WorldWideScience

Sample records for stable drug-free operationally

  1. A thermodynamic study for the optimization of stable operation of free piston Stirling engines

    Energy Technology Data Exchange (ETDEWEB)

    Rogdakis, E.D.; Bormpilas, N.A.; Koniakos, I.K. [National Technical Univerisity, Athens (Greece). Dept. of Mechanical Engineering

    2004-03-01

    One of the most novel applications of the Stirling cycle is in the free piston configuration that was initially designed by W. Beale. In free piston Stirling engines (FPSEs), there are no mechanical linkages coupling the pistons or displacers, the motions of the reciprocating components follow the working gas pressure variations. Fillipo de Monte and G. Benvenuto have recently proposed a linearization technique of the dynamic balance equations. The aim of this paper is to predict the thermodynamic conditions for stable operation of FPSEs and their modeling. The equations of the angular velocity are solved analytically in terms of the working gas mass and the displacer-piston phase angle of the machine. Using the criterion of stable engine cyclic steady operation, a mathematically rigorous form is obtained for the main parameters of the engine. Furthermore, for simplicity reasons, thermodynamic magnitudes are obtained using the Schmidt analysis (isothermal model). (author)

  2. A thermodynamic study for the optimization of stable operation of free piston Stirling engines

    International Nuclear Information System (INIS)

    Rogdakis, E.D.; Bormpilas, N.A.; Koniakos, I.K.

    2004-01-01

    One of the most novel applications of the Stirling cycle is in the free piston configuration that was initially designed by W. Beale. In free piston Stirling engines (FPSEs), there are no mechanical linkages coupling the pistons or displacers, the motions of the reciprocating components follow the working gas pressure variations. Fillipo de Monte and G. Benvenuto have recently proposed a linearization technique of the dynamic balance equations. The aim of this paper is to predict the thermodynamic conditions for stable operation of FPSEs and their modeling. The equations of the angular velocity are solved analytically in terms of the working gas mass and the displacer-piston phase angle of the machine. Using the criterion of stable engine cyclic steady operation, a mathematically rigorous form is obtained for the main parameters of the engine. Furthermore, for simplicity reasons, thermodynamic magnitudes are obtained using the Schmidt analysis (isothermal model)

  3. Engineering more stable, selectable marker-free autoluminescent mycobacteria by one step.

    Science.gov (United States)

    Yang, Feng; Njire, Moses M; Liu, Jia; Wu, Tian; Wang, Bangxing; Liu, Tianzhou; Cao, Yuanyuan; Liu, Zhiyong; Wan, Junting; Tu, Zhengchao; Tan, Yaoju; Tan, Shouyong; Zhang, Tianyu

    2015-01-01

    In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications.

  4. Engineering more stable, selectable marker-free autoluminescent mycobacteria by one step.

    Directory of Open Access Journals (Sweden)

    Feng Yang

    Full Text Available In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications.

  5. Organized polysaccharide fibers as stable drug carriers

    Science.gov (United States)

    Janaswamy, Srinivas; Gill, Kristin L.; Campanella, Osvaldo H.; Pinal, Rodolfo

    2013-01-01

    Many challenges arise during the development of new drug carrier systems, and paramount among them are safety, solubility and controlled release requirements. Although synthetic polymers are effective, the possibility of side effects imposes restrictions on their acceptable use and dose limits. Thus, a new drug carrier system that is safe to handle and free from side effects is very much in need and food grade polysaccharides stand tall as worthy alternatives. Herein, we demonstrate for the first time the feasibility of sodium iota-carrageenan fibers and their distinctive water pockets to embed and release a wide variety of drug molecules. Structural analysis has revealed the existence of crystalline network in the fibers even after encapsulating the drug molecules, and iota-carrageenan maintains its characteristic and reproducible double helical structure suggesting that the composites thus produced are reminiscent of cocrystals. The melting properties of iota-carrageenan:drug complexes are distinctly different from those of either drug or iota-carrageenan fiber. The encapsulated drugs are released in a sustained manner from the fiber matrix. Overall, our research provides an elegant opportunity for developing effective drug carriers with stable network toward enhancing and/or controlling bioavailability and extending shelf-life of drug molecules using GRAS excipients, food polysaccharides, that are inexpensive and non–toxic. PMID:23544530

  6. Research on the intermediate process of a free-piston linear generator from cold start-up to stable operation: Numerical model and experimental results

    International Nuclear Information System (INIS)

    Feng, Huihua; Guo, Chendong; Jia, Boru; Zuo, Zhengxing; Guo, Yuyao; Roskilly, Tony

    2016-01-01

    Highlights: • The intermediate process of free-piston linear generator is investigated for the first time. • “Gradually switching strategy” is the best strategy in the intermediate process. • Switching at the top dead center position timing has the least influences on free-piston linear generator. • After the intermediate process, the operation parameters value is smaller than those before the intermediate process. - Abstract: The free-piston linear generator (FPLG) has more merits than the traditional reciprocating engines (TRE), and has been under extensive investigation. Researchers mainly investigated on the starting process and the stable generating process of FPLG, while there has not been any report on the intermediate process from the engine cold start-up to stable operation process. Therefore, this paper investigated the intermediate process of the FPLG in terms of switching strategy and switching position based on simulation results and test results. Results showed that when the motor force of the linear electric machine (LEM) declined gradually from 100% to 0% with an interval of 50%, and then to a resistance force in the opposite direction of piston velocity (generator mode), the operation parameters of the FPLG showed minimal changes. Meanwhile, the engine operated more smoothly when the LEM switched its working mode from a motor to a generator at the piston dead center, compared with that at the middle stroke or a random switching time. More importantly, after the intermediate process, the operation parameters of FPLG were smaller than that before the intermediate process. As a result, a gradual motor/generator switching strategy was recommended and the LEM was suggested to switch its working mode when the piston arrived its dead center in order to achieve smooth engine operation.

  7. 21 CFR 1405.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Drug-free workplace. 1405.635 Section 1405.635 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.635 Drug-free workplace. Drug-free workplace means a...

  8. 20 CFR 439.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Drug-free workplace. 439.635 Section 439.635 Employees' Benefits SOCIAL SECURITY ADMINISTRATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 439.635 Drug-free workplace. Drug-free workplace means a site for the...

  9. 22 CFR 1509.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Drug-free workplace. 1509.635 Section 1509.635 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1509.635 Drug-free workplace. Drug-free workplace means a site for the...

  10. 28 CFR 83.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Drug-free workplace. 83.635 Section 83.635 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) GOVERNMENT-WIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 83.635 Drug-free workplace. Drug-free workplace means a site for...

  11. 34 CFR 84.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Drug-free workplace. 84.635 Section 84.635 Education Office of the Secretary, Department of Education GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 84.635 Drug-free workplace. Drug-free workplace means a site for the...

  12. 22 CFR 133.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Drug-free workplace. 133.635 Section 133.635 Foreign Relations DEPARTMENT OF STATE MISCELLANEOUS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 133.635 Drug-free workplace. Drug-free workplace means a site for the...

  13. 45 CFR 1173.635 - Drug-free workplace.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Drug-free workplace. 1173.635 Section 1173.635... HUMANITIES NATIONAL ENDOWMENT FOR THE HUMANITIES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1173.635 Drug-free workplace. Drug-free workplace means a site for the...

  14. 49 CFR 32.635 - Drug-free workplace.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Drug-free workplace. 32.635 Section 32.635 Transportation Office of the Secretary of Transportation GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 32.635 Drug-free workplace. Drug-free workplace means a site for the...

  15. 10 CFR 607.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Drug-free workplace. 607.635 Section 607.635 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 607.635 Drug-free workplace. Drug-free workplace means a site for the...

  16. 22 CFR 210.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Drug-free workplace. 210.635 Section 210.635 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 210.635 Drug-free workplace. Drug-free workplace means a site for the...

  17. 36 CFR 1212.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Drug-free workplace. 1212.635... RULES GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1212.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection...

  18. 32 CFR 26.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Drug-free workplace. 26.635 Section 26.635... REGULATIONS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 26.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection...

  19. 22 CFR 1008.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Drug-free workplace. 1008.635 Section 1008.635 Foreign Relations INTER-AMERICAN FOUNDATION GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1008.635 Drug-free workplace. Drug-free workplace means a site for the performance...

  20. 7 CFR 3021.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Drug-free workplace. 3021.635 Section 3021.635..., DEPARTMENT OF AGRICULTURE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 3021.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done...

  1. 45 CFR 1155.635 - Drug-free workplace.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Drug-free workplace. 1155.635 Section 1155.635... HUMANITIES NATIONAL ENDOWMENT FOR THE ARTS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1155.635 Drug-free workplace. Drug-free workplace means a site for the performance...

  2. 45 CFR 630.635 - Drug-free workplace.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Drug-free workplace. 630.635 Section 630.635... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 630.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific...

  3. 2 CFR 182.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Drug-free workplace. 182.635 Section 182.635... Reserved GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 182.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection...

  4. 38 CFR 48.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Drug-free workplace. 48...) GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 48.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific...

  5. 13 CFR 147.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Drug-free workplace. 147.635... FOR DRUG-FREE WORKPLACE (NONPROCUREMENT) Definitions § 147.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific award at which...

  6. 40 CFR 36.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Drug-free workplace. 36.635 Section 36... GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 36.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific...

  7. 43 CFR 43.635 - Drug-free workplace.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Drug-free workplace. 43.635 Section 43.635 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 43.635 Drug-free workplace. Drug-free workplace means a site...

  8. 24 CFR 21.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Drug-free workplace. 21.635 Section... Development GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (GRANTS) Definitions § 21.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific...

  9. 22 CFR 312.635 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Drug-free workplace. 312.635 Section 312.635 Foreign Relations PEACE CORPS GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 312.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done...

  10. Drug-Free School Zones: Taking Charge.

    Science.gov (United States)

    Thomas, Carol F.

    Information for planning and implementing drug-free school zones within a broader school-community prevention and intervention program is provided in this guidebook. The first section provides background information on drug-free school zone legislation and common elements of drug-free school zones. The risk and protective factors for alcohol and…

  11. 29 CFR 1472.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Drug-free workplace. 1472.635 Section 1472.635 Labor... REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1472.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific award at...

  12. 14 CFR 1260.38 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Drug-free workplace. 1260.38 Section 1260... AGREEMENTS General Provisions § 1260.38 Drug-free workplace. Drug-Free Workplace October 2000 (a) Definitions... use of any controlled substance. Drug-free workplace means the site(s) for the performance of work...

  13. 15 CFR 29.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Drug-free workplace. 29.635 Section 29... DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 29.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific award at which...

  14. 29 CFR 94.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 1 2010-07-01 2010-07-01 true Drug-free workplace. 94.635 Section 94.635 Labor Office of the Secretary of Labor GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 94.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in...

  15. 14 CFR 1267.635 - Drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Drug-free workplace. 1267.635 Section 1267... FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1267.635 Drug-free workplace. Drug-free workplace means a site for the performance of work done in connection with a specific award at which...

  16. 48 CFR 223.570 - Drug-free work force.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Drug-free work force. 223.570 Section 223.570 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... TECHNOLOGIES, OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 223.570 Drug-free work force. ...

  17. Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

    DEFF Research Database (Denmark)

    Tran, Thuy; Chakraborty, Anjan; Xi, Xi

    2018-01-01

    The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) wer...

  18. 7 CFR 1710.127 - Drug free workplace.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Drug free workplace. 1710.127 Section 1710.127... and Basic Policies § 1710.127 Drug free workplace. Borrowers are required to comply with the Drug Free Workplace Act of 1988 (Pub. L. 100-690, title V, subtitle D) and the Act's implementing regulations (7 CFR...

  19. 48 CFR 1823.570 - Drug- and alcohol-free workforce.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Drug- and alcohol-free..., OCCUPATIONAL SAFETY, AND DRUG-FREE WORKPLACE Drug-Free Workplace 1823.570 Drug- and alcohol-free workforce. This section sets sets forth NASA requirements for mandatory drug and alcohol testing of certain...

  20. 29 CFR 1472.220 - By when must I publish my drug-free workplace statement and establish my drug-free awareness...

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false By when must I publish my drug-free workplace statement and establish my drug-free awareness program? 1472.220 Section 1472.220 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements...

  1. 43 CFR 43.220 - By when must I publish my drug-free workplace statement and establish my drug-free awareness...

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false By when must I publish my drug-free workplace statement and establish my drug-free awareness program? 43.220 Section 43.220 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients...

  2. Development of stable marker-free nuclear transformation strategy ...

    African Journals Online (AJOL)

    Development of stable marker-free nuclear transformation strategy in the green microalga Chlorella vulgaris. ... into Chlorella by electroporation has very low stability and it is hard to screen the transformants without antibiotic marker genes.

  3. NRC drug-free workplace plan. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    On September 15, 1986, President Reagan signed Executive Order 12564, establishing the goal of a Drug-Free Federal Workplace. The Order made it a condition of employment that all Federal employees refrain from using illegal drugs on or off duty. On July 11, 1987, Congress passed legislation affecting implementation of the Executive Order under Section 503 of the Supplemental Appropriations Act of 1987, Public Law 100-71 (the Act). The Nuclear Regulatory Commission first issued the NRC Drug Testing Plan to set forth objectives, policies, procedures, and implementation guidelines to achieve a drug-free Federal workplace, consistent with the Executive Order and Section 503 of the Act. Revision 1, titled, ``NRC Drug-Free Workplace Plan,`` supersedes the previous version and its supplements and incorporates changes to reflect current guidance from the Department of Justice, the Department of Health and Human Services, as well as other guidance.

  4. NRC drug-free workplace plan. Revision 1

    International Nuclear Information System (INIS)

    1997-11-01

    On September 15, 1986, President Reagan signed Executive Order 12564, establishing the goal of a Drug-Free Federal Workplace. The Order made it a condition of employment that all Federal employees refrain from using illegal drugs on or off duty. On July 11, 1987, Congress passed legislation affecting implementation of the Executive Order under Section 503 of the Supplemental Appropriations Act of 1987, Public Law 100-71 (the Act). The Nuclear Regulatory Commission first issued the NRC Drug Testing Plan to set forth objectives, policies, procedures, and implementation guidelines to achieve a drug-free Federal workplace, consistent with the Executive Order and Section 503 of the Act. Revision 1, titled, ''NRC Drug-Free Workplace Plan,'' supersedes the previous version and its supplements and incorporates changes to reflect current guidance from the Department of Justice, the Department of Health and Human Services, as well as other guidance

  5. A Practical Cryogen-Free CO2 Purification and Freezing Technique for Stable Isotope Analysis.

    Science.gov (United States)

    Sakai, Saburo; Matsuda, Shinichi

    2017-04-18

    Since isotopic analysis by mass spectrometry began in the early 1900s, sample gas for light-element isotopic measurements has been purified by the use of cryogens and vacuum-line systems. However, this conventional purification technique can achieve only certain temperatures that depend on the cryogens and can be sustained only as long as there is a continuous cryogen supply. Here, we demonstrate a practical cryogen-free CO 2 purification technique using an electrical operated cryocooler for stable isotope analysis. This approach is based on portable free-piston Stirling cooling technology and controls the temperature to an accuracy of 0.1 °C in a range from room temperature to -196 °C (liquid-nitrogen temperature). The lowest temperature can be achieved in as little as 10 min. We successfully purified CO 2 gas generated by carbonates and phosphoric acid reaction and found its sublimation point to be -155.6 °C at 0.1 Torr in the vacuum line. This means that the temperature required for CO 2 trapping is much higher than the liquid-nitrogen temperature. Our portable cooling system offers the ability to be free from the inconvenience of cryogen use for stable isotope analysis. It also offers a new cooling method applicable to a number of fields that use gas measurements.

  6. Application of Stable Isotope in Detection of Veterinary Drug Residues

    International Nuclear Information System (INIS)

    Wang Wei; Liu Zhanfeng; Du Xiaoning

    2010-01-01

    In recent years, there has happened a series of significant food safety events worldwide, which lower down consumers' confidence in food safety, and they are taking increasing care about the sources of their foods. The safety problem of animal-origin foods has become a global topic for discussion. Therefore, it is a pressing task to establish a precise, sensitive and reliable method for analyzing veterinary drug residue. An introduction of the present status regarding veterinary drug residue analysis was made in the paper, and it briefly summarized the limit of detection (LOD) and quantification (LOQ) which could be reached in veterinary drug residue analysis by isotopic internal standard method domestically and abroad. The paper also made a review of the progress in applied research of stable isotope labeled compound in veterinary drug residue analysis of, such as, antibiotic medicines, furans and sulfonamides. The paper elucidated the great importance of the application of stable isotopes in the sane development of China's food safety system. (authors)

  7. 41 CFR 105-74.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Drug-free workplace. 105-74.635 Section 105-74.635 Public Contracts and Property Management Federal Property Management... Administration 74-GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 105-74...

  8. 48 CFR 1852.223-74 - Drug- and alcohol-free workforce.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Drug- and alcohol-free... and Clauses 1852.223-74 Drug- and alcohol-free workforce. As prescribed in 1823.570-2, insert the following clause: Drug- and Alcohol-Free Workforce (MAR 1996) (a) Definitions. As used in this clause the...

  9. 7 CFR 1944.654 - Debarment and suspension-drug-free workplace.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Debarment and suspension-drug-free workplace. 1944.654....654 Debarment and suspension—drug-free workplace. (a) For purposes of this subpart, exhibit A of FmHA.... (b) Grantees must also be made aware of the Drug-free Workplace Act of 1988 requirements found in...

  10. 41 CFR 105-74.220 - By when must I publish my drug-free workplace statement and establish my drug-free awareness...

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false By when must I publish my drug-free workplace statement and establish my drug-free awareness program? 105-74.220 Section 105-74.220 Public Contracts and Property Management Federal Property Management Regulations System...

  11. 14 CFR 1274.927 - Debarment and suspension and Drug-Free Workplace.

    Science.gov (United States)

    2010-01-01

    ... Workplace. 1274.927 Section 1274.927 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... suspension and Drug-Free Workplace. Debarment and Suspension and Drug-Free Workplace April 2007 NASA... Suspension (Nonprocurement) and 14 CFR part 1267, Government-wide requirements for Drug-Free Workplace...

  12. Effective action for composite operators and chiral symmetry breakdown in asymptotically free and non-asymptotically free gauge theories

    International Nuclear Information System (INIS)

    Gusynin, V.P.; Miranskij, V.A.

    1987-01-01

    An essential distinction in the relaization of the PCAC dynamics in asymptotically free and non-asymptotically free (with a non-trivial ultraviolet-stable fixed point) gauge theories is revealed. For the latter theories an analytical expressions for the condensate is obtained in the two-loop approximation and arguments of support of a soft behaviour at small distances of composite operators are given. The problem of factorizing the low-energy region for the Wess-Zumino-Witten action is discussed. Besides, the mass relations for pseudoscalar mesons in arbitrary Θ-sector are obtained in the first order in fermion bare masses and the impossibility for spontaneous P and CP-symmetries breaking in vector-like gauge theories at Θ=0 is shown

  13. Hot Melt Extrusion as Solvent-Free Technique for a Continuous Manufacturing of Drug-Loaded Mesoporous Silica

    DEFF Research Database (Denmark)

    Genina, Natalja; Hadi, Batol; Löbmann, Korbinian

    2018-01-01

    The aim of this study is to explore hot melt extrusion (HME) as a solvent-free drug loading technique for preparation of stable amorphous solid dispersions using mesoporous silica (PSi). Ibuprofen and carvedilol were used as poorly soluble active pharmaceutical ingredients (APIs). Due to the high...... friction of an API:PSi mixture below the loading limit of the API, it was necessary to add the polymer Soluplus(®) (SOL) in order to enable the extrusion process. As a result, the APIs were distributed between the PSi and SOL phase after HME. Due to its higher affinity to PSi, ibuprofen was mainly adsorbed...... into the PSi, whereas carvedilol was mainly found in the SOL phase. Intrinsic dissolution rate was highest for HME formulations, containing PSi, compared to pure crystalline (amorphous) APIs and HME formulations without PSi. HME is a feasible solvent-free drug loading technique for preparation of PSi...

  14. Advancing Drug Discovery through Enhanced Free Energy Calculations.

    Science.gov (United States)

    Abel, Robert; Wang, Lingle; Harder, Edward D; Berne, B J; Friesner, Richard A

    2017-07-18

    A principal goal of drug discovery project is to design molecules that can tightly and selectively bind to the target protein receptor. Accurate prediction of protein-ligand binding free energies is therefore of central importance in computational chemistry and computer aided drug design. Multiple recent improvements in computing power, classical force field accuracy, enhanced sampling methods, and simulation setup have enabled accurate and reliable calculations of protein-ligands binding free energies, and position free energy calculations to play a guiding role in small molecule drug discovery. In this Account, we outline the relevant methodological advances, including the REST2 (Replica Exchange with Solute Temperting) enhanced sampling, the incorporation of REST2 sampling with convential FEP (Free Energy Perturbation) through FEP/REST, the OPLS3 force field, and the advanced simulation setup that constitute our FEP+ approach, followed by the presentation of extensive comparisons with experiment, demonstrating sufficient accuracy in potency prediction (better than 1 kcal/mol) to substantially impact lead optimization campaigns. The limitations of the current FEP+ implementation and best practices in drug discovery applications are also discussed followed by the future methodology development plans to address those limitations. We then report results from a recent drug discovery project, in which several thousand FEP+ calculations were successfully deployed to simultaneously optimize potency, selectivity, and solubility, illustrating the power of the approach to solve challenging drug design problems. The capabilities of free energy calculations to accurately predict potency and selectivity have led to the advance of ongoing drug discovery projects, in challenging situations where alternative approaches would have great difficulties. The ability to effectively carry out projects evaluating tens of thousands, or hundreds of thousands, of proposed drug candidates

  15. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

    International Nuclear Information System (INIS)

    Li Yanan; An Feifei; Zhang Xiaohong; Yang Yinlong; Liu Zhuang; Zhang Xiujuan

    2013-01-01

    A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines. (paper)

  16. 24 CFR 1000.46 - Do drug-free workplace requirements apply?

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Do drug-free workplace requirements apply? 1000.46 Section 1000.46 Housing and Urban Development Regulations Relating to Housing and Urban... URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES General § 1000.46 Do drug-free workplace...

  17. 24 CFR 84.13 - Debarment and suspension; Drug-Free Workplace.

    Science.gov (United States)

    2010-04-01

    ... Workplace. 84.13 Section 84.13 Housing and Urban Development Office of the Secretary, Department of Housing... Debarment and suspension; Drug-Free Workplace. (a) Recipients and subrecipients shall comply with the... and subrecipients shall comply with the requirements of the Drug-Free Workplace Act of 1988 (42 U.S.C...

  18. Linear operator inequalities for strongly stable weakly regular linear systems

    NARCIS (Netherlands)

    Curtain, RF

    2001-01-01

    We consider the question of the existence of solutions to certain linear operator inequalities (Lur'e equations) for strongly stable, weakly regular linear systems with generating operators A, B, C, 0. These operator inequalities are related to the spectral factorization of an associated Popov

  19. Addiction treatment and stable housing among a cohort of injection drug users.

    Directory of Open Access Journals (Sweden)

    Anita Palepu

    Full Text Available Unstable housing and homelessness is prevalent among injection drug users (IDU. We sought to examine whether accessing addiction treatment was associated with attaining stable housing in a prospective cohort of IDU in Vancouver, Canada.We used data collected via the Vancouver Injection Drug User Study (VIDUS between December 2005 and April 2010. Attaining stable housing was defined as two consecutive "stable housing" designations (i.e., living in an apartment or house during the follow-up period. We assessed exposure to addiction treatment in the interview prior to the attainment of stable housing among participants who were homeless or living in single room occupancy (SRO hotels at baseline. Bivariate and multivariate associations between the baseline and time-updated characteristics and attaining stable housing were examined using Cox proportional hazard regression models.Of the 992 IDU eligible for this analysis, 495 (49.9% reported being homeless, 497 (50.1% resided in SRO hotels, and 380 (38.3% were enrolled in addiction treatment at the baseline interview. Only 211 (21.3% attained stable housing during the follow-up period and of this group, 69 (32.7% had addiction treatment exposure prior to achieving stable housing. Addiction treatment was inversely associated with attaining stable housing in a multivariate model (adjusted hazard ratio [AHR]=0.71; 95% CI: 0.52-0.96. Being in a partnered relationship was positively associated with the primary outcome (AHR=1.39; 95% CI: 1.02-1.88. Receipt of income assistance (AHR=0.65; 95% CI: 0.44-0.96, daily crack use (AHR=0.69; 95% CI: 0.51-0.93 and daily heroin use (AHR=0.63; 95% CI: 0.43-0.92 were negatively associated with attaining stable housing.Exposure to addiction treatment in our study was negatively associated with attaining stable housing and may have represented a marker of instability among this sample of IDU. Efforts to stably house this vulnerable group may be occurring in contexts

  20. Stable isotope-resolved metabolomics and applications for drug development

    Science.gov (United States)

    Fan, Teresa W-M.; Lorkiewicz, Pawel; Sellers, Katherine; Moseley, Hunter N.B.; Higashi, Richard M.; Lane, Andrew N.

    2012-01-01

    Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response. In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality. PMID:22212615

  1. The synthesis and spectroscopic study of stable free radicals related to piperidine-n-oxyl, including a stable bi-radical

    International Nuclear Information System (INIS)

    Briere, R.

    1965-07-01

    A new synthesis of di-tert-butyl nitroxide using the reaction between tert-butyl magnesium chloride and nitro-tert-butane is presented in the first section. Synthesis and investigation of stable free piperidine-N-oxyl radicals are described in the second section. All these nitroxides have been characterised by their I. R., U. V. and E. P. R. absorption spectra. The final section contains a description of the synthesis of a stable bi-radical of the nitroxide type by condensation of 2,2, 6, 6-tetramethyl-piperid-4-one-l-oxyl with hydrazine. (author) [fr

  2. Distribution of stable free radicals among amino acids of isolated soy proteins.

    Science.gov (United States)

    Lei, Qingxin; Liebold, Christopher M; Boatright, William L; Shah Jahan, M

    2010-09-01

    Application of deuterium sulfide to powdered isolated soy proteins (ISP) was used to quench stable free radicals and produce a single deuterium label on amino acids where free radicals reside. The deuterium labels rendered increases of isotope ratio for the specific ions of radical-bearing amino acids. Isotope ratio measurements were achieved by gas chromatography/mass spectrometry (GC/MS) analyses after the amino acids were released by acidic hydrolysis and converted to volatile derivatives with propyl chloroformate. The isotope enrichment data showed the stable free radicals were located on Ala, Gly, Leu, Ile, Asx (Asp+Asn), Glx (Glu+Gln), and Trp but not on Val, Pro, Met, Phe, Lys, and His. Due to the low abundance of Ser, Thr, and Cys derivatives and the impossibility to accurately measure their isotope ratios, the radical bearing status for these amino acids remained undetermined even though their derivatives were positively identified from ISP hydrolysates. The relative isotope enrichment for radical-bearing amino acids Ala, Gly, Leu, Ile, Asx (Asp+Asn), Glx (Glu+Gln), and Trp were 8.67%, 2.96%, 2.90%, 3.94%, 6.03%, 3.91%, and 21.48%, respectively. Isotope ratio increase for Tyr was also observed but further investigation revealed such increase was mainly from nonspecific deuterium-hydrogen exchange not free radical quenching. The results obtained from the present study provide important information for a better understanding of the mechanisms of free radical formation and stabilization in "dry" ISP.

  3. A free-air system for long-term stable carbon isotope labeling of adult forest trees

    Science.gov (United States)

    Stable carbon (C) isotopes, in particular employed in labeling experiments, are an ideal tool to broaden our understanding of C dynamics in trees and forest ecosystems. Here, we present a free-air exposure system, named isoFACE, designed for long-term stable C isotope labeling in...

  4. Complying with "Drug-Free Workplace" Laws on College and University Campuses.

    Science.gov (United States)

    White, Lawrence

    Beginning with the original executive order in 1986, drug-free workplace legislation has expanded its boundaries to include workers in private companies and state and local agencies and virtually all U.S. colleges and universities. This monograph reviews the Drug-Free Workplace Act of 1988 and its various implementing regulations from the…

  5. Drug-free workplace programmes: New Zealand perspective.

    Science.gov (United States)

    Nolan, Susan

    2008-01-30

    New Zealand (NZ) companies have been introducing Drug & Alcohol Free Workplace Policies and Programmes, which include testing, since 1992. Most "safety-critical" industry sectors are now embracing drug and alcohol testing as part of comprehensive programmes which also have a strong focus on education and rehabilitation. Prison Inmate testing was also introduced in 1998. Lawful drug testing in NZ should be conducted to the strict medico-legal requirements of the Australian/New Zealand Standard, AS/NZS 4308:2001 "Procedures for the collection, detection and quantitation of drugs of abuse in urine." This paper gives an overview of the NZ experience, highlighting the mix of testing options employed, the industry sector trends, the categories of drugs misused, the influence of significant Employment Court Judgements, proposed changes to the AS/NZS 4308(2006), and current oral fluid research projects.

  6. Highly stable porous silicon-carbon composites as label-free optical biosensors.

    Science.gov (United States)

    Tsang, Chun Kwan; Kelly, Timothy L; Sailor, Michael J; Li, Yang Yang

    2012-12-21

    A stable, label-free optical biosensor based on a porous silicon-carbon (pSi-C) composite is demonstrated. The material is prepared by electrochemical anodization of crystalline Si in an HF-containing electrolyte to generate a porous Si template, followed by infiltration of poly(furfuryl) alcohol (PFA) and subsequent carbonization to generate the pSi-C composite as an optically smooth thin film. The pSi-C sensor is significantly more stable toward aqueous buffer solutions (pH 7.4 or 12) compared to thermally oxidized (in air, 800 °C), hydrosilylated (with undecylenic acid), or hydrocarbonized (with acetylene, 700 °C) porous Si samples prepared and tested under similar conditions. Aqueous stability of the pSi-C sensor is comparable to related optical biosensors based on porous TiO(2) or porous Al(2)O(3). Label-free optical interferometric biosensing with the pSi-C composite is demonstrated by detection of rabbit IgG on a protein-A-modified chip and confirmed with control experiments using chicken IgG (which shows no affinity for protein A). The pSi-C sensor binds significantly more of the protein A capture probe than porous TiO(2) or porous Al(2)O(3), and the sensitivity of the protein-A-modified pSi-C sensor to rabbit IgG is found to be ~2× greater than label-free optical biosensors constructed from these other two materials.

  7. Needle-free and microneedle drug delivery in children: a case for disease-modifying antirheumatic drugs (DMARDs).

    Science.gov (United States)

    Shah, Utpal U; Roberts, Matthew; Orlu Gul, Mine; Tuleu, Catherine; Beresford, Michael W

    2011-09-15

    Parenteral routes of drug administration have poor acceptability and tolerability in children. Advances in transdermal drug delivery provide a potential alternative for improving drug administration in this patient group. Issues with parenteral delivery in children are highlighted and thus illustrate the scope for the application of needle-free and microneedle technologies. This mini-review discusses the opportunities and challenges for providing disease-modifying antirheumatic drugs (DMARDs) currently prescribed to paediatric rheumatology patients using such technologies. The aim is to raise further awareness of the need for age-appropriate formulations and drug delivery systems and stimulate exploration of these options for DMARDs, and in particular, rapidly emerging biologics on the market. The ability of needle-free and microneedle technologies to deliver monoclonal antibodies and fusion proteins still remains largely untested. Such an understanding is crucial for future drug design opportunities. The bioavailability, safety and tolerance of delivering biologics into the viable epidermis also need to be studied. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Does media coverage influence the spread of drug addiction?

    Science.gov (United States)

    Ma, Mingju; Liu, Sanyang; Li, Jun

    2017-09-01

    In this paper, a three dimensional drug model is constructed to investigate the impact of media coverage on the spread and control of drug addiction. The dynamical behavior of the model is studied by using the basic reproduction number R0. The drug-free equilibrium is globally asymptotically stable if R0 drug addiction equilibrium is locally stable if R0 > 1. The results demonstrate that the media effect in human population cannot change the stabilities of equilibria but can affect the number of drug addicts. Sensitivity analyses are performed to seek for effective control measures for drug treatment. Numerical simulations are given to support the theoretical results.

  9. Patient goals after tension free vaginal tape operation

    DEFF Research Database (Denmark)

    Glavind, Karin; Bjørk, Jonna; Kousgaard, Sabrina Just

    INTRODUCTION: This prospective study investigates sexual function in women after a tension-free vaginal tape (TVT) operation and compares short-term and long-term effects. METHODS: Sixty-three women had a TVT operation performed at Aalborg University Hospital, Department of Gynecology and Obstetr......INTRODUCTION: This prospective study investigates sexual function in women after a tension-free vaginal tape (TVT) operation and compares short-term and long-term effects. METHODS: Sixty-three women had a TVT operation performed at Aalborg University Hospital, Department of Gynecology...

  10. Hybrid System Modeling and Full Cycle Operation Analysis of a Two-Stroke Free-Piston Linear Generator

    Directory of Open Access Journals (Sweden)

    Peng Sun

    2017-02-01

    Full Text Available Free-piston linear generators (FPLGs have attractive application prospects for hybrid electric vehicles (HEVs owing to their high-efficiency, low-emissions and multi-fuel flexibility. In order to achieve long-term stable operation, the hybrid system design and full-cycle operation strategy are essential factors that should be considered. A 25 kW FPLG consisting of an internal combustion engine (ICE, a linear electric machine (LEM and a gas spring (GS is designed. To improve the power density and generating efficiency, the LEM is assembled with two modular flat-type double-sided PM LEM units, which sandwich a common moving-magnet plate supported by a middle keel beam and bilateral slide guide rails to enhance the stiffness of the moving plate. For the convenience of operation processes analysis, the coupling hybrid system is modeled mathematically and a full cycle simulation model is established. Top-level systemic control strategies including the starting, stable operating, fault recovering and stopping strategies are analyzed and discussed. The analysis results validate that the system can run stably and robustly with the proposed full cycle operation strategy. The effective electric output power can reach 26.36 kW with an overall system efficiency of 36.32%.

  11. 31 CFR 20.635 - Drug-free workplace.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Drug-free workplace. 20.635 Section 20.635 Money and Finance: Treasury Office of the Secretary of the Treasury GOVERNMENTWIDE... workplace means a site for the performance of work done in connection with a specific award at which...

  12. 18 CFR 1316.7 - Drug-free workplace.

    Science.gov (United States)

    2010-04-01

    ... appropriate agency; (7) Make a good-faith effort to maintain a drug-free workplace through implementation of...)(2)), or take such other action as may be in accordance with law or the contract. (e) In addition to... CONDITIONS AND CERTIFICATIONS FOR INCORPORATION IN CONTRACT DOCUMENTS OR ACTIONS Text of Conditions and...

  13. 75 FR 52857 - National Endowment for the Humanities Implementation of OMB Guidance on Drug-Free Workplace...

    Science.gov (United States)

    2010-08-30

    ... Endowment for the Humanities Implementation of OMB Guidance on Drug-Free Workplace Requirements AGENCY... the Governmentwide common rule on drug-free workplace requirements for financial assistance, currently... Federal regulations on drug-free workplace requirements for financial assistance. These changes constitute...

  14. 13 CFR 147.215 - What must I include in my drug-free awareness program?

    Science.gov (United States)

    2010-01-01

    ..., rehabilitation, and employee assistance programs; and (d) The penalties that you may impose upon them for drug...-free awareness program? 147.215 Section 147.215 Business Credit and Assistance SMALL BUSINESS... establish an ongoing drug-free awareness program to inform employees about— (a) The dangers of drug abuse in...

  15. Reactions of inorganic free radicals with liver protecting drugs

    International Nuclear Information System (INIS)

    Gyoergy, I.; Foeldiak, G.; Blazovics, A.; Feher, J.

