05-01

    Lingering fallout--loss of jobs and employer coverage--from the great recession slowed demand for health care services but did little to slow aggressive competition by dominant hospital systems for well-insured patients, according to key findings from the Center for Studying Health System Change's (HSC) 2010 site visits to 12 nationally representative metropolitan communities. Hospitals with significant market clout continued to command high payment rate increases from private insurers, and tighter hospital-physician alignment heightened concerns about growing provider market power. High and rising premiums led to increasing employer adoption of consumer-driven health plans and continued increases in patient cost sharing, but the broader movement to educate and engage consumers in care decisions did not keep pace. State and local budget deficits led to some funding cuts for safety net providers, but an influx of federal stimulus funds increased support to community health centers and shored up Medicaid programs, allowing many people who lost private insurance because of job losses to remain covered. Hospitals, physicians and insurers generally viewed health reform coverage expansions favorably, but all worried about protecting revenues as reform requirements phase in. PMID:21614861

  12. REGULATORY PERSPECTIVE ON MANAGING RISKS AT WOOD TREATING SITES

    EPA Science Inventory

    Over 700 sites in the United States have been identified where wood preserving operations have been conducted. The most common types of wood preservatives found at these sites are creosote, pentachlorophenol (PCP), and copper chromated arsenate (CCA). When properly used and dis...

  13. US Department of Energy wind turbine candidate site program: the regulatory process

    SciTech Connect

    Greene, M.R.; York, K.R.

    1982-06-01

    Sites selected in 1979 as tentative sites for installation of a demonstration MOD-2 turbine are emphasized. Selection as a candidate site in this program meant that the US Department of Energy (DOE) designated the site as eligible for a DOE-purchased and installed meteorological tower. The regulatory procedures involved in the siting and installation of these meteorological towers at the majority of the candidate sites are examined. An attempt is also made, in a preliminary fashion, to identify the legal and regulatory procedures that would be required to put up a turbine at each of these candidate sites. The information provided on each of these sites comes primarily from utility representatives, supplemented by conversations with state and local officials. The major findings are summarized on the following: federal requirements, state requirements, local requirements, land ownership, wind rights, and public attitudes.

  14. The ACA Standards Organizer. A Tool for the Preparation of Camps for Visitation for American Camping Association Camp Accreditation and Site Approval.

    ERIC Educational Resources Information Center

    Chenery, Mary Faeth

    This comprehensive guide helps camp administrators prepare for camp accreditation and site approval visits by the American Camping Association (ACA). The introductory sections outline the purpose and administration of the standards program and provide definitions of camping terms. Standards are organized under one section for camp accreditation…

  15. USEPA SITE PROGRAM APPROACH TO TECHNOLOGY TRANSFER AND REGULATORY ACCEPTANCE

    EPA Science Inventory

    The SITE Program was created to meet the increased demand for innovative technologies for hazardous waste treatment. To accomplish this mission, the program seeks to advance the development, implementation and commercialization of innovative technologies for hazardous waste chara...

  16. 10 CFR 25.35 - Classified visits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Classified visits. 25.35 Section 25.35 Energy NUCLEAR REGULATORY COMMISSION ACCESS AUTHORIZATION Classified Visits § 25.35 Classified visits. (a) The number of classified visits must be held to a minimum. The licensee, certificate holder, applicant for a...

  17. 10 CFR 25.35 - Classified visits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Classified visits. 25.35 Section 25.35 Energy NUCLEAR REGULATORY COMMISSION ACCESS AUTHORIZATION Classified Visits § 25.35 Classified visits. (a) The number of classified visits must be held to a minimum. The licensee, certificate holder, applicant for a...

  18. 10 CFR 25.35 - Classified visits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Classified visits. 25.35 Section 25.35 Energy NUCLEAR REGULATORY COMMISSION ACCESS AUTHORIZATION Classified Visits § 25.35 Classified visits. (a) The number of classified visits must be held to a minimum. The licensee, certificate holder, applicant for a...

  19. 10 CFR 25.35 - Classified visits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Classified visits. 25.35 Section 25.35 Energy NUCLEAR REGULATORY COMMISSION ACCESS AUTHORIZATION Classified Visits § 25.35 Classified visits. (a) The number of classified visits must be held to a minimum. The licensee, certificate holder, applicant for a...

  20. 10 CFR 25.35 - Classified visits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Classified visits. 25.35 Section 25.35 Energy NUCLEAR REGULATORY COMMISSION ACCESS AUTHORIZATION Classified Visits § 25.35 Classified visits. (a) The number of classified visits must be held to a minimum. The licensee, certificate holder, applicant for a...

  1. Identification of the Allosteric Regulatory Site of Insulysin

    SciTech Connect

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W.; Gerrard, Juliet Ann

    2011-06-24

    Background Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Aβ peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. Principal Findings The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Conclusions/Significance Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  2. Identification of the Allosteric Regulatory Site of Insulysin

    SciTech Connect

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W.

    2012-05-25

    Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the A{beta} peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  3. Characterization of nicotine binding to the rat brain P/sub 2/ preparation: the identification of multiple binding sites which include specific up-regulatory site(s)

    SciTech Connect

    Sloan, J.W.

    1984-01-01

    These studies show that nicotine binds to the rat brain P/sub 2/ preparation by saturable and reversible processes. Multiple binding sites were revealed by the configuration of saturation, kinetic and Scatchard plots. A least squares best fit of Scatchard data using nonlinear curve fitting programs confirmed the presence of a very high affinity site, an up-regulatory site, a high affinity site and one or two low affinity sites. Stereospecificity was demonstrated for the up-regulatory site where (+)-nicotine was more effective and for the high affinity site where (-)-nicotine had a higher affinity. Drugs which selectively up-regulate nicotine binding site(s) have been identified. Further, separate very high and high affinity sites were identified for (-)- and (+)-(/sup 3/H)nicotine, based on evidence that the site density for the (-)-isomer is 10 times greater than that for the (+)-isomer at these sites. Enhanced nicotine binding has been shown to be a statistically significant phenomenon which appears to be a consequence of drugs binding to specific site(s) which up-regulate binding at other site(s). Although Scatchard and Hill plots indicate positive cooperatively, up-regulation more adequately describes the function of these site(s). A separate up-regulatory site is suggested by the following: (1) Drugs vary markedly in their ability to up-regulate binding. (2) Both the affinity and the degree of up-regulation can be altered by structural changes in ligands. (3) Drugs with specificity for up-regulation have been identified. (4) Some drugs enhance binding in a dose-related manner. (5) Competition studies employing cold (-)- and (+)-nicotine against (-)- and (+)-(/sup 3/H)nicotine show that the isomers bind to separate sites which up-regulate binding at the (-)- and (+)-nicotine high affinity sites and in this regard (+)-nicotine is more specific and efficacious than (-)-nicotine.

  4. Biological data warehousing system for identifying transcriptional regulatory sites from gene expressions of microarray data.

    PubMed

    Tsou, Ann-Ping; Sun, Yi-Ming; Liu, Chia-Lin; Huang, Hsien-Da; Horng, Jorng-Tzong; Tsai, Meng-Feng; Liu, Baw-Juine

    2006-07-01

    Identification of transcriptional regulatory sites plays an important role in the investigation of gene regulation. For this propose, we designed and implemented a data warehouse to integrate multiple heterogeneous biological data sources with data types such as text-file, XML, image, MySQL database model, and Oracle database model. The utility of the biological data warehouse in predicting transcriptional regulatory sites of coregulated genes was explored using a synexpression group derived from a microarray study. Both of the binding sites of known transcription factors and predicted over-represented (OR) oligonucleotides were demonstrated for the gene group. The potential biological roles of both known nucleotides and one OR nucleotide were demonstrated using bioassays. Therefore, the results from the wet-lab experiments reinforce the power and utility of the data warehouse as an approach to the genome-wide search for important transcription regulatory elements that are the key to many complex biological systems. PMID:16871724

  5. Resident and Faculty Perceptions of Program Strengths and Opportunities for Improvement: Comparison of Site Visit Reports and ACGME Resident Survey Data in 5 Surgical Specialties.

    PubMed

    Caniano, Donna A; Yamazaki, Kenji; Yaghmour, Nicholas; Philibert, Ingrid; Hamstra, Stanley J

    2016-05-01

    Background Resident and faculty views of program strengths and opportunities for improvement (OFIs) offer insight into how stakeholders assess key elements of the learning environment. Objective This study sought (1) to assess the degree to which residents and faculty in 359 programs in 5 surgical specialties (obstetrics and gynecology, orthopaedic surgery, otolaryngology, plastic surgery, and surgery) were aligned or divergent in their respective views of program strengths and OFIs; and (2) to evaluate whether responses to selected questions on the Accreditation Council for Graduate Medical Education (ACGME) Resident Survey correlated with strengths or OFIs identified by the residents during the site visit. Methods Faculty and resident lists of program strengths and OFIs in site visit reports for 2012 and 2013 were aggregated, analyzed, and compared to responses on the Resident Survey. Results While there was considerable alignment in resident and faculty perceptions of program strengths and OFIs, some attributes were more important to one or the other group. Collegiality was valued highly by both stakeholder groups. Responses to 2 questions on the ACGME Resident Survey were associated with resident-identified OFIs in site visit reports pertaining to aspects of the didactic program and responsiveness to resident suggestions for improvement. Conclusions The findings offer program leadership additional insight into how 2 key stakeholder groups view elements of the learning environment as program strengths or OFIs and may serve as useful focal areas for ongoing improvement activities. PMID:27168915

  6. Regulatory supervision of sites for spent fuel and radioactive waste storage in the Russian northwest.

    PubMed

    Shandala, N K; Sneve, M K; Smith, G M; Kiselev, M F; Kochetkov, O A; Savkin, M N; Simakov, A V; Novikova, N Ya; Titov, A V; Romanov, V V; Seregin, V A; Filonova, A V; Semenova, M P

    2008-12-01

    In the 1960s two technical bases for the Northern Fleet were created in the Russian northwest at Andreeva Bay in the Kola Peninsula and Gremikha village on the coast of the Barents Sea. They maintained nuclear submarines, receiving and storing radioactive waste and spent nuclear fuel. No further waste was received after 1985, and the technical bases have since been re-categorised as temporary storage sites. The handling of these materials to put them into a safe condition is especially hazardous because of their degraded state. This paper describes regulatory activities which have been carried out to support the supervision of radiological protection during recovery of waste and spent fuel, and to support regulatory decisions on overall site remediation. The work described includes: an assessment of the radiation situation on-site; the development of necessary additional regulatory rules and standards for radiation protection assurance for workers and the public during remediation; and the completion of an initial threat assessment to identify regulatory priorities. Detailed consideration of measures for the control of radiation exposure of workers and radiation exposure of the public during and after operations and emergency preparedness and response are complete and provided in sister papers. The continuing requirements for regulatory activities relevant to the development and implementation of on-going and future remediation activities are also outlined. The Norwegian Radiation Protection Authority supports the work, as part of the Norwegian Government's plan of action to promote improvements in radiation protection and nuclear safety in northwest Russia. PMID:19029594

  7. DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes

    PubMed Central

    2013-01-01

    Background Abnormal epigenetic marking is well documented in gene promoters of cancer cells, but the study of distal regulatory siteshas lagged behind.We performed a systematic analysis of DNA methylation sites connected with gene expression profilesacross normal and cancerous human genomes. Results Utilizing methylation and expression data in 58 cell types, we developed a model for methylation-expression relationships in gene promoters and extrapolated it to the genome. We mapped numerous sites at which DNA methylation was associated with expression of distal genes. These sites bind transcription factors in a methylation-dependent manner, and carry the chromatin marks of a particular class of transcriptional enhancers. In contrast to the traditional model of one enhancer site per cell type, we found that single enhancer sites may define gradients of expression levels across many different cell types. Strikingly, the identified sites were drastically altered in cancers: hypomethylated enhancer sites associated with upregulation of cancer-related genes and hypermethylated sites with downregulation. Moreover, the association between enhancer methylation and gene deregulation in cancerwas significantly stronger than the association of promoter methylationwith gene deregulation. Conclusions Methylation of distal regulatory sites is closely related to gene expression levels across the genome. Single enhancers may modulate ranges of cell-specific transcription levels, from constantlyopen promoters. In contrast to the remote relationships between promoter methylation and gene dysregulation in cancer, altered methylation of enhancer sites is closely related to gene expression profiles of transformed cells. PMID:23497655

  8. Extraction of Functional Binding Sites from Unique Regulatory Regions: The Drosophila Early Developmental Enhancers

    PubMed Central

    Papatsenko, Dmitri A.; Makeev, Vsevolod J.; Lifanov, Alex P.; Régnier, Mireille; Nazina, Anna G.; Desplan, Claude

    2002-01-01

    The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticated regulatory systems in higher eukaryotes. An elaborate code in their DNA sequence translates both maternal and early embryonic regulatory signals into spatial distribution of transcription factors. One of the most striking features of this code is the redundancy of binding sites for these transcription factors (BSTF). Using this redundancy, we explored the possibility of predicting functional binding sites in a single enhancer region without any prior consensus/matrix description or evolutionary sequence comparisons. We developed a conceptually simple algorithm, Scanseq, that employs an original statistical evaluation for identifying the most redundant motifs and locates the position of potential BSTF in a given regulatory region. To estimate the biological relevance of our predictions, we built thorough literature-based annotations for the best-known Drosophila developmental enhancers and we generated detailed distribution maps for the most robust binding sites. The high statistical correlation between the location of BSTF in these experiment-based maps and the location predicted in silico by Scanseq confirmed the relevance of our approach. We also discuss the definition of true binding sites and the possible biological principles that govern patterning of regulatory regions and the distribution of transcriptional signals. PMID:11875036

  9. Prediction of transcription regulatory sites in Archaea by a comparative genomic approach.

    PubMed

    Gelfand, M S; Koonin, E V; Mironov, A A

    2000-02-01

    Intragenomic and intergenomic comparisons of upstream nucleotide sequences of archaeal genes were performed with the goal of predicting transcription regulatory sites (operators) and identifying likely regulons. Learning sets for the detection of regulatory sites were constructed using the available experimental data on archaeal transcription regulation or by analogy with known bacterial regulons, and further analysis was performed using iterative profile searches. The information content of the candidate signals detected by this method is insufficient for reliable predictions to be made. Therefore, this approach has to be complemented by examination of evolutionary conservation in different archaeal genomes. This combined strategy resulted in the prediction of a conserved heat shock regulon in all euryarchaea, a nitrogen fixation regulon in the methanogens Methanococcus jannaschii and Methanobacterium thermoautotrophicum and an aromatic amino acid regulon in M.thermoautotrophicum. Unexpectedly, the heat shock regulatory site was detected not only for genes that encode known chaperone proteins but also for archaeal histone genes. This suggests a possible function for archaeal histones in stress-related changes in DNA condensation. In addition, comparative analysis of the genomes of three Pyrococcus species resulted in the prediction of their purine metabolism and transport regulon. The results demonstrate the feasibility of prediction of at least some transcription regulatory sites by comparing poorly characterized prokaryotic genomes, particularly when several closely related genome sequences are available. PMID:10637320

  10. An information transmission model for transcription factor binding at regulatory DNA sites

    PubMed Central

    2012-01-01

    Background Computational identification of transcription factor binding sites (TFBSs) is a rapid, cost-efficient way to locate unknown regulatory elements. With increased potential for high-throughput genome sequencing, the availability of accurate computational methods for TFBS prediction has never been as important as it currently is. To date, identifying TFBSs with high sensitivity and specificity is still an open challenge, necessitating the development of novel models for predicting transcription factor-binding regulatory DNA elements. Results Based on the information theory, we propose a model for transcription factor binding of regulatory DNA sites. Our model incorporates position interdependencies in effective ways. The model computes the information transferred (TI) between the transcription factor and the TFBS during the binding process and uses TI as the criterion to determine whether the sequence motif is a possible TFBS. Based on this model, we developed a computational method to identify TFBSs. By theoretically proving and testing our model using both real and artificial data, we found that our model provides highly accurate predictive results. Conclusions In this study, we present a novel model for transcription factor binding regulatory DNA sites. The model can provide an increased ability to detect TFBSs. PMID:22672438

  11. Visiting Professorships

    NASA Astrophysics Data System (ADS)

    Applications are now being accepted for the National Science Foundation (NSF) Visiting Professorships for Women Program. Under this program, women scientists and engineers from industry, government, and academia can be visiting professors at academic institutions in the United States.The program's objectives are to provide opportunities for women to advance their careers in the disciplines of science and engineering that are supported by NSF to provide greater visibility and wider opportunities for women scientists and engineers employed in industry, government, and academic institutions, and to provide encouragement for other women to pursue careers in science and engineering through the awardees' research, lecturing, counseling, and mentoring activities.

  12. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins

    PubMed Central

    Rising, Lisa; Mak, Raymond; Webb, Kristofor; Kaiser, Stephen E.; Zuzow, Nathan; Riviere, Paul; Yang, Bing; Fenech, Emma; Tang, Xin; Lindsay, Scott A.; Christianson, John C.; Hampton, Randolph Y.; Wasserman, Steven A.; Bennett, Eric J.

    2015-01-01

    Summary Insults to endoplasmic reticulum (ER) homeostasis activate the unfolded protein response (UPR), which elevates protein folding and degradation capacity and attenuates protein synthesis. While a role for ubiquitin in regulating the degradation of misfolded ER-resident proteins is well described, ubiquitin-dependent regulation of translational reprogramming during the UPR remains uncharacterized. Using global quantitative ubiquitin proteomics, we identify evolutionarily conserved, site-specific regulatory ubiquitylation of 40S ribosomal proteins. We demonstrate that these events occur on assembled cytoplasmic ribosomes and are stimulated by both UPR activation and translation inhibition. We further show that ER stress-stimulated regulatory 40S ribosomal ubiquitylation occurs on a timescale similar to eIF2α phosphorylation, is dependent upon PERK signaling, and is required for optimal cell survival during chronic UPR activation. In total, these results reveal regulatory 40S ribosomal ubiquitylation as a previously uncharacterized and important facet of eukaryotic translational control. PMID:26051182

  13. Environmental Regulatory Compliance Plan for site: Draft characterization of the Yucca Mountain site:Draft

    SciTech Connect

    1988-01-01

    The objective of the EMMP is to document compliance with the NWPA. To do so, a summary description of site characterization activites is provided, based on the consultation draft of the SCP. Subsequent chpaters identify those technical areas having the potential to be impacted by site characterization activities and the monitoring plans proposed to identify whether those impacts acutally occur. Should monitoring confirm the potential for significant adverse impact, mitigative measures will be developed. In the context of site characterization, mitigation is defined as those changes in site characterization activities that serve to avoid or minimize, to the maximum extent practicle, any significant adverse environmental impacts. Although site characterization activies involve both surface and subsurface activities, it is the surface-based aspect of site characterization that is addressed in detailed by the EMMP. The schedule and duration of these activities is given in the consultation draft of the SCP. A breif summary of all proposed activities is given in the EMMP. 10 refs., 8 figs.

  14. Nevada Test Site Decontamination and Decommissioning Program History, Regulatory Framework, and Lessons Learned

    SciTech Connect

    Michael R. Kruzic, Bechtel Nevada; Patrick S. Morris, Bechtel Nevada; Jerel G. Nelson, Polestar Applied Technology, Inc.

    2005-08-07

    Decontamination and Decommissioning (D&D) of radiologically and/or chemically contaminated facilities at the Nevada Test Site (NTS) are the responsibility of the Environmental Restoration (ER) Project. Facilities identified for D&D are listed in the Federal Facilities Agreement and Consent Order (FFACO) and closed under the Resource Conservation and Recovery Act process. This paper discusses the NTS D&D program, including facilities history, D&D regulatory framework, and valuable lessons learned.

  15. Congressman Clyburn Visit

    ScienceCinema

    Cody, Tom

    2012-06-14

    Congressman James Clyburn visits the new employees of the Savannah River Site. These new jobs the graduates have received are a result of the Recovery Act at work. Lisa Jackson of the Environmental Protection Agency speaks about how the ARRA is in line with President Obama's vision of a better economy and cleaner environment.

  16. Congressman Clyburn Visit

    SciTech Connect

    Cody, Tom

    2010-01-01

    Congressman James Clyburn visits the new employees of the Savannah River Site. These new jobs the graduates have received are a result of the Recovery Act at work. Lisa Jackson of the Environmental Protection Agency speaks about how the ARRA is in line with President Obama's vision of a better economy and cleaner environment.

  17. Early Regulatory Engagement for Successful Site Remediation: the UK Experience - 13173

    SciTech Connect

    Maitland, R.P.; Senior, D.

    2013-07-01

    The Office for Nuclear Regulation (ONR) is an independent safety, security and transport regulator of the UK nuclear industry. ONR regulates all civil nuclear reactor power stations, fuel manufacture, enrichment, spent fuel reprocessing, most defence sites and installations that store and process legacy spent fuel and radioactive waste. The responsibility for funding and strategic direction of decommissioning and radioactive waste management of state owned legacy sites has rested solely with the Nuclear Decommissioning Authority (NDA) since 2005. A key component of NDA's mandate was to encourage new strategic approaches and innovation to dealing with the UK's waste legacy and which deliver value-for-money to the UK taxpayer. ONR, as an agency of the Health and Safety Executive, is entirely independent of NDA and regulates all prescribed activities on NDA's sites. NDA's competition of site management and closure contracts has attracted significant international interest and the formation of consortia comprised of major British, US, French and Swedish organizations bidding for those contracts. The prominence of US organizations in each of those consortia reflects the scale and breadth of existing waste management and D and D projects in the US. This paper will articulate, in broad terms, the challenges faced by international organizations seeking to employ 'off-the-shelf' technology and D and D techniques, successfully employed elsewhere, into the UK regulatory context. The predominantly 'goal-setting' regulatory framework in the UK does not generally prescribe a minimum standard to which a licensee must adhere. The legal onus on licensees in the UK is to demonstrate, whatever technology is selected, that in its applications, risks are reduced 'So Far As Is Reasonably Practicable' or 'SFAIRP'. By the nature of its role, ONR adopts a conservative approach to regulation; however ONR also recognises that in the decommissioning (and ultimately the site closure) domain

  18. Proceedings of the scientific visit on crystalline rock repository development.

    SciTech Connect

    Mariner, Paul E.; Hardin, Ernest L.; Miksova, Jitka

    2013-02-01

    A scientific visit on Crystalline Rock Repository Development was held in the Czech Republic on September 24-27, 2012. The visit was hosted by the Czech Radioactive Waste Repository Authority (RAWRA), co-hosted by Sandia National Laboratories (SNL), and supported by the International Atomic Energy Agency (IAEA). The purpose of the visit was to promote technical information exchange between participants from countries engaged in the investigation and exploration of crystalline rock for the eventual construction of nuclear waste repositories. The visit was designed especially for participants of countries that have recently commenced (or recommenced) national repository programmes in crystalline host rock formations. Discussion topics included repository programme development, site screening and selection, site characterization, disposal concepts in crystalline host rock, regulatory frameworks, and safety assessment methodology. Interest was surveyed in establishing a %E2%80%9Cclub,%E2%80%9D the mission of which would be to identify and address the various technical challenges that confront the disposal of radioactive waste in crystalline rock environments. The idea of a second scientific visit to be held one year later in another host country received popular support. The visit concluded with a trip to the countryside south of Prague where participants were treated to a tour of the laboratory and underground facilities of the Josef Regional Underground Research Centre.

