Science.gov

Sample records for agreement tpa milestone

  1. 324 Building special-case waste assessment in support of the 324 Building closure (TPA milestone M-89-05)

    SciTech Connect

    Hobart, R.L.

    1998-05-12

    Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement Milestone M-89-05 requires US Department of Energy, Richland Operations Office to complete a 324 Building Special Case Waste Assessment in Support of the 324 Building Closure. This document has been prepared with the intent of meeting this regulatory commitment. Alternatives for the Special Case Wastes located in the 324 Building were defined and analyzed. Based on the criteria of safety, environmental, complexity of interfaces, risk, cost, schedule, and long-term operability and maintainability, the best alternative was chosen. Waste packaging and transportation options are also included in the recommendations. The waste disposition recommendations for the B-Cell dispersibles/tank heels and High-Level Vault packaged residuals are to direct them to the Plutonium Uranium Extraction Facility (PUREX) Number 2 storage tunnel.

  2. Southeastern Environmental Resources Alliance [Status report on completion milestones incorporated in the Cooperative Agreement, and draft start-up plan March 24, 1995

    SciTech Connect

    1995-12-31

    The Southeastern Environmental Resources Alliance (SERA) is a joint effort between the US Department of Energy, the states of Georgia and South Carolina, and Westinghouse Savannah River Company (WSRC). The original proposal for SERA, submitted under the Technology Reinvestment Project (TRP), is based on improving the competitiveness of manufacturers within Georgia and South Carolina by addressing the costs associated with environmental and waste management issues. By using the many technologies available through the national laboratories, universities, the Savannah River Site, and the commercial sector, SERA will improve the competitive position of companies that would otherwise have no access to those technologies. This Start-Up Plan details the steps SERA will take to begin effective operations by June 1, 1995, and will focus on the short-term needs of the program. This plan will serve as a supplement to the original SERA proposal, and will address the major milestones included in the Department of Energy`s Cooperative Agreement. Also documented are the planning processes that SERA will use to ensure the long-term viability of the program. The planning process will include additional work elements that are referenced by the original proposal, but, for the purposes of program start-up, are not immediately addressed. The major milestones and schedules are provided for each goal.

  3. Exact milestoning

    SciTech Connect

    Bello-Rivas, Juan M.; Elber, Ron

    2015-03-07

    A new theory and an exact computer algorithm for calculating kinetics and thermodynamic properties of a particle system are described. The algorithm avoids trapping in metastable states, which are typical challenges for Molecular Dynamics (MD) simulations on rough energy landscapes. It is based on the division of the full space into Voronoi cells. Prior knowledge or coarse sampling of space points provides the centers of the Voronoi cells. Short time trajectories are computed between the boundaries of the cells that we call milestones and are used to determine fluxes at the milestones. The flux function, an essential component of the new theory, provides a complete description of the statistical mechanics of the system at the resolution of the milestones. We illustrate the accuracy and efficiency of the exact Milestoning approach by comparing numerical results obtained on a model system using exact Milestoning with the results of long trajectories and with a solution of the corresponding Fokker-Planck equation. The theory uses an equation that resembles the approximate Milestoning method that was introduced in 2004 [A. K. Faradjian and R. Elber, J. Chem. Phys. 120(23), 10880-10889 (2004)]. However, the current formulation is exact and is still significantly more efficient than straightforward MD simulations on the system studied.

  4. Exact milestoning

    PubMed Central

    Bello-Rivas, Juan M.; Elber, Ron

    2015-01-01

    A new theory and an exact computer algorithm for calculating kinetics and thermodynamic properties of a particle system are described. The algorithm avoids trapping in metastable states, which are typical challenges for Molecular Dynamics (MD) simulations on rough energy landscapes. It is based on the division of the full space into Voronoi cells. Prior knowledge or coarse sampling of space points provides the centers of the Voronoi cells. Short time trajectories are computed between the boundaries of the cells that we call milestones and are used to determine fluxes at the milestones. The flux function, an essential component of the new theory, provides a complete description of the statistical mechanics of the system at the resolution of the milestones. We illustrate the accuracy and efficiency of the exact Milestoning approach by comparing numerical results obtained on a model system using exact Milestoning with the results of long trajectories and with a solution of the corresponding Fokker-Planck equation. The theory uses an equation that resembles the approximate Milestoning method that was introduced in 2004 [A. K. Faradjian and R. Elber, J. Chem. Phys. 120(23), 10880-10889 (2004)]. However, the current formulation is exact and is still significantly more efficient than straightforward MD simulations on the system studied. PMID:25747056

  5. Exact milestoning.

    PubMed

    Bello-Rivas, Juan M; Elber, Ron

    2015-03-01

    A new theory and an exact computer algorithm for calculating kinetics and thermodynamic properties of a particle system are described. The algorithm avoids trapping in metastable states, which are typical challenges for Molecular Dynamics (MD) simulations on rough energy landscapes. It is based on the division of the full space into Voronoi cells. Prior knowledge or coarse sampling of space points provides the centers of the Voronoi cells. Short time trajectories are computed between the boundaries of the cells that we call milestones and are used to determine fluxes at the milestones. The flux function, an essential component of the new theory, provides a complete description of the statistical mechanics of the system at the resolution of the milestones. We illustrate the accuracy and efficiency of the exact Milestoning approach by comparing numerical results obtained on a model system using exact Milestoning with the results of long trajectories and with a solution of the corresponding Fokker-Planck equation. The theory uses an equation that resembles the approximate Milestoning method that was introduced in 2004 [A. K. Faradjian and R. Elber, J. Chem. Phys. 120(23), 10880-10889 (2004)]. However, the current formulation is exact and is still significantly more efficient than straightforward MD simulations on the system studied. PMID:25747056

  6. Developmental milestones record - 3 years

    MedlinePlus

    Normal childhood growth milestones - 3 years; Growth milestones for children - 3 years; Childhood growth milestones - 3 years ... provider. Physical and motor milestones for a typical 3-year-old include: Gains about 4 - 5 pounds ...

  7. Developmental milestones record - 9 months

    MedlinePlus

    Growth milestones for children - 9 months; Childhood growth milestones - 9 months; Normal childhood growth milestones - 9 months ... provider. PHYSICAL CHARACTERISTICS AND MOTOR SKILLS A 9-month-old has usually reached the following milestones: Gains ...

  8. Developmental milestones record - 9 months

    MedlinePlus

    Growth milestones for children - 9 months; Childhood growth milestones - 9 months; Normal childhood growth milestones - 9 months ... pushed to encourage walking. Sing songs together. Avoid television time until age 2. Try using a transition ...

  9. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... a cause for concern if not seen by 2 years.) Can run with better coordination . (May still ...

  10. Developmental milestones record - 12 months

    MedlinePlus

    Normal childhood growth milestones - 12 months; Growth milestones for children - 12 months; Childhood growth milestones - 12 months ... care provider. PHYSICAL AND MOTOR SKILLS A 12-month-old child is expected to: Be 3 times ...

  11. Developmental milestones record - 18 months

    MedlinePlus

    Growth milestones for children - 18 months; Normal childhood growth milestones - 18 months; Childhood growth milestones - 18 months ... PHYSICAL AND MOTOR SKILL MARKERS The typical 18-month-old: Has a closed soft spot on the ...

  12. Developmental milestones record - 4 months

    MedlinePlus

    Normal childhood growth milestones - 4 months; Childhood growth milestones - 4 months; Growth milestones for children - 4 months ... provider. PHYSICAL AND MOTOR SKILLS The typical 4-month-old baby should: Slow in weight gain to ...

  13. Developmental milestones record - 6 months

    MedlinePlus

    Normal childhood growth milestones - 6 months; Childhood growth milestones - 6 months; Growth milestones for children - 6 months ... the weight on hands (often occurs by 4 months) Able to pick up a dropped object Able ...

  14. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... cause for concern if not seen by 2 years.) Can run with better coordination. (May still have ...

  15. Developmental milestones record - 4 years

    MedlinePlus

    Normal childhood growth milestones - 4 years; Growth milestones for children - 4 years; Childhood growth milestones - 4 years ... care provider. PHYSICAL AND MOTOR During the fourth year, a child typically: Gains weight at the rate ...

  16. Developmental milestones record

    MedlinePlus

    ... in the early years is to follow your child's development. Most parents also watch for different milestones. Talk ... child's provider if you have concerns about your child's development. Closely watching a "checklist" or calendar of developmental ...

  17. Milestones in Rotorcraft Aeromechanics

    NASA Technical Reports Server (NTRS)

    Johnson, Wayne

    2011-01-01

    The subject of this paper is milestones in rotorcraft aeromechanics. Aeromechanics covers much of what the engineer needs: performance, loads, vibration, stability, flight dynamics, noise. These topics cover many of the key performance attributes, and many of the often-encountered problems in rotorcraft designs. A milestone is a critical achievement, a turning point, an event marking a significant change or stage in development. The milestones identified and discussed include the beginnings of aeromechanics with autogyro analysis, ground resonance, aeromechanics books, unsteady aerodynamics and airloads, nonuniform inflow and wakes, beams and dynamics, comprehensive analysis, computational fluid dynamics, and rotor airloads tests. The focus on milestones limits the scope of the history, but allows the author to acknowledge his choices for key steps in the development of the science and engineering of rotorcraft.

  18. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Advance payments or payable milestones. 603.1105 Section 603.1105 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Post-Award Administration § 603.1105 Advance payments or payable milestones. The contracting officer must: (a) For any expenditure-based TIA...

  19. The Consequences of edTPA

    ERIC Educational Resources Information Center

    Greenblatt, Deborah

    2016-01-01

    States and teacher preparation programs across the country are increasingly using a teacher candidate assessment called edTPA. The purpose? To make sure that teacher candidates are ready and able to teach before they begin their careers. The teacher performance assessment requires candidates to compile a portfolio that consists of lesson plans,…

  20. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business... the original projections, requiring adjustments of future milestone payment amounts (see §...

  1. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business... the original projections, requiring adjustments of future milestone payment amounts (see §...

  2. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business... the original projections, requiring adjustments of future milestone payment amounts (see §...

  3. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business... the original projections, requiring adjustments of future milestone payment amounts (see §...

  4. Beginning Teachers' Perceptions of the California Teaching Performance Assessment (TPA)

    ERIC Educational Resources Information Center

    Campbell, Conni; Ayala, Carlos Cuauhtémoc; Railsback, Gary; Freking, Frederick W.; McKenna, Corey; Lausch, David

    2016-01-01

    The teaching performance assessment (TPA) seeks to measure the knowledge, skills, and competencies of teachers during the credential phase of their training. The TPA was introduced in California in 2004 with programs piloting it and then became mandatory for candidates enrolling in preliminary programs in 2008. Although California has multiple…

  5. Milestones in ataxia

    PubMed Central

    Klockgether, Thomas; Paulson, Henry

    2010-01-01

    The past 25 years have seen enormous progress in the deciphering of the genetic and molecular basis of ataxias resulting in an improved understanding of their pathogenesis. The most significant milestones during this period were the cloning of the genes associated with the common spinocerebellar ataxias (SCAs), ataxia telangiectasia (AT) and Friedreich ataxia (FRDA). To date, the causative mutations of more than 30 SCAs and 20 recessive ataxias have been identified. In addition, there are numerous acquired ataxias with defined molecular causes so that the entire number of distinct ataxia disorders exceeds 50 and possibly approaches 100. Despite this enormous heterogeneity, a few recurrent pathopyhsiological themes stand out. These include protein aggregation, failure of protein homoestasis, perturbations in ion channel function, defects in DNA repair and mitochondrial dysfunction. The clinical phenotypes of the most common ataxia disorders have been firmly established, and their natural history is being studied in ongoing large observational trials. Effective therapies for ataxias are still lacking. However, novel drug targets are under investigation, and it is expected that there will be an increasing number of therapeutic trials in ataxia. PMID:21626557

  6. Milestones in Electron Crystallography

    PubMed Central

    Renault, Ludovic; Chou, Hui-Ting; Chiu, Po-Lin; Hill, Rena M.; Zeng, Xiangyan; Gipson, Bryant; Zhang, Zi Yan; Cheng, Anchi; Unger, Vinzenz; Stahlberg, Henning

    2007-01-01

    Summary Electron crystallography determines the structure of membrane embedded proteins in the two-dimensionally crystallized state by cryo-transmission electron microscopy imaging and computer structure reconstruction. Milestones on the path to the structure are high-level expression, purification of functional protein, reconstitution into two-dimensional lipid membrane crystals, high-resolution imaging, and structure determination by computer image processing. Here we review the current state of these methods. We also created an Internet information exchange platform for electron crystallography, where guidelines for the imaging and data processing method are maintained. The server (http://2dx.org) provides the electron crystallography community with a central information exchange platform, which is structured in blog and Wiki form, allowing visitors to add comments or discussions. It currently offers a detailed step-by-step introduction to image processing with the MRC software program. The server is also a repository for the 2dx software package, a user-friendly image processing system for 2D membrane protein crystals. PMID:17103018

  7. Developmental milestones record - 5 years

    MedlinePlus

    ... milestones for children - 5 years References Feigelman S. The preschool years. In: Kliegman RM, Behrman RE, Jenson HB, ... Duplication for commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map ...

  8. Developmental Milestones of Early Literacy

    MedlinePlus

    ... developmental milestones of early literacy. Younger Than 6 Months: Never Too Young Unlike solid foods , it is ... counts, so have fun with it! 6–12 Months: Developing a Taste for Books Whatever babies are ...

  9. Yucca Mountain Milestone

    SciTech Connect

    Hunt, Rod

    1997-06-09

    The Department of Energy project to determine if the Yucca Mountain site in Nevada is suitable for geologic disposal of high-level nuclear waste reached a major milestone in late April when a 25-foot-diameter tunnel boring machine ``holed through'' completing a five-mile-long, horseshoe-shaped excavation through the mountain. When the cutting-head of the giant machine broke through to daylight at the tunnel's south portal, it ended a 2 1/2-year excavation through the mountain that was completed ahead of schedule and with an outstanding safety record. Video of the event was transmitted live by satellite to Washington, DC, where it was watched by Secretary of Energy Frederico Pena and other high-level DOE officials, signifying the importance of the project's mission to find a repository for high-level nuclear waste and spent nuclear fuel produced by nuclear power plants. This critical undertaking is being performed by DOE's Office of Civilian Radioactive Waste Management (OCRWM). The tunnel is the major feature of the Exploratory Studies Facility (ESF), which serves as an underground laboratory for engineers and scientists to help determine if Yucca Mountain is suitable to serve as a repository for the safe disposal of high-level nuclear waste. Morrison Knudsen's Environmental/Government Group is providing design and construction-management services on the project. The MK team is performing final design for the ESF and viability assessment design for the underground waste repository that will be built only if the site is found suitable for such a mission. In fact, if at anytime during the ESF phase, the site is found unsuitable, the studies will be stopped and the site restored to its natural state.

  10. 10 CFR 603.570 - Determining milestone payment amounts.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Determining milestone payment amounts. 603.570 Section 603.570 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business Evaluation Accounting, Payments, and Recovery of Funds § 603.570...

  11. Speech and Language Developmental Milestones

    MedlinePlus

    ... What are the milestones for speech and language development? The first signs of communication occur when an infant learns that a cry will bring food, comfort, and companionship. Newborns also begin to recognize important sounds in their environment, such as the voice of their mother or ...

  12. 25 Legal and Legislative Milestones

    ERIC Educational Resources Information Center

    Diverse: Issues in Higher Education, 2009

    2009-01-01

    This timeline reflects some of the most significant legal and legislative milestones that have influenced higher education over the 25 years that "Diverse: Issues in Higher Education," formerly "Black Issues in Higher Education," has been in print. The legal battles have primarily involved the settlement of desegregation cases and the use of race…

  13. Developmental milestones record - 5 years

    MedlinePlus

    ... Stays balanced while standing on one foot with eyes closed Shows more skill with simple tools and writing utensils Can copy a triangle Can use a knife to spread soft foods Sensory and mental milestones: Has a vocabulary of more than 2,000 words Speaks in ...

  14. Implementation of nephrology subspecialty curricular milestones.

    PubMed

    Yuan, Christina M; Prince, Lisa K; Oliver, James D; Abbott, Kevin C; Nee, Robert

    2015-07-01

    Beginning in the 2014-2015 training year, the US Accreditation Council for Graduate Medical Education (ACGME) required that nephrology Clinical Competency Committees assess fellows' progress toward 23 subcompetency "context nonspecific" internal medicine subspecialty milestones. Fellows' advancement toward the "ready for unsupervised practice" target milestone now is tracked in each of the 6 competencies: Patient Care, Medical Knowledge, Professionalism, Interpersonal Communication Skills, Practice-Based Learning and Improvement, and Systems-Based Practice. Nephrology program directors and subspecialty societies must define nephrology-specific "curricular milestones," mapped to the nonspecific ACGME milestones. Although the ACGME goal is to produce data that can discriminate between successful and underperforming training programs, the approach is at risk to produce biased, inaccurate, and unhelpful information. We map the ACGME internal medicine subspecialty milestones to our previously published nephrology-specific milestone schema and describe entrustable professional activities and other objective assessment tools that inform milestone decisions. Mapping our schema onto the ACGME subspecialty milestone reporting form allows comparison with the ACGME subspecialty milestones and the curricular milestones developed by the American Society of Nephrology Program Directors. Clinical Competency Committees may easily adapt and directly translate milestone decisions reached using our schema onto the ACGME internal medicine subspecialty competency milestone-reporting format. PMID:25773484

  15. Early Language Milestones and Specific Language Impairment

    ERIC Educational Resources Information Center

    Rudolph, Johanna M.; Leonard, Laurence B.

    2016-01-01

    Delayed appearance of early language milestones can be one of the first signs of a developmental disorder. In this study, we investigated how well late acquisition of language milestones predicted an outcome of specific language impairment (SLI). The sample included 150 children (76 SLI), aged 4 to 7 years old. Milestone information was collected…

  16. Candidate Success and edTPA: Looking at the Data

    ERIC Educational Resources Information Center

    Evans, Lesley A.; Kelly, Mary K.; Baldwin, Joni L.; Arnold, Jackie M.

    2016-01-01

    This descriptive study looks at the correlations between Teacher Performance Assessment (edTPA) data and numerous program data points, including GPA, major GPA, and benchmark assignment scores, gathered in an Early Childhood Education (ECE) program. Previous studies have looked to correlate grade point average (GPA) with pre-service teacher…

  17. Teaching Elementary School Social Studies Methods under edTPA

    ERIC Educational Resources Information Center

    An, Sohyun

    2016-01-01

    This article reports a self-study that analyzes my experience as a teacher educator navigating a turbulent educational landscape with the advent of edTPA. The data consist of my journal entries, the syllabi, handouts, work submitted by my students, and course evaluations. Data were analyzed by using an inductive process to describe how the edTPA…

  18. Three Ways edTPA Prepared Me for the Classroom

    ERIC Educational Resources Information Center

    Butler, Matthew

    2015-01-01

    edTPA, a capstone assessment designed to assess whether new teachers are ready for the job by evaluating their teaching and their analysis of their teaching, helped prepare the author for the classroom in three ways. First, he became accountable to his students. Second, he learned to analyze his teaching. Third, he discovered how to relate…

  19. Genome sequence and characterization of the Tsukamurella bacteriophage TPA2.

    PubMed

    Petrovski, Steve; Seviour, Robert J; Tillett, Daniel

    2011-02-01

    The formation of stable foam in activated sludge plants is a global problem for which control is difficult. These foams are often stabilized by hydrophobic mycolic acid-synthesizing Actinobacteria, among which are Tsukamurella spp. This paper describes the isolation from activated sludge of the novel double-stranded DNA phage TPA2. This polyvalent Siphoviridae family phage is lytic for most Tsukamurella species. Whole-genome sequencing reveals that the TPA2 genome is circularly permuted (61,440 bp) and that 70% of its sequence is novel. We have identified 78 putative open reading frames, 95 pairs of inverted repeats, and 6 palindromes. The TPA2 genome has a modular gene structure that shares some similarity to those of Mycobacterium phages. A number of the genes display a mosaic architecture, suggesting that the TPA2 genome has evolved at least in part from genetic recombination events. The genome sequence reveals many novel genes that should inform any future discussion on Tsukamurella phage evolution. PMID:21183635

  20. A role for Saccharomyces cerevisiae Tpa1 protein in direct alkylation repair.

    PubMed

    Shivange, Gururaj; Kodipelli, Naveena; Monisha, Mohan; Anindya, Roy

    2014-12-26

    Alkylating agents induce cytotoxic DNA base adducts. In this work, we provide evidence to suggest, for the first time, that Saccharomyces cerevisiae Tpa1 protein is involved in DNA alkylation repair. Little is known about Tpa1 as a repair protein beyond the initial observation from a high-throughput analysis indicating that deletion of TPA1 causes methyl methane sulfonate sensitivity in S. cerevisiae. Using purified Tpa1, we demonstrate that Tpa1 repairs both single- and double-stranded methylated DNA. Tpa1 is a member of the Fe(II) and 2-oxoglutarate-dependent dioxygenase family, and we show that mutation of the amino acid residues involved in cofactor binding abolishes the Tpa1 DNA repair activity. Deletion of TPA1 along with the base excision repair pathway DNA glycosylase MAG1 renders the tpa1Δmag1Δ double mutant highly susceptible to methylation-induced toxicity. We further demonstrate that the trans-lesion synthesis DNA polymerase Polζ (REV3) plays a key role in tolerating DNA methyl-base lesions and that tpa1Δmag1revΔ3 triple mutant is extremely susceptible to methylation-induced toxicity. Our results indicate a synergism between the base excision repair pathway and direct alkylation repair by Tpa1 in S. cerevisiae. We conclude that Tpa1 is a hitherto unidentified DNA repair protein in yeast and that it plays a crucial role in reverting alkylated DNA base lesions and cytotoxicity. PMID:25381260

  1. A Role for Saccharomyces cerevisiae Tpa1 Protein in Direct Alkylation Repair*

    PubMed Central

    Shivange, Gururaj; Kodipelli, Naveena; Monisha, Mohan; Anindya, Roy

    2014-01-01

    Alkylating agents induce cytotoxic DNA base adducts. In this work, we provide evidence to suggest, for the first time, that Saccharomyces cerevisiae Tpa1 protein is involved in DNA alkylation repair. Little is known about Tpa1 as a repair protein beyond the initial observation from a high-throughput analysis indicating that deletion of TPA1 causes methyl methane sulfonate sensitivity in S. cerevisiae. Using purified Tpa1, we demonstrate that Tpa1 repairs both single- and double-stranded methylated DNA. Tpa1 is a member of the Fe(II) and 2-oxoglutarate-dependent dioxygenase family, and we show that mutation of the amino acid residues involved in cofactor binding abolishes the Tpa1 DNA repair activity. Deletion of TPA1 along with the base excision repair pathway DNA glycosylase MAG1 renders the tpa1Δmag1Δ double mutant highly susceptible to methylation-induced toxicity. We further demonstrate that the trans-lesion synthesis DNA polymerase Polζ (REV3) plays a key role in tolerating DNA methyl-base lesions and that tpa1Δmag1revΔ3 triple mutant is extremely susceptible to methylation-induced toxicity. Our results indicate a synergism between the base excision repair pathway and direct alkylation repair by Tpa1 in S. cerevisiae. We conclude that Tpa1 is a hitherto unidentified DNA repair protein in yeast and that it plays a crucial role in reverting alkylated DNA base lesions and cytotoxicity. PMID:25381260

  2. Milestones

    NASA Astrophysics Data System (ADS)

    2014-09-01

    Tami Bond, environmental engineer and professor in the Department of Civil and Environmental Engineering at the University of Illinois at Urbana-Champaign, has been selected as a 2014 MacArthur Fellow.

  3. TPA - A COMPUTER PROGRAM TO BALANCE MAPPED TURBOPUMP ASSEMBLIES

    NASA Technical Reports Server (NTRS)

    Walton, J. T.

    1994-01-01

    Accurate simulation of nuclear thermal propulsion systems using computational methods will permit reductions in testing and, thus, the time and cost of achieving a flight ready status for systems utilizing this advanced technology. An accurate simulation must maintain a "balance-of-plant" where the required pump work equals the supplied turbine work. This turbopump assembly balancing must be integrated into the overall system analysis models. TPA was developed to balance turbine and pump work using performance maps. It requires the inlet properties, performance maps, and shaft speed. TPA then computes the exit conditions and work terms. The work terms can then be balanced by varying the input shaft speed. The objective of the pump analysis is to determine the propellant state properties at the pump exit and the pump work. The pump analysis algorithm for liquid flow assumes that the shaft speed, the propellant state properties at the pump entrance, the propellant flow rate, the pump entrance and exit areas, as well as performance curves, are all known. The analysis of both the pump pressure rise and pump efficiency curves is required. The objective of the turbine analysis is to determine the propellant state properties at the turbine exit and the turbine work. The turbine analysis algorithm assumes that the shaft speed, the propellant state properties at the turbine entrance, the propellant flow rate, the turbine root mean square blade diameter, the turbine entrance and exit areas, as well as performance curves, are all known. The analysis also requires the turbine flow parameter curve and the turbine total efficiency curve. TPA is written in FORTRAN 77 to be machine independent. The TPA package includes the NBS+_PH2 code, which is also available separately (LEW-15505). TPA has been successfully implemented on a DEC VAX series computer running VMS, a Sun4 series computer running SunOS, and an IBM PC compatible computer running MS-DOS. Lahey F77L3 EM/32 v. 5.01 or

  4. Shock Hugoniot measurements on Ta to 0. 78 TPa

    SciTech Connect

    Froeschner, K.E.; Lee, R.S.; Chau, H.H.; Weingart, R.C.

    1983-08-18

    Symmetric impact shock Hugoniot measurements have been made on Ta with an electrically exploded foil gun system. The results obtained to date for the Hugoniot of Ta cover the range 0.19 to 0.78 TPa (impact velocities from 4.0 to 9.7 km/s) and agree with data obtained by other researchers to within 2.7% rms. Recent improvements in the system include electromagnetic shielding of impactor and target, continuous measurement of impactor velocity with a Fabry-Perot interferometer and computer-aided analysis of shot film. Conservative extrapolation from current operating conditions indicate that pressures of 1.1 to 1.5 TPa could be achieved with little difficulty.

  5. Cosmological milestones and energy conditions

    NASA Astrophysics Data System (ADS)

    Cattoën, C.; Visser, M.

    2007-05-01

    Until recently, the physically relevant singularities occurring in FRW cosmologies had traditionally been thought to be limited to the big bang, and possibly a big crunch. However, over the last few years, the zoo of cosmological singularities considered in the literature has become considerably more extensive, with big rips and sudden singularities added to the mix, as well as renewed interest in non-singular cosmological events such as bounces and turnarounds. In this talk, we present an extensive catalogue of such cosmological milestones, both at the kinematical and dynamical level. First, using generalized power series, purely kinematical definitions of these cosmological events are provided in terms of the behaviour of the scale factor a(t). The notion of a scale-factor singularity is defined, and its relation to curvature singularities (polynomial and differential) is explored. Second, dynamical information is extracted by using the Friedmann equations (without assuming even the existence of any equation of state) to place constraints on whether or not the classical energy conditions are satisfied at the cosmological milestones. Since the classification is extremely general, and modulo certain technical assumptions complete, the corresponding results are to a high degree model-independent.

  6. 32 CFR 37.575 - What are my responsibilities for determining milestone payment amounts?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false What are my responsibilities for determining milestone payment amounts? 37.575 Section 37.575 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award...

  7. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 603.1105 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT... projected budget for completing the milestone; and (2) Adjust future payable milestones, as needed, if... milestone payment of Federal funds). For this example, the contracting officer should adjust...

  8. Dodecafluoropentane Emulsion Extends Window for tPA Therapy in a Rabbit Stroke Model

    PubMed Central

    Brown, A. T.; Lowery, J. D.; Arthur, M. C.; Roberson, P. K.; Skinner, R. D.

    2016-01-01

    Dodecafluoropentane emulsion (DDFPe) nanodroplets are exceptional oxygen transporters and can protect ischemic brain in stroke models 24 h without reperfusion. Current stroke therapy usually fails to reach patients because of delays following stroke onset. We tested using DDFPe to extend the time window for tissue plasminogen activator (tPA). Longer treatment windows will allow more patients more complete stroke recovery. We test DDFPe to safely extend the time window for tPA thrombolysis to 9 h after stroke. With IACUC approval, randomized New Zealand white rabbits (3.4–4.7 kg, n=30) received angiography and 4-mm blood clot in the internal carotid artery for flow-directed middle cerebral artery occlusion. Seven failed and were discarded. Groups were IV tPA (n=11), DDFPe + tPA (n=7), and no therapy controls (n=5). DDFPe (0.3 ml/kg, 2 % emulsion) IV dosing began at 1 h and continued at 90 min intervals for 6 doses in one test group; the other received saline injections. Both got standard IV tPA (0.9 mg/kg) therapy starting 9 h post stroke. At 24 h, neurological assessment scores (NAS, 0–18) were determined. Following brain removal percent stroke volume (%SV) was measured. Outcomes were compared with Kruskal-Wallis analysis. For NAS, DDFPe + tPA was improved overall, p=0.0015, and vs. tPA alone, p=0.0052. For %SV, DDFPe + tPA was improved overall, p=0.0003 and vs. tPA alone, p=0.0018. NAS controls and tPA alone were not different but %SV was, p=0.0078. With delayed reperfusion, DDFPe + tPAwas more effective than tPA alone in preserving functioning brain after stroke. DDFPe significantly extends the time window for tPA therapy. PMID:26055229

  9. t-PA activity in peripheral blood obtained from pregnant women.

    PubMed

    Ishii, A; Yamada, S; Yamada, R; Hamada, H

    1994-01-01

    Concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured in blood obtained from pregnant women to elucidate the fluctuations in the fibrinolytic system which occur during the course of pregnancy. The t-PA activity was measured with a modified bioimmunoassay using anti-t-PA monoclonal antibody (SP-322) against a single chain of recombinant t-PA. The t-PA antigen was measured by ELISA using the same antibody. PAI activity was determined with a competitive inhibition assay of t-PA activity. In early pregnancy, t-PA activity was found to be close to the standard range seen in nonpregnant women, and gradually decreased during the course of pregnancy, then recovered to rise to the normal range within 48 hours after delivery. The t-PA antigen and PAI activity levels rose slowly during the course of pregnancy, and fell promptly after delivery. t-PA activity and t-PA antigen in levels in umbilical cord blood were higher after vaginal delivery than after cesarean section. These findings suggest that there may be an important physiological balance of the fibrinolytic system between mother and fetus during the course of pregnancy and the puerperium. PMID:7965540

  10. tPA promotes cortical neuron survival via mTOR-dependent mechanisms.

    PubMed

    Grummisch, Julia A; Jadavji, Nafisa M; Smith, Patrice D

    2016-07-01

    Tissue plasminogen activator (tPA) is a thrombolytic agent commonly used in the treatment of ischemic stroke. While the thrombolytic effects of tPA have been well established, the impact of this blood-brain barrier (BBB) crossing drug on neurons is not known. Given the widespread use of tPA in the clinical setting and the strict therapeutic window established for effective use of the drug, we examined the molecular mechanisms mediating the impact of tPA on postnatal cortical neurons isolated from the mouse brain. Dissociated postnatal primary cortical neurons were treated with tPA and the effects on neuron survival were evaluated. Pharmacological inhibitors of several signaling pathways previously implicated in neuroprotection (mTOR, JAK/STAT, MAPK and PKA-dependent mechanisms) were used to pinpoint the mechanistic effectors of tPA on neuron survival in vitro. We report here that tPA treatment results in a time-dependent neuroprotective effect on postnatal cortical neurons that relies predominantly on Janus kinase (JAK) and mammalian target of rapamycin (mTOR) signaling mechanisms. Taken together, these data suggest that tPA promotes neuroprotection in a temporally-regulated manner and that both JAK and mTOR signaling effectors are critical mediators of this neuroprotective effect. The results suggest the possibility of targeting these defined mechanisms to potentially expand the therapeutic window for tPA. PMID:26995507

  11. Application of several advanced oxidation processes for the destruction of terephthalic acid (TPA).

    PubMed

    Thiruvenkatachari, Ramesh; Kwon, Tae Ouk; Jun, Jung Chul; Balaji, Subramanian; Matheswaran, Manickam; Moon, Il Shik

    2007-04-01

    Terephthalic acid (TPA) is widely applied as a raw material in making polyester fiber, polyethylene terephthalate (PET) bottles, polyester films, etc. TPA is toxic and is known to act as endocrine disruptor. TPA wastewater is traditionally treated by biological process and this study aims to evaluate the effectiveness of several advanced oxidation processes on TPA removal. The oxidation processes studied were: UV-TiO(2), UV-H(2)O(2), UV-H(2)O(2)-Fe, O(3), O(3)/Fe, O(3)/TiO(2), UV-O(3)-H(2)O(2)-Fe and UV-O(3)-H(2)O(2)-Fe-TiO(2). The results indicate that the time required for the complete destruction of 50 ppm of TPA can be minimized from 10h using UV-TiO(2) system, to less than 10 min by UV-H(2)O(2)-Fe-O(3) system. Some of the likely organic intermediates identified during TPA destruction include, benzoquinone, benzene, maleic acid and oxalic acid. Possible destruction pathway of TPA has been proposed. TPA degradation by various systems was also analyzed based on the reaction kinetics and operating costs. PMID:17023113

  12. Unstandardized Responses to a "Standardized" Test: The edTPA as Gatekeeper and Curriculum Change Agent

    ERIC Educational Resources Information Center

    Ledwell, Katherine; Oyler, Celia

    2016-01-01

    We examine edTPA (a teacher performance assessment) implementation at one private university during the first year that our state required this exam for initial teaching certification. Using data from semi-structured interviews with 19 teacher educators from 12 programs as well as public information on edTPA pass rates, we explore whether the…

  13. "What about Bilingualism?" A Critical Reflection on the edTPA with Teachers of Emergent Bilinguals

    ERIC Educational Resources Information Center

    Kleyn, Tatyana; López, Dina; Makar, Carmina

    2015-01-01

    Amidst the debates surrounding teacher quality and preparation programs, the edTPA (education Teaching Performance Assessment) has emerged to assess future teachers through a portfolio-based certification process. This study offers the perspective of three faculty members who participated in an experimental configuration of edTPA implementation…

  14. Photon upconversion: from two-photon absorption (TPA) to triplet-triplet annihilation (TTA).

    PubMed

    Ye, Changqing; Zhou, Liwei; Wang, Xiaomei; Liang, Zuoqin

    2016-04-20

    Organic upconversion is a unique process in which low-energy light (usually NIR light) is converted to high-energy light through either the two-photon absorption (TPA) mechanism or the triplet-triplet annihilation (TTA) mechanism. Both TPA upconversion (TPA-UC) and TTA upconversion (TTA-UC) have been actively investigated in recent years due to their intriguing applications in optics, biophotonics, and solar energy utilization. Although they show some similarity (i.e., belonging to the nonlinear two-quantum process and needing focused excitation light), TPA-UC and TTA-UC are very different, such as in mechanism, characteristics involved, molecular design and potential applications. Here, we collectively reviewed these two kinds of upconversion processes and compared their respective characteristics and merits. We also present recent advances made in the areas of TPA- and TTA-UC, the remaining challenges and opportunities, with particular emphasis on molecular engineering of these two active upconversion materials. PMID:26843136

  15. 75 FR 4607 - Free Trade Agreements; Invitation for Applications for Inclusion on Dispute Settlement Rosters...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-28

    ... Settlement Rosters for the U.S.-Chile Free Trade Agreement (``FTA''), the Dominican Republic-Central America.... These agreements include the United States-Chile Free Trade Agreement, the Dominican Republic-Central... (202) 395-7305 (for the U.S.-Chile FTA and U.S.-Peru TPA), Leigh Bacon, Associate General Counsel,...

  16. Effects of TPA on short-circuit current across frog skin

    SciTech Connect

    Mauro, T.; O'Brien, T.G.; Civan, M.M.

    1987-02-01

    TPA (12-O-tetradecanoylphorbol-13-acetate) is an effective tumor promoter that affects a variety of ion transport processes. To examine the relationship between effects on transport and growth and differentiation, the authors have been studying the actions of TPA on frog skin, a particularly well-characterized epithelium. They have reported that high concentrations of TPA stimulate base-line short-circuit current (I/sub SC/) and inhibit the subsequent natriferic action of vasopressin. The current study of 89 preparations extends those findings. The K/sub m/ of the stimulatory effect of TPA is approx. 3 nM; this high affinity indicates that the transport phenomenon does not simply reflect a nonspecific interaction of phorbol ester with the plasma membranes. TPA acts largely or entirely at the mucosal surface of both split and whole skins; thus the sidedness of the effect does not arise from adsorption onto the underlying connective tissue when TPA is applied to the serosal surface of whole skin. Amiloride, an inhibitor of apical Na entry, abolishes I/sub SC/ across frog skins pretreated with TPA. The phorbol ester also increases I/sub SC/ across split skins, preparations which do not produce net Cl transport. The present results indicate that frog skin is highly responsive to TPA at concentrations known to activate protein kinase C in broken-cell preparations. The actions on I/sub SC/ appear to reflect changes in transepithelial Na transport modulated at the apical membranes. The full biochemical events triggered by TPA remain to be clarified; in part, TPA's actions may be mediated by leukotrienes produced by activation of the lipoxygenase pathway of arachidonic acid metabolism.

  17. Impacts of tissue-type plasminogen activator (tPA) on neuronal survival

    PubMed Central

    Chevilley, Arnaud; Lesept, Flavie; Lenoir, Sophie; Ali, Carine; Parcq, Jérôme; Vivien, Denis

    2015-01-01

    Tissue-type plasminogen activator (tPA) a serine protease is constituted of five functional domains through which it interacts with different substrates, binding proteins, and receptors. In the last years, great interest has been given to the clinical relevance of targeting tPA in different diseases of the central nervous system, in particular stroke. Among its reported functions in the central nervous system, tPA displays both neurotrophic and neurotoxic effects. How can the protease mediate such opposite functions remain unclear but several hypotheses have been proposed. These include an influence of the degree of maturity and/or the type of neurons, of the level of tPA, of its origin (endogenous or exogenous) or of its form (single chain tPA versus two chain tPA). In this review, we will provide a synthetic snapshot of our current knowledge regarding the natural history of tPA and discuss how it sustains its pleiotropic functions with focus on excitotoxic/ischemic neuronal death and neuronal survival. PMID:26528141

  18. Polypyrrole layered SPEES/TPA proton exchange membrane for direct methanol fuel cells

    NASA Astrophysics Data System (ADS)

    Neelakandan, S.; Kanagaraj, P.; Sabarathinam, R. M.; Nagendran, A.

    2015-12-01

    Hybrid membranes based on sulfonated poly(1,4-phenylene ether ether sulfone) (SPEES)/tungstophosphoric acid (TPA) were prepared. SPEES/TPA membrane surfaces were modified with polypyrrole (Ppy) by in situ polymerization method to reduce the TPA leaching. The morphology and electrochemical property of the surface coated membranes were studied by SEM, AFM, water uptake, ion exchange capacity, proton conductivity, methanol permeability and tensile strength. The water uptake and the swelling ratio of the surface coated membranes decreased with increasing the Ppy layer. The surface roughness of the hybrid membrane was decreased with an increase in Ppy layer on the membrane surface. The methanol permeability of SPEES/TPA-Ppy4 hybrid membrane was significantly suppressed and found to be 2.1 × 10-7 cm2 s-1, which is 1.9 times lower than pristine SPEES membrane. The SPEES/TPA-Ppy4 membrane exhibits highest relative selectivity (2.86 × 104 S cm-3 s) than the other membrane with low TPA leaching. The tensile strength of hybrid membranes was improved with the introduction of Ppy layer. Combining their lower swelling ratio, high thermal stability and selectivity, SPEES/TPA-Ppy4 membranes could be a promising material as PEM for DMFC applications.

  19. Production of human tissue plasminogen activator (tPA) in Cucumis sativus.

    PubMed

    Asgari, Mishaneh; Javaran, Mokhtar Jalali; Moieni, Ahmad; Masoumiasl, Asad; Abdolinasab, Maryam

    2014-01-01

    Tissue plasminogen activator (tPA) as a serine protease with 72 kD molecular mass and 527 amino acids plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The collective production of this drug in plants such as cucumber, one of the most important vegetables in the world, could reduce its production costs. In this study, after scrutiny of the appropriate regeneration of cucumber plant (Isfahan variety) on MS medium with naphthalene acetic acid hormone (NAA; 0/1 mg L⁻¹) and benzyl amino purine hormone (BAP; 3 mg L⁻¹) hormones, the cloned human tPA gene under the CaMV 35S promoter and NOS terminator into pBI121 plasmid was transferred into cotyledon explants by Agrobacterium tumefaciens strain LBA4404. Subsequent to the regeneration of inoculated explants on the selective medium, the persistence of tPA gene in recombinant plants was confirmed by polymerase chain reaction (PCR) with specific primers. To evaluate the tPA gene expression in transgenic plants, RNA was extracted and the tPA gene transcription was confirmed by reverse-transcription (RT) PCR. Followed the extraction of protein from the leaves of transgenic plants, the presence of tPA protein was confirmed by dot blot and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) analysis in order to survey the production of recombinant tPA protein. The enzyme-linked immunosorbent assay (ELISA) test was used for recombinant tPA protein level in transgenic cucumber plants. It was counted between 0.8 and 1%, and based on this, it was concluded that the presence of three expressions of regulatory factors (CaMV 35S, Kozak, NOS) and KDEL signal in the construct caused the increase of the tPA gene expression in cucumber plants. PMID:24152103

  20. Effect of Fagonia arabica on thrombin induced release of t-PA and complex of PAI-1 tPA in cultured HUVE cells.

    PubMed

    Aloni, Prutha D; Nayak, Amit R; Chaurasia, Sweta R; Deopujari, Jayant Y; Chourasia, Chhaya; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

    2016-07-01

    Fagonia arabica (FA) possesses a thrombolytic property which has been earlier reported in our laboratory. Current study was undertaken to investigate the effect of aqueous extract of FA on thrombin-induced tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) release from cultured human umbilical vein endothelial cell line (HUVE) for studying its clot lytic activity. For this, establishment of cell line model has been done by isolating the cells from human umbilical cord. Cell toxicity was evaluated using XTT assay. Estimation of t-PA and PAI-1 t-PA complex were done using ELISA technique. Thrombin treatment induces the t-PA and PAI-1 release from HUVE cell line, and FA treatment was found to antagonize the thrombin induced t-PA and PAI-1 release. Our preliminary results suggest that FA may be used as an alternative to thrombolytic drug. However, study demands further experiments using animal model of thrombosis to establish the role of FA as a novel thrombolytic drug. PMID:27419084

  1. Pulsed High–Intensity-focused US and Tissue Plasminogen Activator (TPA) Versus TPA Alone for Thrombolysis of Occluded Bypass Graft in Swine

    PubMed Central

    Abi-Jaoudeh, Nadine; Pritchard, William F.; Amalou, Hayet; Linguraru, Marius; Chiesa, Oscar A.; Adams, Joshua D.; Gacchina, Carmen; Wesley, Robert; Maruvada, Subha; McDowell, Briana; Frenkel, Victor; Karanian, John W.; Wood, Bradford J.

    2012-01-01

    Purpose Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high-intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis. Materials and Methods In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area opacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis. Results Combining pHIFU with 0.5 mg of TPA resulted in a 52% ± 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% ± 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups. Conclusions Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose. PMID:22609287

  2. Milestone M4900: Simulant Mixing Analytical Results

    SciTech Connect

    Kaplan, D.I.

    2001-07-26

    This report addresses Milestone M4900, ''Simulant Mixing Sample Analysis Results,'' and contains the data generated during the ''Mixing of Process Heels, Process Solutions, and Recycle Streams: Small-Scale Simulant'' task. The Task Technical and Quality Assurance Plan for this task is BNF-003-98-0079A. A report with a narrative description and discussion of the data will be issued separately.

  3. 14 CFR 1274.908 - Milestone payments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Milestone payments. 1274.908 Section 1274... to the NASA paying office, the original invoice should be submitted to: (ii) If the Recipient is not authorized to submit invoices directly to the NASA paying office, the original invoice should be submitted...

  4. 47 CFR 25.164 - Milestones.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and...

  5. 47 CFR 25.164 - Milestones.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems...) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems licensed on... first space station, place it in the authorized orbit, and operate it in accordance with the...

  6. 47 CFR 25.164 - Milestones.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and...

  7. 47 CFR 25.164 - Milestones.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and...

  8. 47 CFR 25.164 - Milestones.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Milestones. (a) Licensees of geostationary orbit satellite systems other than DBS and DARS satellite systems.... (b) Licensees of non-geostationary orbit satellite systems other than DBS and DARS satellite systems... both non-geostationary orbit satellites and geostationary orbit satellites, other than DBS and...

  9. Milestones in Cancer Research and Discovery

    Cancer.gov

    During the past 250 years, we have witnessed many landmark discoveries in our efforts to make progress against cancer, an affliction known to humanity for thousands of years. This timeline shows a few key milestones in the history of cancer research.

  10. Developmental Milestones in Toddlers with Atypical Development

    ERIC Educational Resources Information Center

    Horovitz, Max; Matson, Johnny L.

    2011-01-01

    The attainment of developmental milestones was examined and compared in 162 infants and toddlers with developmental disabilities, including Down Syndrome (n = 26), Cerebral Palsy (n = 19), Global Developmental Delay (n = 22), Premature birth (n = 66), and Seizure Disorder (n = 29). Toddlers in the Seizures Disorder group began crawling at a…

  11. X-ray diffraction of solid tin to 1.2 TPa

    SciTech Connect

    Lazicki, A.; Rygg, J. R.; Coppari, F.; Smith, R.; Fratanduono, D.; Kraus, R. G.; Collins, G. W.; Briggs, R.; Braun, D. G.; Swift, D. C.; Eggert, J. H.

    2015-08-12

    In this study, we report direct in situ measurements of the crystal structure of tin between 0.12 and 1.2 TPa, the highest stress at which a crystal structure has ever been observed. Using angle-dispersive powder x-ray diffraction, we find that dynamically compressed Sn transforms to the body-centered-cubic (bcc) structure previously identified by ambient-temperature quasistatic-compression studies and by zero-kelvin density-functional theory predictions between 0.06 and 0.16 TPa. However, we observe no evidence for the hexagonal close-packed (hcp) phase found by those studies to be stable above 0.16 TPa. Instead, our results are consistent with bcc up to 1.2 TPa. We conjecture that at high temperature bcc is stabilized relative to hcp due to differences in vibrational free energy.