    1990-01-01

    Liver protecting drugs, silibinin, a flavonolignane, and the dihydroquinoline derivatives, CH 402 and MTDQ-DA, were shown to inhibit processes in which enzymatically or non-enzymatically generated free radicals were involved. Inorganic free radicals (N 3 , (SCN) 2 - , OH, Trp, CO 2 - , O 2 - ) produced by pulse radiolysis readily react with the compounds, which transform into exceptionally long-lived, unreactive transients. Time evolution of the UV and visible spectra indicate that oxidising radicals form a phenoxyl type radical from silibinin, while OH forms an adduct by attacking, simultaneously, at various sites of the molecule. Superoxide radicals reduce silibinin and oxidise CH 402 and MTDQ-DA. It is concluded that the drugs might exhibit antioxidant behavior in living systems. (author)

  16. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    International Nuclear Information System (INIS)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J.

    2012-01-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 ± 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected‐area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: ► Method for NaBH 4 reduced and BSA capped gold nanoparticle was standardized. ► Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. ► Nanoparticles are extremely stable towards pH modification and electrolyte addition. ► Antibiotic conjugated nanoparticles exhibited enhanced antibacterial activity

  17. 76 FR 76609 - Implementation of Office of Management and Budget Guidance on Drug-Free Workplace Requirements

    Science.gov (United States)

    2011-12-08

    ... Implementation of Office of Management and Budget Guidance on Drug-Free Workplace Requirements AGENCY: Office of... Management and Budget (OMB) guidance implementing the portion of the Drug-Free Workplace Act of 1988 (41 U.S... removing its regulation implementing the Governmentwide common rule on drug-free workplace requirements for...

  18. Sodium deoxycholate-decorated zein nanoparticles for a stable colloidal drug delivery system.

    Science.gov (United States)

    Gagliardi, Agnese; Paolino, Donatella; Iannone, Michelangelo; Palma, Ernesto; Fresta, Massimo; Cosco, Donato

    2018-01-01

    The use of biopolymers is increasing in drug delivery, thanks to the peculiar properties of these compounds such as their biodegradability, availability, and the possibility of modulating their physico-chemical characteristics. In particular, protein-based systems such as albumin are able to interact with many active compounds, modulating their biopharmaceutical properties. Zein is a protein of 20-40 kDa made up of many hydrophobic amino acids, generally regarded as safe (GRAS) and used as a coating material. In this investigation, zein was combined with various surfactants in order to obtain stable nanosystems by means of the nanoprecipitation technique. Specific parameters, eg, temperature, pH value, Turbiscan Stability Index, serum stability, in vitro cytotoxicity and entrapment efficiency of various model compounds were investigated, in order to identify the nanoformulation most useful for a systemic drug delivery application. The use of non-ionic and ionic surfactants such as Tween 80, poloxamer 188, and sodium deoxycholate allowed us to obtain nanoparticles characterized by a mean diameter of 100-200 nm when a protein concentration of 2 mg/mL was used. The surface charge was modulated by means of the protein concentration and the nature of the stabilizer. The most suitable nanoparticle formulation to be proposed as a colloidal drug delivery system was obtained using sodium deoxycholate (1.25% w/v) because it was characterized by a narrow size distribution, a good storage stability after freeze-drying and significant feature of retaining lipophilic and hydrophilic compounds. The sodium deoxycholate-coated zein nanoparticles are stable biocompatible colloidal carriers to be used as useful drug delivery systems.

  19. School and work status, drug-free workplace protections, and prescription drug misuse among Americans ages 15-25.

    Science.gov (United States)

    Miller, Ted; Novak, Scott P; Galvin, Deborah M; Spicer, Rebecca S; Cluff, Laurie; Kasat, Sandeep

    2015-03-01

    We assessed the prevalence and characteristics of prescription drug misuse among youth ages 15-25 to examine differences by student and employment status, and associations with workplace antidrug policies and programs. Multivariate logistic regressions analyzed associations in weighted data on the 20,457 young adults in the combined 2004-2008 National Surveys on Drug Use and Health. Demographic controls included sex, race, community size, and age group. After we accounted for demographic controls, at ages 15-25, students were less likely than nonstudents to misuse prescription drugs. Segmenting student from nonstudent groups, working consistently was associated with a further reduction in misuse for those ages 18-25. When we controlled for demographics and substance use history, both Employee Assistance Program (EAP) services and awareness that one's employer had a drug-free workplace policy were associated with significantly lower misuse of prescription drugs (OR = 0.85 for each program, 95% CI [0.73, 1.00] and [0.72, 1.00]). Associations of workplace antidrug policies and programs with marijuana use and with Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria for alcohol abuse and dependence contrasted sharply with these patterns. All four aspects were significantly associated with lower marijuana use. None was associated with problem drinking. Protective effects of drug-free workplace policy and EAPs persist after other substance use was controlled for. Comparing the effects of workplace programs on illicit drug use and problem drinking versus prescription misuse suggests that those protective associations do not result from selection bias. Thus, drug-free workplace policies and EAPs appear to help protect younger workers against prescription misuse. If workplace substance use disorder programs focused prevention messages and interventions on prescription drug misuse, their impact on misuse might increase.

  20. 75 FR 80287 - Environmental Protection Agency Implementation of OMB Guidance on Drug-Free Workplace Requirements

    Science.gov (United States)

    2010-12-22

    ... of omnibus drug legislation on November 18, 1988. Federal agencies issued an interim final common...; FRL- 9242-2] Environmental Protection Agency Implementation of OMB Guidance on Drug-Free Workplace... Protection Agency is removing its regulation implementing the Governmentwide common rule on drug-free...

  1. Prognostic Value of Plasma Pentraxin-3 Levels in Patients with Stable Coronary Artery Disease after Drug-Eluting Stent Implantation

    Directory of Open Access Journals (Sweden)

    Liu Haibo

    2014-01-01

    Full Text Available Pentraxin-3 (PTX3 is an inflammatory marker thought to be more specific to cardiovascular inflammation than C-reactive protein (CRP. Our aim was to assess the prognostic value of PTX3 in patients with stable coronary artery disease (CAD after drug eluting stent (DES implantation. Plasma PTX3 levels were measured before percutaneous coronary intervention (PCI and at 24 h post-PCI in 596 consecutive patients with stable CAD. Patients were followed up for a median of 3 years (range 1–5 for major adverse cardiovascular events (MACEs. We found that the post-PCI plasma PTX3 levels were significantly higher at 24 h after PCI than pre-PCI, patients with MACEs had higher post-PCI PTX3 levels compared with MACEs-free patients, patients with higher post-PCI PTX3 levels (median > 4.384 ng/mL had a higher risk for MACEs than those with PTX3 < 4.384 ng/mL, and post-PCI PTX3, cTnI, multiple stents, and age but not high-sensitivity CRP (hsCRP were independently associated with the prevalence of MACEs after DES implantation. The present study shows that post-PCI PTX3 may be a more reliable inflammatory predictor of long-term MACEs in patients with stable CAD undergoing DES implantation than CRP. Measurement of post-PCI PTX3 levels could provide a rationale for risk stratification of patients with stable CAD after DES implantation.

  2. Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles.

    Science.gov (United States)

    Dangol, Manita; Yang, Huisuk; Li, Cheng Guo; Lahiji, Shayan Fakhraei; Kim, Suyong; Ma, Yonghao; Jung, Hyungil

    2016-02-10

    Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Drug-Free Schools and Communities Act Compliance at Michigan Community Colleges

    Science.gov (United States)

    Custer, Bradley D.

    2018-01-01

    In 1989, Congress passed the Drug-Free Schools and Communities Act Amendments to address illegal alcohol and drug abuse on college campuses. To receive federal funding, each college must comply by implementing an alcohol and drug prevention program, but the federal government and some colleges have paid little attention to this policy. Recently,…

  4. Free energies of stable and metastable pores in lipid membranes under tension.

    Science.gov (United States)

    den Otter, Wouter K

    2009-11-28

    The free energy profile of pore formation in a lipid membrane, covering the entire range from a density fluctuation in an intact bilayer to a large tension-stabilized pore, has been calculated by molecular dynamics simulations with a coarse-grained lipid model. Several fixed elongations are used to obtain the Helmholtz free energy as a function of pore size for thermodynamically stable, metastable, and unstable pores, and the system-size dependence of these elongations is discussed. A link to the Gibbs free energy at constant tension, commonly known as the Litster model, is established by a Legendre transformation. The change of genus upon pore formation is exploited to estimate the saddle-splay modulus or Gaussian curvature modulus of the membrane leaflets. Details are provided of the simulation approach, which combines the potential of mean constraint force method with a reaction coordinate based on the local lipid density.

  5. 75 FR 39133 - Institute of Museum and Library Services Implementation of OMB Guidance on Drug-Free Workplace...

    Science.gov (United States)

    2010-07-08

    ... of Museum and Library Services Implementation of OMB Guidance on Drug-Free Workplace Requirements... regulation implementing the Governmentwide common rule on drug-free workplace requirements for financial... the CFR all Federal regulations on drug-free workplace requirements for financial assistance. These...

  6. γ radiolysis of thymine in oxygen-free aqueous solution in the presence of electron affinic radiosensitizers: identification of stable products

    International Nuclear Information System (INIS)

    Cadet, J.; Guttin-Lombard, M.; Teoule, R.

    1976-01-01

    Radiosensitizers react with nucleic radicals by addition and by electron transfer reactions. A study has been made of the steady-state γ radiolysis of 1 mM thymine in oxygen-free aqueous solutions containing different classes of radiosensitizing drugs: N-oxyl-free radicals (TAN and TMPN), quinones (menadione and naphthoquinone), nitroheterocyclic compounds (metronidazole and 5-nitro-2-furoic acid) and N-ethylmaleimide. Two classes of thymine degradation products were isolated by thin-layer chromatography and characterized by spectroscopic measurements. The main products, irrespective of radiosensitizers, resulting from oxidation reaction were identified as the cis and trans isomers of 5,6-dihydroxy-5, 6-dihydrothymine, N-pyruvyl-N'-formylurea, 6-hydroxy-5,6-dihydrothymine and 5-hydroxy-5,6-dihydrothymine. In the experimental conditions used only N-oxyls and to a lesser extent NEM reacted with 5-hydroxy-5,6-dihydrothymine-6-yl radical, giving stable covalently-bonded addition products with a high yield. TAN showed a higher binding ability with respect to TMPN, which is in good agreement with the rate-constants previously reported for these bimolecular reactions. (author)

  7. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

  8. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    International Nuclear Information System (INIS)

    Zhou, Lin; Liu, Jihua; Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong; Yu, Boyang; Shen, Jian

    2013-01-01

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A–transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A–transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin

  9. A facile drug delivery system preparation through the interaction between drug and iron ion of transferrin

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Lin [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Liu, Jihua [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Wei, Shaohua; Ge, Xuefeng; Zhou, Jiahong, E-mail: zhoujiahong@njnu.edu.cn [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China); Yu, Boyang, E-mail: boyangyu59@163.com [China Pharmaceutical University, Department of Complex Prescription of TCM (China); Shen, Jian [Nanjing Normal University, Jiangsu Key Laboratory Biofunctional Materials, Key Laboratory of Applied Photochemistry, Analysis and Testing Center, College of Chemistry and Materials Science (China)

    2013-09-15

    Many anticancer drugs have the capability to form stable complex with metal ions. Based on such property, a simple method to combine these drugs with transferrin, through the interaction between drug and Fe ion of transferrin, to improve their anticancer activity, is proposed. To demonstrate this technique, the complex of photosensitive anticancer drug hypocrellin A and transferrin was prepared by such facile method. The results indicated that the complex of hypocrellin A and transferrin can stabilize in aqueous solution. In vitro studies have demonstrated the superior cancer cell uptake ability of hypocrellin A-transferrin complex to the free hypocrellin A. Significant damage to such drug-impregnated tumor cells was observed upon irradiation and the cancer cells killing ability of hypocrellin A-transferrin was stronger than the free hypocrellin A within a certain range of concentrations. The above results demonstrated the validity and potential of our proposed strategy to prepare the drug delivery system of this type of anti-cancer drugs and transferrin.

  10. [The free delivery of drugs during hospital consultations].

    Science.gov (United States)

    Haus, Rachel; Moutel, Grégoire; Montuclard, Luc; François, Irène; Frebault, Marie; Rozenbaum, Luc; Bertrandon, Richard; Hervé, Christian

    2003-09-06

    In France, the access to treatment has become a priority and a right. Hence, the supply of care has been reorganised in order to improve the management of the health scourges for all the patients, whether they can pay for what they need or not. The free delivery of drugs (FDD) is part of the services offered by the public hospitals for the low income patients or those who do not yet benefit from social security coverage. As such, it is inscribed within the context of the right to treatment and is a corner stone to a new mission of the public hospital services and care networks. The polyclinic of the Max Fourestier hospital is one of hospitals in the Paris area that supplies medical and surgical consultations to the population and provides drugs free of charge. From April 1, 1999 to the end of June 2000, all the FDD were studied for all the non-hospitalised outpatients who came to the consultations with a prescription for drugs, which could not be supplied in a pharmacy because of lack of revenues or social security coverage. The diseases encountered in the context of FDD were the same as those of the general population. No specificity was revealed in the prescriptions related to vulnerability. If it were necessary, this would confirm the fact that the management of persons in difficulty should be integrated in the provisions of common rights. The treatments concerned were essential, and for some persons life saving, and justifying the interest of FDD without which the health of these individuals would rapidly decline. Furthermore, this study shows the need for careful management of FDD in order to avoid the anarchical and uncontrolled delivery of several prescriptions, source of deleterious drug interactions and iatrogenia. This is the reason for the recommendation to all the staff delivering free drugs that they systematically ask the patients to meet a referring physician and contact the hospital pharmacist when necessary. The FDD request is an ideal occasion for

  11. High beta, sawtooth-free tokamak operation using energetic trapped particles

    International Nuclear Information System (INIS)

    White, R.B.; Bussac, M.N.; Romanelli, F.

    1988-08-01

    It is shown that a population of high energy trapped particles, such as that produced by ion cyclotron heating in tokamaks, can result in a plasma completely stable to both sawtooth oscillations and the fishbone mode. The stable window of operation increases in size with plasma temperature and with trapped particle energy, and provides a means of obtaining a stable plasma with high current and high beta. 13 refs., 2 figs

  12. Electrospun water-stable zein/ethyl cellulose composite nanofiber and its drug release properties

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Hangyi; Wang, Qingqing; Li, Guohui [Key Laboratory of Eco-textiles, Jiangnan University, Wuxi (China); Qiu, Yuyu [Key Laboratory of Eco-textiles, Jiangnan University, Wuxi (China); Laboratory of Natural Medicine, Wuxi Medical School, Jiangnan University (China); Wei, Qufu, E-mail: qfwei@jiangnan.edu.cn [Key Laboratory of Eco-textiles, Jiangnan University, Wuxi (China)

    2017-05-01

    A simple and cost-effective way to prepare water-stable zein-based nanofibers for potential drug delivery was presented in this article. Corn protein zein was co-electrospun with hydrophobic ethyl cellulose. Indomethacin, as a model drug, was incorporated in situ into the composite nanofibers. Scanning electron microscopy and element mapping revealed the morphologies of drug-loaded nanofibers and drug distribution, respectively. Fourier transform infrared spectra confirmed the physical blending among the components. Differential scanning calorimetry and X-ray diffraction demonstrated the physical state of drug and polymers in the nanofiber matrix. The composite nanofibers showed a sustained diffusion-controlled release according to the results of in vitro dissolution tests. - Highlights: • A simple, non-toxic and cost-effective way to improve water stability of zein nanofibers was proposed. • Electrospun zein/ethyl cellulose nanofibers with improved water stability and mechanical strength were prepared. • Indomethacin was homogeneously distributed in the zein/ethyl cellulose nanofibers with no aggregation or cluster. • The zein/ethyl cellulose nanofibers presented a sustained drug release profile, following Fickican diffusion mechanism.

  13. In Vitro Investigation of the Individual Contributions of Ultrasound-Induced Stable and Inertial Cavitation in Targeted Drug Delivery.

    Science.gov (United States)

    Gourevich, Dana; Volovick, Alexander; Dogadkin, Osnat; Wang, Lijun; Mulvana, Helen; Medan, Yoav; Melzer, Andreas; Cochran, Sandy

    2015-07-01

    Ultrasound-mediated targeted drug delivery is a therapeutic modality under development with the potential to treat cancer. Its ability to produce local hyperthermia and cell poration through cavitation non-invasively makes it a candidate to trigger drug delivery. Hyperthermia offers greater potential for control, particularly with magnetic resonance imaging temperature measurement. However, cavitation may offer reduced treatment times, with real-time measurement of ultrasonic spectra indicating drug dose and treatment success. Here, a clinical magnetic resonance imaging-guided focused ultrasound surgery system was used to study ultrasound-mediated targeted drug delivery in vitro. Drug uptake into breast cancer cells in the vicinity of ultrasound contrast agent was correlated with occurrence and quantity of stable and inertial cavitation, classified according to subharmonic spectra. During stable cavitation, intracellular drug uptake increased by a factor up to 3.2 compared with the control. Reported here are the value of cavitation monitoring with a clinical system and its subsequent employment for dose optimization. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  14. Microfluidic Devices for Drug Delivery Systems and Drug Screening

    Science.gov (United States)

    Kompella, Uday B.; Damiati, Safa A.

    2018-01-01

    Microfluidic devices present unique advantages for the development of efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Compared to bulk methods, by efficiently controlling the geometries of the fabricated chip and the flow rates of multiphase fluids, microfluidic technology enables the generation of highly stable, uniform, monodispersed particles with higher encapsulation efficiency. Since the existing preclinical models are inefficient drug screens for predicting clinical outcomes, microfluidic platforms might offer a more rapid and cost-effective alternative. Compared to 2D cell culture systems and in vivo animal models, microfluidic 3D platforms mimic the in vivo cell systems in a simple, inexpensive manner, which allows high throughput and multiplexed drug screening at the cell, organ, and whole-body levels. In this review, the generation of appropriate drug or gene carriers including different particle types using different configurations of microfluidic devices is highlighted. Additionally, this paper discusses the emergence of fabricated microfluidic cell-free protein synthesis systems for potential use at point of care as well as cell-, organ-, and human-on-a-chip models as smart, sensitive, and reproducible platforms, allowing the investigation of the effects of drugs under conditions imitating the biological system. PMID:29462948

  15. 29 CFR 1472.215 - What must I include in my drug-free awareness program?

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false What must I include in my drug-free awareness program? 1472.215 Section 1472.215 Labor Regulations Relating to Labor (Continued) FEDERAL MEDIATION AND CONCILIATION SERVICE GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 1472.215...

  16. Enhancement of centrifugal compressor stable operation using an internal recirculation channel

    Directory of Open Access Journals (Sweden)

    Růžička M.

    2016-12-01

    Full Text Available Centrifugal compressors with a high pressure ratio are widely used in small aircraft turbine engines and turbocharges. At high rotational speeds they have a narrow stable operating region and the commonly used impellers with back swept blades are not able to ensure requested stability. In order to achieve a wider stable operating region, some other anti-surge measures can be used such as an Internal Recirculation Channel (IRC located in the inlet area of the compressor impeller. This paper analyses the influence of various IRC inlet slot geometries on air flow parameters. The flow velocity profiles downstream of the IRC outlet slot are evaluated and the influence of various channel configurations on compressor performance map is shown. Results from experiments as well as CFD simulations enable us to analyse the airflow in IRC and find out its most suitable geometry.

  17. 43 CFR 43.215 - What must I include in my drug-free awareness program?

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What must I include in my drug-free awareness program? 43.215 Section 43.215 Public Lands: Interior Office of the Secretary of the Interior GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Requirements for Recipients Other Than Individuals § 43.215 What must I...

  18. Possible THz gain in superlattices at a stable operation point

    DEFF Research Database (Denmark)

    Wacker, Andreas; Allen, S. J.; Scott, J. S.

    1997-01-01

    We demonstrate that semiconductor superlattices may provide gain at THz frequencies at an operation point which is stable against fluctuations at lower frequency. While an explicit experimental demonstration for the sample considered could not be achieved, the underlying principle of quantum resp...... response is quite general and may prove successful for differently designed superlattices....

  19. Stable tokamak access to, and operation in, the second stability region

    International Nuclear Information System (INIS)

    Todd, A.M.M.; Phillips, M.; Chance, M.; Manickam, J.; Pomphrey, N.

    1987-01-01

    Tokamak operation in the second region of stability to ballooning modes holds promise for economic fusion reactor operation. A second region of stability is confirmed to exist in circular tokamaks with a nearby conducting shell for εβθ>1. In addition to ballooning instabilities with high toroidal mode number n, the presence of low n internal pressure driven modes in low shear regions can pose serious problems for access to the second region. These modes can be present even when ballooning modes with infinite n are stable. Stable access to the second region for all ideal modes is demonstrated with current profile programming that raises the safety factor on axis above unity. Present calculations for stable access using this technique indicate that a conducting wall must be located close to the plasma edge (∼ 0.1 plasma minor radius) to stabilize external modes. Pressure and shear profile optimization could be used to increase this value. As εβθ is raised above unity, the stabilizing wall can be moved to progressively larger major radii. This behaviour is attributed to restabilization of the pressure driven component in low n kink modes. Finally, it is shown that poloidally discontinuous conducting structures are effective in stabilizing low n external kink modes. (author)

  20. 36 CFR 1004.23 - Operating under the influence of alcohol or drugs.

    Science.gov (United States)

    2010-07-01

    ... of alcohol or drugs. 1004.23 Section 1004.23 Parks, Forests, and Public Property PRESIDIO TRUST VEHICLES AND TRAFFIC SAFETY § 1004.23 Operating under the influence of alcohol or drugs. (a) Operating or... alcohol, or a drug, or drugs, or any combination thereof, to a degree that renders the operator incapable...

  1. Highly Stable Operation of Lithium Metal Batteries Enabled by the Formation of a Transient High Concentration Electrolyte Layer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jianming; Yan, Pengfei; Mei, Donghai; Engelhard, Mark H.; Cartmell, Samuel S.; Polzin, Bryant; Wang, Chong M.; Zhang, Jiguang; Xu, Wu

    2016-02-08

    Lithium (Li) metal has been extensively investigated as an anode for rechargeable battery applications due to its ultrahigh specific capacity and the lowest redox potential. However, significant challenges including dendrite growth and low Coulombic efficiency are still hindering the practical applications of rechargeable Li metal batteries. Here, we demonstrate that long-term cycling of Li metal batteries can be realized by the formation of a transient high concentration electrolyte layer near the surface of Li metal anode during high rate discharge process. The highly concentrated Li+ ions in this transient layer will immediately solvate with the available solvent molecules and facilitate the formation of a stable and flexible SEI layer composed of a poly(ethylene carbonate) framework integrated with other organic/inorganic lithium salts. This SEI layer largely suppresses the corrosion of Li metal anode by free organic solvents and enables the long-term operation of Li metal batteries. The fundamental findings in this work provide a new direction for the development and operation of Li metal batteries that could be operated at high current densities for a wide range of applications.

  2. A Compact Unconditionally Stable Method for Time-Domain Maxwell's Equations

    Directory of Open Access Journals (Sweden)

    Zhuo Su

    2013-01-01

    Full Text Available Higher order unconditionally stable methods are effective ways for simulating field behaviors of electromagnetic problems since they are free of Courant-Friedrich-Levy conditions. The development of accurate schemes with less computational expenditure is desirable. A compact fourth-order split-step unconditionally-stable finite-difference time-domain method (C4OSS-FDTD is proposed in this paper. This method is based on a four-step splitting form in time which is constructed by symmetric operator and uniform splitting. The introduction of spatial compact operator can further improve its performance. Analyses of stability and numerical dispersion are carried out. Compared with noncompact counterpart, the proposed method has reduced computational expenditure while keeping the same level of accuracy. Comparisons with other compact unconditionally-stable methods are provided. Numerical dispersion and anisotropy errors are shown to be lower than those of previous compact unconditionally-stable methods.

  3. Stable, metastable and unstable solutions of a spin-1 Ising system based on the free energy surfaces

    Science.gov (United States)

    Keskİin, Mustafa; Özgan, Şükrü

    1990-04-01

    Stable, metastable and unstable solutions of a spin-1 Ising model with bilinear and biquadratic interactions are found by using the free energy surfaces. The free energy expression is obtained in the lowest approximation of the cluster variation method. All these solutions are shown in the two-dimensional phase space, especially the unstable solutions which in some cases are difficult to illustrate in the two-dimensional phase space, found by Keskin et al. recently.

  4. Chiral symmetry breaking in asymptotically free and non-asymptotically free gauge theories

    International Nuclear Information System (INIS)

    Gusynin, V.P.; Miranskij, V.A.

    1986-01-01

    An essential distinction in the realization of the PCAC-dynamics in vector-like asymptotically free and non-asymptotically free (with a non-trival ultraviolet stable fixed point) gauge theories is revealed. For the latter theories an analytical expression for the condensate is obtained in the two-loop approximation and the arguments in support of a soft behaviour at small distances of composite operators are given. The problem of factorizing the low-energy region for the Wess-Zumino-Witten action is discussed

  5. Preparation and properties studies of halogen-free flame retardant form-stable phase change materials based on paraffin/high density polyethylene composites

    International Nuclear Information System (INIS)

    Cai Yibing; Wei Qufu; Huang Fenglin; Gao Weidong

    2008-01-01

    The halogen-free flame retardant form-stable phase change materials (PCM) based on paraffin/high density polyethylene (HDPE) composites were prepared by using twin-screw extruder technique. The structures and properties of the form-stable PCM composites based on intumescent flame retardant system with expandable graphite (EG) and different synergistic additives, such as ammonium polyphosphate (APP) and zinc borate (ZB) were characterized by scanning electronic microscope (SEM), thermogravimetric analyses (TGA), dynamic Fourier-transform infrared (FTIR) spectra, differential scanning calorimeter (DSC) and Cone calorimeter test. The TGA results showed that the halogen-free flame retardant form-stable PCM composites produced a larger amount of charred residue at 700 deg. C, although the onset of weight loss of the halogen-free flame retardant form-stable PCM composites occurred at a lower temperature due to the thermal decomposition of flame retardant. The DSC measurements indicated that the additives of flame retardant had little effect on the thermal energy storage property, and the temperatures of phase change peaks and the latent heat of the paraffin showed better occurrence during the freezing process. The dynamic FTIR monitoring results revealed that the breakdowns of main chains (HDPE and paraffin) and formations of various residues increased with increasing thermo-oxidation temperature. It was also found from the Cone calorimeter tests that the peak of heat release rate (PHRR) decreased significantly. Both the decrease of the PHRR and the structure of charred residue after combustion indicated that there was a synergistic effect between the EG and APP, contributing to the improved flammability of the halogen-free flame retardant form-stable PCM composites

  6. Label-free integrative pharmacology on-target of drugs at the β2-adrenergic receptor

    Science.gov (United States)

    Ferrie, Ann M.; Sun, Haiyan; Fang, Ye

    2011-07-01

    We describe a label-free integrative pharmacology on-target (iPOT) method to assess the pharmacology of drugs at the β2-adrenergic receptor. This method combines dynamic mass redistribution (DMR) assays using an array of probe molecule-hijacked cells with similarity analysis. The whole cell DMR assays track cell system-based, ligand-directed, and kinetics-dependent biased activities of the drugs, and translates their on-target pharmacology into numerical descriptors which are subject to similarity analysis. We demonstrate that the approach establishes an effective link between the label-free pharmacology and in vivo therapeutic indications of drugs.

  7. Stability Analysis of an HIV/AIDS Dynamics Model with Drug Resistance

    Directory of Open Access Journals (Sweden)

    Qianqian Li

    2012-01-01

    Full Text Available A mathematical model of HIV/AIDS transmission incorporating treatment and drug resistance was built in this study. We firstly calculated the threshold value of the basic reproductive number (R0 by the next generation matrix and then analyzed stability of two equilibriums by constructing Lyapunov function. When R0<1, the system was globally asymptotically stable and converged to the disease-free equilibrium. Otherwise, the system had a unique endemic equilibrium which was also globally asymptotically stable. While an antiretroviral drug tried to reduce the infection rate and prolong the patients’ survival, drug resistance was neutralizing the effects of treatment in fact.

  8. 76 FR 10205 - Department of Homeland Security Implementation of OMB Guidance on Drug-Free Workplace Requirements

    Science.gov (United States)

    2011-02-24

    ... Flexibility Act, 5 U.S.C. 605(b), as amended by the Small Business Regulatory Enforcement and Fairness Act of... Guidance on Drug-Free Workplace Requirements AGENCY: Department of Homeland Security (DHS). ACTION: Final... consolidate all Federal regulations on drug-free workplace requirements for financial assistance into one...

  9. Application of stable, nitroxide free radicals in solution to low magnetic fields measurements

    International Nuclear Information System (INIS)

    Besson, Rene

    1973-01-01

    The first attempts to use the Overhauser-Abragam effect for measuring low magnetic fields date back to 1956. However, the instability of the free radical used, PREMY'S Salt, as well as its virtual insolubility in solvents other than water, hampered the development of the nuclear magnetic resonance magnetometer realized in accordance to this principle: dynamic polarization of protons. New free radicals stable and soluble in many solvents, will enhanced the interest in the device. In particular, the use of 2,2,6,6, tetramethyl- piperidine-4-one-1-oxide (TANO or TANONE) leads to a high sensitivity, low field magnetometer. The methods of measurements, the required apparatus and sample preparation are first described. Next the results of measurements made both in high and low magnetic fields with various free radicals in different solvents are presented in tabular and graphical form. These measurements have determined which radical-solvent couple will yield a high dynamic polarization coefficient. In addition, the improvement obtained by complete deuteration of the free radical has been demonstrated. Problems connected with the application of such radicals in solution to the 'double effect probe' of the magnetometer built by LETI at CEN Grenoble and the solutions reached are discussed. (author) [fr

  10. 76 FR 45165 - Implementation of Office of Management and Budget Guidance on Drug-Free Workplace Requirements

    Science.gov (United States)

    2011-07-28

    ... INFORMATION: I. Background The Drug-Free Workplace Act of 1988 (Pub. L. 100-690, Title V, Subtitle D) (41 U.S... rule would not affect current application and enforcement of drug-free workplace requirements, no... Workplace Requirements AGENCY: Office of the Secretary, HUD. ACTION: Final rule. SUMMARY: HUD is moving its...

  11. Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

    DEFF Research Database (Denmark)

    Urban, Philip; Meredith, Ian T; Abizaid, Alexandre

    2015-01-01

    BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9......), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual...... ratio, 0.50; 95% CI, 0.37 to 0.69; Pbleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet...

  12. Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

    Directory of Open Access Journals (Sweden)

    Glen Daniel

    2009-05-01

    Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine

  13. Lipids, aggression, suicidality and impulsivity in drug-naïve/drug-free patients of schizophrenia.

    Science.gov (United States)

    Kavoor, Anjana Rao; Mitra, Sayantanava; Kumar, Sudhir; Sisodia, Anil Kr; Jain, Rakesh

    2017-06-01

    Present study aimed at determining lipid profiles in acutely symptomatic drug-naïve/drug-free patients of schizophrenia, comparing them with healthy controls and exploring relationships between various lipid fractions, aggression, suicidality and impulsivity in this population. This was a cross-sectional hospital-based study, comparing patients with schizophrenia (M=46, F=14; mean age 32.40±6.6 years; 48 drug-free for 10.50±9.2 weeks) with 60 age-sex matched healthy controls. Upon recruitment, fasting venous blood samples of all subjects were analysed for total cholesterol, HDL, LDL, VLDL and TG levels, and patients were rated on PANSS for symptom severity, Modified Overt Aggression Scale for aggression, Impulsivity Rating Scale for impulsivity and Scale for Suicide Ideation for suicidality. The socio-demographic characteristics of the patients were comparable to controls. In patients, total cholesterol, HDL and LDL levels were found to be significantly lower (pimpulsivity (psuicidality (pimpulsivity (pimpulsivity, suicidality and aggression in schizophrenia; providing interesting insights into the biochemical basis of human behaviour and confirming these in a developing-world population. The implications are many, including a need to review judiciously the promotion of weight loss and cholesterol reduction programmes in constitutionally vulnerable population, at least during their acutely-symptomatic states. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Study of the Dynamic Uptake of Free Drug and Nanostructures for Drug Delivery Based on Bioluminescence Measurements

    Directory of Open Access Journals (Sweden)

    Zhongjian Fang

    2017-01-01

    Full Text Available The past two decades have witnessed the great growth of the development of novel drug carriers. However, the releasing dynamics of drug from drug carriers in vivo and the interactions between cells and drug carriers remain unclear. In this paper, liposomes were prepared to encapsulate D-luciferin, which was the substrate of luciferase and served as a model drug. Based on the theoretical calculation of active loading, methods of preparation for liposomes were optimized. Only when D-luciferin was released from liposomes or taken in by the cells could bioluminescence be produced under the catalysis of luciferase. Models of multicellular tumor spheroid (MCTS were built with 4T1-luc cells that expressed luciferase stably. The kinetic processes of uptake and distribution of free drugs and liposomal drugs were determined with models of cell suspension, monolayer cells, MCTS, and tumor-bearing nude mice. The technology platform has been demonstrated to be effective for the study of the distribution and kinetic profiles of various liposomes as drug delivery systems.

  15. Research on the Combustion Characteristics of a Free-Piston Gasoline Engine Linear Generator during the Stable Generating Process

    Directory of Open Access Journals (Sweden)

    Yuxi Miao

    2016-08-01

    Full Text Available The free-piston gasoline engine linear generator (FPGLG is a new kind of power plant consisting of free-piston gasoline engines and a linear generator. Due to the elimination of the crankshaft mechanism, the piston motion process and the combustion heat release process affect each other significantly. In this paper, the combustion characteristics during the stable generating process of a FPGLG were presented using a numerical iteration method, which coupled a zero-dimensional piston dynamic model and a three-dimensional scavenging model with the combustion process simulation. The results indicated that, compared to the conventional engine (CE, the heat release process of the FPGLG lasted longer with a lower peak heat release rate. The indicated thermal efficiency of the engine was lower because less heat was released around the piston top dead centre (TDC. Very minimal difference was observed on the ignition delay duration between the FPGLG and the CE, while the post-combustion period of the FPGLG was significantly longer than that of the CE. Meanwhile, the FPGLG was found to operate more moderately due to lower peak in-cylinder gas pressure and a lower pressure rising rate. The potential advantage of the FPGLG in lower NOx emission was also proven with the simulation results presented in this paper.

  16. Stable isotopes as a tool to differentiate eggs laid by caged, barn, free range, and organic hens.

    Science.gov (United States)

    Rogers, Karyne M

    2009-05-27

    Stable carbon and nitrogen isotope values of whole yolk, delipidized yolk, albumen, and egg membrane were analyzed from 18 different brands of chicken eggs laid under caged, barn, free range, and organic farming regimes. In general, free range and organic egg components showed enrichment of (15)N values up to 4‰ relative to caged and barn laid eggs, suggesting a higher animal protein (trophic) contribution to the chicken's diet than pure plant-based foods and/or that the feed was organically manufactured. One sample of free range and two samples of organic eggs had δ(15)N values within the range of caged or barn laid eggs, suggesting either that these eggs were mislabeled (the hens were raised under "battery" or "barn" conditions, and not permitted to forage outside) or that there was insufficient animal protein gained by foraging to shift the δ(15)N values of their primary food source. δ(13)C values of potential food sources are discussed with respect to dietary intake and contribution to the isotopic signature of the eggs to determine mixing of C(3) and C(4) diets, although they did not elucidate laying regimen. The study finds that stable nitrogen isotope analysis of egg components is potentially a useful technique to unravel dietary differences between caged or barn hens and free range hens (both conventional and organic) and could be further developed as an authentication tool in the egg industry.

  17. Studies on photofading and stable free radical formation in reactive dyed cellulosic systems under their exposure to light

    International Nuclear Information System (INIS)

    Remi, E.; Horvath, O.; Vig, A.; Aranyosi, P.; Rusznak, I.