  19. Identification of the binding sites of regulatory proteins in bacterial genomes

    PubMed Central

    Li, Hao; Rhodius, Virgil; Gross, Carol; Siggia, Eric D.

    2002-01-01

    We present an algorithm that extracts the binding sites (represented by position-specific weight matrices) for many different transcription factors from the regulatory regions of a genome, without the need for delineating groups of coregulated genes. The algorithm uses the fact that many DNA-binding proteins in bacteria bind to a bipartite motif with two short segments more conserved than the intervening region. It identifies all statistically significant patterns of the form W1NxW2, where W1 and W2 are two short oligonucleotides separated by x arbitrary bases, and groups them into clusters of similar patterns. These clusters are then used to derive quantitative recognition profiles of putative regulatory proteins. For a given cluster, the algorithm finds the matching sequences plus the flanking regions in the genome and performs a multiple sequence alignment to derive position-specific weight matrices. We have analyzed the Escherichia coli genome with this algorithm and found ≈1,500 significant patterns, which give rise to ≈160 distinct position-specific weight matrices. A fraction of these matrices match the binding sites of one-third of the ≈60 characterized transcription factors with high statistical significance. Many of the remaining matrices are likely to describe binding sites and regulons of uncharacterized transcription factors. The significance of these matrices was evaluated by their specificity, the location of the predicted sites, and the biological functions of the corresponding regulons, allowing us to suggest putative regulatory functions. The algorithm is efficient for analyzing newly sequenced bacterial genomes for which little is known about transcriptional regulation. PMID:12181488

  20. Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types.

    PubMed

    Kaiser, Vera B; Taylor, Martin S; Semple, Colin A

    2016-08-01

    Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression. Here, we comprehensively characterize the mutational profiles of diverse transcription factor binding sites (TFBSs) across 1,574 completely sequenced cancer genomes encompassing 11 tumour types. We assess the relative rates and impact of the mutational burden at the binding sites of 81 transcription factors (TFs), by comparing the abundance and patterns of single base substitutions within putatively functional binding sites to control sites with matched sequence composition. There is a strong (1.43-fold) and significant excess of mutations at functional binding sites across TFs, and the mutations that accumulate in cancers are typically more disruptive than variants tolerated in extant human populations at the same sites. CTCF binding sites suffer an exceptionally high mutational load in cancer (3.31-fold excess) relative to control sites, and we demonstrate for the first time that this effect is seen in essentially all cancer types with sufficient data. The sub-set of CTCF sites involved in higher order chromatin structures has the highest mutational burden, suggesting a widespread breakdown of chromatin organization. However, we find no evidence for selection driving these distinctive patterns of mutation. The mutational load at CTCF-binding sites is substantially determined by replication timing and the mutational signature of the tumor in question, suggesting that selectively neutral processes underlie the unusual mutation patterns. Pervasive hyper-mutation within transcription factor binding sites rewires the regulatory landscape of the cancer genome, but it is dominated by mutational processes rather than selection. PMID:27490693

  1. Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types

    PubMed Central

    Semple, Colin A.

    2016-01-01

    Disruption of gene regulation is known to play major roles in carcinogenesis and tumour progression. Here, we comprehensively characterize the mutational profiles of diverse transcription factor binding sites (TFBSs) across 1,574 completely sequenced cancer genomes encompassing 11 tumour types. We assess the relative rates and impact of the mutational burden at the binding sites of 81 transcription factors (TFs), by comparing the abundance and patterns of single base substitutions within putatively functional binding sites to control sites with matched sequence composition. There is a strong (1.43-fold) and significant excess of mutations at functional binding sites across TFs, and the mutations that accumulate in cancers are typically more disruptive than variants tolerated in extant human populations at the same sites. CTCF binding sites suffer an exceptionally high mutational load in cancer (3.31-fold excess) relative to control sites, and we demonstrate for the first time that this effect is seen in essentially all cancer types with sufficient data. The sub-set of CTCF sites involved in higher order chromatin structures has the highest mutational burden, suggesting a widespread breakdown of chromatin organization. However, we find no evidence for selection driving these distinctive patterns of mutation. The mutational load at CTCF-binding sites is substantially determined by replication timing and the mutational signature of the tumor in question, suggesting that selectively neutral processes underlie the unusual mutation patterns. Pervasive hyper-mutation within transcription factor binding sites rewires the regulatory landscape of the cancer genome, but it is dominated by mutational processes rather than selection. PMID:27490693

  2. Regulatory Oversight of the Legacy Gunner Uranium Mine and Mill Site in Northern Saskatchewan, Canada - 13434

    SciTech Connect

    Stenson, Ron; Howard, Don

    2013-07-01

    As Canada's nuclear regulator, the Canadian Nuclear Safety Commission (CNSC) is responsible for licensing all aspects of uranium mining, including remediation activities at legacy sites. Since these sites already existed when the current legislation came into force in 2000, and the previous legislation did not apply, they present a special case. The Nuclear Safety and Control Act (NSCA), was written with cradle-to- grave oversight in mind. Applying the NSCA at the end of a 'facilities' life-cycle poses some challenges to both the regulator and the proponent. When the proponent is the public sector, even more challenges can present themselves. Although the licensing process for legacy sites is no different than for any other CNSC license, assuring regulatory compliance can be more complicated. To demonstrate how the CNSC has approached the oversight of legacy sites the history of the Commission's involvement with the Gunnar uranium mine and mill site provides a good case study. The lessons learned from the CNSC's experience regulating the Gunnar site will benefit those in the future who will need to regulate legacy sites under existing or new legislation. (authors)

  3. Case Study of Home-School Visits

    ERIC Educational Resources Information Center

    Aguerrebere, Yolanda

    2009-01-01

    This case study evaluated one site of a California teacher home visit program. Home visits have been an important means of connecting families and schooling. In 1999, California inaugurated a statewide home visit program to promote effective partnership between home and school for low-achieving schools. At this site, families in 3 kindergarten…

  4. Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity.

    PubMed

    Rowan, Sheldon; Siggers, Trevor; Lachke, Salil A; Yue, Yingzi; Bulyk, Martha L; Maas, Richard L

    2010-05-15

    How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal development is not well understood. Pax6 is a dosage-sensitive gene essential for eye development. Here, we identify the Prep1 (pKnox1) transcription factor as a critical dose-dependent upstream regulator of Pax6 expression during lens formation. We show that Prep1 activates the Pax6 lens enhancer by binding to two phylogenetically conserved lower-affinity DNA-binding sites. Finally, we describe a mechanism whereby Pax6 levels are determined by transcriptional synergy of Prep1 bound to the two sites, while timing of enhancer activation is determined by binding site affinity. PMID:20413611

  5. Sequence of the phosphothreonyl regulatory site peptide from inactive maize leaf pyruvate, orthophosphate dikinase

    SciTech Connect

    Roeske, C.A.; Kutny, R.M.; Budde, R.J.A.; Chollet, R.

    1988-05-15

    The regulatory site peptide sequence of phosphorylated inactive pyruvate, orthophosphate dikinase from maize leaf tissue was determined by automated Edman degradation analysis of /sup 32/P-labeled peptides purified by reversed-phase high performance liquid chromatography. The overlapping phosphopeptides were products of a digestion of the (..beta..-/sup 32/P)ADP-inactivated dikinase with either trypsin or Pronase E. The sequence is Thr-Glu-Arg-Gly-Gly-Met-Thr(P)-Ser-His-Ala-Ala-Val-Val-Ala-Arg. The phosphothreonine residue, which appeared as either an anomalous proline or an unidentifiable phenylthiohydantoin derivative during sequencing, was verified by two-dimensional phosphoamino acid analysis of the phosphopeptides and by resequencing the tryptic peptide after dephosphorylation with exogenous alkaline phosphatase. This sequence, starting at position 4, is completely homologous to the previously published sequence of the tryptic dodecapeptide harboring the catalytically essential (phospho)histidyl residue in the active-site domain of the dikinase from the nonphotosynthetic bacterium, Bacteroides symbiosus. These comparative results indicate that the regulatory phosphothreonine causing complete inactivation of maize leaf dikinase is separated from the critical active-site (phospho)histidine by just one intervening residue in the primary sequence.

  6. Early Site Permit Demonstration Program: Regulatory criteria evaluation report. Appendix E

    SciTech Connect

    Not Available

    1993-03-01

    The primary objective of the Early Site Permit Demonstration Program (ESPDP) is to demonstrate successfully the use of 10CFR52 to obtain ESPs for one or more US sites for one (or more) ALWR nuclear power plants. It is anticipated that preparation of the ESP application and interaction with NRC during the application review process will result not only in an ESP for the applicant(s) but also in the development of criteria and definition of processes, setting the precedent that facilitates ESPs for subsequent ESP applications. Because siting regulatory processes and acceptance criteria are contained in over 100 separate documents, comprehensive licensing and technical reviews were performed to establish whether the requirements and documentation are self-consistent, whether the acceptance criteria are sufficiently well-defined and clear, and whether the licensing process leading to the issuance of an ESP is unambiguously specified. This document provides Appendix E which contains a population density report. In this study the proposed US Nuclear Regulatory Commission (NRC) population density and exclusion zone size criteria were evaluated for their potential effectiveness to meet the quantitative public health and safety objectives associated with the NRC Safety Goal Policy. In addition, the individual and societal risks from postulated accidents (based on NUREG-1150 methods) were determined and compared to the quantitative prompt and latent health objective of the safety goal policy.

  7. Radio-ecological characterization and radiological assessment in support of regulatory supervision of legacy sites in northwest Russia.

    PubMed

    Sneve, M K; Kiselev, M; Shandala, N K

    2014-05-01

    The Norwegian Radiation Protection Authority has been implementing a regulatory cooperation program in the Russian Federation for over 10 years, as part of the Norwegian government's Plan of Action for enhancing nuclear and radiation safety in northwest Russia. The overall long-term objective has been the enhancement of safety culture and includes a special focus on regulatory supervision of nuclear legacy sites. The initial project outputs included appropriate regulatory threat assessments, to determine the hazardous situations and activities which are most in need of enhanced regulatory supervision. In turn, this has led to the development of new and updated norms and standards, and related regulatory procedures, necessary to address the often abnormal conditions at legacy sites. This paper presents the experience gained within the above program with regard to radio-ecological characterization of Sites of Temporary Storage for spent nuclear fuel and radioactive waste at Andreeva Bay and Gremikha in the Kola Peninsula in northwest Russia. Such characterization is necessary to support assessments of the current radiological situation and to support prospective assessments of its evolution. Both types of assessments contribute to regulatory supervision of the sites. Accordingly, they include assessments to support development of regulatory standards and guidance concerning: control of radiation exposures to workers during remediation operations; emergency preparedness and response; planned radionuclide releases to the environment; development of site restoration plans, and waste treatment and disposal. Examples of characterization work are presented which relate to terrestrial and marine environments at Andreeva Bay. The use of this data in assessments is illustrated by means of the visualization and assessment tool (DATAMAP) developed as part of the regulatory cooperation program, specifically to help control radiation exposure in operations and to support

  8. Russian Experience in the Regulatory Supervision of the Uranium Legacy Sites - 12441

    SciTech Connect

    Kiselev, M.F.; Romanov, V.V.; Shandala, N.K.; Titov, A.V.; Kiselev, S.M.; Seregin, V.A.; Metlyaev, E.G.; Novikova, N.; Khokhlova, E.A.

    2012-07-01

    Management of the uranium legacy is accompanied with environmental impact intensity of which depends on the amount of the waste generated, the extent of that waste localization and environmental spreading. The question is: how hazardous is such impact on the environment and human health? The criterion for safety assurance is adequate regulation of the uranium legacy. Since the establishment of the uranium industry, the well done regulatory system operates in the FMBA of Russia. Such system covers inter alia, the uranium legacy. This system includes the extent laboratory network of independent control and supervision, scientific researches, regulative practices. The current Russian normative and legal basis of the regulation and its application practice has a number of problems relating to the uranium legacy, connected firstly with the environmental remediation. To improve the regulatory system, the urgent tasks are: -To introduce the existing exposure situation into the national laws and standards in compliance with the ICRP system. - To develop criteria for site remediation and return, by stages, to uncontrolled uses. The similar criteria have been developed within the Russian-Norwegian cooperation for the purpose of remediation of the sites for temporary storage of SNF and RW. - To consider possibilities and methods of optimization for the remediation strategies under development. - To separate the special category - RW resulted from uranium ore mining and dressing. The current Russian RW classification is based on the waste subdivision in terms of the specific activities. Having in mind the new RW-specific law, we receive the opportunity to separate some special category - RW originated from the uranium mining and milling. Introduction of such category can simplify significantly the situation with management of waste of uranium mining and milling processes. Such approach is implemented in many countries and approved by IAEA. The category of 'RW originated from

  9. Genome-wide de novo prediction of cis-regulatory binding sites in prokaryotes

    PubMed Central

    Zhang, Shaoqiang; Xu, Minli; Su, Zhengchang

    2009-01-01

    Although cis-regulatory binding sites (CRBSs) are at least as important as the coding sequences in a genome, our general understanding of them in most sequenced genomes is very limited due to the lack of efficient and accurate experimental and computational methods for their characterization, which has largely hindered our understanding of many important biological processes. In this article, we describe a novel algorithm for genome-wide de novo prediction of CRBSs with high accuracy. We designed our algorithm to circumvent three identified difficulties for CRBS prediction using comparative genomics principles based on a new method for the selection of reference genomes, a new metric for measuring the similarity of CRBSs, and a new graph clustering procedure. When operon structures are correctly predicted, our algorithm can predict 81% of known individual binding sites belonging to 94% of known cis-regulatory motifs in the Escherichia coli K12 genome, while achieving high prediction specificity. Our algorithm has also achieved similar prediction accuracy in the Bacillus subtilis genome, suggesting that it is very robust, and thus can be applied to any other sequenced prokaryotic genome. When compared with the prior state-of-the-art algorithms, our algorithm outperforms them in both prediction sensitivity and specificity. PMID:19383880

  10. Building a dictionary for genomes: Identification of presumptive regulatory sites by statistical analysis

    PubMed Central

    Bussemaker, Harmen J.; Li, Hao; Siggia, Eric D.

    2000-01-01

    The availability of complete genome sequences and mRNA expression data for all genes creates new opportunities and challenges for identifying DNA sequence motifs that control gene expression. An algorithm, “MobyDick,” is presented that decomposes a set of DNA sequences into the most probable dictionary of motifs or words. This method is applicable to any set of DNA sequences: for example, all upstream regions in a genome or all genes expressed under certain conditions. Identification of words is based on a probabilistic segmentation model in which the significance of longer words is deduced from the frequency of shorter ones of various lengths, eliminating the need for a separate set of reference data to define probabilities. We have built a dictionary with 1,200 words for the 6,000 upstream regulatory regions in the yeast genome; the 500 most significant words (some with as few as 10 copies in all of the upstream regions) match 114 of 443 experimentally determined sites (a significance level of 18 standard deviations). When analyzing all of the genes up-regulated during sporulation as a group, we find many motifs in addition to the few previously identified by analyzing the subclusters individually to the expression subclusters. Applying MobyDick to the genes derepressed when the general repressor Tup1 is deleted, we find known as well as putative binding sites for its regulatory partners. PMID:10944202

  11. Regulatory site of inorganic pyrophosphatase. Nonhyperbolic kinetics of enzymatic reaction at low substrate concentrations

    SciTech Connect

    Pavlov, A.R.; Baikov, A.A.; Avaeva, S.M.

    1986-08-10

    The initial rate of PP/sub 1/ hydrolysis by inorganic pyrophosphatase from baker's yeast was analyzed as a function of the concentrations of the Mg-PP/sub 1/ complex (substrate) and Mg/sup 2 +/ ions (activator) at substrate concentrations down to 0.1 ..mu..M. Lineweaver-Burk plots for the enzyme in equilibrium with Mg/sup 2 +/ ions were nonlinear at fixed Mg/sup 2 +/ concentrations, which cannot be explained within the framework of previously proposed models of the reaction. The nonlinearity is retained for the monomeric form of the enzyme and indicates that the enzyme has a regulatory site capable of tightly binding free PP/sub 1/ (K/sub d/ approx. 0.02 ..mu..M). A new model of the reaction is proposed in which Mg-PP/sub 1/, PP/sub 1/, and Mg/sup 2 +/ are bound to the enzyme in random order and filling of the regulatory site decreases the dissociation constant of the protein-Mg complex from 4.7 to 0.025 mM. It was concluded that PP/sub 1/ and Mg/sup 2 +/ are regulators of pyrophosphatase activity under physiological conditions.

  12. Selective small molecule inhibitor of the Mycobacterium tuberculosis fumarate hydratase reveals an allosteric regulatory site

    PubMed Central

    Kasbekar, Monica; Fischer, Gerhard; Mott, Bryan T.; Yasgar, Adam; Hyvönen, Marko; Boshoff, Helena I. M.; Abell, Chris; Barry, Clifton E.; Thomas, Craig J.

    2016-01-01

    Enzymes in essential metabolic pathways are attractive targets for the treatment of bacterial diseases, but in many cases, the presence of homologous human enzymes makes them impractical candidates for drug development. Fumarate hydratase, an essential enzyme in the tricarboxylic acid (TCA) cycle, has been identified as one such potential therapeutic target in tuberculosis. We report the discovery of the first small molecule inhibitor, to our knowledge, of the Mycobacterium tuberculosis fumarate hydratase. A crystal structure at 2.0-Å resolution of the compound in complex with the protein establishes the existence of a previously unidentified allosteric regulatory site. This allosteric site allows for selective inhibition with respect to the homologous human enzyme. We observe a unique binding mode in which two inhibitor molecules interact within the allosteric site, driving significant conformational changes that preclude simultaneous substrate and inhibitor binding. Our results demonstrate the selective inhibition of a highly conserved metabolic enzyme that contains identical active site residues in both the host and the pathogen. PMID:27325754

  13. Selective small molecule inhibitor of the Mycobacterium tuberculosis fumarate hydratase reveals an allosteric regulatory site.

    PubMed

    Kasbekar, Monica; Fischer, Gerhard; Mott, Bryan T; Yasgar, Adam; Hyvönen, Marko; Boshoff, Helena I M; Abell, Chris; Barry, Clifton E; Thomas, Craig J

    2016-07-01

    Enzymes in essential metabolic pathways are attractive targets for the treatment of bacterial diseases, but in many cases, the presence of homologous human enzymes makes them impractical candidates for drug development. Fumarate hydratase, an essential enzyme in the tricarboxylic acid (TCA) cycle, has been identified as one such potential therapeutic target in tuberculosis. We report the discovery of the first small molecule inhibitor, to our knowledge, of the Mycobacterium tuberculosis fumarate hydratase. A crystal structure at 2.0-Å resolution of the compound in complex with the protein establishes the existence of a previously unidentified allosteric regulatory site. This allosteric site allows for selective inhibition with respect to the homologous human enzyme. We observe a unique binding mode in which two inhibitor molecules interact within the allosteric site, driving significant conformational changes that preclude simultaneous substrate and inhibitor binding. Our results demonstrate the selective inhibition of a highly conserved metabolic enzyme that contains identical active site residues in both the host and the pathogen. PMID:27325754

  14. Determining Virtual Environment "Fit": The Relationship Between Navigation Style in a Virtual Field Trip, Student Self-Reported Desire to Visit the Field Trip Site in the Real World, and the Purposes of Science Education

    NASA Astrophysics Data System (ADS)

    Tutwiler, M. Shane; Lin, Ming-Chao; Chang, Chun-Yen

    2013-06-01

    In this study, a follow-up analysis of the data reported in Lin et al. (Learn Media Technol. doi: 10.1080/17439884.2011.629660, 2011), we investigated the relationship between student use of a virtual field trip (VFT) system and the probability of students reporting wanting to visit the national park site upon which the VFT was modeled, controlling for content knowledge and prior visits to the park. Students who were able to navigate the VFT in teams were more likely than their peers who had the system demonstrated by a teacher to want to visit the national park. In addition, students with higher pre-intervention content knowledge were more likely to want to visit the national park than their peers with lower pre-test scores, in both the teacher demonstration and student co-navigation conditions.

  15. Regulatory Closure Options for the Residue in the Hanford Site Single-Shell Tanks

    SciTech Connect

    Cochran, J.R. Shyr, L.J.

    1998-10-05

    Liquid, mixed, high-level radioactive waste (HLW) has been stored in 149 single-shell tanks (SSTS) located in tank farms on the U.S. Department of Energy's (DOE's) Hanford Site. The DOE is developing technologies to retrieve as much remaining HLW as technically possible prior to physically closing the tank farms. In support of the Hanford Tanks Initiative, Sandia National Laboratories has addressed the requirements for the regulatory closure of the radioactive component of any SST residue that may remain after physical closure. There is significant uncertainty about the end state of each of the 149 SSTS; that is, the nature and amount of wastes remaining in the SSTS after retrieval is uncertain. As a means of proceeding in the face of these uncertainties, this report links possible end-states with associated closure options. Requirements for disposal of HLW and low-level radioactive waste (LLW) are reviewed in detail. Incidental waste, which is radioactive waste produced incidental to the further processing of HLW, is then discussed. If the low activity waste (LAW) fraction from the further processing of HLW is determined to be incidental waste, then DOE can dispose of that incidental waste onsite without a license from the U.S. Nuclear Regulatory Commissions (NRC). The NRC has proposed three Incidental Waste Criteria for determining if a LAW fraction is incidental waste. One of the three Criteria is that the LAW fraction should not exceed the NRC's Class C limits.