  12. X-ray diffraction of solid tin to 1.2 TPa

    DOE PAGESBeta

    Lazicki, A.; Rygg, J. R.; Coppari, F.; Smith, R.; Fratanduono, D.; Kraus, R. G.; Collins, G. W.; Briggs, R.; Braun, D. G.; Swift, D. C.; et al

    2015-08-12

    In this study, we report direct in situ measurements of the crystal structure of tin between 0.12 and 1.2 TPa, the highest stress at which a crystal structure has ever been observed. Using angle-dispersive powder x-ray diffraction, we find that dynamically compressed Sn transforms to the body-centered-cubic (bcc) structure previously identified by ambient-temperature quasistatic-compression studies and by zero-kelvin density-functional theory predictions between 0.06 and 0.16 TPa. However, we observe no evidence for the hexagonal close-packed (hcp) phase found by those studies to be stable above 0.16 TPa. Instead, our results are consistent with bcc up to 1.2 TPa. We conjecturemore » that at high temperature bcc is stabilized relative to hcp due to differences in vibrational free energy.« less

  13. Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

    PubMed Central

    Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

    1989-01-01

    1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

  14. Curcumin relieves TPA-induced Th1 inflammation in K14-VEGF transgenic mice.

    PubMed

    Sun, Jun; Zhao, Yi; Jin, Hairong; Hu, Jinhong

    2015-04-01

    Curcumin has been confirmed to have anti-inflammatory properties in addition to the ability to decrease the expression of pro-inflammatory cytokines in keratinocytes. It was suggested that the interleukin-23 (IL-23)/IL-17A cytokine axis played a critical role in the pathogenesis of 12-O-tetradecanoyl phorbol 12-myristate 13-acetate (TPA)-induced K14-VEGF transgenic psoriasis-like mice model. Here, we report that topical use of a curcumin gel formulation inhibited TPA-induced Th1 inflammation in K14-VEGF transgenic mice ears but not Th17 inflammation as expected. Real-time PCR showed that mRNA levels of IL-23, IL-17A, IL-22, IL-6 and TNFα cytokines failed to increase after TPA-induction in K14-VEGF transgenic mice ear skin; but the mRNA level of IFNγ increased significantly at the same time. Furthermore, TPA-induction up-regulated the TCRγδ protein but failed to impact the CCR6 protein, which means that the proliferation of γδ T cells is incapable of IL-17A production. We find that curcumin is capable of relieving TPA-induced inflammation by directly down-regulating IFNγ production. In conclusion, curcumin inhibits TPA-induced Th1 inflammation in K14-VEGF transgenic mice which has not been previously described. PMID:25682767

  15. Found in transition: applying milestones to three unique discharge curricula.

    PubMed

    Meade, Lauren B; Todd, Christine Y; Walsh, Meghan M

    2015-01-01

    Introduction. A safe and effective transition from hospital to post-acute care is a complex and important physician competency. Milestones and Entrustable Professional Activities (EPA) form the new educational rubric in Graduate Medical Education Training. "A safe and effective discharge from the hospital" is an EPA ripe for educational innovation. Methods. The authors collaborated in a qualitative process called mapping to define 22 of 142 Internal Medicine (IM) curricular milestones related to the transition of care. Fifty-five participant units at an Association for Program Directors in Internal Medicine (APDIM) workshop prioritized the milestones, using a validated ranking process called Q-sort. We analyzed the Q-sort results, which rank the milestones in order of priority. We then applied this ranking to three innovative models of training IM residents in the transitions of care: Simulation (S), Discharge Clinic Feedback (DCF) and TRACER (T). Results. We collected 55 Q-sort rankings from particpants at the APDIM workshop. We then identified which milestones are a focus of the three innovative models of training in the transition of care: Simulation = 5 of 22 milestones, Discharge Clinic Feedback = 9 of 22 milestones, and TRACER = 7 of 22 milestones. Milestones identified in each innovation related to one of the top 8 prioritized milestones 75% of the time; thus, more frequently than the milestones with lower priority. Two milestones are shared by all three curricula: Utilize patient-centered education and Ensure succinct written communication. Two other milestones are shared by two curricula: Manage and coordinate care transitions across multiple delivery systems and Customize care in the context of the patient's preferences. If you combine the three innovations, all of the top 8 milestones are included. Discussion. The milestones give us a context to share individual innovations and to compare and contrast using a standardized frame. We demonstrate that the

  16. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Advance payments or payable milestones. 603.1105 Section 603.1105 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT... projected budget for completing the milestone; and (2) Adjust future payable milestones, as needed,...

  17. 43 CFR 3930.30 - Diligent development milestones.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Diligent development milestones. 3930.30... LEASES Management of Oil Shale Exploration Licenses and Leases § 3930.30 Diligent development milestones... diligent development milestones, the BLM may initiate lease cancellation. In order to be...

  18. tPA Deficiency in Mice Leads to Rearrangement in the Cerebrovascular Tree and Cerebroventricular Malformations

    PubMed Central

    Stefanitsch, Christina; Lawrence, Anna-Lisa E.; Olverling, Anna; Nilsson, Ingrid; Fredriksson, Linda

    2015-01-01

    The serine protease tissue-type plasminogen activator (tPA) is used as a thrombolytic agent in the management of ischemic stroke, but concerns for hemorrhagic conversion greatly limits the number of patients that receive this treatment. It has been suggested that the bleeding complications associated with thrombolytic tPA may be due to unanticipated roles of tPA in the brain. Recent work has suggested tPA regulation of neurovascular barrier integrity, mediated via platelet derived growth factor (PDGF)-C/PDGF receptor-α (PDGFRα) signaling, as a possible molecular mechanism affecting the outcome of stroke. To better understand the role of tPA in neurovascular regulation we conducted a detailed analysis of the cerebrovasculature in brains from adult tPA deficient (tPA−/−) mice. Our analysis demonstrates that life-long deficiency of tPA is associated with rearrangements in the cerebrovascular tree, including a reduction in the number of vascular smooth-muscle cell covered, large diameter, vessels and a decrease in vessel-associated PDGFRα expression as compared to wild-type (WT) littermate controls. In addition, we found that ablation of tPA results in an increased number of ERG-positive endothelial cells and increased junctional localization of the tight junction protein ZO1. This is intriguing since ERG is an endothelial transcription factor implicated in regulation of vascular integrity. Based on these results, we propose that the protection of barrier properties seen utilizing these tPA−/− mice might be due, at least in part, to these cerebrovascular rearrangements. In addition, we found that tPA−/− mice displayed mild cerebral ventricular malformations, a feature previously associated with ablation of PDGF-C, thereby providing an in vivo link between tPA and PDGF signaling in central nervous system (CNS) development. Taken together, the data presented here will advance our understanding of the role of tPA within the CNS and in regulation of

  19. Evidence for impairment of behavioural inhibition in performance of operant tasks in tPA-/- mice.

    PubMed

    Ripley, T L; Horwood, J M; Stephens, D N

    2001-11-01

    We have previously shown that mice that lack the serine protease, tissue plasminogen activator (tPA), show over-responding on the active lever during time-out periods in an I.V. cocaine self-administration task. To investigate this effect further, tPA knockout mice (tPA-/-) were tested in a number of operant paradigms for a liquid food reinforcer. tPA-/- and wild-type (WT) control mice acquired a fixed ratio (FR) and a fixed interval (FI) task equally. However, extinction from the FR schedule resulted in a significant decrease in responses on the active and inactive levers in the WT mice whilst responding on the inactive lever remained high in the tPA-/- animals. In a differential reinforcement of low rate (DRL) task, tPA-/- mice acquired the task at a slower rate than WT animals. This was characterised by high levels of responding on the active lever during the first 15 sessions in the tPA-/- mice. Burst responding on the active lever (lever press rate with an inter-response time of less than 3 s) was especially high in these animals. This behaviour pattern resulted in the animals obtaining less reinforcers than the WT controls. Acute cocaine dose-dependently shifted the pattern of behaviour on the active lever towards shorter inter-response times. However, there was no difference between the tPA-/- and WT mice in their sensitivity to cocaine on this task. Repeated administration of a low dose of cocaine did not alter performance on this task in either set of animals. When the DRL task was modified to allow the tPA-/- and WT mice an equal number of reinforced trials per session there was no difference in the ability of the animals to perform the task. This would suggest that the tPA-/- mice have a tendency to over-respond but that this can be overcome when the task is modified to allow equal opportunity to learn. PMID:11682113

  20. The ACGME Milestone Project in ophthalmology.

    PubMed

    Lee, Andrew G; Arnold, Anthony C

    2013-01-01

    The ACGME is moving towards the next generation of accreditation in the USA called the Next Accreditation System (NAS). The NAS is anticipated to reduce the burden on programs to comply with accreditation requirements; to produce meaningful, innovative, and continuous benchmark outcomes data; to use ongoing individual and programmatic milestones to judge performance; and ultimately to produce better trained residents, to improve the quality of care, to reduce health care costs and health care disparities, and to provide objective evidence to the public and other external stakeholders of the quality of graduate medical education across the specialties of medicine. We describe the ACGME milestone development process for ophthalmology. If successful, the NAS will benefit all programs by reducing the programmatic burden and paperwork; increasing accreditation cycle length; and improving all programs through formative and summative feedback. PMID:23768922

  1. Milestones Toward Majorana-Based Quantum Computing

    NASA Astrophysics Data System (ADS)

    Aasen, David; Hell, Michael; Mishmash, Ryan V.; Higginbotham, Andrew; Danon, Jeroen; Leijnse, Martin; Jespersen, Thomas S.; Folk, Joshua A.; Marcus, Charles M.; Flensberg, Karsten; Alicea, Jason

    2016-07-01

    We introduce a scheme for preparation, manipulation, and read out of Majorana zero modes in semiconducting wires with mesoscopic superconducting islands. Our approach synthesizes recent advances in materials growth with tools commonly used in quantum-dot experiments, including gate control of tunnel barriers and Coulomb effects, charge sensing, and charge pumping. We outline a sequence of milestones interpolating between zero-mode detection and quantum computing that includes (1) detection of fusion rules for non-Abelian anyons using either proximal charge sensors or pumped current, (2) validation of a prototype topological qubit, and (3) demonstration of non-Abelian statistics by braiding in a branched geometry. The first two milestones require only a single wire with two islands, and additionally enable sensitive measurements of the system's excitation gap, quasiparticle poisoning rates, residual Majorana zero-mode splittings, and topological-qubit coherence times. These pre-braiding experiments can be adapted to other manipulation and read out schemes as well.

  2. Genetic Counseling Milestones: A Framework for Student Competency Evaluation.

    PubMed

    Guy, Carrie

    2016-08-01

    Graduate medical education has recently increased focus on the development of medical specialty competency milestones to provide a targeted tool for medical resident evaluation. Milestones provide developmental assessment of the attainment of competencies over the course of an educational program. An educational framework is described to explore the development of Genetic Counseling Milestones for the evaluation of the development of genetic counseling competencies by genetic counseling students. The development of Genetic Counseling Milestones may provide a valuable tool to assess genetic counseling students across all program activities. Historical educational context, current practices, and potential benefits and challenges in the development of Genetic Counseling Milestones are discussed. PMID:26462934

  3. Construction Milestone Announced on Green Bank Telescope

    NASA Astrophysics Data System (ADS)

    2000-04-01

    The National Radio Astronomy Observatory announces completion of a major construction milestone on the world's largest fully steerable radio telescope - the National Science Foundation's Green Bank Telescope (GBT). The last of 2,004 aluminum surface panels was recently installed on the GBT's two-acre (100 m x 110 m) collecting dish. The telescope is located at NRAO's Green Bank site, in rural Pocahontas County, West Virginia. The GBT will be used to study everything from the formation of galaxies in the early universe, to the chemical make-up of the dust and gas inside galaxies and in the voids that separate them, to the birth processes of stars. In conjunction with other instruments, it will help make highly accurate radar maps of some familiar objects in our own solar system. The GBT is an engineering marvel. At 485 feet tall, it is comparable in height to the Washington Monument. It weighs 16 million pounds, yet by swiveling the dish in both azimuth and elevation, it can be pointed to any point in the sky with exquisite accuracy. Additionally, the telescope's two-acre collecting dish has many novel features. Most radio telescopes in use today use receivers suspended above the dish by four struts. These struts block some of the surface of the dish, scattering some of the incoming radio waves from celestial objects under study. The GBT's offset feedarm has no struts to block incoming radio waves. The GBT also boasts an active surface. The surface of the dish is composed of 2,004 panels. On the underside of the dish, actuators are located at each corner (i.e., intersection of four panels). These actuators are motors that move the surface panels up and down, keeping the (paraboloid) shape of the dish precisely adjusted, no matter what the tilt of the telescope. The combination of its unblocked aperture and active surface promise that the GBT will display extremely high sensitivity to faint radio signals. The GBT itself is not the only precious national resource in

  4. Suppression of endothelial t-PA expression by prolonged high laminar shear stress

    SciTech Connect

    Ulfhammer, Erik; Carlstroem, Maria; Bergh, Niklas; Larsson, Pia; Karlsson, Lena; Jern, Sverker

    2009-02-06

    Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low ({<=}1.5 dyn/cm{sup 2}) or high (25 dyn/cm{sup 2}) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.

  5. Adenylate cyclase regulation in the spermatogenic cell plasma membrane: Modulating effects of TPA and TCDD

    SciTech Connect

    Beebe, L.E.

    1989-01-01

    This research was designed to compare the effects of TPA, a phorbol ester, and TCDD in a spermatogenic cell population, a target of TCDD toxicity. Membrane-bound adenylate cyclase activity was used an index of membrane function, and was quantified by the amount of {sup 32}P-cAMP formed from {sup 32}P-ATP following chromatographic separation. Exposure to male germ cells in-vitro to TPA and TCDD followed by direct measurement of enzyme activity was used to investigate the potential of each agent to perturb membrane function. TPA and TCDD consistently inhibited adenylate cyclase activity at the levels of G{sub s}-catalytic unit coupling and hormone-receptor activation, as measured by the stimulation of enzyme activity by concomitant addition of forskolin and GTP and FSH and GTP, respectively. The effect on coupling required at least 60 minutes of exposure to TPA or TCDD. Concentration-response curves demonstrated a progressive desensitization with increasing TPA concentration, while TCDD exhibited consistent inhibition over the same concentration range.

  6. CpG and TpA frequencies in the plant system.

    PubMed Central

    Boudraa, M; Perrin, P

    1987-01-01

    Higher plant nuclear sequences reveal avoidance of CpG and TpA doublets. Chloroplast sequences avoid the TpA doublet in all codon positions. The chloroplast genome is not methylated but codon positions II-III and untranslated regions avoid CpG. The mitochondrial genome, also unmethylated, avoids CpG in all codon positions. We therefore deduce that methylation is not sufficient to explain CpG avoidance in the higher plant systems. Other factors must be taken into account such as amino acid composition, codon choices and perhaps stability of the DNA helix. PMID:3497385

  7. Level-2 Milestone 5213. CTS-1 Contract Award Completed

    SciTech Connect

    Leininger, Matt

    2015-09-24

    This report documents the fact that the first commodity technology (CT) system contract award, CTS-1, has been completed. The description of the milestone is: Based on Tri-Lab CTS-1 process and review, LLNL successfully awards the procurement for the next-generation Tri-Lab Linux CTS-1. The milestone completion criterion is: Signed contract. The milestone was completed on September 24th. 2015.

  8. Pediatrics milestone project: next steps toward meaningful outcomes assessment.

    PubMed

    Hicks, Patricia J; Englander, Robert; Schumacher, Daniel J; Burke, Ann; Benson, Bradley J; Guralnick, Susan; Ludwig, Stephen; Carraccio, Carol

    2010-12-01

    In the September 2010 issue of JGME, the Pediatric Milestones Working Group published "The Pediatrics Milestones: Conceptual Framework, Guiding Principles, and Approach to Development", a document that describes the construction of the first iteration of the Pediatric Milestones. These Milestones were developed by the Working Group as a group of practical behavioral expectations for each of the 52 sub-competencies. In constructing these Milestones, the authors were cognizant of the need to ground the Milestones themselves in evidence, theories or other conceptual frameworks that would provide the basis for the ontogeny of development for each sub-competency. During this next phase of the Milestones development, the process will continue with consultation with content experts and consideration of assessment of Milestones. We have described possible measurement tools, explored threats to validity, establishment of benchmarks, and possible approaches to reporting of performance. The vision of the Pediatrics Milestone Project is to understand the development of a pediatrician from entry into medical school through the twilight of a physician's career, and the work will require a collaborative effort of the undergraduate and graduate medical education communities, and the accrediting and certifying bodies. PMID:22132281

  9. 18. INTERIOR OF CIVIL RIGHTS INSTITUTE, MILESTONE GALLERY EXHIBITION OF ...

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

    18. INTERIOR OF CIVIL RIGHTS INSTITUTE, MILESTONE GALLERY EXHIBITION OF THE SIXTEENTH STREET CHURCH, LOOKING NORTHWEST - Sixteenth Street Baptist Church, 1530 Sixth Avenue North, Birmingham, Jefferson County, AL

  10. Racist Ordering, Settler Colonialism, and EdTPA: A Participatory Policy Analysis

    ERIC Educational Resources Information Center

    Tuck, Eve; Gorlewski, Julie

    2016-01-01

    This article tells the story of an intervention by a collective of teacher educators on New York State's adoption of edTPA. Too often in education policy analysis, issues of race are discussed briefly, if at all. This article argues that attending to constructions of race specific to settler colonialism is an important approach to education policy…

  11. Buyer Beware: Lessons Learned from EdTPA Implementation in New York State

    ERIC Educational Resources Information Center

    Greenblatt, Deborah; O'Hara, Kate E.

    2015-01-01

    As states across the country continue their implementation of the Teacher Performance Assessment Portfolio (edTPA), a complex and high-stakes certification requirement for teacher certification, there are important lessons for educators and education advocates to learn from New York State's implementation. As Linda Darling-Hammond, developer and…

  12. Novel Ru (II) complex with TPA derivatives as a donor for dye-sensitized solar cells

    NASA Astrophysics Data System (ADS)

    Kwon, Dong Yuel; Chang, Dong Min; Kim, Young Sik

    2015-01-01

    Novel heteroleptic ruthenium(II) complex [Ru(CF3-ppyd-TPA)(tctpy)]+ (ppyd = 2-phenyl-6-(pyridin-2-yl)pyridine, TPA = triphenylamine, and tctpy = 4,4',4″-tricarboxy-2,2':6',2″-terpyridine) was designed and investigated to increase its molar absorptivity compared to [Ru(ppd)(tctpy)]+ (ppd = 2-(3-(pyridin-2-yl)phenyl)pyridine). Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were performed to gain insight into the factors responsible for the photovoltaic properties of a dye sensitizer. [Ru(CF3-ppyd-TPA)(tctpy)]+ showed a broad absorption spectrum and enhanced the molar extinction coefficient. Significant improvements to light absorption were exhibited by enhancing the metal-to-ligand charge transfer (MLCT) characteristics through the addition of the electron-withdrawing group-CF3 para to the organometallic bond and by increasing the transition dipole moment through the addition of TPA as an electron-donating group compared to the [Ru(ppd)(tctpy)]+. This study suggests that a ruthenium-based dye sensitizer would show improved photovoltaic performance in conversion efficiency for DSSCs by adding electron-donating and electron-withdrawing groups.

  13. Breakers, Benders, and Obeyers: Inquiring into Teacher Educators' Mediation of edTPA

    ERIC Educational Resources Information Center

    Ratner, Andrew R.; Kolman, Joni S.

    2016-01-01

    This article reflects a qualitative exploratory inquiry into the lived experiences of faculty members working within a system of urban schools of education as they supported diverse teacher candidates in completing the Educative Teacher Performance Assessment (edTPA) during its first semesters of high-stakes implementation. Drawing upon…

  14. Developing a Culture of Learning around the edTPA: One University's Journey

    ERIC Educational Resources Information Center

    Miller, Matthew; Carroll, David; Jancic, Mitchell; Markworth, Kimberly

    2015-01-01

    In this article, we discuss how an interdisciplinary faculty team at a midsized public university created supports for the Teacher Performance Assessment (edTPA), a high-stakes performance assessment for preservice candidates being adopted by many states. We provide a general description of our work in contending with the challenge of developing a…

  15. Artificial insemination history: hurdles and milestones

    PubMed Central

    Ombelet, W.; Van Robays, J.

    2015-01-01

    Artificial insemination with homologous (AIH) or donor semen (AID) is nowadays a very popular treatment procedure used for many subfertile women worldwide. The rationale behind artificial insemination is to increase gamete density at the site of fertilisation. The sequence of events leading to today’s common use of artificial insemination traces back to scientific studies and experimentation many centuries ago. Modern techniques used in human artificial insemination programmes are mostly adapted from the work on cattle by dairy farmers wishing to improve milk production by using artificial insemination with sperm of selected bulls with well chosen genetic traits. The main reason for the renewed interest in artificial insemination in human was associated with the refinement of techniques for the preparation of washed motile spermatozoa in the early years of IVF. The history of artificial insemination is reviewed with particular interest to the most important hurdles and milestones. PMID:26175891

  16. Milestones toward Majorana-based quantum computing

    NASA Astrophysics Data System (ADS)

    Alicea, Jason

    Experiments on nanowire-based Majorana platforms now appear poised to move beyond the preliminary problem of zero-mode detection and towards loftier goals of realizing non-Abelian statistics and quantum information applications. Using an approach that synthesizes recent materials growth breakthroughs with tools long successfully deployed in quantum-dot research, I will outline a number of relatively modest milestones that progressively bridge the gap between the current state of the art and these grand longer-term challenges. The intermediate Majorana experiments surveyed in this talk should be broadly adaptable to other approaches as well. Supported by the National Science Foundation (DMR-1341822), Institute for Quantum Information and Matter, and Walter Burke Institute at Caltech.

  17. Artificial insemination history: hurdles and milestones.

    PubMed

    Ombelet, W; Van Robays, J

    2015-01-01

    Artificial insemination with homologous (AIH) or donor semen (AID) is nowadays a very popular treatment procedure used for many subfertile women worldwide. The rationale behind artificial insemination is to increase gamete density at the site of fertilisation. The sequence of events leading to today's common use of artificial insemination traces back to scientific studies and experimentation many centuries ago. Modern techniques used in human artificial insemination programmes are mostly adapted from the work on cattle by dairy farmers wishing to improve milk production by using artificial insemination with sperm of selected bulls with well chosen genetic traits. The main reason for the renewed interest in artificial insemination in human was associated with the refinement of techniques for the preparation of washed motile spermatozoa in the early years of IVF. The history of artificial insemination is reviewed with particular interest to the most important hurdles and milestones. PMID:26175891

  18. 43 CFR 3930.30 - Diligent development milestones.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Diligent development milestones. 3930.30... Management of Oil Shale Exploration Licenses and Leases § 3930.30 Diligent development milestones. (a... lease, POD, and these regulations. If the operator does not maintain or comply with diligent...

  19. Age-aware solder performance models : level 2 milestone completion.

    SciTech Connect

    Neilsen, Michael K.; Vianco, Paul Thomas; Neidigk, Matthew Aaron; Holm, Elizabeth Ann

    2010-09-01

    Legislated requirements and industry standards are replacing eutectic lead-tin (Pb-Sn) solders with lead-free (Pb-free) solders in future component designs and in replacements and retrofits. Since Pb-free solders have not yet seen service for long periods, their long-term behavior is poorly characterized. Because understanding the reliability of Pb-free solders is critical to supporting the next generation of circuit board designs, it is imperative that we develop, validate and exercise a solder lifetime model that can capture the thermomechanical response of Pb-free solder joints in stockpile components. To this end, an ASC Level 2 milestone was identified for fiscal year 2010: Milestone 3605: Utilize experimentally validated constitutive model for lead-free solder to simulate aging and reliability of solder joints in stockpile components. This report documents the completion of this milestone, including evidence that the milestone completion criteria were met and a summary of the milestone Program Review.

  20. FY11 Level-2 Milestone 3953: TLCC2 contract awarded

    SciTech Connect

    Carnes, B

    2011-09-12

    This report documents completion of FY11 L2 milestone No.3953-TLCC2 contract award. This milestone was scheduled for completion on 3/31/11 and was completed on 4/14/11. There is a separate milestone (3856), due at the end of the fiscal year, concerned with installation of the first LLNL SU and early user access. Efforts related to this tri-lab L2 milestone started early in 2010 with the development of tri-lab requirements for the second ASC capacity system procurement. The SOW was then developed along with necessary RFP paperwork and sent to HQ/DOE for their review prior to being released. There was significant delay in getting this step completed which led to this milestone being put at risk for several months. However, once the RFP was approved and released we were able to get the procurement back on track with aggressive proposal response and review timelines.

  1. Preservice Teachers' Adaptations to Tensions Associated with the edTPA during Its Early Implementation in New York and Washington States

    ERIC Educational Resources Information Center

    Meuwissen, Kevin W.; Choppin, Jeffrey M.

    2015-01-01

    The edTPA is a teaching performance assessment (TPA) that the states of New York and Washington implemented as a licensure requirement in 2013. While TPAs are not new modes of assessment, New York and Washington are the first states to use the edTPA specifically as a compulsory, high-stakes policy lever in an effort to strengthen the quality and…

  2. Campaign 2 Level 2 Milestone Review 2009: Milestone # 3131 Grain Scale Simulation of Pore Collapse

    SciTech Connect

    Schwartz, A J

    2009-09-28

    The milestone reviewed on Sept. 16, 2009 was 'High-fidelity simulation of shock initiation of high explosives at the grain scale using coupled hydrodynamics, thermal transport and chemistry'. It is the opinion of the committee that the team has satisfied the milestone. A detailed description of how the goals were met is provided. The milestone leveraged capabilities from ASC Physics and Engineering Materials program combined with experimental input from Campaign 2. A combined experimental-multiscale simulation approach was used to create and validate the various TATB model components. At the lowest length scale, quantum chemical calculations were used to determine equations of state, thermal transport properties and reaction rates for TATB as it is decomposing. High-pressure experiments conducted in diamond anvil cells, gas guns and the Z machine were used to validate the EOS, thermal conductivity, specific heat and predictions of water formation. The predicted reaction networks and chemical kinetic equations were implemented in Cheetah and validated against the lower length scale data. Cheetah was then used within the ASC code ALE3D for high-resolution, thermo-mechanically coupled simulations of pore collapse at the micron size scale to predict conditions for detonation initiation.

  3. Summary of Model Toxics Control Act (MTCA) Potential Impacts Related to Hanford Cleanup and the Tri-Party Agreement (TPA)

    SciTech Connect

    IWATATE, D.F.

    2000-07-14

    This white paper provides an initial assessment of the potential impacts of the Model Toxics Control Act (MTCA) regulations (and proposed revisions) on the Hanford site cleanup and addresses concerns that MTCA might impose inappropriate or unachievable clean-up levels and drive clean-up costs higher. The white paper and supporting documentation (Appendices A and B) provide DOE with a concise and up-to-date review of potential MTCA impacts to cost and schedule for the Hanford site activities. MTCA, Chapter 70.105D RCW, is the State of Washington's risk based law governing clean-up of contaminated sites and is implemented by The Washington Department of Ecology (Ecology) under the MTCA Clean-up Regulations, Chapter 173-340 WAC. Hanford cleanup is subject to the MTCA requirements as Applicable, Relevant and Appropriate Requirements (ARARs) for those areas of Hanford being managed under the authority of the Federal Resource Conservation and Recovery Act (RCRA), Comprehensive Environmental Response, Compensation and Liability Act (CERCLA), and the state Dangerous Waste Regulations. MTCA provides Ecology with authority to implement site clean-up actions under both the federal RCRA and CERCLA regulations as well as the state regulations. Most of the Hanford clean-up actions are being implemented under the CERCLA program, however, there is a trend is toward increased use of MTCA procedures and standards. The application of MTCA to the Hanford clean-up has been an evolving process with some of the Hanford clean-up actions considering MTCA standards as an ARAR and using MTCA procedures for remedy selection. The increased use and application of MTCA standards and procedures could potentially impact both cost and schedule for the Hanford cleanup.

  4. Effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) upon membrane ionic exchanges in sea urchin eggs

    SciTech Connect

    Ciapa, B.; Payan, P. ); Allemand, D. )

    1989-12-01

    The effect of TPA (12-O-tetradecanoylphorbol-13-acetate) upon ionic exchanges was investigated in eggs of the sea urchin Arbacia lixula. Ouabain-sensitive {sup 86}Rb uptake and amiloride-sensitive {sup 24}Na influx were dramatically stimulated after TPA addition, indicating an enhancement of total ionic permeabilities. Stimulation by TPA of both Na{sup +}/H{sup +} and Na{sup +}/K{sup +} exchanges was canceled by amiloride, suggesting that activation of protein kinase C elicits, via Na{sup +}/H{sup +} activity, stimulation of the sodium pump. However, TPA did not stimulate sodium pump activity and Na{sup +}/H{sup +} exchange at the same rate as fertilization, probably because of an absence of calcium-dependent events. Further fertilization of TPA pretreated eggs triggered an enhancement of sodium pump activity when the TPA treatment duration did not exceed 10 minutes. It is suggested that TPA activates preexisting transporting mechanisms in plasma membranes of unfertilized eggs (Na{sup +} stat, pH stat).

  5. Current perspectives on the use of intravenous recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke

    PubMed Central

    Chapman, Sherita N; Mehndiratta, Prachi; Johansen, Michelle C; McMurry, Timothy L; Johnston, Karen C; Southerland, Andrew M

    2014-01-01

    In 1995, the NINDS (National Institute of Neurological Disorders and Stroke) tPA (tissue plasminogen activator) Stroke Study Group published the results of a large multicenter clinical trial demonstrating efficacy of intravenous tPA by revealing a 30% relative risk reduction (absolute risk reduction 11%–15%) compared with placebo at 90 days in the likelihood of having minimal or no disability. Since approval in 1996, tPA remains the only drug treatment for acute ischemic stroke approved by the US Food and Drug Administration. Over the years, an abundance of research and clinical data has supported the safe and efficacious use of intravenous tPA in all eligible patients. Despite such supporting data, it remains substantially underutilized. Challenges to the utilization of tPA include narrow eligibility and treatment windows, risk of symptomatic intracerebral hemorrhage, perceived lack of efficacy in certain high-risk subgroups, and a limited pool of neurological and stroke expertise in the community. With recent US census data suggesting annual stroke incidence will more than double by 2050, better education and consensus among both the medical and lay public are necessary to optimize the use of tPA for all eligible stroke patients. Ongoing and future research should continue to improve upon the efficacy of tPA through more rapid stroke diagnosis and treatment, refinement of advanced neuroimaging and stroke biomarkers, and successful demonstration of alternative means of reperfusion. PMID:24591838

  6. Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies.

    PubMed

    Adibhatla, Rao Muralikrishna; Hatcher, James F

    2008-06-01

    Today there exists only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? Is the animal research truly translational in identifying new agents for stroke treatment? This review summarizes the current state of affairs with plasminogen activators in thrombolytic therapy. In addition to therapeutic value, potential side effects of tPA also exist that aggravate stroke injury and offset the benefits provided by reperfusion of the occluded artery. Thus, combinational options (ultrasound alone or with microspheres/nanobubbles, mechanical dissociation of clot, activated protein C (APC), plasminogen activator inhibitor-1 (PAI-1), neuroserpin and CDP-choline) that could offset tPA toxic side effects and improve efficacy are also discussed here. Desmoteplase, a plasminogen activator derived from the saliva of Desmodus rotundus vampire bat, antagonizes vascular tPA-induced neurotoxicity by competitively binding to low-density lipoprotein related-receptors (LPR) at the blood-brain barrier (BBB) interface, minimizing the tPA uptake into brain parenchyma. tPA can also activate matrix metalloproteinases (MMPs), a family of endopeptidases comprised of 24 mammalian enzymes that primarily catalyze the turnover and degradation of the extracellular matrix (ECM). MMPs have been implicated in BBB breakdown and neuronal injury in the early times after stroke, but also contribute to vascular remodeling, angiogenesis, neurogenesis and axonal regeneration during the later repair phase after stroke. tPA, directly or by activation of MMP-9, could have beneficial effects on recovery after stroke by promoting neurovascular repair through vascular endothelial growth factor (VEGF). However, any treatment regimen directed at MMPs must consider their

  7. Milestones in the history of personality disorders

    PubMed Central

    Crocq, Marc-Antoine

    2013-01-01

    This paper analyzes the major historical milestones in the study of normal and abnormal personality, from antiquity up until the 20th century. Special attention is paid to the interaction between dimensional and typological approaches, which was a major issue during the preparation of DSM-5. Theories of personality started with the humoral theory of Greek medicine. Pinel, and later Esquirol and Prichard, are credited with the first descriptions of abnormal personalities in textbooks of psychiatry. Between the late 19th and early 20th centuries, elaborate systems of normal and abnormal personality, associating to some degree types and dimensions, were devised by a succession of European psychologists, such as Ribot, Heymans, and Lazursky. Emil Kraepelin and Kurt Schneider proposed classifications of abnormal personality types. In parallel, psychoanalysts stressed the role of early life experiences. Towards the mid-20th century, statistical methods were applied to the scientific validation of personality dimensions with pioneers such as Cattell, anticipating the five-factor model. PMID:24174889

  8. AVLIS production plant project schedule and milestones

    SciTech Connect

    Not Available

    1984-11-15

    An AVLIS Production Plant Deployment Schedule for the engineering, procurement, and construction for both the Initial Increment of Production and the fully Activated Plant, has been developed by the project team consisting of Lawrence Livermore National Laboratory, Martin Marietta Energy Systems, Inc. with architect-engineer support from Bechtel National, Inc., Stone and Webster Engineering Corporation, and Westinghouse Corporation. The initial deployment phase consists of six separators modules and the three laser power amplifier modules consistent with the FY84 reference design with a name plate capacity of 5 million separative work units/yr followed by a full plant activation to approximately 13 million separative work units/yr. The AVLIS Production Plant project team's strategy for deployment schedule analysis focused on three schedule options: engineering limited schedule; authorization limited schedule; and funding limited project schedule. The three deployment schedule options developed by AVLIS project team have been classified in ranges such as an optimistic, rapid/moderate, or moderate/pessimistic based on the probability of meeting the individual schedule option's major milestones or program objectives of enriching uranium by the AVLIS process in an effective cost and schedule manner. 47 figures, 7 tables.

  9. ASC Trilab L2 Codesign Milestone 2015

    SciTech Connect

    Trott, Christian Robert; Hammond, Simon David; Dinge, Dennis; Lin, Paul T.; Vaughan, Courtenay T.; Cook, Jeanine; Edwards, Harold C.; Rajan, Mahesh; Hoekstra, Robert J.

    2015-09-01

    For the FY15 ASC L2 Trilab Codesign milestone Sandia National Laboratories performed two main studies. The first study investigated three topics (performance, cross-platform portability and programmer productivity) when using OpenMP directives and the RAJA and Kokkos programming models available from LLNL and SNL respectively. The focus of this first study was the LULESH mini-application developed and maintained by LLNL. In the coming sections of the report the reader will find performance comparisons (and a demonstration of portability) for a variety of mini-application implementations produced during this study with varying levels of optimization. Of note is that the implementations utilized including optimizations across a number of programming models to help ensure claims that Kokkos can provide native-class application performance are valid. The second study performed during FY15 is a performance assessment of the MiniAero mini-application developed by Sandia. This mini-application was developed by the SIERRA Thermal-Fluid team at Sandia for the purposes of learning the Kokkos programming model and so is available in only a single implementation. For this report we studied its performance and scaling on a number of machines with the intent of providing insight into potential performance issues that may be experienced when similar algorithms are deployed on the forthcoming Trinity ASC ATS platform.

  10. Surfactin suppresses TPA-induced breast cancer cell invasion through the inhibition of MMP-9 expression.

    PubMed

    Park, Sun Young; Kim, Ji-Hee; Lee, Young Ji; Lee, Sang Joon; Kim, Younghee

    2013-01-01

    Metastasis is the main cause of cancer mortality. In this study, we investigated the effects of surfactin, a cyclic lipopeptide produced by Bacillus subtilis, on cancer metastasis in vitro and the underlying molecular mechanisms involved. Surfactin inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasion, migration and colony formation of human breast carcinoma cells. Western blot analysis, gelatin zymography and reverse transcription-PCR analysis revealed that matrix metalloproteinase-9 (MMP-9) expression and activation was significantly suppressed by surfactin in a dose-dependent manner. Surfactin attenuated TPA-induced nuclear translocation and activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). Furthermore, surfactin strongly repressed the TPA-induced phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Treatment with specific inhibitors of Akt and ERK suppressed MMP-9 expression and activation. These results suggest that the surfactin-mediated inhibition of breast cancer cell invasion and MMP-9 expression involves the suppression of the NF-κB, AP-1, phosphatidylinositol 3-kinase (PI-3K)/Akt and the ERK signaling pathways. Thus surfactin may have potential value in therapeutic strategies for the treatment of breast cancer metastasis. PMID:23151889

  11. Inhibition of PAI-1 Antiproteolytic Activity Against tPA by RNA Aptamers

    PubMed Central

    Damare, Jared; Brandal, Stephanie

    2014-01-01

    Plasminogen activator inhibitor-1 (PAI-1; SERPINE1) inhibits the plasminogen activators: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). Elevated levels of PAI-1 have been correlated with an increased risk for cardiovascular disease. Pharmacologically suppressing PAI-1 might prevent, or successfully treat PAI-1 related vascular diseases. This can potentially be accomplished by using small RNA molecules (aptamers). This study's goal is to develop RNA aptamers to a region of PAI-1 that will prevent the ability of PAI-1 to interact with the plasminogen activators. The aptamers were generated through a systematic evolution of ligands via exponential enrichment approach that ensures the creation of RNA molecules that bind to our target protein, PAI-1. In vitro assays were used to determine the effect of these aptamers on PAI-1's inhibitory activity. Three aptamers that bind to PAI-1 with affinities in the nanomolar range were isolated. The aptamer clones R10-4 and R10-2 inhibited PAI-1's antiproteolytic activity against tPA and disrupted PAI-1's ability to form a stable covalent complex with tPA. Increasing aptamer concentrations correlated positively with an increase in cleaved PAI-1. To the best of our knowledge, this is the first report of RNA molecules that inhibit the antiproteolytic activity of PAI-1. PMID:24922319

  12. X-ray diffraction of solid tin to 1.2 TPa

    NASA Astrophysics Data System (ADS)

    Lazicki, Amy; Rygg, Ryan; Coppari, Federica; Smith, Ray; Fratanduono, Dayne; Braun, Dave; Kraus, Richard; Swift, Damian; Collins, Gilbert; Eggert, Jon

    2015-06-01

    We present x-ray diffraction studies of solid crystal structure at the highest stress state where such measurements have ever been performed. Using laser-driven ramp compression methods coupled with angle-resolved powder x-ray diffraction at the Omega laser facility, we explore the phase diagram of tin below the melting curve between 0.1 and 1.2 terapascals (TPa). We demonstrate that, at dynamic-compression rates on the order of 107 s-1, tin transforms from the ambient tetragonal beta-Sn phase to the stable high pressure body-centered cubic (bcc) phase with densities consistent with static-compression measurements. Above 0.16 TPa our experiments identify a new feature in the phase diagram: a crystal structure clearly inconsistent with the hexagonal-close-packed (hcp) phase identified at these conditions by ambient-temperature static-compression measurements and by zero-kelvin density functional theory structure predictions. Our results suggest that the bcc phase is stabilized relative to hcp at high temperature, analogous to the heavier group IV metal Pb and numerous other elemental metals, and retains this phase during ramp compression to 1.2 TPa. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  13. 14 CFR 1274.909 - Term of agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... continues until the expiration date indicated on the attached cover sheet unless terminated by either party. If all resources are expended prior to the expiration date of the agreement, the parties have no... expiration date if additional time is required to complete the milestones at no increase in...

  14. Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study

    PubMed Central

    Sati, Jasmine; Mohanty, Biraja Prasad; Garg, Mohan Lal; Koul, Ashwani

    2016-01-01

    Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma. In the Silibinin+DMBA/TPA group, significant reduction in tumor incidence (23%), tumor volume (64.4%), and tumor burden (84.8%) was observed when compared to the DMBA/TPA group. The underlying protective mechanism of Silibinin action was studied at pre-initiation (2 weeks), post-initiation (10 weeks) and promotion (22 weeks) stages of the skin carcinogenesis. The antioxidant nature of Silibinin was evident at the end of 2 weeks of its treatment. However, towards the end of 10 and 22 weeks, elevated lipid peroxidation (LPO) levels indicate the pro-oxidative nature of Silibinin in the cancerous tissue. TUNEL assay revealed enhanced apoptosis in the Silibinin+DMBA/TPA group with respect to the DMBA/TPA group. Therefore, it may be suggested that raised LPO could be responsible for triggering apoptosis in the Silibinin+DMBA/TPA group. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the metabolic profile of the skin /skin tumors. Dimethylamine (DMA), glycerophosphocholine (GPC), glucose, lactic acid, taurine and guanine were identified as the major contributors for separation between the groups from the Principal Component Analysis (PCA) of the metabolite data. Enhanced DMA levels with no alteration in GPC, glucose and lactate levels reflect altered choline metabolism with no marked Warburg effect in skin tumors. However, elevated guanine levels with potent suppression of taurine and glucose levels in the Silibinin+DMBA/TPA group are

  15. Pro-Oxidant Role of Silibinin in DMBA/TPA Induced Skin Cancer: 1H NMR Metabolomic and Biochemical Study.

    PubMed

    Sati, Jasmine; Mohanty, Biraja Prasad; Garg, Mohan Lal; Koul, Ashwani

    2016-01-01

    Silibinin, a major bioactive flavonolignan in Silybum marianum, has received considerable attention in view of its anticarcinogenic activity. The present study examines its anticancer potential against 7, 12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin cancer. Male LACA mice were randomly segregated into 4 groups: Control, DMBA/TPA, Silibinin and Silibinin+DMBA/TPA. Tumors in DMBA/TPA and Silibinin+DMBA/TPA groups were histologically graded as squamous cell carcinoma. In the Silibinin+DMBA/TPA group, significant reduction in tumor incidence (23%), tumor volume (64.4%), and tumor burden (84.8%) was observed when compared to the DMBA/TPA group. The underlying protective mechanism of Silibinin action was studied at pre-initiation (2 weeks), post-initiation (10 weeks) and promotion (22 weeks) stages of the skin carcinogenesis. The antioxidant nature of Silibinin was evident at the end of 2 weeks of its treatment. However, towards the end of 10 and 22 weeks, elevated lipid peroxidation (LPO) levels indicate the pro-oxidative nature of Silibinin in the cancerous tissue. TUNEL assay revealed enhanced apoptosis in the Silibinin+DMBA/TPA group with respect to the DMBA/TPA group. Therefore, it may be suggested that raised LPO could be responsible for triggering apoptosis in the Silibinin+DMBA/TPA group. 1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the metabolic profile of the skin /skin tumors. Dimethylamine (DMA), glycerophosphocholine (GPC), glucose, lactic acid, taurine and guanine were identified as the major contributors for separation between the groups from the Principal Component Analysis (PCA) of the metabolite data. Enhanced DMA levels with no alteration in GPC, glucose and lactate levels reflect altered choline metabolism with no marked Warburg effect in skin tumors. However, elevated guanine levels with potent suppression of taurine and glucose levels in the Silibinin+DMBA/TPA group are

  16. Those Baby 'Milestones' May Have Longer-Term Importance

    MedlinePlus

    ... an important basis for various aspects of later child development." The research team -- led by Edwina Yeung, of ... and underweight. Those are key factors in a child's development, and might "overshadow" any link between movement milestones ...

  17. Hydrogen milestone could help lower fossil fuel refining costs

    SciTech Connect

    Stephen Herring

    2009-10-13

    Hydrogen researchers at the U.S. Department of Energy's Idaho National Laboratory have reached another milestone on the road to reducing carbon emissions and protecting the nation against the effects of peaking world oil production. Stephen Herring, lab

  18. Hydrogen milestone could help lower fossil fuel refining costs

    ScienceCinema

    Stephen Herring

    2010-01-08

    Hydrogen researchers at the U.S. Department of Energy's Idaho National Laboratory have reached another milestone on the road to reducing carbon emissions and protecting the nation against the effects of peaking world oil production. Stephen Herring, lab

  19. tPA-S481A prevents neurotoxicity of endogenous tPA in traumatic brain injury.

    PubMed

    Armstead, William M; Riley, John; Yarovoi, Serge; Cines, Douglas B; Smith, Douglas H; Higazi, Abd Al-Roof

    2012-06-10

    Traumatic brain injury (TBI) is associated with loss of autoregulation due to impaired responsiveness to cerebrovascular dilator stimuli, which leads to cerebral hypoperfusion and neuronal impairment or death. Upregulation of tissue plasminogen activator (tPA) post-TBI exacerbates loss of cerebral autoregulation and NMDA-receptor-mediated impairment of cerebral hemodynamics, and enhances excitotoxic neuronal death. However, the relationship between NMDA-receptor activation, loss of autoregulation, and neurological dysfunction is unclear. Here, we evaluated the potential therapeutic efficacy of a catalytically inactive tPA variant, tPA S481A, that acts by competing with wild-type tPA for binding, cleavage, and activation of NMDA receptors. Lateral fluid percussion brain injury was produced in anesthetized piglets. Pial artery reactivity was measured via a closed cranial window, and cerebrospinal fluid (CSF) extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) was quantified by enzyme-linked immunosorbent assay (ELISA). tPA-S481A prevented impairment of cerebral autoregulation and reduced histopathologic changes after TBI by inhibiting upregulation of the ERK isoform of MAPK. Treatment with this tPA variant provides a novel approach for limiting neuronal toxicity caused by untoward NMDA-receptor activation mediated by increased tPA and glutamate following TBI. PMID:22435890

  20. Level-1 Milestone 350 Definitions v1

    SciTech Connect

    Quinn, T

    2006-11-17

    This milestone is the direct result of work that started seven years ago with the planning for a 100-teraFLOP platform and will be satisfied when 100 teraFLOPS is placed in operation and readied for Stockpile Stewardship Program simulations. The end product of this milestone will be a production-level, high-performance computing system, code named Purple, designed to be used to solve the most demanding stockpile stewardship problems, that is, the large-scale application problems at the edge of our understanding of weapon physics. This fully functional 100 teraFLOPS system must be able to serve a diverse scientific and engineering workload. It must also have a robust code development and production environment, both of which facilitate the workload requirements. This multi-year effort includes major activities in contract management, facilities, infrastructure, system software, and user environment and support. Led by LLNL, the trilabs defined the statement of work for a 100-teraFLOP system that resulted in a contract with IBM known as the Purple contract. LLNL worked with IBM throughout the contract period to resolve issues and collaborated with the Program to resolve contractual issues to ensure delivery of a platform that best serves the Program for a reasonable cost. The Purple system represents a substantial increase in the classified compute resources at LLNL for NNSA. The center computer environment must be designed to accept the Purple system and to scale with the increase of compute resources to achieve required end-to-end services. Networking, archival storage, visualization servers, global file systems, and system software will all be enhanced to support Purple's size and architecture. IBM and LLNL are sharing responsibility for Purple's system software. LLNL is responsible for the scheduler, resource manager, and some code development tools. Through the Purple contract, IBM is responsible for the remainder of the system software including the operating

  1. Milestones on the social accountability journey

    PubMed Central

    Hogenbirk, John C.; Timony, Patrick E.; French, Margaret G.; Strasser, Roger; Pong, Raymond W.; Cervin, Catherine; Graves, Lisa

    2016-01-01

    Abstract Objective To assess the effect of different levels of exposure to the Northern Ontario School of Medicine’s (NOSM’s) distributed medical education programs in northern Ontario on FPs’ practice locations. Design Cross-sectional design using longitudinal survey and administrative data. Setting Canada. Participants All 131 Canadian medical graduates who completed FP training in 2011 to 2013 and who completed their undergraduate (UG) medical degree or postgraduate (PG) residency training or both at NOSM. Intervention Exposure to NOSM’s medical education program at the UG (n = 49) or PG (n = 31) level or both (n = 51). Main outcome measures Primary practice location in September of 2014. Results Approximately 16% (21 of 129) of FPs were practising in rural northern Ontario, 45% (58 of 129) in urban northern Ontario, and 5% (7 of 129) in rural southern Ontario. Logistic regression found that more rural Canadian background years predicted rural practice in northern Ontario or Ontario, with odds ratios of 1.16 and 1.12, respectively. Northern Canadian background, sex, marital status, and having children did not predict practice location. Completing both UG and PG training at NOSM predicted practising in rural and northern Ontario locations with odds ratios of 4.06 to 48.62. Conclusion Approximately 61% (79 of 129) of Canadian medical graduate FPs who complete at least some of their training at NOSM practise in northern Ontario. Slightly more than a quarter (21 of 79) of these FPs practise in rural northern Ontario. The FPs with more years of rural background or those with greater exposure to NOSM’s medical education programs had higher odds of practising in rural northern Ontario. This study shows that NOSM is on the road to reaching one of its social accountability milestones. PMID:27427565

  2. Guide to DCP Study Close-Out: Milestones and Tasks | Division of Cancer Prevention

    Cancer.gov

    This guide assists Consortium Lead Organization (CLO) planning for DCP study close-out. Study close-out tasks are organized under milestones, which help mark progress toward completion of the close-out process. Once tasks associated with a milestone are underway, planning for the next milestone may begin. Click on a milestone to view the associated close-out tasks. |

  3. Shortening the Miles to the Milestones: Connecting EPA-Based Evaluations to ACGME Milestone Reports for Internal Medicine Residency Programs.

