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. "Missing Milestones."

    ERIC Educational Resources Information Center

    Afzal, Nadeem A.; Martin, Diana L.; Atkinson, Patricia I.

    2001-01-01

    Examined the development of seven infants with "missing milestones" in motor development. Found that three children had normal development, three developed global developmental delay, and one was diagnosed with multiple cavernous haemangiomata in the brain. Suggested that missing milestones can be a benign variation of normal motor development or…

  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. 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 1274.908 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL FIRMS Other Provisions and Special Conditions § 1274.908 Milestone payments. Milestone Payments July 2002 (a) By submission of the...

  5. Developmental Milestones.

    PubMed

    Scharf, Rebecca J; Scharf, Graham J; Stroustrup, Annemarie

    2016-01-01

    • On the basis of observational studies (level C), preterm birth is a leading cause of neurodevelopmental disabilities in children, and the degree of neurodevelopmental disability is inversely correlated with gestational age at birth. When comparing performance of preterm children to developmental norms, “corrected age” or age from due date rather than birth date should be used for the first 24 to 36 months. • On the basis of observational studies (level C), clinicians should pay specific attention to sensory function in children born preterm because the incidence of visual and hearing impairments is higher in preterm than term children. Due to the elevated risk of cognitive and behavioral disabilities, clinicians caring for children born preterm should be vigilant when performing developmental assessments to improve outcomes. • On the basis of observational studies (level C), early identification of developmental delays allows for referral to therapeutic services, and children referred for early intervention are more likely to make gains in developmental milestones. PMID:26729779

  6. Developmental milestones record - 3 years

    MedlinePlus

    Normal childhood growth milestones - 3 years; Growth milestones for children - 3 years; Childhood growth milestones - 3 years ... milestones are typical for children in their third year of life. Always keep in mind that some ...

  7. Developmental milestones record - 5 years

    MedlinePlus

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

  8. 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 ...

  9. 14 CFR 1274.908 - Milestone payments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Milestone payments. 1274.908 Section 1274.908 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH... cooperative agreement. (ix) Taxpayer identification number (TIN). (x) While not required, the recipient...

  10. 14 CFR 1274.908 - Milestone payments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Milestone payments. 1274.908 Section 1274.908 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH... cooperative agreement. (ix) Taxpayer identification number (TIN). (x) While not required, the recipient...

  11. 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 ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  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. Developmental milestones record

    MedlinePlus

    ... foot Rides tricycle well Starts school Understands size concepts Understands time concepts School-age child -- 6 to 12 years Begins ... and recognition is of vital importance Understands abstract concepts ... topics include: Developmental milestones record - 2 months ...

  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. Equation-of-state measurements for polystyrene at multi-TPa pressures in laser direct-drive experiments

    SciTech Connect

    Ozaki, N.; Ono, T.; Takamatsu, K.; Tanaka, K.A.; Nakano, M.; Kataoka, T.; Yoshida, M.; Wakabayashi, K.; Nakai, M.; Nagai, K.; Shigemori, K.; Yamanaka, T.; Kondo, K.

    2005-12-15

    Equation-of-state (EOS) measurements for polystyrene in TPa (10 Mbar) pressure regions are presented. Polystyrene Hugoniot data were obtained up to 2.7 TPa using impedance matching techniques with laser direct drive at the GEKKO/HIPER laser facility [N. Miyanaga et al., in Proceedings of the 18th International Conference on Fusion Energy (IAEA, Sorrento, Italy, 2001), IAEA-CN-77] The results were compared with theoretical models and previous experimental data and found to be in good agreement with the previous data obtained by different drive and diagnostic techniques.

  1. Milestones in electron crystallography.

    PubMed

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

    2006-01-01

    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 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.

  2. 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 ...

  3. Milestoning without a Reaction Coordinate

    PubMed Central

    Májek, Peter; Elber, Ron

    2010-01-01

    Milestoning is a method for calculating kinetics and thermodynamics of long time processes typically not accessible for straightforward Molecular Dynamics (MD) simulation. In the Milestoning approach, the system of interest is partitioned into cells by dividing hypersurfaces (Milestones) and transitions are computed between nearby hypersurfaces. Kinetics and thermodynamics are derived from the statistics of these transitions. The original Milestoning work concentrated on systems in which a one-dimensional reaction coordinate or an order parameter could be identified. In many biomolecular processes the reaction proceeds via multiple channels or following more than a single order parameter. A description based on a one-dimensional reaction coordinate may be insufficient. In the present paper we introduce a variation that overcomes this limitation. Following the ideas of Vanden-Eijnden and Venturoli on Voronoi cells that avoid the use of an order parameter (J. Chem. Phys. 2009, 130, 194101), we describe another way to “Milestone” systems without a reaction coordinate. We examine the assumptions of the Milestoning calculations of mean first passage times (MFPT) and describe strategies to weaken these assumptions. The method described in this paper, Directional Milestoning, arranges hypersurfaces in higher dimensions that “tag” trajectories such that efficient calculations can be done and at the same time the assumptions required for exact calculations of MFPTs are satisfied approximately. In the original Milestoning papers trajectories are initiated from an equilibrium set of conformations. Here a more accurate distribution, that mimics the first hitting point distribution, is used. We demonstrate the usage of Directional Milestoning in conformational transitions of alanine dipeptide (in vacuum and in aqueous solution) and compare the correctness, efficiency, and statistical stability of the method with exact MD and with a related method. PMID:20596240

  4. 14 CFR § 1274.908 - Milestone payments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Milestone payments. § 1274.908 Section § 1274.908 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS...) Taxpayer identification number (TIN). (x) While not required, the recipient is strongly encouraged...

  5. 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...

  6. The medical malpractice TPA: Taking it to the next level.

    PubMed

    Sicard, Lauren E; Ruzzo, Loreto

    2016-04-01

    Risk managers whose organizations self-insure their medical professional liabilities often find themselves dealing with their institution's third-party administrator (TPA), the independent entity that manages claims against the organization and its employees. By understanding better the purpose and operations of a TPA, risk managers can enhance their organizations' litigation outcomes while adding new tools to improve patient safety and quality of care. Viewing the TPA simply as an expense item to be reduced to its lowest possible level deprives the organization of a valuable resource in the form of high-quality data on the drivers of professional liability losses. This article identifies the qualities found in an exceptional medical malpractice TPA and suggests ways to create an effective partnership that will reduce the total cost of claims while supporting the risk manager's mission. PMID:27088774

  7. 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 ...

  8. 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…

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. 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.

  14. 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...

  15. 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

  16. Megagauss X: a conference milestone /

    SciTech Connect

    Fowler, C. M.

    2004-01-01

    The first Megagauss Conference now known as MG I, was held in 1965. Thirty-nine years later, we are now attending MG X. As topical conferences go, this is a fairly long time. For comparison, the first IEEE International Pulsed Power Conference was held in 1976. It seems appropriate in the opening address of this 'Milestone' conference to note some highlights of the earlier MG conferences. Some relatively new research lines in progress will also be noted, as well as the speaker's 'wish list' of projects he would like to see pursued. Mention will be made of the growing number of explosive flux compression facilities around the world, as well as some facilities that no longer exist, but that made significant contributions in their time.

  17. 14 CFR 1274.908 - Milestone payments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... July 2002 (a) By submission of the first invoice, the Recipient is certifying that it has an... following milestones: Date PaymentMilestone Amount (c) Upon submission by the recipient of invoices in... after receipt of proper invoice. Payment shall be considered as being made on the date of...

  18. Tri-Party Agreement databases, access mechanism and procedures

    SciTech Connect

    Brulotte, P.J.; Christensen, K.C.

    1993-10-01

    This document contains the information required for the Washington State Department of Ecology (Ecology) and the US Environmental Protection Agency (EPA) to access databases related to the Hanford Federal Facility Agreement and Consent Order [also known as the Tri-Party Agreement (TPA)] (Ecology et al. 1992). It identifies the procedure required to obtain access to the Hanford computer networks and the TPA related databases. It addresses security requirements, access methods, database availability dates, database access procedures, and the minimum computer hardware and software configurations required to operate within the Hanford networks.

  19. [The antioxidative mechanisms of tea polyphenols in inhibiting tumor promotion by TPA].

    PubMed

    Qi, L; Han, C

    1998-01-01

    In the mouse study, topical application of green tea polyphenols (GTP) significantly inhibited TPA-induced increasing of epidermal ornithine decarboxylase (ODC) and increased the activities of several antioxidant enzymes (CAT, GR and GST). In another in vitro study, when GTP was incubated with TPA and mice polymorphonuclear leukocytes (PMNs), TPA induced hydrogen peroxide formation was markedly suppressed with a dose-dependent relationship. The results suggest that the antioxidative effect of GTP may play an important role in inhibiting tumor promotion.

  20. 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…

  1. "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…

  2. 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.

  3. Mild hypothermia markedly reduces ischemia related coronary t-PA release.

    PubMed

    van der Pals, Jesper; Götberg, Matthias; Olivecrona, Göran K; Brogren, Helen; Jern, Sverker; Erlinge, David

    2010-04-01

    In experimentally induced myocardial ischemia, mild hypothermia (33-35 degrees C) has a robust cardioprotective effect. Tissue plasminogen activator (t-PA) is a profibrinolytic enzyme that is released from the vascular endothelial cells in response to ischemia and other injurious stimuli. t-PA has also been found to have proinflammatory properties that could contribute to reperfusion injury. We postulated that hypothermia could attenuate t-PA release in the setting of myocardial ischemia. Sixteen 25-30 kg pigs were anesthetized and a temperature of 37 degrees C was established using an intravascular cooling/warming catheter. The pigs were then randomized to hypothermia (34 degrees C) or control (37 degrees C). A doppler flow wire was placed distal to a percutaneous coronary intervention balloon positioned immediately distal to the first diagonal branch of the left anterior descending artery (LAD). The LAD was then occluded for 10 min in all pigs. Coronary blood flow and t-PA was measured before, during and after ischemia/reperfusion. t-PA was measured in peripheral arterial blood and locally in the venous blood from the coronary sinus. Net t-PA release over the coronary bed was calculated by subtraction of arterial values from coronary sinus values. An estimate of differences in total t-PA release was calculated by multiplying net t-PA release with the relative increase in flow compared to baseline, measured in relative units consisting of ((ng/ml - ng/ml) x (cm/s/cm/s)). There was no observed difference in t-PA levels in peripheral arterial samples. As shown previously, net t-PA release increased during reperfusion. Hypothermia significantly inhibited the increase in t-PA release during reperfusion (peak value 9.44 +/- 4.34 ng/ml vs. 0.79 +/- 0.45 ng/ml, P = 0.02). The effect was even more prominent when an estimation of total t-PA release was performed with mean peak value in the control group 26-fold higher than in the hypothermia group (69.74 +/- 33.86 units vs

  4. Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger.

    PubMed

    Yamamoto, T; Sakaguchi, N; Hachiya, M; Nakayama, F; Yamakawa, M; Akashi, M

    2009-04-01

    Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive oxygen species (ROS) generation in these cells, and phagocytic ability was also stimulated during differentiation. The antioxidant agent N-acetyl-L-cysteine inhibited the TPA-induced differentiation of U937 cells. TPA treatment decreased the expression level of catalase, which catalyzes the decomposition of hydrogen peroxide (H(2)O(2)) to H(2)O and O(2). In contrast, TPA increased the level of manganese superoxide dismutase, which catalyzes the dismutation of superoxide into H(2)O(2) and O(2) without affecting the levels of copper-zinc superoxide dismutase or glutathione peroxidase 1, which removes H(2)O(2) using glutathione as substrate. Treatment of U937 cells with catalase inhibited the enhancement of ROS generation induced by TPA, and blocked the TPA-induced differentiation of U937 cells. Human promyelocytic cell line HL60 cells were also induced to differentiate into macrophages by TPA. However, HP100-1 cells, its variant cell line overexpressing catalase, were resistant to TPA-induced differentiation. Our results suggest that catalase inhibits monocytic differentiation by TPA; the decrease in catalase level and the accumulation of H(2)O(2) are significant events for monocyte/macrophage differentiation by TPA.

  5. 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.

  6. 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.

  7. 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...

  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. 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...

  10. 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...

  11. 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…

  12. Self-Perceived Milestones in Aging.

    ERIC Educational Resources Information Center

    Meyer, Ann Jane

    Theorists and researchers have developed abstract divisions in the life span to mark significant stages. To explore the conceptual labels individuals use to make divisions in their life spans, 92 adults, aged 20 to 55 years, marked significant milestones on a lifeline. Participants also completed a demographic questionnaire. Data on the labels…

  13. Does treatment with t-PA increase the risk of developing epilepsy after stroke?

    PubMed

    Keller, Lena; Hobohm, Carsten; Zeynalova, Samira; Classen, Joseph; Baum, Petra

    2015-10-01

    Patients suffering from ischemic stroke carry an enhanced risk of developing secondary epilepsy. We sought to clarify whether thrombolytic treatment with recombinant tissue plasminogen activator (t-PA) is independently associated with post-stroke epilepsy (PSE). In this observational study, data from 302 stroke patients treated at a single academic neurological department were analyzed retrospectively. Median follow-up was 42 months (maximum 80). Variables included presence of comorbidity, stroke severity, neurological presentation, complications, infarct characteristics, and treatment with t-PA. After univariate analyses, a multivariate analysis was performed to create a model of factors that were significantly associated with PSE, including treatment with t-PA. 13.9 % of patients developed PSE during follow-up. Multivariate analysis identified 5 independent factors for PSE: low Barthel Index at discharge; hemianopia; infection acquired during the hospital stay; involvement of the temporal lobe; involvement of the perirolandic cortex. While the incidence of PSE was higher in patients treated with t-PA (20.6 vs. 10.7 %, univariate analysis; p = 0.020), the effect was lost after adjusting for several factors associated with t-PA treatment [odds ratio for PSE after treatment with t-PA 1.3 (95 % CI 0.6-2.9), p = 0.489]. This study failed to identify treatment with t-PA as an independent risk factor for PSE.

  14. 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.

  15. 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

  16. 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

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

    PubMed Central

    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

  18. 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

  19. 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... projected budget for completing the milestone; and (2) Adjust future payable milestones, as needed,...

  20. 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,...

  1. 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... projected budget for completing the milestone; and (2) Adjust future payable milestones, as needed,...

  2. 10 CFR 603.1105 - Advance payments or payable milestones.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 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,...

  3. 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... projected budget for completing the milestone; and (2) Adjust future payable milestones, as needed,...

  4. 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.

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

    DOE PAGES

    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

  6. 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.

  7. 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.

  8. Changing contraindications for t-PA in acute stroke: review of 20 years since NINDS.

    PubMed

    Parker, Sarah; Ali, Yasmin

    2015-10-01

    When intravenous (IV) tissue-type plasminogen activator (t-PA) was originally approved by the Food and Drug Administration (FDA) for acute ischemic stroke (AIS) in 1996, there was a lengthy list of contraindications. In the 19 years since the approval of t-PA for AIS, it has been used off label and in patients with those contraindications. In February 2015, the list of contraindications for IV t-PA in AIS was revised and several of the previous contraindications were removed. As only 4 % of patients with ischemic stroke receive treatment with IV t-PA, these changes increase the number of patients eligible for treatment. Anytime there is a significant change in the indications and treatment paradigm with a medication, there can be some resistance to the adaptation of the change into physician's treating habits. We seek to review what the changes to t-PA contraindications are, how they came about, as well as the literature on the previously off-label and currently off-label use of IV t-PA for patients with AIS. PMID:26277361

  9. 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

  10. 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.

  11. 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

  12. Toxicological review and oral risk assessment of terephthalic acid (TPA) and its esters: A category approach.

    PubMed

    Ball, Gwendolyn L; McLellan, Clifton J; Bhat, Virunya S

    2012-01-01

    Polyethylene terephthalate, a copolymer of terephthalic acid (TPA) or dimethyl terephthalate (DMT) with ethylene glycol, has food, beverage, and drinking water contact applications. Di-2-ethylhexyl terephthalate (DEHT) is a plasticizer in food and drinking water contact materials. Oral reference doses (RfDs) and total allowable concentrations (TACs) in drinking water were derived for TPA, DMT, and DEHT. Category RfD and TAC levels were also established for nine C(1)-C(8) terephthalate esters. The mode of action of TPA, and of DMT, which is metabolized to TPA, involves urinary acidosis, altered electrolyte elimination and hypercalciuria, urinary supersaturation with calcium terephthalate or calcium hydrogen terephthalate, and crystallization into bladder calculi. Weanling rats were more sensitive to calculus formation than dams. Calculi-induced irritation led to bladder hyperplasia and tumors in rats fed 1000 mg/kg-day TPA. The lack of effects at 142 mg/kg-day supports a threshold for urine saturation with calcium terephthalate, a key event for calculus formation. Chronic dietary DMT exposure in rodents caused kidney inflammation, but not calculi. Chronic dietary DEHT exposure caused general toxicity unrelated to calculi, although urine pH was reduced suggesting the TPA metabolite was biologically-active, but of insufficient concentration to induce calculi. Respective oral reference doses of 0.5, 0.5, and 0.2 mg/kg-day and total allowable drinking water concentrations of 3, 3, and 1 mg/L were derived for TPA, DMT, and DEHT. An oral RfD of 0.2 mg/kg-day for the terephthalate category chemicals corresponded to a drinking water TAC of 1 mg/L.

  13. Clinical implications of the involvement of tPA in neuronal cell death.

    PubMed

    Tsirka, S E

    1997-05-01

    Tissue plasminogen activator (tPA), the serine protease that converts inactive plasminogen to the protease plasmin, was recently shown to mediate neurodegeneration in the mouse hippocampus. Mice deficient in tissue plasminogen activator (tPA) display a dramatic resistance to a paradigm of excitotoxic neuronal death that involves intrahippocampal injection of the excitotoxin. This model is thought to reproduce the mechanism of neuronal death observed during acute (such as ischemic stroke) and degenerative (such as amyotrophic lateral sclerosis) diseases of the nervous system. The requirement for the proteolytic activity of tPA to mediate neuronal death is acute in the adult mouse. Serine protease inhibitors, specific for tPA or the tPA/plasmin proteolytic cascade, are effective in conferring extensive neuroprotection following the excitotoxic injection. These findings suggest possible new ways for interfering with the neuronal death observed in the hippocampus as a result of excitotoxicity. In addition, tPA is produced in the hippocampus primarily by microglial cells, which become activated in response to the neuronal injury. Blocking microglial activation has been shown in other injury paradigms to protect against neuronal death, therefore suggesting another way to retard neurodegeneration in the CNS. Furthermore, after the insult has been inflicted and in the presence of a compromised blood-brain barrier macrophages (cells deriving from the same lineage as microglia) migrate into the brain, where they are thought to contribute to the neuronal cell loss by secreting neurotoxic molecules. If these macrophages/microglia expressed, however, a tPA inhibitor, rather than the possibly neurotoxic tPA, they might be able to protect the neurons from dying.

  14. 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.

  15. t-PA reduces ischemic impairment of blood-brain barrier by strengthening endothelium junction.

    PubMed

    Zhang, Zhongling; Chen, Xuhui; Li, Le; Zhang, Keling; Tian, Shuqing; Gao, Hongmei; Li, Hulun

    2013-09-01

    Cerebral ischemic stroke is one of the most prevalent diseases in senior individuals. Its therapeutical strategies include anticoagulation, thrombolysis and cell protection. Tissue-type plasminogen activator (t-PA) that interacts with thrombin for the lysis of thrombosis is widely used to treat stroke patients in early stage. The mechanism of action of t-PA is not clear. Here, we report a novel role of t-PA in protecting blood-brain barrier and its potential mechanisms. In a model of the blood-brain barrier with human umbilical vascular epithelium cells, we found that t-PA in low concentrations prevented the impairment of the blood-brain barrier as a result of oxygen and glucose deprivation. This protection was fulfilled by strengthening the junctions among vascular endothelia and by upregulating the productions of vascular endothelium growth factor and of zonula occludens-1. Therefore, t-PA may strengthen the junctions of vascular endothelia in the blood-brain barrier to improve the microenvironment of brain cells and, in turn, the outcome of stroke patients.