  16. Identification of Ser-543 as the major regulatory phosphorylation site in spinach leaf nitrate reductase

    NASA Technical Reports Server (NTRS)

    Bachmann, M.; Shiraishi, N.; Campbell, W. H.; Yoo, B. C.; Harmon, A. C.; Huber, S. C.; Davies, E. (Principal Investigator)

    1996-01-01

    Spinach leaf NADH:nitrate reductase (NR) responds to light/dark signals and photosynthetic activity in part as a result of rapid regulation by reversible protein phosphorylation. We have identified the major regulatory phosphorylation site as Ser-543, which is located in the hinge 1 region connecting the cytochrome b domain with the molybdenum-pterin cofactor binding domain of NR, using recombinant NR fragments containing or lacking the phosphorylation site sequence. Studies with NR partial reactions indicated that the block in electron flow caused by phosphorylation also could be localized to the hinge 1 region. A synthetic peptide (NR6) based on the phosphorylation site sequence was phosphorylated readily by NR kinase (NRk) in vitro. NR6 kinase activity tracked the ATP-dependent inactivation of NR during several chromatographic steps and completely inhibited inactivation/phosphorylation of native NR in vitro. Two forms of NRk were resolved by using anion exchange chromatography. Studies with synthetic peptide analogs indicated that both forms of NRk had similar specificity determinants, requiring a basic residue at P-3 (i.e., three amino acids N-terminal to the phosphorylated serine) and a hydrophobic residue at P-5. Both forms are strictly calcium dependent but belong to distinct families of protein kinases because they are distinct immunochemically.

  17. Making Child Care Centers SAFER: A Non-Regulatory Approach to Improving Child Care Center Siting

    PubMed Central

    Somers, Tarah S; Harvey, Margaret L.; Rusnak, Sharee Major

    2011-01-01

    Licensed child care centers are generally considered to be safe because they are required to meet state licensing regulations. As part of their licensing requirements, many states inspect child care centers and include an assessment of the health and safety of the facility to look for hazardous conditions or practices that may harm children. However, most states do not require an environmental assessment of the child care center building or land to prevent a center from being placed on, next to, or inside contaminated buildings. Having worked on several sites where child care centers were affected by environmental contaminants, the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry (ATSDR) endeavor to raise awareness of this issue. One of ATSDR's partner states, Connecticut, took a proactive, non-regulatory approach to the issue with the development its Child Day Care Screening Assessment for Environmental Risk Program. PMID:21563710

  18. Regulatory requirements and tools for environmental assessment of hazardous wastes: Understanding tribal and stakeholder concerns using Department of Energy sites

    PubMed Central

    Burger, Joanna; Powers, Charles; Gochfeld, Michael

    2014-01-01

    Many US governmental and Tribal Nation agencies, as well as state and local entities, deal with hazardous wastes within regulatory frameworks that require specific environmental assessments. In this paper we use Department of Energy (DOE) sites as examples to examine the relationship between regulatory requirements and environmental assessments for hazardous waste sites and give special attention to how assessment tools differ. We consider federal laws associated with environmental protection include the National Environmental Policy Act (NEPA), the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response Compensation and Liability Act (CERCLA), as well as regulations promulgated by the Nuclear Regulatory Commission, Tribal Nations and state agencies. These regulatory regimes require different types of environmental assessments and remedial investigations, dose assessments and contaminant pathways. The DOE case studies illustrate the following points: 1) there is often understandable confusion about what regulatory requirements apply to the site resources, and what environmental assessments are required by each, 2) the messages sent on site safety issued by different regulatory agencies are sometimes contradictory or confusing (e.g. Oak Ridge Reservation), 3) the regulatory frameworks being used to examine the same question can be different, leading to different conclusions (e.g. Brookhaven National Laboratory), 4) computer models used in support of groundwater models or risk assessments are not necessarily successful in convincing Native Americans and others that there is no possibility of risk from contaminants (e.g. Amchitka Island), 5) when given the opportunity to choose between relying on a screening risk assessments or waiting for a full site-specific analysis of contaminants in biota, the screening risk assessment option is rarely selected (e.g. Amchitka, Hanford Site), and finally, 6) there needs to be agreement on whether

  19. Regulatory requirements and tools for environmental assessment of hazardous wastes: understanding tribal and stakeholder concerns using Department of Energy sites.

    PubMed

    Burger, Joanna; Powers, Charles; Gochfeld, Michael

    2010-12-01

    Many US governmental and Tribal Nation agencies, as well as state and local entities, deal with hazardous wastes within regulatory frameworks that require specific environmental assessments. In this paper we use Department of Energy (DOE) sites as examples to examine the relationship between regulatory requirements and environmental assessments for hazardous waste sites and give special attention to how assessment tools differ. We consider federal laws associated with environmental protection include the National Environmental Policy Act (NEPA), the Resource Conservation and Recovery Act (RCRA), the Comprehensive Environmental Response Compensation and Liability Act (CERCLA), as well as regulations promulgated by the Nuclear Regulatory Commission, Tribal Nations and state agencies. These regulatory regimes require different types of environmental assessments and remedial investigations, dose assessments and contaminant pathways. The DOE case studies illustrate the following points: 1) there is often understandable confusion about what regulatory requirements apply to the site resources, and what environmental assessments are required by each, 2) the messages sent on site safety issued by different regulatory agencies are sometimes contradictory or confusing (e.g. Oak Ridge Reservation), 3) the regulatory frameworks being used to examine the same question can be different, leading to different conclusions (e.g. Brookhaven National Laboratory), 4) computer models used in support of groundwater models or risk assessments are not necessarily successful in convincing Native Americans and others that there is no possibility of risk from contaminants (e.g. Amchitka Island), 5) when given the opportunity to choose between relying on a screening risk assessments or waiting for a full site-specific analysis of contaminants in biota, the screening risk assessment option is rarely selected (e.g. Amchitka, Hanford Site), and finally, 6) there needs to be agreement on whether

  20. Site-specific silencing of regulatory elements as a mechanism of X inactivation.

    PubMed

    Calabrese, J Mauro; Sun, Wei; Song, Lingyun; Mugford, Joshua W; Williams, Lucy; Yee, Della; Starmer, Joshua; Mieczkowski, Piotr; Crawford, Gregory E; Magnuson, Terry

    2012-11-21

    The inactive X chromosome's (Xi) physical territory is microscopically devoid of transcriptional hallmarks and enriched in silencing-associated modifications. How these microscopic signatures relate to specific Xi sequences is unknown. Therefore, we profiled Xi gene expression and chromatin states at high resolution via allele-specific sequencing in mouse trophoblast stem cells. Most notably, X-inactivated transcription start sites harbored distinct epigenetic signatures relative to surrounding Xi DNA. These sites displayed H3-lysine27-trimethylation enrichment and DNaseI hypersensitivity, similar to autosomal Polycomb targets, yet excluded Pol II and other transcriptional hallmarks, similar to nontranscribed genes. CTCF bound X-inactivated and escaping genes, irrespective of measured chromatin boundaries. Escape from X inactivation occurred within, and X inactivation was maintained exterior to, the area encompassed by Xist in cells subject to imprinted and random X inactivation. The data support a model whereby inactivation of specific regulatory elements, rather than a simple chromosome-wide separation from transcription machinery, governs gene silencing over the Xi. PMID:23178118

  1. Site-specific silencing of regulatory elements as a mechanism of X-inactivation

    PubMed Central

    Calabrese, J. Mauro; Sun, Wei; Song, Lingyun; Mugford, Joshua W.; Williams, Lucy; Yee, Della; Starmer, Joshua; Mieczkowski, Piotr; Crawford, Gregory E.; Magnuson, Terry

    2012-01-01

    The inactive X chromosome’s (Xi) physical territory is microscopically devoid of transcriptional hallmarks and enriched in silencing-associated modifications. How these microscopic signatures relate to specific Xi sequence is unknown. Therefore, we profiled Xi gene expression and chromatin states at high resolution via allele-specific sequencing in mouse trophoblast stem cells. Most notably, X-inactivated transcription start sites harbored distinct epigenetic signatures relative to surrounding Xi DNA. These sites displayed H3-lysine27-trimethylation enrichment and DNaseI hypersensitivity, similar to autosomal Polycomb targets, yet excluded Pol II and other transcriptional hallmarks, similar to non-transcribed genes. CTCF bound X-inactivated and escaping genes, irrespective of measured chromatin boundaries. Escape from X-inactivation occurred within, and X-inactivation was maintained exterior to, the area encompassed by Xist in cells subject to imprinted and random X-inactivation. The data support a model whereby inactivation of specific regulatory elements, rather than a simple chromosome-wide separation from transcription machinery, governs gene silencing over the Xi. PMID:23178118

  2. Regulatory Framework for Salt Waste Disposal and Tank Closure at the Savannah River Site - 13663

    SciTech Connect

    Thomas, Steve; Dickert, Ginger

    2013-07-01

    The end of the Cold War has left a legacy of approximately 37 million gallons of radioactive waste in the aging waste tanks at the Department of Energy's Savannah River Site (SRS). A robust program is in place to remove waste from these tanks, treat the waste to separate into a relatively small volume of high-level waste and a large volume of low-level waste, and to actively dispose of the low-level waste on-site and close the waste tanks and associated ancillary structures. To support performance-based, risk-informed decision making and to ensure compliance with all regulatory requirements, the U.S. Department of Energy (DOE) and its current and past contractors have worked closely with the South Carolina Department of Health and Environmental Control (SCDHEC), the U.S. Environmental Protection Agency (EPA) and the Nuclear Regulatory Commission (NRC) to develop and implement a framework for on-site low-level waste disposal and closure of the SRS waste tanks. The Atomic Energy Act of 1954, as amended, provides DOE the authority to manage defense-related radioactive waste. DOE Order 435.1 and its associated manual and guidance documents detail this radioactive waste management process. The DOE also has a requirement to consult with the NRC in determining that waste that formerly was classified as high-level waste can be safely managed as either low-level waste or transuranic waste. Once DOE makes a determination, NRC then has a responsibility to monitor DOE's actions in coordination with SCDHEC to ensure compliance with the Title 10 Code of Federal Regulations Part 61 (10CFR61), Subpart C performance objectives. The management of hazardous waste substances or components at SRS is regulated by SCDHEC and the EPA. The foundation for the interactions between DOE, SCDHEC and EPA is the SRS Federal Facility Agreement (FFA). Managing this array of requirements and successfully interacting with regulators, consultants and stakeholders is a challenging task but ensures

  3. Determining Virtual Environment "Fit": The Relationship between Navigation Style in a Virtual Field Trip, Student Self-Reported Desire to Visit the Field Trip Site in the Real World, and the Purposes of Science Education

    ERIC Educational Resources Information Center

    Tutwiler, M. Shane; Lin, Ming-Chao; Chang, Chun-Yen

    2013-01-01

    In this study, a follow-up analysis of the data reported in Lin et al. ("Learn Media Technol." doi: 10.1080/17439884.2011.629660 , 2011), we investigated the relationship between student use of a virtual field trip (VFT) system and the probability of students reporting wanting to visit the national park site upon which the VFT was modeled,…

  4. CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.

    PubMed

    Plasschaert, Robert N; Vigneau, Sébastien; Tempera, Italo; Gupta, Ravi; Maksimoska, Jasna; Everett, Logan; Davuluri, Ramana; Mamorstein, Ronen; Lieberman, Paul M; Schultz, David; Hannenhalli, Sridhar; Bartolomei, Marisa S

    2014-01-01

    CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF's binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site. PMID:24121688

  5. CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation

    PubMed Central

    Plasschaert, Robert N.; Vigneau, Sébastien; Tempera, Italo; Gupta, Ravi; Maksimoska, Jasna; Everett, Logan; Davuluri, Ramana; Mamorstein, Ronen; Lieberman, Paul M.; Schultz, David; Hannenhalli, Sridhar; Bartolomei, Marisa S.

    2014-01-01

    CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF’s binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18th position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site. PMID:24121688

  6. Developing a strategy and closure criteria for radioactive and mixed waste sites in the ORNL remedial action program: Regulatory interface

    SciTech Connect

    Trabalka, J.R.

    1987-09-01

    Some options for stabilization and treatment of contaminated sites can theoretically provide a once-and-for-all solution (e.g., removal or destruction of contaminants). Most realizable options, however, leave contaminants in place (in situ), potentially isolated by physical or chemical, but more typically, by hydrologic measures. As a result of the dynamic nature of the interactions between contaminants, remedial measures, and the environment, in situ stablization measures are likely to have limited life spans, and maintenance and monitoring of performance become an essential part of the scheme. The length of formal institutional control over the site and related questions about future uses of the land and waters are of paramount importance. Unique features of the ORNL site and environs appear to be key ingredients in achieving the very long term institutional control necessary for successful financing and implementation of in situ stabilization. Some formal regulatory interface is necessary to ensure that regulatory limitations and new guidance which can affect planning and implementation of the ORNL Remedial Action Program are communicated to ORNL staff and potential technical and financial limitations which can affect schedules or alternatives for achievement of long-term site stabilization and the capability to meet environmental regulations are provided to regulatory bodies as early as possible. Such an interface should allow decisions on closure criteria to be based primarily on technical merit and protection of human health and the environment. A plan for interfacing with federal and state regulatory authorities is described. 93 refs., 1 fig., 4 tabs.

  7. Allosteric Coupling between the Intracellular Coupling Helix 4 and Regulatory Sites of the First Nucleotide-binding Domain of CFTR

    PubMed Central

    Dawson, Jennifer E.; Farber, Patrick J.; Forman-Kay, Julie D.

    2013-01-01

    Cystic fibrosis is caused by mutations in CFTR (cystic fibrosis transmembrane conductance regulator), leading to folding and processing defects and to chloride channel gating misfunction. CFTR is regulated by ATP binding to its cytoplasmic nucleotide-binding domains, NBD1 and NBD2, and by phosphorylation of the NBD1 regulatory insert (RI) and the regulatory extension (RE)/R region. These regulatory effects are transmitted to the rest of the channel via NBD interactions with intracellular domain coupling helices (CL), particularly CL4. Using a sensitive method for detecting inter-residue correlations between chemical shift changes in NMR spectra, an allosteric network was revealed within NBD1, with a construct lacking RI. The CL4-binding site couples to the RI-deletion site and the C-terminal residues of NBD1 that precede the R region in full-length CFTR. Titration of CL4 peptide into NBD1 perturbs the conformational ensemble in these sites with similar titration patterns observed in F508del, the major CF-causing mutant, and in suppressor mutants F494N, V510D and Q637R NBD1, as well as in a CL4-NBD1 fusion construct. Reciprocally, the C-terminal mutation, Q637R, perturbs dynamics in these three sites. This allosteric network suggests a mechanism synthesizing diverse regulatory NBD1 interactions and provides biophysical evidence for the allosteric coupling required for CFTR function. PMID:24058550

  8. Delivering Regulatory Consents for Decommissioning and Restoration of the Dounreay Nuclear Licensed Site

    SciTech Connect

    Crawford, R.W.; Zyda, P.W.

    2006-07-01

    On behalf of the Nuclear Decommissioning Authority (NDA) the United Kingdom Atomic Energy Authority (UKAEA) has implemented a strategy to translate the near-term Dounreay restoration plan into a suite of land use documents designed to deliver the necessary planning consents to decommission and restore the Dounreay Nuclear Licensed Site. The legal consents and authorizations required to enable UKAEA to commence major projects and progress the decommissioning of the site are highlighted along with the measures taken to secure political, public and regulatory acceptance at the earliest opportunity. The approach taken by UKAEA is explained, focusing particularly on the critical need to secure planning permission and stakeholder approval well before the onset of construction works. The intention is to realize the benefits of forging a close working relationship with the land use regulator, The Highland Council. UKAEA has taken an approach to suitably inform the planning authority, in particular, the production of the Dounreay Planning Framework (DPF) document. This paper describes the role and need for the DPF, focusing on the key purpose of amending the local development plan to secure supportive planning policies and to set a land use context for the subsequent site decommissioning and restoration. This also has the advantage of securing public acceptance through an established legal process. Strategic milestones subsequent to the Highland Council's adoption of the DPF are highlighted, including the submission of phased planning applications and compliance with environmental legislation generally. The paper describes and underscores the need for early engagement of other regulators in the planning process such as the Scottish Environment Protection Agency (SEPA), and the safety regulator, the Nuclear Installations Inspectorate (NII). It describes the linkages amongst land use consents, Best Practicable Environmental Options (BPEO), radioactive substances

  9. Evaluation of inhaler handling-errors, inhaler perception and preference with Spiromax, Easyhaler and Turbuhaler devices among healthy Finnish volunteers: a single site, single visit crossover study (Finhaler)

    PubMed Central

    Sandler, Niklas; Holländer, Jenny; Långström, Disa; Santtila, Pekka; Saukkonen, Anni; Torvinen, Saku

    2016-01-01

    Introduction Correct inhaler technique and device preference are positively correlated with improved adherence and clinical outcomes. This study was designed to investigate inhaler technique mastery and device preference for three different dry powder inhalers, Spiromax, Easyhaler and Turbuhaler. Methods This was a single site, single visit, crossover study assessing device mastery, handling errors and preference using empty Spiromax, Easyhaler and Turbuhaler devices in healthy adult Finnish volunteers. Inhaler naïve adult participants were observed by healthcare professionals (HCPs) to evaluate the proportion of participants achieving device mastery (defined as an absence of HCP observed errors) using a three-step approach: (1) intuitive use (with no instructions), (2) after reading the patient information leaflet and (3) after HCP instruction. HCPs monitored and recorded errors based on device-specific handling error checklists. At the end of the study, participants completed a device preference questionnaire and rated their satisfaction with the three devices. Results Spiromax was correctly used by 37.5% and 93.3% of participants in steps 1 and 2, respectively, compared with 0% and 58.3% with Easyhaler, and 9.2% and 76.7% with Turbuhaler. All three devices showed high mastery (>95%) in step 3. The most common error reported with Spiromax was related to the orientation of the device. Not shaking the device was the most common error with Easyhaler. Errors in priming the device were the most common with Turbuhaler. Spiromax, Easyhaler and Turbuhaler were rated as the ‘easiest device to use’ by 73.1%, 12.6% and 14.3% of participants, respectively. The HCP instructions clearly improved the use of all devices. Conclusion Higher levels of device mastery, including intuitive/ease of use, were reported by naïve users when using Spiromax compared with Easyhaler and Turbuhaler. PMID:27026804

  10. RFI to CMS: An Approach to Regulatory Acceptance of Site Remediation Technologies

    NASA Technical Reports Server (NTRS)

    Rowland, Martin A.

    2001-01-01

    Lockheed Martin made a smooth transition from RCRA Facility Investigation (RFI) at the National Aeronautics and Space Administrations'(NASA) Michoud Assembly Facility (MA-F) to its Corrective Measures Study (CMS) phase within the RCRA Corrective Action Process. We located trichloroethylene (TCE) contamination that resulted from the manufacture of the Apollo Program Saturn V rocket and the Space Shuttle External Tank, began the cleanup, and identified appropriate technologies for final remedies. This was accomplished by establishing a close working relationship with the state environmental regulatory agency through each step of the process, and resulted in receiving approvals for each of those steps. The agency has designated Lockheed Martin's management of the TCE-contamination at the MAF site as a model for other manufacturing sites in a similar situation. In February 1984, the Louisiana Department of Environmental Quality (LDEQ) issued a compliance order to begin the clean up of groundwater contaminated with TCE. In April 1984 Lockheed Martin began operating a groundwater recovery well to capture the TCE plume. The well not only removes contaminants, but also sustains an inward groundwater hydraulic gradient so that the potential offsite migration of the TCE plume is greatly diminished. This effort was successful, and for the agency to give orders and for a regulated industry to follow them is standard procedure, but this is a passive approach to solving environmental problems. The goal of the company thereafter was to take a leadership, proactive role and guide the MAF contamination clean up to its best conclusion at minimum time and lowest cost to NASA. To accomplish this goal, we have established a positive working relationship with LDEQ, involving them interactively in the implementation of advanced remedial activities at MAF as outlined in the following paragraphs.

  11. WarpVisit

    Energy Science and Technology Software Center (ESTSC)

    2015-06-10

    WarpVisit is an insitu simulation application that integrates the Warp laser plasma accelerator simulation framework with Visit a parallel visualization application. WarpVisit is written in python and supports interactive or live mode where user can connect to Warp with the Visit GUI and batch mode for batch for non-interactive use on high-performance computing resources.

  12. Identification of Regulatory DNA Elements Using Genome-wide Mapping of DNase I Hypersensitive Sites during Tomato Fruit Development.

    PubMed

    Qiu, Zhengkun; Li, Ren; Zhang, Shuaibin; Wang, Ketao; Xu, Meng; Li, Jiayang; Du, Yongchen; Yu, Hong; Cui, Xia

    2016-08-01

    Development and ripening of tomato fruit are precisely controlled by transcriptional regulation, which depends on the orchestrated accessibility of regulatory proteins to promoters and other cis-regulatory DNA elements. This accessibility and its effect on gene expression play a major role in defining the developmental process. To understand the regulatory mechanism and functional elements modulating morphological and anatomical changes during fruit development, we generated genome-wide high-resolution maps of DNase I hypersensitive sites (DHSs) from the fruit tissues of the tomato cultivar "Moneymaker" at 20 days post anthesis as well as break stage. By exploring variation of DHSs across fruit development stages, we pinpointed the most likely hypersensitive sites related to development-specific genes. By detecting binding motifs on DHSs of these development-specific genes or genes in the ascorbic acid biosynthetic pathway, we revealed the common regulatory elements contributing to coordinating gene transcription of plant ripening and specialized metabolic pathways. Our results contribute to a better understanding of the regulatory dynamics of genes involved in tomato fruit development and ripening. PMID:27250572

  13. Regulatory analysis for the use of underground barriers at the Hanford Site tank farms

    SciTech Connect

    Hampsten, K.L.

    1994-08-12

    Sixty-seven of the single-shell tanks at the Hanford Site, Richland, Washington, are assumed to have leaked in the past. Some of the waste retrieval options being considered, such as past-practice sluicing (a process that uses hot water to dislodge waste for subsequent removal by pumping), have the potential for increasing releases of dangerous waste from these tanks. Underground barrier systems are being evaluated as a method to mitigate releases of tank waste to the soil and groundwater that may occur during retrieval activities. The following underground barrier system options are among those being evaluated to determine whether their construction at the Single-Shell Tank Farms is viable. (1) A desiccant barrier would be created by circulating air through the subsurface soil to lower and then maintain the water saturation below the levels required for liquids to flow. (2) An injected materials barrier would be created by injecting materials such as grout or silica into the subsurface soils to form a barrier around and under a given tank or tank farm. (3) A cryogenic barrier would be created by freezing subsurface soils in the vicinity of a tank or tank farm. An analysis is provided of the major regulatory requirements that may impact full scale construction and operation of an underground barrier system and a discussion of factors that should be considered throughout the barrier selection process, irrespective of the type of underground barrier system being considered. However, specific barrier systems will be identified when a given regulation will have significant impact on a particular type of barrier technology. Appendix A provides a matrix of requirements applicable to construction and operation of an underground barrier system.