    PubMed

    Choe, John H; Knight, Christopher L; Stiling, Rebekah; Corning, Kelli; Lock, Keli; Steinberg, Kenneth P

    2016-07-01

    The Next Accreditation System requires internal medicine training programs to provide the Accreditation Council for Graduate Medical Education (ACGME) with semiannual information about each resident's progress in 22 subcompetency domains. Evaluation of resident "trustworthiness" in performing entrustable professional activities (EPAs) may offer a more tangible assessment construct than evaluations based on expectations of usual progression toward competence. However, translating results from EPA-based evaluations into ACGME milestone progress reports has proven to be challenging because the constructs that underlay these two systems differ.The authors describe a process to bridge the gap between rotation-specific EPA-based evaluations and ACGME milestone reporting. Developed at the University of Washington in 2012 and 2013, this method involves mapping EPA-based evaluation responses to "milestone elements," the narrative descriptions within the columns of each of the 22 internal medicine subcompetencies. As faculty members complete EPA-based evaluations, the mapped milestone elements are automatically marked as "confirmed." Programs can maintain a database that tallies the number of times each milestone element is confirmed for a resident; these data can be used to produce graphical displays of resident progress along the internal medicine milestones.Using this count of milestone elements allows programs to bridge the gap between faculty assessments of residents based on rotation-specific observed activities and semiannual ACGME reports based on the internal medicine milestones. Although potentially useful for all programs, this method is especially beneficial to large programs where clinical competency committee members may not have the opportunity for direct observation of all residents. PMID:27028030

  4. 14 CFR 1274.908 - Milestone payments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... established accounting system which complies with generally accepted accounting principles, with the..., and accounting for Federal funds received under this agreement. (b) Payments will be made upon the... after receipt of proper invoice. Payment shall be considered as being made on the date of...

  5. Direct Observation Assessment of Milestones: Problems with Reliability

    PubMed Central

    Schott, Meghan; Kedia, Raashee; Promes, Susan B.; Swoboda, Thomas; O’Rourke, Kevin; Green, Walter; Liu, Rachel; Stansfield, Brent; Santen, Sally A.

    2015-01-01

    Introduction Emergency medicine (EM) milestones are used to assess residents’ progress. While some milestone validity evidence exists, there is a lack of standardized tools available to reliably assess residents. Inherent to this is a concern that we may not be truly measuring what we intend to assess. The purpose of this study was to design a direct observation milestone assessment instrument supported by validity and reliability evidence. In addition, such a tool would further lend validity evidence to the EM milestones by demonstrating their accurate measurement. Methods This was a multi-center, prospective, observational validity study conducted at eight institutions. The Critical Care Direct Observation Tool (CDOT) was created to assess EM residents during resuscitations. This tool was designed using a modified Delphi method focused on content, response process, and internal structure validity. Paying special attention to content validity, the CDOT was developed by an expert panel, maintaining the use of the EM milestone wording. We built response process and internal consistency by piloting and revising the instrument. Raters were faculty who routinely assess residents on the milestones. A brief training video on utilization of the instrument was completed by all. Raters used the CDOT to assess simulated videos of three residents at different stages of training in a critical care scenario. We measured reliability using Fleiss’ kappa and interclass correlations. Results Two versions of the CDOT were used: one used the milestone levels as global rating scales with anchors, and the second reflected a current trend of a checklist response system. Although the raters who used the CDOT routinely rate residents in their practice, they did not score the residents’ performances in the videos comparably, which led to poor reliability. The Fleiss’ kappa of each of the items measured on both versions of the CDOT was near zero. Conclusion The validity and

  6. Provider perceptions of barriers to the emergency use of tPA for Acute Ischemic Stroke: A qualitative study

    PubMed Central

    2011-01-01

    Background Only 1-3% of ischemic stroke patients receive thrombolytic therapy. Provider barriers to adhering with guidelines recommending tPA delivery in acute stroke are not well known. The main objective of this study was to describe barriers to thrombolytic use in acute stroke care. Methods Twenty-four hospitals were randomly selected and matched into 12 pairs. Barrier assessment occurred at intervention sites only, and utilized focus groups and structured interviews. A pre-specified taxonomy was employed to characterize barriers. Two investigators independently assigned themes to transcribed responses. Seven facilitators (three emergency physicians, two nurses, and two study coordinators) conducted focus groups and interviews of emergency physicians (65), nurses (62), neurologists (15), radiologists (12), hospital administrators (12), and three others (hospitalists and pharmacist). Results The following themes represented the most important external barriers: environmental and patient factors. Important barriers internal to the clinician included familiarity with and motivation to adhere to the guidelines, lack of self-efficacy and outcome expectancy. The following themes were not substantial barriers: lack of awareness of the existence of acute stroke guidelines, presence of conflicting guidelines, and lack of agreement with the guidelines. Conclusions Healthcare providers perceive environmental and patient-related factors as the primary barriers to adherence with acute stroke treatment guidelines. Interventions focused on increasing physician familiarity with and motivation to follow guidelines may be of highest yield in improving adherence. Improving self-efficacy in performing guideline concordant care may also be useful. Trial Registration ClinicalTrials.gov identifier: NCT00349479 PMID:21548943

  7. MRI evaluation of BBB disruption after adjuvant AcSDKP treatment of stroke with tPA in rat.

    PubMed

    Ding, G; Zhang, Z; Chopp, M; Li, L; Zhang, L; Li, Q; Wei, M; Jiang, Q

    2014-06-20

    The primary limitation of thrombolytic treatment of ischemic stroke with tissue plasminogen activator (tPA) is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4 h after ischemia. Magnetic resonance imaging (MRI) measurements were performed before and after the treatments. Immunohistochemical staining and measurements were performed to confirm MRI findings. Longitudinal MRI permeability measurements with gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) demonstrated that combination treatment of acute embolic stroke with AcSDKP and tPA significantly reduced BBB leakage, compared to tPA monotherapy, at 3 and 6 days (18.3±9.8 mm3 vs. 65.0±21.0 mm3, p<0.001) after the onset of stroke, although BBB leakage was comparable between the two groups prior to the treatments (6.8±4.4 mm3 vs. 4.3±3.3 mm3, p>0.18). The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9 mm3 vs. 188.1±60.8 mm3, p<0.04 at 6 days). Histopathological analysis of the same population of rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059 mm2 vs. 0.172±0.103 mm2, p<0.03) and infarct volume (146.7±35.9 mm3 vs. 199.3±60.4 mm3, p<0.05) compared to the tPA monotherapy at 6days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4h after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy. PMID:24769225

  8. Conformations of tissue plasminogen activator (tPA) orchestrate neuronal survival by a crosstalk between EGFR and NMDAR

    PubMed Central

    Bertrand, T; Lesept, F; Chevilley, A; Lenoir, S; Aimable, M; Briens, A; Hommet, Y; Bardou, I; Parcq, J; Vivien, D

    2015-01-01

    Tissue-type plasminogen activator (tPA) is a pleiotropic serine protease of the central nervous system (CNS) with reported neurotrophic and neurotoxic functions. Produced and released under its single chain form (sc), the sc-tPA can be cleaved by plasmin or kallikrein in a two chain form, tc-tPA. Although both sc-tPA and tc-tPA display a similar fibrinolytic activity, we postulated here that these two conformations of tPA (sc-tPA and tc-tPA) could differentially control the effects of tPA on neuronal survival. Using primary cultures of mouse cortical neurons, our present study reveals that sc-tPA is the only one capable to promote N-methyl-D-aspartate receptor (NMDAR)-induced calcium influx and subsequent excitotoxicity. In contrast, both sc-tPA and tc-tPA are capable to activate epidermal growth factor receptors (EGFRs), a mechanism mediating the antiapoptotic effects of tPA. Interestingly, we revealed a tPA dependent crosstalk between EGFR and NMDAR in which a tPA-dependent activation of EGFRs leads to downregulation of NMDAR signaling and to subsequent neurotrophic effects. PMID:26469972

  9. Catheter-directed Thrombolysis with Argatroban and tPA for Massive Iliac and Femoropopliteal Vein Thrombosis

    SciTech Connect

    Sharifi, Mohsen; Bay, Curt; Nowroozi, Sasan; Bentz, Suzanne; Valeros, Gayle; Memari, Sara

    2013-12-15

    Purpose: Catheter-directed thrombolysis (CDT) is a highly effective approach in the treatment of deep venous thrombosis (DVT). There are no data on the primary use of CDT with argatroban and tissue plasminogen activator (tPA) in patients without heparin-induced thrombocytopenia (HIT). The aim of this study was to evaluate the efficacy and safety of the combined administration of argatroban and tPA during CDT for massive DVT in patients without HIT. Methods: Thirty-three patients with massive symptomatic iliac and femoropopliteal DVT underwent CDT with tPA and argatroban within 28 {+-} 6 h of presentation. The dose of tPA was 0.75-1 mg/h through the infusion port and that of argatroban at 0.3-1 {mu}g/kg/min through the side port of the sheath. The patients were evaluated for the efficacy and safety of CDT and recurrent symptomatic venous thromboembolism (VTE) at a mean follow-up of 22 months. Results: There was no bleeding or iatrogenic pulmonary embolism with the CDT regimen we used. Grade III lysis (complete resolution of thrombus on venography) was achieved in 30 patients (91 %). In 3 patients with additional inferior vena cava filter thrombosis, further thrombectomy of the filter was required. No patient developed recurrent VTE. Conclusion: Concomitant administration of argatroban and tPA is a highly safe and effective regimen for CDT for massive DVT.

  10. Level-2 Milestone 2351: Terascale Simulation Facility Upgrade

    SciTech Connect

    Bailey, A M

    2007-10-02

    This report documents the LLNL TSF upgrade ASC L2 milestone 2351: Terascale Simulation Facility upgrade, due Sept. 30, 2007. The full text of the milestone is included in Attachment 1. The stated goal of the milestone was: 'Complete a 3-MW expansion of electrical power for computing systems in the east computer room of the Terascale Simulation Facility (TSF) and complete the final connection of all air handlers that were delivered as part of the TSF line item'. In this report we detail the upgrade and cover the results of the process to accept the system by testing, adjusting, balancing and finally start-up of the system in accordance with the detailed project commissioning plan to be developed by the system engineers during the design phase of the project. The quarterly reports for the upgrade and the text of the project commissioning plan are included at the end of this document as Attachments 2 and 3.

  11. tPA promotes ADAMTS-4-induced CSPG degradation, thereby enhancing neuroplasticity following spinal cord injury.

    PubMed

    Lemarchant, Sighild; Pruvost, Mathilde; Hébert, Marie; Gauberti, Maxime; Hommet, Yannick; Briens, Aurélien; Maubert, Eric; Gueye, Yatma; Féron, François; Petite, Didier; Mersel, Marcel; do Rego, Jean-Claude; Vaudry, Hubert; Koistinaho, Jari; Ali, Carine; Agin, Véronique; Emery, Evelyne; Vivien, Denis

    2014-06-01

    Although tissue plasminogen activator (tPA) is known to promote neuronal remodeling in the CNS, no mechanism of how this plastic function takes place has been reported so far. We provide here in vitro and in vivo demonstrations that this serine protease neutralizes inhibitory chondroitin sulfate proteoglycans (CSPGs) by promoting their degradation via the direct activation of endogenous type 4 disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4). Accordingly, in a model of compression-induced spinal cord injury (SCI) in rats, we found that administration of either tPA or its downstream effector ADAMTS-4 restores the tPA-dependent activity lost after the SCI and thereby, reduces content of CSPGs in the spinal cord, a cascade of events leading to an improved axonal regeneration/sprouting and eventually long term functional recovery. This is the first study to reveal a tPA-ADAMTS-4 axis and its function in the CNS. It also raises the prospect of exploiting such cooperation as a therapeutic tool for enhancing recovery after acute CNS injuries. PMID:24576594

  12. Extracting the diffusion tensor from molecular dynamics simulation with Milestoning

    SciTech Connect

    Mugnai, Mauro L.; Elber, Ron

    2015-01-07

    We propose an algorithm to extract the diffusion tensor from Molecular Dynamics simulations with Milestoning. A Kramers-Moyal expansion of a discrete master equation, which is the Markovian limit of the Milestoning theory, determines the diffusion tensor. To test the algorithm, we analyze overdamped Langevin trajectories and recover a multidimensional Fokker-Planck equation. The recovery process determines the flux through a mesh and estimates local kinetic parameters. Rate coefficients are converted to the derivatives of the potential of mean force and to coordinate dependent diffusion tensor. We illustrate the computation on simple models and on an atomically detailed system—the diffusion along the backbone torsions of a solvated alanine dipeptide.

  13. [The years in pictures; medical milestones since 1970].

    PubMed

    Langeveld, C H Kees; de Leeuw, Peter W

    2015-01-01

    The end of the year is always a perfect moment to look back. However, looking back over the past year alone is not enough if you want a complete picture of developments in medical science, which is why the Dutch Journal of Medicine (NTvG) has posted a timeline on its website charting medical milestones over the past 45 years. Some of these milestones are illustrated in the infographic in this number, and some interesting patterns can be observed. In this article we discuss various trends, from the increasing tendency to quantify to the rise of evidence-based medicine. PMID:26675654

  14. Waste Cleanup: Status and Implications of Compliance Agreements Between DOE and Its Regulators

    SciTech Connect

    Jones, G. L.; Swick, W. R.; Perry, T. C.; Kintner-Meyer, N.K.; Abraham, C. R.; Pollack, I. M.

    2003-02-26

    This paper discusses compliance agreements that affect the Department of Energy's (DOE) cleanup program. Compliance agreements are legally enforceable documents between DOE and its regulators, specifying cleanup activities and milestones that DOE has agreed to achieve. Over the years, these compliance agreements have been used to implement much of the cleanup activity at DOE sites, which is carried our primarily under two federal laws - the Comprehensive Environmental Response, Compensation, and Liability Act of 1980, as amended (CERCLA) and the Resource Conservation and Recovery Act of 0f 1976, as amended (RCRA). Our objectives were to determine the types of compliance agreements in effect at DOE cleanup sites, DOE's progress in achieving the milestones contained in the agreements, whether the agreements allowed DOE to prioritize work across sites according to relative risk, and possible implications the agreements have on DOE's efforts to improve the cleanup program.

  15. The MILE Guide: Milestones for Improving Learning & Education

    ERIC Educational Resources Information Center

    Partnership for 21st Century Skills, 2009

    2009-01-01

    Every district will benefit from understanding where it sits on the continuum of 21st century skills integration. The Milestones for Improving Learning & Education (MILE) Guide Self-Assessment tool helps districts accomplish this essential first step, covering the primary responsibilities and activities within a district. Subjects covered include:…

  16. Age cohort differences in the developmental milestones of gay men.

    PubMed

    Drasin, Harry; Beals, Kristin P; Elliott, Marc N; Lever, Janet; Klein, David J; Schuster, Mark A

    2008-01-01

    As the social context in which gay men live changes due to greater visibility, greater acceptance, and easier access to gay subculture, gay males may self-identify and take part in gay social activities at earlier ages than in the past. This study examined whether developmental milestones associated with sexual orientation for gay men have changed over the past several decades. A large and diverse sample of 2,402 gay men who responded to a 1994 survey published in a national magazine provided retrospective information on the age at which they reached individual psychological, social, and sexual behavior developmental milestones. We found evidence that individual psychological and sexual behavior milestones (e.g., awareness of attraction to males, having an orgasm with other male) are slowly moving toward earlier chronological ages (by 1 year of age every 8-25 years, p < 0.05), whereas social milestones (e.g., coming out) are moving more rapidly in a similar direction (by 1 year of age every 2-5 years, p < 0.001). The authors perform an innovative sensitivity test to demonstrate the persistence of the finding after correcting for the bias attributable to underrepresentation of those who have not yet self-identified as gay in such samples. PMID:18826167

  17. Social Development and Feeding Milestones of Young Down Syndrome Children.

    ERIC Educational Resources Information Center

    And Others; Cullen, Susan M.

    1981-01-01

    The data revealed that young Down syndrome children attained significantly higher scores on the Vineland Social Maturity Scale and achieved most feeding milestones much earlier if they had no or only mild congenital heart disease, if their parents followed through appropriately with furnished guidance, and if they had "good" muscle tone. (Author)

  18. Apparatus as Milestones in the History of Comparative Psychology

    NASA Technical Reports Server (NTRS)

    Washburn, David A.; Rumbaugh, Duane M.; Putney, R. Thompson

    1994-01-01

    Significant apparatus developments from the history of comparative psychology are reviewed, including the contemporary trend toward computer use in research with nonhuman animals. It is argued that milestone apparatus served not only to open new lines of inquiry but also to shape or delimit the nature of the answers that were obtained.

  19. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Advance payments or payable milestones. 603.1105 Section 603.1105 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT... point is 44% ($40,000 out of the total $90,000 expended, with the balance provided by the...

  20. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Advance payments or payable milestones. 603.1105 Section 603.1105 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT... point is 44% ($40,000 out of the total $90,000 expended, with the balance provided by the...

  1. UDS Recovery Equipment Installation (AFCI CETE Milestone Report)

    SciTech Connect

    Jubin, Robert Thomas

    2009-06-01

    This letter documents the successful installation of the un-dissolved solids (UDS) recovery equipment into the hot-cell in building 7920 at ORNL. This installation (see Figure 1) satisfies the AFCI Level 4 milestone in the CETE Investments and Hot Cell Upgrades work package (OR0915020323) to 'Complete UDS recovery equipment installation' (M4502032306), due 30 June 09.

  2. 43 CFR 3930.30 - Diligent development milestones.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... conditions of the lease, POD, and these regulations. If the operator does not maintain or comply with...) Milestone 1. Within 2 years of the lease issuance date, submit to the proper BLM office an initial POD that meets the requirements of subpart 3931. The operator must revise the POD following subpart 3931, if...

  3. 43 CFR 3930.30 - Diligent development milestones.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... conditions of the lease, POD, and these regulations. If the operator does not maintain or comply with...) Milestone 1. Within 2 years of the lease issuance date, submit to the proper BLM office an initial POD that meets the requirements of subpart 3931. The operator must revise the POD following subpart 3931, if...

  4. Dependence of Proximal GC Boxes and Binding Transcription Factors in the Regulation of Basal and Valproic Acid-Induced Expression of t-PA

    PubMed Central

    Larsson, Pia; Magnusson, Mia; Karlsson, Lena; Bergh, Niklas; Jern, Sverker

    2016-01-01

    Objective. Endothelial tissue-type plasminogen activator (t-PA) release is a pivotal response to protect the circulation from occluding thrombosis. We have shown that the t-PA gene is epigenetically regulated and greatly induced by the histone deacetylase (HDAC) inhibitor valproic acid (VPA). We now investigated involvement of known t-PA promoter regulatory elements and evaluated dependence of potential interacting transcription factors/cofactors. Methods. A reporter vector with an insert, separately mutated at either the t-PA promoter CRE or GC box II or GC box III elements, was transfected into HT-1080 and HUVECs and challenged with VPA. HUVECs were targeted with siRNA against histone acetyl transferases (HAT) and selected transcription factors from the Sp/KLF family. Results. An intact VPA-response was observed with CRE mutated constructs, whereas mutation of GC boxes II and III reduced the magnitude of the induction by 54 and 79% in HT-1080 and 49 and 50% in HUVECs, respectively. An attenuated induction of t-PA mRNA was observed after Sp2, Sp4, and KLF5 depletion. KLF2 and p300 (HAT) were identified as positive regulators of basal t-PA expression and Sp4 and KLF9 as repressors. Conclusion. VPA-induced t-PA expression is dependent on the proximal GC boxes in the t-PA promoter and may involve interactions with Sp2, Sp4, and KLF5. PMID:26966581

  5. Crystal structure searching by free energy surface trekking: application to carbon at 1 TPa

    NASA Astrophysics Data System (ADS)

    Ishikawa, T.; Suzuki, N.; Shimizu, K.

    2014-05-01

    We have developed an ab-initio crystal structure searching method, free energy surface trekking (FEST). This method consists of an ascent-run and a descent-run. First, the system is forced to climb up a free energy surface following by the inversion of the restoring forces acting on the simulation cell (ascent-run). Then, the system climbs down the surface toward neighboring local minima according to the release from the constraint of the inversion immediately after the system crosses the ridges of the surface (descent-run). We have applied the FEST simulations to carbon at terapascal pressures and obtained a BC8-like structure with a tetragonal I41 in addition to the earlier-predicted BC8, R8, and simple cubic structures. This structure is mechanically stable in the pressure range of at least 0.5-3.5 TPa, and has a potential to survive as a metastable structure in carbon at terapascal pressures.

  6. The quest for TPa Hugoniot data: using the DEMG in high velocity pulsed power experiments

    SciTech Connect

    Peterson, Jeff H; Rousculp, Christopher L; Holtkamp, David B; Oro, David M; Griego, Jeffrey R; Atchison, Walter L; Reinovsky, Robert E

    2010-12-20

    ALT-3 is an experiment being designed in collaboration between Russian VNIIEF scientists and LANL that aims to conduct high velocity material experiments to measure shock velocities at pressures near 1 TPa. The DEMG (Disk Explosive Magnetic Generator) is used to drive >60MA currents to accelerate an aluminum liner to speeds in excess of 20 km/s. The 1-D model of the DEMG has been refined from a given current profile to a time-varying inductance. Various techniques are used to model the FOS (Foil Opening Switch) on the DEMG and a refined DEMG model is then used to drive a liner into various targets to determine the optimum design for the experiment and analyze the possible conditions and complications.

  7. Campaign 2 Level 2 Milestone Review 2009: Milestone # 3132 Determine Sustainable TATB Source and Processing Options, and Potential Binder Options

    SciTech Connect

    Schwartz, A J

    2009-09-28

    A presentation was made to the Milestone review committee on September 18, 2009 that outlined the efforts making up the achievement of the Campaign 2, Level 2 Milestone No.3132. After the presentation and review of the collective work, the committee determined that the milestone was successfully completed. Highlights from this review are discussed here. A brief summary of the discussion points includes: (1) It was clear that this work represents a comprehensive collection of experimental, modeling, literature review, and analysis activities with a thorough attention to the details. The deliverables include 2 technical presentations and 5 written reports describing this work. (2) This is a joint LLNL/LANL milestone led by Campaign 2 with leveraging effort from other campaigns and activities at LLNL: (a) The contributing programs included Enhanced Surveillance Campaign (ESC) and Readiness Campaign. Key technical elements of this work were built on scientific advances from the Laboratory Directed Research and Development (LDRD) program. (b) Part of this work covers activities associated with the Enhanced Collaboration (EC) with the Atomic Weapons Establishment (AWE). (3) This Milestone work has supported a high-level Directed Stockpile Work (DSW) Joint DoD/DOE TATB Production Initiative. This is an example of the strong relevance of this Milestone research to current stockpile issues. A summary of the future direction in this research area includes: (1) The Ionic Liquid (IL) re-crystallization process has been demonstrated to improve the performance of recrystallized TATB molecule. However, lower thermal stability of the IL crystallized material (compared to conventional TATB) warrants further study to understand the source of this effect. (2) The compatibility issue needs to be addressed in upcoming work. One concern is how the new solvent and ionic liquid used in the formulation process might behave in the nuclear explosive assembly. Similarly, compatibility studies

  8. Naringenin suppresses TPA-induced tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells.

    PubMed

    Yen, Hung-Rong; Liu, Ching-Ju; Yeh, Chia-Chou

    2015-06-25

    Naringenin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong anti-proliferative properties and the ability to induce apoptosis in hepatoma cell lines. However, there are no reports describing its effects on the invasion and metastasis of hepatoma cell lines, and the detailed molecular mechanisms of its effects are still unclear. In this study, we investigated the mechanisms underlying naringenin-mediated inhibition of 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in human hepatoma cells (HepG2, Huh-7, and HA22T) and murine embryonic liver cells (BNL CL2). Naringenin suppressed MMP-9 transcription by inhibiting activator protein (AP)-1 and nuclear factor-κB (NF-κB) activity. It suppressed TPA-induced AP-1 activity through inhibiting the phosphorylation of the extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and it suppressed TPA-induced inhibition of NF-κB nuclear translocation through IκB. Additionally, it suppressed TPA-induced activation of ERK/phosphatidylinositol 3-kinase/Akt upstream of NF-κB and AP-1. These data suggest that naringenin suppresses the invasiveness and metastatic potential of hepatocellular carcinoma (HCC) by inhibiting multiple signal transduction pathways. PMID:25866363

  9. The mechanism of the action of IFN-gamma and TPA on the modulation of epidermal growth factor receptors of human amnion cells.

    PubMed

    Katoh, T; Higashi, K; Karasaki, Y

    1992-06-01

    We have examined the mechanism of synergistic action occurring between interferon (IFN)-gamma and 12-0-tetradecanoylphorbol-13-acetate (TPA) with respect to the reduction of 125I-epidermal growth factor (125I-EGF) binding to human amnion (WISH) cells [Karasaki Y et al (1989) J Biol Chem 264: 6158-6163]. The cells were treated with protein kinase C (PKC) inhibitors (H7, staurosporine) to investigate the role of PKC in the synergism between IFN-gamma and TPA, since TPA is a strong activator of PKC. The combined effect of IFN-gamma and TPA was blocked by the PKC inhibitor, suggesting that PKC plays an important role in the synergistic action of TPA and IFN-gamma on the inhibition of EGF binding to the cells. The prolonged incubation (24 h) of the cells with TPA resulted in the restoration of EGF binding to the cells. A 24 h treatment of WISH cells with both IFN-gamma and TPA, however, still exhibited greater than 50% inhibition of EGF binding. No PKC activity, however, was observed in the WISH cells treated with both IFN-gamma and TPA for 24 h as well as with TPA alone for 24 h, indicating that IFN-gamma may synergize with the second mediator induced by PKC rather than PKC itself in the reduction of EGF binding to WISH cells. In addition, IFN-gamma showed the synergistic action with calcium ionophores on the reduction of EGF binding to the cells, suggesting that Ca2+ may be one of the second mediators which was induced by TPA and which cooperated with IFN-gamma. PMID:1621011

  10. GTRF Calculations Using Hydra-TH (L3 Milestone THM.CFD.P5.05)

    SciTech Connect

    Bakosi, Jozsef; Christon, Mark A.; Francois, Marianne M.; Lowrie, Robert B.; Nourgaliev, Robert

    2012-09-05

    This report describes the work carried out for completion of the Thermal Hydraulics Methods (THM) Level 3 Milestone THM.CFD.P5.05 for the Consortium for Advanced Simulation of Light Water Reactors (CASL). A series of body-fitted computational meshes have been generated by Numeca's Hexpress/Hybrid, a.k.a. 'Spider', meshing technology for the V5H 3 x 3 and 5 x 5 rod bundle geometries and subsequently used to compute the fluid dynamics of grid-to-rod fretting (GTRF). Spider is easy to use, fast, and automatically generates high-quality meshes for extremely complex geometries, required for the GTRF problem. Hydra-TH has been used to carry out large-eddy simulations on both 3 x 3 and 5 x 5 geometries, using different mesh resolutions. The results analyzed show good agreement with Star-CCM+ simulations and experimental data.

  11. Dehydroglyasperin C suppresses TPA-induced cell transformation through direct inhibition of MKK4 and PI3K.

    PubMed

    Lee, Ji Hoon; Kim, Jong-Eun; Jang, Young Jin; Lee, Charles C; Lim, Tae-Gyu; Jung, Sung Keun; Lee, Eunjung; Lim, Soon Sung; Heo, Yong Seok; Seo, Sang Gwon; Son, Joe Eun; Kim, Jong Rhan; Lee, Chang Yong; Lee, Hyong Joo; Lee, Ki Won

    2016-05-01

    Bioactive natural compounds from plant-derived sources have received substantial interest due to their potential therapeutic and preventive effects toward various human diseases. Licorice (Glycyrrhiza), a frequently-used component in traditional oriental medicines, has been incorporated into recipes not only to enhance taste, but also to treat various conditions including inflammation, chronic fatigue syndrome, and even cancer. Dehydroglyasperin C (DGC) is a major isoflavone found in the root of licorice. In the present study, we investigated the cancer chemopreventive effect of DGC and the underlying molecular mechanisms involved, by analyzing its effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic cell transformation and cyclooxygenase (COX)-2 expression in JB6 P+ mouse epidermal cells. DGC treatment attenuated TPA-induced activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) transcriptional activation, two major regulators of TPA-induced cell transformation, and COX-2 expression. TPA-induced phosphorylation of p38, JNK1/2 and Akt was also suppressed by DGC. Kinase assay data revealed that DGC inhibited the kinase activity of MKK4 and PI3K and this outcome was due to direct physical binding with DGC. Notably, DGC bound directly to MKK4 and PI3K in an ATP-competitive manner. Taken together, these results suggest that DGC exhibits cancer chemopreventive potential via its inhibitory effect on TPA-induced neoplastic cell transformation and COX-2 modulation through regulation of the MKK4 and PI3K pathways. © 2015 Wiley Periodicals, Inc. PMID:25787879

  12. ALMA Telescope Passes Major Milestone with Successful Antenna Link

    NASA Astrophysics Data System (ADS)

    2009-05-01

    The Atacama Large Millimeter/submillimeter Array (ALMA), an immense international telescope project under construction in northern Chile, reached a major milestone on April 30, when two ALMA antennas were linked together as an integrated system to observe an astronomical object for the first time. The milestone achievement, technically termed "First Fringes," came at ALMA’s Operations Support Facility, 9,500 feet above sea level. Faint radio waves emitted by the planet Mars were collected by the two 12-meter diameter ALMA antennas, then processed by state-of-the-art electronics to turn the two antennas into a single, high-resolution telescope system, called an interferometer. Such pairs of antennas are the basic building blocks of imaging systems that enable radio telescopes to deliver pictures that approach or even exceed the resolving power of visible light telescopes. In such a system, each antenna is combined electronically with every other antenna to form a multitude of antenna pairs. Each pair contributes unique information that is used to build a highly-detailed image of the astronomical object under observation. When completed early in the next decade, ALMA’s 66 antennas will provide over a thousand such antenna pairings, with distances between antennas exceeding ten miles. This will enable ALMA to see with a sharpness surpassing that of the best space telescopes. The antennas will operate at an altitude of 16,500 feet, high above the OSF, in one of the best locations on Earth for millimeter-wavelength astronomy, the Chajnantor Plateau in Chile’s Atacama Desert. Last week’s successful Mars observation was conducted at an observing frequency of 104.2 GHz. Astronomers measured the distinctive varying “fringes” detected by the interferometer as the planet moved across the sky. “This is a great success,” said Adrian Russell, North American ALMA Project Director at the National Radio Astronomy Observatory (NRAO), “not because we observed a

  13. Some Important Milestones in the Field of Blood Clotting.

    PubMed

    Doolittle, Russell F

    2016-01-01

    Several different kinds of 'milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen 'new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures. PMID:26667674

  14. Extracting the diffusion tensor from molecular dynamics simulation with Milestoning.

    PubMed

    Mugnai, Mauro L; Elber, Ron

    2015-01-01

    We propose an algorithm to extract the diffusion tensor from Molecular Dynamics simulations with Milestoning. A Kramers-Moyal expansion of a discrete master equation, which is the Markovian limit of the Milestoning theory, determines the diffusion tensor. To test the algorithm, we analyze overdamped Langevin trajectories and recover a multidimensional Fokker-Planck equation. The recovery process determines the flux through a mesh and estimates local kinetic parameters. Rate coefficients are converted to the derivatives of the potential of mean force and to coordinate dependent diffusion tensor. We illustrate the computation on simple models and on an atomically detailed system-the diffusion along the backbone torsions of a solvated alanine dipeptide. PMID:25573551

  15. Milestone Report - M31SW030904 - Sigma Team Coordination Meeting

    SciTech Connect

    Jubin, Robert Thomas

    2010-11-24

    This documents the completion of the FCR&D Level 3 milestone for the Off-Gas Sigma Team - ORNL work package (FTOR11SW0309), “Sigma Team Coordination Meeting” (M31SW030904), due 30 November 10. The subject meeting was held at Idaho National Laboratory on October 12 and 13, 2010. The agenda and meeting minutes are attached to this memo.

  16. Two Relations to Estimate Membrane Permeability Using Milestoning.

    PubMed

    Votapka, Lane W; Lee, Christopher T; Amaro, Rommie E

    2016-08-25

    Prediction of passive permeation rates of solutes across lipid bilayers is important to drug design, toxicology, and other biological processes such as signaling. The inhomogeneous solubility-diffusion (ISD) equation is traditionally used to relate the position-dependent potential of mean force and diffusivity to the permeability coefficient. The ISD equation is derived via the Smoluchowski equation and assumes overdamped system dynamics. It has been suggested that the complex membrane environment may exhibit more complicated damping conditions. Here we derive a variant of the inhomogeneous solubility diffusion equation as a function of the mean first passage time (MFPT) and show how milestoning, a method that can estimate kinetic quantities of interest, can be used to estimate the MFPT of membrane crossing and, by extension, the permeability coefficient. We further describe a second scheme, agnostic to the damping condition, to estimate the permeability coefficient from milestoning results or other methods that compute a probability of membrane crossing. The derived relationships are tested using a one-dimensional Langevin dynamics toy system confirming that the presented theoretical methods can be used to estimate permeabilities given simulation and milestoning results. PMID:27154639

  17. Historical milestones and discoveries that shaped the toxicology sciences.

    PubMed

    Hayes, Antoinette N; Gilbert, Steven G

    2009-01-01

    Knowledge of the toxic and healing properties of plants, animals, and minerals has shaped civilization for millennia. The foundations of modern toxicology are built upon the significant milestones and discoveries of serendipity and crude experimentation. Throughout the ages, toxicological science has provided information that has shaped and guided society. This chapter examines the development of the discipline of toxicology and its influence on civilization by highlighting significant milestones and discoveries related to toxicology. The examples shed light on the beginnings of toxicology, as well as examine lessons learned and re-learned. This chapter also examines how toxicology and the toxicologist have interacted with other scientific and cultural disciplines, including religion, politics, and the government. Toxicology has evolved to a true scientific discipline with its own dedicated scientists, educational institutes, sub-disciplines, professional societies, and journals. It now stands as its own entity while traversing such fields as chemistry, physiology, pharmacology, and molecular biology. We invite you to join us on a path of discovery and to offer our suggestions as to what are the most significant milestones and discoveries in toxicology. Additional information is available on the history section of Toxipedia (www.toxipedia.org). PMID:19157056

  18. Two Relations to Estimate Membrane Permeability Using Milestoning

    PubMed Central

    2016-01-01

    Prediction of passive permeation rates of solutes across lipid bilayers is important to drug design, toxicology, and other biological processes such as signaling. The inhomogeneous solubility-diffusion (ISD) equation is traditionally used to relate the position-dependent potential of mean force and diffusivity to the permeability coefficient. The ISD equation is derived via the Smoluchowski equation and assumes overdamped system dynamics. It has been suggested that the complex membrane environment may exhibit more complicated damping conditions. Here we derive a variant of the inhomogeneous solubility diffusion equation as a function of the mean first passage time (MFPT) and show how milestoning, a method that can estimate kinetic quantities of interest, can be used to estimate the MFPT of membrane crossing and, by extension, the permeability coefficient. We further describe a second scheme, agnostic to the damping condition, to estimate the permeability coefficient from milestoning results or other methods that compute a probability of membrane crossing. The derived relationships are tested using a one-dimensional Langevin dynamics toy system confirming that the presented theoretical methods can be used to estimate permeabilities given simulation and milestoning results. PMID:27154639

  19. t-PA, but not desmoteplase, induces plasmin-dependent opening of a blood-brain barrier model under normoxic and ischaemic conditions.

    PubMed

    Freeman, Roxann; Niego, Be'eri; Croucher, David R; Pedersen, Lars O; Medcalf, Robert L

    2014-05-27

    Tissue-type plasminogen activator (t-PA) is the only thrombolytic treatment available for patients with acute ischaemic stroke. However, t-PA can increase permeability of the blood-brain barrier (BBB). Desmoteplase is a plasminogen activator derived from the common vampire bat, currently under clinical development for ischaemic stroke. We compared how t-PA and desmoteplase influenced BBB permeability using a human in vitro model where primary brain endothelial cells (BEC) and astrocytes are co-cultured on the opposite sides of a porous membrane. Permeability changes were evaluated 6 or 24h post-stimulation by passage of fluorescent albumin across the membrane. Under normoxic conditions, t-PA, but not desmoteplase, increased BBB permeability. Surprisingly, the ability of t-PA to affect the barrier was lost under conditions of oxygen-glucose deprivation (OGD). Addition of plasminogen re-sensitised the BBB to the action of t-PA under both normoxia and OGD, but did not affect the inert behaviour of desmoteplase, even when digested fibrinogen was added to ensure optimal plasmin generation. These observations coincided with plasmin-dependent changes in astrocyte and BEC morphology and disruption of tight junction proteins in BECs, specifically initiated by t-PA but not by desmoteplase. Finally, inhibition of plasmin post-stimulation with t-PA and plasminogen, especially within 2h, protected the BBB against t-PA-mediated barrier opening. Hence t-PA, but not desmoteplase, increases BBB permeability under both normoxic and OGD conditions in a reversible, plasmin-dependent process. The inability of desmoteplase to increase permeability despite its capacity to generate plasmin provides further support for its use as thrombolytic in patients with ischaemic stroke. PMID:24675027

  20. Participation of mitogen-activated protein kinase in thapsigargin- and TPA-induced histamine production in murine macrophage RAW 264.7 cells

    PubMed Central

    Shiraishi, Muneshige; Hirasawa, Noriyasu; Kobayashi, Yuriko; Oikawa, Shinji; Murakami, Akira; Ohuchi, Kazuo

    2000-01-01

    Stimulation of the murine macrophage cell line RAW 264.7 with thapsigargin, an endomembrane Ca2+-ATPase inhibitor, induced histamine production in a time- and concentration-dependent manner. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), also enhanced histamine production. α-Fluoromethylhistidine, a suicide substrate of L-histidine decarboxylase (HDC), suppressed the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production. Both thapsigargin (30 nM) and TPA (30 nM) induced phosphorylation of p44/p42 MAP kinase and p38 MAP kinase. PD98059, a specific inhibitor of MEK-1 which phosphorylates p44/p42 MAP kinase, strongly suppressed both the thapsigargin (30 nM)- and TPA (30 nM)-induced histamine production, whereas SB203580, a specific inhibitor of p38 MAP kinase, inhibited them only partially. The other MEK-1 inhibitor, U-0126, also inhibited both the thapsigargin- and TPA-induced histamine production in a concentration-dependent manner. Thapsigargin (30 nM) and TPA (30 nM) increased the levels of HDC mRNA at 4 h, but PD98059 suppressed both the thapsigargin- and TPA-induced increases in the HDC mRNA level. These findings indicate that thapsigargin and TPA induce histamine production in RAW 264.7 cells by increasing the level of HDC mRNA, and that both the thapsigargin- and TPA-induced histamine production are regulated largely by p44/p42 MAP kinase and partially by p38 MAP kinase.. PMID:10711350

  1. Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA-induced Raji cells deformation.

    PubMed

    Siriwan, D; Miyawaki, C; Miyamoto, T; Naruse, T; Okazaki, K; Tamura, H

    2011-05-15

    Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti-deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety. PMID:22097098

  2. Crystal Structure Searching by Free Energy Surface Trekking: Application to Carbon above 1 TPa

    NASA Astrophysics Data System (ADS)

    Ishikawa, Takahiro; Suzuki, Naoshi; Shimizu, Katsuya

    2013-06-01

    Crystal structure determination of materials under extreme conditions has been one of grand challenges in high-pressure materials science. In computer simulations, the crystal structure searching is carried out by exploring Gibbs free energy surface (GFES) at given pressures and temperatures. Here, we propose a new crystal structure searching technique named as free energy surface trekking (FEST). FEST is based on a very simple idea and consists of an ascent-run and a descent-run. In the ascent-run, the system is forced to ascend GFES from a starting local minimum by following the inversion of the driving force acting on the simulation cell. Then, the system descends it toward a neighboring local minimum by flipping the inverted force at the ridge of GFES. The details of GFES around the starting local minimum are more correctly obtained by more investigating different trekking routes. We have applied FEST to carbon at 1.2 TPa and at 300 K, and successfully obtained the transition from the cubic diamond phase to the previously predicted BC8 phase. In this transition, 3 cell-angles concurrently increase from 90° to 101° in the ascent-run and become 109° through the descent-run, in which the activation energy is approximately 0.17 Ry/atom.

  3. Synchronous fluorescence spectroscopic characterization of DMBA-TPA-induced squamous cell carcinoma in mice

    NASA Astrophysics Data System (ADS)

    Diagaradjane, Parmeswaran; Yaseen, Mohammad A.; Yu, Jie; Wong, Michael S.; Anvari, Bahman

    2006-01-01

    While initially confined to the epidermis, squamous cell carcinoma can eventually penetrate into the underlying tissue if not diagnosed early and treated. The noninvasive early detection of the carcinoma is important to achieve a complete treatment of the disease. Of the various non-invasive optical techniques, the synchronous fluorescence (SF) technique is considered to provide a simplified spectral profile with more sharp spectral signatures of the endogenous fluorophores in complex systems. The potential use of the SF technique in the characterization of the sequential tissue transformation in 7,12-dimethylbenz(a)anthracene-12-O-tetradecanoylphorbol-13-acetate (DMBA-TPA)-induced mouse skin tumor model in conjunction with simple statistical analysis is explored. The SF spectra show distinct differences during the earlier weeks of the tumor-induction period. Intensity ratio variables are calculated and used in three discriminant analyses. All the discriminant analyses show better classification results with accuracy greater than 80%. From the observed differences in the spectral characteristics and the ratio variables that resulted in better classification between groups, it is concluded that tryptophan, collagen, and NADH are the key fluorophores that undergo changes during tissue transformation process and hence they can be targeted as tumor markers to diagnose normal from abnormal tissues using the SF technique.

  4. Russian Nesting Doll Complexes of Molecular Baskets and Zinc Containing TPA Ligands.

    PubMed

    Zhiquan, Lei; Polen, Shane; Hadad, Christopher M; RajanBabu, T V; Badjić, Jovica D

    2016-07-01

    In this study, we examined the structural and electronic complementarities of convex 1-Zn(II), comprising functionalized tris(2-pyridylmethyl)amine (TPA) ligand, and concave baskets 2 and 3, having glycine and (S)-alanine amino acids at the rim. With the assistance of (1)H NMR spectroscopy and mass spectrometry, we found that basket 2 would entrap 1-Zn(II) in water to give equimolar 1-Zn⊂2in complex (K = (2.0 ± 0.2) × 10(3) M(-1)) resembling Russian nesting dolls. Moreover, C3 symmetric and enantiopure basket 3, containing (S)-alanine groups at the rim, was found to transfer its static chirality to entrapped 1-Zn(II) and, via intermolecular ionic contacts, twist the ligand's pyridine rings into a left-handed (M) propeller (circular dichroism spectroscopy). With molecular baskets embodying the second coordination sphere about metal-containing TPAs, the here described findings should be useful for extending the catalytic function and chiral discrimination capability of TPAs. PMID:27305044

  5. Loss of endogenous Nfatc1 reduces the rate of DMBA/TPA-induced skin tumorigenesis

    PubMed Central

    Goldstein, Jill; Roth, Eve; Roberts, Natalie; Zwick, Rachel; Lin, Samantha; Fletcher, Sean; Tadeu, Ana; Wu, Christine; Beck, Amanda; Zeiss, Caroline; Suárez-Fariñas, Mayte; Horsley, Valerie

    2015-01-01

    Immunosuppressive therapies using calcineurin inhibitors, such as cyclosporine A, are associated with a higher incidence of squamous cell carcinoma formation in mice and humans. Calcineurin is believed to suppress tumorigenesis in part through Nfatc1, a transcription factor expressed primarily in hair follicle bulge stem cells in mice. However, mice overexpressing a constitutively active Nfatc1 isoform in the skin epithelium developed increased spontaneous skin squamous cell carcinomas. Because follicular stem cells can contribute to skin tumorigenesis, whether the endogenous expression of Nfatc1 inhibits or enhances skin tumorigenesis is unclear. Here we show that loss of the endogenous expression of Nfatc1 suppresses the rate of DMBA/TPA-induced skin tumorigenesis. Inducible deletion of Nfatc1 in follicular stem cells before tumor initiation significantly reduces the rate of tumorigenesis and the contribution of follicular stem cells to skin tumors. We find that skin tumors from mice lacking Nfatc1 display reduced Hras codon 61 mutations. Furthermore, Nfatc1 enhances the expression of genes involved in DMBA metabolism and increases DMBA-induced DNA damage in keratinocytes. Together these data implicate Nfatc1 in the regulation of skin stem cell–initiated tumorigenesis via the regulation of DMBA metabolism. PMID:26310443

  6. Cloning and characterization of the goadsporin biosynthetic gene cluster from Streptomyces sp. TP-A0584.

    PubMed

    Onaka, Hiroyasu; Nakaho, Mizuho; Hayashi, Keiko; Igarashi, Yasuhiro; Furumai, Tamotsu

    2005-12-01

    The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584. The cluster contains a structural gene, godA, and nine god (goadsporin) genes involved in post-translational modification, immunity and transcriptional regulation. Although the gene organization is similar to typical bacteriocin biosynthetic gene clusters, each goadsporin biosynthetic gene shows low homology to these genes. Goadsporin biosynthesis is initiated by the translation of godA, and the subsequent cyclization, dehydration and acetylation are probably catalysed by godD, godE, godF, godG and godH gene products. godI shows high similarity to the 54 kDa subunit of the signal recognition particle and plays an important role in goadsporin immunity. Furthermore, four goadsporin analogues were produced by site-directed mutagenesis of godA, suggesting that this biosynthesis machinery is used for the heterocyclization of peptides. PMID:16339937

  7. Agreement among 2 x 2 Agreement Indices.

    ERIC Educational Resources Information Center

    Conger, Anthony J.; Ward, David G.

    1984-01-01

    Sixteen measures of reliability for two-category nominal scales are compared. Upon correcting for chance agreement, there are only five distinct indices: Fleiss's modification of A-sub-1, the phi coefficient, Cohen's kappa, and two intraclass coefficients. Recommendations for choosing an agreement index are made based on definitions, magnitude,…

  8. Design, synthesis, and characterization of TPA-thiophene-based amide or imine functionalized molecule for potential optoelectronic devices

    NASA Astrophysics Data System (ADS)

    Sarswat, Prashant K.; Sathyapalan, Amarchand; Zhu, Yakun; Free, Michael L.

    2013-01-01

    New sets of molecules containing tri-phenyl-amine (TPA) core and thiophene unit with amide and imine functional groups are designed, synthesized, characterized, and compared. These are solution processable small molecules with high mobility. The newly designed molecules have better solubility due to the C=N (imine) and CONH2 (amide) moiety as compared to the established molecules with CH=CH (methine) for optoelectronic applications. They have an optimal energy band gap, which indicates their potential utility in a variety of optoelectronic applications. These molecules also show efficient intermolecular charge transfer mechanisms similar to conventional organic semiconducting molecules as evidenced by optical measurements. Density functional theory simulation results show that the localization of the frontier highest occupied molecular orbital is around the TPA core for molecules coupled with imine and amide, and is reasonably stable.