  16. Microglial tissue plasminogen activator (tPA) triggers neuronal apoptosis in vitro.

    PubMed

    Flavin, M P; Zhao, G; Ho, L T

    2000-02-15

    Several CNS disorders feature microglial activation. Microglia are known to have both restorative and cytotoxic capabilities. Neuronal apoptosis has been noted after an acute insult such as ischemia. Microglia may participate in this event. We previously showed that conditioned medium (CM) harvested from peritoneal macrophages or from activated microglia triggered apoptosis in rat hippocampal neurons in culture. We wished to characterize the factor responsible for triggering neuronal death. Quiescent microglia produced CM that did not disrupt hippocampal neurons. Lipopolysaccharide-activated microglia produced CM which resulted in neuronal death. This effect was blocked by plasminogen activator inhibitor-1, by tPA STOP, and by co-incubation with tPA antibody. Recombinant human tPA exaggerated the neurotoxic effects of microglial CM, while tPA alone was toxic only at very high concentrations. This in vitro system, which probably excludes any significant impact of microglial free radicals, suggests that microglial tPA may contribute significantly to hippocampal neuronal death.

  17. 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.

  18. 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

  19. RACIAL DISPARITIES IN TPA TREATMENT RATE FOR STROKE: A POPULATION-BASED STUDY

    PubMed Central

    Hsia, Amie W.; Edwards, Dorothy F.; Morgenstern, Lewis B.; Wing, Jeffrey J.; Brown, Nina C.; Coles, Regina; Loftin, Sarah; Wein, Andrea; Koslosky, Sara S.; Fatima, Sabiha; Fokar, Ali; Gibbons, M. Chris; Jayam-Trouth, Annapurni; Kidwell, Chelsea S.

    2011-01-01

    Background Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (IV tPA) utilization for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Methods Systematic chart abstraction was performed on consecutive hospitalized ischemic stroke patients from all seven acute care hospitals in the District of Columbia from Feb 1, 2008 to Jan 31, 2009. Results Of 1044 ischemic stroke patients, 74%% were black, 19% non-Hispanic white, 5% received IV tPA. Blacks were one third less likely than whites to receive IV tPA (3% vs. 10%, p<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% vs. 21%, p=0.004) and also less likely to be tPA-eligible (5% vs. 13%, p<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with IV tPA than whites (27% vs. 46%, p=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% vs. 76%, p=0.62). Conclusions In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with IV tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population. PMID:21719765

  20. X-ray diffraction of molybdenum under ramp compression to 1 TPa

    NASA Astrophysics Data System (ADS)

    Wang, Jue; Coppari, Federica; Smith, Raymond F.; Eggert, Jon H.; Lazicki, Amy E.; Fratanduono, Dayne E.; Rygg, J. Ryan; Boehly, Thomas R.; Collins, Gilbert W.; Duffy, Thomas S.

    2016-09-01

    Molybdenum (Mo) is a transition metal with a wide range of technical applications. There has long been strong interest in its high-pressure behavior, and it is often used as standard for high-pressure experiments. Combining powder x-ray diffraction and dynamic ramp compression, structural and equation of state data were collected for solid Mo to 1 TPa (10 Mbar). Diffraction results are consistent with Mo remaining in the body-centered-cubic structure into the TPa regime. Stress-density data show that Mo under ramp loading is less compressible than the room-temperature isotherm but more compressible than the single-shock Hugoniot.

  1. Milestones and Experiences of Standardized Documentation.

    PubMed

    Saranto, Kaija; Saba, Virginia; Dykes, Patricia; Kinnunen, Ulla-Mari; Mykkänen, Minna

    2016-01-01

    The purpose of this panel is to discuss milestones and experiences of a standardized nursing terminology for the documentation of nursing practice using Clinical Care Classification as an example. The aim is to describe the value of using the CCC as the standardized nursing terminology and framework for the multidisciplinary care plans and how its interoperability with SNOMED CT, LOINC, and other required terminologies can be used for the electronic health record systems. Further the aim is to discuss the advantages a multidisciplinary documentation system and how it impacts on nursing practice, management, and research as well as highlight the monitoring of nursing documentation. The target audience will enrich their understanding about the possibilities that a standardized multidisciplinary documentation is critical for future data analyses and datamining highlighting nursing practices. PMID:27332328

  2. Milestones in the history of personality disorders.

    PubMed

    Crocq, Marc-Antoine

    2013-06-01

    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.

  3. 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

  4. 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

  5. 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...

  6. Involvement of tissue plasminogen activator "tPA" in ethanol-induced locomotor sensitization and conditioned-place preference.

    PubMed

    Bahi, Amine; Dreyer, Jean-Luc

    2012-01-01

    Ethanol is one of the most abused drugs in the western societies. It is well established that mesolimbic dopaminergic neurons mediate the rewarding properties of ethanol. In our previous studies we have shown that the serine protease tissue plasminogen activator (tPA) is involved in the rewarding properties of morphine and amphetamine. In the current study, we investigated the role of tPA in ethanol-induced behavioral sensitization and conditioned-place preference (CPP). Ethanol treatment dose-dependently induced tPA enzymatic activity in the nucleus accumbens (NAc). In addition, ethanol-induced increase in tPA activity was completely inhibited by pre-treatment with the dopamine D1 and D2 receptor antagonists SCH23390 and raclopride respectively. Furthermore, ethanol-induced locomotor stimulation, behavioral sensitization and conditioned-place preference were enhanced following tPA over-expression in the NAc using a lentiviral vector. In contrast, tPA knock down in the NAc with specific shRNA blocked the rewarding properties of ethanol. The defect of locomotor stimulation in shRNA-injected mice was reversed by microinjections of exogenous recombinant tPA into the nucleus accumbens. Collectively, these results indicate, for the first time, that activation of tPA is effective in enhancing the rewarding effects of ethanol. Targeting the tissue plasminogen activator system would provide new therapeutic approaches to the treatment of alcoholism.

  7. Ascorbic acid inhibits TPA-induced HL-60 cell differentiation by decreasing cellular H₂O₂ and ERK phosphorylation.

    PubMed

    Yiang, Giou-Teng; Chen, Jen-Ni; Wu, Tsai-Kun; Wang, Hsueh-Fang; Hung, Yu-Ting; Chang, Wei-Jung; Chen, Chinshuh; Wei, Chyou-Wei; Yu, Yung-Luen

    2015-10-01

    Retinoic acid (RA), vitamin D and 12-O‑tetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. High‑dose ascorbic acid (>100 µM) induces HL‑60 cell apoptosis and induces a small fraction of HL‑60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an anti‑oxidative stress function. Oxidative stress is required for HL‑60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL‑60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that low‑dose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL‑60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that low‑dose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL‑60 cell differentiation following treatment with TPA.

  8. 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.

  9. 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.

  10. 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.

  11. Draft Genome Sequence of Streptomyces sp. TP-A0874, a Catechoserine Producer

    PubMed Central

    Hosoyama, Akira; Ichikawa, Natsuko; Igarashi, Yasuhiro

    2016-01-01

    We report the draft genome sequence of Streptomyces sp. TP-A0874 isolated from compost. This strain produces catechoserine, a new catecholate-type inhibitor of tumor cell invasion. The genome harbors at least six gene clusters for polyketide and nonribosomal peptide biosyntheses. The biosynthetic gene cluster for catechoserines was identified by bioinformatic analysis. PMID:27795278

  12. 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…

  13. 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…

  14. 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…

  15. Is the EdTPA the Right Choice for Evaluating Teacher Readiness?

    ERIC Educational Resources Information Center

    Parkes, Kelly A.; Powell, Sean R.

    2015-01-01

    The purpose of this article is to describe and analyze the edTPA, a performance assessment created by the Stanford Center for Assessment, Learning, and Equity (SCALE) and administered by Pearson, Inc., to assess the professional readiness of student teachers. We challenge claims made in support of using this assessment, specifically within the…

  16. Male-female differences in the genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.

    PubMed

    Schoenhard, J A; Asselbergs, F W; Poku, K A; Stocki, S A; Gordon, S; Vaughan, D E; Brown, N J; Moore, J H; Williams, Scott M

    2008-12-01

    Tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) directly influence thrombus formation and degradation, and have been identified as risk factors for thromboembolic disease. Prior studies investigated determinants of t-PA and PAI-1 expression, but mainly in Caucasian subjects. The aim of this study was to identify the contributions of genetic and other factors to inter-individual variation in plasma levels of t-PA and PAI-1 in a large-scale population-based sample from urban West Africa. t-PA, PAI-1 and several demographic, anthropometric, and metabolic parameters were measured in 992 residents of Sunyani, the capital of the Brong-Ahafo region of Ghana. In addition, nine gene polymorphisms associated with components of the renin-angiotensin and fibrinolytic systems were determined. We found that BMI, systolic and diastolic blood pressure, total cholesterol, glucose, and triglycerides were all significant predictors of t-PA and PAI-1 in both females and males. In addition, a significant relationship was found between the PAI-1 4G/5G (rs1799768) polymorphism on PAI-1 levels in females, the TPA I/D (rs4646972) polymorphism on t-PA and PAI-1 in males, the renin (rs3730103) polymorphism on t-PA and PAI-1 in males, the ethanolamine kinase 2 (rs1917542) polymorphism on PAI-1 in males, and the renin (rs1464816) polymorphism on t-PA in females and on PAI-1 in males. This study of urban West Africans shows that t-PA and PAI-1 levels are determined by both genetic loci of the fibrinolytic and renin-angiotensin systems and other factors often associated with cardiovascular disease, and that genetic factors differ between males and females.

  17. GRAPHIC REANALYSIS OF THE TWO NINDS-TPA TRIALS CONFIRMS SUBSTANTIAL TREATMENT BENEFIT

    PubMed Central

    Saver, Jeffrey L.; Gornbein, Jeffrey; Starkman, Sidney

    2010-01-01

    Background of Comment/Review Multiple statistical analyses of the two NINDS-TPA Trials have confirmed study findings of benefit of fibrinolytic therapy. A recent graphic analysis departed from best practices in the visual display of quantitative information by failing to take into account the skewed functional importance NIH Stroke Scale raw scores and by scaling change axes at up to twenty times the range achievable by individual patients. Methods Using the publicly available datasets of the 2 NINDS-TPA Trials, we generated a variety of figures appropriate to the characteristics of acute stroke trial data. Results A diverse array of figures all visually delineated substantial benefits of fibrinolytic therapy, including: bar charts of normalized gain and loss; stacked bar, bar, and matrix plots of clinically relevant ordinal ranks; a time series stacked line plot of continuous scale disability weights; and line plot, bubble chart, and person icon array graphs of joint outcome table analysis. The achievable change figure showed substantially greater improvement among TPA than placebo patients, median 66.7% (IQR 0–92.0) vs 50.0% (IQR −7.1 – 80.0), p=0.003. Conclusions On average, under 3 hour patients treated with TPA recovered two-thirds while placebo patients improved only half of the way towards fully normal. Graphical analyses of the two NINDS-TPA trials, when performed according to best practices, is a useful means of conveying details about patient response to therapy not fully delineated by summary statistics, and confirms a valuable treatment benefit of under 3 hour fibrinolytic therapy in acute stroke. PMID:20829518

  18. 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.

  19. 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…

  20. 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

  1. 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.

  2. 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.

  3. Epidemiology of child psychopathology: major milestones.

    PubMed

    Verhulst, Frank C; Tiemeier, Henning

    2015-06-01

    Child psychiatric epidemiology has developed rapidly from descriptive, cross-sectional studies in the 1960s to the current large-scale prospective cohorts that unravel aetiological mechanisms. The objective of the study was to give an overview of epidemiological studies that have influenced child psychiatry. A chronological overview of selected major milestone studies was obtained to demonstrate the development of child psychiatric epidemiology, with a more in-depth discussion of findings and methodological issues exemplified in one cohort, the Generation R Study. Epidemiological studies have been successful in describing the frequency and course of child psychiatric problems. The high expectations that biological factors can be used to better explain, diagnose or predict child psychiatric problems have not been met. More ambitious large-scale child psychiatric cohort studies are needed, carefully applying genetics, neuroscience or other molecular research to better understand how the brain produces maladaptive behaviour. Progress will only be attained if the basic sciences are systematically integrated in cohorts with rigorous epidemiological designs rather than hurriedly inserted in child psychiatric studies.

  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. Allelic imbalance of tissue-type plasminogen activator (t-PA) gene expression in human brain tissue.

    PubMed

    Tjarnlund-Wolf, A; Hultman, K; Curtis, M A; Faull, R L M; Medcalf, R L; Jern, C

    2011-06-01

    We have identified a single-nucleotide polymorphism (SNP) in the t-PA enhancer (-7351C>T), which is associated with endothelial t-PA release in vivo. In vitro studies demonstrated that this SNP is functional at the level of transcription. In the brain, t-PA has been implicated in both physiologic and pathophysiologic processes. The aim of the present study was to examine the effect of the t-PA -7351C>T SNP on t-PA gene expression in human brain tissue. Allelic mRNA expression was measured in heterozygous post-mortem brain tissues using quantitative TaqMan genotyping assay. Protein-DNA interactions were assessed using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP). Significantly higher levels of t-PA mRNA were generated from chromosomes that harboured the wild-type -7351C allele, as compared to those generated from the mutant T allele (for the hippocampus, C to T allelic ratio of ~1.3, p=0.010, n=12; and for the cortex, C to T allelic ratio of ~1.2, p=0.017, n=12). EMSA showed reduced neuronal and astrocytic nuclear protein binding affinity to the T allele, and identified Sp1 and Sp3 as the major transcription factors that bound to the -7351 site. ChIP analyses confirmed that Sp1 recognises this site in intact cells. In conclusion, the t-PA -7351C>T SNP affects t-PA gene expression in human brain tissue. This finding might have clinical implications for neurological conditions associated with enhanced t-PA levels, such as in the acute phase of cerebral ischaemia, and also for stroke recovery.

  7. Hydrogen milestone could help lower fossil fuel refining costs

    ScienceCinema

    Stephen Herring

    2016-07-12

    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

  8. 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 ...

  9. 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

  10. 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

  11. A brief history of hepatitis milestones.

    PubMed

    Trepo, Christian

    2014-02-01

    Hepatitis has been a major plague of mankind. The history of the discovery of causative viruses is one of the most fascinating scientific adventures of this half century. Individualization of several types of hepatitis only emerged after world war two. Their identification has been associated with milestones which revolutionized medicine and public health. The discovery of HBV brought the first ever vaccine not prepared by tissue culture but initially directly from plasma and soon the first vaccine produced by genetic engineering. HBV vaccine proved to be the first "anti-cancer" vaccine by preventing hepatocellular carcinoma and practically eradicating it from childhood in Taiwan. Successful vaccines became also available for HAV and more recently HEV. The discovery of HCV in 1989 opened a new era since it was the first virus was identified by a direct molecular approach. Two billion people are infected with HBV and 350 million are chronic carriers of the virus. The extraordinary effectiveness of HBV vaccination was best illustrated in Taiwan and Singapore where in less than 2 decades HBs Ag carriers dropped from 9,1% to 2,7% and HCC from 27% to 17%. Successful development of nucleos(t)ides analogs make it now possible to fully control disease progression with a daily pill long term therapy. The progress in HCV therapy has been even more spectacular and successful treatment jumped from 6 % with interferon alone in 1986 to more than 80% in 2013 with triple combination therapies. Remarkably chronic hepatitis C is the only chronic disease which is curable. It will be soon possible to eradicate HCV infection with, an all oral, daily single pill (containing several molecules) for 3 to 6 months which will cure over 90% of patients. This unprecedented therapeutic victory benefiting hundred millions of people matches the triumphs over small pox, polio and tuberculosis. The next 10 years should undoubtedly witness cure or full control over all forms of acute and chronic

  12. Polymorphism in the spin-crossover ferric complexes [(TPA)Fe(III)(TCC)]PF6.

    PubMed

    Collet, Eric; Boillot, Marie Laure; Hebert, Johan; Moisan, Nicolas; Servol, Marina; Lorenc, Maciej; Toupet, Loïc; Buron-Le Cointe, Marylise; Tissot, Antoine; Sainton, Joelle

    2009-08-01

    We have identified two polymorphs of the molecular complex [(TPA)Fe((III))(TCC)]PF(6) [TPA = tris(2-pyridylmethyl)amine and TCC = 3,4,5,6-tetrachlorocatecholate dianion]: one is monoclinic and the other is orthorhombic. By lowering the temperature both undergo a thermal spin-crossover between a high-spin (S = 5/2) and a low-spin (S = 1/2) state, which we detected by magnetic, optical and X-ray diffraction measurements. The thermal crossover is only slightly shifted between the polymorphs. Their crystalline structures consist of similar cation layers alternating with PF(6) anion layers, packed differently in the two polymorphs. The magnetic and optical properties of the polymorphs are presented.

  13. Shock wave equation of state experiments at multi-TPa pressures on NIF

    NASA Astrophysics Data System (ADS)

    Celliers, P. M.; Fratanduono, D. E.; Peterson, J. L.; Meezan, N. B.; MacKinnon, A. J.; Braun, D. G.; Millot, M.; Fry, J.; Boehm, K. J.; Collins, G. W.; Nikroo, A.; Fitzsimmons, P.

    2015-06-01

    The National Ignition Facility provides an unprecedented capability to generate steady, planar, ultra-high pressure shock waves (around 10 TPa) in solid samples. Building on successful laser shock equation of state experiments performed on a variety of other laser facilities, we have designed and fielded experiments to perform impedance match experiments on samples of C, Be, quartz and CH, in the range of 3 to 7 TPa. The experiments use a line-imaging VISAR as the primary diagnostic to measure the shock velocity in an Al reference standard and in an array of the four samples. Initial tests with the line-imaging VISAR show that the NIF is capable of driving shocks that are steady for several ns, with smooth planar breakout patterns over a 2 mm diameter spot. Initial results will be discussed. Prepared by LLNL under Contract DE-AC52-07NA27344.

  14. New challenges for the graduate medical educator: implementing the milestones.

    PubMed

    Barr, Karen P; Massagli, Teresa L

    2014-07-01

    Physical medicine and rehabilitation residency programs will face new challenges as they implement the Milestones and establish a Clinical Competency Committee, new requirements in the Accreditation Council of Graduate Medical Education's Next Accreditation System. The milestones require programs to measure the capabilities of individual residents, and programs will be expected to show how residents progress to successively higher levels of behavior during the course of the residency. Program directors will be assisted by a committee of faculty whose role is to assess each individual resident's attainment of milestones and assist in the early identification of residents not making the expected progress. Programs will need to evaluate their assessment programs and will need to create a coherent mix of instruments to evaluate all of the milestones. Because the milestones are based on observable behaviors, a key component of this system will be direct observation by faculty of residents during patient care. However, many faculty are not trained in this skill. Faculty development in observational skills, workplace-based assessment skills, and providing formative feedback will be a very important aspect if the milestones are to be successfully used to help residents make developmental progress in their clinical competence. PMID:24658427

  15. 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. |

  16. 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

  17. Epistatic interactions in genetic regulation of t-PA and PAI-1 levels in a Ghanaian population.

    PubMed

    Penrod, Nadia M; Poku, Kwabena A; Vaughan, Douglas E; Vaughn, Douglas E; Asselbergs, Folkert W; Brown, Nancy J; Moore, Jason H; Williams, Scott M

    2011-01-31

    The proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), act in concert to balance thrombus formation and degradation, thereby modulating the development of arterial thrombosis and excessive bleeding. PAI-1 is upregulated by the renin-angiotensin system (RAS), specifically by angiotensin II, the product of angiotensin converting enzyme (ACE) cleavage of angiotensin I, which is produced by the cleavage of angiotensinogen (AGT) by renin (REN). ACE indirectly stimulates the release of t-PA which, in turn, activates the corresponding fibrinolytic system. Single polymorphisms in these pathways have been shown to significantly impact plasma levels of t-PA and PAI-1 differently in Ghanaian males and females. Here we explore the involvement of epistatic interactions between the same polymorphisms in central genes of the RAS and fibrinolytic systems on plasma t-PA and PAI-1 levels within the same population (n = 992). Statistical modeling of pairwise interactions was done using two-way ANOVA between polymorphisms in the ETNK2, RENIN, ACE, PAI-1, t-PA, and AGT genes. The most significant interactions that associated with t-PA levels were between the ETNK2 A6135G and the REN T9435C polymorphisms in females (p = 0.006) and the REN T9435C and the TPA I/D polymorphisms (p = 0.005) in males. The most significant interactions for PAI-1 levels were with REN T9435C and the TPA I/D polymorphisms (p = 0.001) in females, and the association of REN G6567T with the TPA I/D polymorphisms (p = 0.032) in males. Our results provide evidence for multiple genetic effects that may not be detected using single SNP analysis. Because t-PA and PAI-1 have been implicated in cardiovascular disease these results support the idea that the genetic architecture of cardiovascular disease is complex. Therefore, it is necessary to consider the relationship between interacting polymorphisms of pathway specific genes that predict t-PA and PAI-1 levels.