  14. EXPERIENCE FROM TWO SMALL QUANTITY RH-TRU WASTE SITES IN NAVIGATING THROUGH AN EVOLVING REGULATORY LANDSCAPE

    SciTech Connect

    Biedscheid, Jennifer; Devarakonda, Murthy; Eide, Jim; Kneff, Dennis

    2003-02-27

    Two small quantity transuranic (TRU) waste generator sites have gained considerable experience in navigating through a changing regulatory landscape in their efforts to remove the TRU waste from their sites and proceed with site remediation. The Battelle Columbus Laboratories Decommissioning Project (BCLDP) has the objectives of decontaminating nuclear research buildings and associated grounds and remediating to a level of residual contamination allowing future use without radiological restrictions. As directed by Congress, BCLDP must complete decontamination and decommissioning activities by the end of Fiscal Year (FY) 2006. This schedule requires the containerization of all TRU waste in 2002. BCLDP will generate a total of approximately 27 cubic meters (m3) of remote-handled (RH) TRU waste. Similarly, the Energy Technology Engineering Center (ETEC) is scheduled to close in 2006 pursuant to an agreement between the U.S. Department of Energy (DOE) and Boeing Canoga Park, the management and operating contractor for ETEC. ETEC had 11.0 m3 of RH-TRU and contact-handled (CH) TRU waste in storage, with the requirement to remove this waste in 2002 in order to meet their site closure schedule. The individual milestones for BCLDP and ETEC necessitated the establishment of site-specific programs to direct packaging and characterization of RH-TRU waste before the regulatory framework for the WIPP disposal of RH-TRU waste is finalized. The lack of large infrastructure for characterization activities, as well as the expedited schedules needed to meet regulatory milestones, provided both challenges and opportunities that are unique to small quantity sites. Both sites have developed unique programs for waste characterization based on the same premise, which directs comprehensive waste data collection efforts such that additional characterization will not be required following the finalization of the WIPP RH-TRU waste program requirements. This paper details the BCLDP program

  15. Environmental Regulatory Compliance Plan for Site Characterization; Yucca Mountain Site, Nevada Research and Development Area, Nevada: Revision 1

    SciTech Connect

    1988-12-01

    The DOE is committed to conduct its operations in an environmentally safe and sound manner, and will comply with applicable environmental statutes and regulations. These objectives are described in DOE Order 5400.1 (Environmental Protection Program Requirements). This document -- the Environmental Regulatory Compliance Plan (ERCP) -- is one method of implementing the policy set forth in DOE Order 5400.1 and the NWPA. The ERCP describes the plan by which the DOE will comply with applicable Federal environmental statutes and regulations. The ERCP also discusses how DOE will address State and local environmental statutes and regulations. 180 refs., 27 figs., 1 tab.

  16. The TTSMI database: a catalog of triplex target DNA sites associated with genes and regulatory elements in the human genome

    PubMed Central

    Jenjaroenpun, Piroon; Chew, Chee Siang; Yong, Tai Pang; Choowongkomon, Kiattawee; Thammasorn, Wimada; Kuznetsov, Vladimir A.

    2015-01-01

    A triplex target DNA site (TTS), a stretch of DNA that is composed of polypurines, is able to form a triple-helix (triplex) structure with triplex-forming oligonucleotides (TFOs) and is able to influence the site-specific modulation of gene expression and/or the modification of genomic DNA. The co-localization of a genomic TTS with gene regulatory signals and functional genome structures suggests that TFOs could potentially be exploited in antigene strategies for the therapy of cancers and other genetic diseases. Here, we present the TTS Mapping and Integration (TTSMI; http://ttsmi.bii.a-star.edu.sg) database, which provides a catalog of unique TTS locations in the human genome and tools for analyzing the co-localization of TTSs with genomic regulatory sequences and signals that were identified using next-generation sequencing techniques and/or predicted by computational models. TTSMI was designed as a user-friendly tool that facilitates (i) fast searching/filtering of TTSs using several search terms and criteria associated with sequence stability and specificity, (ii) interactive filtering of TTSs that co-localize with gene regulatory signals and non-B DNA structures, (iii) exploration of dynamic combinations of the biological signals of specific TTSs and (iv) visualization of a TTS simultaneously with diverse annotation tracks via the UCSC genome browser. PMID:25324314

  17. The TTSMI database: a catalog of triplex target DNA sites associated with genes and regulatory elements in the human genome.

    PubMed

    Jenjaroenpun, Piroon; Chew, Chee Siang; Yong, Tai Pang; Choowongkomon, Kiattawee; Thammasorn, Wimada; Kuznetsov, Vladimir A

    2015-01-01

    A triplex target DNA site (TTS), a stretch of DNA that is composed of polypurines, is able to form a triple-helix (triplex) structure with triplex-forming oligonucleotides (TFOs) and is able to influence the site-specific modulation of gene expression and/or the modification of genomic DNA. The co-localization of a genomic TTS with gene regulatory signals and functional genome structures suggests that TFOs could potentially be exploited in antigene strategies for the therapy of cancers and other genetic diseases. Here, we present the TTS Mapping and Integration (TTSMI; http://ttsmi.bii.a-star.edu.sg) database, which provides a catalog of unique TTS locations in the human genome and tools for analyzing the co-localization of TTSs with genomic regulatory sequences and signals that were identified using next-generation sequencing techniques and/or predicted by computational models. TTSMI was designed as a user-friendly tool that facilitates (i) fast searching/filtering of TTSs using several search terms and criteria associated with sequence stability and specificity, (ii) interactive filtering of TTSs that co-localize with gene regulatory signals and non-B DNA structures, (iii) exploration of dynamic combinations of the biological signals of specific TTSs and (iv) visualization of a TTS simultaneously with diverse annotation tracks via the UCSC genome browser. PMID:25324314

  18. A novel method to identify nucleic acid binding sites in proteins by scanning mutagenesis: application to iron regulatory protein.

    PubMed Central

    Neupert, B; Menotti, E; Kühn, L C

    1995-01-01

    We describe a new procedure to identify RNA or DNA binding sites in proteins, based on a combination of UV cross-linking and single-hit chemical peptide cleavage. Site-directed mutagenesis is used to create a series of mutants with single Asn-Gly sequences in the protein to be analysed. Recombinant mutant proteins are incubated with their radiolabelled target sequence and UV irradiated. Covalently linked RNA- or DNA-protein complexes are digested with hydroxylamine and labelled peptides identified by SDS-PAGE and autoradiography. The analysis requires only small amounts of protein and is achieved within a relatively short time. Using this method we mapped the site at which human iron regulatory protein (IRP) is UV cross-linked to iron responsive element RNA to amino acid residues 116-151. Images PMID:7544459

  19. Innovative Regulatory and Technical Approaches for the U.S. Army Corp of Engineers' Linde FUSRAP Site Remediation

    SciTech Connect

    Pitts, J. T.; Coutts, P. W.; Franz, J.; Boyle, J. D.; Rogers, B. C.

    2002-02-27

    The U.S. Department of Energy (USDOE) created the Formerly Utilized Sites Remedial Action Program (FUSRAP) in 1974 to identify, investigate, and cleanup or control radiological contamination at sites used by the Manhattan Engineer District (MED) and the Atomic Energy Commission (AEC) from the 1940s through the 1960s. The USDOE had identified 46 sites in the program and finished remediation at 24 of the smaller ones before the end of 1997. With the passage of the Energy and Water Resources Appropriation Act of 1998 the United States Army Corps of Engineers (USACE) was designated by Congress with responsibility to manage and execute the FUSRAP. The Linde Site located in Tonawanda, New York was operated by the MED from 1942-1946 to extract uranium from several high-grade ores. This natural uranium was subsequently enriched in U-235 elsewhere in the United States and ultimately used to produce energy or weapons. Though in the process of reviewing alternative disposal options by 1995, the USDOE had operated FUSRAP with a strategy requiring virtually all materials remediated be disposed of at only one Nuclear Regulatory Commission licensed facility. The change in management of the FUSRAP in 1997 allowed the disposal policy of low levels of radioactively contaminated materials found at the remaining sites to be reexamined. This paper presents some of the innovative regulatory and technical approaches employed at the Linde Site that are resulting in project cost savings while meeting applicable or relevant and appropriate requirements as well as fulfilling commitments made to the local community.

  20. Mississippi lieutenant governor visits Stennis

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Stennis Space Center Director Gene Goldman (left) stands with Mississippi Lt. Gov. Phil Bryant at the A-3 Test Stand construction site during an Oct. 1 visit by the state official. During his tour, Bryant was updated on construction of the first large test stand at Stennis since the 1960s. The A-3 stand will be used to conduct simulated high-altitude testing on the next generation of rocket engines that will take humans back to the moon and possibly beyond. In addition to touring Stennis facilities, Bryant visited the INFINITY Science Center construction site, where he was updated on work under way to construct a 72,000-square-foot facility that will showcase the science underpinning the missions of NASA and resident agencies at Stennis.

  1. A phylogenetic Gibbs sampler that yields centroid solutions of cis-regulatory sites

    SciTech Connect

    Newberg, Lee A.; Thompson, William A.; Conlan, Sean; Smith, Thomas M.; McCue, Lee Ann; Lawrence, Charles E.

    2007-07-15

    Identification of functionally conserved regulatory elements in sequence data from closely related organisms is becoming feasible, due to the rapid growth of public sequence databases. Closely related organisms are most likely to have common regulatory motifs, however the recent speciation of such organisms results in the high degree of correlation in their genome sequences, confounding the detection of functional elements. Additionally, alignment algorithms that use optimization techniques are limited to the detection of a single alignment that may not be representative. Comparative-genomics studies must be able to address the phylogenetic correlation in the data and efficiently explore the alignment space, in order to make specific and biologically relevant predictions. Results: We describe here a Gibbs sampler that employs a full phylogenetic model and reports an ensemble centroid solution. We describe regulatory motif detection using both simulated and real data, and demonstrate that this approach achieves improved specificity, sensitivity, and positive predictive value over non-phylogenetic algorithms, and over phylogenetic algorithms that report a maximum likelihood solution.

  2. Low affinity binding site clusters confer hox specificity and regulatory robustness.

    PubMed

    Crocker, Justin; Abe, Namiko; Rinaldi, Lucrezia; McGregor, Alistair P; Frankel, Nicolás; Wang, Shu; Alsawadi, Ahmad; Valenti, Philippe; Plaza, Serge; Payre, François; Mann, Richard S; Stern, David L

    2015-01-15

    In animals, Hox transcription factors define regional identity in distinct anatomical domains. How Hox genes encode this specificity is a paradox, because different Hox proteins bind with high affinity in vitro to similar DNA sequences. Here, we demonstrate that the Hox protein Ultrabithorax (Ubx) in complex with its cofactor Extradenticle (Exd) bound specifically to clusters of very low affinity sites in enhancers of the shavenbaby gene of Drosophila. These low affinity sites conferred specificity for Ubx binding in vivo, but multiple clustered sites were required for robust expression when embryos developed in variable environments. Although most individual Ubx binding sites are not evolutionarily conserved, the overall enhancer architecture-clusters of low affinity binding sites-is maintained and required for enhancer function. Natural selection therefore works at the level of the enhancer, requiring a particular density of low affinity Ubx sites to confer both specific and robust expression. PMID:25557079

  3. Regulatory O-GlcNAcylation sites on FoxO1 are yet to be identified

    SciTech Connect

    Fardini, Yann; Perez-Cervera, Yobana; Camoin, Luc; Pagesy, Patrick; Lefebvre, Tony; Issad, Tarik

    2015-06-26

    O-GlcNAcylation is a reversible post-translational modification that regulates cytosolic and nuclear proteins. We and others previously demonstrated that FoxO1 is O-GlcNAcylated in different cell types, resulting in an increase in its transcriptional activity. Four O-GlcNAcylation sites were identified in human FOXO1 but directed mutagenesis of each site individually had modest (T317) or no effect (S550, T648, S654) on its O-GlcNAcylation status and transcriptional activity. Moreover, the consequences of mutating all four sites had not been investigated. In the present work, we mutated these sites in the mouse Foxo1 and found that mutation of all four sites did not decrease Foxo1 O-GlcNAcylation status and transcriptional activity, and would even tend to increase them. In an attempt to identify other O-GlcNAcylation sites, we immunoprecipitated wild-type O-GlcNAcylated Foxo1 and analysed the tryptic digest peptides by mass spectrometry using High-energy Collisional Dissociation. We identified T646 as a new O-GlcNAcylation site on Foxo1. However, site directed mutagenesis of this site individually or together with all four previously identified residues did not impair Foxo1 O-GlcNAcylation and transcriptional activity. These results suggest that residues important for the control of Foxo1 activity by O-GlcNAcylation still remain to be identified. - Highlights: • We mutate four previously identified O-GlcNAcylation sites on Foxo1. • Unexpectedly, these mutations do not reduce Foxo1 O-GlcNAcylation. • These mutation do not reduce Foxo1 transcriptional activity. • We identify a new O-GlcNAcylation site on Foxo1 by mass spectrometry. • Mutation of this site increases Foxo1 transcriptional activity.

  4. Inside Home Visiting Programs.

    ERIC Educational Resources Information Center

    Powell, Douglas R.

    1993-01-01

    Examines the wide variation that exists among home visiting programs in their content, theory, and operation, outlining the theoretical goals and operational dimensions of such programs. Numerous home visiting programs that focus on parents of young children are highlighted. Observes that few programs have been rigorously evaluated using the…

  5. Visiting Scholar Exchange Reports.

    ERIC Educational Resources Information Center

    Rubin, Kyna, Ed.

    1986-01-01

    Provides reports of four United States scholars who visited China as part of the Visiting Scholar Exchange Program. The titles of the reports are (1) "China Journey: A Political Scientist's Look at Yan'an," (2) "The Social Consequences of Land Reclamation in Chinese Coastal Ecosystems," (3) "Anthropology Lectures in South China," and (4) "The Use…

  6. The Sustained Visitation Program.

    ERIC Educational Resources Information Center

    Gatto, Joseph A.

    1979-01-01

    A sustained visitation program was initiated between the Los Angeles Unified School District and the Los Angeles County Museum of Art. The program enables selected students to visit the museum on a regular basis for one semester, during which time they study, photograph, and videotape museum life and artifacts. (KC)

  7. Home Visiting Handbook.

    ERIC Educational Resources Information Center

    Jefferson County Public Schools, Lakewood, CO.

    This handbook describes the home visiting program of the Jefferson County, Colorado public schools, in which teacher assistants, under supervision of the head teacher, visit parents of the children they are responsible for in the preschool center. Section I is an overview of the goals and purpose of the program. Section II describes the program in…

  8. Presidential visit to MSFC

    NASA Technical Reports Server (NTRS)

    1990-01-01

    President George Bush and Alabama Governor Guy Hunt are greeted by Marshall's sixth Center Director Thomas J. Lee (1989-1994) upon their arrival at Redstone Arsenal (RSA) airfield. This was the first sitting president to visit Marshall Space Flight Center (MSFC) since President Kennedy's visit almost 30 years ago.

  9. Hosting the Presidential Visit.

    ERIC Educational Resources Information Center

    Sherouse, Mark A.

    This paper describes the visit of President Bush to the campus of Southern Methodist University (SMU) for the May, 1992 commencement and lessons learned from the experience. The paper describes how SMU made use of lead time and suggests how to estimate cost of such a visit. Discussion of strategies for organizing describes the formation and work…

  10. Serine-15 is the regulatory seryl-phosphorylation site in C sub 4 -leaf phosphoenolpyruvate carboxylase (PEPCase) from maize

    SciTech Connect

    Jiao, Jinan; Chollet, R. )

    1990-05-01

    The {sup 32}P-labeled regulatory site phosphopeptide was purified from a tryptic digest of in vitro phosphorylated/activated dark-form PEPCase by metal ion affinity and reversed-phase chromatography and subjected to automated Edman degradation analysis. The amino acid sequence of this phosphoseryl peptide is His-His-Ser(P)-Ile-Asp-Ala-Gln-Leu-Arg. This nonapeptide, which corresponds exactly to residues 13-21 in the deduced primary sequence of the maize leaf carboxylase, is far removed from a recently identified active-site cysteine (Cys-553) in the C-terminal region of the primary structure. Comparative analysis of the deduced N-terminal sequences of C{sub 3}, C{sub 4}, and CAM leaf PEPCases suggests that the motif of Lys/Arg-X-X-Ser is an important structural requirement of the C{sub 4}- and CAM-leaf protein-serine kinases.

  11. Environmental Protection Department Operations and Regulatory Affairs Division Contingency Plan for Site 300 Waste Accumulation Area(s)

    SciTech Connect

    Levy, R

    2005-07-14

    -specific information for the WAA(s). Site-specific plans are included in Appendix D. A copy of the Contingency Plan (including the site-specific plans) will be distributed to regulatory agencies and to public service organizations, such as local fire departments and hospitals that may be called on to provide emergency services. A copy of the General Plan with the appropriate site-specific plan will be located at the WAA(s), so it can be used in the case of an emergency.

  12. Well-child visits

    MedlinePlus

    ... listening to heart, breath, and stomach sounds) Heart sounds Infantile reflexes and deep tendon reflexes as the child gets older Neonatal jaundice -- first few visits only Palpation Percussion Standard ophthalmic exam Temperature measurement (see also normal body temperature ) Immunization information: ...

  13. Comparative Analysis of Regulatory Elements between Escherichia coli and Klebsiella pneumoniae by Genome-Wide Transcription Start Site Profiling

    PubMed Central

    Qiu, Yu; Nagarajan, Harish; Seo, Joo-Hyun; Cho, Byung-Kwan; Tsai, Shih-Feng; Palsson, Bernhard Ø.

    2012-01-01

    Genome-wide transcription start site (TSS) profiles of the enterobacteria Escherichia coli and Klebsiella pneumoniae were experimentally determined through modified 5′ RACE followed by deep sequencing of intact primary mRNA. This identified 3,746 and 3,143 TSSs for E. coli and K. pneumoniae, respectively. Experimentally determined TSSs were then used to define promoter regions and 5′ UTRs upstream of coding genes. Comparative analysis of these regulatory elements revealed the use of multiple TSSs, identical sequence motifs of promoter and Shine-Dalgarno sequence, reflecting conserved gene expression apparatuses between the two species. In both species, over 70% of primary transcripts were expressed from operons having orthologous genes during exponential growth. However, expressed orthologous genes in E. coli and K. pneumoniae showed a strikingly different organization of upstream regulatory regions with only 20% identical promoters with TSSs in both species. Over 40% of promoters had TSSs identified in only one species, despite conserved promoter sequences existing in the other species. 662 conserved promoters having TSSs in both species resulted in the same number of comparable 5′ UTR pairs, and that regulatory element was found to be the most variant region in sequence among promoter, 5′ UTR, and ORF. In K. pneumoniae, 48 sRNAs were predicted and 36 of them were expressed during exponential growth. Among them, 34 orthologous sRNAs between two species were analyzed in depth, and the analysis showed that many sRNAs of K. pneumoniae, including pleiotropic sRNAs such as rprA, arcZ, and sgrS, may work in the same way as in E. coli. These results reveal a new dimension of comparative genomics such that a comparison of two genomes needs to be comprehensive over all levels of genome organization. PMID:22912590

  14. [The preoperative anaesthetic visit].