  9. Effects of Early Post-Ischemic Reperfusion and tPA on Cerebrovascular Function and Nitrosative Stress in Female Rats.

    PubMed

    Ahnstedt, Hilda; Sweet, Julie; Cruden, Patrick; Bishop, Nicole; Cipolla, Marilyn J

    2016-06-01

    Stroke is a major health issue in women. Our previous studies in male rats showed decreased myogenic tone in middle cerebral arteries (MCAs) after ischemia and reperfusion (I/R), while tone in parenchymal arterioles (PAs) was increased. This vascular response may aggravate stroke damage in males by limiting reperfusion; however, the effect in females is not known. The current study investigated the effect of I/R and tissue plasminogen activator (tPA) on myogenic tone and reactivity of MCAs and PAs in female rats. Nitrosative stress by peroxynitrite and recruitment of inflammatory neutrophils to the microvasculature were also studied. Female rats were subjected to 2-h MCA filament occlusion (n = 16) or sham surgery (n = 17) and given tPA (1 mg/kg, i.v) or vehicle followed by 30-min reperfusion. Myogenic tone and reactivity were measured in isolated and pressurized MCAs and PAs from the same animals. Cerebrovascular F-actin, 3-nitrotyrosine (3-NT, peroxynitrite marker), and intravascular neutrophils were quantified. Myogenic tone and constriction to the nitric oxide synthase inhibitor Nω-nitro-L-arginine were decreased in MCAs but unchanged in PAs after I/R with no effect of tPA. F-actin and 3-NT expression were unaffected by I/R or tPA. Our study showed that MCAs from females, similar to what has been seen in males, are dilated after I/R and have decreased myogenic tone while tone in PAs was unchanged. Increased small vessel resistance may contribute to decreased reperfusion and worse outcome after stroke. PMID:27125535

  10. Analyzing milestoning networks for molecular kinetics: Definitions, algorithms, and examples

    NASA Astrophysics Data System (ADS)

    Viswanath, Shruthi; Kreuzer, Steven M.; Cardenas, Alfredo E.; Elber, Ron

    2013-11-01

    Network representations are becoming increasingly popular for analyzing kinetic data from techniques like Milestoning, Markov State Models, and Transition Path Theory. Mapping continuous phase space trajectories into a relatively small number of discrete states helps in visualization of the data and in dissecting complex dynamics to concrete mechanisms. However, not only are molecular networks derived from molecular dynamics simulations growing in number, they are also getting increasingly complex, owing partly to the growth in computer power that allows us to generate longer and better converged trajectories. The increased complexity of the networks makes simple interpretation and qualitative insight of the molecular systems more difficult to achieve. In this paper, we focus on various network representations of kinetic data and algorithms to identify important edges and pathways in these networks. The kinetic data can be local and partial (such as the value of rate coefficients between states) or an exact solution to kinetic equations for the entire system (such as the stationary flux between vertices). In particular, we focus on the Milestoning method that provides fluxes as the main output. We proposed Global Maximum Weight Pathways as a useful tool for analyzing molecular mechanism in Milestoning networks. A closely related definition was made in the context of Transition Path Theory. We consider three algorithms to find Global Maximum Weight Pathways: Recursive Dijkstra's, Edge-Elimination, and Edge-List Bisection. The asymptotic efficiency of the algorithms is analyzed and numerical tests on finite networks show that Edge-List Bisection and Recursive Dijkstra's algorithms are most efficient for sparse and dense networks, respectively. Pathways are illustrated for two examples: helix unfolding and membrane permeation. Finally, we illustrate that networks based on local kinetic information can lead to incorrect interpretation of molecular mechanisms.

  11. Hydrogen milestone could help lower fossil fuel refining costs

    SciTech Connect

    McGraw, Jennifer

    2009-01-01

    Hydrogen researchers at the U.S. Department of Energy's Idaho National Laboratory have reached another milestone on the road to reducing carbon emissions and protecting the nation against the effects of peaking world oil production. Stephen Herring, laboratory fellow and technical director of the INL High Temperature Electrolysis team, today announced that the latest fuel cell modification has set a new mark in endurance. The group's Integrated Laboratory Scale experiment has now operated continuously for 2,583 hours at higher efficiencies than previously attained. Learn more about INL research at http://www.facebook.com/idahonationallaboratory.

  12. Hydrogen milestone could help lower fossil fuel refining costs

    ScienceCinema

    McGraw, Jennifer

    2013-05-28

    Hydrogen researchers at the U.S. Department of Energy's Idaho National Laboratory have reached another milestone on the road to reducing carbon emissions and protecting the nation against the effects of peaking world oil production. Stephen Herring, laboratory fellow and technical director of the INL High Temperature Electrolysis team, today announced that the latest fuel cell modification has set a new mark in endurance. The group's Integrated Laboratory Scale experiment has now operated continuously for 2,583 hours at higher efficiencies than previously attained. Learn more about INL research at http://www.facebook.com/idahonationallaboratory.

  13. Pulsed-high intensity focused ultrasound enhanced tPA mediated thrombolysis in a novel in vivo clot model, a pilot study

    PubMed Central

    Stone, Michael J.; Frenkel, Victor; Dromi, Sergio; Thomas, Peter; Lewis, Ryan P.; Li, King CP; Horne, McDonald; Wood, Bradford J.

    2007-01-01

    Introduction Thrombotic disease continues to account for significant morbidity and mortality. Ultrasound energy has been investigated as a potential primary and adjunctive treatment for thrombotic disease. We have previously shown that pulsed-high intensity focused ultrasound (HIFU) enhances thrombolysis induced by tissue plasminogen activator (tPA) in vitro, including describing the non-destructive mechanism by which tPA availability and consequent activity is increased. In this study we aimed to determined if the same effects could be achieved in vivo. Materials and Methods In this study, pulsed-HIFU exposures combined with tPA boluses was compared to treatment with tPA alone, HIFU alone and control in a novel in vivo clot model. Clots were formed in the rabbit marginal ear vein and verified using venography and infrared imaging. The efficacy of thrombolytic treatment was monitored via high resolution ultrasonography for five hours post treatment. The cross-sectional area of clots at 4 points along the vein was measured and normalized to the pre-treatment size. Results At five hours the complete recanalization of clots treated with pulsed-HIFU and tPA was significantly different from the partial recanalization seen with tPA treatment alone. tPA treatment alone showed a significant decrease in clot versus control, where HIFU was not significantly different than control. Histological analysis of the vessel walls in the treated veins showed no apparent irreversible damage to endothelial cells or extravascular tissue. Conclusions This study demonstrates that tPA mediated thrombolysis can be significantly enhanced when combined with non-invasive pulsed-HIFU exposures. PMID:17481699

  14. PACAP Interacts with PAC1 Receptors to Induce Tissue Plasminogen Activator (tPA) Expression and Activity in Schwann Cell-Like Cultures

    PubMed Central

    Castorina, Alessandro; Waschek, James A.; Marzagalli, Rubina; Cardile, Venera; Drago, Filippo

    2015-01-01

    Regeneration of peripheral nerves depends on the abilities of rejuvenating axons to migrate at the injury site through cellular debris and altered extracellular matrix, and then grow along the residual distal nerve sheath conduit and reinnervate synaptic targets. Considerable evidence suggest that glial cells participate in this process, although the mechanisms remain to be clarified. In cell culture, regenerating neurites secrete PACAP, a peptide shown to induce the expression of the protease tissue plasminogen activator (tPA) in neural cell types. In the present studies, we tested the hypothesis that PACAP can stimulate peripheral glial cells to produce tPA. More specifically, we addressed whether or not PACAP promoted the expression and activity of tPA in the Schwann cell line RT4-D6P2T, which shares biochemical and physical properties with Schwann cells. We found that PACAP dose- and time-dependently stimulated tPA expression both at the mRNA and protein level. Such effect was mimicked by maxadilan, a potent PAC1 receptor agonist, but not by the PACAP-related homolog VIP, suggesting a PAC1-mediated function. These actions appeared to be mediated at least in part by the Akt/CREB signaling cascade because wortmannin, a PI3K inhibitor, prevented peptide-driven CREB phosphorylation and tPA increase. Interestingly, treatment with BDNF mimicked PACAP actions on tPA, but acted through both the Akt and MAPK signaling pathways, while causing a robust increase in PACAP and PAC1 expression. PACAP6-38 totally blocked PACAP-driven tPA expression and in part hampered BDNF-mediated effects. We conclude that PACAP, acting through PAC1 receptors, stimulates tPA expression and activity in a Akt/CREB-dependent manner to promote proteolytic activity in Schwann-cell like cultures. PMID:25658447

  15. RBC-coupled tPA prevents cerebrovasodilatory impairment and tissue injury in pediatric cerebral hypoxia/ischemia through inhibition of ERK MAPK unregulation

    SciTech Connect

    Ganguly, Kumkum; Armstead, William M; Kiessling, J W; Chen, Xiao - Han; Smith, Douglas H; Higazi, Abd Ar; Cines, Douglas B; Bdeir, Khalil; Zaitsev, Sergei; Muzykantov, Vladimir R

    2008-01-01

    Babies experience hypoxia (H) and ischemia (I) from stroke. The only approved treatment for stroke is fibrinolytic therapy with tissue-type plasminogen activator (tPA). However, tPA potentiates H/I-induced impairment of responses to cerebrovasodilators such as hypercapnia and hypotension, and blockade of tPA-mediated vasoactivity prevents this deleterious effect. Coupling tPA to RBCs reduces its CNS toxicity through spatially confining the drug to the vasculature. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, is upregulated after H/I. In this study we determined if RBC-tPA given before or after cerebral H/I would preserve responses to cerebrovasodilators and prevent neuronal injury mediated through the ERK MAPK pathway. Animals given RBC-tPA maintained responses to cerebrovasodilators at levels equivalent to pre-H/I values. CSF and brain parenchymal ERK MAPK was elevated by H/I and this upregulation was potentiated by tPA, but blunted by RBC-tPA. U 0126, an ERK MAPK antagonist, also maintained cerebrovasodilation post H/I. Neuronal degeneration in CA1 hippocampus and parietal cortex after H/I was exacerbated by tPA, but ameliorated by RBC-tPA and U 0126. These data suggest that coupling tPA to RBCs may offer a novel approach towards increasing the benefit/risk ratio of thrombolytic therapy for CNS disorders associated with H/I.

  16. Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells

    PubMed Central

    Lee, Young-Rae; Noh, Eun-Mi; Han, Ji-Hey; Kim, Jeong-Mi; Hwang, Bo-Mi; Kim, Byeong-Soo; Lee, Sung-Ho; Jung, Sung Hoo; Youn, Hyun Jo; Chung, Eun Yong; Kim, Jong-Suk

    2013-01-01

    Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is an isothiocyanate found in some cruciferous vegetables, especially broccoli. Sulforaphane has been shown to display anti-cancer properties against various cancer cell lines. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in cancer cell invasion. In this study, we investigated the effect of sulforaphane on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. TPA-induced MMP-9 expression and cell invasion were decreased by sulforaphane treatment. TPA substantially increased NF-κB and AP-1 DNA binding activity. Pre-treatment with sulforaphane inhibited TPA-stimulated NF-κB binding activity, but not AP-1 binding activity. In addition, we found that sulforaphane suppressed NF-κB activation, by inhibiting phosphorylation of IκB in TPA-treated MCF-7 cells. In this study, we demonstrated that the inhibition of TPA-induced MMP-9 expression and cell invasion by sulforaphane was mediated by the suppression of the NF-κB pathway in MCF-7 cells. [BMB Reports 2013; 46(4): 201-206] PMID:23615261

  17. Ultraviolet stimulated melanogenesis by human melanocytes is augmented by di-acyl glycerol but not TPA

    SciTech Connect

    Friedmann, P.S.; Wren, F.E.; Matthews, J.N. )

    1990-02-01

    Epidermal melanocytes (MC) synthesize melanin in response to ultraviolet radiation (UVR). The mechanisms mediating the UV-induced activation of melanogenesis are unknown but since UVR induces turnover of membrane phospholipids generating prostaglandins (PGs) and other products, it is possible that one of these might provide the activating signal. We have examined the effects of prostaglandins (PGs) E1, E2, D2, F2 alpha, and di-acyl glycerol upon the UV-induced responses of cultured human MC and the Cloudman S91 melanoma cell line. The PGs had little effect on unirradiated cells and did not alter the response to UVR in either human MC or S91 melanoma cells. However, a synthetic analogue of di-acyl glycerol, 1-oleyl 2-acetyl glycerol (OAG), caused a significant (P less than 0.0001), dose-related augmentation of melanin content both in human MC (seven-fold) and S91 cells (three-fold). UVR caused a significant augmentation of the OAG-induced melanogenesis of both human MC and S91 cells. Since OAG is known to activate protein kinase C, it was possible that the observed modulation of the UVR signal could be via that pathway. Di-octanoyl glycerol, another di-acyl glycerol, which activates kinase C, caused a small (70%) increase in melanogenesis in MC which was not altered by UVR. However, 12-0 tetradecanoyl phorbol 13-acetate (TPA), a potent activator of protein kinase C, had no significant effect on either basal or UV-induced melanin synthesis in either cell type. These data suggest that the UV-induced signal activating melanogenesis could be mediated by di-acyl glycerol. Furthermore, they imply that the signal is transduced via an alternative, pathway that might be independent of protein kinase C.

  18. Predicting real-world functional milestones in schizophrenia.

    PubMed

    Olsson, Anna-Karin; Hjärthag, Fredrik; Helldin, Lars

    2016-08-30

    Schizophrenia is a severe disorder that often causes impairments in major areas of functioning, and most patients do not achieve expected real-world functional milestones. The aim of this study was to identify which variables of demography, illness activity, and functional capacity predict patients' ability to attain real-world functional milestones. Participants were 235 outpatients, 149 men and 86 women, diagnosed with schizophrenia spectrum disorder. Our results showed that younger patients managed to achieve a higher level of functioning in educational level, marital status, and social contacts. Patients' functional capacity was primarily associated with educational level and housing situation. We also found that women needed less support regarding housing and obtained a higher level of marital status as compared with men. Our findings demonstrate the importance of considering current symptoms, especially negative symptoms, and remission stability over time, together with age, duration of illness, gender, educational level, and current functional capacity, when predicting patients' future real-world functioning. We also conclude that there is an advantage in exploring symptoms divided into positive, negative, and general domains considering their probable impact on functional achievements. PMID:27235985

  19. Circulating t-PA antigen predicts major adverse coronary events in patients with stable coronary artery disease--a 13-year follow-up.

    PubMed

    Niessner, Alexander; Graf, Senta; Nikfardjam, Mariam; Speidl, Walter S; Huber-Beckmann, Renate; Zorn, Gerlinde; Wojta, Johann; Huber, Kurt

    2003-08-01

    Thrombus formation after rupture of an atherosclerotic plaque plays a crucial role in coronary artery disease (CAD). A decreased endogenous fibrinolytic system and prothrombotic factors are supposed to influence coronary thrombosis. It was our aim to investigate the predictive value of tissue plasminogen activator (t-PA) antigen, von Willebrand Factor, Lipoprotein (a) and anti-cardiolipin antibodies for major adverse coronary events in patients with stable CAD in a prospective cohort study of more than 10 years. We observed 141 patients with angiographically proven CAD for a median follow-up period of 13 years. t-PA antigen was the only marker predicting coronary events (logistic regression, p = 0.044) with a poor prognosis for patients in the 5th quintile with an odds ratio of 7.3 (compared to the 1st quintile). The odds ratio even increased to 10.0 for coronary events associated with the "natural course" of CAD excluding events due to restenosis. t-PA antigen had a slightly higher prognostic power (ROC curve; AUC = 0.69) than fasting glucose (AUC = 0.68) and cholesterol (AUC = 0.67). Triglycerides influenced plasma levels of t-PA antigen (regression, p < 0.001). The predictive value of t-PA antigen remained significant after adjustment for inflammation (logistic regression, p = 0.013) and extent of CAD (p = 0.045) but disappeared adjusting for insulin resistance (p = 0.12). In conclusion t-PA antigen predicted coronary events during a very long-term follow-up with a comparable prognostic power to established cardiovascular risk factors. Markers of insulin resistance influenced t-PA antigen and its predictive value. PMID:12888883

  20. Relationship between exposure to TPA and appearance of transformed cells in MNNG-initiated transformation of BALB/c 3T3 cells.

    PubMed

    Tsuchiya, T; Umeda, M

    1997-10-01

    In the BALB/c-3T3-cell transformation system, the effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) exposure on the appearance of transformed cells was examined in order to investigate the mechanisms of in vitro tumor promotion. Optimal duration of TPA exposure on N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)-initiated cells was at least 11 days. To investigate the effect of transformation frequencies of altering inoculating cell density at the replating of MNNG-exposed cells and of altering the time of starting TPA exposure, MNNG-exposed cells were replated at various inoculum sizes. With lower inoculum sizes (1 x 10(3) to 3 x 10(4) cells/dish), maximum TPA-induced transformation occurred for TPA commencement at confluence, while with higher inoculum size (1 x 10(5) cells/dish), maximum transformation frequency was observed when TPA exposure was started on day 7 after replating, being some 2 days after confluence. This may suggest that there are different mechanisms involved, depending on inoculum size, and that these may involve cell-cell interactions (at lower inoculum) and mutation expression periods (at higher inoculum). By means of redispersion experiments, it was demonstrated that the appearance of transformed cells begins on about day 7 after replating at a cell density of 1 x 10(4) cells/dish. These results suggest the usefulness of the replating method for optimizing transformation in the BALB/c-3T3-cell transformation assay, and provide insight into the time frame of expression of MNNG-initiated transformants and TPA-induced expansion of these transformants. PMID:9335454

  1. Cortical-layer-specific effects of PACAP and tPA on interneuron migration during post-natal development of the cerebellum.

    PubMed

    Raoult, Emilie; Bénard, Magalie; Komuro, Hitoshi; Lebon, Alexis; Vivien, Denis; Fournier, Alain; Vaudry, Hubert; Vaudry, David; Galas, Ludovic

    2014-07-01

    During early post-natal development of the cerebellum, granule neurons (GN) execute a centripetal migration toward the internal granular layer, whereas basket and stellate cells (B/SC) migrate centrifugally to reach their final position in the molecular layer (ML). We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates in vitro the expression and release of the serine protease tissue-type plasminogen activator (tPA) from GN, but the coordinated role of PACAP and tPA during interneuron migration has not yet been investigated. Here, we show that endogenous PACAP is responsible for the transient arrest phase of GN at the level of the Purkinje cell layer (PCL) but has no effect on B/SC. tPA is devoid of direct effect on GN motility in vitro, although it is widely distributed along interneuron migratory routes in the ML, PCL, and internal granular layer. Interestingly, plasminogen activator inhibitor 1 reduces the migration speed of GN in the ML and PCL, and that of B/SC in the ML. Taken together, these results reveal for the first time that tPA facilitates the migration of both GN and fast B/SC at the level of their intersection in the ML through degradation of the extracellular matrix. Crucial role of tissue plasminogen activator (tPA) in interneuron migration. Interneuron migration is a critical step for normal establishment of neuronal network. This study indicates that, in the post-natal cerebellum, tPA facilitates the opposite migration of immature excitatory granule neurons (GN) and immature inhibitory basket/stellate cells (B/SC) along the same migratory route. These data show that tPA exerts a pivotal role in neurodevelopment. PMID:24646324

  2. Historical milestones and future prospects of cluster ion beam technology

    NASA Astrophysics Data System (ADS)

    Yamada, Isao

    2014-08-01

    Development of technology for processing of surfaces by means of gas cluster ion beams began only about a quarter century ago even though fundamental research related to generation of gas clusters began much earlier. Industrial applications of cluster ion beams did not start to be explored until commercial equipment was first introduced to the ion beam community in around 2000. The technology is now evolving rapidly with industrial equipment being engineered for many diverse surface processing applications which are made possible by the unique characteristics of cluster-ion/solid-surface interactions. In this paper, important historical milestones in cluster ion beam development are described. Present activities related to a wide range of industrial applications in semiconductors, magnetic and optical devices, and bio-medical devices are reviewed. Several emerging new advances in cluster beam applications for the future are also discussed.

  3. Advanced Initiation Systems Manufacturing Level 2 Milestone Completion Summary

    SciTech Connect

    Chow, R; Schmidt, M

    2009-10-01

    Milestone Description - Advanced Initiation Systems Detonator Design and Prototype. Milestone Grading Criteria - Design new generation chip slapper detonator and manufacture a prototype using advanced manufacturing processes, such as all-dry chip metallization and solvent-less flyer coatings. The advanced processes have been developed for manufacturing detonators with high material compatibility and reliability to support future LEPs, e.g. the B61, and new weapons systems. Perform velocimetry measurements to determine slapper velocity as a function of flight distance. A prototype detonator assembly and stripline was designed for low-energy chip slappers. Pictures of the prototype detonator and stripline are shown. All-dry manufacturing processes were used to address compatibility issues. KCP metallized the chips in a physical vapor deposition system through precision-aligned shadow masks. LLNL deposited a solvent-less polyimide flyer with a processes called SLIP, which stands for solvent-less vapor deposition followed by in-situ polymerization. LANL manufactured the high-surface-area (HSA) high explosive (HE) pellets. Test fires of two chip slapper designs, radius and bowtie, were performed at LLNL in the High Explosives Application Facility (HEAF). Test fires with HE were conducted to establish the threshold firing voltages. pictures of the chip slappers before and after test fires are shown. Velocimetry tests were then performed to obtain slapper velocities at or above the threshold firing voltages. Figure 5 shows the slapper velocity as a function of distance and time at the threshold voltage, for both radius and bowtie bridge designs. Both designs were successful at initiating the HE at low energy levels. Summary of Accomplishments are: (1) All-dry process for chip manufacture developed; (2) Solventless process for slapper materials developed; (3) High-surface area explosive pellets developed; (4) High performance chip slappers developed; (5) Low-energy chip

  4. Treatment of a Class II Division 2 Patient with Severe Skeletal Discrepancy by Using a Custom Made TPA Proclination Spring

    PubMed Central

    Paduano, Sergio; Spagnuolo, Gianrico; Biase, Giuseppe di; Cioffi, Iacopo

    2013-01-01

    This case report describes the orthodontic treatment of a boy, aged 15.3 years, with permanent dentition, mesofacial typology, affected with a severe sagittal skeletal Class II division 2 malocclusion, due to a mandibular retrusion. His chief compliant was the position of the maxillary incisors, displaced too palatally, and an impaired facial profile. Herbst and multi-bracket straightwire fixed appliances, together with a custom made modified transpalatal arch (i.e. TPA proclination spring), were used to correct the sagittal discrepancy and to improve the attractiveness of the impaired facial profile. PMID:24155800

  5. Quantum molecular dynamics simulations of the thermophysical properties of shocked liquid ammonia for pressures up to 1.3 TPa.

    PubMed

    Li, Dafang; Zhang, Ping; Yan, Jun

    2013-10-01

    We investigate via quantum molecular-dynamics simulations the thermophysical properties of shocked liquid ammonia up to the pressure 1.3 TPa and temperature 120,000 K. The principal Hugoniot is predicted from the wide-range equation of state, which agrees well with the available experimental measurements up to 64 GPa. Our systematic study of the structural properties demonstrates that the liquid ammonia undergoes a gradual phase transition along the Hugoniot. At about 4800 K, the system transforms into a metallic, complex mixture state consisting of NH3, N2, H2, N, and H. Furthermore, we discuss the implications for the interiors of Uranus and Neptune. PMID:24116573

  6. Certification of Completion of Item 2 of ASC FY07 Level-2 Milestone ID #2380

    SciTech Connect

    Lipari, D A

    2007-03-28

    This report documents the completion of Item 2 of the three milestone deliverables that comprise Milestone ID 2380: Deploy selected Tri-Lab resource manager at LLNL and develop support model. Specifically: LLNL will integrate and support a commercial resource manager software product at LLNL to be used across the tri-lab HPC facilities.

  7. Specialty milestones and the next accreditation system: an opportunity for the simulation community.

    PubMed

    Beeson, Michael S; Vozenilek, John A

    2014-06-01

    The Accreditation for Graduate Medical Education has developed a new process of accreditation, the Next Accreditation System (NAS), which focuses on outcomes. A key component of the NAS is specialty milestones-specific behavior, attributes, or outcomes within the general competency domains. Milestones will mark a level of proficiency of a resident within a competency domain. Each specialty has developed its own set of milestones, with semiannual reporting to begin July 2013, for 7 specialties, and the rest in July 2014.Milestone assessment must be based on objective data. Each specialty will determine optimal methods of measuring milestones, based on ease, cost, validity, and reliability. The simulation community has focused many graduate medical education efforts at training and formative assessment. Milestone assessment represents an opportunity for simulation modalities to offer summative assessment of milestone proficiencies, adding to the potential methods that residency programs will likely use or adapt. This article discusses the NAS, milestone assessment, and the opportunity to the simulation community to become involved in this next stage of graduate medical education assessment. PMID:24614793

  8. Mining agreements III

    SciTech Connect

    Not Available

    1991-01-01

    This book cover the following: Forms of mining agreements; Preliminary letter agreements; Acquisition of mineral interests involving securities; Partnership tax treatment in mining agreements; Non-tax consequences of partnerships under state law; Protection against joint venturers' liabilities; Joint venture decision making; Mining royalties; Commingling and unitization provisions; Indemnification and insurance provisions; Area of interest provision; Dispute resolution; and Non-participation and default provisions.

  9. Misinterpretations in agreement and agreement attraction.

    PubMed

    Patson, Nikole D; Husband, E Matthew

    2016-05-01

    It has been well established that subject-verb number agreement can be disrupted by local noun phrases that differ in number from the subject head noun phrase. In sentence production, mismatches in the grammatical number of the head and local noun phrases lead to agreement errors on the verb as in: the key to the cabinets are. Similarly, although ungrammaticality typically causes disruption in measures of sentence comprehension, the disruption is reduced when the local noun phrase has a plural feature. Using a forced-choice comprehension question method, we report two experiments that provide evidence that comprehenders were likely to misinterpret the number information on the head noun phrase when morphosyntactic number markings on the local noun phrase and verb did not match the head. These results are consistent with a growing body of research that suggests that comprehenders often arrive at a final interpretation of a sentence that is not faithful to the linguistic input. PMID:25624171

  10. The role of PKC/ERK1/2 signaling in the anti-inflammatory effect of tetracyclic triterpene euphol on TPA-induced skin inflammation in mice.

    PubMed

    Passos, Giselle F; Medeiros, Rodrigo; Marcon, Rodrigo; Nascimento, Andrey F Z; Calixto, João B; Pianowski, Luiz F

    2013-01-01

    Inflammation underlies the development and progression of a number of skin disorders including psoriasis, atopic dermatitis and cancer. Therefore, novel antiinflammatory agents are of great clinical interest for prevention and treatment of these conditions. Herein, we demonstrated the underlying molecular mechanisms of the antiinflammatory activity of euphol, a tetracyclic triterpene isolated from the sap of Euphorbia tirucalli, in skin inflammation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in mice. Topical application of euphol (100 μg/ear) significantly inhibited TPA-induced ear edema and leukocyte influx through the reduction of keratinocyte-derived chemokine (CXCL1/KC) and macrophage inflammatory protein (MIP)-2 levels. At the intracellular level, euphol reduced TPA-induced extracellular signal-regulated protein kinase (ERK) activation and cyclooxygenase-2 (COX-2) upregulation. These effects were associated with euphol's ability to prevent TPA-induced protein kinase C (PKC) activation, namely PKCα and PKCδ isozymes. Our data indicate that topical application of euphol markedly inhibits the inflammatory response induced by TPA. Thus, euphol represents a promising agent for the management of skin diseases with an inflammatory component. PMID:23099255

  11. Milestones in Medical Research, The Human Genome and ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... turn Javascript on. Milestones in Medical Research, The Human Genome and ClinicalTrials.gov Past Issues / Fall 2010 ... milestone in understanding the genetic foundation of all human beings; the second, a comprehensive information service to ...

  12. Systemic Inflammatory Response Syndrome in tPA Treated Patients Is Associated with Worse Short-term Functional Outcome

    PubMed Central

    Boehme, Amelia K.; Kapoor, Niren; Albright, Karen C.; Lyerly, Michael J.; Rawal, Pawan V.; Shahripour, Reza Bavarsad; Alvi, Muhammad; Houston, J. Thomas; Sisson, April; Beasley, T. Mark; Alexandrov, Anne W.; Alexandrov, Andrei V.; Miller, David W.

    2013-01-01

    Background and Purpose Systemic Inflammatory Response (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine if differences exist in outcomes in SIRS and non-SIRS IV tPA treated patients. Methods Consecutive patients were retrospectively reviewed for evidence of SIRS during their admission. SIRS was defined as the presence of two or more: body temperature <36° C or >38° C, HR >90, respiratory rate >20 and WBC <4,000/mm or >12,000mm or >10% bands. Patients diagnosed with infection (via positive culture) were excluded. Results Out of 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre-tPA NIHSS, age, and race, SIRS remained a predictor of poor functional outcome at discharge (OR= 2.58, 95% CI, 1.16 – 5.73, p=0.0197). Conclusion In our sample of tPA treated patients, almost 1 out of 5 patients developed SIRS. Further, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay. PMID:23704110

  13. Protective Effect of Fermented Soybean Dried Extracts against TPA-Induced Oxidative Stress in Hairless Mice Skin

    PubMed Central

    Georgetti, Sandra R.; Casagrande, Rúbia; Vicentini, Fabiana T. M. C.; Baracat, Marcela M.; Verri, Waldiceu A.; Fonseca, Maria J. V.

    2013-01-01

    This study evaluated the chemical properties (polyphenol and genistein contents) of soybean extracts obtained by biotransformation and dried by spray dryer at different conditions and their in vivo ability to inhibit 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced biochemical alterations in the skin of hairless mice. By comparing the obtained data with that of the well-known active soybean extract Isoflavin beta, we evaluated the influence of the fermentation and drying process in the extracts efficacy. The results demonstrated that inlet gas temperature and adjuvant concentration for the extract drying process have significantly affected the total polyphenol contents and, to a minor degree, the genistein contents. However, the effect of topical stimulus with TPA, an oxidative stress inducer, which caused significant depletion of reduced glutathione (GSH) and catalase, with increased levels of H2O2 and lipid peroxidation (MDA) in the skin of hairless mice, was significantly prevented by the soybean extracts treatment. These results indicate that the spray drying processing resulted in a product capable of limiting the oxidative stress with possible therapeutic applicability as an antioxidant in pharmaceutical forms. PMID:24073399

  14. Evaluation of adult dTPaP vaccination coverage in France: experience in Lyon city, 2010–2011

    PubMed Central

    2012-01-01

    Background Compliance with official recommendations can be assessed by evaluating vaccination coverage (VC) in populations. The main objective of our study was to assess VC of adults against diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) according to age. The second objective was to explore if vaccination status could be confirmed by documentation. Methods A cross-sectional study was conducted in 680 adults consulting for biological examination in private laboratories in Lyon (France) to evaluate VC for diphtheria, tetanus, poliomyelitis and pertussis (dTPaP) and enabled reported vaccinations to be compared with documented, confirmed vaccinations. Results Verification of documented, confirmed vaccinations disclosed VC of 78.7% for tetanus, 63.6% for poliomyelitis, 57.8% for diphtheria and 10.7% for pertussis. Comparison of confirmed and self-reported vaccinations revealed that a large percentage of people who thought that they were vaccinated were not. VC significantly decreased with age for diphtheria and poliomyelitis and did not vary by gender. The VC rate for pertussis has increased since the 2008 recommendations were made. Conclusions The main thrust of this study was to compare reported and confirmed data. A significant percentage of people wrongly believed that they were up to date with their vaccination. PMID:23114050

  15. A family of uranyl-aromatic dicarboxylate (pht-, ipa-, tpa-) framework hybrid materials: photoluminescence, surface photovoltage and dye adsorption.

    PubMed

    Gao, Xue; Wang, Che; Shi, Zhong-Feng; Song, Jian; Bai, Feng-Ying; Wang, Ji-Xiao; Xing, Yong-Heng

    2015-07-01

    Four uranyl complexes [(UO2)(pht)H2O]·H2O (pht = phthalic acid) (1), (UO2)2(Hipa)4(H2O)2 (Hipa = isophthalic acid) (2), (UO2)(tpa)(DMF)2 (tpa = terephthalic acid) (3) and (UO2)(box)2 (box = benzoic acid) (4) were synthesized by the reaction of UO2(CH3COO)2·2H2O as the metal source and phthalic acid, isophthalic acid, terephthalic acid or benzoic acid as the ligand. They were characterized by elemental analyses, IR, UV-Vis, XRD, single crystal X-ray diffraction analysis and thermal gravimetric analysis. The structural analysis reveals that complex 1 exhibits a one-dimensional chain structure constructed by the building unit [(UO2)2(pht)4(H2O)2] and further extends the chain into a 2D supramolecular architecture by hydrogen bonding interactions. Complex 2 is a discrete [(UO2)2(Hipa)4(H2O)2] structure, and by the hydrogen bonding interaction, forms a 3D supramolecular structure. In complexes 3 and 4, adjacent uranyl polyhedra form a 1D chain through bridging terephthalic acid and benzoic acid, respectively. In order to extend their functional properties, their photoluminescence, surface photovoltage and dye adsorption properties have been studied. PMID:26038888

  16. Inhibition of glutamine-dependent autophagy increases t-PA production in CHO cell fed-batch processes.

    PubMed

    Jardon, Mario A; Sattha, Beheroze; Braasch, Katrin; Leung, Amy O; Côté, Hélène C F; Butler, Michael; Gorski, Sharon M; Piret, James M

    2012-05-01

    Understanding the cellular responses caused by metabolic stress is crucial for the design of robust fed-batch bioprocesses that maximize the expression of recombinant proteins. Chinese hamster ovary cells were investigated in chemically defined, serum-free cultures yielding 10(7) cells/mL and up to 500 mg/L recombinant tissue-plasminogen activator (t-PA). Upon glutamine depletion increased autophagosome formation and autophagic flux were observed, along with decreased proliferation and high viability. Higher lysosomal levels correlated with decreased productivity. Chemical inhibition of autophagy with 3-methyl adenine (3-MA) increased the t-PA yield by 2.8-fold. Autophagy-related MAP1LC3 and LAMP2 mRNA levels increased continuously in all cultures. Analysis of protein quality revealed that 3-MA treatment did not alter glycan antennarity while increasing fucosylation, galactosylation, and sialylation. Taken together, these findings indicate that inhibition of autophagy can considerably increase the yield of biotechnology fed-batch processes, without compromising the glycosylation capacity of cells. Monitoring or genetic engineering of autophagy provides novel avenues to improve the performance of cell culture-based recombinant protein production. PMID:22125188

  17. Non-Proliferation Agreements.

    ERIC Educational Resources Information Center

    Swalec, John J.

    1981-01-01

    Discusses five kinds of cooperative agreements established by the College of Lake County (IL): those with other community colleges/technical institutes; the military; business, industry, and organizations; secondary schools; and community and special interest groups. Pays particular attention to two kinds of agreements with other colleges. (CAM)

  18. Cooperative Agreements Study Report.

    ERIC Educational Resources Information Center

    Lawton, R. E.; Magruder, D.

    During the 1983 meeting of the Florida Legislature, action was taken to begin a systematic study of the level of cooperation between the Florida public schools K-12 program and the community and junior colleges. The goals and objectives of the Cooperative Agreements Study were to review and compile a list of the cooperative agreements and identify…

  19. Comparison of altered expression of histocompatibility antigens with altered immune function in murine spleen cells treated with ultraviolet radiation and/or TPA

    SciTech Connect

    Pretell, J.O.; Cone, R.E.

    1985-02-01

    Previous studies in our laboratory demonstrated that several treatments that inhibited the ability of cells to stimulate the mixed lymphocyte reaction (MLR) also blocked the shedding of histocompatibility antigens and Ia antigens from murine spleen cells. In the present studies, one of these treatments, ultraviolet radiation (UV), was shown to cause an initial loss in the density of H-2K, IA, and IE antigens prior to the block in shedding observed after culture of these cells. Further analysis revealed that the UV-induced loss of antigens could be prevented by the presence of colchicine during irradiation. Biosynthetic analyses revealed the IA antigen synthesis was also inhibited in the UV-irradiated cells. Examination of the effects of a second agent, 12-0-tetradecanoylphorbol-13-acetate (TPA) on the turnover of histocompatibility antigens revealed that the biosynthesis and shedding of these antigens were accelerated by this agent. However, addition of TPA to UV-irradiated cells did not result in a reversal of the UV-induced block in biosynthesis of IA antigens. Results of immune function assays correlated with the biochemical studies: UV-irradiation inhibited the generation of the MLR, but TPA enhanced this reaction, and addition of TPA to mixed lymphocyte cultures with UV-irradiated stimulators did not reverse the UV-induced inhibition. These results suggest that, although the turnover of histocompatibility antigens may be affected by TPA and UV in an antagonistic fashion, additional factors other than the expression of histocompatibility antigens are operating in the inhibition of stimulation of an MLR by UV radiation or its enhancement by TPA.

  20. The inhibitory effects of boldine, glaucine, and probucol on TPA-induced down regulation of gap junction function. Relationships to intracellular peroxides, protein kinase C translocation, and connexin 43 phosphorylation.

    PubMed

    Hu, J; Speisky, H; Cotgreave, I A

    1995-11-01

    The naturally occurring antioxidant boldine and its di-methoxy analogue glucine, as well as the drug antioxidant probucol, all inhibit TPA-induced downregulation of gap junctional intercellular communication in WB-F344 rat liver epithelial cells in dose-dependent manners. The compounds were essentially 100% inhibitory to the effect of TPA (10 nM) at 50 microM each. Analysis of the mechanism of the antitumor promotive action of these agents in vitro revealed that boldine and probucol (both at 10 microM) totally inhibited the TPA-induced accumulation of intracellular oxidants. Additionally, boldine, glaucine, and probucol, each at 50 microM, inhibited TPA-induced translocation of protein kinase C (PKC) to the particulate fraction of the cells, with concomitant inhibition of TPA-induced hyperphosphorylation of gap junctional connexin 43 (cx43) and TPA-induced internalisation of cx43 protein from the plasma membrane of the cells. None of the compounds inhibited the binding of (3H)-PDBu to TPA-specific binding sites in the cells. The results indicate that antioxidant molecules, irrespective of structure, possess common antitumor promotive potential in this model of gap junctional intercellular communication. The data also indicate that the compounds may interfere with the promotive function of TPA, at least in part, by the destruction of oxidants within the cells. Xanthine oxidase was excluded as a major source of such intracellular oxidants because allopurinol (50 microM) did not significantly affect either the accumulation of oxidants in the cells or the downregulation of gap junctional communication in response to TPA. Taken together, these data also suggest that TPA-induced oxidants play a role in the translocation of PKC to cellular membranes and it is at this level where the antioxidants may interfere in TPA-induced downregulation of gap junctional function. PMID:7503766

  1. Geo-Informatics in India: Major Milestones and Present Scenario

    NASA Astrophysics Data System (ADS)

    Gupta, S.; Karnatak, H.; Raju, P. L. N.

    2016-06-01

    Geo-informatics has emerged globally as a useful tool to address spatial problems with significant societal implications that require integrative and innovative approaches for analysis, modelling, managing, and archiving of extensive and diverse data sets. Breakneck technological development and availability of satellite based data and information services in public domain along with real time geo-data n through participatory approaches, in the two last decades have led to a sea-change in our know-how of our natural resources and their effective management at various levels. It has led to a realization that every phenomena and requirement in our day to day life has some spatial, or geographic component that can be predicted and governed more effectively through geoinformatics tool. India also has come a long way in effective utilization of geoinformatics for various applications. This quantum leap owes its foundation in a humble beginning about half century back and almost parallel developments in the country's space programme to a current level where it touches almost all areas of life and living. Though geoinformatics technology (GIT) is believed to reach satisfactory level in the country, Indian geospatial community faces critical challenges with respect to research, education and training along with enhanced the access to the stakeholders and mobilization of the workforce, that are crucial in further penetration of this technology in context to India's development. In this paper we have critically reviewed milestones of GI development and its current utilization status in Indian context.

  2. A [4+2] mixed ligand approach to ruthenium DNA metallointercalators [Ru(tpa)(N-N)](PF(6))(2) using a tris(2-pyridylmethyl)amine (tpa) capping ligand.

    PubMed

    Kraft, Sabine Seeberg née; Bischof, Caroline; Loos, Annette; Braun, Sebastian; Jafarova, Nigar; Schatzschneider, Ulrich

    2009-08-01

    A series of five tris(2-pyridylmethyl)amine (tpa) ruthenium complexes [Ru(tpa)(N-N)](PF(6))(2) with N-N=bpy (2,2'-bipyridine), phen (1,10-phenanthroline), dpq (dipyrido[3,2-d:2',3'-f]quinoxaline), dppz (dipyrido[3,2-a;2',3'-c]phenazine), and dppn (4,5,9,16-tetraazadibenzo[a,c]naphthacene) was prepared and characterized by NMR, UV-Visible (UV/Vis), and fluorescence spectroscopy as well as cyclic voltammetry. Structures optimized with density functional theory methods (DFT, BP86, TZVP) without constraints show C(1) symmetry while in solution, the (1)H and (13)C NMR spectra are in accordance with an average C(s) symmetry. This is thought to be due to a low energy barrier for flipping of the equatorial pyridine ring from one side of the N-N plane to the other. The electronic structure of the compounds was studied with DFT and a change in the highest occupied molecular orbital (HOMO) character from Ru t(2g) for the bpy, phen, and dpq to N-N ligand-based for the dppz and dppn complexes was found. TDDFT calculations showed dominant N-N-based intra-ligand charge transfer (ILCT) transitions in the latter two complexes mixed with metal-to-ligand charge transfer (MLCT) bands found for all five compounds. DNA binding of the complexes was studied with UV/Vis titrations, the fluorescent ethidium bromide displacement assay, and CD spectroscopy. The affinity increases with the aromatic surface area of of the bidentate N-N ligand in the order bpy

  3. Transuranic Waste Program Framework Agreement - December Deliverable July 2012

    SciTech Connect

    Jones, Patricia

    2012-07-19

    Framework agreement deliverables are: (1) 'DOE/NNSA commits to complete removal of all non-cemented above-ground EM Legacy TRU and newly generated TRU currently-stored at Area G as of October 1, 2011, by no later than June 30, 2014. This inventory of above-ground TRU is defined as 3706 cubic meters of material.' (2) 'DOE commits to the complete removal of all newly generated TRU received in Area G during FY 2012 and 2013 by no later than December 31, 2014.' (3) 'Based on projected funding profiles, DOE/NNSA will develop by December 31, 2012, a schedule, including pacing milestones, for disposition of the below-ground TRU requiring retrieval at Area G.' Objectives are to: (1) restore the 'Core Team' to develop the December, 2012 deliverable; (2) obtain agreement on the strategy for below ground water disposition; and (3) establish timeline for completion of the deliverable. Below Grade Waste Strategy is to: (1) Perform an evaluation on below grade waste currently considered retrievable TRU; (2) Only commit to retrieve waste that must be retrieved; (3) Develop the Deliverable including Pacing Milestones based on planned commitments; (4) Align all Regulatory Documents for Consistency; and (5) answer these 3 primary questions, is the waste TRU; is the waste retrievable, can retrieval cause more harm than benefit?

  4. A TPA-caged precursor of (imino)coumarin for "turn-on" fluorogenic detection of Cu(.).

    PubMed

    Hu, Zhangjun; Hu, Jiwen; Wang, Hui; Zhang, Qiong; Zhao, Meng; Brommesson, Caroline; Tian, Yupeng; Gao, Hongwen; Zhang, Xuanjun; Uvdal, Kajsa

    2016-08-24

    We strategize to utilize the precursors of (imino)coumarin fluorophores to deliver novel reactive Cu(+) probes, where tris[(2-pyridyl)-methyl] amine (TPA) works as a reactive receptor towards Cu(+). To verify this strategy, CP1, a representative probe and relevant sensing behaviors towards Cu(+) are presented here. CP1 features good solubility and fast response for monitoring labile copper in aqueous solution and live cells. The sensing mechanism of CP1 is determined by HPLC titration and mass spectrometric analysis. The probe CP1 exhibits a 60-fold fluorescence enhancement and a detection limitation of 10.8 nM upon the detection of Cu(+). CP1 is further applied for imaging labile copper in live cells. This work provides a starting point for future development of Cu(+) probes, based on in situ formation of (imino)coumarin scaffolds, as well as their further investigations of copper signaling and biological events. PMID:27497012

  5. Milestone Age Affects the Role of Health and Emotions in Life Satisfaction: A Preliminary Inquiry

    PubMed Central

    Miron-Shatz, Talya; Bhargave, Rajesh; Doniger, Glen M.

    2015-01-01

    Jill turns 40. Should this change how she evaluates her life, and would a similar change occur when she turns 41? Milestone age (e.g., 30, 40, 50)—a naturally occurring feature in personal timelines—has received much attention is popular culture, but little attention in academic inquiry. This study examines whether milestone birthdays change the way people evaluate their life. We show that life outlook is impacted by this temporal landmark, which appears to punctuate people’s mental maps of their life cycle. At these milestone junctures, people take stock of where they stand and have a more evaluative perspective towards their lives when making life satisfaction judgments. Correspondingly, they place less emphasis on daily emotional experiences. We find that milestone agers (vs. other individuals) place greater weight on health satisfaction and BMI and lesser weight on daily positive emotions in their overall life satisfaction judgments, whereas negative emotions remain influential. PMID:26244348

  6. Academic affairs and global health: how global health electives can accelerate progress towards ACGME milestones.

    PubMed

    Hayward, Alison Schroth; Jacquet, Gabrielle A; Sanson, Tracy; Mowafi, Hani; Hansoti, Bhakti

    2015-12-01

    Global health electives (GHEs) have become a standard offering in many residency programs. Residency electives should aid residents in achieving outcomes in the Accreditation Council for Graduate Medical Education (ACGME) competency domains. In this paper, the authors review existing literature and provide expert opinion to highlight how global health electives can complement traditional training programs to assist residents in achieving ACGME milestones, using emergency medicine residency as an example. Recommendations are provided for identifying exemplary global health electives and for the development of institutional global health elective curricula in order to facilitate milestone achievement. Global health electives can advance progress towards ACGME milestones; however, they may vary greatly in terms of potential for learner advancement. Electives should thus be rigorously vetted to ensure they meet standards that will facilitate this process. Given that milestones are a newly introduced tool for assessing resident educational achievement, very little research is available currently to directly determine impacts, and further study will be needed. PMID:26628320

  7. Milestone Age Affects the Role of Health and Emotions in Life Satisfaction: A Preliminary Inquiry.

    PubMed

    Miron-Shatz, Talya; Bhargave, Rajesh; Doniger, Glen M

    2015-01-01

    Jill turns 40. Should this change how she evaluates her life, and would a similar change occur when she turns 41? Milestone age (e.g., 30, 40, 50)--a naturally occurring feature in personal timelines--has received much attention is popular culture, but little attention in academic inquiry. This study examines whether milestone birthdays change the way people evaluate their life. We show that life outlook is impacted by this temporal landmark, which appears to punctuate people's mental maps of their life cycle. At these milestone junctures, people take stock of where they stand and have a more evaluative perspective towards their lives when making life satisfaction judgments. Correspondingly, they place less emphasis on daily emotional experiences. We find that milestone agers (vs. other individuals) place greater weight on health satisfaction and BMI and lesser weight on daily positive emotions in their overall life satisfaction judgments, whereas negative emotions remain influential. PMID:26244348

  8. Outcomes of Patients Requiring Blood Pressure Control Before Thrombolysis with tPA for Acute Ischemic Stroke

    PubMed Central

    Darger, Bryan; Gonzales, Nicole; Banuelos, Rosa C.; Peng, Hui; Radecki, Ryan P.; Doshi, Pratik B.