  18. 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

  19. Evolution of intracerebral hemorrhage after intravenous tPA: reversal of harmful effects with mast cell stabilization

    PubMed Central

    Marinkovic, Ivan; Mattila, Olli S; Strbian, Daniel; Meretoja, Atte; Shekhar, Shashank; Saksi, Jani; Abo-Ramadan, Usama; Rantanen, Ville; Lindsberg, Perttu J; Tatlisumak, Turgut

    2014-01-01

    Thrombolysis with tissue plasminogen activator (tPA) traditionally demands baseline imaging to rule out intracerebral hemorrhage (ICH), which causes delays in treatment. Preventing possible adverse effects of tPA on ICH would allow rapid on-site thrombolysis in patients with presumed acute ischemic stroke, reducing onset-to-treatment times. We examined how intravenous tPA alters ICH evolution during an extended follow-up, and how mast cell stabilization affects this process. Intracerebral hemorrhage was induced in rats by collagenase injection. Rats received either saline (n=10), tPA (n=13), tPA+low-dose cromoglycate (n=10), or tPA+high-dose cromoglycate (n=10). Magnetic resonance imaging was performed at 24, 48, and 72 hours after ICH induction, together with neurologic evaluations. During 72 hours of follow-up, tPA administration did not significantly increase hematoma volume (mean±s.d. 83.5±14.3 versus 66.7±14.7 μL; P=0.256) or hemispheric expansion (14.5±5.0 versus 11.5±5.0% P=0.457) compared with saline. However, tPA-treated animals had worse neurologic outcomes (P<0.05), and mortality (8/13 versus 3/10). Combining tPA with high-dose cromoglycate mitigated hemispheric expansion (7.4±1.7 versus 14.5±5.0% P=0.01), improved neurologic outcome (P<0.001) and decreased mortality (1/10; P<0.05) compared with tPA alone. Our results suggest tPA increases neurologic deficit in ICH, an effect that was abolished by concomitant mast cell stabilization. Further studies are needed to establish the clinical relevance of these findings. PMID:24169849

  20. t-PA acts as a cytokine to regulate lymphocyte-endothelium adhesion in experimental autoimmune encephalomyelitis.

    PubMed

    Wang, Jinghua; Zhang, Xin; Mu, Lili; Zhang, Mingqing; Gao, Zhongming; Zhang, Jia; Yao, Xiuhua; Liu, Chuanliang; Wang, Guangyou; Wang, Dandan; Kong, Qingfei; Liu, Yumei; Li, Na; Sun, Bo; Li, Hulun

    2014-01-01

    In this study, the capacity for t-PA to affect T cell-brain microvascular endothelial cell adhesion by acting as a cytokine was investigated. Following the treatment of a brain-derived endothelial cell line, bEnd.3, with various concentrations of t-PA, adhesion and transwell migration assays were performed. In the presence of t-PA, enhanced adhesion of T cells to bEnd.3 cells was observed. Using western blot analysis, an increase in ICAM-1 expression was detected for both t-PA-treated bEnd.3 cells and bEnd.3 cells treated with a non-enzymatic form of t-PA. In contrast, when LRP1 was blocked using a specific antibody, upregulation of ICAM-1 was inhibited and cAMP-PKA signaling was affected. Furthermore, using an EAE mouse model, administration of t-PA was associated with an increase in ICAM-1 expression by brain endothelial cells. Taken together, these findings suggest that t-PA can induce ICAM-1 expression in brain microvascular endothelial cells, and this may promote the development of EAE.

  1. Reciprocal actions of NCAM and tPA via a Ras-dependent MAPK activation in rat hippocampal neurons.

    PubMed

    Son, Hyeon; Seuk Kim, Jin; Mogg Kim, Jung; Lee, Sang-Hun; Lee, Yong-Sung

    2002-10-25

    In an attempt to identify the functions of neural cell adhesion molecule (NCAM) and tissue plasminogen activator (tPA) in hippocampal synaptic plasticity, we investigated the relationship between the two molecules by focusing on mitogen-activated protein kinase (MAPK), an essential enzyme in this process. NCAM clustering in cultured hippocampal neurons transiently induced MAPK within 10min. Moreover, soluble NCAM also induced a Ras-dependent MAPK activation. Conversely, MAPK activation led to an increase in the expressions of all three isoforms of NCAM. Treatment of neurons with tPA and plasminogen induced a Ras-dependent MAPK activation and tPA-plasmin degradation of NCAM was mediated in a MAPK-dependent manner. Soluble NCAM transiently inhibited tPA mRNA expression levels in a MAPK-dependent manner, while stimulation of MAPK alone induced tPA reduction in cells. These results collectively indicate that NCAM and tPA reciprocally act as important regulators in the modulation of synaptic plasticity via a Ras-MAPK-involved signaling pathway. In turn, MAPK activation may cause tPA degradation or a decrease in expression to promote synaptic plasticity.

  2. 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

  3. High t-PA release by neonate brain microvascular endothelial cells under glutamate exposure affects neuronal fate.

    PubMed

    Henry, Vincent Jean; Lecointre, Maryline; Laudenbach, Vincent; Ali, Carine; Macrez, Richard; Jullienne, Amandine; Berezowski, Vincent; Carmeliet, Peter; Vivien, Denis; Marret, Stéphane; Gonzalez, Bruno José; Leroux, Philippe

    2013-02-01

    Glutamate excitotoxicity is a consolidated hypothesis in neonatal brain injuries and tissue plasminogen activator (t-PA) participates in the processes through proteolytic and receptor mediated effects. In brain microvascular endothelial cell (nBMEC) cultures from neonates, t-PA content and release upon glutamate are higher than in adult (aBMECs) cultures. Owing to the variety of t-PA substrates and receptor targets, the study was aimed at determining the putative roles of endothelial t-PA in the neonatal brain parenchyma under glutamate challenge. Basal t-PA release was 4.4 fold higher in nBMECs vs aBMECs and glutamate was 20 fold more potent to allow Evans blue vascular permeability in neonate microvessels indicating that, under noxious glutamate (50 μM) exposure, high amounts of endothelial t-PA stores may be mobilized and may access the nervous parenchyma. Culture media from nBMECS or aBMECs challenged by excitotoxic glutamate were applied to neuron cultures at DIV 11. While media from adult cells did not evoke more LDH release in neuronal cultures that under glutamate alone, media from nBMECs enhanced 2.2 fold LDH release. This effect was not observed with media from t-PA(-/-) nBMECs and was inhibited by hr-PAI-1. In Cortical slices from 10 day-old mice, hrt-PA associated with glutamate evoked neuronal necrosis in deeper (more mature) layers, an effect reversed by NMDA receptor GluN1 amino-terminal domain antibody capable of inhibiting t-PA potentiation of the receptor. In superficial layers (less mature), hrt-PA alone inhibited apoptosis, an effect reversed by the EGF receptor antagonist AG1478. Applied to immature neurons in culture (DIV5), media from nBMEC rescued 85.1% of neurons from cell death induced by serum deprivation. In cortical slices, the anti-apoptotic effect of t-PA fitted with age dependent localization of less mature neurons. These data suggest that in the immature brain, propensity of vessels to release high amounts of t-PA may not only

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. TPA decreases 1,25(OH)2D3 binding and calbindin D-28K in renal (MDBK) cells.

    PubMed

    Simboli-Campbell, M; Gagnon, A M; Franks, D J; Welsh, J

    1992-02-01

    The effect of the phorbol ester TPA (12-O-tetradecanoylphorbol 13-acetate) on vitamin D receptors (VDRs) was studied in MDBK cells, a normal bovine renal epithelial cell line. 24 h treatment of MDBK cells with TPA resulted in down-regulation of VDR number, with no change in the binding affinity for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) or approximate molecular weight determined by fast protein liquid chromatography (FPLC). TPA treatment also reduced the level of calbindin D-28K, a vitamin D-dependent renal protein. 4 alpha-Phorbol 12,13-didecanoate (4 alpha-PDD), an inactive phorbol ester, did not affect either 1,25(OH)2D3 binding or calbindin D-28K levels. TPA elicited a significant decrease in membrane-associated protein kinase C (PKC) activity which coincided with the reduction in VDR number and calbindin D-28K. These data support a link between TPA, PKC activity and vitamin D actions in kidney.

  10. 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:…

  11. 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.

  12. 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)

  13. Shock wave equation of state experiments at multi-TPa pressures on NIF

    NASA Astrophysics Data System (ADS)

    Celliers, P. M.; Fratanduono, D. E.; Peterson, J. L.; Meezan, N. B.; MacKinnon, A. J.; Braun, D. G.; Millot, M.; Fry, J.; Boehm, K. J.; Sterne, P. A.; Collins, G. W.; Nikroo, A.; Fitzsimmons, P.

    2015-11-01

    The National Ignition Facility provides an unprecedented capability to generate steady, planar, ultra-high pressure shock waves (up to 10 TPa or more) in solid samples. Building on successful laser shock equation of state experiments performed on a variety of other laser facilities, we have designed and fielded experiments to perform impedance match experiments on samples of C, Be, SiO2 and CH, in the range of 3 to 7 TPa. The experiments use a line-imaging VISAR as the primary diagnostic to measure the shock velocity in an Al reference standard and in an array of the four samples. Initial tests with the line-imaging VISAR show that the NIF is capable of driving shocks that are steady to better than 2% in velocity for several ns, with smooth planar breakout patterns over a 2 mm diameter spot. Hugoniot data points will be compared to current equation-of-state models for the various materials under study. This work was performed under the auspices of the U.S. Department of Energy by LLNL under contract DE-AC52-07NA27344.

  14. Cooperative TPA enhancement via through-space interactions in organic nanodots built from dipolar chromophores

    NASA Astrophysics Data System (ADS)

    Robin, Anne-Claire; Parthasarathy, Venkatakrishnan; Pla-Quintana, Anna; Mongin, Olivier; Terenziani, Francesca; Caminade, Anne-Marie; Majoral, Jean-Pierre; Blanchard-Desce, Mireille

    2010-08-01

    Whereas structure-properties relationships have been widely investigated at the molecular level, supramolecular structure-property relationships have been somewhat overlooked. In many cases, interchromophoric interactions are found to be detrimental (in particular in second-order NLO) and a lot of efforts have been devoted to circumvent and control these effects to achieve efficient NLO materials for electrooptics. At opposite, we have implemented a countermainstream route based on the confinement of push-pull chromophores in close proximity within organic nanodots where both their number and relative position/distance are controlled by covalent attachment onto appropriate organic scaffolds. In such multichromophoric organic superstructures (namely covalent nanoclusters), dipole-dipole interactions can be tuned by playing on the internal architecture (topology, number of chromophoric subunits, length of the covalent linkers) and on the nature and properties (polarity, polarizability) of the chromophoric subunits. Following this strategy, we present the investigation of two series of such organic nanoclusters built from push-pull chromophores where through-space interactions are shown to modify both one-photon (OPA) and two-photon absorption (TPA) of each chromophoric subunits leading to cooperative enhancement of TPA properties and improved transparency.

  15. 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

  16. Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082, an NF-kappaB inhibitor.

    PubMed

    Hansson, Annette; Marín, Yarí E; Suh, Junghan; Rabson, Arnold B; Chen, Suzie; Huberman, Eliezer; Chang, Richard L; Conney, Allan H; Zheng, Xi

    2005-10-01

    The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) is a potent stimulator of differentiation and apoptosis in myeloid leukemia cells. In the present study, we investigated the role of the transcription factor NF-kappaB in TPA-induced growth inhibition and apoptosis in the myeloid leukemia HL-60 cell line and its TPA-resistant cell variant HL-525. Unlike the parental cell line, HL-525 cells are protein kinase C (PKC)-beta deficient and resistant to TPA-induced differentiation and apoptosis. We found that treatment of HL-60 cells with TPA resulted in a concentration-dependent growth inhibition and an increase in apoptotic cells. TPA only had a small effect on growth and apoptosis in HL-525 cells. Treatment of HL-60 cells with TPA (0.64-3.2 nM) caused a rapid activation of NF-kappaB as determined by electrophoresis mobility shift assay (EMSA) and immunocytochemistry. Although the basal level of NF-kappaB activity was low in HL-60 cells, TPA-resistant HL-525 cells had a high basal level of NF-kappaB activity. Treatment of HL-525 cells with higher concentrations of TPA (16-80 nM) resulted in a further increase in NF-kappaB activity. (E)3-[(4-methylphenyl)-sulfonyl]-2-propenenitrile (BAY 11-7082; BAY), which inhibits IkappaB alpha phosphorylation and thus decreases NF-kappaB activation, was found to decrease TPA-induced nuclear translocation of NF-kappaB. Furthermore, BAY enhanced TPA-induced growth inhibition and apoptosis in both HL-60 and HL-525 cells. Results from the present study indicate that inhibition of NF-kappaB by BAY was associated with enhanced TPA-induced growth inhibition and apoptosis in human myeloid leukemia cells. TPA in combination with pharmacological inhibitors of NF-kappaB may improve the therapeutic efficacy of TPA and overcome the resistance to TPA in some myeloid leukemia patients.

  17. Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro

    PubMed Central

    Díaz, V M; Hurtado, M; Thomson, T M; Reventós, J; Paciucci, R

    2004-01-01

    Background: Overexpression of tissue plasminogen activator (t-PA) in pancreatic cancer cells promotes invasion and proliferation in vitro and tumour growth and angiogenesis in vivo. Aims: To understand the mechanisms by which t-PA favours cancer progression, we analysed the surface membrane proteins responsible for binding specifically t-PA and studied the contribution of this interaction to the t-PA promoted invasion of pancreatic cancer cells. Methods: The ability of t-PA to activate plasmin and a fluorogenic plasmin substrate was used to analyse the nature of the binding of active t-PA to cell surfaces. Specific binding was determined in two pancreatic cancer cell lines (SK-PC-1 and PANC-1), and complex formation analysed by co-immunoprecipitation experiments and co-immunolocalisation in tumours. The functional role of the interaction was studied in Matrigel invasion assays. Results: t-PA bound to PANC-1 and SK-PC-1 cells in a specific and saturable manner while maintaining its activity. This binding was competitively inhibited by specific peptides interfering with the interaction of t-PA with annexin II. The t-PA/annexin II interaction on pancreatic cancer cells was also supported by co-immunoprecipitation assays using anti-t-PA antibodies and, reciprocally, with antiannexin II antibodies. In addition, confocal microscopy showed t-PA and annexin II colocalisation in tumour tissues. Finally, disruption of the t-PA/annexin II interaction by a specific hexapeptide significantly decreased the invasive capacity of SK-PC-1 cells in vitro. Conclusion: t-PA specifically binds to annexin II on the extracellular membrane of pancreatic cancer cells where it activates local plasmin production and tumour cell invasion. These findings may be clinically relevant for future therapeutic strategies based on specific drugs that counteract the activity of t-PA or its receptor annexin II, or their interaction at the surface level. PMID:15194650

  18. 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.

  19. 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

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

    PubMed

    Ulfhammer, Erik; 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.

  1. Improvement of photovoltaic performance by substituent effect of donor and acceptor structure of TPA-based dye-sensitized solar cells.

    PubMed

    Inostroza, Natalia; Mendizabal, Fernando; Arratia-Pérez, Ramiro; Orellana, Carlos; Linares-Flores, Cristian

    2016-01-01

    We report a computational study of a series of organic dyes built with triphenylamine (TPA) as an electron donor group. We designed a set of six dyes called (TPA-n, where n = 0-5). In order to enhance the electron-injection process, the electron-donor effect of some specific substituent was studied. Thus, we gave insights into the rational design of organic TPA-based chromophores for use in dye-sensitized solar cells (DSSCs). In addition, we report the HOMO, LUMO, the calculated excited state oxidized potential E(dye*)(eV) and the free energy change for electron-injection ΔGinject(eV), and the UV-visible absorption bands for TPA-n dyes by a time-dependent density functional theory (TDDFT) procedure at the B3LYP and CAM-B3LYP levels with solvent effect. The results demonstrate that the introduction of the electron-acceptor groups produces an intramolecular charge transfer showing a shift of the absorption wavelengths of TPA-n under studies. Graphical Abstract Several organic dyes TPA-n with different donors and acceptors are modeled. A strong conjugation acrros the donor and anchoring groips (TPA-n) bas been studied. Candidate TPA-3 shows a promising results.

  2. Cellulose derivatives carrying triphenylamine (TPA) moieties: synthesis and electro-optical properties.

    PubMed

    Qu, Jinqing; Liao, Wenbo; Chen, Huanqin; Masuda, Toshio

    2009-06-11

    A novel ethyl cellulose derivative [poly(1)] that carries triphenylamine moieties is synthesized with a moderate number-average molecular weight up to 78,200 in 85% yield by the reaction of 4-(diphenylamino)benzoic acid with the residual hydroxy group of ethyl cellulose. Poly(1) is soluble in common organic solvents including toluene, CHCl3, CH2Cl2, and tetrahydrofuran while insoluble in hexane, diethyl ether, and methanol. The polymer emits blue-green fluorescence with quantum yields up to 65% in CHCl3 and displays unique solvatochromism. The cyclic voltammograms of poly(1) indicate that the polymer carrying TPA moieties is electrochemically redox active. The onset temperature of weight loss of the poly(1) is about 177 degrees C according to thermogravimetric analysis in air.

  3. 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.

  4. 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

  5. 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.

  6. What Does It Mean to Be Student Centered? An Institutional Case Study of edTPA Implementation

    ERIC Educational Resources Information Center

    Fayne, Harriet; Qian, Gaoyin

    2016-01-01

    This longitudinal case study investigated how one School of Education (SOE), situated in an urban, commuter, public university, responded to the New York State mandate to require the edTPA for initial teacher certification. In order to engage faculty in the work of program redesign, SOE administrators employed a covert leadership approach. Based…

  7. 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

  8. 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).

  9. Maternal responsiveness and children's achievement of language milestones.

    PubMed

    Tamis-LeMonda, C S; Bornstein, M H; Baumwell, L

    2001-01-01

    This prospective longitudinal study examined the contribution of dimensions of maternal responsiveness (descriptions, play, imitations) to the timing of five milestones in children's (N = 40) early expressive language: first imitations, first words, 50 words in expressive language, combinatorial speech, and the use of language to talk about the past. Events-History Analysis, a statistical technique that estimates the extent to which predictors influence the timing of events, was used. At 9 and 13 months, maternal responsiveness and children's activities (e.g., vocalizations, play) were coded from videotaped interactions of mother-child free play; information about children's language acquisition was obtained through biweekly interviews with mothers from 9 through 21 months. Maternal responsiveness at both ages predicted the timing of children's achieving language milestones over and above children's observed behaviors. Responsiveness at 13 months was a stronger predictor of the timing of language milestones than was responsiveness at 9 months, and certain dimensions of responsiveness were more predictive than others. The multidimensional nature of maternal responsiveness and specificity in mother-child language relations are discussed.

  10. 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

  11. Vascular Risk Factors in Patients with Different Subtypes of Ischemic Stroke May Affect Their Outcome after Intravenous tPA

    PubMed Central

    Ren, Jinma; Nair, Deepak S.; Parker, Sarah; Jahnel, Jan L.; Swanson-Devlin, Teresa G.; Beck, Judith M.; Mathews, Maureen; McNeil, Clayton J.; Upadhyaya, Manas; Gao, Yuan; Dong, Qiang; Wang, David Z.