    1996-01-01

    In light exposed systems of cotton and C.I. Reactive Red 3, C.I. Reactive Black 5 and C.I. Direct Blue 78 azo dyes respectively, generated stable free radicals could be detected. The observed hyperfine splitting of ESR spectra suggest the free radical are formed in the chromophore. Based upon the calculated g-values the location of the generated unpaired electron could be assumed on one of the C atoms of the dye molecule. (author)

  18. a Comparison Between Chemically Dependent Mothers and Drug-Free Mothers: Lifestyle during the Perinatal Period

    Science.gov (United States)

    Uskokovic, Lila Milica

    This study compared maternal lifestyle variables pertinent to the perinatal period in groups of chemically dependent mothers and drug-free mothers. Twenty-nine cocaine -abusing mothers were compared to 29 drug-free mothers carefully matched on age, race, education, and primipara versus multipara status. The drug history of each chemically dependent woman was explicitly documented. The chemically dependent group was subdivided into two groups, mothers who abused cocaine and those who abused cocaine with concomitant opiate use. Each of these two subgroups was compared to its respective matched drug-free control group. Finally, a comparison was made between the two drug subgroups. All subjects were interviewed within 48 hours after delivery using the following measures: State-Trait Anxiety Inventory (A-State), Center for Epidemiologic Studies - Depression Scale, The Self-Esteem Scale, Maternal Adjustment and Maternal Attitude Questionnaire, The Neonatal Perception Inventory, The Psychiatric Epidemiology Research Interview Life Events Scale, Maternal Social Support Index, and Short Marital Adjustment Test. A t-test analysis revealed significant differences (p abused opiates with cocaine did not differ from their controls on depression and maternal adjustment and attitudes. No significant differences were obtained in the drug subgroup comparisons. These results identify increased life events and specific negative affect states that clinical intervention programs should address to assure the best possible outcome for chemically dependent mothers and their infants.

  19. Relative Binding Free Energy Calculations in Drug Discovery: Recent Advances and Practical Considerations.

    Science.gov (United States)

    Cournia, Zoe; Allen, Bryce; Sherman, Woody

    2017-12-26

    Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives

  20. An algorithmic decomposition of claw-free graphs leading to an O(n^3) algorithm for the weighted stable set problem

    OpenAIRE

    Faenza, Y.; Oriolo, G.; Stauffer, G.

    2011-01-01

    We propose an algorithm for solving the maximum weighted stable set problem on claw-free graphs that runs in O(n^3)-time, drastically improving the previous best known complexity bound. This algorithm is based on a novel decomposition theorem for claw-free graphs, which is also intioduced in the present paper. Despite being weaker than the well-known structure result for claw-free graphs given by Chudnovsky and Seymour, our decomposition theorem is, on the other hand, algorithmic, i.e. it is ...

  1. Methylammonium Bismuth Iodide as a Lead-Free, Stable Hybrid Organic-Inorganic Solar Absorber.

    Science.gov (United States)

    Hoye, Robert L Z; Brandt, Riley E; Osherov, Anna; Stevanović, Vladan; Stranks, Samuel D; Wilson, Mark W B; Kim, Hyunho; Akey, Austin J; Perkins, John D; Kurchin, Rachel C; Poindexter, Jeremy R; Wang, Evelyn N; Bawendi, Moungi G; Bulović, Vladimir; Buonassisi, Tonio

    2016-02-18

    Methylammonium lead halide (MAPbX3 ) perovskites exhibit exceptional carrier transport properties. But their commercial deployment as solar absorbers is currently limited by their intrinsic instability in the presence of humidity and their lead content. Guided by our theoretical predictions, we explored the potential of methylammonium bismuth iodide (MBI) as a solar absorber through detailed materials characterization. We synthesized phase-pure MBI by solution and vapor processing. In contrast to MAPbX3, MBI is air stable, forming a surface layer that does not increase the recombination rate. We found that MBI luminesces at room temperature, with the vapor-processed films exhibiting superior photoluminescence (PL) decay times that are promising for photovoltaic applications. The thermodynamic, electronic, and structural features of MBI that are amenable to these properties are also present in other hybrid ternary bismuth halide compounds. Through MBI, we demonstrate a lead-free and stable alternative to MAPbX3 that has a similar electronic structure and nanosecond lifetimes. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Control technique for enhancing the stable operation of distributed generation units within a microgrid

    International Nuclear Information System (INIS)

    Mehrasa, Majid; Pouresmaeil, Edris; Mehrjerdi, Hasan; Jørgensen, Bo Nørregaard; Catalão, João P.S.

    2015-01-01

    Highlights: • A control technique for enhancing the stable operation of distributed generation units is proposed. • Passivity-based control technique is considered to analyze the dynamic and steady-state behaviors. • The compensation of instantaneous variations in the reference current components is considered. • Simulation results confirm the performance of the control scheme within the microgrid. - Abstract: This paper describes a control technique for enhancing the stable operation of distributed generation (DG) units based on renewable energy sources, during islanding and grid-connected modes. The Passivity-based control technique is considered to analyze the dynamic and steady-state behaviors of DG units during integration and power sharing with loads and/or power grid, which is an appropriate tool to analyze and define a stable operating condition for DG units in microgrid technology. The compensation of instantaneous variations in the reference current components of DG units in ac-side, and dc-link voltage variations in dc-side of interfaced converters, are considered properly in the control loop of DG units, which is the main contribution and novelty of this control technique over other control strategies. By using the proposed control technique, DG units can provide the continuous injection of active power from DG sources to the local loads and/or utility grid. Moreover, by setting appropriate reference current components in the control loop of DG units, reactive power and harmonic current components of loads can be supplied during the islanding and grid-connected modes with a fast dynamic response. Simulation results confirm the performance of the control scheme within the microgrid during dynamic and steady-state operating conditions

  3. Label-free detection of cellular drug responses by high-throughput bright-field imaging and machine learning.

    Science.gov (United States)

    Kobayashi, Hirofumi; Lei, Cheng; Wu, Yi; Mao, Ailin; Jiang, Yiyue; Guo, Baoshan; Ozeki, Yasuyuki; Goda, Keisuke

    2017-09-29

    In the last decade, high-content screening based on multivariate single-cell imaging has been proven effective in drug discovery to evaluate drug-induced phenotypic variations. Unfortunately, this method inherently requires fluorescent labeling which has several drawbacks. Here we present a label-free method for evaluating cellular drug responses only by high-throughput bright-field imaging with the aid of machine learning algorithms. Specifically, we performed high-throughput bright-field imaging of numerous drug-treated and -untreated cells (N = ~240,000) by optofluidic time-stretch microscopy with high throughput up to 10,000 cells/s and applied machine learning to the cell images to identify their morphological variations which are too subtle for human eyes to detect. Consequently, we achieved a high accuracy of 92% in distinguishing drug-treated and -untreated cells without the need for labeling. Furthermore, we also demonstrated that dose-dependent, drug-induced morphological change from different experiments can be inferred from the classification accuracy of a single classification model. Our work lays the groundwork for label-free drug screening in pharmaceutical science and industry.

  4. High-Speed and Low-Energy Flip-Flop Operation of Asymmetric Active-Multimode Interferometer Bi-Stable Laser Diodes

    DEFF Research Database (Denmark)

    Jiang, Haisong; Chaen, Yutaka; Hagio, Takuma

    2011-01-01

    High-speed (121/25 ps rise/fall time) and low-switching energy (7.1 and 3.4 fJ) alloptical flip-flop operation of single-wavelength high-mesa asymmetric active-MMI bi-stable laser diodes is demonstrated for the first time using 25 ps long switching pulses.......High-speed (121/25 ps rise/fall time) and low-switching energy (7.1 and 3.4 fJ) alloptical flip-flop operation of single-wavelength high-mesa asymmetric active-MMI bi-stable laser diodes is demonstrated for the first time using 25 ps long switching pulses....

  5. Ensuring Steady Operation of Free-Piston Generator

    OpenAIRE

    Pavel Nemecek

    2006-01-01

    This paper describes Free-Piston Generator (FPG) model and its control for achieving steady operation. A FPG is a special type of combustion engine representing a new approach concerning the conversion of the chemical energy of hydrocarbon fuel into electrical energy. Unlike conventional engines, this type of engine does not use a crankshaft, and generates electric energy directly by a linear movement of pistons.

  6. Ensuring Steady Operation of Free-Piston Generator

    Directory of Open Access Journals (Sweden)

    Pavel Nemecek

    2006-02-01

    Full Text Available This paper describes Free-Piston Generator (FPG model and its control for achieving steady operation. A FPG is a special type of combustion engine representing a new approach concerning the conversion of the chemical energy of hydrocarbon fuel into electrical energy. Unlike conventional engines, this type of engine does not use a crankshaft, and generates electric energy directly by a linear movement of pistons.

  7. Doppler wind lidar using a MOPA semiconductor laser at stable single-frequency operation

    DEFF Research Database (Denmark)

    Rodrigo, Peter John; Pedersen, Christian

    2009-01-01

    for the tapered amplifier section. The specified maximum current values are 0.7 A and 4.0 A for Idfb and Iamp. Although the MOPA-SL has been proven capable of producing single-frequency CW output beam, stable operation at this spectral condition has also been known to highly depend on the drive currents...

  8. The synthesis and spectroscopic study of stable free radicals related to piperidine-n-oxyl, including a stable bi-radical; Syntheses et etudes spectroscopiques de radicaux libres piperidiniques et d'un biradical stable, du type nitroxyde

    Energy Technology Data Exchange (ETDEWEB)

    Briere, R [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires, Laboratoire de chimie organique physique

    1967-06-01

    A new synthesis of di-tert-butyl nitroxide using the reaction between tert-butyl magnesium chloride and nitro-tert-butane is presented in the first section. Synthesis and investigation of stable free piperidine-N-oxyl radicals are described in the second section. All these nitroxides have been characterised by their I. R., U. V. and E. P. R. absorption spectra. The final section contains a description of the synthesis of a stable bi-radical of the nitroxide type by condensation of 2,2, 6, 6-tetramethyl-piperid-4-one-l-oxyl with hydrazine. (author) [French] La premiere partie expose une nouvelle methode de synthase du di-t-butyl nitroxyde, par action d'halogenures de t-butyl magnesium sur le nitro-t-butane (Rdt maximum 45 pour cert, purete 86 pour cent). Une etude de radicaux. libres stables pipericliniques est faite dans une seconde partie. Ces composes sont obtenus par oxydation de derives de la triacetonamine. Les caracteristiques spectroscopiques ultra-violette, infra-rouge, et paramagnetique electronique de ces radicaux sont donnees. La grande inertie chimique du groupement nitroxyde a permis la syn-these d'un biradical stable par formation d'azine d'une cetone radicalaire, ce qui fait 1'objet de la troisieme partie. (auteur)

  9. The generalized heavy free gas thermalization operator

    International Nuclear Information System (INIS)

    Pitcher, H.H.W.

    1963-05-01

    This paper gives an introduction to the generalized heavy free gas (Horowitz) thermalization operator, which is a device for simplifying thermalization calculations. Analytical, experimental,and numerical methods for determining the energy-dependent function f in the operator are discussed. The dependence of f on the nature of the moderator, its temperature, and the absorption of the system are investigated, using a program FOCS which derives f's from DSN (multigroup) thermal spectra; it is found that for most purposes the dependence on absorption is negligible except when Pu240 is present. The sensitivity of calculated spectra and reaction rate to changes in f is considered. f is given for graphite at 300 and 600 deg. K. (author)

  10. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects.

    Science.gov (United States)

    Lagorce, David; Sperandio, Olivier; Galons, Hervé; Miteva, Maria A; Villoutreix, Bruno O

    2008-09-24

    Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses) and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making. This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python) based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries. We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after) experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules) that can be easily tuned.

  11. Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective disorder: the influence of demographic variables and the inpatient drug-free period.

    Science.gov (United States)

    Sharma, R P; Javaid, J I; Davis, J M; Janicak, P G

    1998-09-15

    The relationship between plasma homovanillic acid (pHVA) and schizophrenic symptoms has not been conclusively determined. We reexamine pHVA levels in a new sample of patients with emphasis on demographic variables and the drug-free period. Plasma HVA levels were studied in 54 schizophrenic and schizoaffective-disordered, drug-free inpatients suffering from a psychotic exacerbation. A significant correlation was observed between pHVA levels and the number of inpatient drug-free days in the total sample, as well as the schizophrenic patient subsample. Further, pHVA was significantly and positively correlated with the duration of illness in the schizophrenic patient subsample. Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating Scale factors (anxiety/depression and hostility/suspiciousness), emerged only when considering schizophrenic patients drug-free for more than 2 weeks. No correlation was found between pHVA and the age of illness onset or the duration of the delay of treatment of the first psychotic episode. The effects of antipsychotic withdrawal on levels of pHVA in clinical populations may have to be examined and controlled for in future studies attempting to study the relationship between this metabolite and behavior in acutely ill, drug-free schizophrenic patients.

  12. Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis.

    Science.gov (United States)

    Gao, Xin; Zhang, Wenjing; Yao, Li; Xiao, Yuan; Liu, Lu; Liu, Jieke; Li, Siyi; Tao, Bo; Shah, Chandan; Gong, Qiyong; Sweeney, John A; Lui, Su

    2018-03-01

    Neuroimaging studies have shown both structural and functional abnormalities in patients with schizophrenia. Recently, studies have begun to explore the association between structural and functional grey matter abnormalities. By conducting a meta-analysis on morphometric and functional imaging studies of grey matter alterations in drug-free patients, the present study aims to examine the degree of overlap between brain regions with anatomic and functional changes in patients with schizophrenia. We performed a systematic search of PubMed, Embase, Web of Science and the Cochrane Library to identify relevant publications. A multimodal analysis was then conducted using Seed-based d Mapping software. Exploratory analyses included jackknife, subgroup and meta-regression analyses. We included 15 structural MRI studies comprising 486 drug-free patients and 485 healthy controls, and 16 functional MRI studies comprising 403 drug-free patients and 428 controls in our meta-analysis. Drug-free patients were examined to reduce pharmacological effects on the imaging data. Multimodal analysis showed considerable overlap between anatomic and functional changes, mainly in frontotemporal regions, bilateral medial posterior cingulate/paracingulate gyrus, bilateral insula, basal ganglia and left cerebellum. There were also brain regions showing only anatomic changes in the right superior frontal gyrus, left supramarginal gyrus, right lingual gyrus and functional alternations involving the right angular gyrus. The methodological aspects, patient characteristics and clinical variables of the included studies were heterogeneous, and we cannot exclude medication effects. The present study showed overlapping anatomic and functional brain abnormalities mainly in the default mode (DMN) and auditory networks (AN) in drug-free patients with schizophrenia. However, the pattern of changes differed in these networks. Decreased grey matter was associated with decreased activation within the DMN

  13. Host-guest chemistry of dendrimer-drug complexes: 7. Formation of stable inclusions between acetylated dendrimers and drugs bearing multiple charges.

    Science.gov (United States)

    Fang, Min; Zhang, Jiahai; Wu, Qinglin; Xu, Tongwen; Cheng, Yiyun

    2012-03-15

    Drug molecules bearing multiple charges usually form precipitates with cationic dendrimers, which presents a challenge during the preparation of dendrimer inclusions for these drugs. In the present study, fully acetylated polyamidoamine (PAMAM) dendrimers were proposed as stable vehicles for drug molecules bearing two negative charges such as Congo red and indocyanine green. NMR techniques including (1)H NMR and (1)H-(1)H NOESY were used to characterize the host-guest chemistry of acetylated dendrimer and these guest molecules. The cationic PAMAM dendrimer was found to form a precipitate with Congo red and indocyanine green, but the acetylated one avoided the formation of cross-linking structures in aqueous solutions. NOESY studies revealed the encapsulation of Congo red and indocyanine green within the interior cavities of PAMAM dendrimers at mild acidic conditions and acetylated dendrimers show much stronger ability to encapsulate the guest molecules than cationic ones. Also, UV-vis-NIR studies suggest that acetylated dendrimers significantly improve the photostability of indocyanine green and prevent the formation of indocyanine green J-aggregates in aqueous solutions. The present study provides a new insight into dendrimer-based host-guest systems, especially for those guest molecules bearing multiple charges. © 2012 American Chemical Society

  14. The Reclaim Screw in Mammoth Silos Operating on a Free Surface: Comparison Between Horizontal and Inclined Operation on Free Flowing Bulk Solids

    NARCIS (Netherlands)

    Oosterhuis, E.J.; Schott, Dingena; van Wijk, Arjen

    2004-01-01

    Although the screw conveyor, operating on a free surface, has been used for years as reclaim and storage equipment in mammoth silos, there is no documented knowledge about its spill characteristics. Research at Delft University of Technology together with ESI Eurosilo B.V. on the inclined use of the

  15. Decision of Lead-Time Compression and Stable Operation of Supply Chain

    Directory of Open Access Journals (Sweden)

    Songtao Zhang

    2017-01-01

    Full Text Available A cost optimization strategy and a robust control strategy were studied to realize the low-cost robust operation of the supply chain with lead times. Firstly, for the multiple production lead times which existed in the supply chain, a corresponding inventory state model and a supply chain cost model were constructed based on the Takagi-Sugeno fuzzy control system. Then, by considering the actual inventory level, the lead-time compression cost, and the stock-out cost, a cost optimization strategy was proposed. Furthermore, a fuzzy robust control strategy was proposed to realize the flexible switching among the models. Finally, the simulation results show that the total cost of the supply chain could be reduced effectively by the cost optimization strategy, and the stable operation of the supply chain could be realized by the proposed fuzzy robust control strategy.

  16. Ranking stability and super-stable nodes in complex networks.

    Science.gov (United States)

    Ghoshal, Gourab; Barabási, Albert-László

    2011-07-19

    Pagerank, a network-based diffusion algorithm, has emerged as the leading method to rank web content, ecological species and even scientists. Despite its wide use, it remains unknown how the structure of the network on which it operates affects its performance. Here we show that for random networks the ranking provided by pagerank is sensitive to perturbations in the network topology, making it unreliable for incomplete or noisy systems. In contrast, in scale-free networks we predict analytically the emergence of super-stable nodes whose ranking is exceptionally stable to perturbations. We calculate the dependence of the number of super-stable nodes on network characteristics and demonstrate their presence in real networks, in agreement with the analytical predictions. These results not only deepen our understanding of the interplay between network topology and dynamical processes but also have implications in all areas where ranking has a role, from science to marketing.

  17. The Free Software Movement and the GNU/Linux Operating System

    CERN Multimedia

    CERN. Geneva

    2003-01-01

    Richard Stallman will speak about the purpose, goals, philosophy, methods, status, and future prospects of the GNU operating system, which in combination with the kernel Linux is now used by an estimated 17 to 20 million users world wide.BiographyRichard Stallman is the founder of the Gnu Project, launched in 1984 to develop the free operating system GNU (an acronym for ''GNU's Not Unix''), and thereby give computer users the freedom that most of them have lost. GNU is free software: everyone is free to copy it and redistribute it, as well as to make changes either large or small. Today, Linux-based variants of the GNU system, based on the kernel Linux developed by Linus Torvalds, are in widespread use. There are estimated to be some 20 million users of GNU/Linux systems today. Richard Stallman is the principal author of the GNU Compiler Collection, a portable optimizing compiler which was designed to support diverse architectures and multiple languages. The compiler now supports over 30 different architect...

  18. FAF-Drugs2: Free ADME/tox filtering tool to assist drug discovery and chemical biology projects

    Directory of Open Access Journals (Sweden)

    Miteva Maria A

    2008-09-01

    Full Text Available Abstract Background Drug discovery and chemical biology are exceedingly complex and demanding enterprises. In recent years there are been increasing awareness about the importance of predicting/optimizing the absorption, distribution, metabolism, excretion and toxicity (ADMET properties of small chemical compounds along the search process rather than at the final stages. Fast methods for evaluating ADMET properties of small molecules often involve applying a set of simple empirical rules (educated guesses and as such, compound collections' property profiling can be performed in silico. Clearly, these rules cannot assess the full complexity of the human body but can provide valuable information and assist decision-making. Results This paper presents FAF-Drugs2, a free adaptable tool for ADMET filtering of electronic compound collections. FAF-Drugs2 is a command line utility program (e.g., written in Python based on the open source chemistry toolkit OpenBabel, which performs various physicochemical calculations, identifies key functional groups, some toxic and unstable molecules/functional groups. In addition to filtered collections, FAF-Drugs2 can provide, via Gnuplot, several distribution diagrams of major physicochemical properties of the screened compound libraries. Conclusion We have developed FAF-Drugs2 to facilitate compound collection preparation, prior to (or after experimental screening or virtual screening computations. Users can select to apply various filtering thresholds and add rules as needed for a given project. As it stands, FAF-Drugs2 implements numerous filtering rules (23 physicochemical rules and 204 substructure searching rules that can be easily tuned.

  19. Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles.

    Science.gov (United States)

    Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao

    2017-06-05

    The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

  20. QT interval and dispersion in drug-free anorexia nervosa adolescents: a case control study.

    Science.gov (United States)

    Bomba, Monica; Tremolizzo, Lucio; Corbetta, Fabiola; Nicosia, Franco; Lanfranconi, Francesca; Poggioli, Gianni; Goulene, Karine; Stramba-Badiale, Marco; Conti, Elisa; Neri, Francesca; Nacinovich, Renata

    2017-11-16

    Long QT values have been reported in patients with anorexia nervosa of the restricting type (ANr) potentially increasing the risk of fatal arrhythmia, especially if psychotropic drug treatment is required. Nevertheless, the previous studies on this topic are biased by drug exposure, long disease durations, and small sample sizes. This study is aimed at assessing QTc and QTcd values in ANr adolescents with recent onset and drug free, as compared to subjects affected by psychiatric disorders other than ANr. We evaluated QTc and its dispersion (QTcd) in a population of 77 drug-free ANr female adolescents and compared to an equal number of healthy controls (H-CTRL) and pathological controls (P-CTRL, mixed psychiatric disorders). The QT determination was performed on a standard simultaneous 12-lead ECG in blind by a single experienced investigator. QTc was calculated by the Bazett's formula and QTcd was determined as the difference between the maximum and minimum QTc intervals in different leads. Only for ANr patients, clinico-demographic data, hormones, and electrolytes were obtained. QTc was slightly reduced in ANr patients (27.7 ms, studies are needed to understand if the previously reported increase might be related to other associated chronic disorders, such as hormonal or electrolyte imbalance.

  1. Anesthetic drug wastage in the operation room: A cause for concern

    Directory of Open Access Journals (Sweden)

    Kapil Chaudhary

    2012-01-01

    Full Text Available Context: The cost of anesthetic technique has three main components, i.e., disposable supplies, equipments, and anesthetic drugs. Drug budgets are an easily identifiable area for short-term savings. Aim: To assess and estimate the amount of anesthetic drug wastage in the general surgical operation room. Also, to analyze the financial implications to the hospital due to drug wastage and suggest appropriate steps to prevent or minimize this wastage. Settings and Design: A prospective observational study conducted in the general surgical operation room of a tertiary care hospital. Materials and Methods: Drug wastage was considered as the amount of drug left unutilized in the syringes/vials after completion of a case and any ampoule or vial broken while loading. An estimation of the cost of wasted drug was made. Results: Maximal wastage was associated with adrenaline and lignocaine (100% and 93.63%, respectively. The drugs which accounted for maximum wastage due to not being used after loading into a syringe were adrenaline (95.24%, succinylcholine (92.63%, lignocaine (92.51%, mephentermine (83.80%, and atropine (81.82%. The cost of wasted drugs for the study duration was 46.57% (Rs. 16,044.01 of the total cost of drugs issued/loaded (Rs. 34,449.44. Of this, the cost of wastage of propofol was maximum being 56.27% (Rs. 9028.16 of the total wastage cost, followed by rocuronium 17.80% (Rs. 2856, vecuronium 5.23% (Rs. 840, and neostigmine 4.12% (Rs. 661.50. Conclusions: Drug wastage and the ensuing financial loss can be significant during the anesthetic management of surgical cases. Propofol, rocuronium, vecuronium, and neostigmine are the drugs which contribute maximally to the total wastage cost. Judicious use of these and other drugs and appropriate prudent measures as suggested can effectively decrease this cost.

  2. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles—A Platform for Drug Development

    Directory of Open Access Journals (Sweden)

    Henrika Wickström

    2017-11-01

    Full Text Available Mesoporous silica nanoparticles (MSNs have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV and poorly permeable (BCS class III, IV drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI surface functionalized MSNs, as well as drug-free and drug-loaded MSN–PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  3. Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

    Science.gov (United States)

    Wickström, Henrika; Hilgert, Ellen; Nyman, Johan O; Desai, Diti; Şen Karaman, Didem; de Beer, Thomas; Sandler, Niklas; Rosenholm, Jessica M

    2017-11-21

    Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.

  4. A Computational Drug Metabolite Detection Using the Stable Isotopic Mass-Shift Filtering with High Resolution Mass Spectrometry in Pioglitazone and Flurbiprofen

    Directory of Open Access Journals (Sweden)

    Yohei Miyamoto

    2013-09-01

    Full Text Available The identification of metabolites in drug discovery is important. At present, radioisotopes and mass spectrometry are both widely used. However, rapid and comprehensive identification is still laborious and difficult. In this study, we developed new analytical software and employed a stable isotope as a tool to identify drug metabolites using mass spectrometry. A deuterium-labeled compound and non-labeled compound were both metabolized in human liver microsomes and analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS. We computationally aligned two different MS data sets and filtered ions having a specific mass-shift equal to masses of labeled isotopes between those data using our own software. For pioglitazone and flurbiprofen, eight and four metabolites, respectively, were identified with calculations of mass and formulas and chemical structural fragmentation analysis. With high resolution MS, the approach became more accurate. The approach detected two unexpected metabolites in pioglitazone, i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other approaches such as metabolite-biotransformation list matching and mass defect filtering could not detect. We demonstrated that the approach using computational alignment and stable isotopic mass-shift filtering has the ability to identify drug metabolites and is useful in drug discovery.

  5. A facile construction strategy of stable lipid nanoparticles for drug delivery using a hydrogel-thickened microemulsion system

    Science.gov (United States)

    Chen, Huabing; Xiao, Ling; Du, Danrong; Mou, Dongsheng; Xu, Huibi; Yang, Xiangliang

    2010-01-01

    We report a novel facile method for preparing stable nanoparticles with inner spherical solid spheres and an outer hydrogel matrix using a hot O/W hydrogel-thickened microemulsion with spontaneous stability. The nanoparticles with average diameters of about 30.0 nm and 100.0 nm were constructed by cooling the hot hydrogel-thickened microemulsion at different temperatures, respectively. We explained the application of these nanoparticles by actualizing the cutaneous delivery of drug-loaded nanoparticles. The in vitro skin permeation studies showed that the nanoparticles could significantly reduce the penetration of model drugs through skin and resulted in their dermal uptakes in skin. The sol-gel process of TEOS was furthermore used in the template of HTM to regulate the particle size of nanoparticles. The coating of silica on the surface of nanoparticles could regulate the penetration of drug into skin from dermal delivery to transdermal delivery. This strategy provides a facile method to produce nanoparticles with long-term stability and ease of manufacture, which might have a promising application in drug delivery.

  6. Free and Licensed Operating Systems: Direct Comparison

    Directory of Open Access Journals (Sweden)

    Samy Hagman

    2015-06-01

    Full Text Available When developers comparing open with proprietary code, which should be a civilized debate often degenerates into a flame war. This paper presents a report on code quality metrics that have been collected from four major operating systems on an industrial scale is as follows: FreeBSD, Linux, OpenSolaris and Windows Research Kernel (WRK. This article is not a mysterious crime and it can be concluded as the main finding no significant differences in the quality of the code of these systems.

  7. Label-free recognition of drug resistance via impedimetric screening of breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Bilge Eker

    Full Text Available We present a novel study on label-free recognition and distinction of drug resistant breast cancer cells (MCF-7 DOX from their parental cells (MCF-7 WT via impedimetric measurements. Drug resistant cells exhibited significant differences in their dielectric properties compared to wild-type cells, exerting much higher extracellular resistance (Rextra . Immunostaining revealed that MCF-7 DOX cells gained a much denser F-actin network upon acquiring drug resistance indicating that remodeling of actin cytoskeleton is probably the reason behind higher Rextra , providing stronger cell architecture. Moreover, having exposed both cell types to doxorubicin, we were able to distinguish these two phenotypes based on their substantially different drug response. Interestingly, impedimetric measurements identified a concentration-dependent and reversible increase in cell stiffness in the presence of low non-lethal drug doses. Combined with a profound frequency analysis, these findings enabled distinguishing distinct cellular responses during drug exposure within four concentration ranges without using any labeling. Overall, this study highlights the possibility to differentiate drug resistant phenotypes from their parental cells and to assess their drug response by using microelectrodes, offering direct, real-time and noninvasive measurements of cell dependent parameters under drug exposure, hence providing a promising step for personalized medicine applications such as evaluation of the disease progress and optimization of the drug treatment of a patient during chemotherapy.

  8. Treatment Efficiency of Free and Nanoparticle-Loaded Mitoxantrone for Magnetic Drug Targeting in Multicellular Tumor Spheroids

    Directory of Open Access Journals (Sweden)

    Annkathrin Hornung

    2015-09-01

    Full Text Available Major problems of cancer treatment using systemic chemotherapy are severe side effects. Magnetic drug targeting (MDT employing superparamagnetic iron oxide nanoparticles (SPION loaded with chemotherapeutic agents may overcome this dilemma by increasing drug accumulation in the tumor and reducing toxic side effects in the healthy tissue. For translation of nanomedicine from bench to bedside, nanoparticle-mediated effects have to be studied carefully. In this study, we compare the effect of SPION, unloaded or loaded with the cytotoxic drug mitoxantrone (MTO with the effect of free MTO, on the viability and proliferation of HT-29 cells within three-dimensional multicellular tumor spheroids. Fluorescence microscopy and flow cytometry showed that both free MTO, as well as SPION-loaded MTO (SPIONMTO are able to penetrate into tumor spheroids and thereby kill tumor cells, whereas unloaded SPION did not affect cellular viability. Since SPIONMTO has herewith proven its effectivity also in complex multicellular tumor structures with its surrounding microenvironment, we conclude that it is a promising candidate for further use in magnetic drug targeting in vivo.

  9. High frequency free-electron laser results

    International Nuclear Information System (INIS)

    Boyer, K.; Brau, C.A.; Newman, B.E.; Stein, W.E.; Warren, R.W.; Winston, J.G.; Young, L.M.

    1983-01-01

    By looking at the free-electron laser as a particle accelerator working backwards, Morton realized that the techniques used to accelerate particles could be used to improve the performance of free-electron lasers. In particular, he predicted the capture of electrons in ''stable-phase'' regions, or ''buckets'' in the electron phase space, and proposed that by decelerating the buckets, the trapped electrons could be decelerated to extract significant amounts of their energy as optical radiation. In fact, since electrons not trapped in the stable regions are forever excluded from them--at least in the adiabatic approximation--displacement techniques could also be used to accelerate or decelerate electrons in a free-electron laser. This paper explains the principle behind ''phase-displacement'' acceleration and details an experiment carried out with a 20-MeV electron beam to test these predictions. Results obtained with a tapered-wiggler free-electron laser demonstrate the concepts proposed by Morton for enhanced efficiency. They show deceleration of electrons by as much as 7% and extraction of more than 3% of the total electron-beam energy as laser energy when the laser is operated as an amplifier. The experiment is presently being reconfigured to examine its performance as a laser oscillator

  10. 22 CFR Appendix C to Part 513 - Certification Regarding Drug-Free Workplace Requirements

    Science.gov (United States)

    2010-04-01

    ..., they may be identified in the grant application. If the grantee does not identify the workplaces at the... the workplace(s) on file in its office and make the information available for Federal inspection... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Certification Regarding Drug-Free Workplace...

  11. Effect of Antimalarial Drugs on Plasmodia Cell-Free Protein Synthesis

    Directory of Open Access Journals (Sweden)

    Ana Ferreras

    2002-04-01

    Full Text Available A cell-free system from Plasmodium falciparum able to translate endogenous mRNA was used to determine the effect of artemisinin, chloroquine and primaquine on the protein synthesis mechanism of the parasite. The antimalarial drugs did not inhibit the incorporation of [³H] methionine into parasite proteins even at concentrations higher than the ones found to strongly inhibit the parasite growth. Results clearly indicate that these compounds do not have a direct effect on protein synthesis activity of P. falciparum coded by endogenous mRNA.

  12. Energy stable and high-order-accurate finite difference methods on staggered grids

    Science.gov (United States)

    O'Reilly, Ossian; Lundquist, Tomas; Dunham, Eric M.; Nordström, Jan

    2017-10-01

    For wave propagation over distances of many wavelengths, high-order finite difference methods on staggered grids are widely used due to their excellent dispersion properties. However, the enforcement of boundary conditions in a stable manner and treatment of interface problems with discontinuous coefficients usually pose many challenges. In this work, we construct a provably stable and high-order-accurate finite difference method on staggered grids that can be applied to a broad class of boundary and interface problems. The staggered grid difference operators are in summation-by-parts form and when combined with a weak enforcement of the boundary conditions, lead to an energy stable method on multiblock grids. The general applicability of the method is demonstrated by simulating an explosive acoustic source, generating waves reflecting against a free surface and material discontinuity.

  13. Stable Operation and Electricity Generating Characteristics of a Single-Cylinder Free Piston Engine Linear Generator: Simulation and Experiments

    Directory of Open Access Journals (Sweden)

    Huihua Feng

    2015-01-01

    Full Text Available We present a novel design of a single-cylinder free piston engine linear generator (FPELG incorporating a linear motor as a rebound device. A systematic simulation model of this FPELG system was built containing a kinematic and dynamic model of the piston and mover, a magneto-electric model of the linear generator, a thermodynamic model of the single-cylinder engine, and a friction model between the piston ring and cylinder liner. Simulations were performed to understand the relationships between pre-set motor parameters and the running performance of the FPELG. From the simulation results, it was found that a motor rebound force with a parabolic profile had clear advantages over a force with a triangular profile, such as a higher running frequency and peak cylinder pressure, faster piston motion, etc. The rebound position and the amplitude of rebound force were also determined by simulations. The energy conversion characteristics of the generator were obtained from our FPELG test rig. The parameters of intake pressure, motor frequency, and load resistance were varied over certain ranges, and relationships among these three parameters were obtained. The electricity-generating characteristic parameters include output power and system efficiency, which can measure the quality of matching the controllable parameters. The output power can reach 25.9 W and the system efficiency can reach 13.7%. The results in terms of matching parameters and electricity-generating characteristics should be useful to future research in adapting these engines to various operating modes.

  14. Encapsulation of cisplatin as an anti-cancer drug into boron-nitride and carbon nanotubes: Molecular simulation and free energy calculation

    Energy Technology Data Exchange (ETDEWEB)

    Roosta, Sara [Molecular Simulation Research Laboratory, Department of Chemistry, Iran University of Science & Technology, Tehran (Iran, Islamic Republic of); Hashemianzadeh, Seyed Majid, E-mail: hashemianzadeh@iust.ac.ir [Molecular Simulation Research Laboratory, Department of Chemistry, Iran University of Science & Technology, Tehran (Iran, Islamic Republic of); Ketabi, Sepideh, E-mail: sepidehketabi@yahoo.com [Department of Chemistry, East Tehran Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2016-10-01

    Encapsulation of cisplatin anticancer drug into the single walled (10, 0) carbon nanotube and (10, 0) boron-nitride nanotube was investigated by quantum mechanical calculations and Monte Carlo Simulation in aqueous solution. Solvation free energies and complexation free energies of the cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube complexes was determined as well as radial distribution functions of entitled compounds. Solvation free energies of cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube were − 4.128 kcal mol{sup −1} and − 2457.124 kcal mol{sup −1} respectively. The results showed that cisplatin@ boron-nitride nanotube was more soluble species in water. In addition electrostatic contribution of the interaction of boron- nitride nanotube complex and solvent was − 281.937 kcal mol{sup −1} which really more than Van der Waals and so the electrostatic interactions play a distinctive role in the solvation free energies of boron- nitride nanotube compounds. On the other hand electrostatic part of the interaction of carbon nanotube complex and solvent were almost the same as Van der Waals contribution. Complexation free energies were also computed to study the stability of related structures and the free energies were negative (− 374.082 and − 245.766 kcal mol{sup −1}) which confirmed encapsulation of drug into abovementioned nanotubes. However, boron-nitride nanotubes were more appropriate for encapsulation due to their larger solubility in aqueous solution. - Highlights: • Solubility of cisplatin@ boron-nitride nanotube is larger than cisplatin@ carbon nanotube. • Boron- nitride nanotube complexes have larger electrostatic contribution in solvation free energy. • Complexation free energies confirm encapsulation of drug into the nanotubes in aqueous solution. • Boron- nitride nanotubes are appropriate drug delivery systems compared with carbon nanotubes.