    2015-01-01

    Introduction The purpose of this study was to assess safety and efficacy of thrombolysis in the setting of aggressive blood pressure (BP) control as it compares to standard BP control or no BP control prior to thrombolysis. Methods We performed a retrospective review of patients treated with tissue plasminogen activator (tPA) for acute ischemic stroke (AIS) between 2004–2011. We compared the outcomes of patients treated with tPA for AIS who required aggressive BP control prior to thrombolysis to those requiring standard or no BP control prior to thrombolysis. The primary outcome of interest was safety, defined by all grades of hemorrhagic transformation and neurologic deterioration. The secondary outcome was efficacy, determined by functional status at discharge, and in-hospital deaths. Results Of 427 patients included in the analysis, 89 received aggressive BP control prior to thrombolysis, 65 received standard BP control, and 273 required no BP control prior to thrombolysis. Patients requiring BP control had more severe strokes, with median arrival National Institutes of Health Stroke Scale of 10 (IQR [6–17]) in patients not requiring BP control versus 11 (IQR [5–16]) and 13 (IQR [7–20]) in patients requiring standard and aggressive BP lowering therapies, respectively (p=0.048). In a multiple logistic regression model adjusting for baseline differences, there were no statistically significant differences in adverse events between the three groups (P>0.10). Conclusion We observed no association between BP control and adverse outcomes in ischemic stroke patients undergoing thrombolysis. However, additional study is necessary to confirm or refute the safety of aggressive BP control prior to thrombolysis. PMID:26759644

  9. The Pediatrics Milestones: Conceptual Framework, Guiding Principles, and Approach to Development

    PubMed Central

    Hicks, Patricia J.; Schumacher, Daniel J.; Benson, Bradley J.; Burke, Ann E.; Englander, Robert; Guralnick, Susan; Ludwig, Stephen; Carraccio, Carol

    2010-01-01

    Background The Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Pediatrics (ABP) have partnered to initiate the Pediatrics Milestone Project to further refine the 6 ACGME competencies and to set performance standards as part of the continued commitment to document outcomes of training and program effectiveness. Intervention Members of the Pediatrics Milestone Project Working Group searched the medical literature and beyond to create a synopsis of models and evidence for a developmental ontogeny of the elements for 52 subcompetencies. For each subcompetency, we created a series of Milestones, grounded in the literature. The milestones were vetted with the entire working group, engaging in an iterative process of revisions until reaching consensus that their narrative descriptions (1) included all critical elements, (2) were behaviorally based, (3) were properly sequenced, and (4) represented the educational continuum of training and practice. Outcomes We have completed the first iteration of milestones for all subcompetencies. For each milestone, a synopsis of relevant literature provides background, references, and a conceptual framework. These milestones provide narrative descriptions of behaviors that represent the ontogeny of knowledge, skill, and attitude development across the educational continuum of training and practice. Discussion The pediatrics milestones take us a step closer to meaningful outcome assessment. Next steps include undertaking rigorous study, making appropriate modifications, and setting performance standards. Our aim is to assist program directors in making more reliable and valid judgments as to whether a resident is a “good doctor” and to provide outcome evidence regarding the program's success in developing doctors. PMID:21976091

  10. MILESTONES AND FUTURE DIRECTIONS IN THE SOLVENT EXTRACTION OF CAESIUM

    SciTech Connect

    Moyer, Bruce A

    2011-01-01

    The remarkable development of solvent-extraction (SX) chemistry for caesium separation over the past half a century as driven by the needs of the nuclear industry now constitutes an instructive case study in exploring the limits of selectivity and cycle efficiency in SX. In this review, key milestones in the pursuit of both fundamentals and applications of caesium extraction will be highlighted along with a look at future prospects. The high-yield fission-product 137Cs constitutes a major fraction of the radioactivity in nuclear wastes, and in view of its heat production, environmental mobility, radiation hazard, and even uses as a radiation source, methods have long been sought for its separation. Toward this end, the evolving science has been challenged by daunting requirements for decontamination in the presence of high concentrations of competing cations, and demands for small footprint, modular design, and high throughput place a premium on selectivity and efficiency. Fortunately, the science has also benefited from the peculiar economics of nuclear separations, which have afforded the development of wonderfully sophisticated reagents. With its location in the lower left side of the periodic table, the Cs+ cation has the distinction of having the lowest charge density of any metal cation except short-lived francium. For practical purposes, Cs+ is thus the least hydrated and, in principle, the most directly extractable metal cation. Technologies employing liquid-liquid cation exchange with very large, durable anions like those from the dicarbollide family have therefore been quite effective based solely on solvation principles. Alternatively, researchers have turned to macrocyclic coordinating extractants, such as calix-crown ethers, following principles of molecular recognition, with dramatic results. Overall, strides continue along these lines, though it is apparent that caesium SX has reached a state of excellent fundamental understanding and technical

  11. ALMA Achieves Major Milestone With Antenna-Link Success

    NASA Astrophysics Data System (ADS)

    2007-03-01

    The Atacama Large Millimeter/submillimeter Array (ALMA), an international telescope project, reached a major milestone on March 2, when two ALMA prototype antennas were first linked together as an integrated system to observe an astronomical object. The milestone achievement, technically termed "First Fringes," came at the ALMA Test Facility (ATF) on the grounds of the National Radio Astronomy Observatory's (NRAO) Very Large Array (VLA) radio telescope in New Mexico. NRAO is a facility of the National Science Foundation (NSF), managed by Associated Universities, Incorporated (AUI). AUI also is designated by NSF as the North American Executive for ALMA. ALMA Test Facility ALMA Test Facility, New Mexico: VertexRSI antenna, left; AEC antenna, right. CREDIT: Drew Medlin, NRAO/AUI/NSF Click on image for page of graphics and full information Faint radio waves emitted by the planet Saturn were collected by the two ALMA antennas, then processed by new, state-of-the-art electronics to turn the two antennas into a single, high-resolution telescope system, called an interferometer. Such pairs of antennas are the basic building blocks of multi-antenna imaging systems such as ALMA and the VLA. In such a system, each antenna is combined electronically with every other antenna to form a multitude of pairs. Each pair contributes unique information that is used to build a highly-detailed image of the astronomical object under observation. When completed in 2012, ALMA will have 66 antennas. The successful Saturn observation began at 7:13 p.m., U.S. Mountain Time Friday (0213 UTC Saturday). The planet's radio emissions at a frequency of 104 GigaHertz (GHz) were tracked by the ALMA system for more than an hour. "Our congratulations go to the dedicated team of scientists, engineers and technicians who produced this groundbreaking achievement for ALMA. Much hard work and many long hours went into this effort, and we appreciate it all. This team should be very proud today," said NRAO

  12. Politics of Policy: Assessing the Implementation, Impact, and Evolution of the Performance Assessment for California Teachers (PACT) and edTPA

    ERIC Educational Resources Information Center

    Reagan, Emilie Mitescu; Schram, Thomas; McCurdy, Kathryn; Chang, Te-Hsin; Evans, Carla M.

    2016-01-01

    Summative performance assessments in teacher education, such as the Performance Assessment for California Teachers (PACT) and the edTPA, have been heralded through polices intended to enhance the quality of the teaching profession and raise its stature among other professions. However, the development and implementation of the PACT, and…

  13. Hispolon inhibits TPA-induced invasion by reducing MMP-9 expression through the NF-κB signaling pathway in MDA-MB-231 human breast cancer cells

    PubMed Central

    SUN, YI-SHENG; ZHAO, ZHAO; ZHU, HAN-PING

    2015-01-01

    Hispolon has been demonstrated to possess analgesic, anti-inflammatory and anticancer activities. However, whether hispolon prevents the invasion of breast carcinoma cells and the underlying mechanisms of its action remain unknown. In the present study, various assays, including a matrigel-based Transwell invasion assay and electrophoretic mobility shift assay, were used to investigate the anti-invasion effect of hispolon and explore its mechanism of action. The results revealed that hispolon inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration and invasion of MDA-MB-231 human breast cancer cells at non-toxic concentrations. Hispolon also prevented the TPA-induced secretion of matrix metalloproteinase-9 (MMP-9) and reduced its expression at the transcriptional and translational levels. Furthermore, the phosphorylation of IκBα was reduced by hispolon, which resulted in the suppression of nuclear factor-κB (NF-κB), and p65 phosphorylation and nuclear translocation. An electrophoretic mobility shift assay demonstrated that NF-κB DNA-binding activity was induced by TPA and inhibited by hispolon. In addition, Bay 11–7082, which is a specific inhibitor of NF-κB, functioned in a similar manner as hispolon and blocked the secretion and expression of MMP-9. In conclusion, the results of the present study indicated that hispolon inhibited TPA-induced migration and invasion of MDA-MB-231 cells by reducing the secretion and expression of MMP-9 through the NF-κB signaling pathway. PMID:26171065

  14. Vitros 5600 Syphilis TPA assay: evaluation of an automated chemiluminescence assay for detection of Treponema pallidum antibodies in a high prevalence setting.

    PubMed

    Van den Bossche, Dorien; Florence, Eric; Kenyon, Christopher; Van Esbroeck, Marjan

    2014-11-01

    The performance of the Syphilis TPA assay (Ortho-Clinical Diagnostics) on Vitros 5600 Integrated System was evaluated and demonstrated excellent results. Our data support the use of this assay for test confirmation in the traditional algorithm and for screening for syphilis in a routine automated laboratory setting when using the reverse algorithm. PMID:25299416

  15. Inhibitory Effects of 4'-Demethylnobiletin, a Metabolite of Nobiletin, on 12-O-Tetradecanoylphorbol-13-acetate (TPA)-Induced Inflammation in Mouse Ears.

    PubMed

    Wu, Xian; Song, Mingyue; Rakariyatham, Kanyasiri; Zheng, Jinkai; Wang, Minqi; Xu, Fei; Gao, Zili; Xiao, Hang

    2015-12-30

    Nobiletin (NOB) is major citrus flavonoid with many health-promoting benefits. We reported previously that 4'-demethylnobiletin (4DN), a major metabolite of NOB, significantly inhibited lipopolysaccharide (LPS)-stimulated inflammation in RAW 264.7 macrophages. In this study, we further studied the anti-inflammatory effects of 4DN in TPA-induced skin inflammation in mice. We demonstrated that topical application of 4DN decreased TPA-induced ear edema by >88 ± 4.77% in mice. This inhibitory effect was associated with inhibition on TPA-induced up-regulation of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Immunoblotting results showed that 4DN resulted in profound effects on multiple proteins related with inflammation and carcinogenesis. 4DN significantly decreased the expression levels of iNOS, COX-2, and MMP-9, suppressed phosphorylation of PI3K/Akt and ERK, and increased the levels of HO-1 and NQO1 in TPA-treated mice. Overall, the results demonstrated that 4DN had strong anti-inflammatory effects in vivo, which provided a scientific basis for using NOB to inhibit inflammation-driven diseases. PMID:26651527

  16. Optimization of chemical induction conditions for human herpesvirus 8 (HHV-8) reactivation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) from latently-infected BC-3 cells.

    PubMed

    Ma, Wenbin; Galvin, Teresa A; Ma, Hailun; Ma, Yunkun; Muller, Jacqueline; Khan, Arifa S

    2011-05-01

    Human herpesvirus 8 (HHV-8) persists as episomal DNA in latently-infected cells and can establish two alternative life cycles, latent or lytic. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is a known inducer of HHV-8 in several human primary effusion lymphoma cell lines and has been widely used for HHV-8 reactivation; however, induction conditions have differed, resulting in varying levels of virus expression. We have used HHV-8 latently-infected BC-3 cells as a model to determine critical parameters for optimizing virus reactivation by TPA. We found that cell growth properties and drug treatment conditions were important for maximum reactivation of HHV-8. Addition of TPA to cells in the early log phase of a sigmoidal growth curve, which was tightly associated with high percentage of the cells in early S phase and with lower histone deacetylase activity in the cells, provided the optimum cell conditions for latent virus to switch to lytic replication. Furthermore, increasing TPA concentration (up to 320 ng per ml) at 48 h exposure time resulted in increased virus production. The results demonstrate the use of a step-wise strategy with chemical induction that may facilitate broad detection of latent DNA viruses and novel virus discovery. PMID:21470875

  17. Educational Milestone Development in the First 7 Specialties to Enter the Next Accreditation System

    PubMed Central

    Swing, Susan R.; Beeson, Michael S.; Carraccio, Carol; Coburn, Michael; Iobst, William; Selden, Nathan R.; Stern, Peter J.; Vydareny, Kay

    2013-01-01

    Background The Accreditation Council for Graduate Medical Education (ACGME) Outcome Project introduced 6 general competencies relevant to medical practice but fell short of its goal to create a robust assessment system that would allow program accreditation based on outcomes. In response, the ACGME, the specialty boards, and other stakeholders collaborated to develop educational milestones, observable steps in residents' professional development that describe progress from entry to graduation and beyond. Objectives We summarize the development of the milestones, focusing on 7 specialties, moving to the next accreditation system in July 2013, and offer evidence of their validity. Methods Specialty workgroups with broad representation used a 5-level developmental framework and incorporated information from literature reviews, specialty curricula, dialogue with constituents, and pilot testing. Results The workgroups produced richly diverse sets of milestones that reflect the community's consideration of attributes of competence relevant to practice in the given specialty. Both their development process and the milestones themselves establish a validity argument, when contemporary views of validity for complex performance assessment are used. Conclusions Initial evidence for validity emerges from the development processes and the resulting milestones. Further advancing a validity argument will require research on the use of milestone data in resident assessment and program accreditation. PMID:24404235

  18. Canadian seismic agreement

    SciTech Connect

    Wetmiller, R.J.; Lyons, J.A.; Shannon, W.E.; Munro, P.S.; Thomas, J.T.; Andrew, M.D.; Lamontagne, M.; Wong, C., Anglin, F.M.; Plouffe, M.; Lapointe, S.P.; Adams, J.; Drysdale, J.A. . Geophysics Div.)

    1990-04-01

    This is the twenty-first progress report under the agreement entitled Canadian Seismic Agreement between the US Nuclear Regulatory Commission (NRC) and the Canadian Commercial Corporation. Activities undertaken by the Geophysics Division of the Geological Survey of Canada (GD/GSC) during the period from July 01, 1988 to June 30, 1989 and supported in part by the NRC agreement are described below under four headings; Eastern Canada Telemetred Network and local network developments, Datalab developments, strong motion network developments and earthquake activity. In this time period eastern Canada experienced its largest earthquake in over 50 years. This earthquake, which has been christened the Saguenay earthquake, has provided a wealth of new data pertinent to earthquake engineering studies in eastern North America and is the subject of many continuing studies, which are presently being carried out at GD and elsewhere. 41 refs., 21 figs., 7 tabs.

  19. FFTF Authorization Agreement

    SciTech Connect

    DAUTEL, W.A.

    2000-09-25

    The purpose of the Authorization Agreement is to serve as a mechanism whereby the U.S. Department of Energy, Richland Operations Office (RL) and Fluor Hanford (FH) jointly clarify and agree to key conditions for conducting work safely and efficiently in the Fast Flux Test Facility (FFTF). Work must be accomplished in a manner that achieves high levels of quality while protecting the environment and the safety and health of workers and the public, and complying with applicable contractual and regulatory requirements. It is the intent of this Agreement to address those items of significant importance in establishing and supporting the FFTF Authorization Envelope, but this Agreement in no way alters the terms and conditions of the Project Hanford Management Contract (PHMC), Contract Number DE-AC06-96RL13200.

  20. Canadian Seismic Agreement

    SciTech Connect

    Wetmiller, R.J.; Lyons, J.A.; Shannon, W.E.; Munro, P.S.; Thomas, J.T.; Andrew, M.D.; Lapointe, S.P.; Lamontagne, M.; Wong, C.; Anglin, F.M.; Adams, J.; Cajka, M.G.; McNeil, W.; Drysdale, J.A. )

    1992-05-01

    This is a progress report of work carried out under the terms of a research agreement entitled the Canadian Seismic Agreement'' between the US Nuclear Regulatory Commission (USNRC), the Canadian Commercial Corporation and the Geophysics Division of the Geological Survey of Canada (GD/GSC) during the period from July 01, 1989 to June 30, 1990. The Canadian Seismic Agreement'' supports generally the operation of various seismograph stations in eastern Canada and the collection and analysis of earthquake data for the purpose of mitigating seismic hazards in eastern Canada and the northeastern US. The specific activities carried out in this one-year period are summarized below under four headings; Eastern Canada Telemetred Network and local network developments, Datalab developments, strong-motion network developments and earthquake activity. During this period the first surface fault unequivocably determined to have accompanied a historic earthquake in eastern North America, occurred in northern Quebec.

  1. IL-13 but not IL-4 signaling via IL-4Rα protects mice from papilloma formation during DMBA/TPA two-step skin carcinogenesis

    PubMed Central

    Rothe, Michael; Quarcoo, David; Chashchina, Anna A; Bozrova, Svetlana V; Qin, Zhihai; Nedospasov, Sergei A; Blankenstein, Thomas; Kammertoens, Thomas; Drutskaya, Marina S

    2013-01-01

    Interleukin 4 (IL-4) was shown to be tumor-promoting in full carcinogenesis studies using 3-methylcholanthrene (MCA). Because heretofore the role of IL-4 in DMBA/TPA (9,10-dimethyl-1,2-benz-anthracene/12-O-tetradecanoylphorbol-13-acetate) two-stage carcinogenesis was not studied, we performed such experiments using either IL-4−/− or IL-4Rα−/− mice. We found that IL-4Rα−/− but not IL-4−/− mice have enhanced papilloma formation, suggesting that IL-13 may be involved. Indeed, IL-13−/− mice developed more papillomas after exposure to DMBA/TPA than their heterozygous IL-13-competent littermate controls. However, when tested in a full carcinogenesis experiment, exposure of mice to 25 μg of MCA, both IL-13−/− and IL-13+/− mice led to the same incidence of tumors. While IL-4 enhances MCA carcinogenesis, it does not play a measurable role in our DMBA/TPA carcinogenesis experiments. Conversely, IL-13 does not affect MCA carcinogenesis but protects mice from DMBA/TPA carcinogenesis. One possible explanation is that IL-4 and IL-13, although they share a common IL-4Rα chain, regulate signaling in target cells differently by employing distinct JAK/STAT-mediated signaling pathways downstream of IL-13 or IL-4 receptor complexes, resulting in different inflammatory transcriptional programs. Taken together, our results indicate that the course of DMBA/TPA- and MCA-induced carcinogenesis is affected differently by IL-4 versus IL-13-mediated inflammatory cascades. PMID:24403255

  2. 3'-untranslated region of SP-B mRNA mediates inhibitory effects of TPA and TNF-alpha on SP-B expression.

    PubMed

    Pryhuber, G S; Church, S L; Kroft, T; Panchal, A; Whitsett, J A

    1994-07-01

    Surfactant protein-B (SP-B) is a small hydrophobic polypeptide that enhances spreading and stability of surfactant phospholipids in the alveolus of the lung. Decreased expression of SP-B is associated with respiratory failure in premature infants and in adult patients with acute respiratory distress syndrome (ARDS). Tumor necrosis factor-alpha (TNF-alpha) and 12-O-tetradecanoylphorbol-13 acetate (TPA) cause ARDS-like lung injury in vivo. Inhibitory effects of TPA and TNF-alpha on SP-B mRNA expression in vitro were mediated by decreased SP-B mRNA stability rather than by decreased rate of SP-B gene transcription. In the present study, a human pulmonary adenocarcinoma cell line, NCI H441-4, was stably transfected with expression vectors consisting of the thymidine kinase (TK) promotor and human growth hormone (hGH) gene, in which the hGH 3'-untranslated region (3'-UTR) was replaced by the 2.0-kb human SP-B cDNA [pTKGH(SP-B2.0)] or the 837-bp human SP-B 3'-UTR [pTKGH(SP-B.837)]. The mRNAs and cellular growth hormone protein generated from the chimeric TKGH(SP-B2.0) and TKGH(SP-B.837) genes were each inhibited by approximately 50% by TPA and TNF-alpha. Dexamethasone decreased the inhibitory effects of TPA and TNF-alpha. The inhibition of steady-state hGH-SP-B mRNA by TPA and TNF-alpha was mediated by a cis-active element located in the 3-UTR region of SP-B mRNA. PMID:8048538

  3. The effects of dissociated glucocorticoids RU24858 and RU24782 on TPA-induced skin tumor promotion biomarkers in SENCAR mice.

    PubMed

    Kowalczyk, Piotr; Junco, Jacob J; Kowalczyk, Magdalena C; Sosnowska, Renata; Tolstykh, Olga; Walaszek, Zbigniew; Hanausek, Margaret; Slaga, Thomas J

    2014-06-01

    Glucocorticoids (GCs) are very effective at preventing carcinogen- and tumor promoter-induced skin inflammation, hyperplasia, and mouse skin tumor formation. The effects of GCs are mediated by a well-known transcription factor, the glucocorticoid receptor (GR). GR acts via two different mechanisms: transcriptional regulation that requires DNA-binding (transactivation) and DNA binding-independent protein-protein interactions between GR and other transcription factors, such as nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1; transrepression). We hypothesize that the transrepression activities of the GR are sufficient to suppress skin tumor promotion. We obtained two GCs (RU24858 and RU24782) that have dissociated downstream effects and induce only transrepression activities of the GR in a number of systems. These compounds bind the GR with high affinity and repress AP-1 and NF-κB activities while showing a lack of GR transactivation. RU24858, RU24782, or control full GCs desoximetasone (DES) and fluocinolone acetonide (FA) were applied to the dorsal skin of SENCAR mice prior to application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), two times per week for 2 weeks. DES, FA and RU24858 reversed TPA-induced epidermal hyperplasia and proliferation, while RU24782 treatment had no effect on these markers of skin tumor promotion. All tested compounds decreased TPA-induced c-jun mRNA levels in skin. DES, FA, and RU24858, but not RU24782, were also able to reverse TPA-induced increases in the mRNA levels of COX-2 and iNOS. These findings show that RU24858 but not RU24782 reduced TPA-induced epidermal hyperplasia, proliferation, and inflammation, while both compounds reversed c-jun mRNA increases in the skin. PMID:23852815

  4. FFTF Authorization Agreement

    SciTech Connect

    DAUTEL, W.A.

    2000-02-25

    The purpose of the Authorization Agreement is to serve as a mechanism whereby the U.S. Department of Energy, Richland Operations Office (RL) and Fluor Hanford (FH) jointly clarify and agree to key conditions for conducting work safely and efficiently.

  5. Coefficients for Interrater Agreement.

    ERIC Educational Resources Information Center

    Zegers, Frits E.

    1991-01-01

    The degree of agreement between two raters rating several objects for a single characteristic can be expressed through an association coefficient, such as the Pearson product-moment correlation. How to select an appropriate association coefficient, and the desirable properties and uses of a class of such coefficients--the Euclidean…

  6. HUBBLE PHOTOGRAPHS WARPED GALAXY AS CAMERA PASSES MILESTONE

    NASA Technical Reports Server (NTRS)

    2002-01-01

    observations of ESO 510-G13, WFPC2 passed the milestone of taking its 100,000th image since its installation in the telescope by shuttle astronauts in 1993. Image Credit: NASA and the Hubble Heritage Team (STScI/AURA) Acknowledgment: C. Conselice (U. Wisconsin/STScI)

  7. Countries renew rescue agreement

    NASA Astrophysics Data System (ADS)

    Bush, Susan M.

    To insure long-term continuity for the international satellite search and rescue system, COSPAS/SARSAT, an intergovernmental agreement binding the four sponsoring nations to cooperate was signed July 1 in Paris. According to Russell Vollmers of the National Oceanic and Atmospheric Administration, the agreement is binding for 15 years, with an automatic extension.The system marked the fifth anniversary of its first rescue last year, when on September 10, 1982, three persons were rescued. Begun in the 1970s by NASA as an experiment, COSPAS/SARSAT (a Russian-English acronym) is now a cooperative project among the United States, Canada, France, and the Soviet Union. Its goal is to reduce the time required to rescue air and maritime distress victims and also to locate victims who otherwise may not be found, thus using the satellite system as a life-saving device.

  8. 2014 Report on the Milestones for the US National Plan to Address Alzheimer's Disease.

    PubMed

    Fargo, Keith N; Aisen, Paul; Albert, Marilyn; Au, Rhoda; Corrada, Maria M; DeKosky, Steven; Drachman, David; Fillit, Howard; Gitlin, Laura; Haas, Magali; Herrup, Karl; Kawas, Claudia; Khachaturian, Ara S; Khachaturian, Zaven S; Klunk, William; Knopman, David; Kukull, Walter A; Lamb, Bruce; Logsdon, Rebecca G; Maruff, Paul; Mesulam, Marsel; Mobley, William; Mohs, Richard; Morgan, David; Nixon, Ralph A; Paul, Steven; Petersen, Ronald; Plassman, Brenda; Potter, William; Reiman, Eric; Reisberg, Barry; Sano, Mary; Schindler, Rachel; Schneider, Lon S; Snyder, Peter J; Sperling, Reisa A; Yaffe, Kristine; Bain, Lisa J; Thies, William H; Carrillo, Maria C

    2014-10-01

    With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025. To guide investments, activities, and the measurement of progress toward achieving this 2025 goal, in its first annual plan update (2013) HHS also incorporated into the plan a set of short, medium and long-term milestones. HHS further committed to updating these milestones on an ongoing basis to account for progress and setbacks, and emerging opportunities and obstacles. To assist HHS as it updates these milestones, the Alzheimer's Association convened a National Plan Milestone Workgroup consisting of scientific experts representing all areas of Alzheimer's and dementia research. The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's by 2025. This report presents these Workgroup recommendations. PMID:25341459

  9. Level II Milestone Review of LLNL Program on Grain-Scale Dynamics in Explosives

    SciTech Connect

    Nicol, M F; Benson, D J; Yip, S

    2003-01-14

    This document describes an evaluation of the Level II Milestone achievements of the LLNL program on Grain-Scale Dynamics in Explosives on January 14, 2003. ''The Grain-Scale Dynamics in Explosives Program'' is a mixture of advanced computational methodology and physico-chemical theory applied to understanding deflagration and detonation of plastic-bonded explosives from the nano to the macro scales. At many points, the modeling is tied directly to experiments within the precisions of both. Advances are needed in the experimental, theoretical, and computational aspects of detonations. Work reported in this review represents significant, cross-pollinating advances in each area. The team successfully carried out ALE-3D simulations of deflagration in PBX with grain scale effects. (Milestone requirements 1 and 2), interpreted experimental data on flame speed vs. pressure and sensitivity to global kinetics in terms of ALE-3D simulations (Milestone requirement 3), and used the results of these simulations to develop a continuum reactive flow model that captures some of these effects (Milestone requirement 4). By comparing experiments and detonation velocities in small diameter, unconfined explosives, they found non-idealities that remain at intermediate diameters (ca. 1.5 mm) that require further analysis. In all of these areas, the project team has met, indeed exceeded, their Level II Milestone goals.

  10. 20 CFR 411.545 - How are the outcome payments calculated under the outcome-milestone payment system?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Title XVI amount of payment Phase 1 (120% of Title II PCB) Milestone 1 $335/mo. $670/mo. × 3 mo. work in... Phase 1 milestones $4,708 $4,708 Phase 2 (36% of PCB) Gross Earnings>SGA Title II milestones 1-11 $353... payments (36% of PCB) Title II = 1-36 Monthly cash benefit not payable due to SGA $353 × 36 = $12,708...

  11. 20 CFR 411.545 - How are the outcome payments calculated under the outcome-milestone payment system?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Title XVI amount of payment Phase 1 (120% of Title II PCB) Milestone 1 $335/mo. $670/mo. × 3 mo. work in... Phase 1 milestones $4,708 $4,708 Phase 2 (36% of PCB) Gross Earnings>SGA Title II milestones 1-11 $353... payments (36% of PCB) Title II = 1-36 Monthly cash benefit not payable due to SGA $353 × 36 = $12,708...

  12. 20 CFR 411.545 - How are the outcome payments calculated under the outcome-milestone payment system?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Title XVI amount of payment Phase 1 (120% of Title II PCB) Milestone 1 $335/mo. $670/mo. × 3 mo. work in... Phase 1 milestones $4,708 $4,708 Phase 2 (36% of PCB) Gross Earnings>SGA Title II milestones 1-11 $353... payments (36% of PCB) Title II = 1-36 Monthly cash benefit not payable due to SGA $353 × 36 = $12,708...

  13. 20 CFR 411.545 - How are the outcome payments calculated under the outcome-milestone payment system?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Title XVI amount of payment Phase 1 (120% of Title II PCB) Milestone 1 $335/mo. $670/mo. × 3 mo. work in... Phase 1 milestones $4,708 $4,708 Phase 2 (36% of PCB) Gross Earnings>SGA Title II milestones 1-11 $353... payments (36% of PCB) Title II = 1-36 Monthly cash benefit not payable due to SGA $353 × 36 = $12,708...

  14. Milestones Towards Hot CMC Structures for Operational Space Rentry Vehicles

    NASA Astrophysics Data System (ADS)

    Hald, H.; Weihs, H.; Reimer, T.

    2002-01-01

    Hot structures made of ceramic matrix composites (CMC) for space reentry vehicles play a key role regarding feasibility of advanced and reusable future space transportation systems. Thus realization of applicable flight hardware concerning hot primary structures like a nose cap or body flaps and thermal protection systems (TPS) requires system competence w.r.t. sophisticated know how in material processing, manufacturing and qualification of structural components and in all aspects from process control, use of NDI techniques, arc jet testing, hot structure testing to flight concept validation. This goal has been achieved so far by DLR while following a dedicated development road map since more than a decade culminating at present in the supply of the nose cap system for NASA's X-38; the flight hardware has been installed successfully in October 2001. A number of unique hardware development milestones had to be achieved in the past to finally reach this level of system competence. It is the intention of this paper to highlight the most important technical issues and achievements from the essential projects and developments to finally provide a comprehensive insight into DLR's past and future development road map w.r.t. CMC hot structures for space reentry vehicles. Based on DLR's C/C-SiC material which is produced with the inhouse developed liquid silicon infiltration process (LSI) the development strategy first concentrated on basic material properties evaluation in various arc jet testing facilities. As soon as a basic understanding of oxidation and erosion mechanisms had been achieved further efforts concentrated on inflight verification of both materials and design concepts for hot structures. Consequently coated and uncoated C/C-SiC specimens were integrated into the ablative heat shield of Russian FOTON capsules and they were tested during two missions in 1992 and 1994. Following on, a hot structure experiment called CETEX which principally was a kind of a

  15. Oak Ridge Reservation Federal Facility Agreement for the Environmental Restoration Program. Volume 1, Quarterly report, October--December 1995

    SciTech Connect

    1996-01-01

    This Oak Ridge Reservation Federal Facility Agreement Quarterly Report for the Environmental Restoration Program was prepared to satisfy requirements for progress reporting on Environmental Restoration Program (ER) activities as specified in the Oak Ridge Reservation Federal Facility Agreement (FFA) established between the US Department of Energy (DOE), the US Environmental Protection Agency, and the Tennessee Department of Environment and Conservation. The reporting period covered in this document is October through December 1995. This work was performed under Work Breakdown Structure 1.4.12.2.3.04 (Activity Data Sheet 8304). Publication of this document meets two FFA milestones. The FFA Quarterly Report meets an FFA milestone defined as 30 days following the end of the applicable reporting period. Appendix A of this report meets the FFA milestone for the Annual Removal Action Report for the period FYs 1991--95. This document provides information about ER Program activities conducted on the Oak Ridge Reservation under the FFA. Specifically, it includes information on milestones scheduled for completion during the reporting period, as well as scheduled for completion during the next reporting period (quarter); accomplishments of the ER Program; concerns related to program work; and scheduled activities for the next quarter. It also provides a listing of the identity and assigned tasks of contractors performing ER Program work under the FFA.

  16. Lattice stability and high-pressure melting mechanism of dense hydrogen up to 1.5 TPa

    NASA Astrophysics Data System (ADS)

    Geng, Hua Y.; Hoffmann, R.; Wu, Q.

    2015-09-01

    Lattice stability and metastability, as well as melting, are important features of the physics and chemistry of dense hydrogen. Using ab initio molecular dynamics (AIMD), the classical superheating limit and melting line of metallic hydrogen are investigated up to 1.5 TPa. The computations show that the classical superheating degree is about 100 K, and the classical melting curve becomes flat at a level of 350 K when beyond 500 GPa. This information allows us to estimate the well depth and the potential barriers that must be overcome when the crystal melts. Inclusion of nuclear quantum effects (NQE) using path integral molecular dynamics (PIMD) predicts that both superheating limit and melting temperature are lowered to below room temperature, but the latter never reaches absolute zero. Detailed analysis indicates that the melting is thermally activated, rather than driven by pure zero-point motion (ZPM). This argument was further supported by extensive PIMD simulations, demonstrating the stability of Fddd structure against liquefaction at low temperatures.

  17. Absolute equation of state and opacity measurements of CH plastic to 40 TPa using the National Ignition Facility

    NASA Astrophysics Data System (ADS)

    Doeppner, T.; Swift, D.; Hawreliak, J.; Kritcher, A.; Collins, G.; Glenzer, S.; Rothman, S.; Chapman, D.; Gaffney, J.; Rose, S.; Falcone, R.

    2013-06-01

    We have developed an experimental configuration using a hohlraum-driven spherically-convergent shock to induce pressures into the gigabar range, measuring the Hugoniot radiographically. The shock pressure increases with convergence, so a range of Hugoniot states is obtained from a single experiment. The opacity along the Hugoniot is also deduced, which is essential in gigabar experiments as it changes significantly from its initial value. We are focusing initially on plastics, as we can reliably obtain spherical samples with the desired design of ablator, and the radiographic signal is reasonable. Our initial measurements on NIF used a conservative timing of the x-ray backlighter to allow for uncertainty in the EOS, and probed only part of the pressure range. The shock speed and compression, obtained from radiographic analysis, gave absolute Hugoniot states from 12-41 TPa, which is an order of magnitude greater than previously measured in CH. The measured EOS locus was consistent with the previous measurements, and significantly stiffer than the theoretical EOS used for comparison. Our analysis also gave the variation of opacity along the Hugoniot, which showed a decrease of an order of magnitude, as expected from atomic physics calculations. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  18. Atrazine represses S100A4 gene expression and TPA-induced motility in HepG2 cells.

    PubMed

    Peyre, Ludovic; Zucchini-Pascal, Nathalie; Rahmani, Roger

    2014-03-01

    Atrazine (ATZ) is probably the most widely used herbicide in the world. However there are still many controversies regarding its impacts on human health. Our investigations on the role of pesticides in liver dysfunctions have led us to detect an inhibition of FSP1 expression of 70% at 50μm and around 95% at 500μM of ATZ (p<0.01). This gene encodes the protein S100a4 and is a clinical biomarker of epithelial-mesenchymal transition (EMT), a key step in the metastatic process. Here we investigated the possible effect of ATZ on cell migration and noticed that it prevents the EMT and motility of the HepG2 cells induced by the phorbol ester TPA. ATZ decreases Fak pathway activation but has no effect on the Erk1/2 pathway known to be involved in metastasis in this cell line. These results suggest that ATZ could be involved in cell homeostasis perturbation, potentially through a S100a4-dependant mechanism. PMID:24211529

  19. Purple Level - 1 Milestone Review Committee I/O and Archive Follow-up Demonstration

    SciTech Connect

    Gary, M R

    2006-12-05

    On July 7th 2006, the Purple Level-1 Review Committee convened and was presented with evidence of the completion of Level-2 Milestone 461 (Deploy First Phase of I/O Infrastructure for Purple) which was performed in direct support of the Purple Level-1 milestone. This evidence included a short presentation and the formal documentation of milestone No.461 (see UCRL-TR-217288). Following the meeting, the Committee asked for the following additional evidence: (1) Set a speed measurement/goal/target assuming a number of files that the user needs to get into the archives. Then redo the benchmark using whatever tool(s) the labs prefer (HTAR, for example). Document how long the process takes. (2) Develop a test to read files back to confirm that what the user gets out of the archive is what the user put into the archive. This evidence has been collected and is presented here.

  20. Modeling kinetics and equilibrium of membranes with fields: Milestoning analysis and implication to permeation

    SciTech Connect

    Cardenas, Alfredo E.; Elber, Ron

    2014-08-07

    Coarse graining of membrane simulations by translating atomistic dynamics to densities and fields with Milestoning is discussed. The space of the membrane system is divided into cells and the different cells are characterized by order parameters presenting the number densities. The dynamics of the order parameters are probed with Milestoning. The methodology is illustrated here for a phospholipid membrane system (a hydrated bilayer of DOPC (1,2-dioleoyl-sn-glycero-3-phosphocholine) lipid molecules). Significant inhomogeneity in membrane internal number density leads to complex free energy landscape and local maps of transition times. Dynamics and distributions of cavities within the membrane assist the permeation of nonpolar solutes such as xenon atoms. It is illustrated that quantitative and detailed dynamics of water transport through DOPC membrane can be analyzed using Milestoning with fields. The reaction space for water transport includes at least two slow variables: the normal to the membrane plane, and the water density.

  1. University-Industry Teaming Agreements.

    ERIC Educational Resources Information Center

    Stombler, Milton P.

    1989-01-01

    The use of preaward agreements between the industry and the university collaborating to seek external funding, particularly from government sources, is examined. The agreements describe the parties' obligations in seeking funding and lay the groundwork for subsequent research agreements. Elements of such agreements are discussed to raise awareness…

  2. Optimization of alternate-strand triple helix formation at the 5"-TpA-3" and 5"-ApT-3" junctions.

    PubMed Central

    Brodin, P; Sun, J S; Mouscadet, J F; Auclair, C

    1999-01-01

    Alternate-strand triple helix formation was optimized at the two junction steps, the 5"-TpA-3" and 5"-ApT-3" junctions. Footprint experiments, gel retardation assays and thermal denaturation measures on a sequence appropriately designed with two adjacent alternate-strand polypurine tracts points out that the addition of an adenine residue and the removal of one nucleotide should facilitate the crossing strands at the 5"-TpA-3" junction and at the 5"-ApT-3" junction, respectively. These results provide a 'switch code' for the construction of alternate-strand triple helix forming oligonucleotides which open new possibilities for extending the range of applications of antigene strategy. PMID:10454596

  3. Rocky Flats Cleanup Agreement implementation successes and challenges

    SciTech Connect

    Shelton, D.C.

    1997-02-01

    On July 19, 1996 the US Department of Energy (DOE), State of Colorado (CDPHE), and US Environmental Protection Agency (EPA) entered into an agreement called the Rocky Flats Cleanup Agreement (RFCA) for the cleanup and closure of the Rocky Flats Environmental Technology Site (RFETS or Rocky Flats). Major elements of the agreement include: an Integrated Site-Wide Baseline; up to twelve significant enforceable milestones per year; agreed upon soil and water action levels and standards for cleanup; open space as the likely foreseeable land use; the plutonium and TRU waste removed by 2015; streamlined regulatory process; agreement with the Defense Nuclear Facilities Safety Board (DNFSB) to coordinate activities; and a risk reduction focus. Successful implementation of RFCA requires a substantial effort by the parties to change their way of thinking about RFETS and meet the deliverables and commitments. Substantial progress toward Site closure through the implementation of RFCA has been accomplished in the short time since the signing, yet much remains to be done. Much can be learned from the Rocky Flats experience by other facilities in similar situations.

  4. Level-2 Milestone 3244: Deploy Dawn ID Machine for Initial Science Runs

    SciTech Connect

    Fox, D

    2009-09-21

    This report documents the delivery, installation, integration, testing, and acceptance of the Dawn system, ASC L2 milestone 3244: Deploy Dawn ID Machine for Initial Science Runs, due September 30, 2009. The full text of the milestone is included in Attachment 1. The description of the milestone is: This milestone will be a result of work started three years ago with the planning for a multi-petaFLOPS UQ-focused platform (Sequoia) and will be satisfied when a smaller ID version of the final system is delivered, installed, integrated, tested, accepted, and deployed at LLNL for initial science runs in support of SSP mission. The deliverable for this milestone will be a LA petascale computing system (named Dawn) usable for code development and scaling necessary to ensure effective use of a final Sequoia platform (expected in 2011-2012), and for urgent SSP program needs. Allocation and scheduling of Dawn as an LA system will likely be performed informally, similar to what has been used for BlueGene/L. However, provision will be made to allow for dedicated access times for application scaling studies across the entire Dawn resource. The milestone was completed on April 1, 2009, when science runs began running on the Dawn system. The following sections describe the Dawn system architecture, current status, installation and integration time line, and testing and acceptance process. A project plan is included as Attachment 2. Attachment 3 is a letter certifying the handoff of the system to a nuclear weapons stockpile customer. Attachment 4 presents the results of science runs completed on the system.

  5. Hanford Federal Facility Agreement and Consent Order quarterly progress report for the period ending June 30, 1991

    SciTech Connect

    Not Available

    1991-08-01

    This is the ninth quarterly report as required by the Hanford Federal Facility Agreement and Consent Order (Ecology et al. 1990), also known as the Tri-Party Agreement, established between the US Department of Energy (DOE), the US Environmental Protection Agency (EPA), and the Washington State Department of Ecology (Ecology). The Tri-Party Agreement sets the plan and schedule for achieving regulatory compliance and cleanup of waste sites at the Hanford Site. This report covers progress for the quarter that ended June 30, 1991. A total of 87 milestones have been completed to date. 39 refs., 1 fig.

  6. Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing

    PubMed Central

    van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank

    2016-01-01

    Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the ‘sunburn group’ but persisted and grew in the ‘sub-sunburn group’ (0.06 vs 2.50 SCCs and precursors ≥4mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these ‘usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide – with high mutagenic risk - gives rise to persisting (mainly ‘in situ’) skin carcinomas. PMID:26797757

  7. Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing.

    PubMed

    van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank

    2016-02-16

    Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the 'sunburn group' but persisted and grew in the 'sub-sunburn group' (0.06 vs 2.50 SCCs and precursors ≥4 mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these 'usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide--with high mutagenic risk--gives rise to persisting (mainly 'in situ') skin carcinomas. PMID:26797757

  8. Cytoskeletal reorganization and TPA differently modify AP-1 to induce the urokinase-type plasminogen activator gene in LLC-PK1 cells.

    PubMed Central

    Lee, J S; von der Ahe, D; Kiefer, B; Nagamine, Y

    1993-01-01

    Urokinase-type plasminogen activator (uPA) is an extracellular protease and expressed in various cells that exhibit dynamic changes in cell morphology, suggesting a link between cytoskeletal reorganization (CSR) and uPA expression. CSR can be induced by pharmacological agents, such as by colchicine for microtubule cytoskeleton and by cytochalasin for microfilament cytoskeleton. Using these agents, we previously showed that CSR induced the uPA gene in LLC-PK1 cells independently of the protein kinase C and cAMP-dependent protein kinase. Here we show that the induction of the uPA gene by CSR is mediated by the activation of c-Jun which interacts with an AP-1-like site located 2 kb upstream of the uPA gene. 12-O-tetradecanoylphorbol 13-acetate (TPA) induces the uPA gene through the same elements, but additionally utilizes an adjacent PEA3 element and induces c-fos. Furthermore, CSR induces a greater accumulation and a more pronounced phosphorylation of c-Jun than TPA induction. AP-1 is a positive regulator of growth and oncogenesis, and CSR is an integral part of these processes. Our results provide a view how CSR and AP-1 could be coupled in these processes. We also show that TPA and CSR act synergistically, suggesting a model where an initial activation signal could be amplified by CSR. Images PMID:8346015

  9. A pilot study of orthopaedic resident self-assessment using a milestones’ survey just prior to milestones implementation

    PubMed Central

    Bradley, Kendall E.

    2016-01-01

    Objectives To pilot test if Orthopaedic Surgery residents could self-assess their performance using newly created milestones, as defined by the Accreditation Council on Graduate Medical Education.  Methods In June 2012, an email was sent to Program Directors and administrative coordinators of the154 accredited Orthopaedic Surgery Programs, asking them to send their residents a link to an online survey. The survey was adapted from the Orthopaedic Surgery Milestone Project. Completed surveys were aggregated in an anonymous, confidential database. SAS 9.3 was used to perform the analyses. Results Responses from 71 residents were analyzed. First and second year residents indicated through self-assessment that they had substantially achieved Level 1 and Level 2 milestones. Third year residents reported they had substantially achieved 30/41, and fourth year residents, all Level 3 milestones. Fifth year, graduating residents, reported they had substantially achieved 17 Level 4 milestones, and were extremely close on another 15. No milestone was rated at Level 5, the maximum possible.  Earlier in training, Patient Care and Medical Knowledge milestones were rated lower than the milestones reflecting the other four competencies of Practice Based Learning and Improvement, Systems Based Practice, Professionalism, and Interpersonal Communication. The gap was closed by the fourth year. Conclusions Residents were able to successfully self-assess using the 41 Orthopaedic Surgery milestones. Respondents’ rate improved proficiency over time. Graduating residents report they have substantially, or close to substantially, achieved all Level 4 milestonesMilestone self-assessment may be a useful tool as one component of a program’s overall performance assessment strategy. PMID:26752012

  10. Understanding the function and performance of carbon-enhanced lead-acid batteries : milestone report for the DOE energy storage systems program (FY11 Quarter 3: April through June 2011).

    SciTech Connect

    Ferreira, Summer Rhodes; Shane, Rodney; Enos, David George

    2011-09-01

    This report describes the status of research being performed under CRADA No. SC10/01771.00 (Lead/Carbon Functionality in VRLA Batteries) between Sandia National Laboratories and East Penn Manufacturing, conducted for the U.S. Department of Energy's Energy Storage Systems Program. The Quarter 3 Milestone was completed on time. The milestone entails an ex situ analysis of a control as well as three carbon-containing negative plates in the raw, as cast form as well as after formation. The morphology, porosity, and porosity distribution within each plate was evaluated. In addition, baseline electrochemical measurements were performed on each battery to establish their initial performance. These measurements included capacity, internal resistance, and float current. The results obtained for the electrochemical testing were in agreement with previous evaluations performed at East Penn manufacturing. Cycling on a subset of the received East Penn cells containing different carbons (and a control) has been initiated.

  11. 20 CFR 411.560 - Is it possible to pay a milestone or outcome payment to more than one EN?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (including a State VR agency acting as an EN) to receive payment based on the same milestone or outcome. If the beneficiary has assigned the ticket to more than one EN (or State VR agency acting as an EN) at different times, and more than one EN (or State VR agency) requests payment for the same milestone,...

  12. 20 CFR 411.560 - Is it possible to pay a milestone or outcome payment to more than one EN?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (including a State VR agency acting as an EN) to receive payment based on the same milestone or outcome. If the beneficiary has assigned the ticket to more than one EN (or State VR agency acting as an EN) at different times, and more than one EN (or State VR agency) requests payment for the same milestone,...

  13. 20 CFR 411.560 - Is it possible to pay a milestone or outcome payment to more than one EN?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (including a State VR agency acting as an EN) to receive payment based on the same milestone or outcome. If the beneficiary has assigned the ticket to more than one EN (or State VR agency acting as an EN) at different times, and more than one EN (or State VR agency) requests payment for the same milestone,...

  14. 20 CFR 411.560 - Is it possible to pay a milestone or outcome payment to more than one EN?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (including a State VR agency acting as an EN) to receive payment based on the same milestone or outcome. If the beneficiary has assigned the ticket to more than one EN (or State VR agency acting as an EN) at different times, and more than one EN (or State VR agency) requests payment for the same milestone,...

  15. From Kissing to Coitus? Sex-of-Partner Differences in the Sexual Milestone Achievement of Young Men

    ERIC Educational Resources Information Center

    Smiler, Andrew P.; Frankel, Loren B. W.; Savin-Williams, Ritch C.