    2015-01-01

    Intravenous (IV) tissue-type plasminogen activator (tPA) is the only approved noninvasive therapy for acute ischemic stroke (AIS). However, after tPA treatment, the outcome of patients with different subtypes of stroke according to their vascular risk factors remains to be elucidated. We aim to explore the relationship between the outcome and different risk factors in patients with different subtype of acute strokes treated with IV tPA. Records of patients in this cohort were reviewed. Data collected and analysed included the demographics, vascular risk factors, baseline National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin Scores (mRS), and subtypes of stroke. By using the 90-day mRS, patients were dichotomized into favorable versus unfavorable outcome in each subtype of stroke. We identified the vascular risk factors that are likely associated with the poor outcome in each subtype. Among 570 AIS patients received IV tPA, 217 were in the large artery atherosclerosis (LAA) group, 146 in the small vessel occlusion(SVO) group, and 140 in the cardioaortic embolism(CE) group. Lower NIHSS score on admission was related to favorable outcome in patients in all subtypes. Patients with history of dyslipidemia were likely on statin treatment before their admission and hence less likely to have elevated cholesterol level on admission. Therefore, there was a possible paradoxical effect on the outcome in patients with LAA and SVO subtypes of strokes. SVO patients with history of diabetes had higher risk of unfavorable outcome. SVO patients had favorable outcome if their time from onset to treatment was short. In conclusion, the outcome of patients treated with IV tPA may be related to different vascular risk factors associated with different subtypes of stroke. PMID:26247772

  12. 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,…

  13. 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

  14. The gender-specific role of polymorphisms from the fibrinolytic, renin-angiotensin, and bradykinin systems in determining plasma t-PA and PAI-1 levels.

    PubMed

    Asselbergs, Folkert W; Williams, Scott M; Hebert, Patricia R; Coffey, Christopher S; Hillege, Hans L; Navis, Gerjan; Vaughan, Douglas E; van Gilst, Wiek H; Moore, Jason H

    2006-10-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thus risk for arterial thrombosis. We report here results from a genetic analysis of plasma t-PA and PAI-1 levels in a large population-based sample from the PREVEND study in Groningen, the Netherlands (n = 2,527). We measured polymorphisms from genes of the fibrinolytic system, the renin-angiotensin system (RAS), and the bradykinin system. We found that males had higher levels of natural-log transformed t-PA, and PAI-1 (P < 0.01) compared to females. When stratifying females by menopausal status, PAI-1 levels were only significantly different between pre-menopausal females and males (p < 0.001). Furthermore, we found that age, body mass index, and waist-to-hip ratio were significant predictors of t-PA and PAI-1 in both females and males, and that the regression relationships between these factors and plasma t-PA and PAI-1 were dependent on gender. In addition, we found that the PAI-1 4G/5G polymorphism was a significant predictor of PAI-1 levels in both females and males, that the angiotensin II type I receptor A1166C was a significant predictor of t-PA and PAI-1 levels in females, and that the bradykinin receptor B2 58CT polymorphism was a significant predictor of t-PA levels in females. In conclusion, this large population-based study showed that t-PA and PAI-1 levels are determined by several demographic and genetic factors involved in the fibrinolytic, RAS and bradykinin system. In addition, the results support the idea that the biology of t-PA and PAI-1 is different between females and males.

  15. 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.

  16. Hydrogen milestone could help lower fossil fuel refining costs

    ScienceCinema

    McGraw, Jennifer

    2016-07-12

    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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. The Milestones Passport: A Learner-Centered Application of the Milestone Framework to Prompt Real-Time Feedback in the Emergency Department

    PubMed Central

    Yarris, Lalena M.; Jones, David; Kornegay, Joshua G.; Hansen, Matthew

    2014-01-01

    Background In July 2013, emergency medicine residency programs implemented the Milestone assessment as part of the Next Accreditation System. Objective We hypothesized that applying the Milestone framework to real-time feedback in the emergency department (ED) could affect current feedback processes and culture. We describe the development and implementation of a Milestone-based, learner-centered intervention designed to prompt real-time feedback in the ED. Methods We developed and implemented the Milestones Passport, a feedback intervention incorporating subcompetencies, in our residency program in July 2013. Our primary outcomes were feasibility, including faculty and staff time and costs, number of documented feedback encounters in the first 2 months of implementation, and user-reported time required to complete the intervention. We also assessed learner and faculty acceptability. Results Development and implementation of the Milestones Passport required 10 hours of program coordinator time, 120 hours of software developer time, and 20 hours of faculty time. Twenty-eight residents and 34 faculty members generated 257 Milestones Passport feedback encounters. Most residents and faculty reported that the encounters required fewer than 5 minutes to complete, and 48% (12 of 25) of the residents and 68% (19 of 28) of faculty reported satisfaction with the Milestones Passport intervention. Faculty satisfaction with overall feedback in the ED improved after the intervention (93% versus 54%, P  =  .003), whereas resident satisfaction with feedback did not change significantly. Conclusions The Milestones Passport feedback intervention was feasible and acceptable to users; however, learner satisfaction with the Milestone assessment in the ED was modest. PMID:26279784

  3. 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.

  4. Single or multicellular origin of human T lymphocyte colonies in vitro: modification by 12-o-tetradecanoylphorbol 13-acetate (TPA).

    PubMed

    Singer, J W; Ernst, C; Whalen, C K; Steinmann, L; Fialkow, P J

    1981-04-01

    The assumption that human T lymphocyte colonies have a unicellular origin has been directly tested with peripheral blood mononuclear cells from 2 women heterozygous for the common X-linked glucose-6-phosphate dehydrogenase (G-6-PD) gene (GdB) and the variant GdA. T cells were cultured in semisolid medium in the presence of phytohemagglutinin (PHA) and T lymphocyte growth factor with or without preincubation in suspension culture with PHA (2-stage and 1-stage assays, respectively). The enzyme type of individual T cell colonies was then determined electrophoretically at the lowest colony density with adequate growth (usually less than 100 colonies/dish). In the 2-stage system, 90 of 97 tested colonies had equal amounts of A and B enzyme activities suggesting multicellular origin of the colonies. Similarly, in the single-stage system, 21 of 31 colonies had both A and B enzymes. Increasing the density of the soft agar did not influence the frequency of A/B colonies. However, when 12-O-tetradecanoylphorbol 13-acetate (TPA), a promoter of T cell colony growth shown in other systems to inhibit metabolic cooperation, was added, a striking decrease in frequency of colonies with both G-6-PD types was found. In the 2-stage culture, 0 of 9 colonies had a double-enzyme type and in the single-stage system, the frequency of A/B colonies declined to 9 of 34 (p less than 0.025). The data suggest that despite the apparent multicellular origin of T cell colonies in cultures with TPA, most colonies do originate from single cells when cultured with TPA at low colony densities. Stimulation of cell growth or inhibition of metabolic cooperation between cells by TPA are possible explanations for these differences. PMID:6970773

  5. Human T cell activation. III. Induction of an early activation antigen, EA 1 by TPA, mitogens and antigens

    SciTech Connect

    Hara, T.; Jung, L.K.L.; FU, S.M.

    1986-03-01

    With human T cells activated for 12 hours by 12-o-tetradecanoyl phorbol-13-acetate (TPA) as immunogen, an IgG/sub 2a/ monoclonal antibody, mAb Ea 1, has been generated to a 60KD phosphorylated protein with 32KD and 28KD subunits. The antigen, Ea 1, is readily detected on 60% of isolated thymocytes by indirect immunofluorescence. A low level of Ea 1 expression is detectable on 2-6% of blood lymphocytes. Isolated T cells have been induced to express Ea 1 by TPA, mitogens and anitgens. TPA activated T cells express Ea 1 as early as 1 hour after activation. By 4 hours, greater than 95% of the T cells stain with mAb Ea 1. About 50% of the PHA or Con A activated T cells express Ea 1 with a similar kinetics. Ea 1 expression proceeds that of IL-2 receptor in these activation processes. T cells activated by soluble antigens (tetanus toxoid and PPD) and alloantigens in MLR also express Ea 1 after a long incubation. About 20% of the T cells stain for Ea 1 at day 6. Ea 1 expression is not limited to activated T cells. B cells activated by TPA or anti-IgM Ab plus B cell growth factor express Ea 1. The kinetics of Ea 1 expression is slower and the staining is less intense. Repeated attempts to detect Ea 1 on resting and activated monocytes and granulocytes have not been successful. Ea 1 expression is due to de novo synthesis for its induction is blocked by cycloheximide and actinomycin D. Ea 1 is the earliest activation antigen detectable to-date.

  6. Draft Genome Sequence of Streptomyces sp. TP-A0890, a Producer of FR-900452 and A-74863a

    PubMed Central

    Ichikawa, Natsuko; Hosoyama, Akira; Fujita, Nobuyuki; Igarashi, Yasuhiro

    2015-01-01

    Here, we report the draft genome sequence of Streptomyces sp. TP-A0890, a producer of FR-900452 and A-74863a. The genome was found to contain at least eight polyketide synthase and nonribosomal peptide synthetase gene clusters. A prediction of gene functions based on the sequence similarity allowed us to assign the biosynthetic gene clusters for FR-900452 and A-74863a. PMID:26472848

  7. Charting the Road to Competence: Developmental Milestones for Internal Medicine Residency Training

    PubMed Central

    Green, Michael L.; Aagaard, Eva M.; Caverzagie, Kelly J.; Chick, Davoren A.; Holmboe, Eric; Kane, Gregory; Smith, Cynthia D.; Iobst, William

    2009-01-01

    Background The Accreditation Council for Graduate Medical Education (ACGME) Outcome Project requires that residency program directors objectively document that their residents achieve competence in 6 general dimensions of practice. Intervention In November 2007, the American Board of Internal Medicine (ABIM) and the ACGME initiated the development of milestones for internal medicine residency training. ABIM and ACGME convened a 33-member milestones task force made up of program directors, experts in evaluation and quality, and representatives of internal medicine stakeholder organizations. This article reports on the development process and the resulting list of proposed milestones for each ACGME competency. Outcomes The task force adopted the Dreyfus model of skill acquisition as a framework the internal medicine milestones, and calibrated the milestones with the expectation that residents achieve, at a minimum, the “competency” level in the 5-step progression by the completion of residency. The task force also developed general recommendations for strategies to evaluate the milestones. Discussion The milestones resulting from this effort will promote competency-based resident education in internal medicine, and will allow program directors to track the progress of residents and inform decisions regarding promotion and readiness for independent practice. In addition, the milestones may guide curriculum development, suggest specific assessment strategies, provide benchmarks for resident self-directed assessment-seeking, and assist remediation by facilitating identification of specific deficits. Finally, by making explicit the profession's expectations for graduates and providing a degree of national standardization in evaluation, the milestones may improve public accountability for residency training. PMID:21975701

  8. Variations in Sexual Identity Milestones among Lesbians, Gay Men and Bisexuals

    PubMed Central

    Martos, Alexander; Nezhad, Sheila; Meyer, Ilan H.

    2016-01-01

    Despite a large body of literature covering sexual identity development milestones, we know little about differences or similarities in patterns of identity development among subgroups of the lesbian, gay, and bisexual (LGB) population. For this study, we assessed identity milestones for 396 LGB New Yorkers, ages 18–59. Sexual identity and disclosure milestones, were measured across gender, sexual identity, race/ethnicity, and age cohort subgroups of the LGB sample. Men experienced most sexual identity milestones earlier than women, but they tended to take more time between milestones. LGBs in younger age cohorts experienced sexual identity milestones and disclosure milestones earlier than the older cohorts. Bisexual people experienced sexual identity and disclosure milestones later than gay and lesbian people. Timing of coming out milestones did not differ by race/ethnicity. By comparing differences within subpopulations, the results of this study help build understanding of the varied identity development experiences of people who are often referred to collectively as “the LGB community.” LGB people face unique health and social challenges; a more complete understanding of variations among LGB people allows health professionals and social service providers to provide services that better fit the needs of LGB communities.

  9. Intravitreal tPA Injection and Pneumatic Displacement for Submacular Hemorrhage in a 10-Year-Old Child

    PubMed Central

    Hirose, Hiroshi; Hattori, Tomohiro

    2016-01-01

    Background. Submacular hemorrhage can occur after blunt trauma to the eye. Intravitreal tissue plasminogen activator (tPA) and gas injection are often used for treatment and are effective for submacular hemorrhage caused by age-related macular degeneration. This report describes the clinical outcome in a child with submacular hemorrhage caused by traumatic choroidal rupture who underwent successful intravitreal tPA injection and pneumatic displacement. Case Presentation. A 10-year-old boy developed sudden decrease of vision and a central scotoma in his right eye after trauma. Submacular hemorrhage was found in the eye. Visual acuity was 20/70 OD. Tissue plasminogen activator (12.5 μg in 0.05 mL) and 0.3 mL of pure sulfur hexafluoride were injected into the vitreous cavity under general anesthesia. After surgery, the patient was instructed to maintain a prone position. Displacement of the submacular hemorrhage from the fovea revealed a choroidal rupture, presumed to be the cause of the hemorrhage. After 4 months of follow-up, visual acuity was restored and final visual acuity is 20/16. Conclusion. Intravitreal tPA and gas injection can be an effective treatment for children with submacular hemorrhage. PMID:27722001

  10. Redox-regulation of Erk1/2-directed phosphatase by reactive oxygen species: role in signaling TPA-induced growth arrest in ML-1 cells.

    PubMed

    Traore, Kassim; Sharma, Rajni; Thimmulappa, Rajesh K; Watson, Walter H; Biswal, Shyam; Trush, Michael A

    2008-07-01

    Extracellular signal-regulated kinase (Erk)1/2 activity signals myeloid cell differentiation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Previously, we reported that Erk1/2 activation (phosphorylation) induced by TPA required reactive oxygen species (ROS) as a second messenger. Here, we hypothesized that ROS generated in response to TPA inhibit Erk1/2-directed phosphatase activity, which leads to an increase phosphorylation of Erk1/2 to signal p21(WAF1/Cip1)-mediated growth arrest in ML-1 cells. Incubation of ML-1 cells with TPA resulted in a marked accumulation of phosphorylated Erk1/2, and is subsequent to H2O2 generation. Interestingly, post-TPA-treatment with N-acetylcysteine (NAC) stimulated a marked and a rapid dephosphorylation of Erk1/2, suggesting a regeneration of Erk1/2-directed phospahatase activity by NAC. ROS generation in ML-1 cells induced by TPA was suggested to occur in the mitochondrial electron transport chain (METC) based on the following observations: (i) undifferentiated ML-1 cells not only lack p67-phox and but also express a low level of p47-phox key components required for NADPH oxidase enzymatic activity, (ii) pretreatment with DPI, an inhibitor of NADH- and NADPH-dependent enzymes, or rhein, an inhibitor of complex I, blocked the ROS generation, and (iii) examination of the microarray analysis data and Western blot analysis data revealed an induction of MnSOD expression at both mRNA and protein levels in response to TPA. MnSOD is a key member of the mitochondrial defense system against mitochondrial-derived superoxide. Together, this study suggested that TPA stimulated ROS generation as a second messenger to activate Erk1/2 via a redox-mediated inhibition of Erk1/2-directed phosphatase in ML-1 cells.

  11. Dopamine D3 receptor deletion increases tissue plasminogen activator (tPA) activity in prefrontal cortex and hippocampus.

    PubMed

    Castorina, A; D'Amico, A G; Scuderi, S; Leggio, G M; Drago, F; D'Agata, V

    2013-10-10

    Considerable evidence indicates that dopamine (DA) influences tissue plasminogen activator (tPA)-mediated proteolytic processing of the precursor of brain-derived neurotrophic factor (proBDNF) into mature BDNF (mBDNF). However, specific roles in this process for the dopamine D3 receptor (D3R) and the underlying molecular mechanisms are yet to be fully characterized. In the present study, we hypothesized that D3R deletion could influence tPA activity in the prefrontal cortex and hippocampus. Using D3R knockout (D3(-/-)) mice, we show that receptor inactivation is associated with increased tPA expression/activity both in the prefrontal cortex and, to a greater extent, in the hippocampus. Augmented tPA expression in D3(-/-) mice correlated with increased BDNF mRNA levels, plasmin/plasminogen protein ratio and the conversion of proBDNF into mBDNF, as well as enhanced tPA and mBDNF immunoreactivity, as determined by quantitative real time polymerase chain reaction (qRT-PCR), immunoblot and immunohistochemistry. In addition, when compared to wild-type controls, D3(-/-) mice exhibited increased basal activation of the canonical cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-driven Akt/cAMP-response element-binding protein (CREB) signaling cascade, as determined by the increased Akt phosphorylation both at Thr304 and Ser473 residues, of DA and cAMP-regulated protein of 32kDa (DARPP-32) at Thr34 and a phosphorylation state-dependent inhibition of glycogen synthetase kinase-3β (GSK-3β) at Ser9, a substrate of Akt whose constitutive function impairs normal CREB transcriptional activity through phosphorylation at its Ser129 residue. Accordingly, CREB phosphorylation at Ser133 was significantly increased in D3(-/-) mice, whereas the GSK-3β-dependent phosphorylation at Ser129 was diminished. Altogether, our finding reveals that mice lacking D3Rs show enhanced tPA proteolytic activity on BDNF which may involve, at least in part, a potentiated Akt/CREB signaling

  12. 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

  13. 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.

  14. 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.

  15. Exogenous t-PA Administration Increases Hippocampal Mature BDNF Levels. Plasmin- or NMDA-Dependent Mechanism?

    PubMed Central

    Rodier, Marion; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling. PMID:24670989

  16. Exogenous t-PA administration increases hippocampal mature BDNF levels. plasmin- or NMDA-dependent mechanism?

    PubMed

    Rodier, Marion; Prigent-Tessier, Anne; Béjot, Yannick; Jacquin, Agnès; Mossiat, Claude; Marie, Christine; Garnier, Philippe

    2014-01-01

    Brain-derived neurotrophic factor (BDNF) through TrkB activation is central for brain functioning. Since the demonstration that plasmin is able to process pro-BDNF to mature BDNF and that these two forms have opposite effects on neuronal survival and plasticity, a particular attention has been paid to the link between tissue plasminogen activator (tPA)/plasmin system and BDNF metabolism. However, t-PA via its action on different N-methyl-D-aspartate (NMDA) receptor subunits is also considered as a neuromodulator of glutamatergic transmission. In this context, the aim of our study was to investigate the effect of recombinant (r)t-PA administration on brain BDNF metabolism in rats. In the hippocampus, we found that rt-PA (10 mg/kg) administration induced a progressive increase in mature BDNF levels associated with TrkB activation. In order to delineate the mechanistic involved, plasmin activity was assessed and its inhibition was attempted using tranexamic acid (30 or 300 mg/kg, i.v.) while NMDA receptors were antagonized with MK801 (0.3 or 3 mg/kg, i.p.) in combination with rt-PA treatment. Our results showed that despite a rise in rt-PA activity, rt-PA administration failed to increase hippocampal plasmin activity suggesting that the plasminogen/plasmin system is not involved whereas MK801 abrogated the augmentation in mature BDNF levels observed after rt-PA administration. All together, our results show that rt-PA administration induces increase in hippocampal mature BDNF expression and suggests that rt-PA contributes to the control of brain BDNF synthesis through a plasmin-independent potentiation of NMDA receptors signaling.

  17. 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

  18. 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.

  19. The reaction of [FeII(tpa)] with H2O2 in acetonitrile and acetone--distinct intermediates and yet similar catalysis.

    PubMed

    Mairata i Payeras, Antoni; Ho, Raymond Y N; Fujita, Megumi; Que, Lawrence

    2004-10-11

    The reaction of [FeII(tpa)(OTf)2] (tpa=tris(2-pyridylmethyl)amine) and its related 5-Me3-tpa complex with hydrogen peroxide affords spectroscopically distinct iron(III)-peroxo intermediates in CH3CN and acetone. The reaction in acetonitrile at -40 degrees C results in the formation of the previously reported Fe(III)-OOH intermediate, the end-on hydroperoxo coordination mode of which is established in this paper by detailed resonance Raman isotope-labeling experiments. On the other hand, the reaction in acetone below -40 degrees C leads to the observation of a different peroxo intermediate identified by resonance Raman spectroscopy to be an FeIII-OOC (CH3)2OH species; this represents the first example of an intermediate derived from the adduct of H2O2 and acetone. The peroxoacetone intermediate decays more rapidly than the corresponding FeIII-OOH species and converts to an FeIV=O species by O-O bond homolysis. This decay process is analogous to that observed for [FeIII(tpa)(OOtBu)]2+ and in fact exhibits a comparable enthalpy of activation of 54(3) kJ mol(-1). Thus, with respect to their physical properties at low temperature, the peroxoacetone intermediate resembles [FeIII(tpa)(OOtBu)]2+ more than the corresponding FeIII-OOH species. At room temperature, however, the behavior of the Fe(tpa)/H2O2 combination in acetone in catalytic hydrocarbon oxidations differs significantly from that of the Fe(tpa)/tBuOOH combination and more closely matches that of the Fe(tpa)/H2O2 combination in CH3CN. Like the latter, the Fe(tpa)/H2O2 combination in acetone catalyzes the hydroxylation of cis-1,2-dimethylcyclohexane to its tertiary alcohol with high stereoselectivity and carries out the epoxidation and cis-dihydroxylation of olefins. These results demonstrate the subtle complexity of the Fe(tpa)/H2O2 reaction surface.