    PubMed

    Harms, Christoph; Kindler, Christoph H

    2009-07-01

    Anaesthetists often visit their patients in exceptional situations characterised by preoperative anxiety or distress. Therefore, even brief contact with the patient can be considered intense and meaningful. The initial preoperative anaesthetic visit is the beginning of the relationship between patient and anaesthetist, and should help to explain the planned anaesthetic technique. Preoperative anaesthetic visits are intense and last for 20 minutes on average. They should assert a professional approach to the patient's emotions, particularly to preoperative anxiety, and a structured and clear collection of information including the past history of the patient. These visits should also provide information about the anaesthesia itself and instructions for the patient with respect to the perioperative period. Communication about the side effects and risks of anaesthetic techniques, and the discussion of potential alternatives are mandatory. Worldwide, courts of law increasingly require a documented discussion between the anaesthetist and patient based on risk-benefit evidence. Today, there is in general a shift away from decisions made solely by physicians, reflecting an increased respect for the autonomy of the patient towards a model of shared decision-making and informed choice. Ideally, the preoperative visit follows the four key habits of highly effective clinicians, i.e., to rapidly establish a rapport with the patient and provide an agenda for the visit, to explore the patient's perspectives and expectations, to demonstrate empathy, and to focus on the end of the visit with providing information and including the patient in the decision-making process. Visits are then concluded upon obtaining informed consent from the patient. PMID:19565444

  15. Closure Strategy for a Waste Disposal Facility with Multiple Waste Types and Regulatory Drivers at the Nevada Test Site

    SciTech Connect

    L. Desotell; D. Wieland; V. Yucel; G. Shott; J. Wrapp

    2008-03-01

    The U.S. Department of Energy, National Security Administration Nevada Site Office (NNSA/NSO) is planning to close the 92-Acre Area of the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada Test Site (NTS), which is about 65 miles northwest of Las Vegas, Nevada. Closure planning for this facility must take into account the regulatory requirements for a diversity of waste streams, disposal and storage configurations, disposal history, and site conditions. This paper provides a brief background of the Area 5 RWMS, identifies key closure issues, and presents the closure strategy. Disposals have been made in 25 shallow excavated pits and trenches and 13 Greater Confinement Disposal (GCD) boreholes at the 92-Acre Area since 1961. The pits and trenches have been used to dispose unclassified low-level waste (LLW), low-level mixed waste (LLMW), and asbestiform waste, and to store classified low-level and low-level mixed materials. The GCD boreholes are intermediate-depth disposal units about 10 feet (ft) in diameter and 120 ft deep. Classified and unclassified high-specific activity LLW, transuranic (TRU), and mixed TRU are disposed in the GCD boreholes. TRU waste was also disposed inadvertently in trench T-04C. Except for three disposal units that are active, all pits and trenches are operationally covered with 8-ft thick alluvium. The 92-Acre Area also includes a Mixed Waste Disposal Unit (MWDU) operating under Resource Conservation and Recovery Act (RCRA) Interim Status, and an asbestiform waste unit operating under a state of Nevada Solid Waste Disposal Site Permit. A single final closure cover is envisioned over the 92-Acre Area. The cover is the evapotranspirative-type cover that has been successfully employed at the NTS. Closure, post-closure care, and monitoring must meet the requirements of the following regulations: U.S. Department of Energy Order 435.1, Title 40 Code of Federal Regulations (CFR) Part 191, Title 40 CFR Part 265, Nevada Administrative

  16. Genome-Wide Mapping of Collier In Vivo Binding Sites Highlights Its Hierarchical Position in Different Transcription Regulatory Networks

    PubMed Central

    Dubois, Laurence; Bataillé, Laetitia; Painset, Anaïs; Le Gras, Stéphanie; Jost, Bernard; Crozatier, Michèle; Vincent, Alain

    2015-01-01

    Collier, the single Drosophila COE (Collier/EBF/Olf-1) transcription factor, is required in several developmental processes, including head patterning and specification of muscle and neuron identity during embryogenesis. To identify direct Collier (Col) targets in different cell types, we used ChIP-seq to map Col binding sites throughout the genome, at mid-embryogenesis. In vivo Col binding peaks were associated to 415 potential direct target genes. Gene Ontology analysis revealed a strong enrichment in proteins with DNA binding and/or transcription-regulatory properties. Characterization of a selection of candidates, using transgenic CRM-reporter assays, identified direct Col targets in dorso-lateral somatic muscles and specific neuron types in the central nervous system. These data brought new evidence that Col direct control of the expression of the transcription regulators apterous and eyes-absent (eya) is critical to specifying neuronal identities. They also showed that cross-regulation between col and eya in muscle progenitor cells is required for specification of muscle identity, revealing a new parallel between the myogenic regulatory networks operating in Drosophila and vertebrates. Col regulation of eya, both in specific muscle and neuronal lineages, may illustrate one mechanism behind the evolutionary diversification of Col biological roles. PMID:26204530

  17. Father attendance in nurse home visitation.

    PubMed

    Holmberg, John R; Olds, David L

    2015-01-01

    Our aim was to examine the rates and predictors of father attendance at nurse home visits in replication sites of the Nurse-Family Partnership (NFP). Early childhood programs can facilitate father involvement in the lives of their children, but program improvements require an understanding of factors that predict father involvement. The sample consisted of 29,109 low-income, first-time mothers who received services from 694 nurses from 80 sites. We conducted mixed-model multiple regression analyses to identify population, implementation, site, and nurse influences on father attendance. Predictors of father attendance included a count of maternal visits (B = 0.12, SE = 0.01, F = 3101.77), frequent contact between parents (B = 0.61, SE = 0.02, F = 708.02), cohabitation (B = 1.41, SE = 0.07, F = 631.51), White maternal race (B = 0.77, SE = 0.06, F = 190.12), and marriage (B = 0.42, SE = 0.08, F = 30.08). Random effects for sites and nurses predicted father-visit participation (2.7 & 6.7% of the variance, respectively), even after controlling for population sociodemographic characteristics. These findings suggest that factors operating at the levels of sites and nurses influence father attendance at home visits, even after controlling for differences in populations served. Further inquiry about these influences on father visit attendance is likely to inform program-improvement efforts. PMID:25521707

  18. Father Attendance in Nurse Home Visitation

    PubMed Central

    Holmberg, John R.; Olds, David L.

    2015-01-01

    Our aim was to examine the rates and predictors of father attendance at nurse home visits in replication sites of the Nurse-Family Partnership (NFP). Early childhood programs can facilitate father involvement in the lives of their children, but program improvements require an understanding of factors that predict father involvement. The sample consisted of 29,109 low-income, first-time mothers who received services from 694 nurses from 80 sites. We conducted mixed-model multiple regression analyses to identify population, implementation, site, and nurse influences on father attendance. Predictors of father attendance included a count of maternal visits (B = 0.12, SE = 0.01, F = 3101.77), frequent contact between parents (B = 0.61, SE = 0.02, F = 708.02), cohabitation (B = 1.41, SE = 0.07, F = 631.51), White maternal race (B = 0.77, SE = 0.06, F = 190.12), and marriage (B = 0.42, SE = 0.08, F = 30.08). Random effects for sites and nurses predicted father-visit participation (2.7 & 6.7% of the variance, respectively), even after controlling for population sociodemographic characteristics. These findings suggest that factors operating at the levels of sites and nurses influence father attendance at home visits, even after controlling for differences in populations served. Further inquiry about these influences on father visit attendance is likely to inform program-improvement efforts. PMID:25521707

  19. Using quality improvement to promote implementation and increase well child visits in home visiting.

    PubMed

    Goyal, Neera K; Ammerman, Robert T; Massie, Julie A; Clark, Margaret; Van Ginkel, Judith B

    2016-03-01

    A key goal of home visiting is to connect children with medical homes through anticipatory guidance regarding recommended well child care (WCC). Substantial barriers to WCC among low socioeconomic families can limit achievement of this outcome. Quality improvement strategies have been widely adopted in healthcare but only recently implemented in home visiting to achieve program outcomes. The objective of this initiative was to increase the percentage of infants enrolled in home visiting who completed at least 3 recommended WCC visits in the first 6 months of life within a large, multi-model program comprised of 11 sites. A series of 33 quality improvement cycles were conducted at 3 sites involving 18 home visitors and 139 families with infants in the target age range. These were deployed sequentially, and changes within and across sites were monitored using trend charts over time. Adopted strategies were then implemented program-wide. Initiatives focused on staff training in WCC recommendations, data collection processes, monthly family tracking reports, and enhanced communication with primary care offices. Data were shared in iterative sessions to identify methods for improving adherence. Wide baseline variability across sites was observed, with the percentage of infants with recommended care ranging from 35% to 83%. Over the project timeline, the percentage of infants receiving at least 3 WCC visits in the first 6 months increased from 58% to 86%. Quality improvement within home visiting can be used to improve WCC adherence and provides an example of maximizing implementation of home visiting interventions. PMID:26699456

  20. (3H) 5,7-dichlorokynurenic acid, a high affinity ligand for the NMDA receptor glycine regulatory site

    SciTech Connect

    Hurt, S.D.; Baron, B.M. )

    1991-01-01

    The NMDA subtype of glutamate receptors is allosterically linked to a strychnine-insensitive glycine regulatory site. Kynurenic acid and its halogenated derivatives are non-competitive NMDA antagonists acting at the glycine site. The authors have prepared (3H) 5,7-dichlorokyrurenic acid (DCKA) as an antagonist radioligand and have characterized its binding. 3-Bromo-5,7-DCKA was catalytically dehalogenated in the presence of tritium gas and HPLC purified to yield (3H) 5,7-DCKA with a specific activity of 17.6 Ci/mmol. (3H) 5,7-DCKA bound to rat brain synaptosomes with a Kd of 69 {plus minus} 23 nM and Bmax = 14.5 {plus minus} 3.2 pmoles/mg protein. Binding was 65-70% specific at 10 nM (3H) 5,7-DCKA. This ligand is thus more selective and has higher affinity than (3H) glycine, in addition to being an antagonist.

  1. Predicting Emergency Department Visits

    PubMed Central

    Poole, Sarah; Grannis, Shaun; Shah, Nigam H.

    2016-01-01

    High utilizers of emergency departments account for a disproportionate number of visits, often for nonemergency conditions. This study aims to identify these high users prospectively. Routinely recorded registration data from the Indiana Public Health Emergency Surveillance System was used to predict whether patients would revisit the Emergency Department within one month, three months, and six months of an index visit. Separate models were trained for each outcome period, and several predictive models were tested. Random Forest models had good performance and calibration for all outcome periods, with area under the receiver operating characteristic curve of at least 0.96. This high performance was found to be due to non-linear interactions among variables in the data. The ability to predict repeat emergency visits may provide an opportunity to establish, prioritize, and target interventions to ensure that patients have access to the care they require outside an emergency department setting. PMID:27570684

  2. Functional analysis of the BRI1 receptor kinase by Thr-for-Ser substitution in a regulatory autophosphorylation site

    PubMed Central

    Oh, Man-Ho; Bender, Kyle W.; Kim, Sang Y.; Wu, Xia; Lee, Seulki; Nou, Ill-Sup; Zielinski, Raymond E.; Clouse, Steven D.; Huber, Steven C.

    2015-01-01

    BRI1 becomes highly phosphorylated in vivo upon perception of the ligand, brassinolide, as a result of autophosphorylation and transphosphorylation by its co-receptor kinase, BAK1. Important autophosphorylation sites include those involved in activation of kinase activity and those that are inhibitory, such as Ser-891. The inhibitory sites are autophosphorylated after kinase activation has been achieved and are postulated to contribute to deactivation of the kinase. The function of phosphosites is usually tested by substituting a non-phosphorylatable residue or an acidic residue that can act as a phosphomimetic. What has typically not been examined is substitution of a Thr for a Ser phosphosite (or vice versa) but given that Thr and Ser are not equivalent amino acids this type of substitution may represent a new approach to engineer regulatory phosphorylation. In the present study with BRI1, we substituted Thr at the Ser-891 phosphosite to generate the S891T directed mutant. The recombinant Flag-BRI1 (S891T) cytoplasmic domain protein (the S891T protein) was catalytically active and phosphorylation occurred at the engineered Thr-891 site. However, the S891T recombinant protein autophosphorylated more slowly than the wild-type protein during expression in E. coli. As a result, activation of peptide kinase activity (measured in vitro) was delayed as was transphosphorylation of bacterial proteins in situ. Stable transgenic expression of BRI1 (S891T)-Flag in Arabidopsis bri1-5 plants did not fully rescue the brassinosteroid (BR) phenotype indicating that BR signaling was constrained. Our working model is that restricted signaling in the S891T plants occurs as a result of the reduced rate of activation of the mutant BRI1 kinase by autophosphorylation. These results provide the platform for future studies to critically test this new model in vivo and establish Ser-Thr substitutions at phosphosites as an interesting approach to consider with other protein kinases. PMID

  3. Malaysian Students Visit Thailand.

    ERIC Educational Resources Information Center

    International Understanding at School, 1983

    1983-01-01

    Five students and one coordinator from the Unesco Associated Schools Project undertook a study visit to Bangkok to exchange views and experiences. Future joint projects/activities were discussed, and the students gained some insight into the life of their counterparts in Thailand. (RM)

  4. Revisiting High School Visits

    ERIC Educational Resources Information Center

    Flagel, Andrew

    2012-01-01

    NACAC's anniversary is a great time to follow up on an article on high school visits, a topic of ongoing discussion in every admission and guidance office. The article highlights a variety of potential good outcomes that can be derived from collaborative interactions. Sadly, however, admission representatives are apt to be described by the…

  5. Home Weatherization Visit

    ScienceCinema

    Chu, Steven

    2013-05-29

    Secretary Steven Chu visits a home that is in the process of being weatherized in Columbus, OH, along with Ohio Governor Ted Strickland and Columbus Mayor Michael Coleman. They discuss the benefits of weatherization and how funding from the recovery act is having a direct impact in communities across America.

  6. Floral visitation by the Argentine ant reduces bee visitation and plant seed set.

    PubMed

    Hanna, Cause; Naughton, Ida; Boser, Christina; Alarcón, Ruben; Hung, Keng-Lou James; Holway, David

    2015-01-01

    Ants often visit flowers, but have only seldom been documented to provide effective pollination services. Floral visitation by ants can also compromise plant reproduction in situations where ants interfere with more effective pollinators. Introduced ants may be especially likely to reduce plant reproductive success through floral visitation, but existing experimental studies have found little support for this hypothesis. Here, we combine experimental and observational approaches to examine the importance of floral visitation by the nonnative Argentine ant (Linepithema humile) on plant species native to Santa Cruz Island, California, USA. First, we determine how L. humile affects floral visitor diversity, bee visitation rates, and levels of pollen limitation for the common, focal plant species island morning glory (Calystegia macrostegia ssp. macrostegia). Second, we assess the broader ecological consequences of floral visitation by L. humile by comparing floral visitation networks between invaded and uninvaded sites. The Argentine ant and native ants both visited island morning glory flowers, but L. humile was much more likely to behave aggressively towards other floral visitors and to be the sole floral occupant. The presence of L. humile in morning glory flowers reduced floral visitor diversity, decreased rates of bee visitation, and increased levels of pollen limitation. Network comparisons between invaded and uninvaded. sites revealed differences in both network structure and species-level attributes. In. invaded sites, floral visitors were observed on fewer plant species, ants had a higher per-plant interaction strength relative to that of other visitors, and interaction strengths between bees and plants were weaker. These results illustrate that introduced ants can negatively affect plant reproduction and potentially disrupt pollination services at an ecosystem scale. PMID:26236907

  7. NO-independent regulatory site of direct sGC stimulators like YC-1 and BAY 41-2272

    PubMed Central

    Becker, Eva Maria; Alonso-Alija, Cristina; Apeler, Heiner; Gerzer, Rupert; Minuth, Torsten; Pleiβ, Ulrich; Schmidt, Peter; Schramm, Matthias; Schröder, Henning; Schroeder, Werner; Steinke, Wolfram; Straub, Alexander; Stasch, Johannes-Peter

    2001-01-01

    Background The most important receptor for nitic oxide is the soluble guanylate cyclase (sGC), a heme containing heterodimer. Recently, a pyrazolopyridine derivative BAY 41-2272, structurally related to YC-1, was identified stimulating soluble guanylate cyclase in an NO-independent manner, which results in vasodilatation and antiplatelet activity. The study described here addresses the identification of the NO-independent site on soluble guanylate cyclase. Results We developed a photoaffinity label (3H-meta-PAL) for the direct and NO-independent soluble guanylate cyclase (sGC) stimulator BAY 41-2272 by introducing an azido-group into the tritium labeled compound. The synthesized photoaffinitylabel directly stimulates the purified sGC and shows in combination with NO a synergistic effect on sGC activity. Irradiation with UV light of 3H-meta-PAL together with the highly purified sGC leads to a covalent binding to the α1-subunit of the enzyme. This binding is blocked by unlabeled meta-PAL, YC-1 and BAY 41-2272. For further identification of the NO-independent regulatory site the 3H-meta-PAL labeled sGC was fragmented by CNBr digest. The 3H-meta-PAL binds to a CNBr fragment, consisting of the amino acids 236–290 of the α1-subunit. Determination of radioactivity of the single PTH-cycles from the sequencing of this CNBr fragment detected the cysteines 238 and 243 as binding residues of the 3H-meta-PAL. Conclusions Our data demonstrate that the region surrounding the cysteines 238 and 243 in the α1-subunit of the sGC could play an important role in regulation of sGC activity and could be the target of this new type of sGC stimulators. PMID:11801189

  8. Different papillomaviruses have different repertoires of transcription factor binding sites: convergence and divergence in the upstream regulatory region

    PubMed Central

    García-Vallvé, Santiago; Iglesias-Rozas, José R; Alonso, Ángel; Bravo, Ignacio G

    2006-01-01

    Background Papillomaviruses (PVs) infect stratified squamous epithelia in warm-blooded vertebrates and have undergone a complex evolutionary process. The control of the expression of the early ORFs in PVs depends on the binding of cellular and viral transcription factors to the upstream regulatory region (URR) of the virus. It is believed that there is a core of transcription factor binding sites (TFBS) common to all PVs, with additional individual differences, although most of the available information focuses only on a handful of viruses. Results We have studied the URR of sixty-one PVs, covering twenty different hosts. We have predicted the TFBS present in the URR and analysed these results by principal component analysis and genetic algorithms. The number and nature of TFBS in the URR might be much broader than thus far described, and different PVs have different repertoires of TFBS. Conclusion There are common fingerprints in the URR in PVs that infect primates, although the ancestors of these viruses diverged a long time ago. Additionally, there are obvious differences between the URR of alpha and beta PVs, despite these PVs infect similar histological cell types in the same host, i.e. human. A thorough analysis of the TFBS in the URR might provide crucial information about the differential biology of cancer-associated PVs. PMID:16526953

  9. Regulatory T cells sequentially migrate from the site of tissue inflammation to the draining LN to suppress the alloimmune response

    PubMed Central

    Zhang, Nan; Schröppel, Bernd; Lal, Girdhari; Jakubzick, Claudia; Mao, Xia; Chen, Dan; Yin, Na; Jessberger, Rolf; Ochando, Jordi C.; Ding, Yaozhong; Bromberg, Jonathan S.

    2009-01-01

    To determine site and mechanism of suppression, regulatory T cell (Treg) migration and function were investigated in an islet allograft model. Treg first migrated from blood to the inflammed allografts, this depended on CCR2, CCR4, CCR5, and P- and E-selectin ligands, and was essential for suppression of alloimmunity. In the allograft, Treg were activated, upregulated effector molecules, migrated to the draining lymph nodes (dLN) in a CCR2, CCR5, and CCR7 fashion, and this movement was essential for optimal suppression. Treg inhibited dendritic cell migration in a TGFβ and IL-10 dependent fashion; and suppressed antigen specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and then to dLNs were required for nTreg to differentiate and execute fully their suppressive function, by inhibiting DC in the peripheral tissue, and T effector cell responses in dLN and allografts. PMID:19303390

  10. Regulatory T cells prevent CD8 T cell maturation by inhibiting CD4 Th cells at tumor sites.

    PubMed

    Chaput, Nathalie; Darrasse-Jèze, Guillaume; Bergot, Anne-Sophie; Cordier, Corinne; Ngo-Abdalla, Stacie; Klatzmann, David; Azogui, Orly

    2007-10-15

    Natural regulatory T cells (Tregs) are present in high frequencies among tumor-infiltrating lymphocytes and in draining lymph nodes, supposedly facilitating tumor development. To investigate their role in controlling local immune responses, we analyzed intratumoral T cell accumulation and function in the presence or absence of Tregs. Tumors that grew in normal BALB/c mice injected with the 4T1 tumor cell line were highly infiltrated by Tregs, CD4 and CD8 cells, all having unique characteristics. Most infiltrating Tregs expressed low levels of CD25Rs and Foxp3. They did not proliferate even in the presence of IL-2 but maintained a strong suppressor activity. CD4 T cells were profoundly anergic and CD8 T cell proliferation and cytotoxicity were severely impaired. Depletion of Tregs modified the characteristics of tumor infiltrates. Tumors were initially invaded by activated CD4(+)CD25(-) T cells, which produced IL-2 and IFN-gamma. This was followed by the recruitment of highly cytotoxic CD8(+) T cells at tumor sites leading to tumor rejection. The beneficial effect of Treg depletion in tumor regression was abrogated when CD4 helper cells were also depleted. These findings indicate that the massive infiltration of tumors by Tregs prevents the development of a successful helper response. The Tregs in our model prevent Th cell activation and subsequent development of efficient CD8 T cell activity required for the control of tumor growth. PMID:17911581

  11. Goddard Visiting Scientist Program

    NASA Technical Reports Server (NTRS)

    2000-01-01

    Under this Indefinite Delivery Indefinite Quantity (IDIQ) contract, USRA was expected to provide short term (from I day up to I year) personnel as required to provide a Visiting Scientists Program to support the Earth Sciences Directorate (Code 900) at the Goddard Space Flight Center. The Contractor was to have a pool, or have access to a pool, of scientific talent, both domestic and international, at all levels (graduate student to senior scientist), that would support the technical requirements of the following laboratories and divisions within Code 900: 1) Global Change Data Center (902); 2) Laboratory for Atmospheres (Code 910); 3) Laboratory for Terrestrial Physics (Code 920); 4) Space Data and Computing Division (Code 930); 5) Laboratory for Hydrospheric Processes (Code 970). The research activities described below for each organization within Code 900 were intended to comprise the general scope of effort covered under the Visiting Scientist Program.

  12. Use of enhancer trapping to identify pathogen-induced regulatory events spatially restricted to plant-microbe interaction sites.

    PubMed

    Schroeder, Mercedes; Tsuchiya, Tokuji; He, Shuilin; Eulgem, Thomas

    2016-04-01

    Plant genes differentially expressed during plant-pathogen interactions can be important for host immunity or can contribute to pathogen virulence. Large-scale transcript profiling studies, such as microarray- or mRNA-seq-based analyses, have revealed hundreds of genes that are differentially expressed during plant-pathogen interactions. However, transcriptional responses limited to a small number of cells at infection sites can be difficult to detect using these approaches, as they are under-represented in the whole-tissue datasets typically generated by such methods. This study examines the interactions between Arabidopsis thaliana (Arabidopsis) and the pathogenic oomycete Hyaloperonospora arabidopsidis (Hpa) by enhancer trapping to uncover novel plant genes involved in local infection responses. We screened a β-glucuronidase (GUS) reporter-based enhancer-trap population for expression patterns related to Hpa infection. Several independent lines exhibited GUS expression in leaf mesophyll cells surrounding Hpa structures, indicating a regulatory response to pathogen infection. One of these lines contained a single enhancer-trap insertion in an exon of At1g08800 (MyoB1, Myosin Binding Protein 1) and was subsequently found to exhibit reduced susceptibility to Hpa. Two additional Arabidopsis lines with T-DNA insertions in exons of MyoB1 also exhibited approximately 30% fewer spores than wild-type plants. This study demonstrates that our enhancer-trapping strategy can result in the identification of functionally relevant pathogen-responsive genes. Our results further suggest that MyoB1 either positively contributes to Hpa virulence or negatively affects host immunity against this pathogen. PMID:26095625

  13. Unusual properties of regulatory DNA from the Drosophila engrailed gene: three "pairing-sensitive" sites within a 1.6-kb region.