    2011-01-01

    Scientific information regarding normative patterns of young men's sexual behavior is insufficient, especially regarding the impact of sex of partner. We explored the age at which 255 young adult men achieved several milestones (e.g., first kiss, manual-genital contact, intercourse) as well as the sequence of milestone achievement and stability in…

  16. Brief Report: Ages of Language Milestones as Predictors of Developmental Trajectories in Young Children with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Kover, Sara T.; Edmunds, Sarah R.; Ellis Weismer, Susan

    2016-01-01

    Recognizing early risk markers in young children with autism spectrum disorder (ASD) is critical for timely diagnosis and intervention. The purpose of this study was to extend previous findings regarding language milestones to a longitudinal design, in which ages of expressive language milestones (i.e., first words, first phrases) could serve as…

  17. Motor Milestone Development in Young Children with Autism Spectrum Disorders: An Exploratory Study

    ERIC Educational Resources Information Center

    Liu, Ting

    2012-01-01

    This study aimed to determine if a sample of children currently diagnosed with autism spectrum disorders (ASDs) would have shown motor milestone delays before age three as compared to typically developing children. Given delays in motor skills, the study also strived to determine which specific skills might be delayed. Parents of 44 children who…

  18. 20 CFR 411.535 - Under what circumstances will milestones be paid?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... beneficiary has assigned his or her ticket to the EN. See § 411.575 for other milestone payment criteria. ... earnings were less than the trial work level in each of the 18 months before the ticket was first assigned....500(f)) except as provided in § 411.536 (reconciliation payments). (ii) Significant work...

  19. Sexual Orientation Identity Formation among Gay, Lesbian, and Bisexual Youths: Multiple Patterns of Milestone Experiences.

    ERIC Educational Resources Information Center

    Floyd, Frank J.; Stein, Terry S.

    2002-01-01

    Examined variations in "coming out" for gay, lesbian, and bisexual youths, specifically: the timing and sequence of developmental stages; completion of 10 milestone events involving self-awareness, sexual experiences, and disclosure to others; and immersion in social networks. Found comfort with sexual orientation was greatest in persons with…

  20. Relations of Alcohol Consumption with Smoking Cessation Milestones and Tobacco Dependence

    ERIC Educational Resources Information Center

    Cook, Jessica W.; Fucito, Lisa M.; Piasecki, Thomas M.; Piper, Megan E.; Schlam, Tanya R.; Berg, Kristin M.; Baker, Timothy B.

    2012-01-01

    Objective: Alcohol consumption is associated with smoking cessation failure in both community and clinical research. However, little is known about the relation between alcohol consumption and smoking cessation milestones (i.e., achieving initial abstinence, avoiding lapses and relapse). Our objective in this research was to examine the relations…

  1. 20 CFR 411.540 - How are the payment amounts calculated for each of the milestones?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false How are the payment amounts calculated for each of the milestones? 411.540 Section 411.540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.540 How are...

  2. 20 CFR 411.540 - How are the payment amounts calculated for each of the milestones?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false How are the payment amounts calculated for each of the milestones? 411.540 Section 411.540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.540 How are...

  3. 20 CFR 411.540 - How are the payment amounts calculated for each of the milestones?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false How are the payment amounts calculated for each of the milestones? 411.540 Section 411.540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.540 How are...

  4. 20 CFR 411.540 - How are the payment amounts calculated for each of the milestones?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false How are the payment amounts calculated for each of the milestones? 411.540 Section 411.540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.540 How are...

  5. 20 CFR 411.540 - How are the payment amounts calculated for each of the milestones?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false How are the payment amounts calculated for each of the milestones? 411.540 Section 411.540 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.540 How are...

  6. Puberty: Maturation, Timing and Adjustment, and Sexual Identity Developmental Milestones among Lesbian, Gay, and Bisexual Youth

    ERIC Educational Resources Information Center

    Grossman, Arnold H.; Foss, Alexander H.; D'Augelli, Anthony R.

    2014-01-01

    This study examined pubertal maturation, pubertal timing and outcomes, and the relationship of puberty and sexual identity developmental milestones among 507 lesbian, gay, and bisexual youth. The onset of menarche and spermarche occurred at the mean ages of 12.05 and 12.46, respectively. There was no statistically significant difference in…

  7. Analyzing Milestones in Smoking Cessation: Illustration in a Nicotine Patch Trial in Adult Smokers

    ERIC Educational Resources Information Center

    Shiffman, Saul; Scharf, Deborah M.; Shadel, William G.; Gwaltney, Chad J.; Dang, Qianyu; Paton, Stephanie M.; Clark, Duncan B.

    2006-01-01

    Tests of addiction treatments seldom reveal where treatment exercises its effect (i.e., promoting initial abstinence, preventing lapses, and/or impeding progression from lapse to relapse). The authors illustrate analyses distinguishing effects on these milestones in a randomized trial of high-dose nicotine patch (35 mg; n = 188) versus placebo (n…

  8. Milestones in the Secondary English Curriculum in the United States. ICTE Occasional Paper No. 11.

    ERIC Educational Resources Information Center

    Bleakley, Lou Ann

    Written for students pursuing graduate study, this chronological table lists landmark publications in the secondary English curriculum occurring between 1893 and 1971. For each of the 27 milestones--e.g., "Report of the Committee of Ten on Secondary School Studies" (1893), "Teaching Creative Writing" by Lawrence Conrad (1937), "The Uses of…

  9. Providing lipid-based nutrient supplements does not affect developmental milestones among Malawian children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to assess whether using lipid-based nutrient supplements (LNS) to complement the diets of infants and young children affected when they achieved selected developmental milestones. In rural Malawi, 840 6-month-old healthy infants were enrolled to a randomised trial. Control particip...

  10. From Early to Current Developments in Online Learning at Nova Southeastern University: Reflections on Historical Milestones.

    ERIC Educational Resources Information Center

    Dringus, Laurie P.; Scigliano, John A.

    2000-01-01

    Traces the major historical milestones achieved by Nova Southeastern University in its pioneering of graduate level online learning programs. Highlights include delivery systems; Web-based electronic classrooms; overview of the technology, including telecommunications through UNIX; evaluation and research; and technology used in the School of…

  11. Assessment of pharmacogenomic agreement

    PubMed Central

    Safikhani, Zhaleh; El-Hachem, Nehme; Quevedo, Rene; Smirnov, Petr; Goldenberg, Anna; Juul Birkbak, Nicolai; Mason, Christopher; Hatzis, Christos; Shi, Leming; Aerts, Hugo JWL; Quackenbush, John; Haibe-Kains, Benjamin

    2016-01-01

    In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors’ published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings. PMID:27408686

  12. Assessment of pharmacogenomic agreement.

    PubMed

    Safikhani, Zhaleh; El-Hachem, Nehme; Quevedo, Rene; Smirnov, Petr; Goldenberg, Anna; Juul Birkbak, Nicolai; Mason, Christopher; Hatzis, Christos; Shi, Leming; Aerts, Hugo Jwl; Quackenbush, John; Haibe-Kains, Benjamin

    2016-01-01

    In 2013 we published an analysis demonstrating that drug response data and gene-drug associations reported in two independent large-scale pharmacogenomic screens, Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE), were inconsistent. The GDSC and CCLE investigators recently reported that their respective studies exhibit reasonable agreement and yield similar molecular predictors of drug response, seemingly contradicting our previous findings. Reanalyzing the authors' published methods and results, we found that their analysis failed to account for variability in the genomic data and more importantly compared different drug sensitivity measures from each study, which substantially deviate from our more stringent consistency assessment. Our comparison of the most updated genomic and pharmacological data from the GDSC and CCLE confirms our published findings that the measures of drug response reported by these two groups are not consistent. We believe that a principled approach to assess the reproducibility of drug sensitivity predictors is necessary before envisioning their translation into clinical settings. PMID:27408686

  13. A survey of resident perspectives on surgical case minimums and the impact on milestones, graduation, credentialing, and preparation for practice: AOA critical issues.

    PubMed

    Jeray, Kyle J; Frick, Steven L

    2014-12-01

    Residency education continues to evolve. Several major changes have occurred in the past several years, including emphasis on core competencies, duty-hour restrictions, and call. The Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System (NAS) implemented educational milestones in orthopaedic surgery in July 2013. Additionally, the Residency Review Committee for orthopaedic surgery published suggested surgical case minimums in 2012, which overlap with several of the milestones.We conducted a survey to assess the opinions of orthopaedic residents regarding the ACGME-suggested surgical case minimums and the effects that these may have on resident education and potential future privileges in hospitals. The survey was sent via e-mail to all of the residents participating in the American Orthopaedic Association (AOA) Resident Leadership Forum for both 2011 and 2012. Participants in the Resident Leadership Forum are in either postgraduate year 4 or postgraduate year 5, are selected by the program directors as resident leaders, and represent 80% of the orthopaedic residency programs in the United States. The survey was completed by 157 of the 314 participants. Sixty-nine percent of the participants believed that case logs with minimum numbers of surgical procedures were an effective way to monitor the work but were not necessarily the only way to monitor the educational progress of the residents. Thirty-two percent believed that the minimums should not be required. Overwhelmingly, there was agreement that important cases were missing from the currently proposed sixteen core surgical minimums. Specifically, the residents believed that a minimum number of cases are necessary for distal radial fracture fixation and proximal humeral fracture fixation and possibly have a milestone to reflect the progress of the residents for each fixation.Most residents thought that surgical case minimums are an effective tool in monitoring the progress of

  14. Age of Achievement of Gross Motor Milestones in Infancy and Adiposity at Age 3 Years

    PubMed Central

    Neelon, Sara E. Benjamin; Oken, Emily; Taveras, Elsie M.; Rifas-Shiman, Sheryl L.; Gillman, Matthew W.

    2011-01-01

    Early life physical activity may help prevent obesity but is difficult to measure. The purpose of this study was to examine associations of age of achievement of gross motor milestones in infancy with adiposity at age 3 years. Seven forty one mother/infant dyads participated in a longitudinal study in Massachusetts. Exposures were age of attainment of 4 gross motor milestones—rolling over, sitting up, crawling, and walking. Outcomes were 3-year sum of subscapular and triceps skinfold thickness (SS + TR) for overall adiposity, their ratio (SS:TR) for central adiposity, and body mass index (BMI) z-score. We used linear regression models adjusted for confounders to examine motor milestone achievement and later adiposity. Rolling over (0.04, 95% CI: 0.008, 0.07) and sitting up (0.02, 95% CI: 0.001, 0.05) at ≥6 months were associated with increased SS:TR compared with attainment before 6 months. Walking at ≥15 months was associated with 0.98 mm higher SS + TR (95% CI: 0.05, 1.91) compared with walking before 12 months. Age at crawling was not associated with the outcomes. None of the milestones were associated with BMI z-score. Age of motor milestone achievement was only a modest predictor of adiposity. Later rolling over and sitting up were associated with greater central adiposity, and later age at walking was associated with greater overall adiposity at age 3 years. Although we controlled for birth weight and 6-month weight-for-length in our models, more detailed assessment of early adiposity prior to achievement of motor milestones is needed to help determine causality. PMID:21643834

  15. Oak Ridge Reservation Federal Facility Agreement: Quarterly report for the Environmental Restoration Program. Volume 2, January--March 1996

    SciTech Connect

    1996-04-01

    This report provides information about ER Program activities conducted on the Oak Ridge Reservation under the Federal Facility Agreement (FFA). Specifically, it includes information on milestones scheduled for completion during the reporting period as well as scheduled for completion during the next reporting period (quarter), accomplishments of the ER Program, concerns related to program work, and scheduled activities for the next quarter. It also provides a listing of the identity and assigned tasks of contractors performing ER Program work under the FFA.

  16. Mining Agreements with Indian Tribes

    ERIC Educational Resources Information Center

    Luebben, Tom

    1976-01-01

    The article discusses aspects of negotiating agreements for exploration, development, and mining of hard minerals on Indian Reservations. The agreements discussed are typical of copper agreements, but the general points under discussion are applicable to most hard minerals except for uranium, coal, and oil which are substantially different.…

  17. Agreement with Subjects in Lubukusu

    ERIC Educational Resources Information Center

    Diercks, Michael J. K.

    2010-01-01

    This dissertation examines three topics in the morphosyntax of Lubukusu (Bantu, Kenya), all of which are concerned with agreement with subjects: locative inversion, complementizer agreement, and alternative agreement effects in subject extraction. Each topic reports novel Lubukusu data which are both typologically interesting and theoretically…

  18. Development and testing of single-shell tank waste retrieval technologies: Milestone M-45-01 summary report

    SciTech Connect

    Shen, E.J.

    1994-08-01

    This report summarizes the activities undertaken to develop single-shell tank (SST) waste retrieval technology and complete scale-model testing. Completion of these activities fulfills the commitment of Milestone M-45-01 of the Hanford Federal Facility Agreement and Consent Order (the Tri-Party Agreement). Initial activities included engineering studies that compiled and evaluated data on all known retrieval technologies. Based on selection criteria incorporating regulatory, safety, and operational issues, several technologies were selected for further evaluation and testing. The testing ranged from small-scale, bench-top evaluations of individual technologies to full-scale integrated tests of multiple subsystems operating concurrently as a system using simulated wastes. The current baseline retrieval method for SSTs is hydraulic sluicing. This method has been used successfully in the past to recover waste from SSTs. Variations of this hydraulic or ``past practice`` sluicing may be used to retrieve the waste from the majority of the SSTs. To minimize the potential for releases to the soil, arm-based retrieval systems may be used to recover waste from tanks that are known or suspected to have leaked. Both hydraulic sluicing and arm-based retrieval will be demonstrated in the first SST. Hydraulic sluicing is expected to retrieve most of the waste, and arm-based retrieval will retrieve wastes that remain after sluicing. Subsequent tanks will be retrieved by either hydraulic sluicing or arm-based methods, but not both. The method will be determined by waste characterization, tank integrity (leak status), and presence of in-tank hardware. Currently, it is assumed that approximately 75% of all SSTs will be retrieved by hydraulic sluicing and the remaining tanks by arm-based methods.

  19. 10 CFR Appendix B to 10 Cfr Part 2 - Model Milestones To Be Used By a Presiding Officer as a Guideline in Developing a Hearing...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the Conduct of an Adjudicatory Proceeding in Accordance With 10 CFR 2.332. I. Model Milestones for a Hearing on an Enforcement Action Conducted Under 10 CFR Part 2, Subpart G These model milestones would... adjudicated in the proceeding. The model milestones are based on the Commission's Rules of Practice in 10...

  20. Completion of Level 4 Milestone M4AT-15OR2301039 for the Johnson Noise Thermometry for Drift-free Temperature Measurements Work Package AT-15OR230103

    SciTech Connect

    Britton Jr, Charles L.

    2015-09-14

    This memorandum constitutes our September 2015 level 4 milestone for the project entitled “Johnson Noise Thermometry for Drift-free Temperature Measurements” and satisfies the Milestone/Activity (Conclude HFIR field demonstration of JNT prototype). The progress summary describes the work performed to complete the subject milestone.

  1. Visualization on supercomputing platform level II ASC milestone (3537-1B) results from Sandia.

    SciTech Connect

    Geveci, Berk; Fabian, Nathan; Marion, Patrick; Moreland, Kenneth D.

    2010-09-01

    This report provides documentation for the completion of the Sandia portion of the ASC Level II Visualization on the platform milestone. This ASC Level II milestone is a joint milestone between Sandia National Laboratories and Los Alamos National Laboratories. This milestone contains functionality required for performing visualization directly on a supercomputing platform, which is necessary for peta-scale visualization. Sandia's contribution concerns in-situ visualization, running a visualization in tandem with a solver. Visualization and analysis of petascale data is limited by several factors which must be addressed as ACES delivers the Cielo platform. Two primary difficulties are: (1) Performance of interactive rendering, which is most computationally intensive portion of the visualization process. For terascale platforms, commodity clusters with graphics processors(GPUs) have been used for interactive rendering. For petascale platforms, visualization and rendering may be able to run efficiently on the supercomputer platform itself. (2) I/O bandwidth, which limits how much information can be written to disk. If we simply analyze the sparse information that is saved to disk we miss the opportunity to analyze the rich information produced every timestep by the simulation. For the first issue, we are pursuing in-situ analysis, in which simulations are coupled directly with analysis libraries at runtime. This milestone will evaluate the visualization and rendering performance of current and next generation supercomputers in contrast to GPU-based visualization clusters, and evaluate the performance of common analysis libraries coupled with the simulation that analyze and write data to disk during a running simulation. This milestone will explore, evaluate and advance the maturity level of these technologies and their applicability to problems of interest to the ASC program. Scientific simulation on parallel supercomputers is traditionally performed in four

  2. TPA induction leads to a Th17-like response in transgenic K14/VEGF mice: a novel in vivo screening model of psoriasis.

    PubMed

    Hvid, Henning; Teige, Ingrid; Kvist, Peter Helding; Svensson, Lars; Kemp, Kåre

    2008-08-01

    Psoriasis is a common chronic inflammatory skin disease, characterized by epidermal hyperplasia, immune cell infiltration, increased dermal angiogenesis and local up-regulation of a variety of inflammatory mediators. Psoriasis is thought to be driven primarily by CD4(+) T cells with a T(h)1 and/or T(h)17 phenotype. Transgenic keratin 14 (K14)/vascular endothelial growth factor (VEGF) mice have previously been reported to develop a psoriasis-like phenotype. The aim of this study was to further characterize the model for validation as an in vivo screening model of psoriasis. Inflammation was induced in the ear skin with five topical applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and a significantly increased inflammation was found in TPA-induced K14/VEGF transgenic animals compared with wild-type mice. The amount of VEGF in the ear tissue was significantly elevated resulting in increased dermal angiogenesis. Furthermore, intense epidermal hyperplasia, CD3(+) infiltration and significantly increased amounts of (TNF) tumor necrosis factor alpha, IL-1 beta, IL-6, IL-12/23p40, IL-12p70, IL-22 and IL-17 were detected in the inflamed ear skin. This cytokine profile strongly suggests a T(h)17-mediated inflammation. All findings were a result of induced over-expression of VEGF. Topical treatment with betamethasone-17-valerate (BMS) significantly reduced ear skin inflammation and epidermal hyperplasia and also decreased the CD3(+) infiltration. In conclusion, the TPA-induced phenotype in K14/VEGF animals displayed several features of psoriasis, including a T(h)17 cytokine profile and a chronic-like progression, and can be used as an in vivo screening model of psoriasis. PMID:18579711

  3. Potential O-acyl-substituted (-)-Epicatechin gallate prodrugs as inhibitors of DMBA/TPA-induced squamous cell carcinoma of skin in Swiss albino mice.

    PubMed

    Vyas, Sandeep; Manon, Benu; Vir Singh, Tej; Dev Sharma, Pritam; Sharma, Manu

    2011-04-01

    (-)-Epicatechin-3-gallate (1) is one of the principal catechins of green tea and exhibits cancer-preventive activities in various animal models. However, this compound is unstable in neutral or alkaline medium and, therefore, has a poor bioavailability. To improve its stability, O-acyl derivatives of 1 were prepared by isolating the partially purified tea catechin fraction from green tea extract and treating it with a variety of acylating agents. The resulting derivatives, compounds 2-6, were screened for their antitumor potential against 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced squamous cell carcinogenesis of skin in mice. The results showed that the antitumor activity decreased with the increase in size of the chain length of the acyl groups, i.e., from compound 2, derivative with an Ac group, to compound 6, possessing a valeryl group. Moreover, the C(4) derivative with a branched acyl chain, 5, had a lower activity than the linear C(4) derivative 4. This reduction in the inhibitory activity may be due to the steric hindrance by the two Me groups. Moreover, significant increases in the protein levels analyzed by ELISA of c-Jun, p65, and p53 were observed in the skin of DMBA/TPA treated mice, whereas mice treated with 2 and DMBA/TPA had a similar expression of these transcription factors than the control mice. The prodrug potential of the O-acyl derivatives 2-6 showed that they were adequately stable to be absorbed intact from the intestine, more stable at gastric pH, and suitable for oral administration. PMID:21480506

  4. Biochemical properties of the kringle 2 and protease domains are maintained in the refolded t-PA deletion variant BM 06.022.

    PubMed

    Kohnert, U; Rudolph, R; Verheijen, J H; Weening-Verhoeff, E J; Stern, A; Opitz, U; Martin, U; Lill, H; Prinz, H; Lechner, M

    1992-01-01

    BM 06.022 is a t-PA deletion variant which comprises the kringle 2 and the protease domain. Production of BM 06.022 in Escherichia coli leads to the formation of inactive inclusion bodies, which have to be refolded by an in vitro refolding process to achieve activity and proper structure of the domains. We analysed the biochemical properties of BM 06.022 to obtain some information about the structure of kringle 2 and the protease as compared with the structure of these domains in the intact t-PA molecule. The kinetic analysis of the amidolytic activity of BM 06.022 and CHO-t-PA yielded similar values for kcat (13.9 s-1 and 11.4 s-1 for the single chain forms and 33.9 s-1 and 27.1 s-1 for the two chain forms of BM 06.022 and CHO-t-PA, respectively) and for Km (2.5 mM and 2.1 mM for the single chains forms and 0.5 mM and 0.3 mM for the two chain forms of BM 06.022 and CHO-t-PA, respectively). BM 06.022 and CHO-t-PA have the same plasminogenolytic activity in the absence of CNBr fragments of fibrinogen. However, BM 06.022 has a lower plasminogenolytic activity in the presence of CNBr fragments of fibrinogen and a lower affinity to fibrin as compared with CHO-t-PA. The affinity of BM 06.022 for fibrin is completely suppressed by 0.3 mM epsilon-aminocaproic acid, while the intact t-PA has a residual affinity of approximately 30%. The dissociation constants for the interaction with the lysine analogue epsilon-aminocaproic acid are 0.10 mM and 0.09 mM for BM 06.022 and the intact t-PA, respectively. Furthermore, BM 06.022 and CHO-t-PA are inhibited by PAI-1 in a similar manner. PMID:1321420

  5. Cornerstone Documents, Milestones, and Policies: Shaping the Direction of Public Health Nursing 1890-1950.

    PubMed

    Kub, Joan; Kulbok, Pamela A; Glick, Doris

    2015-01-01

    The interplay of policy, milestone events, and cornerstone documents was critical in the evolution of the specialty of public health nursing (PHN) from 1890-1950. Using our contemporary lens, this article examines PHN development from an historical perspective, including events and milestones driving growth in the early 20th century. Some of the challenges faced by our founding public health nursing leadership are not unlike challenges we face today. In 1950, Ruth Hubbard, a former leader in the National Organization of Public Health Nurses and Director of the Visiting Nurse Society of Philadelphia, spoke of the value of examining the past to forge a new future. This article calls for contemporary public health nurses to act upon the lessons learned from the past, to strengthen the renewed focus on prevention, to develop policies that impact population health, and to foster a vision that will guide us into the future. PMID:26882422

  6. Milestones in Software Engineering and Knowledge Engineering History: A Comparative Review

    PubMed Central

    del Águila, Isabel M.; Palma, José; Túnez, Samuel

    2014-01-01

    We present a review of the historical evolution of software engineering, intertwining it with the history of knowledge engineering because “those who cannot remember the past are condemned to repeat it.” This retrospective represents a further step forward to understanding the current state of both types of engineerings; history has also positive experiences; some of them we would like to remember and to repeat. Two types of engineerings had parallel and divergent evolutions but following a similar pattern. We also define a set of milestones that represent a convergence or divergence of the software development methodologies. These milestones do not appear at the same time in software engineering and knowledge engineering, so lessons learned in one discipline can help in the evolution of the other one. PMID:24624046

  7. Milestones in software engineering and knowledge engineering history: a comparative review.

    PubMed

    del Águila, Isabel M; Palma, José; Túnez, Samuel

    2014-01-01

    We present a review of the historical evolution of software engineering, intertwining it with the history of knowledge engineering because "those who cannot remember the past are condemned to repeat it." This retrospective represents a further step forward to understanding the current state of both types of engineerings; history has also positive experiences; some of them we would like to remember and to repeat. Two types of engineerings had parallel and divergent evolutions but following a similar pattern. We also define a set of milestones that represent a convergence or divergence of the software development methodologies. These milestones do not appear at the same time in software engineering and knowledge engineering, so lessons learned in one discipline can help in the evolution of the other one. PMID:24624046

  8. Post-processing V&V level II ASC milestone (2360) results.

    SciTech Connect

    Chavez, Elmer; Karelitz, David B.; Brunner, Thomas A.; Trucano, Timothy Guy; Moreland, Kenneth D.; Weirs, V. Gregory; Shead, Timothy M.

    2007-09-01

    The 9/30/2007 ASC Level 2 Post-Processing V&V Milestone (Milestone 2360) contains functionality required by the user community for certain verification and validation tasks. These capabilities include loading of edge and face data on an Exodus mesh, run-time computation of an exact solution to a verification problem, delivery of results data from the server to the client, computation of an integral-based error metric, simultaneous loading of simulation and test data, and comparison of that data using visual and quantitative methods. The capabilities were tested extensively by performing a typical ALEGRA HEDP verification task. In addition, a number of stretch criteria were met including completion of a verification task on a 13 million element mesh.

  9. 75 FR 40837 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ....gov . Agreement No.: 011279-027. Title: Latin America Agreement. Parties: ABC Discussion Agreement; Caribbean Shipowners Association; Central America Discussion Agreement; Compania Libra de Navegacion Uruguay S.A.; Inland Shipping Services Association; Venezuelan Discussion Agreement; West Coast of...

  10. Agreements at the Pharmaceutical/University Interface.

    ERIC Educational Resources Information Center

    Ku, Katherine

    1987-01-01

    Specific agreements that arise at the interface between universities and pharmaceutical companies are described including sponsored research agreements, license agreements, clinical study agreements, material transfer agreements, and patient consent forms with respect to commercialization rights. (Author/MLW)

  11. The early antibiotic therapy in septic patients--milestone or sticking point?

    PubMed

    Bernhard, Michael; Lichtenstern, Christoph; Eckmann, Christian; Weigand, Markus A

    2014-01-01

    Sepsis is one of the oldest and most elusive syndromes in medicine. Every effort should be made to treat these patients with the best available evidence. As a milestone, empiric antimicrobial therapy is essential in order to reduce morbidity and mortality of septic patients. As a sticking point, the use of broad-spectrum antimicrobial agents may be associated with induction of resistance among common pathogens. PMID:25672873

  12. Apollo experience report the command and service module milestone review process

    NASA Technical Reports Server (NTRS)

    Brendle, H. L.; York, J. A.

    1974-01-01

    The sequence of the command and service module milestone review process is given, and the Customer Acceptance Readiness Review and Flight Readiness Review plans are presented. Contents of the System Summary Acceptance Documents for the two formal spacecraft reviews are detailed, and supplemental data required for presentation to the review boards are listed. Typical forms, correspondence, supporting documentation, and minutes of a board meeting are included.

  13. Preparing medical students for obstetrics and gynecology milestone level one: a description of a pilot curriculum

    PubMed Central

    Morgan, Helen; Marzano, David; Lanham, Michael; Stein, Tamara; Curran, Diana; Hammoud, Maya

    2014-01-01

    Background The implementation of the Accreditation Council for Graduate Medical Education (ACGME) Milestones in the field of obstetrics and gynecology has arrived with Milestones Level One defined as the level expected of an incoming first-year resident. Purpose We designed, implemented, and evaluated a 4-week elective for fourth-year medical school students, which utilized a multimodal approach to teaching and assessing the Milestones Level One competencies. Methods The 78-hour curriculum utilized traditional didactic lectures, flipped classroom active learning sessions, a simulated paging curriculum, simulation training, embalmed cadaver anatomical dissections, and fresh-frozen cadaver operative procedures. We performed an assessment of student knowledge and surgical skills before and after completion of the course. Students also received feedback on their assessment and management of eight simulated paging scenarios. Students completed course content satisfaction surveys at the completion of each of the 4 weeks. Results Students demonstrated improvement in knowledge and surgical skills at the completion of the course. Paging confidence trended toward improvement at the completion of the course. Student satisfaction was high for all of the course content, and the active learning components of the curriculum (flipped classroom, simulation, and anatomy sessions) had higher scores than the traditional didactics in all six categories of our student satisfaction survey. Conclusions This pilot study demonstrates a practical approach for preparing fourth-year medical students for the expectations of Milestones Level One in obstetrics and gynecology. This curriculum can serve as a framework as medical schools and specific specialties work to meet the first steps of the ACGME's Next Accreditation System. PMID:25430640

  14. Yang-Mills Theory at 60: Milestones, Landmarks and Interesting Questions

    NASA Astrophysics Data System (ADS)

    Chau, Ling-Lie

    On the auspicious occasion of celebrating the 60th anniversary of the Yang-Mills theory, and Professor Yang's many other important contributions to physics and mathematics, I will highlight the impressive milestones and landmarks that have been established in the last 60 years, as well as some interesting questions that are worthy of answers from future researches. The paper is written (without equations) for the interest of non-scientists as well as of scientists.

  15. Yang-Mills theory at 60: Milestones, landmarks and interesting questions

    NASA Astrophysics Data System (ADS)

    Chau, Ling-Lie

    2015-12-01

    On the auspicious occasion of celebrating the 60th anniversary of the Yang-Mills theory, and Professor Yang’s many other important contributions to physics and mathematics, I will highlight the impressive milestones and landmarks that have been established in the last 60 years, as well as some interesting questions that still lie before us. The paper is written (without equations) for the interest of non-scientists as well as of scientists.

  16. From theory to practice: making entrustable professional activities come to life in the context of milestones.

    PubMed

    Englander, Robert; Carraccio, Carol

    2014-10-01

    Entrustable professional activities (EPAs) are gaining traction across the globe as a practical way to teach and assess competencies in the clinical setting. Full-scale implementation, though, has only taken place in obstetrics-gynecology in the Netherlands and in psychiatry in Australia and New Zealand. As with any conceptual framework, implementation in different contexts will require adaptations. For example, implementation in the United States will need to incorporate the Accreditation Council for Graduate Medical Education's competencies and the recently completed milestones for each of the specialties. In this issue, an article by Aylward and colleagues describes the process for implementing a handoff communication EPA, using milestones as the basis for the assessment tool. The explicit linkage of the milestones with the EPA assessment allows a more definitive "picture" of the learner to emerge at each advancing level of performance of the EPA. This "picture" can be shared with those directly observing the learner and thus provides a potential model for a more reliable assessment of learners performing EPAs and perhaps a more consistent approach to entrustment decisions. The authors hope that Aylward and colleagues' article will be one of many that aim to help the medical education community understand how to implement EPAs as a framework for competency demonstration, as educators try to determine what works, under what conditions and in what settings. Only through a committed effort to share lessons learned can the promise of the theory be translated to practice in the field. PMID:24892405

  17. Collaborative Negotiations: A Successful Approach for Negotiation Compliance Milestones for the transition of the PFP Hanford Nuclear Reservation

    SciTech Connect

    HOPKINS, A.M.

    2003-02-01

    The new approach to negotiations was termed collaborative (win-win) rather than positional (win-lose). Collaborative negotiations were conducted to establish milestones for the decommissioning of the Plutonium Finishing Plant, PFP.

  18. 20 CFR 411.580 - Can an EN receive payments for milestones or outcome payment months that occur before the...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....580 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.580 Can an EN receive payments for milestones or outcome...

  19. Milestones in Medical Research, The Human Genome and ClinicalTrials.gov | NIH MedlinePlus the Magazine

    MedlinePlus

    ... first, a major milestone in understanding the genetic foundation of all human beings; the second, a comprehensive ... out more about the importance of clinical trials starting on page 4 . Our cover story in this ...

  20. Skills agreement. Recipe for success.

    PubMed

    Nolan, Alexis

    2007-06-21

    The aims of the national health Sector Skills Agreement need regional and local implementation by stakeholders to become reality. Work in the East of England will produce a first regional skills agreement later this year. The Harlow Project is producing award winning process on recuitment and retention. PMID:17847967

  1. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    PubMed Central

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; Sano, T.; Kodama, R.

    2016-01-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions. PMID:27193942

  2. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    NASA Astrophysics Data System (ADS)

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; Sano, T.; Kodama, R.

    2016-05-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.

  3. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals.

    PubMed

    Ozaki, N; Nellis, W J; Mashimo, T; Ramzan, M; Ahuja, R; Kaewmaraya, T; Kimura, T; Knudson, M; Miyanishi, K; Sakawa, Y; Sano, T; Kodama, R

    2016-01-01

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). These results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. The systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions. PMID:27193942

  4. The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

    PubMed

    Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

    2016-08-17

    Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. PMID:27435387

  5. Absolute Hugoniot measurements of polystyrene between 3 and 12 TPa using radiography of a converging shock at the National Ignition Facility

    NASA Astrophysics Data System (ADS)

    Doeppner, T.; Kritcher, A. L.; Swift, D. C.; Bachmann, B.; Hawreliak, J.; Colllins, G. W.; Glenzer, S.; Rothman, S. D.; Kraus, D.; Falcone, R. W.

    2015-06-01

    A converging shock was induced with hohlraum-driven soft x-ray radiation on a solid, spherical sample of poly alpha-methyl styrene. The time-history of density profiles through the sample was measured by x-ray radiography using a laser-heated backlighter and a streak camera, viewing a diameter across the sample through slots in the hohlraum wall. Profile-matching in radius and time was used to increase the accuracy of density inferred from the transmission. The speed and compression of the shock were measured from the density profiles. The shock pressure increased with convergence, so a range of Hugoniot states was obtained from a single experiment. Using a laser power based on the early part of a ``high foot'' pulse from ignition experiments, the low end of the pressure range was brought down to 2 TPa, overlapping states accessible by experiments in plane geometry, and ensuring that the opacity of the compressed sample was the same as for unshocked material, simplifying the analysis. Shock states were measured up to 12 TPa, when the shock was close to the center of the sample. This is several times higher than has been obtained by other methods and is an absolute measurement. Performed under the auspices of the US DOE by LLNL under Contract DE-AC52-07NA27344.

  6. Dynamic compression of dense oxide (Gd3Ga5O12) from 0.4 to 2.6 TPa: Universal Hugoniot of fluid metals

    DOE PAGESBeta

    Ozaki, N.; Nellis, W. J.; Mashimo, T.; Ramzan, M.; Ahuja, R.; Kaewmaraya, T.; Kimura, T.; Knudson, M.; Miyanishi, K.; Sakawa, Y.; et al

    2016-05-19

    Materials at high pressures and temperatures are of great current interest for warm dense matter physics, planetary sciences, and inertial fusion energy research. Shock-compression equation-of-state data and optical reflectivities of the fluid dense oxide, Gd3Ga5O12 (GGG), were measured at extremely high pressures up to 2.6 TPa (26 Mbar) generated by high-power laser irradiation and magnetically-driven hypervelocity impacts. Above 0.75 TPa, the GGG Hugoniot data approach/reach a universal linear line of fluid metals, and the optical reflectivity most likely reaches a constant value indicating that GGG undergoes a crossover from fluid semiconductor to poor metal with minimum metallic conductivity (MMC). Thesemore » results suggest that most fluid compounds, e.g., strong planetary oxides, reach a common state on the universal Hugoniot of fluid metals (UHFM) with MMC at sufficiently extreme pressures and temperatures. Lastly, the systematic behaviors of warm dense fluid would be useful benchmarks for developing theoretical equation-of-state and transport models in the warm dense matter regime in determining computational predictions.« less

  7. Toddlers’ Fine Motor Milestone Achievement Is Associated with Early Touchscreen Scrolling

    PubMed Central

    Bedford, Rachael; Saez de Urabain, Irati R.; Cheung, Celeste H. M.; Karmiloff-Smith, Annette; Smith, Tim J.

    2016-01-01

    Touchscreen technologies provide an intuitive and attractive source of sensory/cognitive stimulation for young children. Despite fears that usage may have a negative impact on toddlers’ cognitive development, empirical evidence is lacking. The current study presents results from the UK Toddler Attentional Behaviours and LEarning with Touchscreens (TABLET) project, examining the association between toddlers’ touchscreen use and the attainment of developmental milestones. Data were gathered in an online survey of 715 parents of 6- to 36-month-olds to address two research questions: (1) How does touchscreen use change from 6 to 36 months? (2) In toddlers (19–36 months, i.e., above the median age, n = 366), how does retrospectively reported age of first touchscreen usage relate to gross motor (i.e., walking), fine motor (i.e., stacking blocks), and language (i.e., producing two-word utterances) milestones? In our sample, the proportion of children using touchscreens, as well as the average daily usage time, increased with age (youngest quartile, 6–11 months: 51.22% users, 8.53 min per day; oldest quartile, 26–36 months: 92.05% users, average use of 43.95 min per day). In toddlers, aged 19–36 months, age of first touchscreen use was significantly associated with fine motor (stacking blocks), p = 0.03, after controlling for covariates age, sex, mother’s education (a proxy for socioeconomic status) as well as age of early fine motor milestone achievement (pincer grip). This effect was only present for active scrolling of the touchscreen p = 0.04, not for video watching. No significant relationships were found between touchscreen use and either gross motor or language milestones. Touchscreen use increases rapidly over the first 3 years of life. In the current study, we find no evidence to support a negative association between the age of first touchscreen usage and developmental milestones. Indeed, earlier touchscreen use, specifically scrolling of the screen

  8. Toddlers' Fine Motor Milestone Achievement Is Associated with Early Touchscreen Scrolling.

    PubMed

    Bedford, Rachael; Saez de Urabain, Irati R; Cheung, Celeste H M; Karmiloff-Smith, Annette; Smith, Tim J

    2016-01-01

    Touchscreen technologies provide an intuitive and attractive source of sensory/cognitive stimulation for young children. Despite fears that usage may have a negative impact on toddlers' cognitive development, empirical evidence is lacking. The current study presents results from the UK Toddler Attentional Behaviours and LEarning with Touchscreens (TABLET) project, examining the association between toddlers' touchscreen use and the attainment of developmental milestones. Data were gathered in an online survey of 715 parents of 6- to 36-month-olds to address two research questions: (1) How does touchscreen use change from 6 to 36 months? (2) In toddlers (19-36 months, i.e., above the median age, n = 366), how does retrospectively reported age of first touchscreen usage relate to gross motor (i.e., walking), fine motor (i.e., stacking blocks), and language (i.e., producing two-word utterances) milestones? In our sample, the proportion of children using touchscreens, as well as the average daily usage time, increased with age (youngest quartile, 6-11 months: 51.22% users, 8.53 min per day; oldest quartile, 26-36 months: 92.05% users, average use of 43.95 min per day). In toddlers, aged 19-36 months, age of first touchscreen use was significantly associated with fine motor (stacking blocks), p = 0.03, after controlling for covariates age, sex, mother's education (a proxy for socioeconomic status) as well as age of early fine motor milestone achievement (pincer grip). This effect was only present for active scrolling of the touchscreen p = 0.04, not for video watching. No significant relationships were found between touchscreen use and either gross motor or language milestones. Touchscreen use increases rapidly over the first 3 years of life. In the current study, we find no evidence to support a negative association between the age of first touchscreen usage and developmental milestones. Indeed, earlier touchscreen use, specifically scrolling of the screen, was

  9. Use of Developmental Milestones in Pediatric Residency Training and Practice: Time to Rethink the Meaning of the Mean

    PubMed Central

    Sices, Laura

    2009-01-01

    Objective Pediatricians frequently report the use of developmental milestones in monitoring young children’s development, despite evidence that use of screening tools improves detection of developmental delays. Methods Core texts in the field of pediatrics and developmental-behavioral pediatrics were reviewed for content and presentation on child development. Most texts included and many focused on developmental milestones, many with an emphasis on 50th percentile milestone data. Problems and limitations in the use of 50th percentile milestones to monitor young children’s development and to identify children whose development is suspicious for delay, include questionable utility in clinical decision making and the potential to increase parental anxiety. Results The recommendation is made to reconsider a focus on 50th percentile milestone data in pediatric training and practice, in favor of measures that have better clinical utility and are more psychometrically sound. Conclusion A conceptual approach to the presentation of developmental milestones differentiates the use of the 10th, 50th, and 90th percentiles of age of achievement of skills, based on the clinical purpose of surveillance. PMID:17353732

  10. Suspension agreements: The status quota

    SciTech Connect

    1996-01-01

    Since the initial filing of anti-dumping actions uranium imports from the former Soviet Union, a maze of filings, agreements, amendments, bills, measures, and deals have emerged on which only the closest observers remain current. Even with all the actions that have taken place, none of the parties appear content with the status quo and changes to the agreements are ongoing. Given this dynamic state of affairs, a recap of events and a summary of the current agreements is helpful for understanding the concerns of the involved parties and digesting future events.

  11. OPEC agreement and its implications

    SciTech Connect

    Not Available

    1983-01-01

    Following lengthy and intensive negotiations, OPEC recently reached agreement on new prices and production quotas. Although the agreement has been met by general skepticism, Bankers Trust believes that the chances of defending the new marker price are reasonably good. Saudi willingness to reduce oil production and earnings to shield less financially secure OPEC members from the full impact of production cuts provides added and much-needed strength to the organization. If indeed the OPEC agreement proves successful, product prices in the important US market may have already bottomed out.

  12. 76 FR 30360 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ....gov . Agreement No.: 011707-007. Title: Gulf/South America Discussion Agreement. Parties: BBC... Cooperative Working Agreement. Parties: COSCO Terminals America, Inc.; SSA Containers, Inc., and SSA...

  13. Cerebroprotective effects of TAK-937, a novel cannabinoid receptor agonist, in permanent and thrombotic focal cerebral ischemia in rats: therapeutic time window, combination with t-PA and efficacy in aged rats.

    PubMed

    Murakami, Koji; Suzuki, Motohisa; Suzuki, Noriko; Hamajo, Kazuhiro; Tsukamoto, Tetsuya; Shimojo, Masato

    2013-08-14

    Some occluded arteries of acute ischemic stroke (AIS) patients are not recanalized, even if thrombolytic therapy is performed. Considering such clinical settings, we examined the potential cerebroprotective efficacy of TAK-937, a novel cannabinoid receptor agonist, in young adult and aged rats with a permanent middle cerebral artery occlusion (MCAO) model and conducted a combination study with TAK-937 and tissue type plasminogen activator (t-PA) in a rat thrombotic MCAO model. TAK-937 significantly reduced infarct volume when it was administered 3 and 5h after permanent MCAO in young adult rats. A thrombotic MCAO was induced by photo-irradiation of the middle cerebral artery with Rose Bengal administration and a permanent MCAO was produced by thermoelectric coagulation of occluded arteries. TAK-937 (10, 30 and 100μg/kg/h) was intravenously infused 1, 3, 5, or 8-24h after MCAO. t-PA (3 or 10mg/kg) was intravenously administered 1, 1.5 or 2h after MCAO. Infarct volume was determined using a 2,3,5-triphenyltetrazolium chloride staining method 24 or 48h after MCAO. The combined treatment of TAK-937 with t-PA significantly reduced the cerebral infarction compared with t-PA treatment alone in a rat thrombotic MCAO model. TAK-937 reduced infarct volume of aged rats as well, when it was administered 1h after permanent MCAO. These results suggest that TAK-937 exerts protective effects regardless of age and has a wide therapeutic time window in permanent occlusion. Furthermore, combined treatment of TAK-937 with t-PA would provide more therapeutic efficacy compared to t-PA treatment alone. PMID:23791950

  14. Developmental Milestones

    MedlinePlus

    ... think there’s a problem. Watch the video » Child Development: It’s Better to Know (in Spanish) Learn why ... to do if you have concerns about your child's development. Watch this Spanish language video » Related Pages ...

  15. GME Milestone.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Thanks to years of TMA advocacy, the 2015 legislature more than tripled 2013 graduate medical education monies under an expansion initiative to help secure a pathway for doctors-in-training to enter the workforce. PMID:27532810

  16. Preemie Milestones

    MedlinePlus

    ... should be doing at this age. At 2 Months (8 Weeks) Motor Moves hands and legs actively ... interactions with mother or primary caregiver At 4 Months (16 Weeks) Motor Brings hands together, or to ...

  17. 12-O-Tetradecanoyl phorbol-13-acetate (TPA)-induced growth arrest is increased by silibinin by the down-regulation of cyclin B1 and cdc2 and the up-regulation of p21 expression in MDA-MB231 human breast cancer cells.

    PubMed

    Kim, Sangmin; Lee, Hye Sook; Lee, Se-Kyung; Kim, Sung Hoon; Hur, Sung Mo; Kim, Jee Soo; Kim, Jung-Han; Choe, Jun-Ho; Shin, Incheol; Yang, Jung-Hyun; Lee, Jeong Eon; Nam, Seok Jin

    2010-12-01

    TPA is a potent regulator of cell growth, including cell proliferation and differentiation. In this study, we determined the effect of silibinin on TPA-induced growth arrest in breast cancer cells. Silibinin increased growth arrest of the G2/M phase in a dose-dependent fashion. Silibinin decreased the basal level of cyclin B1 and cdc2 expression, which is involved in S phase and G2/M transition. In addition, TPA-induced G2/M phase arrest was increased by silibinin. Under the same conditions, TPA-induced down-regulation of cyclin B1 and cdc2 was decreased by silibinin. In contrast, TPA-induced p21 expression was further increased by silibinin. To determine the regulatory mechanism of TPA-induced growth arrest, we pretreated cells with various inhibitors, such as UO126, SB203580, and LY294002. Interestingly, TPA-induced growth arrest was significantly increased by LY294002, but not by UO126 and SB203580. In addition, TPA-induced down-regulation of cyclin B1 was inhibited by LY294002; however, the basal level of p21 was increased by TPA and TPA-induced p21 expression was further increased by LY294002. Finally, adenoviral constitutively active-Akt (Ad-CA-Akt) overexpression regulated the up-regulation of cyclin B1 and the down-regulation of p21. Therefore, we have demonstrated that silibinin has an additive effect on TPA-induced growth arrest through the PI-3-kinase/Akt-dependent pathway. PMID:20554189

  18. Quick Guide: Power Purchase Agreements

    SciTech Connect

    2010-06-25

    Introduction to Federal power purchase agreements (PPAs), including available FEMP services and technical assistance as well as questions to ask when evaluating PPAs for a Federal renewable energy project.

  19. Good Agreements Make Good Friends

    PubMed Central

    Han, The Anh; Pereira, Luís Moniz; Santos, Francisco C.; Lenaerts, Tom

    2013-01-01

    When starting a new collaborative endeavor, it pays to establish upfront how strongly your partner commits to the common goal and what compensation can be expected in case the collaboration is violated. Diverse examples in biological and social contexts have demonstrated the pervasiveness of making prior agreements on posterior compensations, suggesting that this behavior could have been shaped by natural selection. Here, we analyze the evolutionary relevance of such a commitment strategy and relate it to the costly punishment strategy, where no prior agreements are made. We show that when the cost of arranging a commitment deal lies within certain limits, substantial levels of cooperation can be achieved. Moreover, these levels are higher than that achieved by simple costly punishment, especially when one insists on sharing the arrangement cost. Not only do we show that good agreements make good friends, agreements based on shared costs result in even better outcomes. PMID:24045873

  20. Application Agreement and Integration Services

    NASA Technical Reports Server (NTRS)

    Driscoll, Kevin R.; Hall, Brendan; Schweiker, Kevin

    2013-01-01

    Application agreement and integration services are required by distributed, fault-tolerant, safety critical systems to assure required performance. An analysis of distributed and hierarchical agreement strategies are developed against the backdrop of observed agreement failures in fielded systems. The documented work was performed under NASA Task Order NNL10AB32T, Validation And Verification of Safety-Critical Integrated Distributed Systems Area 2. This document is intended to satisfy the requirements for deliverable 5.2.11 under Task 4.2.2.3. This report discusses the challenges of maintaining application agreement and integration services. A literature search is presented that documents previous work in the area of replica determinism. Sources of non-deterministic behavior are identified and examples are presented where system level agreement failed to be achieved. We then explore how TTEthernet services can be extended to supply some interesting application agreement frameworks. This document assumes that the reader is familiar with the TTEthernet protocol. The reader is advised to read the TTEthernet protocol standard [1] before reading this document. This document does not re-iterate the content of the standard.