  20. Evidence-based milestone ages as a framework for developmental surveillance

    PubMed Central

    Dosman, Cara F; Andrews, Debbi; Goulden, Keith J

    2012-01-01

    Developmental surveillance is the process of monitoring child development over time to promote healthy development and to identify possible problems. Standardized developmental screeners have greater sensitivity than milestone-based history taking. Unfortunately, Canadian screening guidelines, to date, are sparse, logistical barriers to implementation have slowed uptake of screening tests and physicians continue to rely on milestones. When using clinical impression as a framework for surveillance, clinicians may not know when to consider a milestone delayed because developmental attainments exist within an age range and there is an absence of referenced percentiles on available published tables, which are particularly problematic for the cognitive and social-emotional sectors, which are less familiar to physicians. A novel, five-sector milestone framework with upper limits, referenced to the best available level of evidence, is presented. This framework may be used in teaching and may help physicians to better recognize failed milestones to facilitate early identification of children at risk for developmental disorders. PMID:24294064

  1. Evidence-based milestone ages as a framework for developmental surveillance.

    PubMed

    Dosman, Cara F; Andrews, Debbi; Goulden, Keith J

    2012-12-01

    Developmental surveillance is the process of monitoring child development over time to promote healthy development and to identify possible problems. Standardized developmental screeners have greater sensitivity than milestone-based history taking. Unfortunately, Canadian screening guidelines, to date, are sparse, logistical barriers to implementation have slowed uptake of screening tests and physicians continue to rely on milestones. When using clinical impression as a framework for surveillance, clinicians may not know when to consider a milestone delayed because developmental attainments exist within an age range and there is an absence of referenced percentiles on available published tables, which are particularly problematic for the cognitive and social-emotional sectors, which are less familiar to physicians. A novel, five-sector milestone framework with upper limits, referenced to the best available level of evidence, is presented. This framework may be used in teaching and may help physicians to better recognize failed milestones to facilitate early identification of children at risk for developmental disorders.

  2. 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 ...

  3. Agreement, Shells, and Focus.

    ERIC Educational Resources Information Center

    Simpson, Andrew; Wu, Zoe

    2002-01-01

    Reconsiders development and licensing of agreement as a syntactic projection and argues for a productive developmental relation between agreement and the category of focus. Suggests that focus projections are initially selected by a variety of functional heads with real semantic content, then, over time decays into a simple concord shell. Upon…

  4. 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)

  5. 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…

  6. The Helsinki Agreement

    ERIC Educational Resources Information Center

    Babel: Journal of the Australian Federation of Modern Language Teachers' Associations, 1977

    1977-01-01

    A reprint of sections of the Helsinki agreement dealing with foreign languages and civilization, and cooperation and exchanges in the field of education. The agreement supports wider knowledge of foreign languages and promotes exchanges, cooperation, lexicography, and specialized programs in adult education. (AMH)

  7. 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.

  8. Epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels.

    PubMed

    Asselbergs, Folkert W; Williams, Scott M; Hebert, Patricia R; Coffey, Christopher S; Hillege, Hans L; Navis, Gerjan; Vaughan, Douglas E; van Gilst, Wiek H; Moore, Jason H

    2007-03-01

    Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) directly influence thrombus formation and degradation and thereby risk for arterial thrombosis. Activation of the renin-angiotensin system has been linked to the production of PAI-1 expression via the angiotensin II type 1 receptor (AT1R). In addition, bradykinin can induce the release of t-PA through a B2 receptor mechanism. In the present study, we aimed to investigate the epistatic effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based sample (n=2527). We demonstrated a strong significant interaction within genetic variations of the bradykinin B2 gene (P=0.002) and between ACE and bradykinin B2 (p=0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels (P=0.006). In both females and males, the bradykinin B2 gene interacted with AT1R gene on plasma PAI-1 levels (P=0.026 and P=0.039, respectively). In addition, the current study found a borderline significant interaction between PAI 4G5G and ACE I/D on plasma t-PA and PAI-1 levels. These results support the idea that the interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems might play an important role in t-PA and PAI-1 biology.

  9. 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

  10. 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

  11. 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.

  12. Synthesis, structure and properties of one novel 2D Mn-heterocyclic carboxylic acid complex [Mn(TPA)Cl(H 2O)] n

    NASA Astrophysics Data System (ADS)

    Zhu, Peng; Li, Hui-Min

    2011-04-01

    A novel 2D layer complex [Mn(TPA)Cl(H 2O)] n ( 1) has been synthesized by two methods through the reaction of MnCl 2 and TPC or TPA under hydrothermal conditions and characterized by single crystal X-ray diffraction, elemental analysis, infrared spectrometry (IR), powder X-ray diffraction (XRD) and thermogravimetric analysis (TGA), where heterocyclic carboxylic acid ligand TPA = 2-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)acetic acid, TPC = 2-(5-(pyridin-2-yl)-2H-tetrazol-2-yl)acetonitrile. The distorted octahedral Mn(II) centers are bridged by carboxylic O atoms resulting in the formation of a 1D chain. Then the 1D chains are connected with each other through TPA ligands into a 2D (3,3)-connected topology framework. The H-bonding interactions extend the complex into a three-dimensional network, and such weak interactions further stabilized the complex. Furthermore, solid-state fluorescence spectrum of complex 1 exhibits intense broad emissions at 396 nm at room temperature, which is red-shifted by 21 nm relative to that of free ligand TPA.

  13. 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.

  14. 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

  15. 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

  16. Protective effect of fermented soybean dried extracts against TPA-induced oxidative stress in hairless mice skin.

    PubMed

    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

  17. 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.

  18. 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

  19. 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.

  20. Drive theory and home run milestones in baseball: an historical analysis.

    PubMed

    Goldschmied, Nadav; Harris, Michael; Vira, Damien; Kowalczyk, Jason

    2014-02-01

    The purpose of this investigation was to test whether the performance of the home run hitters in Major League Baseball adhered to predictions of Drive Theory. 24 baseball players who have hit at least 505 home runs were included in the sample. Their performance was assessed around the time in which they reached a significant home run career milestone, operationalized as either 500 or 600 home runs, or surpassing the league's home run record. As predicted, the players were found to require significantly more at-bats to complete the 5 home runs before the milestone, when stress was assumed to be mounting, than the 5 home runs after the milestone. In contrast, those players who reached the personal landmark from 1988 (the suspected commencement of the so-called "Steroid Era") onwards required the same number of at-bats before and after the milestone.

  1. 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.

  2. Prognostic value of tissue-type plasminogen activator (tPA) and its complex with the type-1 inhibitor (PAI-1) in breast cancer

    PubMed Central

    Witte, J H de; Sweep, C G J; Klijn, J G M; Grebenschikov, N; Peters, H A; Look, M P; Tienoven, ThH van; Heuvel, J J T M; Vries, J Bolt-De; Benraad, ThJ; Foekens, J A

    1999-01-01

    The prognostic value of tissue-type plasminogen activator (tPA) measured in samples derived from 865 patients with primary breast cancer using a recently developed enzyme-linked immunosorbent assay (ELISA) was evaluated. Since the assay could easily be adapted to the assessment of the complex of tPA with its type-1 inhibitor (PAI-1), it was investigated whether the tPA:PAI-1 complex also provides prognostic information. To this end, cytosolic extracts and corresponding detergent extracts of 100 000 g pellets obtained after ultracentrifugation when preparing the cytosolic fractions for routine steroid hormone receptor determination were assayed. Statistically significant correlations were found between the cytosolic levels and those determined in the pellet extracts (Spearman correlation coefficient rs = 0.75, P < 0.001 for tPA and r = 0.50, P < 0.001 for tPA:PAI-1 complex). In both Cox univariate and multivariate analysis elevated levels of (total) tPA determined in the pellet extracts, but not in cytosols, were associated with prolonged relapse-free (RFS) and overall survival (OS). In contrast, high levels of the tPA:PAI-1 complex measured in cytosols, but not in the pellet extracts, were associated with a poor RFS and OS. The prognostic information provided by the cytosolic tPA:PAI-1 complex was comparable to that provided by cytosolic (total) PAI-1. Furthermore, the estimated levels of free, uncomplexed tPA and PAI-1, in cytosols and in pellet extracts, were related to patient prognosis in a similar way as the (total) levels of tPA and PAI-1 respectively. Determination of specific forms of components of the plasminogen activation system, i.e. tPA:PAI-1 complex and free, uncomplexed tPA and/or PAI-1, may be considered a useful adjunct to the analyses of the separate components (tPA and/or PAI-1) and provide valuable additional prognostic information with respect to survival of breast cancer patients. © 1999 Cancer Research Campaign PMID:10390010

  3. Inhibitory effect of the flowers of artichoke (Cynara cardunculus) on TPA-induced inflammation and tumor promotion in two-stage carcinogenesis in mouse skin.

    PubMed

    Yasukawa, Ken; Matsubara, Hideki; Sano, Yuri

    2010-07-01

    The methanol extract of the flowers of artichoke (Cynara cardunculus) exhibited remarkable antitumor activity in an in vivo two-stage carcinogenesis test in mice, using 7,12-dimethylbenz[a]anthracene as an initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as a promoter. From the active fraction of the methanol extract, four triterpene alcohols and their corresponding acetates were isolated and identified. These compounds were evaluated for their inhibitory effects on TPA-induced inflammation (1 microg/ear) in mice and showed marked anti-inflammatory effects, with a 50% inhibitory dose of 0.50-0.91 micromol/ear.

  4. 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

  5. Milestones Contributing to the Evolution of Craniofacial Surgery.

    PubMed

    Tadisina, Kashyap Komarraju; Orra, Susan; Gharb, Bahar Bassiri; Rampazzo, Antonio; Papay, Francis; Zins, James E

    2015-11-01

    Craniofacial surgery (CFS) has a rich history of collaboration with a wide variety of surgical and nonsurgical specialties. This has resulted in a large volume of publications across this spectrum of subspecialties cataloging the advancements across the field. The authors aim to analyze the characteristics of the most cited articles in CFS. A literature search was performed using the Thomson/Reuters Web of Knowledge database to identify the top 50 most cited articles in CFS. The articles were analyzed for journal distribution, total citations, year of publication, citations per year, number of authors, type of article, institution, departmental affiliation, national affiliation, and top contributors. The articles were extracted from an assortment of 21 journals. The number of citations per article ranged from 115 to 1092 (average of 185). Forty-eight percent of articles were published in the 1990s, and 22% in the 2000s. The average number of years since publication until the present time was 21.34 (range 6-45 y). The most cited article (1092 citations and 52 citations/y) was an article by McCarthy et al on human mandible lengthening via gradual distraction. Departmental distribution indicated that the majority were attributable to departments of Plastic and Reconstructive Surgery for 21 articles (42%). Twenty articles were categorized under cranial defect/bone substitutes, 12 under craniosynostosis, 7 under surgical modeling, 6 under distraction osteogenesis, and the remaining 5 under other. These articles qualitatively represent important milestones in CFS. This study affirms the potential value of "number of citations" as a meaningful metric when assessing the importance of an article within CFS.

  6. 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

  7. 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.

  8. Attenuation of BPDE-induced p53 accumulation by TPA is associated with a decrease in stability and phosphorylation of p53 and down-regulation of NF-κB activation: Role of p38 MAP kinase

    PubMed Central

    Mukherjee, Jagat J.; Sikka, Harish C.

    2005-01-01

    DNA damage caused by benzo[a]pyrene (BP) or other PAHs induce p53 protein as a protective measure to eliminate the possibility of mutagenic fixation of the DNA damage. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits p53 response induced by BP and other DNA-damaging agents and may cause tumor promotion. The molecular mechanism of attenuation of BP-induced p53 response by TPA is not known. We investigated the effect of TPA on p53 response in BPDE-treated mouse epidermal JB6(P+) Cl 41 cells. BPDE treatment induced p53 accumulation which was attenuated significantly by TPA. Cells treated with BPDE and TPA showed increased ratio of Mdm2 to p53 proteins in p53 immunoprecipitate and decreased p53 life span compared to BPDE-treated cells indicating p53 destabilization by TPA. TPA also inhibited BPDE-induced p53 phosphorylation at serine15. Activation of both ERKs and p38 MAPK by BPDE and attenuation of BPDE-induced p53 accumulation by U0126 or SB202190, specific inhibitor of MEK1/2 or p38 MAPK, indicate the role of ERKs and p38 MAPK in p53 accumulation. Interestingly, TPA potentiated BPDE-induced activation of ERKs whereas p38 MAPK activation was significantly inhibited by TPA, suggesting that inhibition of p38 MAPK is involved in p53 attenuation by TPA. Furthermore SB202190 treatment caused decreased p53 stability and inhibition of phosphorylation of p53 at serine 15 in BPDE-treated cells. We also observed that TPA or SB202190 attenuated BPDE-induced NF-κB activation in JB6 (Cl 41) cells harboring NF-κB reporter plasmid. To our knowledge this is the first report that TPA inhibits chemical carcinogen-induced NF-κB activation. Interference of TPA with BPDE-induced NF-κB activation implicates abrogation of p53 function which has been discussed. Overall our data suggest that abrogation of BPDE-induced p53 response and of NF-κB activation by TPA is mediated by impairment of signaling pathway involving p38 MAPK. PMID:16244358

  9. 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)

  10. Agreements in Virtual Organizations

    NASA Astrophysics Data System (ADS)

    Pankowska, Malgorzata

    This chapter is an attempt to explain the important impact that contract theory delivers with respect to the concept of virtual organization. The author believes that not enough research has been conducted in order to transfer theoretical foundations for networking to the phenomena of virtual organizations and open autonomic computing environment to ensure the controllability and management of them. The main research problem of this chapter is to explain the significance of agreements for virtual organizations governance. The first part of this chapter comprises explanations of differences among virtual machines and virtual organizations for further descriptions of the significance of the first ones to the development of the second. Next, the virtual organization development tendencies are presented and problems of IT governance in highly distributed organizational environment are discussed. The last part of this chapter covers analysis of contracts and agreements management for governance in open computing environments.

  11. 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.

  12. Novel non-invasive distribution measurement of texture profile analysis (TPA) in salmon fillet by using visible and near infrared hyperspectral imaging.

    PubMed

    Wu, Di; Sun, Da-Wen; He, Yong

    2014-02-15

    This study developed a pushbroom visible and near-infrared hyperspectral imaging system in the wavelength range of 400-1758 nm to determine the spatial distribution of texture profile analysis (TPA) parameters of salmon fillets. Six TPA parameters (hardness, adhesiveness, chewiness, springiness, cohesiveness, and gumminess) were analysed. Five spectral features (mean, standard deviation, skew, energy, and entropy) and 22 image texture features obtained from graylevel co-occurrence matrix (GLCM) were extracted from hyperspectral images. Quantitative models were established with the extracted spectral and image texture signatures of samples based on partial least squares regression (PLSR). The results indicated that spectral features had better ability to predict TPA parameters of salmon samples than image texture features, and Spectral Set I (400-1000 nm) performed better than Spectral II (967-1634 nm). On the basis of the wavelengths selected by regression coefficients of PLSR models, instrumental optimal wavelengths (IOW) and predictive optimal wavelengths (POW) were further chosen to reduce the high dimensionality of the hyperspectral image data. Our results show that hyperspectral imaging holds promise as a reliable and rapid alternative to traditional universal testing machines for measuring the spatial distribution of TPA parameters.

  13. 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.

  14. 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

  15. 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…

  16. Ulinastatin decreases permeability of blood--brain barrier by inhibiting expression of MMP-9 and t-PA in postoperative aged rats.

    PubMed

    Ma, Li; Zhang, Hui; Liu, Yong-zhe; Yin, Yan-ling; Ma, Ya-qun; Zhang, Sheng-suo

    2016-01-01

    Tissue-type plasminogen activator (t-PA) and matrix metalloproteinase-9 (MMP-9) have been reported to play important roles in increased permeability of blood-brain barrier (BBB) under many pathological circumstances. We have showed that Ulinastatin, a broad-spectrum serine protease inhibitor, could alleviate inflammation in the hippocampus of aged rats following partial hepatectomy. In this study, we investigate the expression and potential roles of t-PA and MMP-9 in the protective effect of Ulinastatin. We found that partial hepatectomy increased Evans blue leakage in hippocampus at day 1 and 3 postoperatively. Furthermore, surgery decreased the protein levels of claudin-5, ZO-1, and NF-kB p65 while upregulating the mRNA and protein levels of t-PA and MMP-9 in brain capillaries. All these effects caused by surgery were partially reversed by administering Ulinastatin. Our study sheds light on the roles of t-PA and MMP-9 of BBB in post-surgical neuroinflammation and postoperative cognitive dysfunction. Besides, it could also help to understand the mechanism of Ulinastatin alleviating neuroinflammation.

  17. 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

  18. Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

    PubMed

    Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

    2015-07-01

    Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice.

  19. Anti-diphtheria antibody seroprotection rates are similar 10 years after vaccination with dTpa or DTPa using a mathematical model.

    PubMed

    Cheuvart, Brigitte; Burgess, Margaret; Zepp, Fred; Mertsola, Jussi; Wolter, Joanne; Schuerman, Lode

    2004-12-01

    The reduced antigen content diphtheria, tetanus and pertussis (dTpa) vaccine (Boostrixtrade mark) has been shown to induce a strong booster response to all the vaccine components in 4-6 year olds. However, anti-diphtheria antibody levels were observed to be lower when compared to the "full strength" paediatric DTPa vaccine. To assess the impact of this difference on long-term protection, a mathematical model was developed to predict diphtheria antibody decay over time. The model was based on a linear decrease in log-transformed antibody concentrations after the first year post-vaccination. When applied to data collected 3.5 years after vaccination of 4-6 year olds with either DTPa or dTpa, the model predicted that 10 years post-vaccination, 98.6% of subjects vaccinated with dTpa were likely to remain seroprotected against diphtheria, compared to 99.6% vaccinated with DTPa. Therefore, the difference observed in diphtheria antibody geometric mean concentrations 1 month after booster vaccination at 4-6 years with dTpa or DTPa is unlikely to be of clinical relevance 10 years later at the time of the adolescent booster.

  20. Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

    PubMed

    Noh, Eun-Mi; Park, Yeon-Ju; Kim, Jeong-Mi; Kim, Mi-Seong; Kim, Ha-Rim; Song, Hyun-Kyung; Hong, On-Yu; So, Hong-Seob; Yang, Sei-Hoon; Kim, Jong-Suk; Park, Samg Hyun; Youn, Hyun-Jo; You, Yong-Ouk; Choi, Ki-Bang; Kwon, Kang-Beom; Lee, Young-Rae

    2015-10-01

    Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

  1. Growth-dependent AIB and meAIB uptake in LLC-PK/sub 1/ cells: effects of differentiation inducers and of TPA

    SciTech Connect

    Amsler, K.; Shaffer, C.; Cook, J.S.

    1983-01-01

    Cultured pig kidney cells designated LLC-PK/sub 1/, previously shown to acquire Na/sup +/-dependent concentrative transport of hexoses as the cells become growth arrested, also show Na/sup +/-dependent concentrative uptake of the amino acid analogs /sup 2/-aminoisobutyric acid (AIB) and (methyl) meAIB. This A system-like transport is most active in sparse, growing cultures and becomes stepped down at confluence. The cell/medium equilibrium distribution ratio of the lipophilic cation tetraphenylphosphonium ion (TPP/sup +/) decreases in parallel fashion, suggesting that a decrease in membrane potential may be a major factor in the stepdown. Differentiation inducers (hexamethylene bisacetamide) and phosphodiesterase inhibitors (theophylline, methylisobutyl xanthine) accelerate the stepdown, but even in the presence of these compounds addition of the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) results in the maintenance of a high level of AIB and meAIB uptake. In all these respects the changes in A system like amino acid transport are the reciprocal of those seen for concentrative hexose transport, although the driving force appears to be the same for both systems. The TPA analogs phorbol and 4-0-methyl TPA which are inactive in tumor promotion are inactive in this system as well. In confluent, already stepped-down cultures, addition of TPA leads to a rapid (2-6 hour) stimulation of AIB and meAIB uptake. The enhancement is sensitive to cycloheximide and actinomycin D. 30 references, 6 figures.