    PubMed

    Kassis, J A

    1994-03-01

    We have previously shown that a 2-kb fragment of engrailed DNA can suppress expression of a linked marker gene, white, in the P element vector CaSpeR. This suppression is dependent on the presence of two copies of engrailed DNA-containing P elements (P[en]) in proximity in the Drosophila genome (either in cis or in trans). In this study, the 2-kb fragment was dissected and found to contain three fragments of DNA which could mediate white suppression [called "pairing-sensitive sites" (PS)]. A PS site was also identified in regulatory DNA from the Drosophila escargot gene. The eye colors of six different P[en] insertions in the escargot gene suggest an interaction between P[en]-encoded and genome-encoded PS sites. I hypothesize that white gene expression from P[en] is repressed by the formation of a protein complex which is initiated at the engrailed PS sites and also requires interactions with flanking genomic DNA. Genes were sought which influence the function of PS sites. Mutations in some Polycomb and trithorax group genes were found to affect the eye color from some P[en] insertion sites. However, different mutations affected expression from different P[en] insertion sites and no one mutation was found to affect expression from all P[en] insertion sites examined. These results suggest that white expression from P[en] is not directly regulated by members of the Polycomb and trithorax group genes, but in some cases can be influenced by them. I propose that engrailed PS sites normally act to promote interactions between distantly located engrailed regulatory sites and the engrailed promoter. PMID:8005412

  14. Regulatory SNPs and transcriptional factor binding sites in ADRBK1, AKT3, ATF3, DIO2, TBXA2R and VEGFA

    PubMed Central

    Buroker, Norman E

    2014-01-01

    Abstract Regulatory single nucleotide polymorphisms (rSNPs) which change the transcriptional factor binding sites (TFBS) for transcriptional factors (TFs) to bind DNA were reviewed for the ADRBK1 (GRK2), AKT3, ATF3, DIO2, TBXA2R and VEGFA genes. Changes in the TFBS where TFs attach to regulate these genes may result in human sickness and disease. The highlights of this previous work were reviewed for these genes. PMID:25483406

  15. Sensing kuuki among visiting nurses.

    PubMed

    Shimamura, Atsuko; Suwa, Sayuri; Tsujimura, Mayuko

    2016-04-01

    This study aimed to explore how visiting nurses in Japan sense Kuuki (mood or atmosphere) in the homes of patients and families. Participants were 15 Japanese visiting nurses with experience sensing kuuki in homes of patients and families. Data were collected through two 90 min focus group interviews with experienced visiting nurses, and a qualitative content analysis was performed. The qualitative analysis showed that experienced visiting nurses sensed kuuki in eight ways. Kuuki differs based on type of illness, state of health and number of visits. Sensitivity to kuuki is thought to be linked to understanding of patient and family feelings, changes in the physical condition of patients and evaluation of nursing care delivery. Perception of kuuki also contributes to care planning especially on the very first home visit and when visiting terminally ill patients. PMID:27184700

  16. Single Visit versus Multiple Visit Root Canal Therapy

    PubMed Central

    Singla, Rajesh; Marwah, Nikhil; Dutta, Samir

    2008-01-01

    Aim: The purpose of this study was to determine clinical success rate of single visit verses multiple visit root canal treatment in cariously exposed vital primary molars. Material& methods: 40 children in age group of 4 to 7 years were divided equally into two treatment groups and recall visits were carried out after one week, one month and three months and six months. Results: Statistically no significant difference was found. Conclusion: Multiple visit and single visit root canal treatment demonstrated almost equal success but most important aspect for success in pulpectomy cases is the indication of each case and then its subsequent treatment, be it multiple or single visit root canal treatment. PMID:25206084

  17. 3MRA: A MULTI-MEDIA HUMAN AND ECOLOGICAL MODELING SYSTEM FOR SITE-SPECIFIC TO NATIONAL SCALE REGULATORY APPLICATIONS

    EPA Science Inventory

    3MRA provides a technology that fully integrates the full dimensionality of human and ecological exposure and risk assessment, thus allowing regulatory decisions a more complete expression of potential adverse health effects related to the disposal and reuse of contaminated waste...

  18. Visit a Farm? Surely Not!

    ERIC Educational Resources Information Center

    Graham, Bill

    2012-01-01

    Popular myth has it that visiting a farm can be dangerous, but there are only a few occasions when children have become ill during a school visit to a farm. Simple, sensible precautions, including wearing appropriate clothing, such as trousers and wellington boots (if wet) or sensible shoes, and careful hand-washing, are all that is required. The…

  19. School's in Session: Visitation Day.

    ERIC Educational Resources Information Center

    Hulbert, Barbara T.

    1997-01-01

    Describes a parent program at Dryden Middle School in New York in which parents attend school for the entire day with their children. Includes information on parent orientation, structure of the visit, and students' reactions to parental visitation. Notes the importance of publicity, preparation, organization, and follow-up activities for program…

  20. STS-124 crew visits Stennis

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's John C. Stennis Space Center Deputy Director Gene Goldman (center) welcomed members of the STS-124 Discovery space shuttle crew during their July 23 visit to the center. Crew members who visited Stennis were (l to r) Pilot Ken Ham, Mission Specialist Karen Nyberg, Kelly, and Mission Specialists Ron Garan and Mike Fossum.

  1. The NORM technology connection web site : streamlined access to NORM-related service company and regulatory information.

    SciTech Connect

    Smith, K. P.; Richmond, P.; LePoire, D. J.; Arnish, J. J.; Johnson, R.

    2000-11-08

    Argonne National Laboratory has developed an Internet web site providing access to critical information needed to support decisions on the management and disposal of wastes containing naturally occurring radioactive material (NORM). The NORM Technology Connection web site provides current information on (1) service companies that provide support on NORM issues (e.g., site characterization and remediation, sample analysis, radiation safety training, disposal) and (2) existing applicable NORM regulations and guidelines. A third element of the site is an electronic mail list that allows users to post or respond to questions about the management of NORM. Development of the NORM Technology Connection web site was funded by the U.S. Department of Energy, Office of Fossil Energy. It is hosted and maintained by the Interstate Oil and Gas Compact Commission. The web site is publicly available; access is free, as is participation by any of the service companies.

  2. Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 1. Methodology

    NASA Astrophysics Data System (ADS)

    Massmann, Joel; Freeze, R. Allan

    1987-02-01

    This paper puts in place a risk-cost-benefit analysis for waste management facilities that explicitly recognizes the adversarial relationship that exists in a regulated market economy between the owner/operator of a waste management facility and the government regulatory agency under whose terms the facility must be licensed. The risk-cost-benefit analysis is set up from the perspective of the owner/operator. It can be used directly by the owner/operator to assess alternative design strategies. It can also be used by the regulatory agency to assess alternative regulatory policy, but only in an indirect manner, by examining the response of an owner/operator to the stimuli of various policies. The objective function is couched in terms of a discounted stream of benefits, costs, and risks over an engineering time horizon. Benefits are in the form of revenues for services provided; costs are those of construction and operation of the facility. Risk is defined as the cost associated with the probability of failure, with failure defined as the occurrence of a groundwater contamination event that violates the licensing requirements established for the facility. Failure requires a breach of the containment structure and contaminant migration through the hydrogeological environment to a compliance surface. The probability of failure can be estimated on the basis of reliability theory for the breach of containment and with a Monte-Carlo finite-element simulation for the advective contaminant transport. In the hydrogeological environment the hydraulic conductivity values are defined stochastically. The probability of failure is reduced by the presence of a monitoring network operated by the owner/operator and located between the source and the regulatory compliance surface. The level of reduction in the probability of failure depends on the probability of detection of the monitoring network, which can be calculated from the stochastic contaminant transport simulations. While

  3. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in the United States. Preliminary background report

    SciTech Connect

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    This report is a summary of a series of preliminary reports describing the laws and regulatory programs of the United states and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). A brief summary of public utility regulatory programs, energy facility siting programs, and municipal franchising authority is presented in this report to identify how such programs and authority may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. Subsequent reports will (1) describe public utility rate regulatory procedures and practices as they might affect an ICES, (2) analyze each of the aforementioned regulatory programs to identify impediments to the development of ICES, and (3) recommend potential changes in legislation and regulatory practices and procedures to overcome such impediments.

  4. Scheduling the Remediation of Port Hope: Logistical and Regulatory Challenges of a Multiple Site Urban Remediation Project - 13119

    SciTech Connect

    Ferguson Jones, Andrea; Lee, Angela; Palmeter, Tim

    2013-07-01

    The Port Hope Project is part of the larger CAN$1.28 billion Port Hope Area Initiative (PHAI), a community-based program for the development and implementation of a safe, local, long-term management solution for historic Low-Level Radioactive Waste (LLRW) in the Municipalities of Port Hope and Clarington, Ontario, Canada. Atomic Energy of Canada (AECL) is the Project Proponent, Public Works and Government Services (PWGSC) is managing the procurement of services and the MMM Group Limited - Conestoga Rovers and Associates Joint Venture (MMM-CRA Joint Venture) is providing detailed design and construction oversight and administration services for the Project. The Port Hope Project includes the construction of a long-term waste management facility (LTWMF) in the Municipality of Port Hope and the remediation of 18 (eighteen) large-scale LLRW, numerous small-scale sites still being identified and industrial sites within the Municipality. The total volume to be remediated is over one million cubic metres and will come from sites that include temporary storage sites, ravines, beaches, parks, private commercial and residential properties and vacant industrial sites all within the urban area of Port Hope. Challenges that will need to be overcome during this 10 year project include: - Requirements stipulated by the Environmental Assessment (EA) that affect Project logistics and schedule. - Coordination of site remediation with the construction schedule at the LTWMF. - Physical constraints on transport routes and at sites affecting production rates. - Despite being an urban undertaking, seasonal constrains for birds and fish (i.e., nesting and spawning seasons). - Municipal considerations. - Site-specific constraints. - Site interdependencies exist requiring consideration in the schedule. Several sites require the use of an adjacent site for staging. (authors)

  5. Dimers of π Protein Bind the A+T-Rich Region of the R6K γ Origin near the Leading-Strand Synthesis Start Sites: Regulatory Implications

    PubMed Central

    Krüger, Ricardo; Filutowicz, Marcin

    2000-01-01

    The replication of γ origin, a minimal replicon derived from plasmid R6K, is controlled by the Rep protein π. At low intracellular concentrations, π activates the γ origin, while it inhibits replication at elevated concentrations. Additionally, π acts as a transcription factor (auto)repressing its own synthesis. These varied regulatory functions depend on π binding to reiterated DNA sequences bearing a TGAGNG motif. However, π also binds to a “non-iteron” site (i.e., not TGAGNG) that resides in the A+T-rich region adjacent to the iterons. This positioning places the non-iteron site near the start sites for leading-strand synthesis that also occur in the A+T-rich region of γ origin. We have hypothesized that origin activation (at low π levels) would require the binding of π monomers to iterons, while the binding of π dimers to the non-iteron site (at high π levels) would be required to inhibit priming. Although monomers as well as dimers can bind to an iteron, we demonstrate that only dimers bind to the non-iteron site. Two additional pieces of data support the hypothesis of negative replication control by π binding to the non-iteron site. First, π binds to the non-iteron site about eight times less well than it binds to a single iteron. Second, hyperactive variants of π protein (called copy-up) either do not bind to the non-iteron site or bind to it less well than wild-type π. We propose a replication control mechanism whereby π would directly inhibit primer formation. PMID:10762246

  6. Using a Consensus Conference to Characterize Regulatory Concerns Regarding Bioremediation of Radionuclides and Heavy Metals in Mixed Wastes at DOE Sites

    SciTech Connect

    Lach, Denise

    2005-06-01

    We have spent this first part of the project preparing background material for conference participants and making arrangements for the conference itself. Material regarding state regulatory constraints to the use of bioremediation in the cleanup of radionuclides and heavy metals at DOE sites around the country has been added to the Bioremediation Briefing paper for participants. The Steering Committee has been formulated and will hold their first meeting via phone conference on Monday, September 13, 2005. On the agenda is identification of conference participants, experts, and initial issues likely to be addressed. Human Subjects approval has been secured from the University. The ''pre-test'' has been developed and is ready to implement. The Consensus Conference will be held in Phoenix, AZ during January and February 2005; we are working with the Chamber of Commerce to find an appropriate site.

  7. Crohn's Disease: The First Visit

    PubMed Central

    Farraye, Francis A.

    2011-01-01

    A Crohn's disease patient's first visit to a new practice is the optimal time to collect important clinical data and identify appropriate therapies. A methodologic approach to this visit is crucial. The focus of this visit should be on preparing the patient for the initiation of treatment, with particular attention to the necessary steps prior to the use of immunosuppressive and biologic agents. This paper is intended to provide recommendations and a checklist for the initial assessment and evaluation of patients with Crohn's disease. PMID:21528042

  8. From work plan to rod and beyond: Lessons learned on regulatory issues at the Weldon Spring Site

    SciTech Connect

    MacDonell, M.; Peterson, J.; Uhlmeyer, T.; Ferguson, R.

    1993-11-01

    Compliance with applicable or relevant and appropriate requirements (ARARs) is a key element of successful cleanup activities at environmental restoration sites. A number of ARAR issues were raised during the, planning, assessment, and implementation of restoration activities at a US Department of Energy (DOE) mixed waste site in Missouri. Resolutions were developed for issues ranging from storage time requirements to land disposal restrictions. This paper discusses ARAR issues and resolutions.

  9. Astronaut Steve Swanson Visits Goddard

    NASA Video Gallery

    On Tuesday, 3 March 2015, a special guest visited NASA Goddard Space Flight Center during his time back on Earth. Steven Swanson, NASA astronaut, intrigued the audience by highlighting his adventur...

  10. Preparing for an Office Visit

    MedlinePlus

    ... a Neurologist Preparing for an Office Visit Your Rights as a Patient Family & Friends Communities Research Matters Donate Clinical Trials Animal Research Resources Neurology Now Magazine Patient Education Brochures ...

  11. Skylab mission report, third visit

    NASA Technical Reports Server (NTRS)

    1974-01-01

    An evaluation is presented of the operational and engineering aspects of the third Skylab visit, including information on the performance of the command and service module and the experiment hardware, the crew's evaluation of the visit, and other visit-related areas of interest such as biomedical observations. The specific areas discussed are contained in the following: (1) solar physics and astrophysics investigations; (2) Comet Kohoutek experiments; (3) medical experiments; (4) earth observations, including data for the multispectral photographic facility, the earth terrain camera, and the microwave radiometer/scattermometer and altimeter; (5) engineering and technology experiments; (6) food and medical operational equipment; (7) hardware and experiment anomalies; and (8) mission support, mission objectives, flight planning, and launch phase summary. Conclusions discussed as a result of the third visit to Skylab involve the advancement of the sciences, practical applications, the durability of man and systems in space, and spaceflight effectiveness and economy.

  12. Free Energy Landscape of Lipid Interactions with Regulatory Binding Sites on the Transmembrane Domain of the EGF Receptor

    PubMed Central

    2016-01-01

    Lipid molecules can bind to specific sites on integral membrane proteins, modulating their structure and function. We have undertaken coarse-grained simulations to calculate free energy profiles for glycolipids and phospholipids interacting with modulatory sites on the transmembrane helix dimer of the EGF receptor within a lipid bilayer environment. We identify lipid interaction sites at each end of the transmembrane domain and compute interaction free energy profiles for lipids with these sites. Interaction free energies ranged from ca. −40 to −4 kJ/mol for different lipid species. Those lipids (glycolipid GM3 and phosphoinositide PIP2) known to modulate EGFR function exhibit the strongest binding to interaction sites on the EGFR, and we are able to reproduce the preference for interaction with GM3 over other glycolipids suggested by experiment. Mutation of amino acid residues essential for EGFR function reduce the binding free energy of these key lipid species. The residues interacting with the lipids in the simulations are in agreement with those suggested by experimental (mutational) studies. This approach provides a generalizable tool for characterizing the interactions of lipids that bind to specific sites on integral membrane proteins. PMID:27109430

  13. AGU Members Visit Capitol Hill

    NASA Astrophysics Data System (ADS)

    Von Holle, Kate

    2007-06-01

    More than 200 scientists and engineers from around the United States convened in Washington, D.C., on 1-2 May 2007 to participate in the annual Science Engineering and Technology (SET) Congressional Visits Day (CVD). The AGU Office of Public Affairs frequently helps to arrange for members' visits to their congressional delegations, but CVD is a unique event during which AGU members can team up with a larger group of scientists and engineers to promote federal funding of scientific research.

  14. Visiting Vehicle Ground Trajectory Tool

    NASA Technical Reports Server (NTRS)

    Hamm, Dustin

    2013-01-01

    The International Space Station (ISS) Visiting Vehicle Group needed a targeting tool for vehicles that rendezvous with the ISS. The Visiting Vehicle Ground Trajectory targeting tool provides the ability to perform both realtime and planning operations for the Visiting Vehicle Group. This tool provides a highly reconfigurable base, which allows the Visiting Vehicle Group to perform their work. The application is composed of a telemetry processing function, a relative motion function, a targeting function, a vector view, and 2D/3D world map type graphics. The software tool provides the ability to plan a rendezvous trajectory for vehicles that visit the ISS. It models these relative trajectories using planned and realtime data from the vehicle. The tool monitors ongoing rendezvous trajectory relative motion, and ensures visiting vehicles stay within agreed corridors. The software provides the ability to update or re-plan a rendezvous to support contingency operations. Adding new parameters and incorporating them into the system was previously not available on-the-fly. If an unanticipated capability wasn't discovered until the vehicle was flying, there was no way to update things.

  15. An interferon regulatory factor binding site in the U5 region of the bovine leukemia virus long terminal repeat stimulates Tax-independent gene expression.

    PubMed

    Kiermer, V; Van Lint, C; Briclet, D; Vanhulle, C; Kettmann, R; Verdin, E; Burny, A; Droogmans, L

    1998-07-01

    Bovine leukemia virus (BLV) replication is controlled by both cis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication. PMID:9621009

  16. Savannah River Site Public and regulatory involvement in the transuranic (TRU) program and their effect on decisions to dispose of Pu-238 heat source tru waste onsite

    SciTech Connect

    Bert Crapse, H.M.; Sonny, W.T.

    2007-07-01

    The key to successful public involvement at the Savannah River Site (SRS) has been and continues to be vigorous, up-front involvement of the public and state regulators with technical experts. The SRS Waste Management Program includes all forms of radioactive waste. All of the decisions associated with the management of these wastes are of interest to the public and successful program implementation would be impossible without including the public up-front in the program formulation. Serious problems can result if program decisions are made without public involvement, and if the public is informed after key decisions are made. This paper will describe the regulatory and public involvement program and their effects on the decisions concerning the disposal at the Savannah River Site (SRS) of heat source Pu-238 TRU waste. As can be imagined, a decision to dispose of TRU waste onsite versus shipment to the Waste Isolation Pilot Plan (WIPP) in New Mexico for disposal is of considerable interest to the stakeholders in South Carolina. The interaction between the stakeholders not only include the general public, but also the South Carolina Department of Health and Environmental Control (SCDHEC) and Region IV of the Environmental Protection Agency (EPA). The discussions, educational sessions, and negotiations include resolution of equity issues as well and moved forward to an understanding of the difficulties including risk management faced by the Ship-to- WIPP program. Once the program was better understood, the real negotiations concerning equity, safety, and risk to workers from handling Pu-238 waste could begin. This paper will also discuss the technical, regulatory, and public involvement aspects of disposal onsite that must be properly communicated if the program is to be successful. The Risk Based End State Vision Report for the Savannah River Site includes a variance that proposes on-site near surface disposal of waste from the program to produce Pu-238 heat sources

  17. Site-specific regulatory interaction between spinach leaf sucrose-phosphate synthase and 14-3-3 proteins

    NASA Technical Reports Server (NTRS)

    Toroser, D.; Athwal, G. S.; Huber, S. C.; Davies, E. (Principal Investigator)

    1998-01-01

    We report an Mg2+-dependent interaction between spinach leaf sucrose-phosphate synthase (SPS) and endogenous 14-3-3 proteins, as evidenced by co-elution during gel filtration and co-immunoprecipitation. The content of 14-3-3s associated with an SPS immunoprecipitate was inversely related to activity, and was specifically reduced when tissue was pretreated with 5-aminoimidazole-4-carboxamide riboside, suggesting metabolite control in vivo. A synthetic phosphopeptide based on Ser-229 was shown by surface plasmon resonance to bind a recombinant plant 14-3-3, and addition of the phosphorylated SPS-229 peptide was found to stimulate the SPS activity of an SPS:14-3-3 complex. Taken together, the results suggest a regulatory interaction of 14-3-3 proteins with Ser-229 of SPS.

  18. A home visit program for CAPD.

    PubMed

    Warmington, V

    1996-01-01

    In the U.K. in the last five years a reassessment of the central role of the hospital has taken place, with a fundamental shift in care for people with increased dependencies to community settings. For patients using peritoneal dialysis a need has been realized for a home-visiting service by specialist renal nurses who can manage and coordinate the program of care, thus reducing the strain on hospital resources. In addition, the provision of a community nurse to visit the patient at home means that ongoing education and training can be undertaken in a suitable learning environment. The home-visiting program creates an opportunity to develop an holistic care plan using strategies of general health promotion as well as practical nursing care. This paper highlights the experiences of a pioneering model of community continuous ambulatory peritoneal dialysis care in the South London. Auditing of this unusually funded post has shown significant reductions in peritonitis, exit-site infections, and hospital admissions in this growing patient population. PMID:8728249

  19. Functional analysis of the BRI1 receptor kinase by Thr-for-Ser substitution in a regulatory autophosphorylation site

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BRI1 becomes highly phosphorylated in vivo upon perception of the ligand, brassinolide, as a result of autophosphorylation and transphosphorylation by its co-receptor kinase, BAK1. Important autophosphorylation sites include those involved in activation of kinase activity and those that are inhibito...

  20. Regulatory guidance document

    SciTech Connect

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  1. Characterisation of multiple regulatory domains spanning the major transcriptional start site of the FUS gene, a candidate gene for motor neurone disease.

    PubMed

    Khursheed, Kejhal; Wilm, Thomas P; Cashman, Christine; Quinn, John P; Bubb, Vivien J; Moss, Diana J

    2015-01-21

    Fused-In-Sarcoma (FUS) is a candidate gene for neurological disorders including motor neurone disease and Parkinson׳s disease in addition to various types of cancer. Recently it has been reported that over expression of FUS causes motor neurone disease in mouse models hence mutations leading to changes in gene expression may contribute to the development of neurodegenerative disease. Genome evolutionary conservation was used to predict important cis-acting DNA regulators of the FUS gene promoter that direct transcription. The putative regulators identified were analysed in reporter gene assays in cells and in chick embryos. Our analysis indicated in addition to regulatory domains 5' of the transcriptional start site an important regulatory domain resides in intron 1 of the gene itself. This intronic domain functioned both in cell lines and in vivo in the neural tube of the chick embryo including developing motor neurones. Our data suggest the interaction of multiple domains including intronic domains are involved in expression of FUS. A better understanding of the regulation of expression of FUS may give insight into how its stimulus inducible expression may be associated with neurological disorders. PMID:25451114

  2. Regulatory acceptance of the proposed well abandonment program for the present landfill, Operable Unit 7, Rocky Flats Environmental Technology Site, Golden, Colorado

    SciTech Connect

    Wood, M.R.