  1. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are..., sex, or disability. (d) What is the duration of required agreements? Agreements between FNS and...

  2. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are..., sex, or disability. (d) What is the duration of required agreements? Agreements between FNS and...

  3. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are..., sex, or disability. (d) What is the duration of required agreements? Agreements between FNS and...

  4. 76 FR 31962 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ....gov . Agreement No.: 012128. Title: Southern Africa Agreement A Cooperative Working Agreement. Parties... Atlantic Coast of the United States and ports in the Bahamas and the Republic of South Africa. Agreement...

  5. 77 FR 33459 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-06

    ... to be exchanged, and delete obsolete language from the agreement. Agreement No.: 012128-001. Title... Agreement and to share the cost of same. Agreement No.: 012173. Title: Hyundai/MOL/APL Asia/Latin...

  6. Effects of garlic on cellular doubling time and DNA strand breaks caused by UV light and BPL, enhanced with catechol and TPA

    SciTech Connect

    Baturay, N.Z.; Gayle, F.; Liu, S.; Kreidinger, C.

    1995-11-01

    3T3 cell cultures were exposed to UV light and Beta-Propiolactone. Neoplastic cell transformation (TF) was demonstrated after concurrent addition of catechol, or repeated addition of TPA. Addition of garlic to all fluences/concentrations of the carcinogen/cocarcinogen/promoter groups reduced the number of transformed foci/dish by at least 40%. Since the cell cycle is prolonged following exposure to carcinogens, it is likely the cell requires a longer time to repair this damage. The doubling time (DT) was extended from 12 to 36 hrs. when cells were exposed to BPL and from 12 o 28 hrs. when cells were exposed to 3.0J/M2/sec. If an anticarcinogenic compound is also added, it is reasonable to assume that the cell cycle may be further elongated. The cell cycle, denoted by DT was lengthened from 12 to 47 hrs and from 12 to 86 hrs for BPL and UVC, respectively. The extensions occurred in a dope dependent manner. The concentrations of the cocarcinogen and promoter remained constant throughout the experiment. When strand breaks were determined at the same dose sequences, by alkaline elution, more repair was seen with garlic where the lowest and middle doses of BPL were used and almost no decrease in % DNA eluted was seen with UVC exposed cells. With catechol, there was a two-fold decrease in % DNA eluted at the lowest and middle fluences. When TPA was added, all three fluences of UVC showed more than a threefold decrease in % DNA eluted. BPS with both TPA and catechol, again showed a reduction in strand breaks only low and middle doses. Both a direct-acting alkylating agent, BPL, and a physical carcinogen, UVC, were homogeneously affected, in terms of doubling time, but not when strand break repair was examined. A separate mechanism may be responsible for repair, and the mechanism associated with combinations of physical carcinogen enhancing agents combined with some non-carcinogens may be more profoundly affected by some natural products.

  7. THE COST OF POSITIONAL NEGOTIATIONS VERSUS COLLABORATIVE OR RELATIONAL NEGOTIATIONS FOR NEGOTIATING COMPLIANCE MILESTONES AT HANFORD WA

    SciTech Connect

    HOPKINS, A.M.

    2004-02-26

    The Hanford site is subject to the Hanford Federal Facility Agreement and Consent Order (HFFACO), an order on consent signed by the DOE, the U. S. Environmental Protection Agency, (EPA) and the Washington Department of Ecology (WDOE). Under the HFFCCO, negotiations for transition milestones begin within six months after the issuance of a shutdown order. In the case of the PFP, the Nuclear Materials disposition and stabilization activities, a DOE responsibility, were necessary as precursor activities to Transition. This situation precipitated a crisis in the negotiations between the agencies, and formal negotiations initiated in 1997 ended in failure. The negotiations reached impasse on several key regulatory and operational issues. The 1997 negotiation was characterized by a strongly positional style. DOE and the regulatory personnel took hard lines early in the negotiations and were unable to move to resolution of key issues after a year and a half. This resulted in unhappy stakeholders, poor publicity, and work delays as well as wounded relationships between DOE and the regulatory community. The PFP is a former plutonium metal production facility. The operating mission of the PFP ended with a DOE Headquarters shutdown letter in October of 1996. Generally, the receipt of a shutdown letter initiates the start of Transition (as the first step of Decommissioning) of a facility. In the 2000-2001 PFP negotiations, a completely different approach was suggested and eventually initiated: Collaborative or Relational Negotiations. The relational negotiation style resulted in agreement between the agencies on all key issues within 6 months of initiation. All parties were very pleased with the results and all parties were relieved that protracted negotiations sessions were not needed with the new style of working together collaboratively to serve each other's interests without compromising each party's needs. The characteristics of collaborative negotiations included building

  8. Piloting a Structured Practice Audit to Assess ACGME Milestones in Written Handoff Communication in Internal Medicine

    PubMed Central

    Martin, Shannon K.; Farnan, Jeanne M.; McConville, John F.; Arora, Vineet M.

    2015-01-01

    Background Written communication skills are integral to patient care handoffs. Residency programs require feasible assessment tools that provide timely formative and summative feedback, ideally linked to the Accreditation Council for Graduate Medical Education Milestones. Objective We describe the use of 1 such tool—UPDATED—to assess written handoff communication skills in internal medicine interns. Methods During 2012–2013, the authors piloted a structured practice audit at 1 academic institution to audit written sign-outs completed by 45 interns, using the UPDATED tool, which scores 7 aspects of sign-out communication linked to milestones. Intern sign-outs were audited by trained faculty members throughout the year. Results were incorporated into intern performance reviews and Clinical Competency Committees. Results A total of 136 sign-outs were audited (averaging 3.1 audits per intern). In the first trimester, 14 interns (31%) had satisfactory audit results. Five interns (11%) had critical deficiencies and received immediate feedback, and the remaining 26 (58%) were assigned future audits due to missing audits or unsatisfactory scores. In the second trimester, 21 interns (68%) had satisfactory results, 1 had critical deficiencies, and 9 (29%) required future audits. Nine of the 10 remaining interns in the final trimester had satisfactory audits. Faculty time was estimated at 10 to 15 minutes per sign-out audited. Conclusions The UPDATED audit is a milestone-based tool that can be used to assess written sign-out communication skills in internal medicine residency programs. Future work is planned to adapt the tool for use by senior supervisory residents to appraise sign-outs in real time. PMID:26221442

  9. 1.2.1.1 Harvest, Collection and Storage Quarter 3 Milestone Report

    SciTech Connect

    Lynn M Wendt; William A Smith; Kara G Cafferty; Ian J Bonner; Qiyang Huang; Rachel D Colby

    2014-07-01

    Single pass baling of corn stover is required in order to meet targets for the herbaceous biomass 2017 logistics design case. Single-pass pass stover harvest is based on the grain harvest and generally results in stover with a moisture content of 30-50% wet basis (w.b). Aerobic storage of corn stover with high moisture results in high levels of dry matter loss (DML), up to 25%. Anaerobic storage (ensiling) reduces DML to less than 5%, but additional costs are associated with handling and transporting the extra moisture in the biomass. This milestone provides a best-estimate of costs for using high moisture feedstock within the conventional baled logistics system. The costs of three (3) anaerobic storage systems that reduce dry matter losses (bale wrap, silage tube, and silage drive over pile) are detailed in this milestone and compared to both a conventional dry-baled corn stover case and a high moisture bale case, both stored aerobically. The total logistics cost (harvest, collection, storage, and transportation) of the scenarios are as follows: the conventional multi-pass dry bale case and the single-pass high moisture case stored aerobically were nearly equivalent at $61.15 and $61.24/DMT. The single-pass bale wrap case was the lowest at $57.63/DMT. The bulk anaerobic cases were the most expensive at $84.33 for the silage tube case and $75.97 for the drive over pile, which reflect the additional expense of transporting high-moisture bulk material; however, a reduction in preprocessing costs may occur because these feedstocks are size reduced in the field. In summary, the costs estimates presented in this milestone report can be used to determine if anaerobic storage of high-moisture corn stover is an economical option for dry matter preservation.

  10. Completion of Hanford Tanks Initiative characterization milestone T04-98-523

    SciTech Connect

    IWATATE, D.F.

    1998-10-23

    The HTI subsurface characterization task will use the Hanford Cone Penetrometer platform (CPP) to deploy soil sensor and sampling probes into the vadose zone/soils around AX-104 during FY-99. This document provides copies of the first data collected from the HTI sensor probes during vendor field developmental tests performed at a Cold test site in the Hanford 200 East area. Conduct of the initial test also established completion of a major contractor milestone of the HTI Characterization task (MS T04-98-523: Complete preparation of the HTICP probes and transfer to Hanford/HTI. Conduct an initial MSP push using the CPP).

  11. The case for a milestone-based simulation curriculum in modern neuroendovascular training.

    PubMed

    Spiotta, Alejandro M; Turner, Raymond D; Turk, Aquilla S; Chaudry, M Imran

    2016-04-01

    The role of simulation in formal neuroendovascular training has not been defined. This report details the general principles underlying the use of simulation in training, the critical aspects of the simulation environment which would aid it as a teaching tool specific to the field of neuroendovascular care, summarizes the available evidence to support a milestone-based curriculum, and outlines an example of what such a curriculum would entail. Building on these foundations, we articulate the rationale for the development and widespread adoption of a simulation curriculum for formal neuroendovascular training. PMID:25646131

  12. Gender agreement and multiple referents

    PubMed Central

    Finocchiaro, Chiara; Mahon, Bradford Z.; Caramazza, Alfonso

    2010-01-01

    We report a new pattern of usage in current, spoken Italian that has implications for both psycholinguistic models of language production and linguistic theories of language change. In Italian, gender agreement is mandatory for both singular and plural nouns. However, when two or more nouns of different grammatical gender appear in a conjoined noun phrase (NP), masculine plural agreement is required. In this study, we combined on-line and off-line methodologies in order to assess the mechanisms involved in gender marking in the context of multiple referents. The results of two pronoun production tasks showed that plural feminine agreement was significantly more difficult than plural masculine agreement. In a separate study using offline judgements of acceptability, we found that agreement violations in Italian are tolerated more readily in the case of feminine conjoined noun phrases (e.g., la mela e la banana ‘the:fem apple:fem and the: fem banana: fem’) than masculine conjoined noun phrases (e.g., il fiore e il libro ‘the:mas flower: mas and the:mas book:mas’). Implications of these results are discussed both at the level of functional architecture within the language production system and at the level of changes in language use.* PMID:21037930

  13. Synthesis, fine structure of 19F NMR and fluorescence of novel amorphous TPA derivatives having perfluorinated cyclopentenyl and benzo[b]thiophene unit

    NASA Astrophysics Data System (ADS)

    Wu, Bian-Peng; Pang, Mei-Li; Tan, Ting-Feng; Meng, Ji-ben

    2013-04-01

    Three novel triphenylamine (TPA) derivatives having perfluorinated cyclopentenyl and benzo[b]thiophene unit are obtained from 4-bromo-N,N-diphenyl-2-methylbenzo[b]thiophen-5-amine. The new compounds are expected to find their use in thin film devices as charge transport materials and host organic light-emitting materials. It is found that the new compounds show relatively strong fluorescence either in solution or in solid state, and are amorphous due to a special conformation which is elucidated by the fine structure of 19F NMR. Molecular structure and properties of these compounds is characterized by 1H NMR, 13C NMR (broadband decoupled), ESI-HRMS, elemental analysis and thermal analysis (DSC). Fluorescent quantum yield in solution is measured using 9,10-diphenylanthrancene (DPA) as standard fluorescent substance.

  14. Anti-tissue plasminogen activator (tPA) as an effective therapy of neonatal hypoxia-ischemia with and without inflammation.

    PubMed

    Yang, Dianer; Kuan, Chia-Yi

    2015-04-01

    Hypoxic-ischemic brain injury is an important cause of neurodevelopmental deficits in neonates. Intrauterine infection and the ensuing fetal inflammatory responses augment hypoxic-ischemic brain injury and attenuate the efficacy of therapeutic hypothermia. Here, we review evidences from preclinical studies suggesting that the induction of brain parenchymal tissue-type plasminogen activator (tPA) plays an important pathogenic role in these conditions. Moreover, administration of a stable-mutant form of plasminogen activator inhibitor-1 called CPAI confers potent protection against hypoxic-ischemic injury with and without inflammation via different mechanisms. Besides intracerebroventricular injection, CPAI can also be administered into the brain using a noninvasive intranasal delivery strategy, adding to its applicability in clinical use. In sum, the therapeutic potential of CPAI in neonatal care merits further investigation with large-animal models of hypoxia-ischemia and cerebral palsy. PMID:25475942

  15. Experience and Grammatical Agreement: Statistical Learning Shapes Number Agreement Production

    ERIC Educational Resources Information Center

    Haskell, Todd R.; Thornton, Robert; MacDonald, Maryellen C.

    2010-01-01

    A robust result in research on the production of grammatical agreement is that speakers are more likely to produce an erroneous verb with phrases such as "the key to the cabinets", with a singular noun followed by a plural one, than with phrases such as "the keys to the cabinet", where a plural noun is followed by a singular. These asymmetries are…

  16. Table-top Generation and Spectroscopic Study of ~10 TPa High-Energy Density Materials with C60 Hypervelocity (v ~ 100 km/s) Impact

    NASA Astrophysics Data System (ADS)

    Bae, Young

    2013-06-01

    Intense bursts of soft x-rays were discovered by Bae et al. in hypervelocity (v ~ 100 km/s) impact of bio and water nanoparticles at the Brookhaven National Lab (BNL) in 1994. In the experiment, the nanoparticles were directly impacted on and detected by Si particle detectors that also detected the soft x-rays. Energy deposition measurements through thin films revealed that the impact generated pressures were ~10 TPa, and the photon energies in the range of 75-100 eV for Si targets. The conversion efficiency from the kinetic energy to the radiation energy was unexpectedly high, ~38%, which was attributed to Dicke Superradiance of collective quantum states in High-Energy Density Materials (HEDM), Metastable Innershell Molecular States (MIMS). This talk presents recent experimental results obtained in a table-top apparatus completely different from and orders of magnitude smaller than that at BNL. In the new setup, hypervelocity (v 100 km/s) C60+ ions impacted on Al targets, and the impact generated soft x-rays were detected off-axis and analyzed using three Si photodiode detectors with selective energy response curves. The photon energy was determined to be ~70 eV with the kinetic-energy to photon-energy conversion efficiency of ~35% in confirmation of the results by Bae et al. at BNL. The present results demonstrate a new way of generation and spectroscopic study of HEDM with pressures exceeding 10 TPa, and show the pathway to scaling up the soft x-ray generation method for a wide range of applications from lithography to inertial fusion. This work was supported by DTRA under the contract HDTRA1-12-C-0094.

  17. Spermine synthase overexpression in vivo does not increase susceptibility to DMBA/TPA skin carcinogenesis or Min-Apc intestinal tumorigenesis.

    PubMed

    Welsh, Patricia A; Sass-Kuhn, Suzanne; Prakashagowda, Chethana; McCloskey, Diane; Feith, David

    2012-04-01

    Numerous studies have demonstrated a link between elevated polyamine biosynthesis and neoplastic growth, but the specific contribution of spermine synthase to epithelial tumor development has never been explored in vivo. Mice with widespread overexpression of spermine synthase (CAG-SpmS) exhibit decreased spermidine levels, increased spermine and a significant rise in tissue spermine:spermidine ratio. We characterized the response of CAG-SpmS mice to two-stage skin chemical carcinogenesis as well as spontaneous intestinal carcinogenesis induced by loss of the Apc tumor suppressor in Apc (Min) (/+) (Min) mice. CAG-SpmS mice maintained the canonical increases in ornithine decarboxylase (ODC) activity, polyamine content and epidermal thickness in response to tumor promoter treatment of the skin. The induction of S-adenosylmethionine decarboxylase (AdoMetDC) activity and its product decarboxylated AdoMet were impaired in CAG-SpmS mice, and the spermine:spermidine ratio was increased 3-fold in both untreated and 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated skin. The susceptibility to 7,12-dimethylbenz[a]anthracene (DMBA)/TPA skin carcinogenesis was not altered in CAG-SpmS mice, and SpmS overexpression did not modify the previously described tumor resistance of mice with targeted antizyme expression or the enhanced tumor response in mice with targeted spermidine/spermine-N ( 1) -acetyltransferase expression. CAG-SpmS/Min mice also exhibited elevated spermine:spermidine ratios in the small intestine and colon, yet their tumor multiplicity and size was similar to Min mice. Therefore, studies in two of the most widely used tumorigenesis models demonstrate that increased spermine synthase activity and the resulting elevation of the spermine:spermidine ratio does not alter susceptibility to tumor development initiated by c-Ha-Ras mutation or Apc loss. PMID:22258329

  18. Reversal of the TPA-induced inhibition of gap junctional intercellular communication by Chaga mushroom (Inonotus obliquus) extracts: effects on MAP kinases.

    PubMed

    Park, Jung-Ran; Park, Joon-Suk; Jo, Eun-Hye; Hwang, Jae-Woong; Kim, Sun-Jung; Ra, Jeong-Chan; Aruoma, Okezie I; Lee, Yong-Soon; Kang, Kyung-Sun

    2006-01-01

    Chaga mushroom (Inonotus obliquus) has continued to receive attention as a folk medicine with indications for the treatment of cancers and digestive diseases. The anticarcinogenic effect of Chaga mushroom extract was investigated using a model system of gap junctional intercellular communication (GJIC) in WB-F344 normal rat liver epithelial cells. The cells were pre-incubated with Chaga mushroom extracts (5, 10, 20 microg/ml) for 24 h and this was followed by co-treatment with Chaga mushroom extracts and TPA (12-O-tetradecanoylphorbol-13-acetate, 10 ng/ml) for 1 h. The inhibition of GJIC by TPA (12-O-tetradecanoylphorbol-13-acetate), promoter of cancer, was prevented with treatment of Chaga mushroom extracts. Similarly, the increased phosphorylated ERK1/2 and p38 protein kinases were markedly reduced in Chaga mushroom extracts-treated cells. There was no change in the JNK kinase protein level, suggesting that Chaga mushroom extracts could only block the activation of ERK1/2 and p38 MAP kinase. The Chaga mushroom extracts further prevented the inhibition of GJIC through the blocking of Cx43 phosphorylation. Indeed cell-to-cell communication through gap junctional channels is a critical factor in the life and death balance of cells because GJIC has an important function in maintaining tissue homeostasis through the regulation of cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Thus Chaga mushroom may act as a natural anticancer product by preventing the inhibition of GJIC through the inactivation of ERK1/2 and p38 MAP kinase. PMID:17012771

  19. Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model.

    PubMed

    Wang, Kai; Zhou, Xiaorong; Huang, Yanming; Khalil, Mazen; Wiktor, Dominik; van Giezen, J J J; Penn, Marc S

    2010-09-01

    Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion. PMID:20694285

  20. Developmental trajectories and milestones of lesbian, gay, and bisexual young people.

    PubMed

    Savin-Williams, Ritch C; Cohen, Kenneth M

    2015-01-01

    Lesbian, gay, and bisexual (LGB) young people experience a variety of developmental trajectories that consist of milestones, the sequence and timing of which differ across individuals. They include early feelings of being different from peers, the onset of same-sex attraction, questioning one's sexuality, first same-sex sexual experience, recognition and self-labelling, disclosure to others, first romantic relationship, and self-acceptance. The invention of 'gay youth' during the 1970s and 1980s is briefly reviewed with an emphasis on the ways in which the portrait created by early research fails to capture the developmental trajectories of millennial young people. Although some young people struggle with mental health problems as they navigate these milestones, research documents the complexity, variety, and normative nature of the vast majority of LGB young people. A growing chorus of developmental, behavioural, and social scientists now emphasize that many contemporary young people forego sexual confusion, recognize the sex or gender to which they are attracted to and love, and believe they are as mentally healthy as heterosexual young people. PMID:26555639

  1. CORD-AEUS: consensus document for the emergency ultrasound milestone project.

    PubMed

    Lewiss, Resa E; Pearl, Michelle; Nomura, Jason T; Baty, Gillian; Bengiamin, Rimon; Duprey, Kael; Stone, Michael; Theodoro, Daniel; Akhtar, Saadia

    2013-07-01

    In 2012, the Accreditation Council for Graduate Medical Education (ACGME) designated ultrasound (US) as one of 23 milestone competencies for emergency medicine (EM) residency graduates. With increasing scrutiny of medical educational programs and their effect on patient safety and health care delivery, it is imperative to ensure that US training and competency assessment is standardized. In 2011, a multiorganizational committee composed of representatives from the Council of Emergency Medicine Residency Directors (CORD), the Academy of Emergency Ultrasound of the Society for Academic Emergency Medicine (SAEM), the Ultrasound Section of the American College of Emergency Physicians (ACEM), and the Emergency Medicine Residents' Association was formed to suggest standards for resident emergency ultrasound (EUS) competency assessment and to write a document that addresses the ACGME milestones. This article contains a historical perspective on resident training in EUS and a table of core skills deemed to be a minimum standard for the graduating EM resident. A survey summary of focused EUS education in EM residencies is described, as well as a suggestion for structuring education in residency. Finally, adjuncts to a quantitative measurement of resident competency for EUS are offered. PMID:23859589

  2. Markovian and Non-Markovian Modeling of Membrane Dynamics with Milestoning.

    PubMed

    Cardenas, Alfredo E; Elber, Ron

    2016-08-25

    We exploit atomically detailed simulations and the milestoning theory to extract coarse grained models of membrane kinetics and thermodynamics. Non-Markovian and Markovian theories for the phosphate group displacements are used to coarsely represent membrane motions. The construction of the two models makes it possible to examine their consistency and accuracy. The equilibrium and fluctuations of the phosphate groups along the normal to the membrane plane are estimated, and milestoning equations are constructed and solved. An optimal Markovian model is constructed that reproduces exactly the equilibrium and mean first passage time (MFPT) of the non-Markovian model. The equilibrium solution of both models is favorably compared to distributions obtained from straightforward molecular dynamics simulations. The picture for the kinetics is complex. Multiple local relaxation times of the mass density are illustrated emphasizing the non-Markovian characteristics of the process. In Markovian modeling, only a single relaxation time is assumed for a state. Mapping of particle dynamics to the dynamics of a field density offers a new way of coarse graining complex systems as membranes that may bridge between atomically detailed models and phenomenological descriptions of macroscopic membranes. PMID:27016332

  3. Williston basin. Milestone test renews interest in Red Wing Creek field's meteor crater

    SciTech Connect

    Rountree, R.

    1983-04-01

    New drilling in the vicinity of Red Wing Creek field in McKenzie County, North Dakota has renewed interest in an area that has intrigued geologists for a number of years. Red Wing Creek was discovered in 1972 by True Oil Co. and has demonstrated better per-acre oil recovery than any other oil field in the Williston Basin. Fully developed several years ago, the field produces from what has been described as the central peak of an astrobleme, within a meteor crater. The current test by Milestone Petroleum Inc. is permitted to 14,200 ft and is being drilled on the rim of the crater, in SW SW 35-148n-101w, approx. a mile south of Red Wing production. The primary objective is the Ordovician Red River; but plans call for drilling deeper, through the Winnipeg, to below the Mississippian sediments that produce at Red Wing Creek field. At least 3 unsuccessful Red River tests have been drilled in or near the field in earlier years, but not in the area where Milestone is drilling. Production at Red Wing has come from porosity zones in a Mississippian oil column that measured 2600 ft in the original well; the better wells are in the heart of the field, on a rebound cone in the center of the crater.

  4. A milestone-based approach to breast imaging instruction for residents.

    PubMed

    Harvey, Jennifer A; Nicholson, Brandi T; Rochman, Carrie M; Peppard, Heather R; Pease, Clinton S; DeMartini, Nicholas A

    2014-06-01

    Residency is historically an apprenticeship, learning through observation and instruction with varying degrees of structure. Since July 2013, the Next Accreditation System (NAS) of the ACGME has required the use of progressive milestones for each radiology residency rotation. The authors describe how a breast imaging curriculum can be structured to comply with the NAS. The breast imaging rotations move from basic recognition and management of suspicious findings, through the detection of more subtle findings and learning of biopsy skills, and finally to the synthesis and management of more advanced findings. Likewise, patient communication moves from sharing imaging findings to the more challenging situation of breaking the bad news of a cancer diagnosis. This progression of skills mirrors the objectives of levels 1 to 4 of the NAS. Learning objectives have been adapted to form very specific milestones for each rotation, which results in a shared responsibility between residents and faculty members. Using clear expectations may improve the uniformity of teaching, resident satisfaction, and facilitate performance review for residents who are struggling. Didactic lectures, case-based conferences, teaching file cases, and assigned readings provide different approaches to education, allowing variation in learning styles. Performance on the breast imaging section on the ACR Diagnostic Radiology In-Training examination at our institution has risen from below the 50th percentile to around the 80th percentile beginning in 2011. PMID:24780508

  5. Milestones toward Majorana-based quantum computing: Fusion rule detection and topological qubit validation

    NASA Astrophysics Data System (ADS)

    Mishmash, Ryan V.; Aasen, David; Hell, Michael; Higginbotham, Andrew; Danon, Jeroen; Leijnse, Martin; Jespersen, Thomas S.; Folk, Joshua A.; Marcus, Charles M.; Flensberg, Karsten; Alicea, Jason

    We introduce a scheme for preparation, manipulation, and readout of Majorana zero modes in semiconducting wires coated with mesoscopic superconducting islands. Our approach synthesizes recent advances in materials growth with tools commonly used in quantum-dot experiments, including gate-control of tunnel barriers and Coulomb effects, charge sensing, and charge pumping. Recently, we have outlined a sequence of relatively modest milestones which interpolate between zero-mode detection and longer term quantum computing applications. In this talk, I will discuss two of these milestones: (1) detection of fusion rules for non-Abelian anyons using either proximal charge sensing or Majorana-mediated charge pumping and (2) validation of a prototype topological qubit via unconventional scaling relations between the time-averaged qubit splitting and its decoherence times T1 and T2. Both of these proposed experiments require only a single wire with two islands--a hardware configuration already available in the laboratory. Furthermore, these pre-braiding experiments can be adapted to other manipulation and readout schemes as well.

  6. Certification of Completion of ASC FY08 Level-2 Milestone ID #2933

    SciTech Connect

    Lipari, D A

    2008-06-12

    This report documents the satisfaction of the completion criteria associated with ASC FY08 Milestone ID No.2933: 'Deploy Moab resource management services on BlueGene/L'. Specifically, this milestone represents LLNL efforts to enhance both SLURM and Moab to extend Moab's capabilities to schedule and manage BlueGene/L, and increases portability of user scripts between ASC systems. The completion criteria for the milestone are the following: (1) Batch jobs can be specified, submitted to Moab, scheduled and run on the BlueGene/L system; (2) Moab will be able to support the markedly increased scale in node count as well as the wiring geometry that is unique to BlueGene/L; and (3) Moab will also prepare and report statistics of job CPU usage just as it does for the current systems it supports. This document presents the completion evidence for both of the stated milestone certification methods: Completion evidence for this milestone will be in the form of (1) documentation--a report that certifies that the completion criteria have been met; and (2) user hand-off. As the selected Tri-Lab workload manager, Moab was chosen to replace LCRM as the enterprise-wide scheduler across Livermore Computing (LC) systems. While LCRM/SLURM successfully scheduled jobs on BG/L, the effort to replace LCRM with Moab on BG/L represented a significant challenge. Moab is a commercial product developed and sold by Cluster Resources, Inc. (CRI). Moab receives the users batch job requests and dispatches these jobs to run on a specific cluster. SLURM is an open-source resource manager whose development is managed by members of the Integrated Computational Resource Management Group (ICRMG) within the Services and Development Division at LLNL. SLURM is responsible for launching and running jobs on an individual cluster. Replacing LCRM with Moab on BG/L required substantial changes to both Moab and SLURM. While the ICRMG could directly manage the SLURM development effort, the work to enhance Moab

  7. MRMC analysis of agreement studies

    NASA Astrophysics Data System (ADS)

    Gallas, Brandon D.; Anam, Amrita; Chen, Weijie; Wunderlich, Adam; Zhang, Zhiwei

    2016-03-01

    The purpose of this work is to present and evaluate methods based on U-statistics to compare intra- or inter-reader agreement across different imaging modalities. We apply these methods to multi-reader multi-case (MRMC) studies. We measure reader-averaged agreement and estimate its variance accounting for the variability from readers and cases (an MRMC analysis). In our application, pathologists (readers) evaluate patient tissue mounted on glass slides (cases) in two ways. They evaluate the slides on a microscope (reference modality) and they evaluate digital scans of the slides on a computer display (new modality). In the current work, we consider concordance as the agreement measure, but many of the concepts outlined here apply to other agreement measures. Concordance is the probability that two readers rank two cases in the same order. Concordance can be estimated with a U-statistic and thus it has some nice properties: it is unbiased, asymptotically normal, and its variance is given by an explicit formula. Another property of a U-statistic is that it is symmetric in its inputs; it doesn't matter which reader is listed first or which case is listed first, the result is the same. Using this property and a few tricks while building the U-statistic kernel for concordance, we get a mathematically tractable problem and efficient software. Simulations show that our variance and covariance estimates are unbiased.

  8. Form 6 - gas balancing agreement

    SciTech Connect

    Not Available

    1990-01-01

    In 1988, a special Committee of the Rocky Mountain Mineral Law Foundation undertook a project to draft a model from gas balancing agreement. This project was initiated at the request of a number of Foundation members who felt that a model form gas balancing agreement would facilitate the negotiation of operating agreement, since gas balancing issues had become sticking points in the process. The Committee was composed of attorneys representing a wide cross-section of the oil and gas industry including both major and independent oil companies, production companies with interstate pipeline affiliates, and private practitioners. The Committee attempted to address the more controversial issues in gas balancing with optional provisions in the Form. To facilitate the negotiation process, the number of optional provisions was minimized. This form may be used as an Appendix to the new A.A.P.L. Form 610-1989 Model Form Operating Agreement. This book includes provision of this Form which are: Ownership of gas production; Balancing of production accounts; Cash balancing upon depletion; Deliverability tests; Nominations; Statements; Payment of taxes; Operating expenses; Overproducing allowable; Payment of leasehold burdens; Operator's liability; Successors and assigns; Audits; Arbitration; and Operator's fees.

  9. University of Scranton: Master Agreement.

    ERIC Educational Resources Information Center

    Scranton Univ., PA.

    This document is the collective bargaining agreement between the University of Scranton and its faculty effective September 1, 1975 until August 31, 1976. Its provisions include all full-time faculty members associated with the Reading Clinic and Counseling Center, full-time faculty assigned to the Department of Physical Education, full-time…

  10. Articulation Agreements Ease the Way.

    ERIC Educational Resources Information Center

    Reese, Susan

    2002-01-01

    Articulation agreements between secondary and postsecondary institutions often provide for granting college credit for course work completed at another institution. They have been described as programs designed to create pathways of learning that ease the transition of students from secondary to postsecondary levels. (JOW)

  11. Block Transfer Agreement Evaluation Project

    ERIC Educational Resources Information Center

    Bastedo, Helena

    2010-01-01

    The objective of this project is to evaluate for the British Columbia Council on Admissions and Transfer (BCCAT) the effectiveness of block transfer agreements (BTAs) in the BC Transfer System and recommend steps to be taken to improve their effectiveness. Findings of this study revealed that institutions want to expand block credit transfer;…

  12. Making an Exercise Buddy Agreement

    MedlinePlus

    ... meet your needs. Print out two copies and fill them out together. Then, to make it “official,” both of you should sign them and keep a copy. Review Your Progress Refer back to your agreement at a set time to ...

  13. Limiting technology by negotiated agreement

    SciTech Connect

    Carnesale, A.

    1983-01-01

    The author concentrates on anti-ballistic missile (ABM) systems as an example of a continuing effort to limit technology by negotiated agreement. He first discusses the ABM treaty of 1972, ratified by both the US and the USSR. Afterwards, he briefly treats each of the following: ballistic missile defense (BMD) dilemmas; nature of the BMD choice; technology; economics; deterrence; nuclear warfighting; relations with allies; arms control; Star Wars; and on limiting technology.

  14. 78 FR 8533 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-06

    ... Agreement. Parties: Crowley Latin America Services, LLC and Dole Ocean Cargo Express, Inc. Filing Party... scope of the agreement, clarifies language in the agreement, and makes technical corrections to...

  15. 77 FR 38288 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-27

    ... . Agreement No.: 012177. Title: MSC/Maersk Line U.S.-Panama Space Charter Agreement. Parties: Mediterranean... agreement authorizes MSC to charter space to Maersk Line in the trade between ports in Panama and ports...

  16. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  17. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  18. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  19. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  20. 40 CFR 35.1615 - Substate agreements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 CFR 33.240 (Intergovernmental agreements). A State may enter into an agreement with a substate... STATE AND LOCAL ASSISTANCE Cooperative Agreements for Protecting and Restoring Publicly Owned...

  1. 78 FR 15951 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ... agreement. Agreement No.: 012196. Title: MSC/CSAV Ecuador--North Europe Vessel Sharing Agreement. Parties... on the U.S. East Coast on the one hand, and from ports on the U.S. East Coast to Panama and...

  2. 75 FR 20849 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    ... geographic scope of the Agreement. Agreement No.: 011830-008. Title: Indamex Cross Space Charter, Sailing and... Limited Slot Charter and Sailing Agreement. Parties: Tropical Shipping & Construction Co., Ltd. and...

  3. 75 FR 11180 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ....gov . Agreement No.: 011730-003. Title: GWF/Dole Space Charter and Sailing Agreement. Parties: Dole... China-US Pacific Coast Two-Loop Space Charter, Sailing and Cooperative Working Agreement. Parties:...

  4. 78 FR 54646 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-05

    .... Agreement No.: 012220. Title: Crowley/Seaboard Space Charter and Sailing Agreement. Parties: Crowley Latin.../America Cruise Ferries, Inc. Space Charter and Sailing Agreement. Parties: Crowley Latin America...

  5. Oak Ridge Reservation Federal Facility Agreement. Quarterly report for the Environmental Restoration Program. Volume 4, July 1995--September 1995

    SciTech Connect

    1995-10-01

    This quarterly progress report satisfies requirements for the Environmental Restoration (ER) Program that are specified in the Oak Ridge Reservation Federal Facility Agreement (FFA) established between the U.S. Department of Energy (DOE), the U.S. Environmental Protection Agency (EPA), and the Tennessee Department of Environment and Conservation (TDEC). The reporting period covered herein is July through September 1995 (fourth quarter of FY 1995). Sections 1.1 and 1.2 provide respectively the milestones scheduled for completion during the reporting period and a list of documents that have been proposed for transmittal during the following quarter but have not been approved as FY 1995 commitments.

  6. Oak Ridge Reservation Federal Facility Agreement for the Environmental Restoration Program. Volume 4. Quarterly report, July--September 1993

    SciTech Connect

    Not Available

    1993-10-01

    This quarterly progress report satisfies requirements for the Environmental Restoration (ER) Program that are specified in the Oak Ridge Reservation (ORR) Federal Facility Agreement (FFA) established between the U.S. Department of Energy (DOE), the U.S. Environmental protection Agency (EPA), and the Tennessee Department of Environment and Conservation (TDEC). The reporting period covered is July through September 1993 (fourth quarter of FY 1993). Sections 1.1 and 1.2 provide respectively the milestones scheduled for completion during the reporting period and a list of documents that have been proposed for transmittal during the following quarter but have not been approved as FY 1994 commitments.

  7. Oak Ridge reservation federal facility agreement for the Environmental Restoration Program. Volume 1. Quarterly report, October--December 1993

    SciTech Connect

    Not Available

    1994-01-01

    This quarterly progress report satisfies requirements for the Environmental Restoration (ER) Program that are specified in the Oak Ridge Reservation (ORR) Federal Facility Agreement (FFA) established between the U.S. Department of Energy (DOE), the U.S. Environmental Protection Agency (EPA), and the Tennessee Department of Environment and Conservation (TDEC). The reporting period covered is October through December 1993 (first quarter of FY 1994). Sections 1.1 and 1.2 provide respectively the milestones scheduled for completion during the reporting period and a list of documents that have been proposed for transmittal during the following quarter but have not been approved as FY 1994 commitments.

  8. Data co-processing for extreme scale analysis level II ASC milestone (4745).

    SciTech Connect

    Rogers, David; Moreland, Kenneth D.; Oldfield, Ron A.; Fabian, Nathan D.

    2013-03-01

    Exascale supercomputing will embody many revolutionary changes in the hardware and software of high-performance computing. A particularly pressing issue is gaining insight into the science behind the exascale computations. Power and I/O speed con- straints will fundamentally change current visualization and analysis work ows. A traditional post-processing work ow involves storing simulation results to disk and later retrieving them for visualization and data analysis. However, at exascale, scien- tists and analysts will need a range of options for moving data to persistent storage, as the current o ine or post-processing pipelines will not be able to capture the data necessary for data analysis of these extreme scale simulations. This Milestone explores two alternate work ows, characterized as in situ and in transit, and compares them. We nd each to have its own merits and faults, and we provide information to help pick the best option for a particular use.

  9. ASC Tri-lab Co-design Level 2 Milestone Report 2015

    SciTech Connect

    Hornung, Rich; Jones, Holger; Keasler, Jeff; Neely, Rob; Pearce, Olga; Hammond, Si; Trott, Christian; Lin, Paul; Vaughan, Courtenay; Cook, Jeanine; Hoekstra, Rob; Bergen, Ben; Payne, Josh; Womeldorff, Geoff

    2015-09-23

    In 2015, the three Department of Energy (DOE) National Laboratories that make up the Advanced Sci- enti c Computing (ASC) Program (Sandia, Lawrence Livermore, and Los Alamos) collaboratively explored performance portability programming environments in the context of several ASC co-design proxy applica- tions as part of a tri-lab L2 milestone executed by the co-design teams at each laboratory. The programming environments that were studied included Kokkos (developed at Sandia), RAJA (LLNL), and Legion (Stan- ford University). The proxy apps studied included: miniAero, LULESH, CoMD, Kripke, and SNAP. These programming models and proxy-apps are described herein. Each lab focused on a particular combination of abstractions and proxy apps, with the goal of assessing performance portability using those. Performance portability was determined by: a) the ability to run a single application source code on multiple advanced architectures, b) comparing runtime performance between \

  10. Milestones in the history of hemoglobin research (in memory of professor Titus H.J. Huisman).

    PubMed

    Thein, Swee Lay

    2011-01-01

    Professor Titus H.J. Huisman is best known for his work on hemoglobin (Hb) variants. To date, more than 1,000 Hb variants have been discovered and characterized, of which about one-third were discovered in Titus Huisman's laboratory at the Medical College of Georgia, Augusta, GA, USA. A registry of these Hb variants and other information, a legacy from Professor Huisman, is now available online, at HbVar database (hhtp://globin.bx.psu.edu/hbvar). During the last century, major developments in Hb research have been made using physical, chemical, physiological and genetic methods. This review highlights the milestones and key developments in Hb research most relevant to hematologists, and that have impacted our understanding and management of the thalassemias and sickle cell disease. PMID:21932936

  11. Project Milestone. Analysis of Range Extension Techniques for Battery Electric Vehicles

    SciTech Connect

    Neubauer, Jeremy; Wood, Eric; Pesaran, Ahmad

    2013-07-01

    This report documents completion of the July 2013 milestone as part of NREL’s Vehicle Technologies Annual Operating Plan with the U.S. Department of Energy. The objective was to perform analysis on range extension techniques for battery electric vehicles (BEVs). This work represents a significant advancement over previous thru-life BEV analyses using NREL’s Battery Ownership Model, FastSim,* and DRIVE.* Herein, the ability of different charging infrastructure to increase achievable travel of BEVs in response to real-world, year-long travel histories is assessed. Effects of battery and cabin thermal response to local climate, battery degradation, and vehicle auxiliary loads are captured. The results reveal the conditions under which different public infrastructure options are most effective, and encourage continued study of fast charging and electric roadway scenarios.

  12. Simulations of thermodynamics and kinetics on rough energy landscapes with milestoning.

    PubMed

    Bello-Rivas, Juan M; Elber, Ron

    2016-03-01

    We investigated by computational means the kinetics and stationary behavior of stochastic dynamics on an ensemble of rough two-dimensional energy landscapes. There are no obvious separations of temporal scales in these systems, which constitute a simple model for the behavior of glasses and some biomaterials. Even though there are significant computational challenges present in these systems due to the large number of metastable states, the Milestoning method is able to compute their kinetic and thermodynamic properties exactly. We observe two clearly distinguished regimes in the overall kinetics: one in which diffusive behavior dominates and another that follows an Arrhenius law (despite the absence of a dominant barrier). We compare our results with those obtained with an exactly-solvable one-dimensional model, and with the results from the rough one-dimensional energy model introduced by Zwanzig. © 2015 Wiley Periodicals, Inc. PMID:26265358

  13. A multi-center milestone study of clinical vertebral CT segmentation.

    PubMed

    Yao, Jianhua; Burns, Joseph E; Forsberg, Daniel; Seitel, Alexander; Rasoulian, Abtin; Abolmaesumi, Purang; Hammernik, Kerstin; Urschler, Martin; Ibragimov, Bulat; Korez, Robert; Vrtovec, Tomaž; Castro-Mateos, Isaac; Pozo, Jose M; Frangi, Alejandro F; Summers, Ronald M; Li, Shuo

    2016-04-01

    A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention. PMID:26878138

  14. 20 CFR 411.581 - Can an EN receive milestone and outcome payments for months after a beneficiary takes his or her...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... assigned to an EN (or State VR agency acting as an EN) takes his or her ticket out of assignment (see § 411.145), the EN (or State VR agency) can receive payments under its elected payment system for milestones... EN or State VR agency based on the same milestone or outcome....

  15. 20 CFR 411.581 - Can an EN receive milestone and outcome payments for months after a beneficiary takes his or her...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... assigned to an EN (or State VR agency acting as an EN) takes his or her ticket out of assignment (see § 411.145), the EN (or State VR agency) can receive payments under its elected payment system for milestones... EN or State VR agency based on the same milestone or outcome....

  16. 20 CFR 411.581 - Can an EN receive milestone and outcome payments for months after a beneficiary takes his or her...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... assigned to an EN (or State VR agency acting as an EN) takes his or her ticket out of assignment (see § 411.145), the EN (or State VR agency) can receive payments under its elected payment system for milestones... EN or State VR agency based on the same milestone or outcome....

  17. 20 CFR 411.581 - Can an EN receive milestone and outcome payments for months after a beneficiary takes his or her...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... assigned to an EN (or State VR agency acting as an EN) takes his or her ticket out of assignment (see § 411.145), the EN (or State VR agency) can receive payments under its elected payment system for milestones... EN or State VR agency based on the same milestone or outcome....

  18. Early Language Milestones Predict Later Language, but not Autism Symptoms in Higher Functioning Children with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Kenworthy, Lauren; Wallace, Gregory L.; Powell, Kelly; Anselmo, Cheryl; Martin, Alex; Black, David O.

    2012-01-01

    Language ability is a known predictor of outcome in children with autism but plays a more controversial role for higher functioning children with autism spectrum disorders (ASD). We studied the relationship between early language milestones and later structural language, adaptive functioning and autism symptoms in a sample of 76 children (mean age…

  19. 20 CFR 411.566 - May an EN use outcome or milestone payments to make payments to the beneficiary?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false May an EN use outcome or milestone payments to make payments to the beneficiary? 411.566 Section 411.566 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.566...

  20. 20 CFR 411.566 - May an EN use outcome or milestone payments to make payments to the beneficiary?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false May an EN use outcome or milestone payments to make payments to the beneficiary? 411.566 Section 411.566 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.566...

  1. 20 CFR 411.536 - Under what circumstances can we make a reconciliation payment under the outcome-milestone payment...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Under what circumstances can we make a reconciliation payment under the outcome-milestone payment system? 411.536 Section 411.536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network...

  2. 20 CFR 411.536 - Under what circumstances can we make a reconciliation payment under the outcome-milestone payment...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 2 2014-04-01 2014-04-01 false Under what circumstances can we make a reconciliation payment under the outcome-milestone payment system? 411.536 Section 411.536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network...

  3. 20 CFR 411.536 - Under what circumstances can we make a reconciliation payment under the outcome-milestone payment...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 2 2012-04-01 2012-04-01 false Under what circumstances can we make a reconciliation payment under the outcome-milestone payment system? 411.536 Section 411.536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network...

  4. 20 CFR 411.536 - Under what circumstances can we make a reconciliation payment under the outcome-milestone payment...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Under what circumstances can we make a reconciliation payment under the outcome-milestone payment system? 411.536 Section 411.536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network...

  5. 20 CFR 411.566 - May an EN use outcome or milestone payments to make payments to the beneficiary?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false May an EN use outcome or milestone payments to make payments to the beneficiary? 411.566 Section 411.566 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.566...

  6. 20 CFR 411.566 - May an EN use outcome or milestone payments to make payments to the beneficiary?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false May an EN use outcome or milestone payments to make payments to the beneficiary? 411.566 Section 411.566 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.566...

  7. 20 CFR 411.575 - How does the EN request payment for milestones or outcome payment months achieved by a...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 411.575 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.575 How does the EN request payment for milestones or... payment for a month if— (i)(A) Social Security disability benefits and Federal SSI cash benefits are...

  8. 20 CFR 411.560 - Is it possible to pay a milestone or outcome payment to more than one EN?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Is it possible to pay a milestone or outcome payment to more than one EN? 411.560 Section 411.560 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.560 Is...

  9. 20 CFR 411.566 - May an EN use outcome or milestone payments to make payments to the beneficiary?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false May an EN use outcome or milestone payments to make payments to the beneficiary? 411.566 Section 411.566 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.566...

  10. 20 CFR 411.536 - Under what circumstances can we make a reconciliation payment under the outcome-milestone payment...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Under what circumstances can we make a reconciliation payment under the outcome-milestone payment system? 411.536 Section 411.536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network...

  11. 20 CFR 411.545 - How are the outcome payments calculated under the outcome-milestone payment system?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the outcome-milestone payment system? 411.545 Section 411.545 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND SELF-SUFFICIENCY PROGRAM Employment Network Payment Systems § 411.545 How... II disability insurance benefit payable under section 223 of the Social Security Act for...

  12. 20 CFR 411.575 - How does the EN request payment for milestones or outcome payment months achieved by a...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... outcome payment months achieved by a beneficiary who assigned a ticket to the EN? The EN (or State VR... provided as described in the IWP/IPE. (a) Milestone payments. (1) We will pay the EN (or State VR agency... VR agency's) elected payment system in effect at the time the beneficiary assigned a ticket to the...

  13. 20 CFR 411.575 - How does the EN request payment for milestones or outcome payment months achieved by a...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... outcome payment months achieved by a beneficiary who assigned a ticket to the EN? The EN (or State VR... provided as described in the IWP/IPE. (a) Milestone payments. (1) We will pay the EN (or State VR agency... VR agency's) elected payment system in effect at the time the beneficiary assigned a ticket to the...

  14. 20 CFR 411.575 - How does the EN request payment for milestones or outcome payment months achieved by a...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... outcome payment months achieved by a beneficiary who assigned a ticket to the EN? The EN (or State VR... provided as described in the IWP/IPE. (a) Milestone payments. (1) We will pay the EN (or State VR agency... VR agency's) elected payment system in effect at the time the beneficiary assigned a ticket to the...

  15. 20 CFR 411.575 - How does the EN request payment for milestones or outcome payment months achieved by a...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... outcome payment months achieved by a beneficiary who assigned a ticket to the EN? The EN (or State VR... provided as described in the IWP/IPE. (a) Milestone payments. (1) We will pay the EN (or State VR agency... VR agency's) elected payment system in effect at the time the beneficiary assigned a ticket to the...