  2. Interaction of human tissue plasminogen activator (t-PA) with pregnancy zone protein: a comparative study with t-PA-alpha2-macroglobulin interaction.

    PubMed

    Sánchez, M C; Chiabrando, G A; Guglielmone, H A; Bonacci, G R; Rabinovich, G A; Vides, M A

    1998-08-01

    Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein strongly related to alpha2-macroglobulin (alpha2-M). Interactions of tissue plasminogen activator (t-PA) with PZP and alpha2-M were both investigated in vitro and the complexes were analyzed by polyacrylamide gel electrophoresis (PAGE). The results demonstrated that PZP-t-PA complex formation was evident within 1 h of incubation, whereas alpha2-M-t-PA complexes were formed after 18 h. Conclusions were supported by the following evidence: (i) PZP and alpha2-M complexes revealed changes of the mobility rate in non-denaturing PAGE, similar to those observed with alpha-Ms-chymotrypsin; (ii) both PZP and alpha2-M formed complexes of molecular size >360 kDa by SDS-PAGE, in accordance with the covalent binding of t-PA, which was previously reported for other proteinases; and (iii) PZP underwent a specific cleavage of the bait region with appearence of fragments of 85-90 kDa as judged by reducing SDS-PAGE. In contrast, the proteolytic attack on alpha2-M was found to occur more slowly, requiring several hours of incubation with t-PA for generation of an appreciable amount of fragments of 85-90 kDa. The appearance of free SH-groups of alpha-Ms was further investigated by titration with 5, 5'-dithiobis(2-nitrobenzoic acid). The maximal level of SH-groups raised was 3.9 mol/mol of PZP and 3.5 mol/mol of alpha2-M, indicating approximately one SH-group for each 180-kDa subunit. Finally, t-PA activity in PZP-t-PA complex was evaluated by measuring the hydrolysis of the chromogenic substrate Flavigen t-PA. Our results revealed that prolongation of the incubation period of this complex increased t-PA-mediated hydrolysis of Flavigen t-PA until a plateau was reached, approximately between 60 and 120 min. The present study suggests that PZP, by binding to t-PA, may contribute to the control of the activity of proteinases derived from fibrinolytic systems.

  3. Plasma Is the Physiologic Buffer of tPA Mediated Fibrinolysis: Rationale for Plasma First Resuscitation after Life-Threatening Hemorrhage

    PubMed Central

    Moore, Hunter B; Moore, Ernest E; Gonzalez, Eduardo; Wiener, Gregory; Chapman, Michael P; Dzieciatkowska, Monika; Sauaia, Angela; Banerjee, Anirban; Hansen, Kirk C; Silliman, Christopher

    2015-01-01

    Background Pre-hospital resuscitation with crystalloid exacerbates fibrinolysis, which is associated with high mortality. We hypothesize that plasma compared to crystalloid resuscitation prevents hyperfibrinolysis in a tissue plasminogen activator (tPA) rich environment via preservation of proteins essential for regulation of fibrinolysis. Study Design Healthy individuals donated blood, which was assayed using a native (non activated) thrombelastography (TEG). Whole-blood (WB) was mixed with normal saline (NS) or platelet poor plasma (PPP) at progressive dilutions. TPA was added to promote a fibrinolytic environment. In a separate experiment PPP was run through 100 KD filter and liquid remaining on top of the filter (TFP) and below the filter (BFP) was obtained. Whole blood was diluted by 50% with TFP, BPF and NS and assayed with tPA TEG challenge. TFP and BFP were assayed for protein concentration and protein composition. Results NS and PPP dilution of WB with out tPA did not affect clot lysis at 30 minutes (LY30) (NS Spearman’s Rho 0.300 p=0.186 and PPP 0.294 p=0.288). When tPA was added NS dilution of whole blood increased LY30 in a percentage dependent manner (0.844 p<0.001) but did not significantly increase with PPP dilution (0.270 p=0.202). The difference in LY30 from WB to diluted WB with PPP (mean change −1.05 95% CI −9.42 to 7.33) was similar with TFP (1.23 95%CI −5.20 to 7.66 p=0.992). However, both BPF (37.65 95%CI 24.47 to 50.82 p=0.001) and NS (47.36 95%CI 34.3–60.45 p<0.001) showed large increases in fibrinolysis compared to PPP. Conclusions Crystalloid and plasma dilution of whole blood does not increase fibrinolysis. However NS dilution of WB, increases susceptibility to tPA mediated fibrinolysis. Plasma resuscitation, simulated by plasma dilution of whole blood, attenuates increased susceptibility to tPA mediate fibrinolysis. The benefits of plasma resuscitation are mediated through preservation of plasma proteins. PMID:25840538

  4. Highly effective fibrinolysis by a sequential synergistic combination of mini-dose tPA plus low-dose mutant proUK.

    PubMed

    Pannell, Ralph; Li, Shelley; Gurewich, Victor

    2015-01-01

    Results of thrombolysis by monotherapy with either tPA or proUK have not lived up to expectations. Since these natural activators are inherently complementary, this property can be utilized to a synergistic advantage; and yet, this has undergone little evaluation. ProUK is no longer available because at pharmacological concentrations it converts to UK in plasma. Therefore, a single site proUK mutant, M5, was developed to address this problem and was used in this study. Fibrinolysis was measured using preformed fluoresceinated 24 h old clots in a plasma milieu rather than by the standard automated method, because proUK/M5 is sensitive to inactivation by thrombin and activation by plasmin. The shortest 50% clot lysis time that could be achieved by tPA or M5 alone was determined: mean times were 55 and 48 minutes respectively. These bench marks were matched by 6% of the tPA monotherapy dose combined with 40% that of M5: mean lysis time 47 minutes with less associated fibrinogenolysis. Results showed that the tPA effect was limited to initiating fibrinolysis which was completed by M5 and then tcM5. Plasma C1-inhibitor inhibited fibrinogenolysis by M5, providing protection from side effects not available for proUK. In conclusion, by utilizing the complementary properties and sequential modes of action of each activator, more efficient fibrinolysis with less non-specific effects can be achieved than with traditional monotherapy. In vivo validation is needed, but in a previous clinical trial using a similar combination of tPA and proUK (5% and 50% monotherapy doses) very promising results have already been obtained. PMID:25811605

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

    ... 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... Title XVI amount of payment Phase 1 (120% of Title II PCB) Milestone 1 $335/mo. $670/mo. × 3 mo. work...

  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. 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

  17. 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

  18. 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…

  19. 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...

  20. 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...

  1. "Educate, Don't Segregate": Twenty Legal and Legislative Milestones in Higher Education

    ERIC Educational Resources Information Center

    Black Issues in Higher Education, 2004

    2004-01-01

    This timeline reflects some of the most significant legal and legislative milestones that have influenced higher education almost as long as Black Issues In Higher Education has been in print. The ongoing legal battles have primarily involved the further desegregation of schools and the use of race and gender in scholarships and university…

  2. 20 CFR 411.535 - Under what circumstances will milestones be paid?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... paid? 411.535 Section 411.535 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND... earnings were less than the trial work level in each of the 18 months before the ticket was first assigned to an EN. All work and earnings counted toward reaching the four Phase 1 milestones must occur...

  3. 20 CFR 411.535 - Under what circumstances will milestones be paid?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... paid? 411.535 Section 411.535 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND... earnings were less than the trial work level in each of the 18 months before the ticket was first assigned to an EN. All work and earnings counted toward reaching the four Phase 1 milestones must occur...

  4. 20 CFR 411.535 - Under what circumstances will milestones be paid?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... paid? 411.535 Section 411.535 Employees' Benefits SOCIAL SECURITY ADMINISTRATION THE TICKET TO WORK AND... earnings were less than the trial work level in each of the 18 months before the ticket was first assigned to an EN. All work and earnings counted toward reaching the four Phase 1 milestones must occur...

  5. 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...

  6. 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…

  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. 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…

  9. 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…

  10. Effects of Family and Friend Support on LGB Youths' Mental Health and Sexual Orientation Milestones

    ERIC Educational Resources Information Center

    Shilo, Guy; Savaya, Riki

    2011-01-01

    This study examined the effects of social support components and providers on mental health and sexual orientation (SO) milestones of lesbian, gay, and bisexual (LGB) youths. Data were collected on 461 self-identified LGB adolescents and young adults. Family acceptance and support yielded the strongest positive effect on self-acceptance of SO,…

  11. 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…

  12. Outcomes and milestone achievement differences for very low-birth-weight multiples compared with singleton infants.

    PubMed

    Kirkby, Sharon; Genen, Linda; Turenne, Wendy; Dysart, Kevin

    2010-06-01

    We examined if very low-birth-weight (VLBW) infants of multiple gestation pregnancies experience more complications and take longer to achieve clinical milestones compared with similar singletons. We performed a retrospective analysis of all infants less than 1500 g at birth in a large neonatal database. Singletons were compared with twins and higher-order multiples for demographic, morbidities, and process milestones including feeding, respiratory, thermoregulation, and length of stay. Multivariable regression analyses were performed to control for potential confounding variables. A total of 5507 infants were included: 3792 singletons, 1391 twins, and 324 higher-order multiples. There were no differences in Apgar scores, small for gestational age status, and incidence of necrotizing enterocolitis, severe retinopathy of prematurity, severe intraventricular hemorrhage, sepsis, bronchopulmonary dysplasia, or the need for surgery. Multiples had higher rates of apnea and patent ductus arteriosus than singletons. VLBW multiples achieved milestones at similar rates in most areas compared with singletons except for the achievement of full oral feedings. Length of stay, after controlling for confounding variables, did not differ between the groups. Compared with singletons, VLBW multiples had similar morbidity and achieved most feeding and thermoregulation milestones at similar rates.

  13. 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...

  14. Vouchers in Hong Kong: A New Milestone of Early Childhood Education?

    ERIC Educational Resources Information Center

    Yuen, Gail W. K.

    2007-01-01

    The Hong Kong government has recently introduced a voucher system to early childhood education, indicating that the new policy is a milestone in the field. The overall goal of the policy is to improve the provision of early childhood education for the benefit of the children. Public debates reveal the unfamiliar nature of the subject to the local…

  15. 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…

  16. 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

  17. Enhancing mitochondrial respiration suppresses tumor promoter TPA-induced PKM2 expression and cell transformation in skin epidermal JB6 cells.

    PubMed

    Wittwer, Jennifer A; Robbins, Delira; Wang, Fei; Codarin, Sarah; Shen, Xinggui; Kevil, Christopher G; Huang, Ting-Ting; Van Remmen, Holly; Richardson, Arlan; Zhao, Yunfeng

    2011-09-01

    Differentiated cells primarily metabolize glucose for energy via the tricarboxylic acid cycle and oxidative phosphorylation, but cancer cells thrive on a different mechanism to produce energy, characterized as the Warburg effect, which describes the increased dependence on aerobic glycolysis. The M2 isoform of pyruvate kinase (PKM2), which is responsible for catalyzing the final step of aerobic glycolysis, is highly expressed in cancer cells and may contribute to the Warburg effect. However, whether PKM2 plays a contributing role during early cancer development is unclear. In our studies, we have made an attempt to elucidate the effects of varying mitochondrial respiration substrates on skin cell transformation and expression of PKM2. Tumorigenicity in murine skin epidermal JB6 P+ (promotable) cells was measured in a soft agar assay using 12-O-tetradecanoylphorbol-13-acetate (TPA) as a tumor promoter. We observed a significant reduction in cell transformation upon pretreatment with the mitochondrial respiration substrate succinate or malate/pyruvate. We observed that increased expression and activity of PKM2 in TPA-treated JB6 P+ cells and pretreatment with succinate or malate/pyruvate suppressed the effects. In addition, TPA treatment also induced PKM2 whereas PKM1 expression was suppressed in mouse skin epidermal tissues in vivo. In comparison with JB6 P+ cells, the nonpromotable JB6 P- cells showed no increase in PKM2 expression or activity upon TPA treatment. Knockdown of PKM2 using a siRNA approach significantly reduced skin cell transformation. Thus, our results suggest that PKM2 activation could be an early event and play a contributing role in skin tumorigenesis.

  18. Immunotherapy prolongs the serum CEA-TPA-CA15.3 lead time at the metastatic progression in endocrine-dependent breast cancer patients: a retrospective longitudinal study.

    PubMed

    Nicolini, A; Carpi, A; Ferrari, P; Rossi, G

    2008-05-01

    In metastatic breast cancer tumour markers' increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA-TPA-CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA-TPA-CA15.3 lead time (m+/-sd, months) was significantly longer than in group c (12.1+/-12.9 vs 2.4+/-4.0) (P=0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset (P=0.003) while in the group c the difference was near to significance (P=0.05). The CEA-TPA-CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA-TPA-CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.

  19. Aromatic-turmerone attenuates invasion and expression of MMP-9 and COX-2 through inhibition of NF-κB activation in TPA-induced breast cancer cells.

    PubMed

    Park, Sun Young; Kim, Young Hun; Kim, YoungHee; Lee, Sang-Joon

    2012-12-01

    Recent evidence suggests that breast cancer is one of the most common forms of malignancy in females, and metastasis from the primary cancer site is the main cause of death. Aromatic (ar)-turmerone is present in Curcuma longa and is a common remedy and food. In the present study, we investigated the inhibitory effects of ar-turmerone on expression and enzymatic activity levels of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase (MMP)-9 and cyclooxygenaase-2 (COX-2) in breast cancer cells. Our data indicated that ar-turmerone treatment significantly inhibited enzymatic activity and expression of MMP-9 and COX-2 at non-cytotoxic concentrations. However, the expression of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, MMP-2, and COX-1 did not change upon ar-turmerone treatment. We found that ar-turmerone inhibited the activation of NF-κB, whereas it did not affect AP-1 activation. Moreover, The ChIP assay revealed that in vivo binding activities of NF-κB to the MMP-9 and COX-2 promoter were significantly inhibited by ar-turmerone. Our data showed that ar-turmerone reduced the phosphorylation of PI3K/Akt and ERK1/2 signaling, whereas it did not affect phosphorylation of JNK or p38 MAPK. Thus, transfection of breast cancer cells with PI3K/Akt and ERK1/2 siRNAs significantly decreased TPA-induced MMP-9 and COX-2 expression. These results suggest that ar-turmerone suppressed the TPA-induced up-regulation of MMP-9 and COX-2 expression by blocking NF-κB, PI3K/Akt, and ERK1/2 signaling in human breast cancer cells. Furthermore, ar-turmerone significantly inhibited TPA-induced invasion, migration, and colony formation in human breast cancer cells.

  20. 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…

  1. 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.…

  2. Effects of lowering the aluminium content of a dTpa vaccine on its immunogenicity and reactogenicity when given as a booster to adolescents.

    PubMed

    Theeten, H; Van Damme, P; Hoppenbrouwers, K; Vandermeulen, C; Leback, E; Sokal, E M; Wolter, J; Schuerman, L

    2005-02-10

    As aluminium in vaccines has been associated with the incidence of local side effects occurring after vaccination, this observer-blind randomised clinical trial was designed to evaluate the effect of lowering the aluminium content of a combined reduced-antigen-content dTpa vaccine on immunogenicity and safety when administered to healthy adolescents aged 10-18 years. A total of 647 subjects were enrolled, 224 (35%) received a dTpa formulation with 0.5 mg aluminium, 209 (32%) a formulation with 0.3 mg aluminium and 214 (33%) a formulation with 0.133 mg aluminium. One month after boostering, all subjects were seroprotected against diphtheria and tetanus toxoids. All subjects were seropositive for anti-FHA and anti-PRN but 4% of the initially seronegatives in both reduced aluminium groups did not seroconvert for anti-PT. Booster responses did not differ significantly between groups for any antibody, but post booster vaccination anti-PT GMC's differed significantly between groups and decreased when vaccine aluminium content decreased. No clear difference between study groups in local or general side effects was demonstrated. The most frequently reported symptoms after vaccination were injection site pain (89.5-90.7%), fatigue (42.1-47.4%) and headache (41.1-45.1%). This study showed that the aluminium content has a specific influence on the immunogenicity of this dTpa vaccine.

  3. 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

  4. Emergency Medicine Residents Consistently Rate Themselves Higher than Attending Assessments on ACGME Milestones

    PubMed Central

    Goldflam, Katja; Bod, Jessica; Della-Giustina, David; Tsyrulnik, Alina

    2015-01-01

    Introduction In 2012 the Accreditation Council for Graduate Medical Education (ACGME) introduced the Next Accreditation System (NAS), which implemented milestones to assess the competency of residents and fellows. While attending evaluation and feedback is crucial for resident development, perhaps equally important is a resident’s self-assessment. If a resident does not accurately self-assess, clinical and professional progress may be compromised. The objective of our study was to compare emergency medicine (EM) resident milestone evaluation by EM faculty with the same resident’s self-assessment. Methods This is an observational, cross-sectional study that was performed at an academic, four-year EM residency program. Twenty-five randomly chosen residents completed milestone self-assessment using eight ACGME sub-competencies deemed by residency leadership as representative of core EM principles. These residents were also evaluated by 20 faculty members. The milestone levels were evaluated on a nine-point scale. We calculated the average difference between resident self-ratings and faculty ratings, and used sample t-tests to determine statistical significance of the difference in scores. Results Eighteen residents evaluated themselves. Each resident was assessed by an average of 16 attendings (min=10, max=20). Residents gave themselves statistically significant higher milestone ratings than attendings did for each sub-competency examined (p<0.0001). Conclusion Residents over-estimated their abilities in every sub-competency assessed. This underscores the importance of feedback and assessment transparency. More attention needs to be paid to methods by which residency leadership can make residents’ self-perception of their clinical ability more congruent with that of their teachers and evaluators. The major limitation of our study is small sample size of both residents and attendings. PMID:26594293

  5. 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.

  6. Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells

    PubMed Central

    2014-01-01

    Background Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. Methods Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. Results Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 μM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 μM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Conclusions These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro. PMID:24885456

  7. 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.

  8. 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

  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... America Discussion Agreement; and Zim Integrated Shipping Services, Ltd. Filing Party: Wayne R. Rohde,...

  10. Byzantine agreement method without authentication

    SciTech Connect

    Reischuk, R.K.

    1983-12-01

    This invention relates to a method for achieving Byzantine agreement without authentication among n 100 communicating processors using event counting and thresholding rather than message exchanges and evaluations.

  11. Experience and grammatical agreement: Statistical learning shapes number agreement production

    PubMed Central

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

    2009-01-01

    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 thought to reflect core language production processes. Previous accounts have attributed error patterns to a syntactic number feature present on plurals but not singulars. An alternative approach is presented in which a process similar to structural priming contributes to the error asymmetry via speakers' past experiences with related agreement constructions. A corpus analysis and two agreement production studies test this account. The results suggest that agreement production is shaped by statistical learning from past language experience. Implications for accounts of agreement are discussed. PMID:19942213

  12. Effects of molarity and solvents on the optical properties of the solutions of tris[4-(5-dicyanomethylidenemethyl-2-thienyl)phenyl]amine (TDCV-TPA) and structural properties of its film

    NASA Astrophysics Data System (ADS)

    Gündüz, Bayram

    2013-12-01

    The surface morphology of the tris[4-(5-dicyanomethylidenemethyl-2-thienyl)phenyl]amine (TDCV-TPA) film was investigated by high performance atomic force microscopy and the surface roughness parameters such as roughness average (sa), root mean square roughness (sq), surface skewness (ssk) and surface kurtosis (sku) of the TDCV-TPA film were obtained. The TDCV-TPA film indicated the low valleys with bumpy surface. The optical properties of the solutions of the small-molecule semiconducting dye TDCV-TPA for different high molarities, lower molarities and different solvents were investigated in detail. The molar extinction coefficient, optical band gap, angle values of refraction of the TDCV-TPA decreased with increasing molarity, while the absorbance at maximum absorption wavelengths, angle of incidence, electric susceptibility, real part values of the optical conductivity of the TDCV-TPA increased with increasing molarity. The maximum molar extinction coefficient (ɛmax) at λmax values (510 and 509 nm) of the solutions of the TDCV-TPA for 0.024 and 0.010 mM were found to be 1.175 × 105 and 1.931 × 105 L mol-1 cm-1, respectively. The maximum mass extinction coefficient (αmax) of the solutions of the TDCV-TPA for 0.024 and 0.010 mM were found to be 163.226 and 268.247 L g-1 cm-1, respectively. The optical band gap (Eg) values of the TDCV-TPA for 1, 2 and 3 mM were found to be 1.916, 1.898 and 1.892 eV, respectively. The absorption band edge for DCM varied from 1.882 to 1.997 eV, while the absorption band edge for chloroform varied from 1.923 to 2.027 eV. To obtain lower optical band gap of the TDCV-TPA can be prefered DCM solvent.