  15. Encapsulation of cisplatin as an anti-cancer drug into boron-nitride and carbon nanotubes: Molecular simulation and free energy calculation

    International Nuclear Information System (INIS)

    Roosta, Sara; Hashemianzadeh, Seyed Majid; Ketabi, Sepideh

    2016-01-01

    Encapsulation of cisplatin anticancer drug into the single walled (10, 0) carbon nanotube and (10, 0) boron-nitride nanotube was investigated by quantum mechanical calculations and Monte Carlo Simulation in aqueous solution. Solvation free energies and complexation free energies of the cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube complexes was determined as well as radial distribution functions of entitled compounds. Solvation free energies of cisplatin@ carbon nanotube and cisplatin@ boron-nitride nanotube were − 4.128 kcal mol"−"1 and − 2457.124 kcal mol"−"1 respectively. The results showed that cisplatin@ boron-nitride nanotube was more soluble species in water. In addition electrostatic contribution of the interaction of boron- nitride nanotube complex and solvent was − 281.937 kcal mol"−"1 which really more than Van der Waals and so the electrostatic interactions play a distinctive role in the solvation free energies of boron- nitride nanotube compounds. On the other hand electrostatic part of the interaction of carbon nanotube complex and solvent were almost the same as Van der Waals contribution. Complexation free energies were also computed to study the stability of related structures and the free energies were negative (− 374.082 and − 245.766 kcal mol"−"1) which confirmed encapsulation of drug into abovementioned nanotubes. However, boron-nitride nanotubes were more appropriate for encapsulation due to their larger solubility in aqueous solution. - Highlights: • Solubility of cisplatin@ boron-nitride nanotube is larger than cisplatin@ carbon nanotube. • Boron- nitride nanotube complexes have larger electrostatic contribution in solvation free energy. • Complexation free energies confirm encapsulation of drug into the nanotubes in aqueous solution. • Boron- nitride nanotubes are appropriate drug delivery systems compared with carbon nanotubes.

  16. Dynamics of epidemic spreading model with drug-resistant variation on scale-free networks

    Science.gov (United States)

    Wan, Chen; Li, Tao; Zhang, Wu; Dong, Jing

    2018-03-01

    Considering the influence of the virus' drug-resistant variation, a novel SIVRS (susceptible-infected-variant-recovered-susceptible) epidemic spreading model with variation characteristic on scale-free networks is proposed in this paper. By using the mean-field theory, the spreading dynamics of the model is analyzed in detail. Then, the basic reproductive number R0 and equilibriums are derived. Studies show that the existence of disease-free equilibrium is determined by the basic reproductive number R0. The relationships between the basic reproductive number R0, the variation characteristic and the topology of the underlying networks are studied in detail. Furthermore, our studies prove the global stability of the disease-free equilibrium, the permanence of epidemic and the global attractivity of endemic equilibrium. Numerical simulations are performed to confirm the analytical results.

  17. PROCESS OF CHANGES OF MAINTENANCE-FREE ONBOARD SYSTEM OPERATIONAL STATUS BETWEEN SCHEDULED MAINTENANCES

    Directory of Open Access Journals (Sweden)

    Andrey Mikhaylovich Bronnikov

    2017-01-01

    Full Text Available In this article the authors consider the problem of simulating the process of a maintenance-free between scheduled maintenance aircraft system operational status changes, which failure during the flight leads to the disaster. On-board equipment with automatic self-repair between routine maintenance in the event the components fail is called maintenance-free. During operation, onboard equipment accumulates failures maintaining its functions with a safety level not lower than the required minimum. Trouble shooting is carried out either at the end of between-maintenance period (as a rule, or after the failure, which led to the functions disorder or to the decrease below the target level of flight safety (as an exception. The system contains both redundant and nonredundant units and elements with the known failure rates. The system can be in one of the three states: operable, extreme, failed. The excessive redundant elements allow the system to accumulate failures which are repaired during the routine maintenance. The process of system operational status changes is described with the discrete-continuous model in the flight time. Basing on the information about the probabilities of the on-board equipment being in an operable, extreme or failed state, it is possible to calculate such complex efficiency indicators as the average loss of sorties, the average operating costs, the expected number of emergency recovery operations and others. Numerical studies have been conducted to validate the proposed model. It is believed that maintenance work completely updates the system. The analysis of these indicators will allow to evaluate the maintenance-free aircraft equipment operation efficiency, as well as to make an effectiveness comparison with other methods of technical operation. The model can be also used to assess the technical operation systems performance. The model can be used to optimize the period between maintenance.

  18. Serum and plasma for total and free anticonvulsant drug analyses: effects on EMIT assays and ultrafiltration devices.

    Science.gov (United States)

    Godolphin, W; Trepanier, J; Farrell, K

    1983-01-01

    The suitability of serum and plasma anticoagulated with heparin, EDTA, citrate, or oxalate was assessed for analysis of free and total phenytoin, carbamazepine, and valproic acid. The free fraction was isolated by ultrafiltration through FreeLevel devices (Syva, Palo Alto, CA). Serum, heparin, and EDTA plasma were satisfactory for both free and total phenytoin and carbamazepine. EDTA could not be used for EMIT (Syva) analysis of valproate. Citrate and, to a lesser degree, oxalate cause a significant negative interference in the concentration of these three drugs as measured both by EMIT and gas-liquid chromatography.

  19. Mass spectrometry imaging of illicit drugs in latent fingerprints by matrix-free and matrix-assisted desorption/ionization techniques.

    Science.gov (United States)

    Skriba, Anton; Havlicek, Vladimir

    2018-02-01

    Compared with classical matrix-assisted laser-desorption ionization mass spectrometry (MALDI), the matrix free-based strategies generate a cleaner background, without significant noise or interference coming from an applied matrix, which is beneficial for the analysis of small molecules, such as drugs of abuse. In this work, we probed the detection efficiency of methamphetamine, heroin and cocaine in nanostructure-assisted laser desorption-ionization (NALDI) and desorption electrospray ionization and compared the sensitivity of these two matrix-free tools with a standard MALDI mass spectrometry experiment. In a typical mass spectrometry imaging (MSI) setup, papillary line latent fingerprints were recorded as a mixture a common skin fatty acid or interfering cosmetics with a drug. In a separate experiment, all drugs (1 µL of 1 μM standard solution) were detected by all three ionization techniques on a target. In the case of cocaine and heroin, NALDI mass spectrometry was the most sensitive and revealed signals even from 0.1 μM solution. The drug/drug contaminant (fatty acid or cosmetics) MSI approach could be used by law enforcement personnel to confirm drug abusers of having come into contact with the suspected drug by use of fingerprint scans at time of apprehension which can aid in reducing the work of lab officials.

  20. Drugs@FDA: FDA Approved Drug Products

    Science.gov (United States)

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing ... Download Drugs@FDA Express for free Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  1. Highly water-soluble, porous, and biocompatible boron nitrides for anticancer drug delivery.

    Science.gov (United States)

    Weng, Qunhong; Wang, Binju; Wang, Xuebin; Hanagata, Nobutaka; Li, Xia; Liu, Dequan; Wang, Xi; Jiang, Xiangfen; Bando, Yoshio; Golberg, Dmitri

    2014-06-24

    Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.

  2. Possibility of Q>5 stable, steady-state operation in ITER with moderate βN and H-factor

    International Nuclear Information System (INIS)

    Polevoi, A.R.; Mukhovatov, V.S.; Shimada, M.; Medvedev, S.Yu.; Ivanov, A.A.; Poshekhonov, Yu.Yu.; Pustovitov, V.D.; Chu, M.S.

    2003-01-01

    A possibility of steady state stable operation in ITER with Q>5 and moderate requirements for plasma confinement is investigated. It is shown that there is some parametrical space for such operation where the ideal kink modes could be stabilised by the first wall. It is found that operational space where the ideal kink modes can be stabilised by the conducting wall could be noticeably extended by a relatively small reduction of the pressure peaking factor. The resistive wall mode stabilisation in ITER is discussed. (author)

  3. Thermal-Hydraulic Experiment To Test The Stable Operation Of A PIUS Type Reactor

    International Nuclear Information System (INIS)

    Irianto, Djoko; Kanji, T.; Kukita, Y.

    1996-01-01

    An advanced type of reaktor concept as the Process Inherent Ultimate Safety (PIUS) reactor was based on intrinsically passive safety considerations. The stable operation of a PIUS type reactor is based on the automation of circulation pump speed. An automatic circulation pump speed control system by using a measurement of the temperature distribution in the lower density lock is proposed the PIUS-type reactor. In principle this control system maintains the fluid temperature at the axial center of the lower density lock at average of the fluid temperatures below and above the lower density lock. This control system will prevent the poison water from penetrating into the core during normal operation. The effectiveness of this control system was successfully confirmed by a series of experiments using atmospheric pressure thermal-hydraulic test loop which simulated the PIUS principle. The experiments such as: start-up and power ramping tests for normal operation simulation and loss of feedwater test for an accident condition simulation, carried out in JAERI

  4. Robust and Stable Disturbance Observer of Servo System for Low-Speed Operation

    DEFF Research Database (Denmark)

    Lee, Kyo Beum; Blaabjerg, Frede

    2007-01-01

    A new scheme to estimate the moment of inertia in the servo motor drive system in very low speed is proposed in this paper. The speed estimation scheme in most servo drive systems for low-speed operation is sensitive to the variation of machine parameter, especially the moment of inertia....... To estimate the motor inertia value, the observer using the Radial Basis Function Network (RBFN) is applied. A control law for stabilizing the system and adaptive laws for updating both of the weights in the RBFN and a bounding constant are established so that the whole closed-loop system is stable...

  5. Advances towards QH-mode viability for ELM-stable operation in ITER

    International Nuclear Information System (INIS)

    Garofalo, A.M.; Burrell, K.H.; DeBoo, J.C.; Schaffer, M.J.; Snyder, P.B.; Solomon, W.M.; Park, J.-K.; Lanctot, M.J.; Reimerdes, H.; McKee, G.R.; Schmitz, L.

    2011-01-01

    The application of static, non-axisymmetric, nonresonant magnetic fields (NRMFs) to high beta DIII-D plasmas has allowed sustained operation with a quiescent H-mode (QH-mode) edge and both toroidal rotation and neutral beam injected torque near zero. Previous studies have shown that QH-mode operation can be accessed only if sufficient radial shear in the plasma flow is produced near the plasma edge. In past experiments, this flow shear was produced using neutral beam injection (NBI) to provide toroidal torque. In recent experiments, this torque was nearly completely replaced by the torque from applied NRMFs. The application of the NRMFs does not degrade the global energy confinement of the plasma. Conversely, the experiments show that the energy confinement quality increases with lower plasma rotation. Furthermore, the NRMF torque increases plasma resilience to locked modes at low rotation. These results open a path towards QH-mode utilization as an edge-localized mode (ELM)-stable H-mode in the self-heated burning plasma scenario, where toroidal momentum input from NBI may be small or absent.

  6. A Probabilistic Model of Illegal Drug Trafficking Operations in the Eastern Pacific and Caribbean Sea

    Science.gov (United States)

    2013-09-01

    production, drug-trafficking, and drug consumption . The South American countries in the Andean region, particularly Colombia, Peru, and Bolivia, are... cocoa production in these three countries at 187,500 hectares in 2010. This is down from a peak in 2007 of 232,500 hectares. Combining the Andean...operations. They tax cocoa farmers and buyers and have controlling interests in various operations of the drug supply chain (Seelke et al., 2011). When the

  7. Impaired Urine Dilution Capability in HIV Stable Patients

    Directory of Open Access Journals (Sweden)

    Waldo H. Belloso

    2014-01-01

    Full Text Available Renal disease is a well-recognized complication among patients with HIV infection. Viral infection itself and the use of some antiretroviral drugs contribute to this condition. The thick ascending limb of Henle’s loop (TALH is the tubule segment where free water clearance is generated, determining along with glomerular filtration rate the kidney’s ability to dilute urine. Objective. We analyzed the function of the proximal tubule and TALH in patients with HIV infection receiving or not tenofovir-containing antiretroviral treatment in comparison with healthy seronegative controls, by applying a tubular physiological test, hyposaline infusion test (Chaimowitz’ test. Material & Methods. Chaimowitz’ test was performed on 20 HIV positive volunteers who had normal renal functional parameters. The control group included 10 healthy volunteers. Results. After the test, both HIV groups had a significant reduction of serum sodium and osmolarity compared with the control group. Free water clearance was lower and urine osmolarity was higher in both HIV+ groups. Proximal tubular function was normal in both studied groups. Conclusion. The present study documented that proximal tubule sodium reabsorption was preserved while free water clearance and maximal urine dilution capability were reduced in stable HIV patients treated or not with tenofovir.

  8. Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering

    Science.gov (United States)

    Rogozhnikov, Dmitry; O'Brien, Paul J.; Elahipanah, Sina; Yousaf, Muhammad N.

    2016-12-01

    There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

  9. Applications of stable isotopes in clinical pharmacology

    NARCIS (Netherlands)

    Schellekens, Reinout C A; Stellaard, Frans; Woerdenbag, Herman J; Frijlink, Henderik W; Kosterink, Jos G W

    2011-01-01

    This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the

  10. Antiviral Information Management System (AIMS): a prototype for operational innovation in drug development.

    Science.gov (United States)

    Jadhav, Pravin R; Neal, Lauren; Florian, Jeff; Chen, Ying; Naeger, Lisa; Robertson, Sarah; Soon, Guoxing; Birnkrant, Debra

    2010-09-01

    This article presents a prototype for an operational innovation in knowledge management (KM). These operational innovations are geared toward managing knowledge efficiently and accessing all available information by embracing advances in bioinformatics and allied fields. The specific components of the proposed KM system are (1) a database to archive hepatitis C virus (HCV) treatment data in a structured format and retrieve information in a query-capable manner and (2) an automated analysis tool to inform trial design elements for HCV drug development. The proposed framework is intended to benefit drug development by increasing efficiency of dose selection and improving the consistency of advice from US Food and Drug Administration (FDA). It is also hoped that the framework will encourage collaboration among FDA, industry, and academic scientists to guide the HCV drug development process using model-based quantitative analysis techniques.

  11. Addressing drug adherence using an operations management model.

    Science.gov (United States)

    Nunlee, Martin; Bones, Michelle

    2014-01-01

    OBJECTIVE To provide a model that enables health systems and pharmacy benefit managers to provide medications reliably and test for reliability and validity in the analysis of adherence to drug therapy of chronic disease. SUMMARY The quantifiable model described here can be used in conjunction with behavioral designs of drug adherence assessments. The model identifies variables that can be reproduced and expanded across the management of chronic diseases with drug therapy. By creating a reorder point system for reordering medications, the model uses a methodology commonly seen in operations research. The design includes a safety stock of medication and current supply of medication, which increases the likelihood that patients will have a continuous supply of medications, thereby positively affecting adherence by removing barriers. CONCLUSION This method identifies an adherence model that quantifies variables related to recommendations from health care providers; it can assist health care and service delivery systems in making decisions that influence adherence based on the expected order cycle days and the expected daily quantity of medication administered. This model addresses the possession of medication as a barrier to adherence.

  12. 41 CFR 105-74.205 - What must I include in my drug-free workplace statement?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What must I include in my drug-free workplace statement? 105-74.205 Section 105-74.205 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION...

  13. 41 CFR 105-74.215 - What must I include in my drug-free awareness program?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What must I include in my drug-free awareness program? 105-74.215 Section 105-74.215 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION...

  14. 41 CFR 105-74.210 - To whom must I distribute my drug-free workplace statement?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false To whom must I distribute my drug-free workplace statement? 105-74.210 Section 105-74.210 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION...

  15. High-field/ high-frequency EPR study on stable free radicals formed in sucrose by gamma-irradiation.

    Science.gov (United States)

    Georgieva, Elka R; Pardi, Luca; Jeschke, Gunnar; Gatteschi, Dante; Sorace, Lorenzo; Yordanov, Nicola D

    2006-06-01

    The EPR spectrum of sucrose irradiated by high-energy radiation is complex due to the presence of more than one radical species. In order to decompose the spectrum and elucidate the radical magnetic parameters a high-field (HF(-)EPR) study on stable free radicals in gamma-irradiated polycrystalline sucrose (table sugar) was performed at three different high frequencies--94, 190 and 285 GHz as well as at the conventional X-band. We suggest a presence of three stable radicals R1, R2 and R3 as the main radical species. Due to the increase of g-factor resolution at high fields the g-tensors of these radicals could be extracted by accurate simulations. The moderate g-anisotropy suggests that all three radicals are carbon-centred. Results from an earlier ENDOR study on X-irradiated sucrose single crystals (Vanhaelewyn et al., Appl Radiat Isot, 52, 1221 (2000)) were used for analyzing of the spectra in more details. It was confirmed that the strongest hyperfine interaction has a relatively small anisotropy, which indicates either the absence of alpha-protons or a strongly distorted geometry of the radicals.

  16. I. Dissociation free energies of drug-receptor systems via non-equilibrium alchemical simulations: a theoretical framework.

    Science.gov (United States)

    Procacci, Piero

    2016-06-01

    In this contribution I critically revise the alchemical reversible approach in the context of the statistical mechanics theory of non-covalent bonding in drug-receptor systems. I show that most of the pitfalls and entanglements for the binding free energy evaluation in computer simulations are rooted in the equilibrium assumption that is implicit in the reversible method. These critical issues can be resolved by using a non-equilibrium variant of the alchemical method in molecular dynamics simulations, relying on the production of many independent trajectories with a continuous dynamical evolution of an externally driven alchemical coordinate, completing the decoupling of the ligand in a matter of a few tens of picoseconds rather than nanoseconds. The absolute binding free energy can be recovered from the annihilation work distributions by applying an unbiased unidirectional free energy estimate, on the assumption that any observed work distribution is given by a mixture of normal distributions, whose components are identical in either direction of the non-equilibrium process, with weights regulated by the Crooks theorem. I finally show that the inherent reliability and accuracy of the unidirectional estimate of the decoupling free energies, based on the production of a few hundreds of non-equilibrium independent sub-nanosecond unrestrained alchemical annihilation processes, is a direct consequence of the funnel-like shape of the free energy surface in molecular recognition. An application of the technique to a real drug-receptor system is presented in the companion paper.

  17. Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

    Science.gov (United States)

    Cooper, Lilli; Seth, Rohit; Rhodes, Elizabeth; Alousi, Mohammed; Sivakumar, Bran

    2017-01-01

    Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

    Science.gov (United States)

    Kumar, Sunil; Kang, T. W.; Bala, Suman; Kamboj, Sunil; Jeon, H. C.

    2018-04-01

    A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

  19. Treatment of Childhood Diarrhoea by Operators of Drug Stores in ...

    African Journals Online (AJOL)

    We recommend an urgent program of intervention targeted specifically at drug store operator/attendants on the management of diarrhoea in the short term while ORT instructions and management of diarrhoea be incorporated into health education curriculum in primary and secondary schools in Nigeria. Nigerian Medical ...

  20. Free software to analyse the clinical relevance of drug interactions with antiretroviral agents (SIMARV®) in patients with HIV/AIDS.

    Science.gov (United States)

    Giraldo, N A; Amariles, P; Monsalve, M; Faus, M J

    Highly active antiretroviral therapy has extended the expected lifespan of patients with HIV/AIDS. However, the therapeutic benefits of some drugs used simultaneously with highly active antiretroviral therapy may be adversely affected by drug interactions. The goal was to design and develop a free software to facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. A comprehensive Medline/PubMed database search of drug interactions was performed. Articles that recognized any drug interactions in HIV disease were selected. The publications accessed were limited to human studies in English or Spanish, with full texts retrieved. Drug interactions were analyzed, assessed, and grouped into four levels of clinical relevance according to gravity and probability. Software to systematize the information regarding drug interactions and their clinical relevance was designed and developed. Overall, 952 different references were retrieved and 446 selected; in addition, 67 articles were selected from the citation lists of identified articles. A total of 2119 pairs of drug interactions were identified; of this group, 2006 (94.7%) were drug-drug interactions, 1982 (93.5%) had an identified pharmacokinetic mechanism, and 1409 (66.5%) were mediated by enzyme inhibition. In terms of clinical relevance, 1285 (60.6%) drug interactions were clinically significant in patients with HIV (levels 1 and 2). With this information, a software program that facilitates identification and assessment of the clinical relevance of antiretroviral drug interactions (SIMARV ® ) was developed. A free software package with information on 2119 pairs of antiretroviral drug interactions was designed and developed that could facilitate analysis, assessment, and clinical decision making according to the clinical relevance of drug interactions in patients with HIV/AIDS. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Perhaps More Consideration of Pavlovian-Operant Interaction May Improve the Clinical Efficacy of Behaviorally Based Drug Treatment Programs.

    Science.gov (United States)

    Troisi, Joseph R

    2013-01-01

    Drug abuse remains costly. Drug-related cues can evoke cue-reactivity and craving, contributing to relapse. The Pavlovian extinction-based cue-exposure therapy (CET) has not been very successful in treating drug abuse. A functional operant analysis of complex rituals involved in CET is outlined and reinterpreted as an operant heterogeneous chain maintained by observing responses, conditioned reinforcers, and discriminative stimuli. It is further noted that operant functions are not predicated on Pavlovian processes but can be influenced by them in contributing to relapse; several empirical studies from the animal and human literature highlight this view. Cue-reactivity evoked by Pavlovian processes is conceptualized as an operant establishing/motivating operation. CET may be more effective in incorporating an operant-based approach that takes into account the complexity of Pavlovian-operant interaction. Extinction of the operant chain coupled with the shaping of alternative behaviors is proposed as an integrated therapy. It is proposed that operant-based drug abuse treatments (contingency management, voucher programs, and the therapeutic work environment) might consider incorporating cue-reactivity, as establishing/motivating operations, to increase long-term success-a hybrid approach based on Pavlovian-operant interaction.

  2. Perhaps More Consideration of Pavlovian–Operant Interaction May Improve the Clinical Efficacy of Behaviorally Based Drug Treatment Programs

    Science.gov (United States)

    Troisi, Joseph R.

    2014-01-01

    Drug abuse remains costly. Drug-related cues can evoke cue-reactivity and craving, contributing to relapse. The Pavlovian extinction-based cue-exposure therapy (CET) has not been very successful in treating drug abuse. A functional operant analysis of complex rituals involved in CET is outlined and reinterpreted as an operant heterogeneous chain maintained by observing responses, conditioned reinforcers, and discriminative stimuli. It is further noted that operant functions are not predicated on Pavlovian processes but can be influenced by them in contributing to relapse; several empirical studies from the animal and human literature highlight this view. Cue-reactivity evoked by Pavlovian processes is conceptualized as an operant establishing/motivating operation. CET may be more effective in incorporating an operant-based approach that takes into account the complexity of Pavlovian–operant interaction. Extinction of the operant chain coupled with the shaping of alternative behaviors is proposed as an integrated therapy. It is proposed that operant-based drug abuse treatments (contingency management, voucher programs, and the therapeutic work environment) might consider incorporating cue-reactivity, as establishing/motivating operations, to increase long-term success—a hybrid approach based on Pavlovian–operant interaction. PMID:25346551

  3. Stable operation of a Secure QKD system in the real-world setting

    Science.gov (United States)

    Tomita, Akihisa

    2007-06-01

    Quantum Key Distribution (QKD) now steps forward from the proof of principle to the validation of the practical feasibility. Nevertheless, the QKD technology should respond to the challenges from the real-world such as stable operation against the fluctuating environment, and security proof under the practical setting. We report our recent progress on stable operation of a QKD system, and key generation with security assurance. A QKD system should robust to temperature fluctuation in a common office environment. We developed a loop-mirror, a substitution of a Faraday mirror, to allow easy compensation for the temperature dependence of the device. Phase locking technique was also employed to synchronize the system clock to the quantum signals. This technique is indispensable for the transmission system based on the installed fiber cables, which stretch and shrink due to the temperature change. The security proof of QKD, however, has assumed the ideal conditions, such as the use of a genuine single photon source and/or unlimited computational resources. It has been highly desirable to give an assurance of security for practical systems, where the ideal conditions are no longer satisfied. We have constructed a theory to estimate the leakage information on the transmitted key under the practically attainable conditions, and have developed a QKD system equipped with software for secure key distillation. The QKD system generates the final key at the rate of 2000 bps after 20 km fiber transmission. Eavesdropper's information on the final key is guaranteed to be less than 2-7 per bit. This is the first successful generation of the secure key with quantitative assurance of the upper bound of the leakage information. It will put forth the realization of highly secure metropolitan optical communication network against any types of eavesdropping.

  4. Adiabatic evolution of decoherence-free subspaces and its shortcuts

    Science.gov (United States)

    Wu, S. L.; Huang, X. L.; Li, H.; Yi, X. X.

    2017-10-01

    The adiabatic theorem and shortcuts to adiabaticity for time-dependent open quantum systems are explored in this paper. Starting from the definition of dynamical stable decoherence-free subspace, we show that, under a compact adiabatic condition, the quantum state remains in the time-dependent decoherence-free subspace with an extremely high purity, even though the dynamics of the open quantum system may not be adiabatic. The adiabatic condition mentioned here in the adiabatic theorem for open systems is very similar to that for closed quantum systems, except that the operators required to change slowly are the Lindblad operators. We also show that the adiabatic evolution of decoherence-free subspaces depends on the existence of instantaneous decoherence-free subspaces, which requires that the Hamiltonian of open quantum systems be engineered according to the incoherent control protocol. In addition, shortcuts to adiabaticity for adiabatic decoherence-free subspaces are also presented based on the transitionless quantum driving method. Finally, we provide an example that consists of a two-level system coupled to a broadband squeezed vacuum field to show our theory. Our approach employs Markovian master equations and the theory can apply to finite-dimensional quantum open systems.

  5. Air-stable memory array of bistable rectifying diodes based on ferroelectric-semiconductor polymer blends

    Science.gov (United States)

    Kumar, Manasvi; Sharifi Dehsari, Hamed; Anwar, Saleem; Asadi, Kamal

    2018-03-01

    Organic bistable diodes based on phase-separated blends of ferroelectric and semiconducting polymers have emerged as promising candidates for non-volatile information storage for low-cost solution processable electronics. One of the bottlenecks impeding upscaling is stability and reliable operation of the array in air. Here, we present a memory array fabricated with an air-stable amine-based semiconducting polymer. Memory diode fabrication and full electrical characterizations were carried out in atmospheric conditions (23 °C and 45% relative humidity). The memory diodes showed on/off ratios greater than 100 and further exhibited robust and stable performance upon continuous write-read-erase-read cycles. Moreover, we demonstrate a 4-bit memory array that is free from cross-talk with a shelf-life of several months. Demonstration of the stability and reliable air operation further strengthens the feasibility of the resistance switching in ferroelectric memory diodes for low-cost applications.

  6. Pentacene appended to a TEMPO stable free radical: the effect of magnetic exchange coupling on photoexcited pentacene.

    Science.gov (United States)

    Chernick, Erin T; Casillas, Rubén; Zirzlmeier, Johannes; Gardner, Daniel M; Gruber, Marco; Kropp, Henning; Meyer, Karsten; Wasielewski, Michael R; Guldi, Dirk M; Tykwinski, Rik R

    2015-01-21

    Understanding the fundamental spin dynamics of photoexcited pentacene derivatives is important in order to maximize their potential for optoelectronic applications. Herein, we report on the synthesis of two pentacene derivatives that are functionalized with the [(2,2,6,6-tetramethylpiperidin-1-yl)oxy] (TEMPO) stable free radical. The presence of TEMPO does not quench the pentacene singlet excited state, but does quench the photoexcited triplet excited state as a function of TEMPO-to-pentacene distance. Time-resolved electron paramagnetic resonance experiments confirm that triplet quenching is accompanied by electron spin polarization transfer from the pentacene excited state to the TEMPO doublet state in the weak coupling regime.

  7. Complexation of Polyelectrolytes with Hydrophobic Drug Molecules in Salt-Free Solution: Theory and Simulations.

    Science.gov (United States)

    Lei, Qun-Li; Hadinoto, Kunn; Ni, Ran

    2017-04-18

    The delivery and dissolution of poorly soluble drugs is challenging in the pharmaceutical industry. One way to significantly improve the delivery efficiency is to incorporate these hydrophobic small molecules into a colloidal polyelectrolyes(PE)-drug complex in their ionized states. Despite its huge application value, the general mechanism of PE collapse and complex formation in this system has not been well understood. In this work, by combining a mean-field theory with extensive molecular simulations, we unveil the phase behaviors of the system under dilute and salt-free conditions. We find that the complexation is a first-order-like phase transition triggered by the hydrophobic attraction between the drug molecules. Importantly, the valence ratio between the drug molecule and PE monomer plays a crucial role in determining the stability and morphology of the complex. Moreover, the sign of the zeta potential and the net charge of the complex are found to be inverted as the hydrophobicity of the drug molecules increases. Both theory and simulation indicate that the complexation point and complex morphology and the electrostatic properties of the complex have a weak dependence on chain length. Finally, the dynamics aspect of PE-drug complexation is also explored, and it is found that the complex can be trapped into a nonequilibrium glasslike state when the hydropobicity of the drug molecule is too strong. Our work gives a clear physical picture behind the PE-drug complexation phenomenon and provides guidelines to fabricate the colloidal PE-drug complex with the desired physical characteristics.

  8. A GALA lipopeptide mediates pH- and membrane charge dependent fusion with stable giant unilamellar vesicles

    DEFF Research Database (Denmark)

    Etzerodt, Thomas P.; Trier, Sofie; Henriksen, Jonas R.

    2012-01-01

    sporadic and there is a strong need to characterize and increase our understanding of the membrane fusion properties of these peptides. Many fusion studies have focused on the ability of free peptides in solution that mediate fusion between liposomes. For drug delivery purposes it is a necessity to attach......,2-diamino propanoic acid (Dap) moiety, yielding the lipopeptide dimyristoyl-Dap-GALA (DMDGALA). We have investigated DMDGALA as a component in large unilamellar vesicles (LUVs) and demonstrate pH-triggered fusion of peptide containing LUVs with stable target giant unilamellar vesicles (GUVs), which were...

  9. A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

    Science.gov (United States)

    Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

    2016-06-01

    The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Auditory verbal learning in drug-free Ecstasy polydrug users.

    Science.gov (United States)

    Fox, H. C.; Toplis, A. S.; Turner, J. J. D.; Parrott, A. C.

    2001-12-01

    Drug-free Ecstasy polydrug users have shown impairment on tasks of verbal working memory and memory span. Current research aims to investigate how these deficits may affect the learning of verbal material by administration of the Auditory Verbal Learning Task (AVLT) (Rey, 1964). The task provides a learning curve by assessing immediate memory span over multiple trials. Learning strategies are further analysed by tendencies to confabulate as well as demonstrate either proactive or retroactive interference elicited by a novel 'distractor' list. Three groups completed the task: two groups of 14 Ecstasy users (short- and long-term) and one group of 14 polydrug controls. Compared with controls both Ecstasy groups recalled significantly fewer words and made more confabulation errors on the initial three recall trials as well as a delayed recall trial. Long-term users demonstrated increased confabulation on the initial trials and the novel 'distractor7' trial, compared with short-term users. Only following repeated presentations were both short- and long-term users shown to perform at control levels. As such, deficits in verbal learning may be more related to storage and/or retrieval problems than problems associated with capacity per se. No interference errors were demonstrated by either of the Ecstasy groups. However, a high level of intrusion errors may indicate selective working memory problems associated with longer-term use of the drug. Copyright 2001 John Wiley & Sons, Ltd.

  11. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  12. Hydrogels synthesised through photoinitiator-free photopolymerisation technique for delivering drugs including a tumour-tracing porphyrin

    International Nuclear Information System (INIS)

    Ng, Loo-Teck; Swami, Salesh; Gordon-Thomson, Clare

    2006-01-01

    Hydrogels were synthesised using the photoinitiator-free photopolymerisation technique involving interactions between donor/acceptor pairs for delivering drugs of different molecular weights including a porphyrin used as a tumour-tracing agent. N-(5-hydroxy) pentylmaleimide, an acceptor, formed hydrogels with N-vinyl-2-pyrrolidinone, 2-hydroxyethyl methacrylate and N-vinylcaprolactum. Glucosamine, an effective H-donor in enhancing polymerisation as shown by Differential Photocalorimetric results, was found unsuitable for hydrogel preparation. Drugs of different molecular weights releasing at the same rate was discussed. The hydrogels were found to have no toxic effects and were biocompatible with a human keratinocyte cell line

  13. Free radicals, oxygen and radiosensitizing drugs: a very brief introduction

    International Nuclear Information System (INIS)

    Willson, R.

    1981-01-01

    A review is presented of the historical aspects of the search for radiation sensitizing drugs. Metronidazole, Flagyl and misonidazole are undergoing clincial trials as the result of basic free radical and cellular research. Studies at the molecular, biochemical and cellular levels are described. From the information obtained it now appears that several processes may be involved in sensitization: interference with charge recombination due to a sensitizer having a high electron affinity; an increase in the yield of oxidizing hydroxyl radicals by electron sequestration; interference with radical combination reactions due to a sensitizer having a high one electron oxidation potential; oxidation or organic radicals so fixing them; formation of products which are toxic; and changes in the biochemistry of the cell. 106 references, 4 figures

  14. Highly air stable passivation of graphene based field effect devices.

    Science.gov (United States)

    Sagade, Abhay A; Neumaier, Daniel; Schall, Daniel; Otto, Martin; Pesquera, Amaia; Centeno, Alba; Elorza, Amaia Zurutuza; Kurz, Heinrich

    2015-02-28

    The sensitivity of graphene based devices to surface adsorbates and charge traps at the graphene/dielectric interface requires proper device passivation in order to operate them reproducibly under ambient conditions. Here we report on the use of atomic layer deposited aluminum oxide as passivation layer on graphene field effect devices (GFETs). We show that successful passivation produce hysteresis free DC characteristics, low doping level GFETs stable over weeks though operated and stored in ambient atmosphere. This is achieved by selecting proper seed layer prior to deposition of encapsulation layer. The passivated devices are also demonstrated to be robust towards the exposure to chemicals and heat treatments, typically used during device fabrication. Additionally, the passivation of high stability and reproducible characteristics is also shown for functional devices like integrated graphene based inverters.

  15. A Proposal of Operational Risk Management Method Using FMEA for Drug Manufacturing Computerized System

    Science.gov (United States)

    Takahashi, Masakazu; Nanba, Reiji; Fukue, Yoshinori

    This paper proposes operational Risk Management (RM) method using Failure Mode and Effects Analysis (FMEA) for drug manufacturing computerlized system (DMCS). The quality of drug must not be influenced by failures and operational mistakes of DMCS. To avoid such situation, DMCS has to be conducted enough risk assessment and taken precautions. We propose operational RM method using FMEA for DMCS. To propose the method, we gathered and compared the FMEA results of DMCS, and develop a list that contains failure modes, failures and countermeasures. To apply this list, we can conduct RM in design phase, find failures, and conduct countermeasures efficiently. Additionally, we can find some failures that have not been found yet.