    1995-07-01

    The regulatory agencies approved a well abandonment program for the Present Landfill, Operable Unit (OU) 7 at the Rocky Flats Environmental Technology Site, only three months after preparation. The proposed well abandonment program consists of abandoning 26 of the 54 existing monitoring wells in OU 7 that are currently sampled quarterly as Resource Conservation and Recovery Act (RCRA) compliance wells or sitewide groundwater protection wells. Well abandonment was proposed on the basis that the purpose of each well has been fulfilled, the wells fall under the footprint of the landfill cap, the presence of the wells would compromise the integrity of the cap because holes would have to be cut in the synthetic liner, and unequal compaction of the fill material around the wells would potentially cause differential settlement of the cap. The proposal provided the technical justification to abandon the wells in place. The timely approval of the proposal by the regulatory agencies will allow the abandonment of the wells during fiscal year 1995 under the sitewide Well Abandonment and Replacement Program (WARP). Cost savings resulting from a decrease in the number of wells to be sampled under the groundwater monitoring program are estimated at $416,000 per year. This paper presents a summary of the well abandonment program, discusses the timely approvals required for implementation, and present the potential cost savings that can be achieved through implementation of the program.

  3. Regulatory roles of conserved phosphorylation sites in the activation T-loop of the MAP kinase ERK1

    PubMed Central

    Lai, Shenshen; Pelech, Steven

    2016-01-01

    The catalytic domains of most eukaryotic protein kinases are highly conserved in their primary structures. Their phosphorylation within the well-known activation T-loop, a variable region between protein kinase catalytic subdomains VII and VIII, is a common mechanism for stimulation of their phosphotransferase activities. Extracellular signal–regulated kinase 1 (ERK1), a member of the extensively studied mitogen-activated protein kinase (MAPK) family, serves as a paradigm for regulation of protein kinases in signaling modules. In addition to the well-documented T202 and Y204 stimulatory phosphorylation sites in the activation T-loop of ERK1 and its closest relative, ERK2, three additional flanking phosphosites have been confirmed (T198, T207, and Y210 from ERK1) by high-throughput mass spectrometry. In vitro kinase assays revealed the functional importance of T207 and Y210, but not T198, in negatively regulating ERK1 catalytic activity. The Y210 site could be important for proper conformational arrangement of the active site, and a Y210F mutant could not be recognized by MEK1 for phosphorylation of T202 and Y204 in vitro. Autophosphorylation of T207 reduces the catalytic activity and stability of activated ERK1. We propose that after the activation of ERK1 by MEK1, subsequent slower phosphorylation of the flanking sites results in inhibition of the kinase. Because the T207 and Y210 phosphosites of ERK1 are highly conserved within the eukaryotic protein kinase family, hyperphosphorylation within the kinase activation T-loop may serve as a general mechanism for protein kinase down-regulation after initial activation by their upstream kinases. PMID:26823016

  4. Structure of the Pseudokinase VRK3 Reveals a Degraded Catalytic Site, a Highly Conserved Kinase Fold, and a Putative Regulatory Binding Site

    PubMed Central

    Scheeff, Eric D.; Eswaran, Jeyanthy; Bunkoczi, Gabor; Knapp, Stefan; Manning, Gerard

    2009-01-01

    Summary About 10% of all protein kinases are predicted to be enzymatically inactive pseudokinases, but the structural details of kinase inactivation have remained unclear. We present the first structure of a pseudokinase, VRK3, and that of its closest active relative, VRK2. Profound changes to the active site region underlie the loss of catalytic activity, and VRK3 cannot bind ATP because of residue substitutions in the binding pocket. However, VRK3 still shares striking structural similarity with VRK2, and appears to be locked in a pseudoactive conformation. VRK3 also conserves residue interactions that are surprising in the absence of enzymatic function; these appear to play important architectural roles required for the residual functions of VRK3. Remarkably, VRK3 has an “inverted” pattern of sequence conservation: although the active site is poorly conserved, portions of the molecular surface show very high conservation, suggesting that they form key interactions that explain the evolutionary retention of VRK3. PMID:19141289

  5. Virtual visits for Parkinson disease

    PubMed Central

    Venkataraman, Vinayak; Donohue, Sean J.; Biglan, Kevin M.; Wicks, Paul

    2014-01-01

    Summary We sought to characterize recommendations and feedback of patients with Parkinson disease, each offered a free telemedicine consultation with a specialist. Visits consisted of history, neurologic examination, and recommendations. Midway through the program, patients were asked to complete an online satisfaction survey. From August 2012 to May 2013, 55 patients in 5 states (mean age 67.8 years) participated, with 80% of visits conducted from their home. Patients with Parkinson disease were recommended to exercise (86%), change current medication (63%), and add new medication (53%). Thirty-three of 35 consecutive patients completed a survey. Patient satisfaction exceeded 90% for virtually all aspects of the visit measured. Providing care to patients in their homes via telemedicine is feasible, results in changes to care, and is well-received. PMID:24790799

  6. 76 FR 81959 - Notice of Proposed Information Collection: Comment Request; Homelessness Prevention Study Site...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... Study Site Visits AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice. SUMMARY: The... following information: Title of Proposal: Homelessness Prevention Study Site Visits. OMB Control Number, if... requirements associated with HUD's Homelessness Prevention Study Site Visits. This information...

  7. Intestinal lamina propria retaining CD4+CD25+ regulatory T cells is a suppressive site of intestinal inflammation.

    PubMed

    Makita, Shin; Kanai, Takanori; Nemoto, Yasuhiro; Totsuka, Teruji; Okamoto, Ryuichi; Tsuchiya, Kiichiro; Yamamoto, Masafumi; Kiyono, Hiroshi; Watanabe, Mamoru

    2007-04-15

    It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only does active suppression by regulatory T (T(REG)) cells play an important role in the normal intestinal homeostasis, but also that its dysregulation of immune response leads to the development of inflammatory bowel disease. In this study, we demonstrate that murine CD4(+)CD25(+) T cells residing in the intestinal lamina propria (LP) constitutively express CTLA-4, glucocorticoid-induced TNFR, and Foxp3 and suppress proliferation of responder CD4(+) T cells in vitro. Furthermore, cotransfer of intestinal LP CD4(+)CD25(+) T cells prevents the development of chronic colitis induced by adoptive transfer of CD4(+)CD45RB(high) T cells into SCID mice. When lymphotoxin (LT)alpha-deficient intercrossed Rag2 double knockout mice (LTalpha(-/-) x Rag2(-/-)), which lack mesenteric lymph nodes and Peyer's patches, are transferred with CD4(+)CD45RB(high) T cells, they develop severe wasting disease and chronic colitis despite the delayed kinetics as compared with the control LTalpha(+/+) x Rag2(-/-) mice transferred with CD4(+)CD45RB(high) T cells. Of note, when a mixture of splenic CD4(+)CD25(+) T(REG) cells and CD4(+)CD45RB(high) T cells are transferred into LTalpha(-/-) x Rag2(-/-) recipients, CD4(+)CD25(+) T(REG) cells migrate into the colon and prevent the development of colitis in LTalpha(-/-) x Rag2(-/-) recipients as well as in the control LTalpha(+/+) x Rag2(-/-) recipients. These results suggest that the intestinal LP harboring CD4(+)CD25(+) T(REG) cells contributes to the intestinal immune suppression. PMID:17404275

  8. Grandparent Visitation Rights: Successful Acquisition of Court-Ordered Visitation

    ERIC Educational Resources Information Center

    Henderson, Tammy L.

    2005-01-01

    The author examined 65 cases in which grandparents successfully acquired court-ordered visitation with their grandchildren to understand how courts shape family development and how social scientists might support families who are engaged in legal disputes. Using grounded theory methods, two categories explained grandparents' success at acquiring…

  9. Visitation arrangements for impaired parents.

    PubMed

    Montgomery, Stephen A; Street, David F

    2011-07-01

    Forensic mental health professionals are frequently asked to evaluate the parenting skills of divorcing parents because the court seeks help in determining the custody, visitation, and parenting time arrangements for the children. When one of the parents is impaired, the court wants to know the way to help the children have a good relationship with that parent and keep the children safe. There is little empirical research to answer such questions. In this article, the authors describe their methodology for providing useful clinical information to the court to help guide their decisions regarding visitation with impaired parents. PMID:21683915

  10. Stennis visits Lake Cormorant school

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Alexis Harry, assistant director of Astro Camp at NASA's John C. Stennis Space Center, talks with students at Lake Cormorant (Miss.) Elementary School during a 'Living and Working in Space' presentation March 30. Stennis hosted the school presentation during a visit to the Oxford area. Harry, who also is a high school biology teacher in Slidell, La., spent time discussing space travel with students and answering questions they had about the experience, including queries about how astronauts eat, sleep and drink in space. The presentation was sponsored by the NASA Office of External Affairs and Education at Stennis. For more information about NASA education initiatives, visit: http://education.ssc.nasa.gov/.

  11. Developing a Mentor-Protege Program. Job-Visitation Activity. Project Report.

    ERIC Educational Resources Information Center

    Rosales, Mary Lou; Smith, Armenia

    This guidebook is designed for use by teachers implementing a mentor-protege job-site visitation program to help vocational students, particularly nontraditional students, understand and gain more knowledge about selected vocational fields. The first section of the guide reports on the job site visitation program implemented in the Ysleta…

  12. Lessons Learned from WIPP Site Characteriztion, Performance Assessment, and Regulatory Review Related to Radionuclide Migration through Water-Conducting Features

    SciTech Connect

    Beauheim, R.L.: Larson. K.W.

    1998-11-11

    Many lessons have been learned over the past 24 years as the Waste Isolation Pilot Plant (WIPP) project has progressed from initial site characterization to final licensing that may be of relevance to other nuclear-waste-disposal projects. These lessons pertain to the manner in which field and laboratory investigations are planned, how experiments are interpreted, how conceptual and numerical models are developed and simplified~ and how defensibility and credibility are achieved and maintained. These lessons include 1) Site characterization and performance assessment (PA) should evolve together through an iterative process, with neither activity completely dominating the other. 2) Defensibility and credibility require a much greater depth of understanding than can be represented in PA models. 3) Experimentalists should be directly involved in model and parameter abstraction and simplification for PA. 4) External expert review should be incorporated at all stages of a project~ not just after an experiment or modeling activity is completed. 5) Key individuals should be retained for the life of a project or a process must be established to transfer their working knowledge to new individuals. 6) An effective QA program needs to be stable and consistent for the duration of a project and rests on best scientific practices. All of these lessons relate to the key point that consideration must be given from the earliest planning stages to maximizing the defensibility and credibility of all work.

  13. Internet-Based Medical Visit and Diagnosis for Common Medical Problems: Experience of First User Cohort

    PubMed Central

    Shevchik, Grant J.; Paone, Suzanne; Martich, G. Daniel

    2011-01-01

    Abstract Objective Internet-based medical visits, or “structured e-Visits,” allow patients to report symptoms and seek diagnosis and treatment from their doctor over a secure Web site, without calling or visiting the physician's office. While acceptability of e-Visits has been investigated, outcomes associated with e-Visits, that is, whether patients receiving diagnoses receive appropriate care or need to return to the doctor, remain unexplored. Materials and Methods: The first 156 e-Visit users from a large family medicine practice were surveyed regarding their experience with the e-Visit and e-Visit outcomes. In addition, medical records for patients making e-Visits were reviewed to examine need for follow-up care within 7 days. Results: Interviews were completed with 121 patients (77.6% participation). The most common type of e-Visit was for “other” symptoms or concerns (37%), followed by sinus/cold symptoms (35%). Back pain, urinary symptoms, cough, diarrhea, conjunctivitis, and vaginal irritation were each less frequent (<10%). A majority, 61% completed e-Visits with their own physician. The majority of patients (57.0%) reported receipt of a diagnosis without need for follow-up beyond a prescription; 75% of patients thought the e-Visit was as good as or better than an in-person visit, and only 11.6% felt that their concerns or questions were incompletely addressed. In a review of medical records, 16.9% had a follow-up visit within 7 days, mostly for the same condition. Four of these were on the same day as the e-Visit, including one emergency department visit. Conclusions: Outcomes for the e-Visit suggest that it is an appropriate and potentially cost-saving addition to in-person delivery of primary care. PMID:21457013

  14. 28 CFR 540.47 - Media visits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Media visits. 540.47 Section 540.47... PERSONS IN THE COMMUNITY Visiting Regulations § 540.47 Media visits. Requirements for media visits are governed by the provisions on contact with news media (see subpart E of this part). A media...

  15. The Visiting Teacher in Texas Public Schools.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin. Div. of Guidance Services.

    This brochure sketches the range of services provided by visiting teachers in the Texas Public Schools and offers suggestions for establishing a visiting teacher program in other school systems. The rationale for the visiting teacher program is outlined first followed by an explanation of who the visiting teacher is. Twenty functions of the…

  16. 28 CFR 540.47 - Media visits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Media visits. 540.47 Section 540.47... PERSONS IN THE COMMUNITY Visiting Regulations § 540.47 Media visits. Requirements for media visits are governed by the provisions on contact with news media (see subpart E of this part). A media...

  17. Using a Consensus Conference to Characterize Regulatory Concerns Regarding Bioremediation of Radionuclides and Heavy Metals in Mixed Waste at DOE Sites

    SciTech Connect

    Denise Lach; Stephanie Sanford

    2006-09-01

    A consensus workshop was developed and convened with ten state regulators to characterize concerns regarding emerging bioremediation technology to be used to clean-up radionuclides and heavy metals in mixed wastes at US DOE sites. Two questions were explored: integrated questions: (1) What impact does participation in a consensus workshop have on the knowledge, attitudes, and practices of state regulators regarding bioremediation technology? (2) How effective is a consensus workshop as a strategy for eliciting and articulating regulators’ concerns regarding the use of bioremediation to clean up radionuclides and heavy metals in mixed wastes at U.S. Department of Energy Sites around the county? State regulators met together for five days over two months to learn about bioremediation technology and develop a consensus report of their recommendations regarding state regulatory concerns. In summary we found that panel members: - quickly grasped the science related to bioremediation and were able to effectively interact with scientists working on complicated issues related to the development and implementation of the technology; - are generally accepting of in situ bioremediation, but concerned about costs, implementation (e.g., institutional controls), and long-term effectiveness of the technology; - are concerned equally about technological and implementation issues; and - believed that the consensus workshop approach to learning about bioremediation was appropriate and useful. Finally, regulators wanted decision makers at US DOE to know they are willing to work with DOE regarding innovative approaches to clean-up at their sites, and consider a strong relationship between states and the DOE as critical to any effective clean-up. They do not want perceive themselves to be and do not want others to perceive them as barriers to successful clean-up at their sites.

  18. Pituitary Ets-1 and GABP bind to the growth factor regulatory sites of the rat prolactin promoter.

    PubMed

    Schweppe, R E; Gutierrez-Hartmann, A

    2001-03-01

    Ets factors play a critical role in oncogenic Ras- and growth factor-mediated regulation of the proximal rat prolactin (rPRL) promoter in pituitary cells. The rPRL promoter contains two key functional Ets binding sites (EBS): a composite EBS/Pit-1 element located at -212 and an EBS that co-localizes with the basal transcription element (BTE, or A-site) located at -96. Oncogenic Ras exclusively signals to the -212 site, which we have named the Ras response element (RRE); whereas the response of multiple growth factors (FGFs, EGF, IGF, insulin and TRH) maps to both EBSs. Although Ets-1 and GA binding protein (GABP) have been implicated in the Ras and insulin responses, respectively, the precise identity of the pituitary Ets factors that specifically bind to the RRE and BTE sites remains unknown. In order to identify the Ets factor(s) present in GH4 and GH3 nuclear extracts (GH4NE and GH3NE) that bind to the EBSs contained in the RRE and BTE, we used EBS-RRE and BTE oligonucleotides in electrophoretic mobility shift assays (EMSAs), antibody supershift assays, western blot analysis of partially purified fractions and UV-crosslinking studies. EMSAs, using either the BTE or EBS-RRE probes, identified a specific protein-DNA complex, designated complex A, which contains an Ets factor as determined by oligonucleotide competition studies. Using western blot analysis of GH3 nuclear proteins that bind to heparin-Sepharose, we have shown that Ets-1 and GABP, which are MAP kinase substrates, co-purify with complex A, and supershift analysis with specific antisera revealed that complex A contains Ets-1, GABPalpha and GABPbeta1. In addition, we show that recombinant full-length Ets-1 binds equivalently to BTE and EBS-RRE probes, while recombinant GABPalpha/beta preferentially binds to the BTE probe. Furthermore, comparing the DNA binding of GH4NE containing both Ets-1 and GABP and HeLa nuclear extracts devoid of Ets-1 but containing GABP, we were able to show that the EBS

  19. Potential regulatory phosphorylation sites in a Medicago truncatula plasma membrane proton pump implicated during early symbiotic signaling in roots.

    PubMed

    Nguyen, Thao T; Volkening, Jeremy D; Rose, Christopher M; Venkateshwaran, Muthusubramanian; Westphall, Michael S; Coon, Joshua J; Ané, Jean-Michel; Sussman, Michael R

    2015-08-01

    In plants and fungi the plasma membrane proton pump generates a large proton-motive force that performs essential functions in many processes, including solute transport and the control of cell elongation. Previous studies in yeast and higher plants have indicated that phosphorylation of an auto-inhibitory domain is involved in regulating pump activity. In this report we examine the Medicago truncatula plasma membrane proton pump gene family, and in particular MtAHA5. Yeast complementation assays with phosphomimetic mutations at six candidate sites support a phosphoregulatory role for two residues, suggesting a molecular model to explain early Nod factor-induced changes in the plasma membrane proton-motive force of legume root cells. PMID:26188545

  20. HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells

    PubMed Central

    Zhang, Shaofei; Zhu, Iris; Deng, Tao; Furusawa, Takashi; Rochman, Mark; Vacchio, Melanie S.; Bosselut, Remy; Yamane, Arito; Casellas, Rafael; Landsman, David; Bustin, Michael

    2016-01-01

    The activation of naïve B lymphocyte involves rapid and major changes in chromatin organization and gene expression; however, the complete repertoire of nuclear factors affecting these genomic changes is not known. We report that HMGN proteins, which bind to nucleosomes and affect chromatin structure and function, co-localize with, and maintain the intensity of DNase I hypersensitive sites genome wide, in resting but not in activated B cells. Transcription analyses of resting and activated B cells from wild-type and Hmgn−/− mice, show that loss of HMGNs dampens the magnitude of the transcriptional response and alters the pattern of gene expression during the course of B-cell activation; defense response genes are most affected at the onset of activation. Our study provides insights into the biological function of the ubiquitous HMGN chromatin binding proteins and into epigenetic processes that affect the fidelity of the transcriptional response during the activation of B cell lymphocytes. PMID:27112571

  1. The usage of visual indicators in regulatory monitoring at hard-bottom finfish aquaculture sites in Newfoundland (Canada).

    PubMed

    Hamoutene, Dounia; Salvo, Flora; Donnet, Sebastien; Dufour, Suzanne C

    2016-07-15

    Finfish aquaculture can be installed over hard and patchy substrates where grab sampling is challenging and use of video can be an appropriate tool to document benthic changes. Video monitoring can show visual indicators of enrichment, namely flocculent matter, Beggiatoa-like mats, and opportunistic polychaete complexes (OPC). We examined factors influencing presence of indicators using 52 video monitoring reports collected in Newfoundland, Canada. The main driving factor was distance to cage, with indicators showing a higher probability of occurrence within 10m from cages due to low current velocities. Indicators were less prevalent on sites dominated by hard substrates while OPC in particular were restricted to depths >35m. Beggiatoa-like bacteria covered a larger surface than the two other indicators; however, our results suggest the necessity of amalgamating information related to all the indicators (including bare stations that could indicate anoxia) to establish a more accurate evaluation of aquaculture impact. PMID:27105727

  2. Beautiful Science: Worth a Visit

    ERIC Educational Resources Information Center

    Bingham, Frederick M.

    2013-01-01

    For those in the profession of teaching physics who reside in or plan to visit the Los Angeles area, I would highly recommend a trip to the Huntington Library in San Marino, specifically to a permanent exhibit entitled "Beautiful Science: Ideas that Changed the World" in the Dibner Hall of the History of Science. The exhibit contains original…

  3. Visiting School Campuses: Reporter Guide

    ERIC Educational Resources Information Center

    Carr, Sarah

    2013-01-01

    Spending time in schools and classrooms can be one of the best ways for novice reporters to dive into the education beat, and for veteran journalists to find fresh inspiration. While it is certainly not necessary for every story, education journalists should try their best to make time to visit schools. Classroom observations and campus tours help…

  4. School Visits: The Author's Viewpoint.

    ERIC Educational Resources Information Center

    Miles, Betty; Avi

    1987-01-01

    Two authors of children's books discuss the elements of a successful school visit, including how to select and contact an author; fees; choosing dates; having books available; planning collaboratively with authors, principals, teachers, and parents; organizing the schedule; the author as critic; publicity; travel plans; autographs; and follow-up.…

  5. Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia.

    PubMed

    Merner, Nancy D; Chandler, Madison R; Bourassa, Cynthia; Liang, Bo; Khanna, Arjun R; Dion, Patrick; Rouleau, Guy A; Kahle, Kristopher T

    2015-01-01

    Many encoded gene products responsible for neurodevelopmental disorders (NDs) like autism spectrum disorders (ASD), schizophrenia (SCZ), intellectual disability (ID), and idiopathic generalized epilepsy (IGE) converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5) Cl(-) transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS), functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD) in human ASD (R952H and R1049C) and SCZ (R952H) previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W) with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection (SSC) revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs. PMID:26528127

  6. Regulatory domain or CpG site variation in SLC12A5, encoding the chloride transporter KCC2, in human autism and schizophrenia

    PubMed Central

    Merner, Nancy D.; Chandler, Madison R.; Bourassa, Cynthia; Liang, Bo; Khanna, Arjun R.; Dion, Patrick; Rouleau, Guy A.; Kahle, Kristopher T.