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

    PubMed

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

    2015-05-01

    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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  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. Putting the pediatrics milestones into practice: a consensus roadmap and resource analysis.

    PubMed

    Schumacher, Daniel J; Spector, Nancy D; Calaman, Sharon; West, Daniel C; Cruz, Mario; Frohna, John G; Gonzalez Del Rey, Javier; Gustafson, Kristina K; Poynter, Sue Ellen; Rosenbluth, Glenn; Southgate, W Michael; Vinci, Robert J; Sectish, Theodore C

    2014-05-01

    The Accreditation Council for Graduate Medical Education has partnered with member boards of the American Board of Medical Specialties to initiate the next steps in advancing competency-based assessment in residency programs. This initiative, known as the Milestone Project, is a paradigm shift from traditional assessment efforts and requires all pediatrics residency programs to report individual resident progression along a series of 4 to 5 developmental levels of performance, or milestones, for individual competencies every 6 months beginning in June 2014. The effort required to successfully make this shift is tremendous given the number of training programs, training institutions, and trainees. However, it holds great promise for achieving training outcomes that align with patient needs; developing a valid, reliable, and meaningful way to track residents' development; and providing trainees with a roadmap for learning. Recognizing the resources needed to implement this new system, the authors, all residency program leaders, provide their consensus view of the components necessary for implementing and sustaining this effort, including resource estimates for completing this work. The authors have identified 4 domains: (1) Program Review and Development of Stakeholders and Participants, (2) Assessment Methods and Validation, (3) Data and Assessment System Development, and (4) Summative Assessment and Feedback. This work can serve as a starting point and framework for collaboration with program, department, and institutional leaders to identify and garner necessary resources and plan for local and national efforts that will ensure successful transition to milestones-based assessment.

  2. 20 CFR 411.580 - Can an EN receive payments for milestones or outcome payment months that occur before the...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....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...

  3. 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...

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Greater length-for-age increases the odds of attaining motor milestones in Vietnamese children aged 5-18 months.

    PubMed

    Kulkarni, Shibani; Ramakrishnan, Usha; Dearden, Kirk A; Marsh, David R; Ha, Tran Thu; Tran, Thach Duc; Pachón, Helena

    2012-01-01

    Early childhood malnutrition has been associated with delayed development. Limited data exist however about the timing of developmental delay early in life. We assessed motor milestone (MM) achievement using the World Health Organization's windows of achievement for gross motor milestones. We performed secondary analysis of baseline data of 158 Vietnamese children aged 5-18 months from a randomized community intervention trial. Median age of motor milestone achievement was compared to WHO reported medians. Multivariate logistic regression was used to identify socioeconomic, anthropometric and dietary factors associated with motor milestone achievement during the windows of achievement. Thirty four per cent of the children were stunted. Median age of MM achievement of Vietnamese children lagged by 2.4-3.7 months, compared to the WHO median for all MMs. Greater length-for-age increased the odds for walking with assistance, standing alone and walking alone by more than 3 times. Greater weight-for-age increased the odds by 3.6 for hand-and-knees crawling. Likewise, frequency of daily complementary feeding raised the odds by 3.6 for standing with assistance. In this first application of WHO windows of achievement in Viet Nam, pre-schoolers achieved motor milestones later than WHO reported median age. High prevalence of stunting and association of length-for-age with motor milestone achievement underscore the importance of addressing chronic malnutrition to optimize children's growth and development.

  10. Federal Facility Agreement progress report

    SciTech Connect

    Not Available

    1993-10-01

    The (SRS) Federal Facility Agreement (FFA) was made effective by the US. Environmental Protection Agency Region IV (EPA) on August 16, 1993. To meet the reporting requirements in Section XXV of the Agreement, the FFA Progress Report was developed. The FFA Progress Report is the first of a series of quarterly progress reports to be prepared by the SRS. As such this report describes the information and action taken to September 30, 1993 on the SRS units identified for investigation and remediation in the Agreement. This includes; rubble pits, runoff basins, retention basin, seepage basin, burning pits, H-Area Tank 16, and spill areas.

  11. 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.

  12. 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

  13. 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.

  14. Empirical agreement in model validation.

    PubMed

    Jebeile, Julie; Barberousse, Anouk

    2016-04-01

    Empirical agreement is often used as an important criterion when assessing the validity of scientific models. However, it is by no means a sufficient criterion as a model can be so adjusted as to fit available data even though it is based on hypotheses whose plausibility is known to be questionable. Our aim in this paper is to investigate into the uses of empirical agreement within the process of model validation.

  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. GME Milestone.

    PubMed

    Sorrel, Amy Lynn

    2016-08-01

    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.

  17. 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 ...

  18. 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 ...

  19. 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.

  20. 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...

  1. 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...

  2. 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

  3. Displacement of submacular hemorrhage associated with age-related macular degeneration using vitrectomy and submacular tPA injection followed by intravitreal ranibizumab

    PubMed Central

    Sandhu, Sukhpal Singh; Manvikar, Sridhar; Steel, David Henry William

    2010-01-01

    Background/aims: To evaluate retrospectively the clinical outcomes of patients presenting with submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD), treated by vitrectomy, submacular tissue plasminogen activator (tPA) injection and pneumatic displacement of SMH with air followed by postoperative intravitreal ranibizumab (RZB). Methods: Patients with SMH and nAMD had 25-guage vitrectomy and subretinal tPA (12.5 micrograms/0.1 mL) with fluid/air exchange. Intravitreal RZB was administered postoperatively to patients eligible for National Health Service (NHS) funded treatment. Results: Of the total of 16 patients, 11 (68.7%) had complete displacement of SMH. The remaining five had residual SMH, mainly subretinal pigment epithelium in location. Three of the four patients who previously had a failed expansile gas pneumatic displacement were successfully displaced with vitrectomy surgery. At presentation 5/16 (31.3%) patients were eligible for NHS funded intravitreal RZB. This increased to 12 patients after the vitrectomy procedure (75.0%). At 6 months postoperatively all improved by ≥1 line. Ten of the 16 patients (63%) improved by ≥2 lines, with 10 of the 12 patients (83%) treated with RZB improving by ≥2 lines. Conclusion: Vitrectomy/subretinal tPA/air to displace SMH followed by intravitreal RZB injection can stabilize/improve vision in patients with nAMD. This technique displaces hemorrhage not displaced by attempted expansile gas techniques. PMID:20668667

  4. 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

  5. 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.

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

    DOE PAGES

    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. Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

    PubMed Central

    Kristiansen, Søren; Jørgensen, Lars Mønster; Hansen, Morten Høgh; Nielsen, Dorte; Sölétormos, György

    2015-01-01

    The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring. PMID:26339655

  8. 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

  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. Gender agreement and multiple referents.

    PubMed

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

    2008-01-01

    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

  11. Gender agreement and multiple referents.

    PubMed

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

    2008-01-01

    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.

  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. The effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels are dependent on environmental context.

    PubMed

    Asselbergs, Folkert W; Williams, Scott M; Hebert, Patricia R; Coffey, Christopher S; Hillege, Hans L; Snieder, Harold; Navis, Gerjan; Vaughan, Douglas E; van Gilst, Wiek H; Moore, Jason H

    2007-11-01

    Thrombosis is a key factor in the pathophysiology of cardiovascular disease. Important biochemical constituents of the fibrinolytic system, affecting thrombosis, include tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1). Both t-PA and PAI-1 are determined by multiple genetic and environmental factors. We aimed to investigate whether the effects of polymorphism in genes from the renin-angiotensin, bradykinin, and fibrinolytic systems on t-PA or PAI-1 levels are dependent on environmental factors in a large population-based sample from the PREVEND study in Groningen, The Netherlands (n = 2,527). We found strong evidence (P t-PA in females and males and on PAI-1 in males. Only suggestive evidence (P t-PA and PAI-1 there was at least one BDKRB2-body size combination that exhibited suggestive (P t-PA and PAI-1 is dependent on the environmental context such as body size and alcohol use. The present study emphasizes the importance of including environmental factors in genetic analyses to fully comprehend the genetic architecture of a specific trait.

  14. 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

  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. Authenticated algorithms for Byzantine agreement

    SciTech Connect

    Dolev, D.; Strong, H.R.

    1983-11-01

    Reaching agreement in a distributed system in the presence of fault processors is a central issue for reliable computer systems. Using an authentication protocol, one can limit the undetected behavior of faulty processors to a simple failure to relay messages to all intended targets. In this paper the authors show that, in spite of such an ability to limit faulty behavior, and no matter what message types or protocols are allowed, reaching (Byzantine) agreement requires at least t+1 phases or rounds of information exchange, where t is an upper bound on the number of faulty processors. They present algorithms for reaching agreement based on authentication that require a total number of messages sent by correctly operating processors that is polynomial in both t and the number of processors, n. The best algorithm uses only t+1 phases and o(nt) messages. 9 references.

  17. 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

  18. 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.

  19. Early Events in Helix Unfolding Under External Forces: A Milestoning Analysis

    PubMed Central

    Kreuzer, Steven M; Elber, Ron; Moon, Tess J

    2012-01-01

    Initial events of helix breakage as a function of load are considered using Molecular Dynamics simulations and Milestoning analysis. A helix length of ~100 amino acids is considered as a model for typical helices found in molecular machines and as a model that minimizes end effects for early events of unfolding. Transitions of individual amino acids (averaged over the helix’s interior residues) are examined and its surrounding hydrogen bonds are considered. Dense kinetic networks are constructed that, with Milestoning analysis, provide the overall kinetics of early breakage events. Network analysis and selection of MaxFlux pathways illustrate that load impacts unfolding mechanisms in addition to time scales. At relatively high (100pN) load levels, the principal intermediate is the 310-helix, while at relatively low (10pN) levels the π-helix is significantly populated, albeit not as an unfolding intermediate. Coarse variables are examined at different levels of resolution; the rate of unfolding illustrates remarkable stability under changes in the coarsening. Consistent prediction of about ~5ns for the time of a single amino-acid unfolding event are obtained. Hydrogen bonds are much faster coarse variables (by about 2 orders of magnitude) compared to backbone torsional transition, which gates unfolding and thereby provides the appropriate coarse variable for the initiation of unfolding. PMID:22471347

  20. 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.

  1. 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)

  2. 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;…

  3. 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.

  4. 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

  5. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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 basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  6. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  7. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  8. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  9. 48 CFR 16.702 - Basic agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Basic agreements. 16.702... AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 16.702 Basic agreements. (a) Description. A basic... attachment the required and applicable clauses agreed upon in the basic agreement. A basic agreement is not...

  10. 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

  11. Characterization of the human spr2 promoter: induction after UV irradiation or TPA treatment and regulation during differentiation of cultured primary keratinocytes.

    PubMed Central

    Gibbs, S; Lohman, F; Teubel, W; van de Putte, P; Backendorf, C

    1990-01-01

    We have isolated genomic clones from several members of the UV and TPA inducible human spr2 gene-family in order to analyse the regulation of these genes at a molecular level. From one of these members, the spr2-1 gene, we have identified and sequenced the regulatory region. By using CAT fusion plasmids and a liposome mediated transfection procedure we show that the isolated promoter region contains all the cis-elements necessary for induced expression after UV irradiation or phorbolester treatment of cultured human keratinocytes. Additionally the spr2-1 promoter is shown to be regulated aswell during the normal process of keratinocyte differentiation. This makes the spr2-1 promoter sequence an ideal tool to study the molecular mechanisms by which environmental agents such as UV radiation and chemical tumor promoters interfere with normal gene expression during cell proliferation and differentiation. Images PMID:2388825

  12. 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

  13. 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...

  14. 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:...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 77 FR 61751 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-11

    ... Agreement. Parties: Crowley Latin America Services, LLC and A.P. Moller-Maersk A/S Filing Party: Wayne R... . Agreement No.: 012155-001. Title: MSC/Zim South America East Coast Vessel Sharing Agreement....

  1. 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.

  2. Measurement Challenges in International Agreements

    NASA Astrophysics Data System (ADS)

    Luke, John

    2006-10-01

    Making measurements in support of international agreements can pose many challenges both from a policy and science point of view. Policy issues may arise because physics measurements made in the area of arms control or disarmament may be deemed too intrusive since they could possibly reveal sensitive information about the material that is being interrogated. Therefore, agreements must include a framework for safeguarding against the potential release of this information. Most of the scientific issues center around the fact that it is desirable to make high quality measurements without any operator interaction. This leads to the development of instrumentation and software that are very stable and robust. Due to different concerns, policy and science priorities may be at odds with one another. Therefore, it is the scientist's challenge - in this field - to keep policy makers informed by conveying what is technically possible and what is not in a manner that is easily understood and also negotiable. In this paper we will discuss some of the technology that has been developed to address some of these challenges in various international and model agreements. We will discuss the principle of informational barrier used in these measurement technologies to safeguard the release of sensitive information. We will also discuss some of the pitfalls that may arise when policy is ill informed about the physical constraints in the making of measurements of nuclear materials.

  3. 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.

  4. 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.

  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. 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 \

  7. 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.

  8. 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.

  9. 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.

  10. Tank waste remediation system milestone report magnetic separation of tank waste: Surrogate system separations report

    SciTech Connect

    Avens, L.R.; Worl, L.A.; Schake, A.R.; Padilla, D.D.; de Aguero, K.J.; Prenger, F.C.; Stewart, W.F.; Hill, D.D.

    1994-01-14

    High-level radioactive waste (HLW) has been stored in large underground storage tanks (UST) at the US Department of Energy`s Hanford Site since 1944. More than 253,000 m{sup 3} of waste have been accumulated in 177 tanks. The waste consists of many different chemicals and are in the form of liquids, slurries, salt cakes and sludges. A magnetic separation effort at Los Alamos National Laboratory is funded through the Tank Waste Remediation System (TWRS) to explore the use of high-gradient magnetic separation (HGMS) for tank waste segregation. The concept is to concentrate into a low volume waste stream, all or most of the magnetic components, which include actinide compounds, most of the fission products and precious metals. As a first step in this process investigations were made on surrogate systems. This milestone report discusses the HGMS results on these systems.

  11. 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

  12. 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.

  13. 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, 2013 CFR

    2013-01-01

    ... Part 2, Subparts B, C, and L. The model milestones include only the most significant events in the..., C and M. The model milestones include only the most significant events in the proceeding, and are... 10 CFR 2.332. B Appendix B to 10 CFR Part 2 Energy NUCLEAR REGULATORY COMMISSION AGENCY RULES...

  14. 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, 2014 CFR

    2014-01-01

    ... Part 2, Subparts B, C, and L. The model milestones include only the most significant events in the..., C and M. The model milestones include only the most significant events in the proceeding, and are... 10 CFR 2.332. B Appendix B to 10 CFR Part 2 Energy NUCLEAR REGULATORY COMMISSION AGENCY RULES...

  15. 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

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 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...

  16. 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

    ... 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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

    ... 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...

  4. 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...

  5. 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...

  6. From kissing to coitus? Sex-of-partner differences in the sexual milestone achievement of young men.

    PubMed

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

    2011-08-01

    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 sex-of-partner preferences as a function of sex-of-partner experiences. Mean ages of milestone achievement were consistent with the extant empirical literature. Men with only female partners were younger at first kiss and first relationship, and older at first intercourse than men with only male partners; they also reported an almost universal sequence of milestone achievement and little change in sex-of-partner preferences. Most men with male partners reported increased preference for male partners over time. Men with partners of both sexes tended to demonstrate patterns consistent with the relevant sex-of-partner group. Findings suggested a common male sexual trajectory and sex-of-partner dependent trajectories.

  7. 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

  8. 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…

  9. 32 CFR 78.7 - Standard agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Standard agreement. 78.7 Section 78.7 National... VOLUNTARY STATE TAX WITHHOLDING FROM RETIRED PAY § 78.7 Standard agreement. Standard Agreement For Voluntary..., hereafter referred to as the “Standard Agreement,” establishes administrative procedures and...

  10. 48 CFR 3416.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Basic agreements. 3416.702... CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Agreements 3416.702 Basic agreements. (a)-(d) (e) Negotiated overhead rates. Basic agreements may include negotiated overhead rates for...

  11. 78 FR 26779 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... reflects the suspension of the agreement, effective May 1, 2013 through April 14, 2015. Agreement No... the fact that the parties have agreed to charter and rationalize vessel space among themselves and...). Agreement No.: 012206. Title: Industria Armamento Meridionale S.P.A./K-Line Space Charter Agreement....

  12. 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...

  13. 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....

  14. 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....

  15. 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....

  16. 5 CFR 2421.20 - Election agreement.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 3 2014-01-01 2014-01-01 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....

  17. 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....

  18. 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...

  19. 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...

  20. 7 CFR 1415.11 - Restoration agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Restoration agreements. 1415.11 Section 1415.11... Restoration agreements. (a) Restoration agreements are only authorized to be used in conjunction with... a restoration agreement is needed. Such a determination is also subject to the availability...

  1. 7 CFR 1415.11 - Restoration agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Restoration agreements. 1415.11 Section 1415.11... Restoration agreements. (a) Restoration agreements are only authorized to be used in conjunction with... a restoration agreement is needed. Such a determination is also subject to the availability...

  2. 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....

  3. 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....

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 77 FR 10743 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-23

    ... . Agreement No.: 011353-036. Title: The Credit Agreement. Parties: Crowley Latin America Services, LLC; Dole..., DC 20006-4007. Synopsis: The amendment deletes Crowley Latin American Services, LLC and a King Ocean entity as a party to the Agreement. Agreement No.: 012155. Title: MSC/Zim South America East Coast...

  11. 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....

  12. 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....

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 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...

  4. 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.

  5. 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

  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, 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...

  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, 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...

  10. 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...

  11. Perceptions of patient provider agreements

    PubMed Central

    Albrecht, Jennifer S.; Khokhar, Bilal; Pradel, Françoise; Campbell, Michelle; Palmer, Jacqueline; Harris, Ilene; Palumbo, Francis

    2016-01-01

    Objectives Use of patient provider agreements (PPAs) is increasing, yet there is limited evidence on the effectiveness of PPAs to prevent prescription opioid misuse and diversion, and few guidelines for providers. We conducted eight focus groups to understand patient and prescriber perceptions of PPAs. Methods We recruited 40 patients who had been asked to sign a PPA and 40 prescribers who had administered at least one PPA. We developed topic guides for the two groups based on prior literature. Focus groups were audio-recorded and transcribed verbatim. Two investigators independently performed the content analysis of the transcripts and reached consensus on recurring themes. Key findings PPA use varied according to physician specialty. General practitioners used PPAs the least but reported increasing pressure from liability insurers to use them. Many patients reported signing a PPA in the emergency room of a hospital. Prescribers and patients reported a lack of understanding among patients concerning the purpose and content of the PPA. Prescribers questioned the legal status of the PPA, while patients believed that the PPA was a legal document intended to protect prescribers. Patients and prescribers valued PPA content items differently, although both groups agreed that signing a PPA would not prevent opioid misuse. Conclusions We identified several themes concerning the administration, content, effectiveness and utility of PPAs that highlight areas of research to improve PPAs. We also describe trends requiring further investigation. Understanding content of importance to patients will facilitate the development of a patient-centred PPA. PMID:27293486

  12. 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

  13. Topical (+)-catechin emulsified gel prevents DMBA/TPA-induced squamous cell carcinoma of the skin by modulating antioxidants and inflammatory biomarkers in BALB/c mice.