  16. Spatial distribution of theobromine--a low MW drug--in tissues via matrix-free NALDI-MS imaging.

    Science.gov (United States)

    Tata, Alessandra; Montemurro, Chiara; Porcari, Andreia M; Silva, Kamila C; Lopes de Faria, José B; Eberlin, Marcos N

    2014-09-01

    The ability of nano-assisted laser desorption-ionization mass spectrometry imaging (NALDI-IMS) to provide selective chemical monitoring with appropriate spatial distribution of a low molecular drug in a biological tissue was investigated. NALDI-IMS is a matrix-free laser desorption ionization (LDI) protocol based on imprinting of tissue constituents on a nanostructured surface. Using the accumulation of theobromine in rat kidney as a model, NALDI-IMS was found to provide well-resolved images of the special distribution of this low molecular weight (MW) drug in tissue. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

    International Nuclear Information System (INIS)

    2016-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  18. Comparison of Therapeutic Effect of Anti-Cryptosporidium Nano-Nitazoxanide (NTZ with Free form of this Drug in Neonatal Rat

    Directory of Open Access Journals (Sweden)

    F. Sedighi

    2016-07-01

    Full Text Available Introduction & Objective: Cryptosporidiosis caused by Cryptosporidium, which is a protozoan parasite, has a worldwide distribution. The infection is through fecal-oral route, direct or indi-rect contact, food or water. The treatment of cryptosporidiosis is difficult and the anti-parasitic agents are not effective. The purpose of this study was encapsulation of nitazoxanide in solid lipid nano-particles (SLN and investigation of its anti-Cryptosporidium effect and its comparison with free drug in the neonatal rat. Materials & Methods: Nitazoxanide was encapsulated by HPH method with 2 mg/Kg concentra-tion in SLN nanoparticles. The oocysts were collected from calves and purified by sucrose floatation. A total of 72 Wistar neonatal rats were categorized in 6 groups of 12 rats including four infected groups treated by free drug, encapsulated nano drug, colloidal carriers without drug (SLN and olive oil; an infected control group and a healthy control group that received PBS. 5 × 105 of oocyts inoculated orally into the sample groups. Finally, intestine of each rat was homogenized in PBS by rotor and the homogenized material was passed through a sieve. Then, floated oocysts in sucrose solution were counted by hemocytometer. Results: Treatment by nitazoxanide significantly decreased the number of parasites in the treatment groups. This decrease at day 6 was more than day 3. Nano nitazoxanide had more effects on parasites than free drug. This difference at day 3 of treatment was not significant (p= 0.182 but at day 6 was statistically significant (P< 0.001. Conclusion: Using nano-nitazoxanide could be a more effective way in the treatment of Cryp-tosporidium infections. (Sci J Hamadan Univ Med Sci 2016; 23 (2:134-140

  19. Drug Facts

    Medline Plus

    Full Text Available ... Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used Drugs in the Past Drug Use ... Videos Information About Drugs Alcohol ...

  20. Ethanol self-administration in free-flying honeybees (Apis mellifera L.) in an operant conditioning protocol.

    Science.gov (United States)

    Sokolowski, Michel B C; Abramson, Charles I; Craig, David Philip Arthur

    2012-09-01

    This study examines the effect of ethanol (EtOH) on continuous reinforcement schedules in the free-flying honeybee (Apis mellifera L.). As fermented nectars may be encountered naturally in the environment, we designed an experiment combining the tools of laboratory research with minimal disturbance to the natural life of honeybees. Twenty-five honeybees were trained to fly from their colonies to a fully automated operant chamber with head poking as the operant response. Load size, intervisit interval, and interresponse times (IRTs) served as the dependent variables and were monitored over the course of a daily training session consisting of many visits. Experimental bees were tested using an ABA design in which sucrose only was administered during condition A and a 5% EtOH sucrose solution was administered during condition B. Control bees received sucrose solution only. Most bees continued to forage after EtOH introduction. EtOH significantly reduced the load size and the intervisit interval with no significant effect on IRTs. However, a look on individual data shows large individual differences suggesting the existence of different kinds of behavioral phenotypes linked to EtOH consumption and effects. Our results contribute to the study of EtOH consumption as a normal phenomenon in an ecological context and open the door to schedule-controlled drug self-administration studies in honeybees. Copyright © 2012 by the Research Society on Alcoholism.

  1. Development of new S-band RF window for stable high-power operation in linear accelerator RF system

    Science.gov (United States)

    Joo, Youngdo; Lee, Byung-Joon; Kim, Seung-Hwan; Kong, Hyung-Sup; Hwang, Woonha; Roh, Sungjoo; Ryu, Jiwan

    2017-09-01

    For stable high-power operation, a new RF window is developed in the S-band linear accelerator (Linac) RF systems of the Pohang Light Source-II (PLS-II) and the Pohang Accelerator Laboratory X-ray Free-Electron Laser (PAL-XFEL). The new RF window is designed to mitigate the strength of the electric field at the ceramic disk and also at the waveguide-cavity coupling structure of the conventional RF window. By replacing the pill-box type cavity in the conventional RF window with an overmoded cavity, the electric field component perpendicular to the ceramic disk that caused most of the multipacting breakdowns in the ceramic disk was reduced by an order of magnitude. The reduced electric field at the ceramic disk eliminated the Ti-N coating process on the ceramic surface in the fabrication procedure of the new RF window, preventing the incomplete coating from spoiling the RF transmission and lowering the fabrication cost. The overmoded cavity was coupled with input and output waveguides through dual side-wall coupling irises to reduce the electric field strength at the waveguide-cavity coupling structure and the possibility of mode competitions in the overmoded cavity. A prototype of the new RF window was fabricated and fully tested with the Klystron peak input power, pulse duration and pulse repetition rate of 75 MW, 4.5 μs and 10 Hz, respectively, at the high-power test stand. The first mass-produced new RF window installed in the PLS-II Linac is running in normal operation mode. No fault is reported to date. Plans are being made to install the new RF window to all S-band accelerator RF modules of the PLS-II and PAL-XFEL Linacs. This new RF window may be applied to the output windows of S-band power sources like Klystron as wells as the waveguide windows of accelerator facilities which operate in S-band.

  2. Stable, high-order computation of impedance-impedance operators for three-dimensional layered medium simulations

    Science.gov (United States)

    Nicholls, David P.

    2018-04-01

    The faithful modelling of the propagation of linear waves in a layered, periodic structure is of paramount importance in many branches of the applied sciences. In this paper, we present a novel numerical algorithm for the simulation of such problems which is free of the artificial singularities present in related approaches. We advocate for a surface integral formulation which is phrased in terms of impedance-impedance operators that are immune to the Dirichlet eigenvalues which plague the Dirichlet-Neumann operators that appear in classical formulations. We demonstrate a high-order spectral algorithm to simulate these latter operators based upon a high-order perturbation of surfaces methodology which is rapid, robust and highly accurate. We demonstrate the validity and utility of our approach with a sequence of numerical simulations.

  3. Stable, high-order computation of impedance-impedance operators for three-dimensional layered medium simulations.

    Science.gov (United States)

    Nicholls, David P

    2018-04-01

    The faithful modelling of the propagation of linear waves in a layered, periodic structure is of paramount importance in many branches of the applied sciences. In this paper, we present a novel numerical algorithm for the simulation of such problems which is free of the artificial singularities present in related approaches. We advocate for a surface integral formulation which is phrased in terms of impedance-impedance operators that are immune to the Dirichlet eigenvalues which plague the Dirichlet-Neumann operators that appear in classical formulations. We demonstrate a high-order spectral algorithm to simulate these latter operators based upon a high-order perturbation of surfaces methodology which is rapid, robust and highly accurate. We demonstrate the validity and utility of our approach with a sequence of numerical simulations.

  4. Radiation-induced free radical reactions in polymer/drug systems for controlled release: an EPR investigation

    Energy Technology Data Exchange (ETDEWEB)

    Faucitano, A. E-mail: chemrad@unipv.it; Buttafava, A.; Montanari, L.; Cilurzo, F.; Conti, B.; Genta, I.; Valvo, L

    2003-05-01

    The primary and secondary free radical intermediates in the gamma radiolysis of poly(D,L-lactide-co-glycolide) (PLGA) and clonazepam loaded PLGA microspheres were investigated by matrix EPR spectroscopy in the temperature range 77-298 K. Drug-polymer interactions were found to be important leading to significant deviations of the G(radicals) from the additivity law. In particular, in the mixed system a stabilization of the polymer matrix with respect to the radiation damage was detected, witnessed by a decrease of the overall polymer radicals yield which is accompanied by an increase of the drug radicals yield. These effects have been attributed to the scavenging properties of the nitro group with respect to electrons and polymer radicals. It is conceivable that such conclusions be of general application for all pharmaceutical formulations containing drugs bearing nitro groups in their chemical structure.

  5. Formulation of stable protein powders by supercritical fluid drying

    NARCIS (Netherlands)

    Jovanović, N.

    2007-01-01

    Protein pharmaceuticals are potent drugs for the treatment of several chronic and life-threatening diseases. However, the complex and sensitive nature of protein molecules requires special attention in the development of stable dosage forms. Developing stable aqueous protein formulations is often a

  6. Uses of stable isotopes

    International Nuclear Information System (INIS)

    Axente, Damian

    1998-01-01

    The most important fields of stable isotope use with examples are presented. These are: 1. Isotope dilution analysis: trace analysis, measurements of volumes and masses; 2. Stable isotopes as tracers: transport phenomena, environmental studies, agricultural research, authentication of products and objects, archaeometry, studies of reaction mechanisms, structure and function determination of complex biological entities, studies of metabolism, breath test for diagnostic; 3. Isotope equilibrium effects: measurement of equilibrium effects, investigation of equilibrium conditions, mechanism of drug action, study of natural processes, water cycle, temperature measurements; 4. Stable isotope for advanced nuclear reactors: uranium nitride with 15 N as nuclear fuel, 157 Gd for reactor control. In spite of some difficulties of stable isotope use, particularly related to the analytical techniques, which are slow and expensive, the number of papers reporting on this subject is steadily growing as well as the number of scientific meetings organized by International Isotope Section and IAEA, Gordon Conferences, and regional meeting in Germany, France, etc. Stable isotope application development on large scale is determined by improving their production technologies as well as those of labeled compound and the analytical techniques. (author)

  7. Cold vacuum drying residual free water test description

    International Nuclear Information System (INIS)

    Pajunen, A.L.

    1997-01-01

    Residual free water expected to remain in a Multi-Canister Overpack (MCO) after processing in the Cold Vacuum Drying (CVD) Facility is investigated based on three alternative models of fuel crevices. Tests and operating conditions for the CVD process are defined based on the analysis of these models. The models consider water pockets constrained by cladding defects, water constrained in a pore or crack by flow through a porous bed, and water constrained in pores by diffusion. An analysis of comparative reaction rate constraints is also presented indicating that a pressure rise test can be used to show MCO's will be thermally stable at operating temperatures up to 75 C

  8. Multi-stable perception balances stability and sensitivity

    Directory of Open Access Journals (Sweden)

    Alexander ePastukhov

    2013-03-01

    Full Text Available We report that multi-stable perception operates in a consistent, dynamical regime, balancing the conflicting goals of stability and sensitivity. When a multi-stable visual display is viewed continuously, its phenomenal appearance reverses spontaneously at irregular intervals. We characterized the perceptual dynamics of individual observers in terms of four statistical measures: the distribution of dominance times (mean and variance and the novel, subtle dependence on prior history (correlation and time-constant.The dynamics of multi-stable perception is known to reflect several stabilizing and destabilizing factors. Phenomenologically, its main aspects are captured by a simplistic computational model with competition, adaptation, and noise. We identified small parameter volumes (~3% of the possible volume in which the model reproduced both dominance distribution and history-dependence of each observer. For 21 of 24 data sets, the identified volumes clustered tightly (~15% of the possible volume, revealing a consistent `operating regime' of multi-stable perception. The `operating regime' turned out to be marginally stable or, equivalently, near the brink of an oscillatory instability. The chance probability of the observed clustering was <0.02.To understand the functional significance of this empirical `operating regime', we compared it to the theoretical `sweet spot' of the model. We computed this `sweet spot' as the intersection of the parameter volumes in which the model produced stable perceptual outcomes and in which it was sensitive to input modulations. Remarkably, the empirical `operating regime' proved to be largely coextensive with the theoretical `sweet spot'. This demonstrated that perceptual dynamics was not merely consistent but also functionally optimized (in that it balances stability with sensitivity. Our results imply that multi-stable perception is not a laboratory curiosity, but reflects a functional optimization of perceptual

  9. Conflict Resolution Performance in an Experimental Study of En Route Free Maneuvering Operations

    Science.gov (United States)

    Doble, Nathan A.; Barhydt, Richard; Hitt, James M., II

    2005-01-01

    NASA has developed a far-term air traffic management concept, termed Distributed Air/Ground Traffic Management (DAG-TM). One component of DAG-TM, En Route Free Maneuvering, allows properly trained flight crews of equipped autonomous aircraft to assume responsibility for separation from other autonomous aircraft and from Instrument Flight Rules (IFR) aircraft. Ground-based air traffic controllers continue to separate IFR traffic and issue flow management constraints to all aircraft. To examine En Route Free Maneuvering operations, a joint human-in-the-loop experiment was conducted in summer 2004 at the NASA Ames and Langley Research Centers. Test subject pilots used desktop flight simulators to resolve traffic conflicts and adhere to air traffic flow constraints issued by subject controllers. The experimental airspace integrated both autonomous and IFR aircraft at varying traffic densities. This paper presents a subset of the En Route Free Maneuvering experimental results, focusing on airborne and ground-based conflict resolution, and the effects of increased traffic levels on the ability of pilots and air traffic controllers to perform this task. The results show that, in general, increases in autonomous traffic do not significantly impact conflict resolution performance. In addition, pilot acceptability of autonomous operations remains high throughout the range of traffic densities studied. Together with previously reported findings, these results continue to support the feasibility of the En Route Free Maneuvering component of DAG-TM.

  10. Urinary cotinine testing as pre-operative assessment of patients undergoing free flap surgery.

    Science.gov (United States)

    Reinbold, C; Rausky, J; Binder, J-P; Revol, M

    2015-02-01

    The identified risks of smoking with regard to operated tissues are so elevated that it is clearly dangerous to operate a smoker when the proposed intervention is neither vital nor urgent. The aim of this prospective study was to evaluate a simple method of screening patients who smoke, with the evaluation carried out before agreeing to carry out free tissue transfer. The purpose of the testing was to hold the patient responsible for his actions and minimize smoking-related complications by cancelling or postponing the planned operation if the patient continued to smoke. Screening included use of a standardized questionnaire at the first consultation and detection of cotinine using a urine test strip 7 days before the scheduled surgery. Patients were informed that in the event of positive results, the operation would not take place. A six-week preoperative smoking cessation period was mandatory. Seventy-six patients were included in this study. Among them, 25 (32.9%) reported being former smokers and 11 (14.5%) admitted in the initial questionnaire to being active smokers. Six patients (7.9%), including one self-reported non-smoker, tested positive for cotinine, and their operations were cancelled. Screening using a questionnaire and cotinine detection appeared to constitute a simple, inexpensive, rapid and reliable test. It allowed us to refuse to operate 6 non-compliant patients and was thereby likely to diminish morbidity in the free tissue transfers carried out in our ward. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Coincidence of role expectations between staff and volunteer members of drug free community coalitions.

    Science.gov (United States)

    Goldstein, Marc B; Sapere, Heather; Daviau, John

    2017-08-01

    Community coalitions have proliferated as a means of addressing a range of complex community problems. Such coalitions often consist of a small paid staff and volunteer members. The present study examines one likely contributor to coalition effectiveness: the degree of agreement on role expectations between paid staff and volunteer members. Role confusion occurs when paid staff and volunteers differ in their expectations of who is responsible for accomplishing specific tasks. Staff and volunteer members from 69 randomly selected Drug Free Coalitions in the United States as well as 21 Drug Free Coalitions in Connecticut were asked to respond to an online survey asking about 37 specific coalition tasks critical for effective coalition functioning and the degree to which paid staff and/or voluntary members should be responsible for accomplishing each. Our final sample consisted of 476 individuals from 35 coalitions. Using coalitions as the unit of analysis, we found significant differences between paid staff and volunteer coalition members on nine tasks reflecting four domains: meeting leadership and participation, (2) planning and implementation leadership, (3) publicity/media relations, and (4) logistical functions. Implications of these differences and ways that evaluators could help coalitions deal with differing role expectations were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  13. Label-free detection of protein biomolecules secreted from a heart-on-a-chip model for drug cardiotoxicity evaluation

    Science.gov (United States)

    DeLuna, Frank; Zhang, Yu Shrike; Bustamante, Gilbert; Li, Le; Lauderdale, Matthew; Dokmeci, Mehmet R.; Khademhosseini, Ali; Ye, Jing Yong

    2018-02-01

    Efficient methods for the accurate analysis of drug toxicities are in urgent demand as failures of newly discovered drug candidates due to toxic side effects have resulted in about 30% of clinical attrition. The high failure rate is partly due to current inadequate models to study drug side effects, i.e., common animal models may fail due to its misrepresentation of human physiology. Therefore, much effort has been allocated in the development of organ-on-a-chip models which offer a variety of human organ models mimicking a multitude of human physiological conditions. However, it is extremely challenging to analyze the transient and long-term response of the organ models to drug treatments during drug toxicity tests, as the proteins secreted from the organ-on-a-chip model are minute due to its volumetric size, and current methods for detecting said biomolecules are not suitable for real-time monitoring. As protein biomolecules are being continuously secreted from the human organ model, fluorescence techniques are practically impossible to achieve real-time fluorescence labeling in the dynamically changing environment, thus making a label-free approach highly desirable for the organ-on-achip applications. In this paper, we report the use of a photonic-crystal biosensor integrated with a microfluidic system for sensitive label-free bioassays of secreted protein biomolecules from a heart-on-the-chip model created with cardiomyocytes derived from human induced pluripotent stem cells.

  14. 26 S proteasomes function as stable entities

    DEFF Research Database (Denmark)

    Hendil, Klavs B; Hartmann-Petersen, Rasmus; Tanaka, Keiji

    2002-01-01

    , shuttles between a free state and the 26-S proteasome, bringing substrate to the complex. However, S5a was not found in the free state in HeLa cells. Besides, all subunits in PA700, including S5a, exchanged at similar low rates. It therefore seems that 26-S proteasomes function as stable entities during...

  15. Multivariate Stable Isotope Analysis to Determine Linkages between Benzocaine Seizures

    Science.gov (United States)

    Kemp, H. F.; Meier-Augenstein, W.; Collins, M.; Salouros, H.; Cunningham, A.; Harrison, M.

    2012-04-01

    In July 2010, a woman was jailed for nine years in the UK after the prosecution successfully argued that attempting to import a cutting agent was proof of involvement in a conspiracy to supply Cocaine. That landmark ruling provided law enforcement agencies with much greater scope to tackle those involved in this aspect of the drug trade, specifically targeting those importing the likes of benzocaine or lidocaine. Huge quantities of these compounds are imported into the UK and between May and August 2010, four shipments of Benzocaine amounting to more then 4 tons had been seized as part of Operation Kitley, a joint initiative between the UK Border Agency and the Serious Organised Crime Agency (SOCA). By diluting cocaine, traffickers can make it go a lot further for very little cost, leading to huge profits. In recent years, dealers have moved away from inert substances, like sugar and baby milk powder, in favour of active pharmaceutical ingredients (APIs), including anaesthetics like Benzocaine and Lidocaine. Both these mimic the numbing effect of cocaine, and resemble it closely in colour, texture and some chemical behaviours, making it easier to conceal the fact that the drug has been diluted. API cutting agents have helped traffickers to maintain steady supplies in the face of successful interdiction and even expand the market in the UK, particularly to young people aged from their mid teens to early twenties. From importation to street-level, the purity of the drug can be reduced up to a factor of 80 and street level cocaine can have a cocaine content as low as 1%. In view of the increasing use of Benzocaine as cutting agent for Cocaine, a study was carried out to investigate if 2H, 13C, 15N and 18O stable isotope signatures could be used in conjunction with multivariate chemometric data analysis to determine potential linkage between benzocaine exhibits seized from different locations or individuals to assist with investigation and prosecution of drug

  16. 75 FR 6006 - Office of Safe and Drug-Free Schools; Cooperative Civic Education and Economic Education Exchange...

    Science.gov (United States)

    2010-02-05

    ... DEPARTMENT OF EDUCATION Office of Safe and Drug-Free Schools; Cooperative Civic Education and Economic Education Exchange Program Catalog of Federal Domestic Assistance (CFDA) Number: 84.304A. ACTION... the Cooperative Civic Education and Economic Education Exchange Program. The notice stated that a list...

  17. Monolithic Highly Stable Yb-Doped Femtosecond Fiber Lasers for Applications in Practical Biophotonics

    DEFF Research Database (Denmark)

    Liu, Xiaomin; Lægsgaard, Jesper; Turchinovich, Dmitry

    2012-01-01

    in the development of all-fiber nonlinear-optical laser control schemes, which resulted in the demonstration of highly stable monolithic, i.e., not containing any free-space elements, lasers with direct fiber-end delivery of femtosecond pulses. This paper provides an overview of the progress in the development...... of such all-fiber mode-locked lasers based on Yb-fiber as gain medium, operating at the wavelength around 1 $\\mu$m, and delivering femtosecond pulses reaching tens of nanojoules of energy.......Operational and environmental stability of ultrafast laser systems is critical for their applications in practical biophotonics. Mode-locked fiber lasers show great promise in applications such as supercontinuum sources or multiphoton microscopy systems. Recently, substantial progress has been made...

  18. An experimental study of the stable and unstable operation of an LPP gas turbine combustor

    Science.gov (United States)

    Dhanuka, Sulabh Kumar

    A study was performed to better understand the stable operation of an LPP combustor and formulate a mechanism behind the unstable operation. A unique combustor facility was developed at the University of Michigan that incorporates the latest injector developed by GE Aircraft Engines and enables operation at elevated pressures with preheated air at flow-rates reflective of actual conditions. The large optical access has enabled the use of a multitude of state-of-the-art laser diagnostics such as PIV and PLIF, and has shed invaluable light not only into the GE injector specifically but also into gas turbine combustors in general. Results from Particle Imaging Velocimetry (PIV) have illustrated the role of velocity, instantaneous vortices, and key recirculation zones that are all critical to the combustor's operation. It was found that considerable differences exist between the iso-thermal and reacting flows, and between the instantaneous and mean flow fields. To image the flame, Planar Laser Induced Fluorescence (PLIF) of the formaldehyde radical was successfully utilized for the first time in a Jet-A flame. Parameters regarding the flame's location and structure have been obtained that assist in interpreting the velocity results. These results have also shown that some of the fuel injected from the main fuel injectors actually reacts in the diffusion flame of the pilot. The unstable operation of the combustor was studied in depth to obtain the stability limits of the combustor, behavior of the flame dynamics, and frequencies of the oscillations. Results from simultaneous pressure and high speed chemiluminescence images have shown that the low frequency dynamics can be characterized as flashback oscillations. The results have also shown that the stability of the combustor can be explained by simple and well established premixed flame stability mechanisms. This study has allowed the development of a model that describes the instability mechanism and accurately

  19. Drug Facts

    Medline Plus

    Full Text Available ... 4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from drugs. But she's afraid ...

  20. Hybrid nanostructured drug carrier with tunable and controlled drug release

    International Nuclear Information System (INIS)

    Depan, D.; Misra, R.D.K.

    2012-01-01

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: ► The novel synthesis of a hybrid nanostructured drug carrier is described. ► The drug carrier exhibits high drug loading ability and is physically stable. ► The high drug release is ascribed to a cavitation-type process.

  1. Water-free transfer method for CVD-grown graphene and its application to flexible air-stable graphene transistors.

    Science.gov (United States)

    Kim, Hyun Ho; Chung, Yoonyoung; Lee, Eunho; Lee, Seong Kyu; Cho, Kilwon

    2014-05-28

    Transferring graphene without water enables water-sensitive substrates to be used in graphene electronics. A polymeric bilayer (PMMA/PBU) is coated on graphene as a supporting layer for the water-free transfer process and as an excellent passivation layer that enhances device operation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. High-Order Entropy Stable Formulations for Computational Fluid Dynamics

    Science.gov (United States)

    Carpenter, Mark H.; Fisher, Travis C.

    2013-01-01

    A systematic approach is presented for developing entropy stable (SS) formulations of any order for the Navier-Stokes equations. These SS formulations discretely conserve mass, momentum, energy and satisfy a mathematical entropy inequality. They are valid for smooth as well as discontinuous flows provided sufficient dissipation is added at shocks and discontinuities. Entropy stable formulations exist for all diagonal norm, summation-by-parts (SBP) operators, including all centered finite-difference operators, Legendre collocation finite-element operators, and certain finite-volume operators. Examples are presented using various entropy stable formulations that demonstrate the current state-of-the-art of these schemes.

  3. Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

    DEFF Research Database (Denmark)

    Bodenlenz, Manfred; Höfferer, Christian; Magnes, Christoph

    2012-01-01

    and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1. CONCLUSIONS: Novel membrane-free probes and wearable multi...

  4. Operational Radiation Protection in Synchrotron Light and Free Electron Laser Facilities

    Energy Technology Data Exchange (ETDEWEB)

    Liu, James C.; Rokni, Sayed H.; /SLAC; Vylet, Vaclav; /Jefferson Lab

    2009-12-11

    The 3rd generation synchrotron radiation (SR) facilities are storage ring based facilities with many insertion devices and photon beamlines, and have low injection beam power (< few tens of watts), but extremely high stored beam power ({approx} 1 GW). The 4th generation x-ray free electron laser (FEL) facilities are based on an electron Linac with a long undulator and have high injection beam power (a few kW). Due to its electron and photon beam characteristics and modes of operation, storage ring and photon beamlines have unique safety aspects, which are the main subjects of this paper. The shielding design limits, operational modes, and beam losses are first reviewed. Shielding analysis (source terms and methodologies) and interlocked safety systems for storage ring and photon beamlines (including SR and gas bremsstrahlung) are described. Specific safety issues for storage ring top-off injection operation and FEL facilities are discussed. The operational safety program, e.g., operation authorization, commissioning, training, and radiation measurements, for SR facilities is also presented.

  5. Operational Radiation Protection in Synchrotron Light and Free Electron Laser Facilities

    International Nuclear Information System (INIS)

    Liu, James C.; Rokni, Sayed H.; Vylet, Vaclav

    2009-01-01

    The 3rd generation synchrotron radiation (SR) facilities are storage ring based facilities with many insertion devices and photon beamlines, and have low injection beam power (< few tens of watts), but extremely high stored beam power (∼ 1 GW). The 4th generation x-ray free electron laser (FEL) facilities are based on an electron Linac with a long undulator and have high injection beam power (a few kW). Due to its electron and photon beam characteristics and modes of operation, storage ring and photon beamlines have unique safety aspects, which are the main subjects of this paper. The shielding design limits, operational modes, and beam losses are first reviewed. Shielding analysis (source terms and methodologies) and interlocked safety systems for storage ring and photon beamlines (including SR and gas bremsstrahlung) are described. Specific safety issues for storage ring top-off injection operation and FEL facilities are discussed. The operational safety program, e.g., operation authorization, commissioning, training, and radiation measurements, for SR facilities is also presented.

  6. The effect of solvents and hydrophilic additive on stable coating and controllable sirolimus release system for drug-eluting stent.

    Science.gov (United States)

    Kim, Seong Min; Park, Sung-Bin; Bedair, Tarek M; Kim, Man-Ho; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2017-09-01

    Various drug-eluting stents (DESs) have been developed to prevent restenosis after stent implantation. However, DES still needs to improve the drug-in-polymer coating stability and control of drug release for effective clinical treatment. In this study, the cobalt-chromium (CoCr) alloy surface was coated with biodegradable poly(D,L-lactide) (PDLLA) and sirolimus (SRL) mixed with hydrophilic Pluronic F127 additive by using ultrasonic spray coating system in order to achieve a stable coating surface and control SRL release. The degradation of PDLLA/SRL coating was studied under physiological solution. It was found that adding F127 reduced the degradation of PDLLA and improved the coating stability during 60days. The effects of organic solvent such as chloroform and tetrahydrofuran (THF) on the coating uniformity were also examined. It was revealed that THF produced a very smooth and uniform coating compared to chloroform. The patterns of in vitro drug release according to the type of organic solvent and hydrophilic additive proposed the possibility of controllable drug release design in DES. It was found that using F127 the drug release was sustained regardless of the organic solvent used. In addition, THF was able to get faster and controlled release profile when compared to chloroform. The structure of SRL molecules in different organic solvents was investigated using ultra-small angle neutron scattering. Furthermore, the structure of SRL is concentration-dependent in chloroform with tight nature under high concentration, but concentration-independent in THF. These results strongly demonstrated that coating stability and drug release patterns can be changed by physicochemical properties of various parameters such as organic solvents, additive, and coating strategy. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Subcutaneous drug infusions: a review of problems and solutions.

    Science.gov (United States)

    Mitten, T

    2001-02-01

    Subcutaneous drug infusion using a portable syringe driver has had a significant impact on patient comfort in palliative care. It permits the continuous delivery of a range of drug therapies, so bypassing problems of dysphagia, weakness and the inability of many patients in the terminal phase to take oral medication. The devices are not problem-free, however. Mechanical problems, reactions at the infusion site and difficulties with the mixing of drugs in the syringe are all widely recognized. This article reviews some general issues with the operation of portable syringe drivers, and discusses a range of potential problems and their solutions.

  8. Accelerating the commercialization on new technologies. [free market operation of federal alternate energy sources programs

    Science.gov (United States)

    Kuehn, T. J.; Nawrocki, P. M.

    1978-01-01

    It is suggested that federal programs for hastening the adoption of alternative energy sources must operate within the free market structure. Five phases of the free market commercialization process are described. Federal role possibilities include information dissemination and funding to stimulate private sector activities within these five phases, and federally sponsored procedures for accelerating commercialization of solar thermal small power systems are considered.

  9. Feedback control of a primary pump for safe and stable operation of a PIUS-type reactor

    International Nuclear Information System (INIS)

    Tasaka, K.; Imai, S.; Masaoka, H.; Tamaki, M.; Kukita, Y.

    1993-01-01

    A new automatic pump speed control system by using a measurement of the temperature distribution in the lower density lock is proposed for the PIUS-type reactor. This control system maintains the fluid temperature at the axial center of the lower density lock at the average of the fluid temperatures below and above the density lock in order to prevent the poison water from penetrating into the core during normal operation. The effectiveness of this control system was successfully confirmed by a series of experiments such as start-up and power ramping tests for the stable normal operation and a loss-of-feedwater test for the safe shutdown in an accident condition, using a small scale atmospheric pressure test loop which simulated the PIUS principle. (orig.)

  10. Small scale thermal-hydraulic experiment for stable operation of a pius-type reactor

    International Nuclear Information System (INIS)

    Tasaka, K.; Tamaki, M.; Imai, S.; Irianto, I.D.; Tsuji, Y.; Kukita, Y.

    1994-01-01

    Thermal-hydraulic experiments using a small-scale atmospheric pressure test loop have been performed for the Process Inherent Ultimate Safety (PIUS)-type reactor to develop the new pump speed feedback control system. Three feedback control systems based on the measurement of flow rate, differential pressure, and fluid temperature distribution in the lower density lock have been proposed and confirmed by a series of experiments. Each of the feedback control systems had been verified in the simulation experiment such as a start-up simulation test. The automatic pump speed control based on the fluid temperature at the lower density lock was quite effective to maintain the stratified interface between primary water and borated pool water for stable operation of the reactor. (author)

  11. 76 FR 12719 - Safe Schools/Healthy Students Program; Office of Safe and Drug-Free Schools; Safe Schools/Healthy...

    Science.gov (United States)

    2011-03-08

    ... DEPARTMENT OF EDUCATION Safe Schools/Healthy Students Program; Office of Safe and Drug- Free Schools; Safe Schools/Healthy Students Program; Catalog of Federal Domestic Assistance (CFDA) Numbers: 84... priorities, requirements, and definitions under the Safe Schools/Healthy Students (SS/HS) program. Since...

  12. Statistical optimization of thermo-alkali stable xylanase production from Bacillus tequilensis strain ARMATI

    Directory of Open Access Journals (Sweden)

    Ameer Khusro

    2016-07-01

    Conclusions: The cellulase-free xylanase showed an alkali-tolerant and thermo-stable property with potentially applicable nature at industrial scale. This statistical approach established a major contribution in enzyme production from the isolate by optimizing independent factors and represents a first reference on the enhanced production of thermo-alkali stable cellulase-free xylanase from B. tequilensis.

  13. Cancer therapy leading to state of cancer metabolism depression for efficient operation of small dosage cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Ponizovskiy MR

    2015-04-01

    Full Text Available “Prolonged medical starvation” as the method of cancer therapy was borrowed from folk healers Omelchenko A and Breuss R. Author was convinced in efficiency of this method of cancer treatment via examination of cured patients and on own experience. The mechanism of this method of cancer therapy operates via Warburg effect targeting that promotes efficient cancer treatment with small cytotoxic drugs. Just it was described the mechanism of Warburg effect as well as mechanism transmutation of mitochondrial function in cancer metabolism which are exhibited in connection with operation of described method cancer therapy. There were described the biochemical and biophysical mechanisms of formations resistance to some cytotoxic drugs and recurrence cancer disease after disease remission which occur sometimes as result of treatment with great dosage of cytotoxic drugs. Also it was described the benefits of use the method “Prolonged medical starvation” with decreased dosage of cytotoxic drugs for cancer treatment. The significance of this work that it was substantiated the mechanism operation of combination “Prolonged medical starvation” with small dosages cytotoxic drugs of cancer treatment, which mechanism leads to prevention recurrence cancer disease and resistance to anticancer drugs in comparison with intensive anticancer chemotherapy with great dosages of cytotoxic drugs in cancer therapy. Also the offered concepts of cancer therapy mechanism gave possibility to explain mechanisms of some results of experiments eliminating the doubts of the authors these experiments.

  14. Creciendo Sin Drogas: Guia de Prevencion para Padres (Growing Up Drug-Free: A Parent's Guide to Prevention).

    Science.gov (United States)

    Office of Elementary and Secondary Education (ED), Washington, DC. Safe and Drug Free Schools Program.

    This publication is part of the Department of Education's ongoing effort to provide information to emerging populations in their native language on how to create and maintain drug-free and safe schools across the nation. Throughout the publication are personal stories and artwork of elementary and secondary school students that promote the message…

  15. Thermal hydraulic numerical investigation of the heavy liquid metal free surface of MYRRHA spallation target experimental

    International Nuclear Information System (INIS)

    Batta, A.; Class, A.

    2015-01-01

    The first advanced design of accelerator-driven systems (ADS) is currently being built in SCK-CEN (Mol, Belgium): MYRRHA (Multi-purpose hybrid research reactor for high-tech applications). The experiment investigates the free surface design of the MYRRHA target. The free surface lead-bismuth eutectic (LBE) liquid metal experiment is a full-scale model of the concentric MYRRHA target. The design of the target is combined with CFD simulations using a volume of fluid method accounting for mass transfer across the free surface. The model used has been validated with water experimental results. The design of the target enables a high fluid velocity and a stable surface at the beam entry. In the current work, we present numerical results of Star- CD simulations employing a high-resolution interface-capturing scheme in conjunction with the cavitation model for the nominal operation conditions. Thermal hydraulic of the target is considered for the nominal flow rate and nominal heat load. Results show that the target has a very stable free surface configuration for the considered flow rate and heat load

  16. The use of carbon stable isotope ratios in drugs characterization

    Energy Technology Data Exchange (ETDEWEB)

    Magdas, D. A., E-mail: gabriela.cristea@itim-cj.ro; Cristea, G., E-mail: gabriela.cristea@itim-cj.ro; Bot, A., E-mail: gabriela.cristea@itim-cj.ro; Mirel, V., E-mail: gabriela.cristea@itim-cj.ro [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath Str., 400293 Cluj-Napoca (Romania)

    2013-11-13

    Isotopic Ratio Mass Spectrometry (IRMS) is an effective toll to be used for drug product authentication. The isotopic composition could be used to assist in the differentiation between batches of drugs and assist in the identification of counterfeit materials on the market. Only two factors affect the isotopic ratios in pharmaceutical components: the isotopic composition of the raw materials and the synthetic processes performed upon them. Counterfeiting of pharmaceutical drugs threatens consumer confidence in drug products companies' economical well-being. In this preliminary study, the analyzed samples consist in two types of commercially available analgesics, which were purchases from Romanian pharmacies. Differences in δ{sup 13}C between batches from −29.7 to −31.6% were observed, demonstrating that this method can be used to differentiate among individual drug batches and subsequently identify counterfeits on the market. On the other hand, carbon isotopic ratios differences among producers were recorded, the variations being between −31.3 to −34.9% for the same type of analgesic, but from different manufactures.