    2015-01-01

    Many encoded gene products responsible for neurodevelopmental disorders (NDs) like autism spectrum disorders (ASD), schizophrenia (SCZ), intellectual disability (ID), and idiopathic generalized epilepsy (IGE) converge on networks controlling synaptic function. An increase in KCC2 (SLC12A5) Cl− transporter activity drives the developmental GABA excitatory-inhibitory sequence, but the role of KCC2 in human NDs is essentially unknown. Here, we report two rare, non-synonymous (NS), functionally-impairing variants in the KCC2 C-terminal regulatory domain (CTRD) in human ASD (R952H and R1049C) and SCZ (R952H) previously linked with IGE and familial febrile seizures, and another novel NS KCC2 variant in ASD (R1048W) with highly-predicted pathogenicity. Exome data from 2517 simplex families in the ASD Simon Simplex Collection (SSC) revealed significantly more KCC2 CTRD variants in ASD cases than controls, and interestingly, these were more often synonymous and predicted to disrupt or introduce a CpG site. Furthermore, full gene analysis showed ASD cases are more likely to contain rare KCC2 variants affecting CpG sites than controls. These data suggest genetically-encoded dysregulation of KCC2-dependent GABA signaling may contribute to multiple human NDs. PMID:26528127

  7. Savannah River Site Public and Regulatory Involvement in the Cercla Low-Level Waste (LLW) Program and Their Effect on Decisions to Dispose of LLW Generated by Cercla

    SciTech Connect

    Belencan, H.

    2008-07-01

    The key to successful public involvement at the Savannah River Site (SRS) has been and continues to be vigorous, up-front involvement of the public, federal and state regulators with technical experts. The SRS Waste Management Program includes all forms of radioactive waste. All of the decisions associated with the management of these wastes are of interest to the public and successful program implementation would be impossible without including the public up-front in the program formulation. Serious problems can result if program decisions are made without public involvement, and if the public is informed after key decisions are made. This paper will describe the regulatory and public involvement program and their effects on the decisions concerning the disposal at the Savannah River Site (SRS) of LLW generated from CERCLA Removal and Remedial Actions. At SRS the Deactivation and Decommissioning (D and D) project has generated large amounts of LLW from the removal of buildings and processing facilities. The D and D project is expected to generate even larger amounts of LLW in the future. The most cost effective disposal alternated is to use the onsite LLW disposal facility in E-Area. The E-Area LLW Facility is owned and operated by the Department of Energy (DOE) under its authority granted by the Atomic Energy Act of 1954, as amended. Since the disposal of CERCLA generated waste is also governed by the Environmental Protection Agency (EPA) CERCLA regulations, it is important that EPA, DOE, and the South Carolina Department of Health and Environmental Control (SCDHEC) work together to resolve any conflicts in implementation of the D and D project so that all regulations are followed and the project can be continued successfully. An issue of particular significance will be described in this paper that, were it not resolved successfully, would have jeopardized the completion of one project and resulted in higher overall project costs. The EPA determined in review of

  8. Insights into structural and regulatory roles of Sec16 in COPII vesicle formation at ER exit sites

    PubMed Central

    Yorimitsu, Tomohiro; Sato, Ken

    2012-01-01

    COPII-coated buds are formed at endoplasmic reticulum exit sites (ERES) to mediate ER-to-Golgi transport. Sec16 is an essential factor in ERES formation, as well as in COPII-mediated traffic in vivo. Sec16 interacts with multiple COPII proteins, although the functional significance of these interactions remains unknown. Here we present evidence that full-length Sec16 plays an important role in regulating Sar1 GTPase activity at the late steps of COPII vesicle formation. We show that Sec16 interacts with Sec23 and Sar1 through its C-terminal conserved region and hinders the ability of Sec31 to stimulate Sec23 GAP activity toward Sar1. We also find that purified Sec16 alone can self-assemble into homo-oligomeric complexes on a planar lipid membrane. These features ensure prolonged COPII coat association within a preformed Sec16 cluster, which may lead to the formation of ERES. Our results indicate a mechanistic relationship between COPII coat assembly and ERES formation. PMID:22675024

  9. Virtual screening of gene expression regulatory sites in non-coding regions of the infectious salmon anemia virus

    PubMed Central

    2014-01-01

    Background Members of the Orthomyxoviridae family, which contains an important fish pathogen called the infectious salmon anemia virus (ISAV), have a genome consisting of eight segments of single-stranded RNA that encode different viral proteins. Each of these segments is flanked by non-coding regions (NCRs). In other Orthomyxoviruses, sequences have been shown within these NCRs that regulate gene expression and virulence; however, only the sequences of these regions are known in ISAV, and a biological role has not yet been attributed to these regions. This study aims to determine possible functions of the NCRs of ISAV. Results The results suggested an association between the molecular architecture of NCR regions and their role in the viral life cycle. The available NCR sequences from ISAV isolates were compiled, alignments were performed to obtain a consensus sequence, and conserved regions were identified in this consensus sequence. To determine the molecular structure adopted by these NCRs, various bioinformatics tools, including RNAfold, RNAstructure, Sfold, and Mfold, were used. This hypothetical structure, together with a comparison with influenza, yielded reliable secondary structure models that lead to the identification of conserved nucleotide positions on an intergenus level. These models determined which nucleotide positions are involved in the recognition of the vRNA/cRNA by RNA-dependent RNA polymerase (RdRp) or mRNA by the ribosome. Conclusions The information obtained in this work allowed the proposal of previously unknown sites that are involved in the regulation of different stages of the viral cycle, leading to the identification of new viral targets that may assist future antiviral strategies. PMID:25069483

  10. Study of the impacts of regulations affecting the acceptance of Integrated Community Energy Systems: public utility, energy facility siting and municipal franchising regulatory programs in Arizona. Preliminary background report

    SciTech Connect

    Feurer, D.A.; Weaver, C.L.; Gallagher, K.C.; Hejna, D.; Rielley, K.J.

    1980-01-01

    This report is one of a series of preliminary reports describing the laws and regulatory programs of the United States and each of the 50 states affecting the siting and operation of energy generating facilities likely to be used in Integrated Community Energy Systems (ICES). Public utility regulatory statutes, energy facility siting programs, and municipal franchising authority are examined to identify how they may impact on the ability of an organization, whether or not it be a regulated utility, to construct and operate an ICES. This report describes laws and regulatory programs in Arizona. The Arizona state constitution establishes the Arizona Corporation Commission to regulate public service corporations. Within the area of its jurisdiction, the Commission has exclusive power and may not be interfered with by the legislature except in one narrow instance as described in the case Corporation Commission v. Pacific Greyhound Lines.

  11. STS-128 crew visits Stennis

    NASA Technical Reports Server (NTRS)

    2009-01-01

    Astronauts C.J. Sturckow (seated, left) and Pat Forrester (seated, right) sign autographs during their Oct. 7 visit to Stennis Space Center. The astronauts visited the rocket engine testing facility to thank Stennis employees for contributions to their recent STS-128 space shuttle mission. All three of the main engines used on the mission were tested at Stennis. Sturckow served as commander for the STS-128 flight; Forrester was a mission specialist. During a 14-day mission aboard space shuttle discovery, the STS-128 crew delivered equipment and supplies to the International Space Station, including science and storage racks, a freezer to store research samples, a new sleeping compartment and an exercise treadmill. The mission featured three spacewalks to replace experiments and install new equipment at the space station.

  12. Florivory and pollinator visitation: a cautionary tale.

    PubMed

    Tsuji, Kaoru; Dhami, Manpreet K; Cross, David J R; Rice, Carolyn P; Romano, Nic H; Fukami, Tadashi

    2016-01-01

    Florivory, or damage to flowers by herbivores, can make flowers less attractive to pollinators, potentially resulting in reduced plant fitness. However, not many studies have combined observations with experiments to assess the causal link between florivory and pollination. We conducted field observations at eight sites in northern California, combined with field experiments that involved artificial floral damage, to study the effect of florivory on pollination in the hummingbird-pollinated sticky monkeyflower, Mimulus aurantiacus We used two indicators of pollinator visitation, stigma closure and the presence of microorganisms in floral nectar. The field observations revealed that stigma closure was less frequent in damaged flowers than in intact flowers. In the experiments, however, floral damage did not decrease stigma closure or microbial detection in nectar. Instead, neighbouring flowers were similar for both indicators. These results suggest that the observed negative association between florivory and pollination is not causal and that the location of flowers is more important to pollinator visitation than florivory in these populations of M. aurantiacus. PMID:27178063

  13. Florivory and pollinator visitation: a cautionary tale

    PubMed Central

    Tsuji, Kaoru; Dhami, Manpreet K.; Cross, David J.R.; Rice, Carolyn P.; Romano, Nic H.; Fukami, Tadashi

    2016-01-01

    Florivory, or damage to flowers by herbivores, can make flowers less attractive to pollinators, potentially resulting in reduced plant fitness. However, not many studies have combined observations with experiments to assess the causal link between florivory and pollination. We conducted field observations at eight sites in northern California, combined with field experiments that involved artificial floral damage, to study the effect of florivory on pollination in the hummingbird-pollinated sticky monkeyflower, Mimulus aurantiacus. We used two indicators of pollinator visitation, stigma closure and the presence of microorganisms in floral nectar. The field observations revealed that stigma closure was less frequent in damaged flowers than in intact flowers. In the experiments, however, floral damage did not decrease stigma closure or microbial detection in nectar. Instead, neighbouring flowers were similar for both indicators. These results suggest that the observed negative association between florivory and pollination is not causal and that the location of flowers is more important to pollinator visitation than florivory in these populations of M. aurantiacus. PMID:27178063

  14. Arctic Visiting Speakers Series (AVS)

    NASA Astrophysics Data System (ADS)

    Fox, S. E.; Griswold, J.

    2011-12-01

    The Arctic Visiting Speakers (AVS) Series funds researchers and other arctic experts to travel and share their knowledge in communities where they might not otherwise connect. Speakers cover a wide range of arctic research topics and can address a variety of audiences including K-12 students, graduate and undergraduate students, and the general public. Host applications are accepted on an on-going basis, depending on funding availability. Applications need to be submitted at least 1 month prior to the expected tour dates. Interested hosts can choose speakers from an online Speakers Bureau or invite a speaker of their choice. Preference is given to individuals and organizations to host speakers that reach a broad audience and the general public. AVS tours are encouraged to span several days, allowing ample time for interactions with faculty, students, local media, and community members. Applications for both domestic and international visits will be considered. Applications for international visits should involve participation of more than one host organization and must include either a US-based speaker or a US-based organization. This is a small but important program that educates the public about Arctic issues. There have been 27 tours since 2007 that have impacted communities across the globe including: Gatineau, Quebec Canada; St. Petersburg, Russia; Piscataway, New Jersey; Cordova, Alaska; Nuuk, Greenland; Elizabethtown, Pennsylvania; Oslo, Norway; Inari, Finland; Borgarnes, Iceland; San Francisco, California and Wolcott, Vermont to name a few. Tours have included lectures to K-12 schools, college and university students, tribal organizations, Boy Scout troops, science center and museum patrons, and the general public. There are approximately 300 attendees enjoying each AVS tour, roughly 4100 people have been reached since 2007. The expectations for each tour are extremely manageable. Hosts must submit a schedule of events and a tour summary to be posted online

  15. Regulatory Requirements and Technical Analysis for Department of Energy Regulated Performance Assessments of Shallow-Trench Disposal of Low-Level Radioactive Waste at the Nevada Test Site

    NASA Astrophysics Data System (ADS)

    Crowe, B.; Black, P.; Tauxe, J.; Yucel, V.; Rawlinson, S.; Colarusso, A.; DiSanza, F.

    2001-12-01

    The National Nuclear Security Administration, Nevada Operations Office (NNSA/NV) operates and maintains two active facilities on the Nevada Test Site (NTS) that dispose Department of Energy (DOE) defense-generated low-level radioactive (LLW), mixed radioactive, and classified waste in shallow trenches, pits and large-diameter boreholes. The operation and maintenance of the LLW disposal sites are self-regulated under DOE Order 435.1, which requires review of a Performance Assessment for four performance objectives: 1) all pathways 25 mrem/yr limit; 2) atmospheric pathways 10 mrem/yr limit; 3) radon flux density of 20 pCi/m2/s; and 4) groundwater resource protection (Safe Drinking Water Act; 4 mrem/yr limit). The inadvertent human intruder is protected under a dual 500- and 100-mrem limit (acute and chronic exposure). In response to the Defense Nuclear Facilities Safety Board Recommendation 92 2, a composite analysis is required that must examine all interacting sources for compliance against both 30 and 100 mrem/yr limits. A small component of classified transuranic waste is buried at intermediate depths in 3-meter diameter boreholes at the Area 5 LLW disposal facility and is assessed through DOE-agreement against the requirements of the Environmental Protection Agency (EPA)'s 40 CFR 191. The hazardous components of mixed LLW are assessed against RCRA requirements. The NTS LLW sites fall directly under three sets of federal regulations and the regulatory differences result not only in organizational challenges, but also in different decision objectives and technical paths to completion. The DOE regulations require deterministic analysis for a 1,000-year compliance assessment supplemented by probabilistic analysis under a long-term maintenance program. The EPA regulations for TRU waste are probabilistically based for a compliance interval of 10,000 years. Multiple steps in the assessments are strongly dependent on assumptions for long-term land use policies

  16. The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor beta1 gene through an Egr-1 binding site.

    PubMed Central

    Yoo, Y D; Chiou, C J; Choi, K S; Yi, Y; Michelson, S; Kim, S; Hayward, G S; Kim, S J

    1996-01-01

    Increases in transforming growth factor beta1 (TGF-beta1) mRNA and biological activity in the early phase of human cytomegalovirus (CMV) infection in fibroblasts are paralleled by increased TGF-beta1-chloramphenicol acetyltransferase (CAT) reporter gene activity. To determine how CMV infection transactivates the TGF-beta1 promoter, we examined the effects of the cotransfected IE2 regulatory protein of human CMV on 5'-deleted TGF-beta1 promoter-CAT reporter genes in transient DNA transfection assays. Two upstream TGF-beta1 promoter regions each containing an Egr-1 consensus site were shown to be important for IE2-induced transactivation in a cell type that displayed greatly reduced nonspecific activity. Furthermore, transfer of an Egr-l site from between positions -125 and -98, but not point mutant versions of this site, to a heterologous promoter also conveyed IE2 responsiveness. Addition of an IE2 expression vector or use of the U373 A45 astrocytoma cell line expressing IE2 also produced synergistic stimulation of GAL4-Egr-l-mediated activation of a target promoter containing GAL4 binding sites. The 80-kDa IE2 protein present in A45 cells proved to selectively bind to glutathione S-transferase (GST)-Egr-1 beads. The results of in vitro protein binding assays also revealed that an intact in vitro-translated IE2 protein bound directly to the GST-Egr-1 fusion protein through the zinc finger domain of the Egr-1 protein and that this binding activity was abolished by deletion of parts of the zinc finger DNA-binding domain. Similarly, the Egr-1 protein was found to associate preferentially with a small region within the C-terminal half of the IE2 protein adjacent to the DNA-binding and dimerization domains that are important for both transactivation and downregulation. We conclude from these observations that IE2 may regulate transcription of the TGF-beta1 gene as well as other potential cellular targets by virtue of its ability to interact with the Egr-1 DNA

  17. Regulatory and institutional issues impending cleanup at US Department of Energy sites: Perspectives gained from an office of environmental restoration workshop

    SciTech Connect

    Fallon, W E; Gephart, J M; Gephart, R E; Quinn, R D; Stevenson, L A

    1991-05-01

    The US Department of Energy's (DOE) nuclear weapons and energy operations are conducted across a nation-wide industrial complex engaged in a variety of manufacturing, processing, testing, and research and development activities. The overall mission of DOE Office of Environmental Restoration and Waste Management (EM) is to protect workers, the public, and the environment from waste materials generated by past, current, and future DOE activities and to bring the DOE complex into compliance with all applicable laws, regulations, and agreements related to health, safety, and the environment. EM addresses this broad mandate through related and interdependent programs that include corrective actions, waste operations, environmental restoration, and technology development. The EM Office of Environmental Restoration (EM-40) recognizes the importance of implementing a complex-wide process to identify and resolve those issues that may impede progress towards site cleanup. As a first step in this process, FM-40 sponsored an exercise to identify and characterize major regulatory and institutional issues and to formulate integrated action steps towards their resolution. This report is the first product of that exercise. It is intended that the exercise described here will mark the beginning of an ongoing process of issue identification, tracking, and resolution that will benefit cleanup activities across the DOE complex.

  18. Highly recurring sequence elements identified in eukaryotic DNAs by computer analysis are often homologous to regulatory sequences or protein binding sites.

    PubMed Central

    Bodnar, J W; Ward, D C

    1987-01-01

    We have used computer assisted dot matrix and oligonucleotide frequency analyses to identify highly recurring sequence elements of 7-11 base pairs in eukaryotic genes and viral DNAs. Such elements are found much more frequently than expected, often with an average spacing of a few hundred base pairs. Furthermore, the most abundant repetitive elements observed in the ovalbumin locus, the beta-globin gene cluster, the metallothionein gene and the viral genomes of SV40, polyoma, Herpes simplex-1 and Mouse Mammary Tumor Virus were sequences shown previously to be protein binding sites or sequences important for regulating gene expression. These sequences were present in both exons and introns as well as promoter regions. These observations suggest that such sequences are often highly overrepresented within the specific gene segments with which they are associated. Computer analysis of other genetic units, including viral genomes and oncogenes, has identified a number of highly recurring sequence elements that could serve similar regulatory or protein-binding functions. A model for the role of such reiterated sequence elements in DNA organization and function is presented. PMID:3822840

  19. 28 CFR 540.42 - Visiting times.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Visiting times. 540.42 Section 540.42 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Visiting Regulations § 540.42 Visiting times. (a) Each Warden shall establish...

  20. 28 CFR 540.42 - Visiting times.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Visiting times. 540.42 Section 540.42 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Visiting Regulations § 540.42 Visiting times. (a) Each Warden shall establish...

  1. 28 CFR 540.42 - Visiting times.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Visiting times. 540.42 Section 540.42 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Visiting Regulations § 540.42 Visiting times. (a) Each Warden shall establish...

  2. 28 CFR 540.42 - Visiting times.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Visiting times. 540.42 Section 540.42 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Visiting Regulations § 540.42 Visiting times. (a) Each Warden shall establish...

  3. 42 CFR 409.48 - Visits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... care, only one visit may be covered. (4) A visit is initiated with the delivery of covered home health services and ends at the conclusion of delivery of covered home health services. In those circumstances in... 42 Public Health 2 2012-10-01 2012-10-01 false Visits. 409.48 Section 409.48 Public Health...

  4. 42 CFR 409.48 - Visits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... care, only one visit may be covered. (4) A visit is initiated with the delivery of covered home health services and ends at the conclusion of delivery of covered home health services. In those circumstances in... 42 Public Health 2 2011-10-01 2011-10-01 false Visits. 409.48 Section 409.48 Public Health...

  5. 42 CFR 409.48 - Visits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... care, only one visit may be covered. (4) A visit is initiated with the delivery of covered home health services and ends at the conclusion of delivery of covered home health services. In those circumstances in... 42 Public Health 2 2010-10-01 2010-10-01 false Visits. 409.48 Section 409.48 Public Health...

  6. 42 CFR 409.48 - Visits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... care, only one visit may be covered. (4) A visit is initiated with the delivery of covered home health services and ends at the conclusion of delivery of covered home health services. In those circumstances in... 42 Public Health 2 2014-10-01 2014-10-01 false Visits. 409.48 Section 409.48 Public Health...

  7. 42 CFR 409.48 - Visits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... care, only one visit may be covered. (4) A visit is initiated with the delivery of covered home health services and ends at the conclusion of delivery of covered home health services. In those circumstances in... 42 Public Health 2 2013-10-01 2013-10-01 false Visits. 409.48 Section 409.48 Public Health...

  8. 28 CFR 540.42 - Visiting times.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Visiting times. 540.42 Section 540.42 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT CONTACT WITH PERSONS IN THE COMMUNITY Visiting Regulations § 540.42 Visiting times. (a) Each Warden shall establish...

  9. Beautiful Science: Worth a Visit

    NASA Astrophysics Data System (ADS)

    Bingham, Frederick M.

    2013-03-01

    For those in the profession of teaching physics who reside in or plan to visit the Los Angeles area, I would highly recommend a trip to the Huntington Library in San Marino, specifically to a permanent exhibit entitled "Beautiful Science: Ideas that Changed the World" in the Dibner Hall of the History of Science. The exhibit contains original books and manuscripts from the library's own collections. The sheer magnitude of human achievement represented here and the amount of effort and money that must have been required to amass these books boggles the mind.

  10. Defining regulatory and phosphoinositide-binding sites in the human WIPI-1 β-propeller responsible for autophagosomal membrane localization downstream of mTORC1 inhibition

    PubMed Central

    2012-01-01

    Background Autophagy is a cytoprotective, lysosomal degradation system regulated upon induced phosphatidylinositol 3-phosphate (PtdIns(3)P) generation by phosphatidylinositol 3-kinase class III (PtdIns3KC3) downstream of mTORC1 inhibition. The human PtdIns(3)P-binding β-propeller protein WIPI-1 accumulates at the initiation site for autophagosome formation (phagophore), functions upstream of the Atg12 and LC3 conjugation systems, and localizes at both the inner and outer membrane of generated autophagosomes. In addition, to a minor degree WIPI-1 also binds PtdIns(3,5)P2. By homology modelling we earlier identified 24 evolutionarily highly conserved amino acids that cluster at two opposite sites of the open Velcro arranged WIPI-1 β-propeller. Results By alanine scanning mutagenesis of 24 conserved residues in human WIPI-1 we define the PtdIns-binding site of human WIPI-1 to critically include S203, S205, G208, T209, R212, R226, R227, G228, S251, T255, H257. These amino acids confer PtdIns(3)P or PtdIns(3,5)P2 binding. In general, WIPI-1 mutants unable to bind PtdIns(3)P/PtdIns(3,5)P2 lost their potential to localize at autophagosomal membranes, but WIPI-1 mutants that retained PtdIns(3)P/PtdIns(3,5)P2 binding localized at Atg12-positive phagophores upon mTORC1 inhibition. Both, downregulation of mTOR by siRNA or cellular PtdIns(3)P elevation upon PIKfyve inhibition by YM201636 significantly increased the localization of WIPI-1 at autophagosomal membranes. Further, we identified regulatory amino acids that influence the membrane recruitment of WIPI-1. Exceptional, WIPI-1 R110A localization at Atg12-positive membranes was independent of autophagy stimulation and insensitive to wortmannin. R112A and H185A mutants were unable to bind PtdIns(3)P/PtdIns(3,5)P2 but localized at autophagosomal membranes, although in a significant reduced number of cells when compared to wild-type WIPI-1. Conclusions We identified amino acids of the WIPI-1 β-propeller that confer PtdIns(3