  16. Phonological Milestones for African American English-Speaking Children Learning Mainstream American English as a Second Dialect

    ERIC Educational Resources Information Center

    Pearson, Barbara Z.; Velleman, Shelley L.; Bryant, Timothy J.; Charko, Tiffany

    2009-01-01

    Purpose: This study provides milestones for phonological development in African American English (AAE) speakers who are learning Mainstream American English (MAE) as a second dialect. Method: The Dialect Sensitive Language Test (DSLT; H. Seymour, T. Roeper, & J. G. de Villiers, 2000) was administered to a nationwide sample of typically developing…

  17. American Geriatrics Society/Association of Directors of Geriatric Academic Programs curricular milestones for graduating geriatric fellows.

    PubMed

    Parks, Susan M; Harper, G Michael; Fernandez, Helen; Sauvigne, Karen; Leipzig, Rosanne M

    2014-05-01

    This article describes the curricular milestones for geriatric fellows and the process used to develop them. The curricular milestones were developed to determine what every graduating geriatric fellow should be able to demonstrate to ensure that they will be able to practice effectively and safely in all care settings and with different older adult populations. Three major domains were identified: Caring for the Elderly Patient, Systems-Based Care for Elder Patients, and Geriatric Syndromes. Six hundred thirty-five geriatricians each reviewed and commented on one domain. These geriatricians represented important stakeholder groups: geriatric fellowship program directors; Association of Directors of Geriatric Academic Programs (ADGAP) members, who are primarily geriatric program and fellowship directors; the American Geriatrics Society (AGS) and ADGAP Education Committee; the AGS Teacher's Section; Geriatric Academic Career Award awardees; and through the American Board of Internal Medicine and the American Board of Family Medicine, board-certified geriatricians who spend more than 50% of their time in clinical practice. The AGS and ADGAP boards approved the final set of 76 Geriatric Curricular Milestones, which were posted on the Portal of Geriatric Online Education in December 2012. These curricular milestones are intended to assist geriatric fellowship directors as they develop curricula and assessments to inform program director reporting to the Accreditation Council for Graduate Medical Education in the Next Accreditation System, which begins in July 2014. PMID:24749808

  18. FIELD MEASUREMENT TECHNOLOGY FOR MERCURY IN SOIL AND SEDIMENT MILESTONE INC.'S DIRECT MERCURY ANALYZER (DMA)-80

    EPA Science Inventory

    Milestone's Direct Mercury Analyzer (DMA-80) was demonstrated under the U.S. Environmental Protection Agency Superfund Innovative Technology Evaluation Program in May 2003 at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee. The purpose of the Demonstration was to...

  19. Service Level Agreements in BREIN

    NASA Astrophysics Data System (ADS)

    Koller, Bastian; Frutos, Henar Munoz; Laria, Giuseppe

    With electronic business (eBusiness) becoming ubiquitous, the traditional ways of doing commerce need to be changed or completely replaced to support the end users effectively in performing their business. This includes especially the representation of business relationships with an electronic format to allow for automated processing of the respective parts of e.g. contractual obligations. One prominent representation tool are Service Level Agreements. Conceptually established as paper representation to describe parts of contracts of telecom operators, SLAs have become a research topic in the ICT domain now since several years.

  20. 7 CFR 1948.98 - Grant agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Grant agreements. 1948.98 Section 1948.98 Agriculture... § 1948.98 Grant agreements. The following Grant Agreements are a part of this regulation. (a) Exhibit A of this subpart is a Grant Agreement for Growth Management and Housing Planning Grants for...

  1. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  2. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  3. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  4. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Election agreement. 2421.20 Section 2421... Election agreement. Election agreement means an agreement under part 2422 of this subchapter signed by all... representation election in an appropriate unit....

  5. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  6. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  7. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  8. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  9. 40 CFR 46.170 - Fellowship agreement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Fellowship agreement. 46.170 Section 46... FELLOWSHIPS Award § 46.170 Fellowship agreement. (a) The “Fellowship Agreement” (EPA Form 5770-8) is the written agreement, including amendments, between EPA and you. The fellowship agreement will state...

  10. 77 FR 506 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-05

    ... . Agreement No.: 011707-008. Title: Gulf/South America Discussion Agreement. Parties: BBC Chartering... restates the agreement. Agreement No.: 012149. Title: MSC/CMA CGM U.S. East Coast-West Coast South America... Coast and the Bahamas, on the one hand, and the West Coast of South America, on the other. By Order...

  11. 77 FR 54911 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    .... Agreement No.: 011426-052. Title: West Coast of South America Discussion Agreement. Parties: Compania... . Agreement No.: 011075-075. Title: Central America Discussion Agreement. Parties: Crowley Latin America... Shipping Company, SA; Seaboard Marine Ltd.; South Pacific Shipping Company, Ltd. (dba Ecuadorian Line);...

  12. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  13. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  14. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  15. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  16. 25 CFR 163.71 - Agreement funding.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Agreement funding. 163.71 Section 163.71 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER GENERAL FORESTRY REGULATIONS Cooperative Agreements § 163.71 Agreement funding. In cooperative agreements, the Secretary is authorized to advance...

  17. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  18. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  19. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  20. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  1. 46 CFR 356.41 - Management agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 8 2012-10-01 2012-10-01 false Management agreements. 356.41 Section 356.41 Shipping..., Management Agreements and Exclusive or Long-Term Contracts § 356.41 Management agreements. (a) An owner or bareboat charterer of a Fishing Industry Vessel may enter into a management agreement with a Non-Citizen...

  2. 75 FR 19402 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-14

    .... Agreement No.: 012042-002. Title: MOL/ELJSA Slot Exchange Agreement. Parties: Evergreen Line Joint Service.... Title: MOL/APL/HMM Asia/USWC Slot Charter Agreement. Parties: American President Lines, Ltd.; APL Co... sold, and updates party addresses. Agreement No.: 012044-003. Title: MOL/CMA CGM Slot Charter...

  3. 77 FR 61751 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ... revises the geographic scope of the Agreement by adding Mexico and deleting Panama. It also revises the... restates the Agreement. Agreement No.: 012184-000. Title: Crowley/Maersk Line Panama-U.S. Space Charter... agreement authorizes Crowley to charter space to Maersk Line in the trade from Panama to the U.S....

  4. 48 CFR 1819.7210 - Agreement terminations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7210 Agreement terminations. (a) Agreements may be terminated for cause or on a voluntary basis by the mentor or the protégé. The procedures for agreement termination are outlined in the mentor-protégé agreement...

  5. 48 CFR 1819.7210 - Agreement terminations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7210 Agreement terminations. (a) Agreements may be terminated for cause or on a voluntary basis by the mentor or the protégé. The procedures for agreement termination are outlined in the mentor-protégé agreement...

  6. 48 CFR 1819.7210 - Agreement terminations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7210 Agreement terminations. (a) Agreements may be terminated for cause or on a voluntary basis by the mentor or the protégé. The procedures for agreement termination are outlined in the mentor-protégé agreement...

  7. 48 CFR 1819.7210 - Agreement terminations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7210 Agreement terminations. (a) Agreements may be terminated for cause or on a voluntary basis by the mentor or the protégé. The procedures for agreement termination are outlined in the mentor-protégé agreement...

  8. 46 CFR 535.201 - Subject agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE OCEAN COMMON CARRIER AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Scope § 535.201 Subject agreements. (a) Ocean common carrier agreements. This part applies to agreements by or among ocean...

  9. 46 CFR 535.201 - Subject agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE OCEAN COMMON CARRIER AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Scope § 535.201 Subject agreements. (a) Ocean common carrier agreements. This part applies to agreements by or among ocean...

  10. 46 CFR 535.201 - Subject agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE OCEAN COMMON CARRIER AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984 Scope § 535.201 Subject agreements. (a) Ocean common carrier agreements. This part applies to agreements by or among ocean...

  11. 2 CFR 182.620 - Cooperative agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... agreement. Cooperative agreement means an award of financial assistance that, consistent with 31 U.S.C. 6305... development agreements as defined in 15 U.S.C. 3710a. ... MANAGEMENT AND BUDGET GOVERNMENTWIDE GUIDANCE FOR GRANTS AND AGREEMENTS NATIONAL POLICY...

  12. 7 CFR 1948.98 - Grant agreements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Grant agreements. 1948.98 Section 1948.98 Agriculture... § 1948.98 Grant agreements. The following Grant Agreements are a part of this regulation. (a) Exhibit A of this subpart is a Grant Agreement for Growth Management and Housing Planning Grants for...

  13. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  14. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  15. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  16. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  17. 27 CFR 70.485 - Closing agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Closing agreements. 70.485... Relating to Alcohol, Tobacco, Firearms, and Explosives Administrative Remedies § 70.485 Closing agreements... taxable period ending prior or subsequent to the date of such agreement. A closing agreement may...

  18. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... Basic agreements may need to be revised before the annual review due to mandatory statutory requirements... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A...

  19. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  20. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  1. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  2. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  3. 7 CFR 947.111 - Marketing agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Marketing agreement. 947.111 Section 947.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing... Definitions § 947.111 Marketing agreement. Marketing agreement means Marketing Agreement No. 114, as amended....

  4. Calculated distortions of duplex DNA by a cis, syn cyclobutane thymine dimer are unaffected by a 3' TpA step.

    PubMed Central

    Cooney, M G; Miller, J H

    1997-01-01

    Molecular dynamics simulations were performed on the duplex DNA dodecamers d(CGCGAA TT CGCG): d(CGCGAATTCGCG) and d(GCACGAA TT AAG): d(CTTAATTCGTGC), where TT denotes a cis, syn cyclobutane thymine dimer. The constant temperature and pressure algorithm of the AMBER 4.1 molecular-modeling package was used with explicit water and counterions, periodic boundary conditions and electrostatic interactions evaluated by the particle-mesh Ewald method. Results were analyzed by the CURVES algorithm and its implementation in DIALS and WINDOWS. Calculated distortions of DNA structure by the thymine dimer were qualitatively and quantitatively similar for the two sequences. Despite the enhanced flexibility of the native TpA dinucleotide step, major deviations from the B-DNA values of helicoidal parameters were found only at the Ap and p dinucleotide steps in both sequences. Only the AT base pairs of the two sequences that contain the 5' thymine of the dimers exhibited weakened Watson-Crick hydrogen bonds and anomalous stretching. Hence, we conclude that the pattern of structural perturbations responsible for recognition of cis, syn thymine dimers by repair enzymes is not sensitive to their sequence context. PMID:9060440

  5. Bioassay-guided chemical study of the anti-inflammatory effect of Senna villosa (Miller) H.S. Irwin & Barneby (Leguminosae) in TPA-induced ear edema.

    PubMed

    Susunaga-Notario, Ana del Carmen; Pérez-Gutiérrez, Salud; Zavala-Sánchez, Miguel Angel; Almanza-Pérez, Julio Cesar; Gutiérrez-Carrillo, Atilano; Arrieta-Báez, Daniel; López-López, Ana Laura; Román-Ramos, Rubén; Flores-Sáenz, José Luis Eduardo; Alarcón-Aguilar, Francisco Javier

    2014-01-01

    Senna villosa (Miller) is a plant that grows in México. In traditional Mexican medicine, it is used topically to treat skin infections, pustules and eruptions and to heal wounds by scar formation. However, studies of its potential anti-inflammatory effects have not been performed. The aim of the present study was to determine the anti-inflammatory effect of extracts from the leaves of Senna villosa and to perform a bioassay-guided chemical study of the extract with major activity in a model of ear edema induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). The results reveal that the chloroform extract from Senna villosa leaves has anti-inflammatory and anti-proliferative properties. Nine fractions were obtained from the bioassay-guided chemical study, including a white precipitate from fractions 2 and 3. Although none of the nine fractions presented anti-inflammatory activity, the white precipitate exhibited pharmacological activity. It was chemically characterized using mass spectrometry and infrared and nuclear magnetic resonance spectroscopy, resulting in a mixture of three aliphatic esters, which were identified as the principal constituents: hexyl tetradecanoate (C20H40O2), heptyl tetradecanoate (C21H42O2) and octyl tetradecanoate (C22H44O2). This research provides, for the first time, evidence of the anti-inflammatory and anti-proliferative properties of compounds isolated from Senna villosa. PMID:25029073

  6. Poly-γ-Glutamic Acid Induces Apoptosis via Reduction of COX-2 Expression in TPA-Induced HT-29 Human Colorectal Cancer Cells

    PubMed Central

    Shin, Eun Ju; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Kim, Myung Sunny; Hur, Haeng Jeon; Hwang, Jin-Taek

    2015-01-01

    Poly-γ-glutamic acid (PGA) is one of the bioactive compounds found in cheonggukjang, a fast-fermented soybean paste widely utilized in Korean cooking. PGA is reported to have a number of beneficial health effects, and interestingly, it has been identified as a possible anti-cancer compound through its ability to promote apoptosis in cancer cells, although the precise molecular mechanisms remain unclear. Our findings demonstrate that PGA inhibits the pro-proliferative functions of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a known chemical carcinogen in HT-29 human colorectal cancer cells. This inhibition was accompanied by hallmark apoptotic phenotypes, including DNA fragmentation and the cleavage of poly (ADP-ribose) polymerase (PARP) and caspase 3. In addition, PGA treatment reduced the expression of genes known to be overexpressed in colorectal cancer cells, including cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Lastly, PGA promoted activation of 5' adenosine monophosphate-activated protein (AMPK) in HT-29 cells. Taken together, our results suggest that PGA treatment enhances apoptosis in colorectal cancer cells, in part by modulating the activity of the COX-2 and AMPK signaling pathways. These anti-cancer functions of PGA make it a promising compound for future study. PMID:25854428

  7. Regulated proteolytic processing of Reelin through interplay of tissue plasminogen activator (tPA), ADAMTS-4, ADAMTS-5, and their modulators.

    PubMed

    Krstic, Dimitrije; Rodriguez, Myriam; Knuesel, Irene

    2012-01-01

    The extracellular signaling protein Reelin, indispensable for proper neuronal migration and cortical layering during development, is also expressed in the adult brain where it modulates synaptic functions. It has been shown that proteolytic processing of Reelin decreases its signaling activity and promotes Reelin aggregation in vitro, and that proteolytic processing is affected in various neurological disorders, including Alzheimer's disease (AD). However, neither the pathophysiological significance of dysregulated Reelin cleavage, nor the involved proteases and their modulators are known. Here we identified the serine protease tissue plasminogen activator (tPA) and two matrix metalloproteinases, ADAMTS-4 and ADAMTS-5, as Reelin cleaving enzymes. Moreover, we assessed the influence of several endogenous protease inhibitors, including tissue inhibitors of metalloproteinases (TIMPs), α-2-Macroglobulin, and multiple serpins, as well as matrix metalloproteinase 9 (MMP-9) on Reelin cleavage, and described their complex interplay in the regulation of this process. Finally, we could demonstrate that in the murine hippocampus, the expression levels and localization of Reelin proteases largely overlap with that of Reelin. While this pattern remained stable during normal aging, changes in their protein levels coincided with accelerated Reelin aggregation in a mouse model of AD. PMID:23082219

  8. Hugoniot and opacity measurements of polystyrene and carbon up to 80 TPa from radiography of converging shocks at the National Ignition Facility

    NASA Astrophysics Data System (ADS)

    Kritcher, A. L.; Doeppner, T.; Swift, D. C.; Bachmann, B.; Kraus, D.; Hawreliak, J.; Gaffney, J.; Collins, G.; Glenzer, S.; Chapman, D.; Rothman, S. D.; Rose, S.; Falcone, R. W.

    2015-06-01

    Converging shocks were induced with hohlraum-driven x-ray radiation on spherical samples of poly alpha-methyl styrene and diamond. The time-history of density profiles through the sample was measured by x-ray radiography using a laser-heated backlighter and a streak camera, viewing a diameter across the sample through slots in the hohlraum wall. Profile-matching in radius and time was used to increase the accuracy of density inferred from the transmission. The shock temperature reached several hundred eV, causing ionization which significantly reduced the opacity to the 9 kV x-ray energy. The opacity change at the shock was inferred from the change in apparent mass inside a radiographic marker layer. The speed and compression of the shock were measured from the density profiles. The shock pressure increased with convergence, so a range of Hugoniot states was obtained from each experiment. Shock states were measured between 10 and 80 TPa. Presently at Washington State University.

  9. The oil and gas joint operating agreement

    SciTech Connect

    Not Available

    1990-01-01

    This book covers the following topics: introduction to the AAPL model form operating agreement; property provisions of the operating agreement; Article 6---the drilling and development article; duties and obligations revisited---who bear what risk of loss; operator's liens; accounting procedure joint operations; insurance; taking gas in kind absent a balancing agreement; RMMLF Form 5 Gas Balancing Agreement; tax partnerships for nontax professionals; alternative agreement forms.

  10. International Agreement on Planetary Protection

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The maintenance of a NASA policy, is consistent with international agreements. The planetary protection policy management in OSS, with Field Center support. The advice from internal and external advisory groups (NRC, NAC/Planetary Protection Task Force). The technology research and standards development in bioload characterization. The technology research and development in bioload reduction/sterilization. This presentation focuses on: forward contamination - research on the potential for Earth life to exist on other bodies, improved strategies for planetary navigation and collision avoidance, and improved procedures for sterile spacecraft assembly, cleaning and/or sterilization; and backward contamination - development of sample transfer and container sealing technologies for Earth return, improvement in sample return landing target assessment and navigation strategy, planning for sample hazard determination requirements and procedures, safety certification, (liaison to NEO Program Office for compositional data on small bodies), facility planning for sample recovery system, quarantine, and long-term curation of 4 returned samples.

  11. Annual Progress Report on the Development of Waste Tank Leak Monitoring and Detection and Mitigation Activities in Support of M-45-08

    SciTech Connect

    DEFIGH PRICE, C.

    2000-09-25

    Milestone M-45-09E of the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement or TPA) [TPA 1996] requires submittal of an annual progress report on the development of waste tank leak detection, monitoring, and mitigation (LDMM) activities associated with the retrieval of waste from single-shell tanks (SSTs). This report details progress for fiscal year 2000, building on the current LDMM strategy and including discussion of technologies, applications, cost, schedule, and technical data. The report also includes discussion of demonstrations conducted and recommendations for additional testing. Tri-Party Agreement Milestones M-45-08A and M-45-08B required design and demonstration of LDMM systems for initial retrieval of SST waste. These specific milestones have recently been deleted as part of the M-45-00A change package. Future LDMM development work has been incorporated into specific technology demonstration milestones and SST waste retrieval milestones in the M-45-03 and M-45-05 milestone series.

  12. Suppression of TPA-induced cancer cell invasion by Peucedanum japonicum Thunb. extract through the inhibition of PKCα/NF-κB-dependent MMP-9 expression in MCF-7 cells.

    PubMed

    Kim, Jeong-Mi; Noh, Eun-Mi; Kim, Ha-Rim; Kim, Mi-Seong; Song, Hyun-Kyung; Lee, Minok; Yang, Sei-Hoon; Lee, Guem-San; Moon, Hyoung-Chul; Kwon, Kang-Beom; Lee, Young-Rae

    2016-01-01

    Metastatic cancers spread from their site of origin (the primary site) to other parts of the body. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is important in metastatic cancers as it plays a major role in cancer cell invasion. The present study examined the inhibitory effect of an ethanol extract of Peucedanum japonicum Thunb. (PJT) on MMP-9 expression and the invasion of MCF-7 breast cancer cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis, gelatin zymography, and reverse transcription-quantitative PCR revealed that PJT significantly suppressed MMP-9 expression and activation in a dose-dependent manner. Furthermore, PJT attenuated TPA-induced nuclear translocation and the transcriptional activation of nuclear factor (NF)-κB. The results indicated that the PJT-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involved the suppression of the PKCα/NF-κB pathway in MCF-7 cells. Thus, the inhibition of MMP-9 expression by PJT may have potential value as a therapy for restricting the invasiveness of breast cancer. PMID:26717978

  13. Luteolin 8-C-β-fucopyranoside inhibits invasion and suppresses TPA-induced MMP-9 and IL-8 via ERK/AP-1 and ERK/NF-κB signaling in MCF-7 breast cancer cells.

    PubMed

    Park, Su-Ho; Kim, Jung-Hee; Lee, Dong-Hun; Kang, Jeong-Woo; Song, Hyuk-Hwan; Oh, Sei-Ryang; Yoon, Do-Young

    2013-11-01

    Matrix metalloproteinase 9 (MMP-9) and interleukin-8 (IL-8) play major roles in tumor progression and invasion of breast cancer cells. The present study was undertaken to investigate the inhibitory mechanism of cell invasion by luteolin 8-C-β-fucopyranoside (named as LU8C-FP), a C-glycosylflavone, in human breast cancer cells. We investigated whether LU8C-FP would inhibit MMP-9 activation and IL-8 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 breast cancer cells. LU8C-FP suppressed TPA-induced MMP-9 and IL-8 secretion and mRNA expression via inhibition of the MAPK signaling pathway and down-regulation of nuclear AP-1 and NF-κB. TPA-induced phosphorylation of ERK 1/2 was suppressed by LU8C-FP, whereas JNK and p38 MAPK phosphorylation were unaffected. In addition, LU8C-FP blocked the ERK 1/2 pathways following expression of MMP-9 and IL-8. These results suggest LU8C-FP may function to suppress invasion of breast cancer cells through the ERK/AP-1 and ERK/NF-κB signaling cascades. PMID:23933110

  14. Kinetics of O2 Entry and Exit in Monomeric Sarcosine Oxidase via Markovian Milestoning Molecular Dynamics.

    PubMed

    Bucci, Anthony; Yu, Tang-Qing; Vanden-Eijnden, Eric; Abrams, Cameron F

    2016-06-14

    The flavoenzyme monomeric sarcosine oxidase (MSOX) catalyzes a complex set of reactions currently lacking a consensus mechanism. A key question that arises in weighing competing mechanistic models of MSOX function is to what extent ingress of O2 from the solvent (and its egress after an unsuccessful oxidation attempt) limits the overall catalytic rate. To address this question, we have applied to the MSOX/O2 system the relatively new simulation method of Markovian milestoning molecular dynamics simulations, which, as we recently showed [ Yu et al. J. Am. Chem. Soc. 2015 , 137 , 3041 ], accurately predicted the entry and exit kinetics of CO in myoglobin. We show that the mechanism of O2 entry and exit, in terms of which possible solvent-to-active-site channels contribute to the flow of O2, is sensitive to the presence of the substrate-mimicking competitive inhibitor 2-furoate in the substrate site. The second-order O2 entry rate constants were computed to be 8.1 × 10(6) and 3.1 × 10(6) M(-1) s(-1) for bound and apo MSOX, respectively, both of which moderately exceed the experimentally determined second-order rate constant of (2.83 ± 0.07) × 10(5) M(-1) s(-1) for flavin oxidation by O2 in MSOX. This suggests that the rate of flavin oxidation by O2 is likely not strongly limited by diffusion from the solvent to the active site. The first-order exit rate constants were computed to be 10(7) s(-1) and 7.2 × 10(6) s(-1) for the apo and bound states, respectively. The predicted faster entry and slower exit of O2 for the bound state indicate a longer residence time within MSOX, increasing the likelihood of collisions with the flavin isoalloxazine ring, a step required for reduction of molecular O2 and subsequent reoxidation of the flavin. This is also indirectly supported by previous experimental evidence favoring the so-called modified ping-pong mechanism, the distinguishing feature of which is an intermediate complex involving O2, the flavin, and the oxidized

  15. Canada's health promotion survey as a milestone in public health research.

    PubMed

    Rootman, Irving; Warren, Reg; Catlin, Gary

    2010-01-01

    This commentary describes the contribution of the 1985 Canadian National Health Promotion Survey to the development of public health research and policy-making in Canada and argues that on the basis of that contribution, it should be considered to be a public health research milestone. In terms of research, among its contributions which subsequently have been adopted in other survey studies were: going beyond risk factors to operationalize concepts implicit in the Ottawa Charter for Health Promotion; empowering users to participate in knowledge translation, sharing and transfer; ensuring sufficient sample sizes for each jurisdiction to be able to confidently generalize to its population; establishing a model as well as questions for subsequent health surveys; encouraging widespread use of data through making them available early; and developing and using an explicit social marketing strategy to reach target audiences, including the general public. With regard to policy-making, among its contributions which have been adopted were: using survey data to develop and enhance healthy public policy initiatives; encouraging researchers to work with policy-makers in developing policies; using survey data to contribute to the evaluation of public health initiatives; engaging policy-makers in the development of surveys; and encouraging the use of survey data for advocacy. PMID:21370775

  16. Colloidal nanocrystals for quality lighting and displays: milestones and recent developments

    NASA Astrophysics Data System (ADS)

    Erdem, Talha; Demir, Hilmi Volkan

    2016-06-01

    Recent advances in colloidal synthesis of nanocrystals have enabled high-quality high-efficiency light-emitting diodes, displays with significantly broader color gamut, and optically-pumped lasers spanning the whole visible regime. Here we review these colloidal platforms covering the milestone studies together with recent developments. In the review, we focus on the devices made of colloidal quantum dots (nanocrystals), colloidal quantum rods (nanorods), and colloidal quantum wells (nanoplatelets) as well as those of solution processed perovskites and phosphor nanocrystals. The review starts with an introduction to colloidal nanocrystal photonics emphasizing the importance of colloidal materials for light-emitting devices. Subsequently,we continue with the summary of important reports on light-emitting diodes, in which colloids are used as the color converters and then as the emissive layers in electroluminescent devices. Also,we review the developments in color enrichment and electroluminescent displays. Next, we present a summary of important reports on the lasing of colloidal semiconductors. Finally, we summarize and conclude the review presenting a future outlook.

  17. OUTLINING THE WINDOWS OF ACHIEVEMENT OF INTERSUBJECTIVE MILESTONES IN TYPICALLY DEVELOPING TODDLERS.

    PubMed

    Sadurní Brugué, Marta; Pérez Burriel, Marc

    2016-07-01

    Babies are born with an innate drive or intrinsic motive formation with which to communicate and share meanings with others and that some authors have called intersubjectivity (S. Bråten & C. Trevarthen, 2007; C. Trevarthen, 1974, 2001). Around the ninth month of life, this motivation changes and passes from a person-to-person dyadic (primary intersubjectivity) to a person-person-object relationship (secondary intersubjectivity). S. Bråten and C. Trevarthen (2007) also proposed a third form or layer of intersubjectivity known as tertiary intersubjectivity. One hundred fifteen free-play sessions of 27 mother-child dyads (13 girls and 14 boys ages 9-37 months) were filmed and categorized using the Level of Intersubjective Attunement Scale (LISA-T; M. Pérez Burriel & M. Sadurní Brugué, 2014; M. Sadurní Brugué & M. Pérez Burriel, 2012). Results from these nine hierarchical levels are presented, following a developmental sequence or population trajectory around an interindividual variability. In this article, we propose viewing these age-related levels as windows of achievement of intersubjective milestones. The statistical analysis suggested a redesign of the LISA-T levels of intersubjectivity; thus, results from this redesign and the debate on the implications of these transitions in infant mental health development are presented. PMID:27348723

  18. Multiscale Estimation of Binding Kinetics Using Brownian Dynamics, Molecular Dynamics and Milestoning

    PubMed Central

    Votapka, Lane W.; Amaro, Rommie E.

    2015-01-01

    The kinetic rate constants of binding were estimated for four biochemically relevant molecular systems by a method that uses milestoning theory to combine Brownian dynamics simulations with more detailed molecular dynamics simulations. The rate constants found using this method agreed well with experimentally and theoretically obtained values. We predicted the association rate of a small charged molecule toward both a charged and an uncharged spherical receptor and verified the estimated value with Smoluchowski theory. We also calculated the kon rate constant for superoxide dismutase with its natural substrate, O2 −, in a validation of a previous experiment using similar methods but with a number of important improvements. We also calculated the kon for a new system: the N-terminal domain of Troponin C with its natural substrate Ca2+. The kon calculated for the latter two systems closely resemble experimentally obtained values. This novel multiscale approach is computationally cheaper and more parallelizable when compared to other methods of similar accuracy. We anticipate that this methodology will be useful for predicting kinetic rate constants and for understanding the process of binding between a small molecule and a protein receptor. PMID:26505480

  19. Supportive care in lung cancer: milestones over the past 40 years.

    PubMed

    Molassiotis, Alex; Uyterlinde, Wilma; Hollen, Patricia J; Sarna, Linda; Palmer, Patricia; Krishnasamy, Meinir

    2015-01-01

    The evolution of supportive care in lung cancer (LC) is the focus of this article, which aims to present an overall picture of the developments in the field, highlight milestones over the past four decades, and provide directions for future research and practice. Although in the 1970s this study was minimal, from the 1980s onwards, there was an expansion of the range of topics covered in the literature, reflecting the importance of supportive care to clinical practice. These areas include the identification of supportive care needs in LC, symptoms and symptom management, psychosocial aspects and coping with LC (including support of caregivers), quality of life issues and the development and testing of patient-reported outcomes, the option of best supportive care versus treatment, smoking cessation before and after diagnosis of LC, and service delivery models. This article celebrates the evolution of supportive LC care over the past 40 years alongside recognizing that more work needs to be done in the future and new research foci need to be developed to meet the current needs of patients with LC. The role and the continuous efforts of the International Association of the Study of Lung Cancer, including the sixteenth World Conference on Lung Cancer in 2015 to meet this goal, will be crucial and strategic in the future. PMID:25325780

  20. Achieving competence in colonoscopy: Milestones and the need for a new endoscopic curriculum in gastroenterology training

    PubMed Central

    Stanford, Sara B; Lee, Stephanie; Masaquel, Candace; Lee, Robert H

    2015-01-01

    Colonoscopy is considered to be the most effective tool for reducing colorectal cancer (CRC) morbidity and mortality. As a result, certifying trainee competence in the performance of colonoscopy is critical to maximizing CRC screening and prevention efforts. Guidelines on training and accreditation around the world have been revised to emphasize the attainment of milestones in the technical and cognitive skills necessary to perform the procedure. To meet this challenge, new evaluation systems have been developed to measure trainee competence through all aspects of colonoscopy training. These changes stem from increased recognition that procedural numbers alone do not necessarily guarantee trainees’ proficiency in the performance of colonoscopy. Variability in endoscopic practice and in CRC screening outcomes also point to deficiencies in the current approach towards colonoscopy instruction. However, technological innovations hold great promise in training endoscopists to perform high quality colonoscopy. Furthermore, potential advances in the use of feedback as a training tool provide new avenues for research. This review summarizes the latest evidence on the effort to define, evaluate and promote the achievement of competence in colonoscopy among trainees. PMID:26675559

  1. FINAL REPORT: SUNSHINE STATE SOLAR GRID INITIATIVE (SUNGRIN) PHASE 1 (Critical Milestone Review Version)

    SciTech Connect

    Meeker, Rick; Steurer, Mischa; Li, Hui; Edrington, Chris; Dale, Steinar; Faruque, MD Omar; Schoder, Karl; McLaren, Peter G.; Liu, Liming; Ravindra, Harsha; Henry, Shawn; Zhou, Yan; Liu, Xiaohu; Springstroh, Aaron; Click, David; Reedy, Robert; Moaveni, Houtan; Davis, Kristopher; Cromer, Charlie; Pappalardo, Anthoney; Krueger, Rodica; Domijan, Alexander; Islam, Arif; Islam, Mujahidil; Damole, Ademole

    2012-03-30

    This report provides details on the activities and accomplishments of Phase 1 of the Sunshine State Solar Grid Initiative (SUNGRIN) Project for the period beginning 4/28/2010 and ending 12/31/2011. SUNGRIN is a five-phase high-penetration solar PV project within the Systems Integration (SI) area of the Solar Energy Technologies (SETP) Program, under the SunShot Initiative. SUNGRIN is focused on understanding and enabling high-penetration grid-connected solar PV through simulation assisted studies of actual Florida utility high-penetration distribution circuits as well as substations and, to a limited extent, the bulk power system. Each phase builds and expands upon the efforts of the previous phase, leading to a comprehensive examination and understanding of high-penetration solar PV issues, from the solar resource to the conversion and integration technologies to the electric power system, with Florida and it’s utility partners providing the broad range of conditions and system integration scenarios necessary to develop useful insight and solutions. This phase, Phase 1, was funded with American Recovery and Reinvestment Act (ARRA) funds. This version of the final report is organized to align with statement of project objectives (SOPO) critical milestones.

  2. Introducing the Guard-Stage-Milestone Approach for Specifying Business Entity Lifecycles

    NASA Astrophysics Data System (ADS)

    Hull, Richard; Damaggio, Elio; Fournier, Fabiana; Gupta, Manmohan; Heath, Fenno (Terry); Hobson, Stacy; Linehan, Mark; Maradugu, Sridhar; Nigam, Anil; Sukaviriya, Piyawadee; Vaculin, Roman

    A promising approach to managing business operations is based on business entities with lifecycles (BEL's) (a.k.a. business artifacts), i.e., key conceptual entities that are central to guiding the operations of a business, and whose content changes as they move through those operations. A BEL type includes both an information model that captures, in either materialized or virtual form, all of the business-relevant data about entities of that type, and a lifecycle model, that specifies the possible ways an entity of that type might progress through the business by responding to events and invoking services, including human activities. Most previous work on BEL's has focused on the use of lifecycle models based on variants of finite state machines. This paper introduces the Guard-Stage-Milestone (GSM) meta-model for lifecycles, which is an evolution of the previous work on BEL's. GSM lifecycles are substantially more declarative than the finite state machine variants, and support hierarchy and parallelism within a single entity instance. The GSM operational semantics are based on a form of Event-Condition-Action (ECA) rules, and provide a basis for formal verification and reasoning. This paper provides an informal, preliminary introduction to the GSM approach, and briefly overviews selected research directions.

  3. Sexual Agreements among Gay Male Couples

    PubMed Central

    Hoff, Colleen H.; Beougher, Sean C.

    2009-01-01

    Many gay male couples make agreements about whether or not to permit sex with outside partners, yet little is known about the development and maintenance of these agreements, their impact on relationships, and whether they are an effective HIV prevention strategy. Using semi-structured, qualitative interviews, 39 gay male couples were asked about their sexual agreements and about other relationship dynamics that might affect their agreements. Analysis revealed a wide range of agreement types, all of which are presented along a continuum rather than as discrete categories. For couples with open agreements, most placed rules or conditions limiting when, where, how often, and with whom outside sex was permitted. Although motivations for having agreements varied, HIV prevention did not rank as a primary factor for any couple. Most couples had congruous agreements; however, a small number reported discrepancies which may increase HIV transmission risk. How couples handled breaks in their agreements also varied, depending on what condition was broken, whether it was disclosed, and the partner's reaction. Additional results include differences in agreement type and motivations for having an agreement based on couple serostatus. Overall, agreements benefited couples by providing boundaries for the relationship, supporting a non-heteronormative identity, and fulfilling the sexual needs of the couple. Future prevention efforts involving gay couples must address the range of agreement types and the meanings couples ascribe to them, in addition to tempering safety messages with the relationship issues that are important to and faced by gay couples. PMID:18686027

  4. Cooperative agreement 926 (SETI Institute)

    NASA Astrophysics Data System (ADS)

    Marshall, John R.

    1996-01-01

    Research activities carried out as part of cooperative agreement 926 are summarized. A portable, field deployable X-ray diffractometer-spectrometer was developed that can analyze rock surfaces and loose granular materials without the need for sample acquisition or preparation. The device was deployed on the Russian Marsokhod rover at the NASA Ames Research Center. Techniques and technological innovations were developed that provide the basis for a new kind of X-ray source. In the area of x-ray analysis techniques, artificial diffraction spectra were created to determine how complex mineral mixtures can be analyzed by diffractometry when only broad fingerprint patterns emerge from the analyses. USML-2 tapes were analyzed. A preliminary, but successful computer code was developed to simulate the behavior of agglomerating granular matter as it may occur in martian dust storms. The model is based on dipole-dipole interactions. In the area of aeolian comminution, using a particle impelling crossbow device , it was possible to elucidate the processes involved in reptation sand transport likely to occur on Mars and Earth. A theoretical model was developed that relates the microscopic cratering mechanisms during saltation-reptation to the megascopic impact processes caused by meteorites. Abstracts of two conference papers as well as five short articles published or submitted for publication are included as attachments.

  5. Monitoring of Biomedical License Agreements

    PubMed Central

    Keller, George H.; Ferguson, Steven M.; Pan, Percy

    2009-01-01

    Because technology licensed from research organizations can play a significant role in drug innovation and the generation of novel biomedical products, licensee performance under such agreements must be effectively monitored. This is necessary so that resultant benefits, including public health improvement, may be returned to the innovator(s) as well as society at large. The tasks that comprise monitoring are varied, but all come under the general heading of ‘enforcement of license provisions’. Since 1996, the license monitoring and enforcement program established by the US National Institutes of Health (NIH) Group has collected about $US17 million in unpaid and underpaid license royalties through formal financial audits and other investigative activities. During the same period, the Office of Technology Transfer (OTT) settled more than 60 cases of suspected patent infringement, generating around 60 new licenses and collected both back and ongoing royalties. As these numbers show, an active and effective monitoring program is an essential part of any technology transfer or biomedical licensing program. PMID:19960074

  6. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  7. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  8. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT, AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  9. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  10. 22 CFR 124.1 - Manufacturing license agreements and technical assistance agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Manufacturing license agreements and technical... ARMS REGULATIONS AGREEMENTS, OFF-SHORE PROCUREMENT AND OTHER DEFENSE SERVICES § 124.1 Manufacturing... manufacturing license agreements, technical assistance agreements, distribution agreements, or...

  11. Tat-CBR1 inhibits inflammatory responses through the suppressions of NF-κB and MAPK activation in macrophages and TPA-induced ear edema in mice

    SciTech Connect

    Kim, Young Nam; Kim, Dae Won; Jo, Hyo Sang; Shin, Min Jea; Ahn, Eun Hee; Ryu, Eun Ji; Yong, Ji In; Cha, Hyun Ju; Kim, Sang Jin; Yeo, Hyeon Ji; Youn, Jong Kyu; Hwang, Jae Hyeok; Jeong, Ji-Heon; Kim, Duk-Soo; Cho, Sung-Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2015-07-15

    Human carbonyl reductase 1 (CBR1) plays a crucial role in cell survival and protects against oxidative stress response. However, its anti-inflammatory effects are not yet clearly understood. In this study, we examined whether CBR1 protects against inflammatory responses in macrophages and mice using a Tat-CBR1 protein which is able to penetrate into cells. The results revealed that purified Tat-CBR1 protein efficiently transduced into Raw 264.7 cells and inhibited lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2), nitric oxide (NO) and prostaglandin E{sub 2} (PGE{sub 2}) expression levels. In addition, Tat-CBR1 protein leads to decreased pro-inflammatory cytokine expression through suppression of nuclear transcription factor-kappaB (NF-κB) and mitogen activated protein kinase (MAPK) activation. Furthermore, Tat-CBR1 protein inhibited inflammatory responses in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation when applied topically. These findings indicate that Tat-CBR1 protein has anti-inflammatory properties in vitro and in vivo through inhibition of NF-κB and MAPK activation, suggesting that Tat-CBR1 protein may have potential as a therapeutic agent against inflammatory diseases. - Highlights: • Transduced Tat-CBR1 reduces LPS-induced inflammatory mediators and cytokines. • Tat-CBR1 inhibits MAPK and NF-κB activation. • Tat-CBR1 ameliorates inflammation response in vitro and in vivo. • Tat-CBR1 may be useful as potential therapeutic agent for inflammation.

  12. 75 FR 8719 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ... under the Shipping Act of 1984. Interested parties may submit comments on the agreements to the... ports of Miami, FL and George Town, Grand Cayman. Agreement No.: 012091. Title: HLAG/HSDG Slot...

  13. 14 CFR 437.35 - Agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... TRANSPORTATION LICENSING EXPERIMENTAL PERMITS Requirements to Obtain an Experimental Permit Operational Safety Documentation § 437.35 Agreements. An applicant must enter into the agreements required by § 437.63, and...

  14. 14 CFR 437.35 - Agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... TRANSPORTATION LICENSING EXPERIMENTAL PERMITS Requirements to Obtain an Experimental Permit Operational Safety Documentation § 437.35 Agreements. An applicant must enter into the agreements required by § 437.63, and...

  15. 37 CFR 42.409 - Settlement agreements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... OF COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Derivation After Institution of Derivation Proceeding § 42.409 Settlement agreements. An agreement or understanding under 35 U.S.C. 135(e)...

  16. 75 FR 31438 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... Lines Joint Service Agreement. Filing Party: Tara L. Leiter, Esq.; Blank Rome, LLP; Watergate; 600 New... Service Agreement. Filing Party: Tara L. Leiter, Esq.; Blank Rome, LLP; Watergate; 600 New...

  17. 75 FR 6397 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ....gov . Agreement No.: 011346-019. Title: Israel Trade Conference Agreement. Parties: A.P. Moller-Maersk..., Esq.; Chairman; Israel Trade Conference; 80 Wall Street, Suite 1117; New York, NY 10005-3602....

  18. 48 CFR 1542.1203 - Processing agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... MANAGEMENT CONTRACT ADMINISTRATION Novation and Change of Name Agreements 1542.1203 Processing agreements. (a... required documentary evidence. (2) Verify the accuracy of the list of contracts through the...

  19. 75 FR 7265 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ....gov . Agreement No.: 011426-047. Title: West Coast of South America Discussion Agreement. Parties: A.P....; Mediterranean Shipping Company, SA; Seaboard Marine Ltd.; South Pacific Shipping Company, Ltd.; and...

  20. 78 FR 30302 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... . Agreement No.: 011707-010. Title: Gulf/South America Discussion Agreement. Parties: Industrial Maritime....; Associate Counsel & Environmental Officer; CMA CGM (America) LLC; 5701 Lake Wright Drive; Norfolk, VA...

  1. 37 CFR 42.409 - Settlement agreements.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... OF COMMERCE TRIAL PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Derivation After Institution of Derivation Proceeding § 42.409 Settlement agreements. An agreement or understanding under 35 U.S.C. 135(e)...

  2. 76 FR 43686 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    .... Agreement No.: 012133. Title: Mitsui O.S.K. Lines/Kawasaki Kisen Kaisha Space Charter Agreement. Parties: Kawasaki Kisen Kaisha, Ltd. and Mitsui O.S.K. Lines, Ltd. Filing Party: John P. Meade, Esq.;...

  3. 77 FR 24712 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... existing services. Agreement No.: 012165. Title: MOL/APL/HMM Asia/USEC Slot Charter Agreement. Parties... to charter space to APL and HMM on certain vessels MOL operates or on which MOL has space...

  4. 76 FR 63618 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-13

    ... Singapore. Agreement No.: 012138. Title: CSAV/CCNI Venezuela Space Charter Agreement. Parties: Compana Sud... Venezuela. Dated: October 7, 2011. By Order of the Federal Maritime Commission. Karen V. Gregory,...

  5. 42 CFR 460.154 - Enrollment agreement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... agreement which contains, at a minimum, the following information: (a) Applicant's name, sex, and date of... service provider. (q) A statement that the PACE organization has an agreement with CMS and the...

  6. 75 FR 74732 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... after November 24, 2010. Agreement No.: 012111. Title: Hainan PO Shipping Co., Ltd. and TS Lines Ltd. Slot Charter Agreement. Parties: Hainan PO Shipping Co., Ltd. and T.S. Lines Ltd. Filing Party: Neal...

  7. 78 FR 23251 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ..., Vengrow & Textor, LLP; 61 Broadway, Suite 3000, New York, NY 10006-2802 Synopsis: The agreement authorizes...; 61 Broadway, Suite 3000, New York, NY 10006- 2802. Synopsis: The agreement authorizes the parties...

  8. 77 FR 68121 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-15

    ..., Sailing and Cooperative Working Agreement. Parties: Priority RoRo Services, LLC and Marine Express, Inc.../Ro Space Charter and Sailing Agreement. Parties: Crowley Latin America Services, LLC and Priority...

  9. 76 FR 12962 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-09

    ....gov . Agreement No.: 011885-002. Title: CMA CGM/MSC Reciprocal Space Charter, Sailing and Cooperative... Coast Two-Loop Space Charter, Sailing and Cooperative Working Agreement. Parties: A.P. Moller-Maersk...

  10. 76 FR 61704 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-05

    ... requirement. Agreement No.: 012136. Title: HSDG/ML/MSC Space Charter Agreement. Parties: Hamburg-Sud, A.P... authorizes Hamburg-Sud and Maersk to charter space to Med Shipping in the trade between U.S. Atlantic...

  11. 76 FR 68187 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ....gov . Agreement No.: 012034-004. Title: Hamburg Sud/Maersk Line Vessel Sharing Agreement. Parties: Hamburg-Sud and A.P. Moeller-Maersk A/S. ] Filing Party: Wayne Rohde, Esq.; Cozen O'Connor; 1627 I...

  12. 78 FR 55697 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-11

    ... . Agreement No.: 012139-001. Title: OVSA/MSC Space Charter Agreement. Parties: Hamburg-Sud, MSC Mediterranean... Sud North America, Inc.; Hanjin Shipping Company, Ltd.; Hapag-Lloyd (America), Inc; Horizon Lines,...

  13. 77 FR 71192 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-29

    ....: 012190. Title: HSDG-GWF Space Charter Agreement. Parties: Hamburg Sud and Great White Fleet Liner..., DC 20006-4007. Synopsis: The agreement authorizes Hamburg Sud to charter space to Great White...

  14. 75 FR 54884 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ...: HLAG/HSDG Trans-Atlantic Space Charter Agreement. Parties: Hamburg Sud and Hapag-Lloyd. Filing Parties...: The agreement authorizes Hapag-Lloyd to charter space to Hamburg Sud in the trade between New York...

  15. 77 FR 74013 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ... Agreement. Parties: Hamburg Sud and Compania Chilena De Navegacion Interoceanica, S.A. Filing Party: Wayne R... agreement authorizes Hamburg Sud to charter space to CCNI in the trade between ports in California and...

  16. Brief Report: Ages of Language Milestones as Predictors of Developmental Trajectories in Young Children with Autism Spectrum Disorder.

    PubMed

    Kover, Sara T; Edmunds, Sarah R; Ellis Weismer, Susan

    2016-07-01

    Recognizing early risk markers in young children with autism spectrum disorder (ASD) is critical for timely diagnosis and intervention. The purpose of this study was to extend previous findings regarding language milestones to a longitudinal design, in which ages of expressive language milestones (i.e., first words, first phrases) could serve as predictors of developmental trajectories in a heterogeneous sample of young children with ASD (N = 98; age at first assessment: M = 32 months, SD = 5). Age of first words predicted trajectories of expressive language and adaptive skills; number of words predicted each outcome examined. Because these aspects of early language show promise as potential indicators of later functional outcomes, future research on developmental processes as they relate to individual differences will be particularly informative. PMID:26936159

  17. 78 FR 51757 - Negotiated Service Agreement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ... Agreement within the GEPS 3 product. Id. at 2. \\1\\ Notice of United States Postal Service of Filing a... Commission first approved the addition of a GEPS negotiated service agreement to the competitive product list... Postal Service therefore requests that the Commission add the Agreement to the GEPS 3 product. Id....

  18. 48 CFR 519.7010 - Agreement contents.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Agreement contents. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7010 Agreement contents. The contents of the Agreement must contain: (a) Names, addresses (including facsimile, e-mail, and...

  19. 48 CFR 519.7010 - Agreement contents.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Agreement contents. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7010 Agreement contents. The contents of the Agreement must contain: (a) Names, addresses (including facsimile, e-mail, and...

  20. 48 CFR 519.7010 - Agreement contents.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Agreement contents. 519... SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS GSA Mentor-Protégé Program 519.7010 Agreement contents. The contents of the Agreement must contain: (a) Names, addresses (including facsimile, e-mail, and...