  17. Effectiveness of music therapy in state-trait anxiety rate of addicts in drug-free rehabilitation stage

    Directory of Open Access Journals (Sweden)

    E Soleimani

    2016-02-01

    Full Text Available Objective: This study was an attempt to investigate the effect of music therapy on addicts’ state-trait anxiety rate in the stage of drug-free rehabilitation. Method: A quasi-experimental research design, along with pretest-posttest and control group was employed for the conduct of this study. The statistical population of the study included the addicts in the rehabilitation stage who had referred to the clean collaborators rehabilitation camp in Ardebil province in November 2014. From this population, the number of 32 addicts in 16-50-year-old age range was selected as the participants of the study by convenience sampling method. State-Trait Anxiety Inventory was used for data collection. Results: The results of multivariate covariant analysis showed that there is a significant difference between control and experimental groups in state and trait anxiety. In other words, the state and trait anxiety of addicts in the experimental group had been reduced after music therapy. Conclusion: Considering the obtained results, it can be concluded that music therapy alone or along other psychological interventions can be an effective method for reducing addicts’ anxiety in drug-free rehabilitation stage.

  18. Oscillations-free PID control of anesthetic drug delivery in neuromuscular blockade.

    Science.gov (United States)

    Medvedev, Alexander; Zhusubaliyev, Zhanybai T; Rosén, Olov; Silva, Margarida M

    2016-07-25

    The PID-control of drug delivery or the neuromuscular blockade (NMB) in closed-loop anesthesia is considered. The NMB system dynamics portrayed by a Wiener model can exhibit sustained nonlinear oscillations under realistic PID gains and for physiologically feasible values of the model parameters. Such oscillations, also repeatedly observed in clinical trials, lead to under- and over-dosing of the administered drug and undermine patient safety. This paper proposes a tuning policy for the proportional PID gain that via bifurcation analysis ensures oscillations-free performance of the control loop. Online estimates of the Wiener model parameters are needed for the controller implementation and monitoring of the closed-loop proximity to oscillation. The nonlinear dynamics of the PID-controlled NMB system are studied by bifurcation analysis. A database of patient models estimated under PID-controlled neuromuscular blockade during general anesthesia is utilized, along with the corresponding clinical measurements. The performance of three recursive algorithms is compared in the application at hand: an extended Kalman filter, a conventional particle filter (PF), and a PF making use of an orthonormal basis to estimate the probability density function from the particle set. It is shown that with a time-varying proportional PID gain, the type of equilibria of the closed-loop system remains the same as in the case of constant controller gains. The recovery time and frequency of oscillations are also evaluated in simulation over the database of patient models. Nonlinear identification techniques based on model linearization yield biased parameter estimates and thus introduce superfluous uncertainty. The bias and variance of the estimated models are related to the computational complexity of the identification algorithms, highlighting the superiority of the PFs in this safety-critical application. The study demonstrates feasibility of the proposed oscillation-free control

  19. PLLA-PHB fiber membranes obtained by solvent-free electrospinning for short-time drug delivery.

    Science.gov (United States)

    Cao, K; Liu, Y; Olkhov, A A; Siracusa, V; Iordanskii, A L

    2018-02-01

    Fibers of poly(L-lactic acid) (PLLA)/polyhydroxybutyrate (PHB) with different concentrations of the drug dipyridamole (DPD) were prepared using solvent-free melt electrospinning to obtain a polymeric drug delivery system. The electrospun fibers were morphologically, structurally, thermally, and dynamically characterized. Crazes that resemble lotus root crevices were interestingly observed in the 7:3 PLLA/PHB fibers with 1% DPD. The crystallinity of PLLA slightly decreased as PHB was incorporated, and the addition of DPD significantly reduced the melting temperature of the composite. The interactions between PLLA and PHB mainly occurred at a proportion of 7:3, and drug encapsulation in the fibers was verified. The kinetic profiles of drug release demonstrated the predominant multiple patterns involving a diffusional stage in the short-term mode of release and kinetic process related to the hydrolysis of the biopolymers. Furthermore, the dynamic behavior of the polymer molecules was evaluated based on the segmental mobility using probe electron spin resonance spectroscopy. The segmental mobility in the amorphous fraction of PLLA decreased with increasing PLLA content. The 9:1 PLLA/PHB system was more resistant to polymer hydrolysis than to the 7:3 system and the rate of diffusion transport was approximately two times higher for the 7:3 PLLA/PHB fibers than for the 9:1 PLLA/PHB fibers.

  20. Syntheses and study of pyrrolidinic nitroxide free radicals. Preparation of a nitroxide-type stable bi-radical; Synthese et etudes de radicaux libres nitroxydes pyrrolidiniques. Preparation d'un biradical stable du type nitroxyde

    Energy Technology Data Exchange (ETDEWEB)

    Dupeyre, R M [Commissariat a l' Energie Atomique, Grenoble (France). Centre d' Etudes Nucleaires, Laboratoire de chimie organique physique

    1967-12-01

    Syntheses and study of pyrrolidinic nitroxide free radicals: These radicals are obtained by oxidation, with hydrogen peroxide, of pyrrolidinic amines prepared from triacetonamine by ring contraction. The U. V,, I. R, and E.P.R. spectral characteristics have been determined. The oxidation of these amines with hydrogen peroxide has led also to rupture of the pentagonal ring; some of the decomposition products have been identified. The high chemical stability of the nitroxide group has made it possible to synthesize and study a stable bi-radical. (author) [French] Syntheses et etudes de radicaux libres nitroxydes pyrrolidiniques: Ces radicaux sont obtenus par oxydation l'eau oxygenee d'amines pyrrolidiniques preparees a partir de la triacetonamine par contraction de cycle. Les caracteristiques spectroscopiques ultra-violettes, infra-rouge et resonance paramagnetique sont determinees. Cependant, 1'oxydation de ces amines a l'eau oxygenee a entraine la coupure du cycle pentagonal et identification de certaines substances de decomposition obtenues. La grande stabilite chimique de groupement nitroxyde a permis la synthese et l'etude d'un biradical stable. (auteur)

  1. Drug-resistant tuberculosis in Mumbai, India: An agenda for operations research

    Science.gov (United States)

    Mistry, Nerges; Tolani, Monica; Osrin, David

    2012-01-01

    Operations research (OR) is well established in India and is also a prominent feature of the global and local agendas for tuberculosis (TB) control. India accounts for a quarter of the global burden of TB and of new cases. Multidrug-resistant TB is a significant problem in Mumbai, India’s most populous city, and there have been recent reports of totally resistant TB. Much thought has been given to the role of OR in addressing programmatic challenges, by both international partnerships and India’s Revised National TB Control Programme. We attempt to summarize the major challenges to TB control in Mumbai, with an emphasis on drug resistance. Specific challenges include diagnosis of TB and defining cure, detecting drug resistant TB, multiple sources of health care in the private, public and informal sectors, co-infection with human immunodeficiency virus (HIV) and a concurrent epidemic of non-communicable diseases, suboptimal prescribing practices, and infection control. We propose a local agenda for OR: modeling the effects of newer technologies, active case detection, and changes in timing of activities, and mapping hotspots and contact networks; modeling the effects of drug control, changing the balance of ambulatory and inpatient care, and adverse drug reactions; modeling the effects of integration of TB and HIV diagnosis and management, and preventive drug therapy; and modeling the effects of initiatives to improve infection control. PMID:24501697

  2. Drug Facts

    Medline Plus

    Full Text Available ... can call 1-800-662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  3. Numerical and experimental results of a passive free yawing downwind wind turbine

    Energy Technology Data Exchange (ETDEWEB)

    Verelst, D.R.S.

    2013-09-15

    The background of this PhD study concerns a medium sized 3 bladed wind turbine in a free yawing and downwind configuration. Largely funded by an EU Marie-Curie IAPP grant, the project was jointly setup by the renewable energy consultant 3E, DTU Wind Energy and the TU Delft. The 3 bladed free yawing downwind concept is pursued in an attempt to increase the robustness of a wind turbine by eliminating the traditionally actively controlled, and sometimes failure prone yawing mechanism. Under certain conditions, such as for remote (off shore) and off grid applications, a decreased failure rate can increase the economical competitiveness significantly compared to more traditional power supplies. This work presents aeroelastic analysis and results of a wind tunnel test campaign for the 3 bladed free yawing downwind concept. The investigated topics concern free yawing stability and how it is affected by coning angle, blade sweep, and blade flexibility using both numerical and experimental methods. The wind tunnel tests were organized in the Open Jet Facility of the TU Delft, and the thesis discusses the experiment's design, construction, operation, and gives an analysis of the results. It provides a dataset to compare aeroelastic simulations with experimental results for varying yawed inflow conditions and free yawing stability. The experimental data scope is limited to rotor speed, tower base bending moment, yaw angle, and blade root flapwise bending moments measurements. Other work covered during the PhD study is a parametric blade sweep investigation for the NREL 5MW turbine, and a detailed study on load extrapolation methods based on aeroelastic simulations. It is concluded that the 3 bladed, free yawing, and downwind wind turbine can operate in a stable manner. However, numerical studies indicate a less stable operating region when the rotor flow is about to stall. The experiments confirmed the free yawing stability, but the unstable region indicated in the

  4. [Startup, stable operation and process failure of EBPR system under the low temperature and low dissolved oxygen condition].

    Science.gov (United States)

    Ma, Juan; Li, Lu; Yu, Xiao-Jun; Wei, Xue-Fen; Liu, Juan-Li

    2015-02-01

    A sequencing batch reactor (SBR) was started up and operated with alternating anaerobic/oxic (An/O) to perform enhanced biological phosphorus removal (EBPR) under the condition of 13-16 degrees C. The results showed that under the condition of low temperature, the EBPR system was successfully started up in a short time (<6 d). The reactor achieved a high and stable phosphorus removal performance with an influent phosphate concentration of 20 mg x L(-1) and the dissolved oxygen (DO) concentration of 2 mg x L(-1). The effluent phosphate concentration was lower than 0.5 mg x L(-1). It was found that decreasing DO had an influence on the steady operation of EBPR system. As DO concentration of aerobic phase decreased from 2 mg x L(-1) to 1 mg x L(-1), the system could still perform EBPR and the phosphorus removal efficiency was greater than 97.4%. However, the amount of phosphate released during anaerobic phase was observed to decrease slightly compared with that of 2 mg x L(-1) DO condition. Moreover, the phosphorus removal performance of the system deteriorated immediately and the effluent phosphate concentration couldn't meet the national integrated wastewater discharge standard when DO concentration was further lowered to 0.5 mg x L(-1). The experiments of increasing DO to recover phosphorus removal performance of the EBPR suggested the process failure resulted from low DO was not reversible in the short-term. It was also found that the batch tests of anoxic phosphorus uptake using nitrite and nitrate as electron acceptors had an impact on the stable operation of EBPR system, whereas the resulting negative influence could be recovered within 6 cycles. In addition, the mixed liquid suspended solids (MLSS) of the EBPR system remained stable and the sludge volume index (SVI) decreased to a certain extend in a long run, implying long-term low temperature and low DO condition favored the sludge sedimentation.

  5. Ultrasound assisted synthesis of stable oil in milk emulsion: Study of operating parameters and scale-up aspects.

    Science.gov (United States)

    Patil, Leena; Gogate, Parag R

    2018-01-01

    In the present work, application of ultrasound and stirring individually or in combination for improved emulsification of turmeric oil in skimmed milk has been investigated. The effect of different operating parameters/strategies such as addition of surfactant, sodium dodecyl sulfate (SDS), at different concentrations, quantity of oil phase, applied power, sonication time and duty cycle on the droplet size have been investigated. The stability of emulsion was analyzed in terms of the fraction of the emulsion that remains stable for a period of 28days. Optimized set of major emulsification process variables has been used at higher emulsion volumes. The effectiveness of treatment approach was analyzed based on oil droplet size, energy density and the time required for the formation of stable emulsion. It was observed that the stable emulsion at 50mL capacity with mean droplet diameter of about 235.4nm was obtained with the surfactant concentration of 5mg/mL, 11% of rated power (power density: 0.31W/mL) and irradiation time of 5min. The emulsion stability was higher in the case of ultrasound assisted approach as compared to the stirring. For the preparation of stable emulsion at 300mL capacity, it was observed that the sequential approach, i.e., stirring followed by ultrasound, gave lower mean droplet diameter (232.6nm) than the simultaneous approach, i.e., ultrasound and stirring together (257.9nm). However, the study also revealed that the simultaneous approach required very less time (15min) to synthesize stable emulsion as compared to the sequential approach (30min stirring and 60min ultrasound). It was successfully demonstrated that the ultrasound-assisted emulsification in the presence of SDS could be used for the preparation of stable turmeric oil-dairy emulsions, also providing insights into the role of SDS in increasing the stability of emulsions and of ultrasound in giving lower droplet sizes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The Astromag superconducting magnet facility configured for a free-flying satellite

    Science.gov (United States)

    Green, M. A.; Smoot, G. F.

    1992-01-01

    The magnet parameters of a free-flying version of Astromag and the parameters of the space cryogenic system for the magnet are presented. Consideration is given to the free-flyer version of the Astromag magnet. The diameter of the magnet, its cryostat, the satellite and the two instruments is limited by the 4.27-m shroud diameter of the Atlas IIa. The magnet coil must use a stable reliable superconductor which can carry the full magnet current at 4.2 K at a peak induction in the coil of 7.5 T. The magnet must operate in the persistent mode. The changes in the overall design and operating requirements for the free-flying-design Astromag suggest that the coils, the cryogenic system, and the charging system can be simplified without a loss of required magnet function. Attention is given to switches, trim coils, and plumbing in the low field region between the coils; the magnet charging system and the quench protection system; and cooled helium supply to the magnet gas-cooled electrical leads.

  7. Stochastic stability assessment of a semi-free piston engine generator concept

    Science.gov (United States)

    Kigezi, T. N.; Gonzalez Anaya, J. A.; Dunne, J. F.

    2016-09-01

    Small engines, as power generators with low-noise and vibration characteristics, are needed in two niche application areas: as electric vehicle range extenders and as domestic micro Combined Heat and Power systems. A recent semi-free piston design known as the AMOCATIC generator fully meets this requirement. The engine potentially allows for high energy conversion efficiencies at resonance derived from having a mass and spring assembly. As with free-piston engines in general, stability and control of piston motion has been cited as the prime challenge limiting the technology's widespread application. Using physical principles, we derive in this paper two important results: an energy balance criterion and a related general stability criterion for a semi-free piston engine. Control is achieved by systematically designing a Proportional Integral (PI) controller using a control-oriented engine model for which a specific stability condition is stated. All results are presented in closed form throughout the paper. Simulation results under stochastic pressure conditions show that the proposed energy balance, stability criterion, and PI controller, operate as predicted to yield stable engine operation at fixed compression ratio.

  8. Drug Facts

    Medline Plus

    Full Text Available ... the computer will read the text to you. This website talks about drug abuse, addiction, and treatment. Watch Videos ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her daughter to stay away from ...

  9. Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

    Science.gov (United States)

    Valavanidis, Athanasios; Vlachogianni, Thomais; Fiotakis, Konstantinos

    2009-01-01

    Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS) in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR) and spin-trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2•−) and hydroxyl (HO•) radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT) solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis). Also, we observed synergistic effects in the generation of HO•, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc.) and ambient particulate matter (PM), such as PM10, PM2.5 and diesel exhaust particles (DEP). The highest synergistic effects was observed with the asbestos fibres (freshly grounded), PM2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase. PMID:19440393

  10. Tobacco Smoke: Involvement of Reactive Oxygen Species and Stable Free Radicals in Mechanisms of Oxidative Damage, Carcinogenesis and Synergistic Effects with Other Respirable Particles

    Directory of Open Access Journals (Sweden)

    Konstantinos Fiotakis

    2009-02-01

    Full Text Available Tobacco smoke contains many toxic, carcinogenic and mutagenic chemicals, as well as stable and unstable free radicals and reactive oxygen species (ROS in the particulate and the gas phase with the potential for biological oxidative damage. Epidemiological evidence established that smoking is one of the most important extrinsic factor of premature morbidity and mortality. The objective of this study was to investigate oxidative and carcinogenic mechanisms of tobacco and synergistic action with other respirable particles in the respiratory system of smokers. Electron Paramagnetic Resonance (EPR and spin- trapping techniques were used to study stable free radicals in the cigarette tar, and unstable superoxide anion (O2·- and hydroxyl (HO· radicals in the smoke Results showed that the semiquinone radical system has the potential for redox recycling and oxidative action. Further, results proved that aqueous cigarette tar (ACT solutions can generate adducts with DNA nucleobases, particularly the mutagenic 8-hydroxy-2’-deoxyguanosine (a biomarker for carcinogenesis.Also, we observed synergistic effects in the generation of HO·, through the Fenton reaction, with environmental respirable particles (asbestos fibres, coal dust, etc. and ambient particulate matter (PM, such as PM10, PM2.5 and diesel exhaust particles (DEP. The highest synergistic effects was observed with the asbestos fibres (freshly grounded, PM2.5 and DEP. Finally, we discuss results from our previous study of conventional cellulose acetate filters and “bio-filters” with hemoglobin impregnated activated carbon, which showed that these filters do not substantially alter the free radical content of smoke in the particulate and in the gaseous phase.

  11. Supermolecular drug challenge to overcome drug resistance in cancer cells.

    Science.gov (United States)

    Onishi, Yasuhiko; Eshita, Yuki; Ji, Rui-Cheng; Kobayashi, Takashi; Onishi, Masayasu; Mizuno, Masaaki; Yoshida, Jun; Kubota, Naoji

    2018-06-04

    Overcoming multidrug resistance (MDR) of cancer cells can be accomplished using drug delivery systems in large-molecular-weight ATP-binding cassette transporters before entry into phagolysosomes and by particle-cell-surface interactions. However, these hypotheses do not address the intratumoral heterogeneity in cancer. Anti-MDR must be related to alterations of drug targets, expression of detoxification, as well as altered proliferation. In this study, it is shown that the excellent efficacy and sustainability of anti-MDR is due to a stable ES complex because of the allosteric facilities of artificial enzymes when they are used as supramolecular complexes. The allosteric effect of supermolecular drugs can be explained by the induced-fit model and can provide stable feedback control systems through the loop transfer function of the Hill equation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Free-anchored Nb2O5@graphene networks for ultrafast-stable lithium storage

    Science.gov (United States)

    Deng, Qinglin; Li, Mengjiao; Wang, Junyong; Jiang, Kai; Hu, Zhigao; Chu, Junhao

    2018-05-01

    Orthorhombic Nb2O5 (T-Nb2O5) has structural merit but poor electrical conductivity, limiting their applications in energy storage. Although graphene is frequently adopted to effectively improve its electrochemical properties, the ordinary modified methods cannot meet the growing demands for high-performance. Here, we demonstrate that different graphene modified routes play a vital role in affecting the electrochemical performances of T-Nb2O5. By only manual shaking within one minute, Nb2O5 nano-particles can be rapidly adsorbed onto graphene, then the free-anchored T-Nb2O5@graphene three-dimensional networks can be successfully prepared based on hydrogel method. As for the application in lithium-ion batteries, it performs outstanding rate character (129 mA h g-1 (25C rate), 110 mA h g-1 (50C rate) and 90 mA h g-1 (100C rate), correspond to 79%, 67% and 55% capacity of 0.5C rate, respectively) and excellent long-term cycling feature (˜70% capacity retention after 20000 cycles). Moreover, it still maintains similar ultrafast-stable lithium storage performances when Cu foil is substituted by Al foil as current collector. In addition, relevant kinetics mechanisms are also expounded. This work provides a versatile strategy for the preparation of graphene modified Nb2O5 or other types of nanoparticles.

  13. High-speed highly temperature stable 980 nm VCSELs operating at 25 Gb/s at up to 85 °C for short reach optical interconnects

    Science.gov (United States)

    Mutig, Alex; Lott, James A.; Blokhin, Sergey A.; Moser, Philip; Wolf, Philip; Hofmann, Werner; Nadtochiy, Alexey M.; Bimberg, Dieter

    2011-03-01

    The progressive penetration of optical communication links into traditional copper interconnect markets greatly expands the applications of vertical cavity surface emitting lasers (VCSELs) for the next-generation of board-to-board, moduleto- module, chip-to-chip, and on-chip optical interconnects. Stability of the VCSEL parameters at high temperatures is indispensable for such applications, since these lasers typically reside directly on or near integrated circuit chips. Here we present 980 nm oxide-confined VCSELs operating error-free at bit rates up to 25 Gbit/s at temperatures as high as 85 °C without adjustment of the drive current and peak-to-peak modulation voltage. The driver design is therefore simplified and the power consumption of the driver electronics is lowered, reducing the production and operational costs. Small and large signal modulation experiments at various temperatures from 20 up to 85 °C for lasers with different oxide aperture diameters are presented in order to analyze the physical processes controlling the performance of the VCSELs. Temperature insensitive maximum -3 dB bandwidths of around 13-15 GHz for VCSELs with aperture diameters of 10 μm and corresponding parasitic cut-off frequencies exceeding 22 GHz are observed. Presented results demonstrate the suitability of our VCSELs for practical high speed and high temperature stable short-reach optical links.

  14. High-power spallation target using a heavy liquid metal free surface flow

    International Nuclear Information System (INIS)

    Litfin, K.; Fetzer, J.R.; Batta, A.; Class, A.G.; Wetzel, Th.

    2015-01-01

    A prototype of a heavy liquid metal free surface target as proposed for the multi-purpose hybrid research reactor for high-tech applications in Mol, Belgium, has been set up and experimentally investigated at the Karlsruhe Liquid Metal Laboratory. A stable operation was demonstrated in a wide range of operating conditions and the surface shape was detected and compared with numerical pre-calculations employing Star-CD. Results show a very good agreement of experiment and numerical predictions which is an essential input for other windowless target designs like the META:LIC target for the European Spallation Source. (author)

  15. Forensic Stable Isotope Biogeochemistry

    Science.gov (United States)

    Cerling, Thure E.; Barnette, Janet E.; Bowen, Gabriel J.; Chesson, Lesley A.; Ehleringer, James R.; Remien, Christopher H.; Shea, Patrick; Tipple, Brett J.; West, Jason B.

    2016-06-01

    Stable isotopes are being used for forensic science studies, with applications to both natural and manufactured products. In this review we discuss how scientific evidence can be used in the legal context and where the scientific progress of hypothesis revisions can be in tension with the legal expectations of widely used methods for measurements. Although this review is written in the context of US law, many of the considerations of scientific reproducibility and acceptance of relevant scientific data span other legal systems that might apply different legal principles and therefore reach different conclusions. Stable isotopes are used in legal situations for comparing samples for authenticity or evidentiary considerations, in understanding trade patterns of illegal materials, and in understanding the origins of unknown decedents. Isotope evidence is particularly useful when considered in the broad framework of physiochemical processes and in recognizing regional to global patterns found in many materials, including foods and food products, drugs, and humans. Stable isotopes considered in the larger spatial context add an important dimension to forensic science.

  16. Entropy Stable Summation-by-Parts Formulations for Compressible Computational Fluid Dynamics

    KAUST Repository

    Carpenter, M.H.

    2016-11-09

    A systematic approach based on a diagonal-norm summation-by-parts (SBP) framework is presented for implementing entropy stable (SS) formulations of any order for the compressible Navier–Stokes equations (NSE). These SS formulations discretely conserve mass, momentum, energy and satisfy a mathematical entropy equality for smooth problems. They are also valid for discontinuous flows provided sufficient dissipation is added at shocks and discontinuities to satisfy an entropy inequality. Admissible SBP operators include all centred diagonal-norm finite-difference (FD) operators and Legendre spectral collocation-finite element methods (LSC-FEM). Entropy stable multiblock FD and FEM operators follows immediately via nonlinear coupling operators that ensure conservation, accuracy and preserve the interior entropy estimates. Nonlinearly stable solid wall boundary conditions are also available. Existing SBP operators that lack a stability proof (e.g. weighted essentially nonoscillatory) may be combined with an entropy stable operator using a comparison technique to guarantee nonlinear stability of the pair. All capabilities extend naturally to a curvilinear form of the NSE provided that the coordinate mappings satisfy a geometric conservation law constraint. Examples are presented that demonstrate the robustness of current state-of-the-art entropy stable SBP formulations.

  17. Multi-purposable filaments of HPMC for 3D printing of medications with tailored drug release and timed-absorption.

    Science.gov (United States)

    Kadry, Hossam; Al-Hilal, Taslim A; Keshavarz, Ali; Alam, Farzana; Xu, Changxue; Joy, Abraham; Ahsan, Fakhrul

    2018-04-20

    Three-dimensional printing (3DP), though developed for nonmedical applications and once regarded as futuristic only, has recently been deployed for the fabrication of pharmaceutical products. However, the existing feeding materials (inks and filaments) that are used for printing drug products have various shortcomings, including the lack of biocompatibility, inadequate extrudability and printability, poor drug loading, and instability. Here, we have sought to develop a filament using a single pharmaceutical polymer, with no additives, which can be multi-purposed and manipulated by computational design for the preparation of tablets with desired release and absorption patterns. As such, we have used hydroxypropyl-methylcellulose (HPMC) and diltiazem, a model drug, to prepare both drug-free and drug-impregnated filaments, and investigated their thermal and crystalline properties, studied the cytotoxicity of the filaments, designed and printed tablets with various infill densities and patterns. By alternating the drug-free and drug-impregnated filaments, we fabricated various types of tablets, studied the drug release profiles, and assessed oral absorption in rats. Both diltiazem and HPMC were stable at extrusion and printing temperatures, and the drug loading was 10% (w/w). The infill density, as well as infill patterns, influenced the drug release profile, and thus, when the infill density was increased to 100%, the percentage of drug released dramatically declined. Tablets with alternating drug-free and drug-loaded layers showed delayed and intermittent drug release, depending on when the drug-loaded layers encountered the dissolution media. Importantly, the oral absorption patterns accurately reproduced the drug release profiles and showed immediate, extended, delayed and episodic absorption of the drug from the rat gastrointestinal tract (GIT). Overall, we have demonstrated here that filaments for 3D printers can be prepared from a pharmaceutical polymer with no

  18. Conduct of operations: establishing operational focus and setting operational standards

    International Nuclear Information System (INIS)

    Lane, L.; McGuigan, K.

    1998-01-01

    Due to the nature of our business, we have often tended to focus on the technological aspects of the nuclear industry. The focus of this paper is directed towards the importance of addressing the people skills, attitudes, and 'culture' within, and surrounding, our facilities as key areas of improvement. Within Ontario Hydro Nuclear (OLIN) we have developed the terminology 'event free' operation and 'event free' culture. 'Event Free' recognizes errors as a part of human performance. 'Event Free' takes into account human weaknesses, and provides tools (such as standards) to manage, control, and mitigate errors. In essence, 'Event Free' encompasses two concepts: 1. Prevent errors from occurring; 2. If an error is made, catch it before it can affect safe operation of the facility, learn from the error, and ensure that it does not happen again. In addressing these business realities, Ontario Hydro has identified a number of key support mechanisms and corresponding performance standards that are essential for achieving operating excellence and an 'event free' business culture. This paper will discuss two operational aspects of an 'event free' culture, the first being a set of expectations to enhance the culture, and the second an example of cultural change: 1. Operating Standards - establishing clear expectations for human performance in operating staff; 2. Operational Focus - the understanding that, as a nuclear worker, you should consider every task, activity, in fact everything you do in this business, for the potential to affect safe and reliable operation of a nuclear facility. Note that although the term 'Operational' appears in the title, this concept applies to every individual in the nuclear business, from the cleaner, to the Board of Directors, to the external supplier. (author)

  19. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  20. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  1. Towards accurate free energy calculations in ligand protein-binding studies.

    Science.gov (United States)

    Steinbrecher, Thomas; Labahn, Andreas

    2010-01-01

    Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties of biomolecule binding, would be invaluable in the study of biological systems. In addition, as the mode of action of many pharmaceuticals is based upon their inhibition or activation of biomolecule targets, predictive models of small molecule receptor binding are very helpful tools in rational drug design. Since the goal here is normally to design a new compound with a high inhibition strength, one of the most important thermodynamic properties is the binding free energy DeltaG(0). The prediction of binding constants has always been one of the major goals in the field of computational chemistry, because the ability to reliably assess a hypothetical compound's binding properties without having to synthesize it first would save a tremendous amount of work. The different approaches to this question range from fast and simple empirical descriptor methods to elaborate simulation protocols aimed at putting the computation of free energies onto a solid foundation of statistical thermodynamics. While the later methods are still not suited for the screenings of thousands of compounds that are routinely performed in computational drug design studies, they are increasingly put to use for the detailed study of protein ligand interactions. This review will focus on molecular mechanics force field based free energy calculations and their application to the study of protein ligand interactions. After a brief overview of other popular methods for the calculation of free energies, we will describe recent advances in methodology and a variety of exemplary studies of molecular dynamics

  2. Dynamical SUSY breaking in meta-stable vacua

    International Nuclear Information System (INIS)

    Intriligator, Kenneth; Seiberg, Nathan; Shih, David

    2006-01-01

    Dynamical supersymmetry breaking in a long-lived meta-stable vacuum is a phenomenologically viable possibility. This relatively unexplored avenue leads to many new models of dynamical supersymmetry breaking. Here, we present a surprisingly simple class of models with meta-stable dynamical supersymmetry breaking: N = 1 supersymmetric QCD, with massive flavors. Though these theories are strongly coupled, we definitively demonstrate the existence of meta-stable vacua by using the free-magnetic dual. Model building challenges, such as large flavor symmetries and the absence of an R-symmetry, are easily accommodated in these theories. Their simplicity also suggests that broken supersymmetry is generic in supersymmetric field theory and in the landscape of string vacua

  3. Deep saturated Free Electron Laser oscillators and frozen spikes

    Energy Technology Data Exchange (ETDEWEB)

    Ottaviani, P.L. [ENEA - Centro Ricerche Bologna, via Martiri di Monte Sole, 4, IT 40129, Bologna (Italy); Pagnutti, S., E-mail: simonetta.pagnutti@enea.it [ENEA - Centro Ricerche Bologna, via Martiri di Monte Sole, 4, IT 40129, Bologna (Italy); Dattoli, G., E-mail: giuseppe.dattoli@enea.it [ENEA - Centro Ricerche Frascati, via E. Fermi, 45, IT 00044, Frascati, Roma (Italy); Sabia, E., E-mail: elio.sabia@enea.it [ENEA - Centro Ricerche Frascati, via E. Fermi, 45, IT 00044, Frascati, Roma (Italy); Petrillo, V., E-mail: vittoria.petrillo@mi.infn.it [Universita' degli Studi di Milano, via Celoria 16, IT 20133, Milano (Italy); INFN - Mi, via Celoria 16, IT 20133, Milano (Italy); Slot, P.J.M. van der, E-mail: p.j.m.vanderslot@utwente.nl [Mesa+ Institute for Nanotechnology, University of Twente, P.O.Box 217, 7500 AE, Enschede (Netherlands); Biedron, S., E-mail: sandra.biedron@colostate.edu [Department of Electrical and Computer Engineering Colorado State University (United States); Milton, S., E-mail: milton@engr.colostate.edu [Department of Electrical and Computer Engineering Colorado State University (United States)

    2016-10-21

    We analyze the behavior of Free Electron Laser (FEL) oscillators operating in the deep saturated regime and point out the formation of sub-peaks of the optical pulse. These are very stable configurations and the sub-peaks are found to have a duration corresponding to the coherence length. We speculate on the physical mechanisms underlying their growth and attempt an identification with natural mode-locked structures in FEL oscillators. Their impact on the intra-cavity nonlinear harmonic generation is also discussed along with the possibility of exploiting them as cavity out-coupler.

  4. Daylight operation of a free space, entanglement-based quantum key distribution system

    Energy Technology Data Exchange (ETDEWEB)

    Peloso, Matthew P; Gerhardt, Ilja; Ho, Caleb; Lamas-Linares, AntIa; Kurtsiefer, Christian [Centre for Quantum Technologies, National University of Singapore, 3 Science Drive 2, Singapore 117543 (Singapore)], E-mail: christian.kurtsiefer@gmail.com

    2009-04-15

    Many quantum key distribution (QKD) implementations using a free space transmission path are restricted to operation at night time in order to distinguish the signal photons used for a secure key establishment from the background light. Here, we present a lean entanglement-based QKD system overcoming that limitation. By implementing spectral, spatial and temporal filtering techniques, we establish a secure key continuously over several days under varying light and weather conditions.

  5. Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery.

    Science.gov (United States)

    Thamphiwatana, Soracha; Fu, Victoria; Zhu, Jingying; Lu, Diannan; Gao, Weiwei; Zhang, Liangfang

    2013-10-01

    We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.

  6. Coaxial Electrospray of Curcumin-Loaded Microparticles for Sustained Drug Release.

    Directory of Open Access Journals (Sweden)

    Shuai Yuan

    Full Text Available Curcumin exhibits superior anti-inflammatory, antiseptic and analgesic activities without significant side effects. However, clinical dissemination of this natural medicine is limited by its low solubility and poor bio-availability. To overcome this limitation, we propose to encapsulate curcumin in poly(lactic-co-glycolic acid (PLGA microparticles (MPs by an improved coaxial electrospray (CES process. This process is able to generate a stable cone-jet mode in a wide range of operation parameters in order to produce curcumin-loaded PLGA MPs with a clear core-shell structure and a designated size of several micrometers. In order to optimize the process outcome, the effects of primary operation parameters such as the applied electric voltages and the liquid flow rates are studied systemically. In vitro drug release experiments are also carried out for the CES-produced MPs in comparison with those by a single axial electrospray process. Our experimental results show that the CES process can be effectively controlled to encapsulate drugs of low aqueous solubility for high encapsulation efficiency and optimal drug release profiles.

  7. Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine.

    Science.gov (United States)

    Paine, Mary F; Widmer, Wilbur W; Pusek, Susan N; Beavers, Kimberly L; Criss, Anne B; Snyder, Jennifer; Watkins, Paul B

    2008-04-01

    We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates. The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine. By randomized crossover design, 18 healthy volunteers received cyclosporine (5 mg/kg) with 240 mL orange juice (control), GFJ, or furanocoumarin-free GFJ. Blood was collected over 24 h. Juice treatments were separated by > or = 1 wk. The effects of diluted extracts of each juice and of purified furanocoumarins on [3H]cyclosporine translocation in Caco-2 cells were then compared. The median (range) dose-corrected cyclosporine area under the curve and the maximum concentration with GFJ (P or = 0.50), were significantly higher than those with orange juice [15.6 (6.7-33.5) compared with 11.3 (4.8-22.0) x 10(-3) h/L and 3.0 (1.6-5.8) compared with 2.4 (1.1-3.1) mL(-1), respectively]. The median time to reach maximum concentration and terminal elimination half-life were not significantly different between the juices (2-3 and 7-8 h, respectively; P > or = 0.08). Relative to vehicle, the GFJ extract, orange juice extract, and purified furanocoumarins partially increased apical-to-basolateral and decreased basolateral-to-apical [3H]cyclosporine translocation in Caco-2 cells, whereas the furanocoumarin-free GFJ extract had negligible effects. Reanalysis of the clinical juices identified polymethoxyflavones as candidate P-glycoprotein inhibitors in orange juice but not in GFJ. Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.

  8. Design techniques for a stable operation of cryogenic field-programmable gate arrays

    Science.gov (United States)

    Homulle, Harald; Visser, Stefan; Patra, Bishnu; Charbon, Edoardo

    2018-01-01

    In this paper, we show how a deep-submicron field-programmable gate array (FPGA) can be operated more stably at extremely low temperatures through special firmware design techniques. Stability at low temperatures is limited through long power supply wires and reduced performance of various printed circuit board components commonly employed at room temperature. Extensive characterization of these components shows that the majority of decoupling capacitor types and voltage regulators are not well behaved at cryogenic temperatures, asking for an ad hoc solution to stabilize the FPGA supply voltage, especially for sensitive applications. Therefore, we have designed a firmware that enforces a constant power consumption, so as to stabilize the supply voltage in the interior of the FPGA. The FPGA is powered with a supply at several meters distance, causing significant resistive voltage drop and thus fluctuations on the local supply voltage. To achieve the stabilization, the variation in digital logic speed, which directly corresponds to changes in supply voltage, is constantly measured and corrected for through a tunable oscillator farm, implemented on the FPGA. The impact of the stabilization technique is demonstrated together with a reconfigurable analog-to-digital converter (ADC), completely implemented in the FPGA fabric and operating at 15 K. The ADC performance can be improved by at most 1.5 bits (effective number of bits) thanks to the more stable supply voltage. The method is versatile and robust, enabling seamless porting to other FPGA families and configurations.