    PubMed

    Monga, Jitender; Aggarwal, Vaibhav; Suthar, Sharad Kumar; Monika; Nongalleima, Khumukcham; Sharma, Manu

    2014-12-01

    An emulsified gel of (+)-catechin was developed and evaluated topically against 7,12-dimethylbenz(a)anthracene-induced and 12-O-tetradecanoylphorbol-13-acetate-promoted (DMBA-induced and TPA-promoted) squamous cell carcinoma of the skin in BALB/c mice. The biological evaluation outcome indicated that the (+)-catechin emulsified gel increased the activity of oxidative stress biomarkers glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPx), whereas it decreased the level of malondialdehyde (MDA). The mechanistic study showed that genes implicated in the inflammation and cancer, such as cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-κB), and inducible nitric-oxide synthase (iNOS), were down-regulated by (+)-catechin emulsified gel while inhibiting an inflammatory mediator prostaglandin E2 (PGE2). The (+)-catechin emulsified gel further suppressed the activity of pro-inflammatory cytokines, viz. tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). The in vitro permeation study revealed that release of (+)-catechin from an emulsified gel base reached a steady state after 6 h, while pH of the entire emulsified gel was found to be between 6.2 and 6.5 that falls well within the normal pH range of the skin.

  14. 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

    2014-07-15

    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.

  15. 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

  16. 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...

  17. 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...

  18. 75 FR 61757 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-06

    ....: 012071-001. Title: APL/Hanjin Reciprocal Space Charter Agreement. Parties: American President Lines, Ltd... Agreement. Parties: Eagle Marine Services, Ltd.; Ports of America Outer Harbor Terminal, LLC; Port...

  19. 75 FR 150 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... the members to address issues relating to environmental initiatives and the reduction of air and water pollution. Agreement No.: 012008-004. Title: The 360 Quality Association Agreement. Parties: NYKCool AB...

  20. 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...

  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. 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...

  3. 47 CFR 51.303 - Preexisting agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) INTERCONNECTION... interconnection agreements between an incumbent LEC and a telecommunications carrier, including those negotiated... approval pursuant to section 252(e) of the Act. (b) Interconnection agreements negotiated before February...

  4. 77 FR 71001 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-28

    ..., updates both parties address, and various other changes. Agreement No.: 012187-000. Title: Siem Car Carrier Pacific AS/Hoegh Autoliners, Inc. Space Charter Agreement. Parties: Siem Car Carrier Pacific...

  5. 32 CFR 37.1260 - Cooperative agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Definitions of Terms Used in This Part § 37.1260 Cooperative... the cooperative agreement. The term does not include “cooperative research and development...

  6. 77 FR 1689 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-11

    ... . Agreement No.: 012150. Title: COSCON/POS Space Charter and Sailing Agreement. Parties: COSCO Container Lines... COSCO to charter space to Hainan POS in the trade between U.S. West Coast ports and ports in China...

  7. 75 FR 20849 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-21

    .... Agreement No.: 011075-073. Title: Central America Discussion Agreement. Parties: APL Co. PTE Ltd.; Crowley Latin America Services, LLC.; Dole Ocean Cargo Express; Great White Fleet; King Ocean Services...

  8. Milestones of critical thinking: a developmental model for medicine and nursing.

    PubMed

    Papp, Klara K; Huang, Grace C; Lauzon Clabo, Laurie M; Delva, Dianne; Fischer, Melissa; Konopasek, Lyuba; Schwartzstein, Richard M; Gusic, Maryellen

    2014-05-01

    Critical thinking is essential to a health professional's competence to assess, diagnose, and care for patients. Defined as the ability to apply higher-order cognitive skills (conceptualization, analysis, evaluation) and the disposition to be deliberate about thinking (being open-minded or intellectually honest) that lead to action that is logical and appropriate, critical thinking represents a "meta-competency" that transcends other knowledge, skills, abilities, and behaviors required in health care professions. Despite its importance, the developmental stages of critical thinking have not been delineated for nurses and physicians. As part of a task force of educators who considered different developmental stage theories, the authors have iteratively refined and proposed milestones in critical thinking. The attributes associated with unreflective, beginning, practicing, advanced, accomplished, and challenged critical thinkers are conceived as independent of an individual's level of training. Depending on circumstances and environmental factors, even the most experienced clinician may demonstrate attributes associated with a challenged thinker. The authors use the illustrative case of a patient with abdominal pain to demonstrate how critical thinking may manifest in learners at different stages of development, analyzing how the learner at each stage applies information obtained in the patient interaction to arrive at a differential diagnosis and plan for evaluation. The authors share important considerations and provide this work as a foundation for the development of effective approaches to teaching and promoting critical thinking and to establishing expectations for learners in this essential meta-competency.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

    PubMed Central

    About, Imad

    2016-01-01

    Dental Mesenchymal Stem Cells (MSCs), including Dental Pulp Stem Cells (DPSCs), Stem Cells from Human Exfoliated Deciduous teeth (SHED), and Stem Cells From Apical Papilla (SCAP), have been extensively studied using highly sophisticated in vitro and in vivo systems, yielding substantially improved understanding of their intriguing biological properties. Their capacity to reconstitute various dental and nondental tissues and the inherent angiogenic, neurogenic, and immunomodulatory properties of their secretome have been a subject of meticulous and costly research by various groups over the past decade. Key milestone achievements have exemplified their clinical utility in Regenerative Dentistry, as surrogate therapeutic modules for conventional biomaterial-based approaches, offering regeneration of damaged oral tissues instead of simply “filling the gaps.” Thus, the essential next step to validate these immense advances is the implementation of well-designed clinical trials paving the way for exploiting these fascinating research achievements for patient well-being: the ultimate aim of this ground breaking technology. This review paper presents a concise overview of the major biological properties of the human dental MSCs, critical for the translational pathway “from bench to clinic.”

  17. Legal issues critical in software license agreements.

    PubMed

    Manfredi, M J; Peterson, D M

    1989-05-01

    The complex legal aspects of software license agreements are addressed in this final part of a three-part series. A healthcare organization that has selected a software vendor and has reviewed the central provisions of a licensing agreement must then take a close look at the other provisions of the agreement. These include numerous legal provisions, regulatory requirements, and ancillary agreements related to maintenance and access to the software.

  18. 34 CFR 84.620 - Cooperative agreement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Cooperative agreement. 84.620 Section 84.620 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.620 Cooperative agreement. Cooperative agreement means an award...

  19. 23 CFR 633.206 - Project agreements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 23 Highways 1 2013-04-01 2013-04-01 false Project agreements. 633.206 Section 633.206 Highways... CONTRACT PROVISIONS Federal-Aid Contracts (Appalachian Contracts) § 633.206 Project agreements. (a) Project agreements executed for projects under the Appalachian program shall contain the following paragraphs:...

  20. 23 CFR 633.206 - Project agreements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 23 Highways 1 2014-04-01 2014-04-01 false Project agreements. 633.206 Section 633.206 Highways... CONTRACT PROVISIONS Federal-Aid Contracts (Appalachian Contracts) § 633.206 Project agreements. (a) Project agreements executed for projects under the Appalachian program shall contain the following paragraphs:...

  1. 23 CFR 633.206 - Project agreements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 23 Highways 1 2012-04-01 2012-04-01 false Project agreements. 633.206 Section 633.206 Highways... CONTRACT PROVISIONS Federal-Aid Contracts (Appalachian Contracts) § 633.206 Project agreements. (a) Project agreements executed for projects under the Appalachian program shall contain the following paragraphs:...

  2. 23 CFR 633.206 - Project agreements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 23 Highways 1 2011-04-01 2011-04-01 false Project agreements. 633.206 Section 633.206 Highways... CONTRACT PROVISIONS Federal-Aid Contracts (Appalachian Contracts) § 633.206 Project agreements. (a) Project agreements executed for projects under the Appalachian program shall contain the following paragraphs:...

  3. 19 CFR 118.3 - Written agreement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Written agreement. 118.3 Section 118.3 Customs... CENTRALIZED EXAMINATION STATIONS General Provisions § 118.3 Written agreement. The applicant tentatively selected to operate a CES must sign a written agreement with CBP before commencing operations. Failure...

  4. 5 CFR 370.105 - Written agreements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The...

  5. 19 CFR 118.3 - Written agreement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Written agreement. 118.3 Section 118.3 Customs... CENTRALIZED EXAMINATION STATIONS General Provisions § 118.3 Written agreement. The applicant tentatively selected to operate a CES must sign a written agreement with CBP before commencing operations. Failure...

  6. 5 CFR 370.105 - Written agreements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The...

  7. 19 CFR 118.3 - Written agreement.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Written agreement. 118.3 Section 118.3 Customs... CENTRALIZED EXAMINATION STATIONS General Provisions § 118.3 Written agreement. The applicant tentatively selected to operate a CES must sign a written agreement with CBP before commencing operations. Failure...

  8. 19 CFR 118.3 - Written agreement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Written agreement. 118.3 Section 118.3 Customs... CENTRALIZED EXAMINATION STATIONS General Provisions § 118.3 Written agreement. The applicant tentatively selected to operate a CES must sign a written agreement with CBP before commencing operations. Failure...

  9. 5 CFR 370.105 - Written agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The...

  10. 5 CFR 370.105 - Written agreements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The...

  11. 78 FR 75345 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ...@fmc.gov . Agreement No.; 011314-002. Title: CSAV/Trans Global Cooperative Working Agreement. Parties: Compania Sud Americana de Vapores S.A. and Trans Global Shipping NV. Filing Party: Walter H. Lion Esq.; Mc... party Swordfish Shipping Inc. to Trans Global Shipping NV and changes the agreement's termination...

  12. 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...

  13. 48 CFR 519.7010 - Agreement contents.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 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...

  14. 48 CFR 1819.7209 - Credit agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Credit agreements. 1819... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7209 Credit agreements. (a) The credit permits the mentor to include the cost it expends on a mentor-protégé agreement...

  15. 48 CFR 1819.7209 - Credit agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Credit agreements. 1819... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7209 Credit agreements. (a) The credit permits the mentor to include the cost it expends on a mentor-protégé agreement...

  16. 49 CFR 1325.2 - Credit agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 9 2011-10-01 2011-10-01 false Credit agreements. 1325.2 Section 1325.2... OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXTENSION OF CREDIT TO CANDIDATES FOR FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.2 Credit agreements. (a) All agreements to extend credit...

  17. 49 CFR 1325.2 - Credit agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Credit agreements. 1325.2 Section 1325.2... OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXTENSION OF CREDIT TO CANDIDATES FOR FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.2 Credit agreements. (a) All agreements to extend credit...

  18. 49 CFR 1325.2 - Credit agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 9 2012-10-01 2012-10-01 false Credit agreements. 1325.2 Section 1325.2... OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXTENSION OF CREDIT TO CANDIDATES FOR FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.2 Credit agreements. (a) All agreements to extend credit...

  19. 49 CFR 1325.2 - Credit agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 9 2013-10-01 2013-10-01 false Credit agreements. 1325.2 Section 1325.2... OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXTENSION OF CREDIT TO CANDIDATES FOR FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.2 Credit agreements. (a) All agreements to extend credit...

  20. 48 CFR 1819.7209 - Credit agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Credit agreements. 1819... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7209 Credit agreements. (a) The credit permits the mentor to include the cost it expends on a mentor-protégé agreement...

  1. 48 CFR 1819.7209 - Credit agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Credit agreements. 1819... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7209 Credit agreements. (a) The credit permits the mentor to include the cost it expends on a mentor-protégé agreement...

  2. 49 CFR 1325.2 - Credit agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 9 2014-10-01 2014-10-01 false Credit agreements. 1325.2 Section 1325.2... OF TRANSPORTATION (CONTINUED) CARRIER RATES AND SERVICE TERMS EXTENSION OF CREDIT TO CANDIDATES FOR FEDERAL OFFICE OR THEIR REPRESENTATIVES § 1325.2 Credit agreements. (a) All agreements to extend credit...

  3. 48 CFR 1819.7209 - Credit agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Credit agreements. 1819... ADMINISTRATION SOCIOECONOMIC PROGRAMS SMALL BUSINESS PROGRAMS NASA Mentor-Protégé Program 1819.7209 Credit agreements. (a) The credit permits the mentor to include the cost it expends on a mentor-protégé agreement...

  4. 77 FR 42310 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... . Agreement No.: 012119-001. Title: Maersk Line/CMA CGM TP5 Space Charter Agreement. Parties: A.P. Moller... Glovis Co., Ltd. Space Charter Agreement. Parties: Siem Car Carrier Pacific AS; Hyundai Glovis Co., Ltd..., Japan, Philippines, Singapore, and China), and authorizes the mutual chartering of space between...

  5. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 4 2012-01-01 2012-01-01 false Agreements. 247.4 Section 247.4 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are necessary for agencies to administer...

  6. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 4 2011-01-01 2011-01-01 false Agreements. 247.4 Section 247.4 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are necessary for agencies to administer...

  7. 7 CFR 247.4 - Agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 4 2010-01-01 2010-01-01 false Agreements. 247.4 Section 247.4 Agriculture Regulations of the Department of Agriculture (Continued) FOOD AND NUTRITION SERVICE, DEPARTMENT OF AGRICULTURE CHILD NUTRITION PROGRAMS COMMODITY SUPPLEMENTAL FOOD PROGRAM § 247.4 Agreements. (a) What agreements are necessary for agencies to administer...

  8. 46 CFR Sec. 3 - Standby agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 8 2014-10-01 2014-10-01 false Standby agreements. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION B-CONTROL AND UTILIZATION OF PORTS FEDERAL PORT CONTROLLERS Sec. 3 Standby agreements. The Director, NSA, may negotiate the standard form of service agreement, specified...

  9. 46 CFR Sec. 3 - Standby agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 8 2013-10-01 2013-10-01 false Standby agreements. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION B-CONTROL AND UTILIZATION OF PORTS FEDERAL PORT CONTROLLERS Sec. 3 Standby agreements. The Director, NSA, may negotiate the standard form of service agreement, specified...

  10. 46 CFR Sec. 3 - Standby agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 8 2011-10-01 2011-10-01 false Standby agreements. Sec. 3 Section 3 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION B-CONTROL AND UTILIZATION OF PORTS FEDERAL PORT CONTROLLERS Sec. 3 Standby agreements. The Director, NSA, may negotiate the standard form of service agreement, specified...

  11. 76 FR 38177 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-29

    ... space in the trade from Vietnam to U.S. West Coast. Agreement No.: 012132. Title: Crowley/King Ocean Charter and Sailing Agreement. Parties: Crowley Latin America Services, LLC and King Ocean Services..., DC 20006. Synopsis: The agreement authorizes King Ocean to charter space to Crowley in the...

  12. 77 FR 28880 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-16

    ... geographic scope of the agreement. Agreement No.: 012170. Title: Crowley/SC Line Space Charter and Sailing Agreement. Parties: Crowley Latin America Services, LLC and SC Line. Filing Party: Wayne R. Rohde, Esquire... authorizes SC Line to charter space to Crowley in the trade between the U.S. Atlantic Coast and ports...

  13. 77 FR 5013 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-01

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  14. 77 FR 45610 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreement Filed The Commission hereby gives notice of the filing of the following agreement under the Shipping Act of 1984. Interested parties may submit comments on the agreement to the...

  15. 78 FR 25443 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-01

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  16. 78 FR 23251 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-18

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  17. 76 FR 51033 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreement Filed The Commission hereby gives notice of the filing of the following agreement under the Shipping Act of 1984. Interested parties may submit comments on the agreement to the...

  18. 76 FR 52954 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreement Filed The Commission hereby gives notice of the filing of the following agreement under the Shipping Act of 1984. Interested parties may submit comments on the agreement to the...

  19. 77 FR 40881 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-11

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  20. 76 FR 31962 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-02

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  1. 76 FR 34992 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  2. 77 FR 50688 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-22

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreement Filed The Commission hereby gives notice of the filing of the following agreement under the Shipping Act of 1984. Interested parties may submit comments on the agreement to the...

  3. 77 FR 54911 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  4. 78 FR 30302 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  5. 76 FR 81933 - Notice of Agreements Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreements Filed The Commission hereby gives notice of the filing of the following agreements under the Shipping Act of 1984. Interested parties may submit comments on the agreements to...

  6. 46 CFR 535.404 - Agreement provisions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Agreement provisions. 535.404 Section 535.404 Shipping 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 Filing of Agreements §...

  7. 48 CFR 416.702 - Basic agreements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Basic agreements. 416.702... CONTRACT TYPES TYPES OF CONTRACTS Agreements 416.702 Basic agreements. Promptly after execution by the Government, the HCA shall furnish to the Senior Procurement Executive a copy of each basic...

  8. 48 CFR 416.702 - Basic agreements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Basic agreements. 416.702... CONTRACT TYPES TYPES OF CONTRACTS Agreements 416.702 Basic agreements. Promptly after execution by the Government, the HCA shall furnish to the Senior Procurement Executive a copy of each basic...

  9. 48 CFR 416.702 - Basic agreements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Basic agreements. 416.702... CONTRACT TYPES TYPES OF CONTRACTS Agreements 416.702 Basic agreements. Promptly after execution by the Government, the HCA shall furnish to the Senior Procurement Executive a copy of each basic...

  10. 48 CFR 416.702 - Basic agreements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Basic agreements. 416.702... CONTRACT TYPES TYPES OF CONTRACTS Agreements 416.702 Basic agreements. Promptly after execution by the Government, the HCA shall furnish to the Senior Procurement Executive a copy of each basic...

  11. 48 CFR 416.702 - Basic agreements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Basic agreements. 416.702... CONTRACT TYPES TYPES OF CONTRACTS Agreements 416.702 Basic agreements. Promptly after execution by the Government, the HCA shall furnish to the Senior Procurement Executive a copy of each basic...

  12. 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...

  13. The Pros and Cons of Petroleum Agreements.

    ERIC Educational Resources Information Center

    Lipton, Charles J.

    1980-01-01

    A mineral agreements expert discusses the options open to tribes, from the most standard lease form to arrangements as yet untried by Indian Nations. Discussion covers 18 basic provisions for inclusion in agreements, tax considerations, and basic forms of petroleum agreements (leases, joint ventures, production sharing, and service contracts).…

  14. 5 CFR 370.105 - Written agreements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Written agreements. 370.105 Section 370... TECHNOLOGY EXCHANGE PROGRAM § 370.105 Written agreements. Before the detail begins, the agency and private sector organization must enter into a written agreement with the individual(s) detailed. The...

  15. 19 CFR 118.3 - Written agreement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Written agreement. 118.3 Section 118.3 Customs... CENTRALIZED EXAMINATION STATIONS General Provisions § 118.3 Written agreement. The applicant tentatively selected to operate a CES must sign a written agreement with Customs before commencing operations....

  16. 78 FR 35649 - Negotiated Service Agreement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-13

    ... Commission is noticing a recent Postal Service filing concerning an amendment to the 2013 Singapore Post... inbound market dominant services with Singapore Post Limited (2013 Agreement).\\1\\ The 2013 Agreement... Foreign Postal Operators 1 Negotiated Service Agreement (with Singapore Post Limited), June 4,...

  17. 29 CFR 102.62 - Election agreements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 2 2012-07-01 2012-07-01 false Election agreements. 102.62 Section 102.62 Labor... Act § 102.62 Election agreements. (a) Consent election agreements with final regional director determinations of post-election disputes. Where a petition has been duly filed, the employer and any...

  18. 29 CFR 102.62 - Election agreements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 2 2013-07-01 2013-07-01 false Election agreements. 102.62 Section 102.62 Labor... Act § 102.62 Election agreements. (a) Consent election agreements with final regional director determinations of post-election disputes. Where a petition has been duly filed, the employer and any...

  19. 10 CFR 607.620 - Cooperative agreement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Cooperative agreement. 607.620 Section 607.620 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.620 Cooperative agreement. Cooperative agreement means an award...

  20. 75 FR 3466 - Notice of Agreement Filed

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-21

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Agreement Filed The Commission hereby gives notice of the filing of the following agreement under the Shipping Act of 1984. Interested parties may submit comments on the agreement to the Secretary, Federal Maritime Commission,...