  9. Epidemic spreading on dynamical networks with temporary hubs and stable scale-free degree distribution

    International Nuclear Information System (INIS)

    Wu, An-Cai

    2014-01-01

    Recent empirical analyses of some realistic dynamical networks have demonstrated that their degree distributions are stable scale-free (SF), but the instantaneous well-connected hubs at one point of time can quickly become weakly connected. Motivated by these empirical results, we propose a simple toy dynamical agent-to-agent contact network model, in which each agent stays at one node of a static underlay network and the nearest neighbors swap their positions with each other. Although the degree distribution of the dynamical network model at any one time is equal to that in the static underlay network, the numbers and identities of each agent’s contacts will change over time. It is found that the dynamic interaction tends to suppress epidemic spreading in terms of larger epidemic threshold, smaller prevalence (the fraction of infected individuals) and smaller velocity of epidemic outbreak. Furthermore, the dynamic interaction results in the prevalence to undergo a phase transition at a finite threshold of the epidemic spread rate in the thermodynamic limit, which is in contradiction to the absence of an epidemic threshold in static SF networks. Some of these findings obtained from heterogeneous mean-field theory are in good agreement with numerical simulations. (paper)

  10. Operator control systems and methods for swing-free gantry-style cranes

    Science.gov (United States)

    Feddema, John T.; Petterson, Ben J.; Robinett, III, Rush D.

    1998-01-01

    A system and method for eliminating swing motions in gantry-style cranes while subject to operator control is presented. The present invention comprises an infinite impulse response ("IIR") filter and a proportional-integral ("PI") feedback controller (50). The IIR filter receives input signals (46) (commanded velocity or acceleration) from an operator input device (45) and transforms them into output signals (47) in such a fashion that the resulting motion is swing free (i.e., end-point swinging prevented). The parameters of the IIR filter are updated in real time using measurements from a hoist cable length encoder (25). The PI feedback controller compensates for modeling errors and external disturbances, such as wind or perturbations caused by collision with objects. The PI feedback controller operates on cable swing angle measurements provided by a cable angle sensor (27). The present invention adjusts acceleration and deceleration to eliminate oscillations. An especially important feature of the present invention is that it compensates for variable-length cable motions from multiple cables attached to a suspended payload.

  11. Wind tunnel tests of a free yawing downwind wind turbine

    DEFF Research Database (Denmark)

    Verelst, David Robert; Larsen, Torben J.; van Wingerden, Jan-Willem

    2014-01-01

    . The discussed test cases show that the turbine is stable while operating in free yawing conditions. Further, the effect of the tower shadow passage on the blade flapwise strain measurement is evaluated. Finally, data from the experiment is compared with preliminary simulations using DTU Wind Energy......This research paper presents preliminary results on a behavioural study of a free yawing downwind wind turbine. A series of wind tunnel tests was performed at the TU Delft Open Jet Facility with a three bladed downwind wind turbine and a rotor radius of 0.8 meters. The setup includes an off...... the shelf three bladed hub, nacelle and generator on which relatively flexible blades are mounted. The tower support structure has free yawing capabilities provided at the base. A short overview on the technical details of the experiment is given as well as a brief summary of the design process...

  12. Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

  13. Scavenging of free-radical metabolites of aniline xenobiotics and drugs by amino acid derivatives: toxicological implications of radical-transfer reactions.

    Science.gov (United States)

    Michail, Karim; Baghdasarian, Argishti; Narwaley, Malyaj; Aljuhani, Naif; Siraki, Arno G

    2013-12-16

    We investigated a novel scavenging mechanism of arylamine free radicals by poly- and monoaminocarboxylates. Free radicals of arylamine xenobiotics and drugs did not react with oxygen in peroxidase-catalyzed reactions; however, they showed marked oxygen uptake in the presence of an aminocarboxylate. These free-radical intermediates were identified using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and electron paramagnetic resonance (EPR) spectrometry. Diethylenetriaminepentaacetic acid (DTPA), a polyaminocarboxylate, caused a concentration-dependent attenuation of N-centered radicals produced by the peroxidative metabolism of arylamines with the subsequent formation of secondary aliphatic carbon-centered radicals stemming from the cosubstrate molecule. Analogously, N,N-dimethylglycine (DMG) and N-methyliminodiacetate (MIDA), but not iminodiacetic acid (IDA), demonstrated a similar scavenging effect of arylamine-derived free radicals in a horseradish peroxidase/H2O2 system. Using human promyelocytic leukemia (HL-60) cell lysate as a model of human neutrophils, DTPA, MIDA, and DMG readily reduced anilinium cation radicals derived from the arylamines and gave rise to the corresponding carbon radicals. The rate of peroxidase-triggered polymerization of aniline was studied as a measure of nitrogen-radical scavenging. Although, IDA had no effect on the rate of aniline polymerization, this was almost nullified in the presence of DTPA and MIDA at half of the molar concentration of the aniline substrate, whereas a 20 molar excess of DMPO caused only a partial inhibition. Furthermore, the yield of formaldehyde, a specific reaction endproduct of the oxidation of aminocarboxylates by aniline free-radical metabolites, was quantitatively determined. Azobenzene, a specific reaction product of peroxidase-catalyzed free-radical dimerization of aniline, was fully abrogated in the presence of DTPA, as confirmed by GC/MS. Under aerobic conditions, a radical-transfer reaction

  14. Effects of response-shock interval and shock intensity on free-operant avoidance responding in the pigeon1

    Science.gov (United States)

    Klein, Marty; Rilling, Mark

    1972-01-01

    Two experiments investigated free-operant avoidance responding with pigeons using a treadle-pressing response. In Experiment I, pigeons were initially trained on a free-operant avoidance schedule with a response-shock interval of 32 sec and a shock-shock interval of 10 sec, and were subsequently exposed to 10 values of the response-shock parameter ranging from 2.5 to 150 sec. The functions relating response rate to response-shock interval were similar to the ones reported by Sidman in his 1953 studies employing rats, and were independent of the order of presentation of the response-shock values. Shock rates decreased as response-shock duration increased. In Experiment II, a free-operant avoidance schedule with a response-shock interval of 20 sec and a shock-shock interval of 5 sec was used, and shock intensities were varied over five values ranging from 2 to 32 mA. Response rates increased markedly as shock intensity increased from 2 to 8 mA, but rates changed little with further increases in shock intensity. Shock rates decreased as intensity increased from 2 to 8 mA, and showed little change as intensity increased from 8 to 32 mA. PMID:4652617

  15. Sperm-Hybrid Micromotor for Targeted Drug Delivery.

    Science.gov (United States)

    Xu, Haifeng; Medina-Sánchez, Mariana; Magdanz, Veronika; Schwarz, Lukas; Hebenstreit, Franziska; Schmidt, Oliver G

    2018-01-23

    A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing  toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.

  16. The Application of a Free Swimming Remotely Operated Vehicle in Aquaculture

    Directory of Open Access Journals (Sweden)

    R. Klepaker

    1987-01-01

    Full Text Available In 1985, SINTEF and SIMRAD Subsea A/S started to develop an autonomous free swimming vehicle. The project was to develop a prototype of a small vehicle, in order to obtain knowledge and experience in designing, controlling and operating such vehicles. This was ready for testing at the end of 1985. The vehicle is controlled by an acoustic data telemetry system. The vehicle has a built-in television camera and containers for other sensors. It is suitable for inspection purposes. This paper describes the vehicle and some of the principles used.

  17. Ballooning stable high beta tokamak equilibria

    International Nuclear Information System (INIS)

    Tuda, Takashi; Azumi, Masafumi; Kurita, Gen-ichi; Takizuka, Tomonori; Takeda, Tatsuoki

    1981-04-01

    The second stable regime of ballooning modes is numerically studied by using the two-dimensional tokamak transport code with the ballooning stability code. Using the simple FCT heating scheme, we find that the plasma can locally enter this second stable regime. And we obtained equilibria with fairly high beta (β -- 23%) stable against ballooning modes in a whole plasma region, by taking into account of finite thermal diffusion due to unstable ballooning modes. These results show that a tokamak fusion reactor can operate in a high beta state, which is economically favourable. (author)

  18. Use of stable isotopes to identify dietary differences across subpopulations and sex for a free-ranging generalist herbivore.

    Science.gov (United States)

    Walter, W David

    2014-01-01

    Carbon and nitrogen isotopes in tissues can be used to understand plants consumed by various taxa, but can they provide additional information about consumers? Values of δ(13)C and δ(15)N were assessed from tissue of free-ranging elk (Cervus elaphus) occupying disparate habitats of mixed prairie-oak savannah that contained C3 agricultural crops in a C4-dominated landscape and in key plants consumed by elk. Muscle and hoof samples were collected from female and male elk in two subpopulations (forested land and grassland) from private land and one subpopulation from the Wichita Mountains Wildlife Refuge (refuge) in 2001-2006. Previous research identified differences between mean muscle δ(13)C and δ(15)N and mean hoof δ(13)C and δ(15)N indicating that isotopes differed between tissues of varying metabolic activity. Mean δ(13)C in hoof of elk on forested land and grassland were lower than hoof δ(13)C from elk in the refuge indicating greater long-term consumption of C3 plants by elk on forested land and grassland subpopulations. The δ(15)N in hoof was greater for elk outside the refuge than that for elk in the refuge. Interaction of sex and subpopulation only occurred for hoof δ(15)N suggesting that factors such as tissue type, sex, and habitat need to be considered to understand free-ranging ecology of generalist herbivores using stable isotopes. Availability of C3 agricultural crops high in percent nitrogen on a nearly annual basis in a C4-dominated landscape was likely driving differences in tissue δ(13)C and δ(15)N among subpopulations of free-ranging elk. An increase in tissue δ(15)N resulted from an increase in the consumption of higher δ(15)N in forage for sexes and subpopulations of a free-ranging ungulate in North America but δ(15)N should be further evaluated as an index of nutrition for subpopulations of generalist herbivores.

  19. Free Radical Imaging Using In Vivo Dynamic Nuclear Polarization-MRI.

    Science.gov (United States)

    Utsumi, Hideo; Hyodo, Fuminori

    2015-01-01

    Redox reactions that generate free radical intermediates are essential to metabolic processes, and their intermediates can produce reactive oxygen species, which may promote diseases related to oxidative stress. The development of an in vivo electron spin resonance (ESR) spectrometer and its imaging enables us noninvasive and direct measurement of in vivo free radical reactions in living organisms. The dynamic nuclear polarization magnetic resonance imaging (DNP-MRI), also called PEDRI or OMRI, is also a new imaging method for observing free radical species in vivo. The spatiotemporal resolution of free radical imaging with DNP-MRI is comparable with that in MRI, and each of the radical species can be distinguished in the spectroscopic images by changing the frequency or magnetic field of ESR irradiation. Several kinds of stable nitroxyl radicals were used as spin probes to detect in vivo redox reactions. The signal decay of nitroxyl probes, which is determined with in vivo DNP-MRI, reflects the redox status under oxidative stress, and the signal decay is suppressed by prior administration of antioxidants. In addition, DNP-MRI can also visualize various intermediate free radicals from the intrinsic redox molecules. This noninvasive method, in vivo DNP-MRI, could become a useful tool for investigating the mechanism of oxidative injuries in animal disease models and the in vivo effects of antioxidant drugs. © 2015 Elsevier Inc. All rights reserved.

  20. Quantum Gate Operations in Decoherence-Free Subspace with Superconducting Charge Qubits inside a Cavity

    International Nuclear Information System (INIS)

    Yi-Min, Wang; Yan-Li, Zhou; Lin-Mei, Liang; Cheng-Zu, Li

    2009-01-01

    We propose a feasible scheme to achieve universal quantum gate operations in decoherence-free subspace with superconducting charge qubits placed in a microwave cavity. Single-logic-qubit gates can be realized with cavity assisted interaction, which possesses the advantages of unconventional geometric gate operation. The two-logic-qubit controlled-phase gate between subsystems can be constructed with the help of a variable electrostatic transformer. The collective decoherence can be successfully avoided in our well-designed system. Moreover, GHZ state for logical qubits can also be easily produced in this system

  1. Stochastic stability assessment of a semi-free piston engine generator concept

    International Nuclear Information System (INIS)

    Kigezi, T N; Anaya, J A Gonzalez; Dunne, J F

    2016-01-01

    Small engines, as power generators with low-noise and vibration characteristics, are needed in two niche application areas: as electric vehicle range extenders and as domestic micro Combined Heat and Power systems. A recent semi-free piston design known as the AMOCATIC generator fully meets this requirement. The engine potentially allows for high energy conversion efficiencies at resonance derived from having a mass and spring assembly. As with free-piston engines in general, stability and control of piston motion has been cited as the prime challenge limiting the technology's widespread application. Using physical principles, we derive in this paper two important results: an energy balance criterion and a related general stability criterion for a semi-free piston engine. Control is achieved by systematically designing a Proportional Integral (PI) controller using a control-oriented engine model for which a specific stability condition is stated. All results are presented in closed form throughout the paper. Simulation results under stochastic pressure conditions show that the proposed energy balance, stability criterion, and PI controller, operate as predicted to yield stable engine operation at fixed compression ratio. (paper)

  2. Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

    Science.gov (United States)

    Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

    2009-01-01

    In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

  3. Sodium deoxycholate mediated enhanced solubilization and stability of hydrophobic drug Clozapine in pluronic micelles

    Science.gov (United States)

    Singla, Pankaj; Singh, Onkar; Chabba, Shruti; Aswal, V. K.; Mahajan, Rakesh Kumar

    2018-02-01

    In this report, the solubilization behaviour of a hydrophobic drug Clozapine (CLZ) in micellar suspensions of pluronics having different hydrophilic lipophilic balance (HLB) ratios viz. P84, F127 and F108 in the absence and presence of bile salt sodium deoxycholate (SDC) has been studied. UV-Vis spectroscopy has been exploited to determine the solubilization capacity of the investigated micellar systems in terms of drug loading efficiency, average number of drug molecules solubilized per micelle (ns), partition coefficient (P) and standard free energy of solubilization (Δ G°). The morphological and structural changes taking place in pluronics in different concentration regimes of SDC and with the addition of drug CLZ has been explored using dynamic light scattering (DLS) and small angle neutron scattering (SANS) measurements. The SANS results revealed that aggregation behaviour of pluronic-SDC mixed micelles gets improved in the presence of drug. The micropolarity measurements have been performed to shed light on the locus of solubilization of the drug in pure and mixed micellar systems. The compatibility between CLZ and drug carriers (pluronics and SDC) was confirmed using powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR) techniques. Among the investigated systems, P84-SDC mixed system was found to be highly efficient for CLZ loading. The long term stability data indicated that CLZ loaded P84-SDC mixed micellar formulation remained stable for 3 months at room temperature. Further, it was revealed that the CLZ loaded P84-SDC mixed micelles are converted into CLZ loaded pure P84 micelles at 30-fold dilutions which remain stable up to 48-fold dilutions. The results from the present studies suggest that P84-SDC mixed micelles can serve as suitable delivery vehicles for hydrophobic drug CLZ.

  4. Adjusting inkjet printhead parameters to deposit drugs into micro-sized reservoirs

    Directory of Open Access Journals (Sweden)

    Mau Robert

    2016-09-01

    Full Text Available Drug delivery systems (DDS ensure that therapeutically effective drug concentrations are delivered locally to the target site. For that reason, it is common to coat implants with a degradable polymer which contains drugs. However, the use of polymers as a drug carrier has been associated with adverse side effects. For that reason, several technologies have been developed to design polymer-free DDS. In literature it has been shown that micro-sized reservoirs can be applied as drug reservoirs. Inkjet techniques are capable of depositing drugs into these reservoirs. In this study, two different geometries of micro-sized reservoirs have been laden with a drug (ASA using a drop-on-demand inkjet printhead. Correlations between the characteristics of the drug solution, the operating parameters of the printhead and the geometric parameters of the reservoir are shown. It is indicated that wettability of the surface play a key role for drug deposition into micro-sized reservoirs.

  5. Preparation of three- and four-qubit decoherence-free states via Zeno-like measurements

    International Nuclear Information System (INIS)

    Shao, Xiao-Qiang; Zhang, Shou; Zhao, Yong-Fang; Chen, Li; Yeon, Kyu-Hwang

    2010-01-01

    Enlightened by the idea of purification through Zeno-like measurements (Nakazato et al 2003 Phys. Rev. Lett. 90 060401), we propose a scheme for generating three- and four-qubit decoherence-free states with respect to collective amplitude damping. The whole system is in a star configuration of a spin network and the outer spin qubits construct the decoherence-free state via measuring the state of central spin qubit at intervals of τ repeatedly. An interesting feature is found: namely, that in order to prepare the three-qubit decoherence-free state successfully, the value of τ for the projected time-evolution operator must be set definitely, while this restrictive condition is relaxed for achieving the four-qubit decoherence-free state. The simulation results reveal that the fidelity approaches one asymptotically, and the corresponding success probability reaches a stable value by increasing the number of measurements N.

  6. Spectrophotometric determination of mefenamic acid excreted as free drug in urine of human beings

    International Nuclear Information System (INIS)

    Naseer, M.M.; Nawaz, R.; Shafique, M.; Rehman, R.

    2007-01-01

    Urinary excretion of free mefenamic acid was investigated in 16 healthy human volunteers, eight males and eight females, following the oral administration of 500 mg tablet of mefenamic acid. Urine samples were collected at pre-determined schedule and drug concentration was determined by spectrophotometric method. The total recovery of free mefenamic acid was 1.526 +- 0.128 and 1.193 +- 0.112% in male and female volunteers respectively. The average +- S.E values for diuresis, pH and rate of excretion of mefenamic acid was 0.0160 +- 0.004 mL/min./kg of body weight, 6.22 +- 0.167, 0.077 +- 0.016 micro g min/sup -1/kg/sup -1/in male while 0.0084 +- 0.0023mL min/sup -1/kg-1 of body weight, 6.35 +- 0.164, 0.054 +- 0.008 micro g min/sup -1/kg/sup -1/respectively in female volunteers. The results obtained are different from the earlier studies due to variability in dose, gender variation, fluctuation in urine pH, environmental conditions and nutritional ingredients. (author)

  7. The continuous spectrum and the effect of parametric resonance. The case of bounded operators

    International Nuclear Information System (INIS)

    Skazka, V V

    2014-01-01

    The paper is concerned with the Mathieu-type differential equation u ″ =−A 2 u+εB(t)u in a Hilbert space H. It is assumed that A is a bounded self-adjoint operator which only has an absolutely continuous spectrum and B(t) is almost periodic operator-valued function. Sufficient conditions are obtained under which the Cauchy problem for this equation is stable for small ε and hence free of parametric resonance. Bibliography: 10 titles

  8. Escherichia coli cell-free protein synthesis and isotope labeling of mammalian proteins.

    Science.gov (United States)

    Terada, Takaho; Yokoyama, Shigeyuki

    2015-01-01

    This chapter describes the cell-free protein synthesis method, using an Escherichia coli cell extract. This is a cost-effective method for milligram-scale protein production and is particularly useful for the production of mammalian proteins, protein complexes, and membrane proteins that are difficult to synthesize by recombinant expression methods, using E. coli and eukaryotic cells. By adjusting the conditions of the cell-free method, zinc-binding proteins, disulfide-bonded proteins, ligand-bound proteins, etc., may also be produced. Stable isotope labeling of proteins can be accomplished by the cell-free method, simply by using stable isotope-labeled amino acid(s) in the cell-free reaction. Moreover, the cell-free protein synthesis method facilitates the avoidance of stable isotope scrambling and dilution over the recombinant expression methods and is therefore advantageous for amino acid-selective stable isotope labeling. Site-specific stable isotope labeling is also possible with a tRNA molecule specific to the UAG codon. By the cell-free protein synthesis method, coupled transcription-translation is performed from a plasmid vector or a PCR-amplified DNA fragment encoding the protein. A milligram quantity of protein can be produced with a milliliter-scale reaction solution in the dialysis mode. More than a thousand solution structures have been determined by NMR spectroscopy for uniformly labeled samples of human and mouse functional domain proteins, produced by the cell-free method. Here, we describe the practical aspects of mammalian protein production by the cell-free method for NMR spectroscopy. © 2015 Elsevier Inc. All rights reserved.

  9. Truly quasi-solid-state lithium cells utilizing carbonate free polymer electrolytes on engineered LiFePO_4

    International Nuclear Information System (INIS)

    Nair, Jijeesh R.; Cíntora-Juárez, Daniel; Pérez-Vicente, Carlos; Tirado, José L.; Ahmad, Shahzada; Gerbaldi, Claudio

    2016-01-01

    Highlights: • Carbonate free truly quasi-solid-state polymer electrolytes for lithium batteries. • Simple and easy up scalable preparation by solvent free thermal curing. • LiFePO_4 cathode engineered by PEDOT:PSS interphase at the current collector. • Direct polymerization over the engineered electrode surface in one pot. • Stable lithium polymer cells operating in a wide temperature range. - Abstract: Stable and safe functioning of a Li-ion battery is the demand of modern generation. Herein, we are demonstrating the application of an in-situ free radical polymerisation process (thermal curing) to fabricate a polymer electrolyte that possesses mechanical robustness, high thermal stability, improved interfacial and ion transport characteristics along with stable cycling at ambient conditions. The polymer electrolyte is obtained by direct polymerization over the electrode surface in one pot starting from a reactive mixture comprising an ethylene oxide-based dimethacrylic oligomer (BDM), dimethyl polyethylene glycol (DPG) and lithium salt. Furthermore, an engineered cathode is used, comprising a LiFePO_4/PEDOT:PSS interface at the current collector that improves the material utilization at high rates and mitigates the corrosive effects of LiTFSI on aluminium current collector. The lithium cell resulting from the newly elaborated multiphase assembly of the composite cathode with the DPG-based carbonate-free polymer electrolyte film exhibits excellent reversibility upon prolonged cycling at ambient as well as elevated temperatures, which is found to be superior compared to previous reports on uncoated electrodes with polymer electrolytes.

  10. Student Athletes Work toward a Drug-Free School.

    Science.gov (United States)

    Oberman, Jerome P.

    1989-01-01

    Describes the Student Athlete Leadership Program (SALP), part of the Long Beach (New York) City School District's comprehensive drug education program. SALP trains high-profile high school athletes to conduct drug and alcohol prevention activities in the elementary schools. (FMW)

  11. Revolving drug funds at front-line health facilities in Vientiane, Lao PDR.

    Science.gov (United States)

    Murakami, H; Phommasack, B; Oula, R; Sinxomphou, S

    2001-03-01

    Pharmaceutical cost recovery programmes, which have been mainly implemented in Africa, are gradually spreading to Southeast Asian countries that formerly belonged to the socialist bloc. This report describes the economic and operational realities of revolving drug funds (RDFs) at district hospitals and health centres in the capital of the Lao PDR by reviewing research conducted by the implementing department. People in the municipality spent an average of US$11 on drugs in 1996. The RDFs comprised only 3% of the total yearly drug sales in the municipality, whereas private pharmacies accounted for 75%. The RDFs were forced to operate in conjunction with the remaining government drug endowment and the thriving private pharmacies. This scheme has provided a stable supply of essential drugs. The assurance of drug availability at the front-line health facilities has resulted in increased utilization of the facilities despite the introduction of a drug fee. The cost recovery rate was 107% at health centres and 108% at district hospitals in two monitored districts during the 10 months from November 1997. Decentralized financial management was essential for cost recovery, allowing timely adjustment of selling prices as purchase prices rapidly inflated after the Asian economic crisis. The health staff observed that the people perceived drugs as everyday commodities that they should buy and take based on self-diagnosis and personal preference. Adaptation of the public health authorities to market-oriented thinking along with the establishment of pharmaceutical cost recovery occurred with few problems. However, both financial and operational management capacity at the municipal level pose a major challenge to policy clarification and scheme setting, especially in procurement, control of prescribing practices and the integration of drug dispensing with other components of quality clinical care.

  12. Towards more stable operation of the Tokyo Tier2 center

    Science.gov (United States)

    Nakamura, T.; Mashimo, T.; Matsui, N.; Sakamoto, H.; Ueda, I.

    2014-06-01

    (Tokyo to New York and Tokyo to Los Angeles). The new line will be connected to LHCONE for the more improvement of the connectivity. In this circumstance, we are working for the further stable operation. For instance, we have newly introduced GPFS (IBM) for the non-grid disk storage, while Disk Pool Manager (DPM) are continued to be used as Tier2 disk storage from the previous system. Since the number of files stored in a DPM pool will be increased with increasing the total amount of data, the development of stable database configuration is one of the crucial issues as well as scalability. We have started some studies on the performance of asynchronous database replication so that we can take daily full backup. In this report, we would like to introduce several improvements in terms of the performances and stability of our new system and possibility of the further improvement of local I/O performance in the multi-core worker node. We also present the status of the wide area network connectivity from Japan to US and/or EU with LHCONE.

  13. Towards more stable operation of the Tokyo Tier2 center

    International Nuclear Information System (INIS)

    Nakamura, T; Mashimo, T; Matsui, N; Sakamoto, H; Ueda, I

    2014-01-01

    (Tokyo to New York and Tokyo to Los Angeles). The new line will be connected to LHCONE for the more improvement of the connectivity. In this circumstance, we are working for the further stable operation. For instance, we have newly introduced GPFS (IBM) for the non-grid disk storage, while Disk Pool Manager (DPM) are continued to be used as Tier2 disk storage from the previous system. Since the number of files stored in a DPM pool will be increased with increasing the total amount of data, the development of stable database configuration is one of the crucial issues as well as scalability. We have started some studies on the performance of asynchronous database replication so that we can take daily full backup. In this report, we would like to introduce several improvements in terms of the performances and stability of our new system and possibility of the further improvement of local I/O performance in the multi-core worker node. We also present the status of the wide area network connectivity from Japan to US and/or EU with LHCONE.

  14. A study on the gas-solid particle flows in a needle-free drug delivery device

    Science.gov (United States)

    Rasel, Md. Alim Iftekhar; Taher, Md. Abu; Kim, H. D.

    2013-08-01

    Different systems have been used over the years to deliver drug particles to the human skin for pharmaceutical effect. Research has been done to improve the performance and flexibility of these systems. In recent years a unique system called the transdermal drug delivery has been developed. Transdermal drug delivery opened a new door in the field of drug delivery as it is more flexible and offers better performance than the conventional systems. The principle of this system is to accelerate drug particles with a high speed gas flow. Among different transdermal drug delivery systems we will concentrate on the contour shock tube system in this paper. A contoured shock tube is consists of a rupture chamber, a shock tube and a supersonic nozzle section. The drug particles are retained between a set of bursting diaphragm. When the diaphragm is ruptured at a certain pressure, a high speed unsteady flow is initiated through the shock tube which accelerates the particles. Computational fluid dynamics is used to simulate and analyze the flow field. The DPM (discrete phase method) is used to model the particle flow. As an unsteady flow is initiated though the shock tube the drag correlation proposed by Igra et al is used other than the standard drag correlation. The particle velocities at different sections including the nozzle exit are investigated under different operating conditions. Static pressure histories in different sections in the shock tube are investigated to analyze the flow field. The important aspects of the gas and particle dynamics in the shock tube are discussed and analyzed in details.

  15. Outlook of the process of storage of oncology drugs from the logistic operator in Colombia

    Directory of Open Access Journals (Sweden)

    Pedro Vicente Sánchez-Calvera

    2014-05-01

    Full Text Available This article mainly on the problem of  storage of oncology drugs, which is an important element in the supply chain, applied in the context of warehouse management of oncology drugs, in the logistics operator and providers of health services institutions (IPS for its acronym in Spanish of Bogotá DC and in the contex of a macro project "Methodological proposal for the definition of policies , rules of negotation and coordination in supply management of oncology drugs in Colombia," funded by Colciencias and the Universidad Nacional of Colombia. This article presents the current situation of oncology drugs, marking a characterization, diagnosis and identification and startegies evaluated under different scenarios. Finally, it is presented a proposal of improvement applied tranversely to storage processes including labels such as just in Time and the application of information and communication technologies (ICT.

  16. Exploring the Limits and Utility of Operant Conditioning in the Treatment of Drug Addiction

    Science.gov (United States)

    Silverman, Kenneth

    2004-01-01

    This article describes a research program to develop an operant treatment for cocaine addiction in low-income, treatment-resistant methadone patients. The treatment's central feature is an abstinence reinforcement contingency in which patients earn monetary reinforcement for providing cocaine-free urine samples. Success and failure of this…

  17. Mid-term follow-up of aortic root remodelling compared to Bentall operation.

    Science.gov (United States)

    Bassano, C; De Matteis, G M; Nardi, P; Buratta, M M; Zeitani, J; De Paulis, R; Chiariello, L

    2001-05-01

    Aortic valve sparing with root remodelling has proven useful in cases of aortic regurgitation secondary to ascending aorta disease. An excessive rate of re-operation for recurrent aortic regurgitation after this conservative approach might compensate the prosthesis-related risk of the Bentall operation. From January 1995 to September 2000, 69 consecutive patients with aortic expansive aneurysm and concomitant aortic valve disease, were submitted to the Bentall operation (group A, n=37) in the presence of an abnormal valve, or to root remodelling (group B, n=32) in cases of secondary aortic incompetence. One patient in group A and four in group B had Marfan syndrome. The follow-up was 1021 patient-months (range, 1-68 months) in group A and 926 in group B (1-64 months). The event-free survival was calculated using the Kaplan-Meier method, and the difference between curves was evaluated using the Mantel-Cox log-rank test. The operative mortality was 5% in group A and 0% in group B. One patient died at follow-up in group A and none in group B. Four patients (three Marfan) in group B were re-operated on because of recurrent aortic regurgitation. The 5-year event-free survival was 88+/-7% in group A and 82+/-8% in group B (P=0.58). Early residual aortic regurgitation remained stable over time only in patients with good early results. Mid-term follow-up failed to reveal statistically significant differences in the clinical outcome between remodelling and the Bentall operation. Our results support the widespread use of root remodelling, provided that an indication to this conservative approach is achieved after careful, case-by-case evaluation. A good early operative result is likely to remain stable over time.

  18. Stable and biocompatible genipin-inducing interlayer-crosslinked micelles for sustained drug release

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yu; Zhang, Xiaojin, E-mail: zhangxj@cug.edu.cn [China University of Geosciences, Faculty of Materials Science and Chemistry (China)

    2017-05-15

    To develop the sustained drug release system, here we describe genipin-inducing interlayer-crosslinked micelles crosslinked via Schiff bases between the amines of amphiphilic linear-hyperbranched polymer poly(ethylene glycol)-branched polyethylenimine-poly(ε-caprolactone) (PEG-PEI-PCL) and genipin. The generation of Schiff bases was confirmed by the color changes and UV-Vis absorption spectra of polymeric micelles after adding genipin. The particle size, morphology, stability, in vitro cytotoxicity, drug loading capacity, and in vitro drug release behavior of crosslinked micelles as well as non-crosslinked micelles were characterized. The results indicated that genipin-inducing interlayer-crosslinked micelles had better stability and biocompatibility than non-crosslinked micelles and glutaraldehyde-inducing interlayer-crosslinked micelles. In addition, genipin-inducing interlayer-crosslinked micelles were able to improve drug loading capacity, reduce the initial burst release, and achieve sustained drug release.

  19. Development of stable monolithic wide-field Michelson interferometers.

    Science.gov (United States)

    Wan, Xiaoke; Ge, Jian; Chen, Zhiping

    2011-07-20

    Bulk wide-field Michelson interferometers are very useful for high precision applications in remote sensing and astronomy. A stable monolithic Michelson interferometer is a key element in high precision radial velocity (RV) measurements for extrasolar planets searching and studies. Thermal stress analysis shows that matching coefficients of thermal expansion (CTEs) is a critical requirement for ensuring interferometer stability. This requirement leads to a novel design using BK7 and LAK7 materials, such that the monolithic interferometer is free from thermal distortion. The processes of design, fabrication, and testing of interferometers are described in detail. In performance evaluations, the field angle is typically 23.8° and thermal sensitivity is typically -2.6×10(-6)/°C near 550 nm, which corresponds to ∼800 m/s/°C in the RV scale. Low-cost interferometer products have been commissioned in multiple RV instruments, and they are producing high stability performance over long term operations. © 2011 Optical Society of America

  20. [Progress in stable isotope labeled quantitative proteomics methods].

    Science.gov (United States)

    Zhou, Yuan; Shan, Yichu; Zhang, Lihua; Zhang, Yukui

    2013-06-01

    Quantitative proteomics is an important research field in post-genomics era. There are two strategies for proteome quantification: label-free methods and stable isotope labeling methods which have become the most important strategy for quantitative proteomics at present. In the past few years, a number of quantitative methods have been developed, which support the fast development in biology research. In this work, we discuss the progress in the stable isotope labeling methods for quantitative proteomics including relative and absolute quantitative proteomics, and then give our opinions on the outlook of proteome quantification methods.

  1. "This body does not want free medicines": South African consumer perceptions of drug quality.

    Science.gov (United States)

    Patel, Aarti; Gauld, Robin; Norris, Pauline; Rades, Thomas

    2010-01-01

    OBJECTIVES Like many other developing countries, South Africa provides free medicines through its public health care facilities. Recent policies encourage generic substitution in the private sector. This study explored South African consumer perceptions of drug quality and whether these perceptions influenced how people procured and used their medicines. METHODS The study was undertaken in Durban, Cape Town and Johannesburg in South Africa between December 2005 and January 2006. A combination of purposive and snowball sampling was used to recruit participants from low and middle socio-economic groups as well as the elderly and teenagers. Data were collected through 12 focus group discussions involving a total of 73 participants. Interviews were tape-recorded. Thematic analysis was performed on the transcripts. RESULTS Irrespective of socio-economic status, respondents described medicine quality in terms of the effect the medicine produced on felt symptoms. Generic medicines, as well as medicines supplied without charge by the state, were considered to be poor quality and treated with suspicion. Respondents obtained medicines from three sources: public sector hospitals and/or clinics, dispensing doctors and community pharmacies. Cost, avoidance of feeling 'second-class', receiving individualized care and choice in drug selection were the main determinants influencing their procurement behaviour. Selection of over-the-counter medicines was influenced by prior knowledge of products, through advertising and previous use. Participants perceived that they had limited influence on selection of prescription medicines. Generic substitution would be supported if the doctor, rather than the pharmacist, recommended it. CONCLUSIONS Our findings emphasize the importance of meaningful consumer involvement in the development of national medicines policies, and strategic campaigns targeting consumers and prescribers regarding the quality of generic and essential medicines. Where

  2. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

    Science.gov (United States)

    Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco; Cirillo, Giuseppe; Vittorio, Orazio; Puoci, Francesco; Picci, Nevio; Iemma, Francesca

    2013-04-01

    Native gelatin, N, N'-ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

  3. Generalization of free-operant avoidance behavior in pigeons1

    Science.gov (United States)

    Klein, Marty; Rilling, Mark

    1974-01-01

    Three groups of four pigeons, trained to press a treadle on a free-operant avoidance schedule, were given auditory discrimination training. Alternating 2-min components of avoidance and no shock were paired with either a tone or white noise. The pigeons were subsequently given two types of generalization tests, with and without avoidable shocks scheduled. Two of the groups, trained interdimensionally, produced excitatory and inhibitory generalization gradients along the tone frequency dimension. A predicted post-discrimination gradient was computed from the algebraic summation of these gradients of excitation and inhibition. The predicted gradient was compared with the actual post-discrimination gradient obtained from the third group of pigeons that had been given intradimensional discrimination training on the tone frequency dimension. The predicted postdiscrimination gradient agreed in shape with the empirical postdiscrimination gradient. The results in general support Spence's (1937) gradient interaction theory. PMID:16811735

  4. Association of drug transporter expression with mortality and progression-free survival in stage IV head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Rolf Warta

    Full Text Available Drug transporters such as P-glycoprotein (ABCB1 have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels of a subset of drug transporters by quantitative reverse transcription polymerase chain reaction (qRT-PCR or protein expression by tissue microarray (TMA in tumor samples of therapy naïve stage IV head and neck squamous cell carcinoma (HNSCC (qRT-PCR, n = 40; TMA, n = 61, this in situ study re-examined the significance of transporter expression for progression-free survival (PFS and overall survival (OS. Data from The Cancer Genome Atlas database was used to externally validate the respective findings (n = 317. In general, HNSCC tended to lower expression of drug transporters compared to normal epithelium. High ABCB1 mRNA tumor expression was associated with both favorable progression-free survival (PFS, p = 0.0357 and overall survival (OS, p = 0.0535. Similar results were obtained for the mRNA of ABCC1 (MRP1, multidrug resistance-associated protein 1; PFS, p = 0.0183; OS, p = 0.038. In contrast, protein expression of ATP7b (copper transporter ATP7b, mRNA expression of ABCG2 (BCRP, breast cancer resistance protein, ABCC2 (MRP2, and SLC31A1 (hCTR1, human copper transporter 1 did not correlate with survival. Cluster analysis however revealed that simultaneous high expression of SLC31A1, ABCC2, and ABCG2 indicates poor survival of HNSCC patients. In conclusion, this study militates against the intuitive dogma where high expression of drug efflux transporters indicates poor survival, but demonstrates that expression of single drug transporters might indicate even improved survival. Prospectively, combined analysis of the 'transportome' should rather be performed as it likely unravels meaningful data on the impact of drug transporters on survival of patients with HNSCC.

  5. Long-term use of short- and long-acting nitrates in stable angina pectoris.

    Science.gov (United States)

    Kosmicki, Marek Antoni

    2009-05-01

    Long-acting nitrates are effective antianginal drugs during initial treatment. However, their therapeutic value is compromised by the rapid development of tolerance during sustained therapy, which means that their clinical efficacy is decreased during long-term use. Sublingual nitroglycerin (NTG), a short-acting nitrate, is suitable for the immediate relief of angina. In patients with stable angina treated with oral long-acting nitrates, NTG maintains its full anti-ischemic effect both after initial oral ingestion and after intermittent long-term oral administration. However, NTG attenuates this effect during continuous treatment, when tolerance to oral nitrates occurs, and this is called cross-tolerance. In stable angina long-acting nitrates are considered third-line therapy because a nitrate-free interval is required to avoid the development of tolerance. Nitrates vary in their potential to induce the development of tolerance. During long-lasting nitrate therapy, except pentaerythritol tetranitrate (PETN), one can observe the development of reactive oxygen species (ROS) inside the muscular cell of a vessel wall, and these bind with nitric oxide (NO). This leads to decreased NO activity, thus, nitrate tolerance. PETN has no tendency to form ROS, and therefore during long-term PETN therapy, there is probably no tolerance or cross-tolerance, as during treatment with other nitrates.

  6. Case Study: The Effect of 32 Weeks of Figure-Contest Preparation on a Self-Proclaimed Drug-Free Female's Lean Body and Bone Mass.

    Science.gov (United States)

    Petrizzo, John; DiMenna, Frederick J; Martins, Kimberly; Wygand, John; Otto, Robert M

    2017-12-01

    To achieve the criterion appearance before competing in a physique competition, athletes undergo preparatory regimens involving high-volume intense resistance and aerobic exercise with hypocaloric energy intake. As the popularity of "drug-free" competition increases, more athletes are facing this challenge without the recuperative advantage provided by performance-enhancing drugs. Consequently, the likelihood of loss of lean body and/or bone mass is increased. The purpose of this investigation was to monitor changes in body composition for a 29-year-old self-proclaimed drug-free female figure competitor during a 32-week preparatory regimen comprising high-volume resistance and aerobic exercise with hypocaloric energy intake. We used dual-energy x-ray absorptiometry (DXA) to evaluate regional fat and bone mineral density. During the initial 22 weeks, the subject reduced energy intake and engaged in resistance (4-5 sessions/week) and aerobic (3 sessions/week) training. During the final 10 weeks, the subject increased exercise frequency to 6 (resistance) and 4 (aerobic) sessions/week while ingesting 1130-1380 kcal/day. During this 10-week period, she consumed a high quantity of protein (~55% of energy intake) and nutritional supplements. During the 32 weeks, body mass and fat mass decreased by 12% and 55%, respectively. Conversely, lean body mass increased by 1.5%, an amount that exceeded the coefficient of variation associated with DXA-derived measurement. Total bone mineral density was unchanged throughout. In summary, in preparation for a figure competition, a self-proclaimed drug-free female achieved the low body-fat percentage required for success in competition without losing lean mass or bone density by following a 32-week preparatory exercise and nutritional regimen.

  7. Indolealkylamines: biotransformations and potential drug-drug interactions.

    Science.gov (United States)

    Yu, Ai-Ming

    2008-06-01

    Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.

  8. Apoptosis induction with electric pulses - A new approach to cancer therapy with drug free

    International Nuclear Information System (INIS)

    Tang, Liling; Yao, Chenguo; Sun, Caixin

    2009-01-01

    Electrical pulses have been widely used in biomedical fields, whose applications depend on the parameters such as durations and electric intensity. Conventional electroporation (0.1-1 kV/cm, 100 μs) has been used in cell fusion, transfection and electrochemotherapy. Recent studies with high-intensity (MV/cm) electric field applications with durations of several tens of nanoseconds can affect intracellular signal transduction and intracellular structures with plasma intact, resulting in an application of intracellular manipulation. The most recent development is the finding that parameters between those two ranges could be used to induce apoptosis of cancer cells. Proposal of apoptosis induction and tumor inhibition has advantages to pursue the treatment of cancer free of cytotoxic drugs.

  9. Sense of Humor, Stable Affect, and Psychological Well-Being

    Directory of Open Access Journals (Sweden)

    Arnie Cann

    2014-08-01

    Full Text Available A good sense of humor has been implicated as a quality that could contribute to psychological well-being. The mechanisms through which sense of humor might operate include helping to reappraise threats, serving as a character strength, or facilitating happiness. The current research attempts to integrate these possibilities by examining whether a good sense of humor might operate globally by helping to maintain a more stable positive affect. Stable positive affect has been shown to facilitate more effective problem solving and to build resilience. However, not all humor is adaptive humor, so we also examine the roles that different styles of humor use might play. Individual differences in humor styles were used to predict stable levels of affect. Then, in a longitudinal design, humor styles and stable affect were used to predict subsequent resilience and psychological health. The results indicated that stable affect was related to resilience and psychological well-being, and that a sense of humor that involves self-enhancing humor, humor based on maintaining a humorous perspective about one’s experiences, was positively related to stable positive affect, negatively related to stable negative affect, and was mediated through stable affect in influencing resilience, well-being and distress. Thus, while a good sense of humor can lead to greater resilience and better psychological health, the current results, focusing on stable affect, find only self-enhancing humor provides reliable benefits.

  10. First operation of a harmonic lasing self-seeded free electron laser

    International Nuclear Information System (INIS)

    Schneidmiller, E.A.; Faatz, B.; Kuhlmann, M.; Roensch-Schulenburg, J.; Schreiber, S.; Tischer, M.; Yurkov, M.V.

    2016-12-01

    Harmonic lasing is a perspective mode of operation of X-ray FEL user facilities that allows to provide brilliant beams of higher energy photons for user experiments. Another useful application of harmonic lasing is so called Harmonic Lasing Self-Seeded Free Electron Laser (HLSS FEL) that allows to improve spectral brightness of these facilities. In the past, harmonic lasing has been demonstrated in the FEL oscillators in infrared and visible wavelength ranges, but not in high-gain FELs and not at short wavelengths. In this paper we report on the first evidence of the harmonic lasing and the first operation of the HLSS FEL at the soft X-ray FEL user facility FLASH in the wavelength range between 4.5 nm and 15 nm. Spectral brightness was improved in comparison with Self-Amplified Spontaneous emission (SASE) FEL by a factor of six in the exponential gain regime. A better performance of HLSS FEL with respect to SASE FEL in the post-saturation regime with a tapered undulator was observed as well. The first demonstration of harmonic lasing in a high-gain FEL and at short wavelengths paves the way for a variety of applications of this new operation mode in X-ray FELs.

  11. Handelman's hierarchy for the maximum stable set problem

    NARCIS (Netherlands)

    Laurent, M.; Sun, Z.

    2014-01-01

    The maximum stable set problem is a well-known NP-hard problem in combinatorial optimization, which can be formulated as the maximization of a quadratic square-free polynomial over the (Boolean) hypercube. We investigate a hierarchy of linear programming relaxations for this problem, based on a

  12. Research on Utilizing a Multivariate Feedback Algorithm to Maintain Stable Operation of Variable Energy Electron Accelerators

    International Nuclear Information System (INIS)

    Van Ausdeln, L.A.; Cordes, G.A.; Haskell, K.J.; Jones, J.L.

    2002-01-01

    Measurements performed utilizing particle accelerators rely on the stability and reproducibility of the accelerator operation, most notably for beam flux (beam current) and beam energy. This can be vital when the measurements rely on previous calibrations performed to establish a standard on which to base the end result of the measurement. The authors have designed a monitoring and control virtual instrument (VI) based on National Instruments LabVIEW TM which calls external modeling code that is written in a standard programming language. The LabVIEWTM virtual instrument allows the user to monitor multiple accelerator parameters while permitting user control of the most important four of these parameters which determine machine operation. The external modeling code, the Advanced Data Validation and Verification System (ADVVS), incorporates as a kernel the Universal Process Model (UPM) software from Triant Technologies, Inc. The kernel executes the accelerator modeling function based on previously acquired history data of the relevant parameters for accelerator operation for conditions of interest. This history data is stored as a reference set prior to subsequent operation. During accelerator operation, 11 accelerator parameters are input to ADVVS from the LabVIEW TM virtual instrument. The ADVVS uses the reference files to predict the eleven parameter values that would normally be expected for optimal accelerator operation. The set of 11 model values is the nearest model state. This multivariate modeling approach presented two principal advantages: 1. The ADVVS allowed rapid detection of anomalous accelerator behavior variant from normal accelerator behavior recorded in the reference set of the kernel. 2. The ADVVS presented a methodology to incrementally tune the accelerator back to optimal operation, thus maintaining highly stable and reproducible operation. In the future, this methodology may also be utilized to tune the accelerator initially or move

  13. Clinical and sociodemographic correlates of severe insomnia in psychotropic drug-free, Asian outpatients with major depressive disorder.

    Science.gov (United States)

    Srisurapanont, Manit; Likhitsathian, Surinporn; Chua, Hong Choon; Udomratn, Pichet; Chang, Sungman; Maneeton, Narong; Maneeton, Benchaluk; Chen, Chia-Hui; Shih-Yen Chan, Edwin; Bautista, Dianne; Bin Sulaiman, Ahmad Hatim

    2015-11-01

    Little has been known regarding the correlates of severe insomnia in major depressive disorder (MDD). This post-hoc analysis aimed to examine the sociodemographic and clinical correlates of severe insomnia in psychotropic drug-free, Asian adult outpatients with MDD. Participants were psychotropic drug-free patients with MDD, aged 18-65 years. By using the Symptom Checklist-90 Items, Revised (SCL-90-R), a score of 4 (severe distress) on any one of three insomnia items was defined as severe insomnia. Other measures included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the nine psychopathology subscales of SCL-90-R, the Physical and Mental Component Summaries of Short Form Health Survey (SF-36 PCS and SF-36 MCS), and the Sheehan Disability Scale (SDS). Of 528 participants, their mean age being 39.5 (SD=13.26) years, 64.2% were females, and 239 (45.3%) had severe insomnia. The logistic regression model revealed that low educational qualifications (less than secondary school completion), high SCL-90-R Depression scores, high SCL-90-R Anxiety scores, and low SF-36 PCS scores were independently correlated with severe insomnia (p'sdepression and anxiety severity, and poor physical health. These findings may implicate the treatment of comorbid MDD and severe insomnia, for example, sleep hygiene education, pharmacological treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Wind tunnel tests of a free yawing downwind wind turbine

    DEFF Research Database (Denmark)

    Verelst, David Robert; Larsen, Torben J.; van Wingerden, J.W.

    2012-01-01

    During February and April 2012 a series of wind tunnel tests were performed at the TU Delft Open Jet Facility (OJF) with a three bladed downwind wind turbine and a rotor radius of 0.8 meters. The setup includes an off the shelf three bladed hub, nacelle and generator on which relatively flexible ...... in free yawing conditions. Further, the effect of the tower shadow passage on the blade flapwise strain measurement is evaluated. Finally, data from the experiment is compared with preliminary simulations using DTU Wind Energy's aeroelastic simulation program HAWC2....... blades are mounted. The tower support structure has free yawing capabilities provided at the tower base. A short overview on the technical details of the experiment is provided as well as a brief summary of the design process. The discussed test cases show that the turbine is stable while operating...

  15. Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals.

    Science.gov (United States)

    Stanjek-Cichoracka, A; Żegleń, S; Ramos, P; Pilawa, B; Wojarski, J

    2018-06-01

    The immunosuppressive drugs used in solid organ transplantation or autoimmunological processes were studied by electron paramagnetic resonance (EPR) spectroscopy to estimate their free radical scavenging activity. The interactions of immunosuppressants with free radicals were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free radicals. The EPR spectra of DPPH and DPPH interacting with individual drugs were compared. Kinetic studies were performed, and the effect of ultraviolet (UV) irradiation on the free radical scavenging activity of the tested drugs was determined. The free radical scavenging activity of non-irradiated drugs decreased in the order: rapamycin > mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the free radical scavenging activity of all the tested immunosuppressive drugs, and the effect was highest for tacrolimus. For the non-irradiated samples, the speed of free radical interactions decreased in the order: ciclosporin > tacrolimus > mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the speed of interactions of the immunosuppressive drugs with the model DPPH free radicals. Electron paramagnetic resonance spectroscopy is useful for obtaining information on interactions of immunosuppressive drugs with free radicals. We hypothesized that the long-term immunosuppressive effects of these drugs after transplantation or during autoimmune disorders may be mediated by anti-inflammatory action in addition to the known receptor/cell cycle inhibition. © 2018 John Wiley & Sons Ltd.

  16. Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

    Science.gov (United States)

    Lamprou, Dimitrios A.; Venkatpurwar, Vinod; Kumar, M. N. V. Ravi

    2013-01-01

    Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ∼280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics. PMID:23724054

  17. Requirements and design of a high stable infrared free electron laser at LBL

    International Nuclear Information System (INIS)

    Kim, K.J.; Berz, M.; Chattopadhyay, S.; Gough, R.; Kim, C.; Kung, A.H.; Xie, M.; Edighoffer, J.; Stein, W.

    1990-06-01

    An infrared free electron laser (IRFEL) is being designed for the Chemical Dynamics Research Laboratory (CDRL) at LBL. The FEL is based on a 50 MeV RF linac operating in synchronization to the Advanced Light Source (ALS), and will produce intense (100 μJ per micropulse), narrow bandwidth (narrower than 0.1%) radiation between 3 μ and 50 μ. In the design, we pay particular attention to the FEL stability issues and require that the fluctuations in electron beam energy and in timing be less than 0.05% and 0.1 ps, respectively. The FEL spectrum can then be stabilized to about 10 -3 , or if grating is used, to 10 -4 . We discuss various sources of fluctuations in the gun, the bunchers and the accelerator sections, as well as the feedback and feedforward schemes to reduce these fluctuations. The accelerator structure is chosen to be of the side coupled, standing wave type for easier control. The beam transport is made isochronous to avoid the coupling between the energy and the timing fluctuations. 9 refs., 2 figs

  18. Some New Components of the Moduli Scheme MP3(2; -1; 2; 0 of Stable Coherent Torsion Free Sheaves of Rank 2 on P3

    Directory of Open Access Journals (Sweden)

    M. A. Zavodchikov

    2012-01-01

    Full Text Available In this paper we consider Giseker-Maruyama moduli scheme M := MP3(2;¡1; 2; 0 of stable coherent torsion free sheaves of rank 2 with Chern classes c1 = -1, c2 = 2, c3 = 0 on 3-dimensional projective space P3. We will de¯ne two sets of sheaves M1 and M2 in M and we will prove that closures of M1 and M2 in M are irreducible components of dimensions 15 and 19, accordingly.

  19. Why Are Drugs So Hard to Quit?

    Medline Plus

    Full Text Available ... Get YouTube Red. Working... Not now Try it free Find out why Close Why Are Drugs So ... Dr. Nora Volkow on Addiction: A Disease of Free Will - Duration: 21:12. National Institute on Drug ...

  20. A remotely operated drug delivery system with an electrolytic pump and a thermo-responsive valve

    KAUST Repository

    Yi, Ying

    2015-07-22

    Implantable drug delivery devices are becoming attractive due to their abilities of targeted and controlled dose release. Currently, two important issues are functional lifetime and non-controlled drug diffusion. In this work, we present a drug delivery device combining an electrolytic pump and a thermo-responsive valve, which are both remotely controlled by an electromagnetic field (40.5 mT and 450 kHz). Our proposed device exhibits a novel operation mechanism for long-term therapeutic treatments using a solid drug in reservoir approach. Our device also prevents undesired drug liquid diffusions. When the electromagnetic field is on, the electrolysis-induced bubble drives the drug liquid towards the Poly (N-Isopropylacrylamide) (PNIPAM) valve that consists of PNIPAM and iron micro-particles. The heat generated by the iron micro-particles causes the PNIPAM to shrink, resulting in an open valve. When the electromagnetic field is turned off, the PNIPAM starts to swell. In the meantime, the bubbles are catalytically recombined into water, reducing the pressure inside the pumping chamber, which leads to the refilling of the fresh liquid from outside the device. A catalytic reformer is included, allowing more liquid refilling during the limited valve\\'s closing time. The amount of body liquid that refills the drug reservoir can further dissolve the solid drug, forming a reproducible drug solution for the next dose. By repeatedly turning on and off the electromagnetic field, the drug dose can be cyclically released, and the exit port of the device is effectively controlled.

  1. A remotely operated drug delivery system with an electrolytic pump and a thermo-responsive valve

    KAUST Repository

    Yi, Ying; Zaher, Amir; Yassine, Omar; Kosel, Jü rgen; Foulds, Ian G.

    2015-01-01

    Implantable drug delivery devices are becoming attractive due to their abilities of targeted and controlled dose release. Currently, two important issues are functional lifetime and non-controlled drug diffusion. In this work, we present a drug delivery device combining an electrolytic pump and a thermo-responsive valve, which are both remotely controlled by an electromagnetic field (40.5 mT and 450 kHz). Our proposed device exhibits a novel operation mechanism for long-term therapeutic treatments using a solid drug in reservoir approach. Our device also prevents undesired drug liquid diffusions. When the electromagnetic field is on, the electrolysis-induced bubble drives the drug liquid towards the Poly (N-Isopropylacrylamide) (PNIPAM) valve that consists of PNIPAM and iron micro-particles. The heat generated by the iron micro-particles causes the PNIPAM to shrink, resulting in an open valve. When the electromagnetic field is turned off, the PNIPAM starts to swell. In the meantime, the bubbles are catalytically recombined into water, reducing the pressure inside the pumping chamber, which leads to the refilling of the fresh liquid from outside the device. A catalytic reformer is included, allowing more liquid refilling during the limited valve's closing time. The amount of body liquid that refills the drug reservoir can further dissolve the solid drug, forming a reproducible drug solution for the next dose. By repeatedly turning on and off the electromagnetic field, the drug dose can be cyclically released, and the exit port of the device is effectively controlled.

  2. Food, drugs, and droods: a historical consideration of definitions and categories in American food and drug law.

    Science.gov (United States)

    Grossman, Lewis A

    2008-07-01

    This Article explores the evolution and interaction of the legal and cultural categories "food" and "drug" from the late nineteenth century to the present. The federal statutory definitions of "food" and "drug" have always been ambiguous and plastic, providing the FDA with significant regulatory flexibility. Nevertheless, the agency is not necessarily free to interpret the definitions however it chooses. "Food" and "drug" are not only product classes defined by food and drug law, but also fundamental cultural concepts. This Article demonstrates that the FDA, as well as Congress and the courts, have operated within a constraining cultural matrix that has limited their freedom to impose their preferred understandings of these categories on American society. Nonetheless, history also provides ample evidence that lawmakers possess substantial power to mold the legal categories of "food" and "drug" so as to advance desired policies. One explanation for this regulatory flexibility in the face of deep-seated cultural conceptions is the indeterminate nature of the extralegal notions of "food" and "drug." The terms, as commonly understood, embrace nebulous, overlapping, and constantly evolving realms. Moreover, the relationship between culture and law is not a one-way street with respect to these categories. Although the regulatory apparatus has always had to take into account the extralegal understandings of "food" and "drug," the law in turn has exerted significant influence over their meaning in broader culture.

  3. Improving the Communication Pattern in Matrix-Vector Operations for Large Scale-Free Graphs by Disaggregation

    Energy Technology Data Exchange (ETDEWEB)

    Kuhlemann, Verena [Emory Univ., Atlanta, GA (United States); Vassilevski, Panayot S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2013-10-28

    Matrix-vector multiplication is the key operation in any Krylov-subspace iteration method. We are interested in Krylov methods applied to problems associated with the graph Laplacian arising from large scale-free graphs. Furthermore, computations with graphs of this type on parallel distributed-memory computers are challenging. This is due to the fact that scale-free graphs have a degree distribution that follows a power law, and currently available graph partitioners are not efficient for such an irregular degree distribution. The lack of a good partitioning leads to excessive interprocessor communication requirements during every matrix-vector product. Here, we present an approach to alleviate this problem based on embedding the original irregular graph into a more regular one by disaggregating (splitting up) vertices in the original graph. The matrix-vector operations for the original graph are performed via a factored triple matrix-vector product involving the embedding graph. And even though the latter graph is larger, we are able to decrease the communication requirements considerably and improve the performance of the matrix-vector product.

  4. Study on the flow reduction of forced flow superconducting magnet and its stable operation condition

    Energy Technology Data Exchange (ETDEWEB)

    Sugimoto, Makoto [Japan Atomic Energy Research Inst., Naka, Ibaraki (Japan). Naka Fusion Research Establishment

    2001-03-01

    The forced flow superconducting coil especially made from a Cable-in-Conduit Conductor (CICC) is applied for large-scale devices such as fusion magnets and superconducting magnet energy storage (SMES) because it has high mechanical and electrical performance potential. The flow reduction phenomena caused by AC loss generation due to the pulsed operation was found based on the experimental results of three forced flow superconducting coils. And relation between the AC loss generation and flow reduction was defined from viewpoint of the engineering design and operation of the coils. Also the mechanism of flow reduction was investigated and stable operation condition under the flow reduction was clarified for forced flow superconducting coils. First, experiments of three different large-scale superconducting coils were carried out and experimental database of the flow reduction by AC loss generation was established. It was found experimentally that the flow reduction depends on the AC loss generation (W/m{sup 3}) in all of coils. It means the stable operation condition is defined not only the electro magnetism of superconducting coil but also flow condition. Mechanism of the flow reduction was investigated based on the experimental database. Hydraulics was applied to supercritical helium as a coolant. Also performances of the cryogenic pump by which coolant are supplied to the coil and friction of the superconductor as cooling path is considered for hydraulic estimation. The flow reduction of the coil is clarified and predictable by the equations of continuity, momentum and energy balance. Also total mass flow rate of coolant was discussed. The estimation method in the design phase was developed for total mass flow rate which are required under the flow reduction by AC losses. The friction of the superconductor and performance of cryogenic pump should be required for precise prediction of flow reduction. These values were obtained by the experiment data of coil and

  5. Research on the operation characteristics of a free-piston linear generator: Numerical model and experimental results

    International Nuclear Information System (INIS)

    Guo, Chendong; Feng, Huihua; Jia, Boru; Zuo, Zhengxing; Guo, Yuyao; Roskilly, Tony

    2017-01-01

    Highlights: • The operation process of free-piston linear generator is investigated. • The larger the motor force at the starting process, the fewer circulations of the piston reciprocating to meet ignition condition. • The “gradually switching strategy” is the best strategy in the intermediate process. • During the generating process, engines indicated power is 2.9 kW with an efficiency of 37.3% under medium load. - Abstract: Free piston linear generator (FPLG) shows unique operation characteristics due to the elimination of crankshaft and connecting rod mechanism. This paper investigates its operation characteristics during each operating process based on the simulation and experiment results. During the starting process, the larger motor force during the starting process, the fewer times of reciprocating pistons which meet the condition of ignition. When the motor force reached 300 N, the prototype could adopt one-stroke starting strategy. During the intermediate process, it was found that the “gradually switching strategy” could help to achieve a smoother operation during the intermediate process. And the values of the operation parameters after the intermediate process were lower than those before the intermediate process. During the generating process, cycle-to-cycle variations were observed for piston TDC and in-cylinder gas pressure from the experimental results. According to the experimental results of the FPLG during the generating process, the calculated engine indicated power is 2.9 kW, and the corresponding indicated thermal efficiency is 37.3%. Additionally, based on the comparison of the FPLG performance, it is found that the parameters of the FPLG during the generating process are smaller than those when it was operated during the second stage of the starting process, while much higher than those during the first stage of the starting process.

  6. Protein-free transfection of CHO host cells with an IgG-fusion protein: selection and characterization of stable high producers and comparison to conventionally transfected clones.

    Science.gov (United States)

    Lattenmayer, Christine; Loeschel, Martina; Schriebl, Kornelia; Steinfellner, Willibald; Sterovsky, Thomas; Trummer, Evelyn; Vorauer-Uhl, Karola; Müller, Dethardt; Katinger, Hermann; Kunert, Renate

    2007-04-15

    In order to improve the current techniques of cell cultivation in the absence of serum, we have developed a protein-free transfection protocol for CHO cells, based on the Nucleofector technology. After starting with a heterogeneous pool of primary transfectants which express the fusion protein EpoFc, we isolated single clones and compared them with parallel clones generated by lipofection in serum-dependent cultivation. Our intensive characterization program was based on determination of specific productivity (q(p)) and analysis of genetic parameters. In two nucleofection experiments, transfection with 5 microg of DNA resulted in best productivities of the primary cell pools. After subcloning, the q(p) could be raised up to 27 pg x cells(-1) x day(-1). While the serum-dependent transfectants exhibited specific productivities up to 57 pg x cells(-1) x day(-1) in serum-dependent cultivation, a significant decrease that resulted in the range of q(p) of the protein-free transfectants was observed after switching to protein-free conditions. Investigation of genetic parameters revealed higher mRNA levels and gene copy numbers (GCN) for the protein-free adapted serum-dependent transfectants. Therefore, we assume that problems during protein-free adaptation (PFA) lead to a less efficient translation machinery after serum deprivation. We describe the generation of stable-producing recombinant CHO clones by protein-free transfection of a protein-free adapted host cell line, which reduces the risk of adverse clonal changes after PFA. The main advantage of this approach is the earlier predictability of clone behavior, which makes the generation of production clones by protein-free transfection, a viable and highly efficient strategy for recombinant cell line development. (c) 2006 Wiley Periodicals, Inc.

  7. Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

    DEFF Research Database (Denmark)

    Marshall, Alison D; Cunningham, Evan B; Nielsen, Stine

    2018-01-01

    for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co......-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis...... of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver....

  8. The free energy profile of tubulin straight-bent conformational changes, with implications for microtubule assembly and drug discovery.

    Directory of Open Access Journals (Sweden)

    Lili X Peng

    2014-02-01

    Full Text Available αβ-tubulin dimers need to convert between a 'bent' conformation observed for free dimers in solution and a 'straight' conformation required for incorporation into the microtubule lattice. Here, we investigate the free energy landscape of αβ-tubulin using molecular dynamics simulations, emphasizing implications for models of assembly, and modulation of the conformational landscape by colchicine, a tubulin-binding drug that inhibits microtubule polymerization. Specifically, we performed molecular dynamics, potential-of-mean force simulations to obtain the free energy profile for unpolymerized GDP-bound tubulin as a function of the ∼12° intradimer rotation differentiating the straight and bent conformers. Our results predict that the unassembled GDP-tubulin heterodimer exists in a continuum of conformations ranging between straight and bent, but, in agreement with existing structural data, suggests that an intermediate bent state has a lower free energy (by ∼1 kcal/mol and thus dominates in solution. In agreement with predictions of the lattice model of microtubule assembly, lateral binding of two αβ-tubulins strongly shifts the conformational equilibrium towards the straight state, which is then ∼1 kcal/mol lower in free energy than the bent state. Finally, calculations of colchicine binding to a single αβ-tubulin dimer strongly shifts the equilibrium toward the bent states, and disfavors the straight state to the extent that it is no longer thermodynamically populated.

  9. Performance evaluation of free piston compressor coupling organic Rankine cycle under different operating conditions

    International Nuclear Information System (INIS)

    Han, Yongqiang; Kang, Jianjian; Zhang, Guangpan; Liu, Zhongchang; Tian, Jing; Chai, Jiahong

    2014-01-01

    Highlights: • An ORC-FPC is proposed to recover the waste heat of exhaust gas. • The simulation model has been established in GT-Suite ver. 7.0. • Performances of ORC-FPC under different operating conditions have been evaluated. • Performances prediction of the ORC-FPC for real application has been made in the paper. - Abstract: An organic Rankine cycle coupling free piston compressor (ORC-FPC) system has been proposed, which is used in recovering the waste heat of exhaust gas from the stationary compressed nature gas (CNG) fueled internal combustion compressor. The free piston compressor functions as an expander in ORC and operates reciprocally to compress natural gas in compression cylinders to demanded pressure. After capturing the waste heat available and turning into vapor in evaporator, the working fluid R245ca can provide power to drive the free piston moving reciprocally in expander. The model of ORC-FPC built up in the GT-suite ver. 7.0 assists evaluating performances of this system under different operating conditions. In this paper, the operating condition includes two aspects: thermodynamic state of working fluid and input power. The purpose of simulation based on the model is to specify appropriate thermodynamic states of working fluid which yield high value of η (the ratio of work produced by the power piston to enthalpy reduction of working fluid in the power cylinder) and k (the ratio of output CNG’s mass to enthalpy reduction of working fluid in the power cylinder) value. Performances of the ORC-FPC under different input power, which determined by the operating frequency and injection quantity of the heated working fluid, have also been evaluated. Results show that when the heated working fluid is at 11.5 bar and 383 K, the system achieves better performances than other thermodynamic states, of which k is 601.1 mg/kJ and η is 44.3%. Based on the optimum thermodynamic state and the principle of obtaining the maximum k, the specific input

  10. Punishing second-order free riders before first-order free riders: The effect of pool punishment priority on cooperation

    OpenAIRE

    Ozono, Hiroki; Kamijo, Yoshio; Shimizu, Kazumi

    2017-01-01

    Second-order free riders, who do not owe punishment cost to first-order free riders in public goods games, lead to low cooperation. Previous studies suggest that for stable cooperation, it is critical to have a pool punishment system with second-order punishment, which gathers resources from group members and punishes second-order free riders as well as first-order free riders. In this study, we focus on the priority of punishment. We hypothesize that the pool punishment system that prioritiz...

  11. Indolealkylamines: Biotransformations and Potential Drug–Drug Interactions

    OpenAIRE

    Yu, Ai-Ming

    2008-01-01

    Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug–drug interactions (DDIs). A stable, principal metabolite of an IAA drug of ab...

  12. Investigation and prevention of droplet splashing during operation of a sodium free jet flow

    International Nuclear Information System (INIS)

    Stoppel, L.; Gordeev, S.; Wetzel, T.; Fellmoser, F.; Daubner, M.

    2010-01-01

    Many accelerator application concepts consider liquid metal as a windowless target, at which the particle beam does directly hit the liquid. One of such concepts is studied in the European project ''DIRAC-Secondary beams - Design Study''. This project is focused on the preliminary research work for construction of a new international particle accelerator - Facility for Antiproton and Ion Research (FAIR) in Darmstadt. The planned accelerator is aimed to work with high-energy heavy-ions, such as U 238 . One of the key elements of the FAIR facility is a liquid-metal-target, made in the form of a rectangular shaped Lithium jet aligned with the gravity vector. In the course of preliminary investigations the theoretical and practical conditions for a stable liquid-metal-jet conforming to the FAIR-requirements have been studied in the Karlsruhe Liquid Metal Laboratory (KALLA) sodium facility. The acquired scientific and technological results can be transferred to liquid-metal targets in nuclear applications, for example, the IFMIF-Target for the study of fusion reactor materials and the Myrrah/XT-ADS target. The main goals of the KALLA-part of the project were to design and build a facility for experimental research on hydrodynamic phenomena of the free surface liquid metal flow as well as to look at technological problems influencing the hydrodynamic stability of such flows. One of such problems emerged already during the startup of the facility: Splashing of liquid metal drops in the vacuum volume of the target box. As a result of such splashing process, liquid metal droplets are accumulated on various internal constructional elements of the target box, for example, on the inspection windows. This effect prohibits long term operation with the facility. The present paper describes the methods used to reduce the splashing to a minimum. (orig.)

  13. Scaffold-free 3D bio-printed human liver tissue stably maintains metabolic functions useful for drug discovery.

    Science.gov (United States)

    Kizawa, Hideki; Nagao, Eri; Shimamura, Mitsuru; Zhang, Guangyuan; Torii, Hitoshi

    2017-07-01

    The liver plays a central role in metabolism. Although many studies have described in vitro liver models for drug discovery, to date, no model has been described that can stably maintain liver function. Here, we used a unique, scaffold-free 3D bio-printing technology to construct a small portion of liver tissue that could stably maintain drug, glucose, and lipid metabolism, in addition to bile acid secretion. This bio-printed normal human liver tissue maintained expression of several kinds of hepatic drug transporters and metabolic enzymes that functioned for several weeks. The bio-printed liver tissue displayed glucose production via cAMP/protein kinase A signaling, which could be suppressed with insulin. Bile acid secretion was also observed from the printed liver tissue, and it accumulated in the culture medium over time. We observed both bile duct and sinusoid-like structures in the bio-printed liver tissue, which suggested that bile acid secretion occurred via a sinusoid-hepatocyte-bile duct route. These results demonstrated that our bio-printed liver tissue was unique, because it exerted diverse liver metabolic functions for several weeks. In future, we expect our bio-printed liver tissue to be applied to developing new models that can be used to improve preclinical predictions of long-term toxicity in humans, generate novel targets for metabolic liver disease, and evaluate biliary excretion in drug development.

  14. Biodegradable gelatin-based nanospheres as pH-responsive drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Curcio, Manuela; Altimari, Ilaria; Spizzirri, Umile Gianfranco, E-mail: g.spizzirri@unical.it; Cirillo, Giuseppe [University of Calabria, Department of Pharmacy, Health and Nutrition Sciences (Italy); Vittorio, Orazio [NEST Scuola Normale Superiore, Istituto Nanoscienze-CNR (Italy); Puoci, Francesco; Picci, Nevio; Iemma, Francesca [University of Calabria, Department of Pharmacy, Health and Nutrition Sciences (Italy)

    2013-04-15

    Native gelatin, N,N Prime -ethylenebisacrylamide, and sodium methacrylate were inserted into a spherical crosslinked structure by a solvent-free emulsion polymerization method, in which sunflower seed oil containing different amounts of lecithin was selected as continuous phase. Nanogels were characterized by morphological analysis, particle size distribution, and determination of swelling degree. Different dimensional distributions (100-500 nm) and water affinities were obtained by varying the amount of surfactant in the polymerization feed. Nanogels were non-toxic on human bone marrow mesenchymal stromal cells and enzymatically stable in the gastric tract, with weight losses ranging from 58 to 20 % in pancreatin solution. Release profiles of diclofenac sodium salt from the nanogels were evaluated at different pH and found to depend on crosslinking degree and drug-polymer interactions; while in pancreatin solution, a complete release of the drug was observed. The release mechanism and the diffusional contribution were evaluated by semiempirical equations.

  15. 1-Dodecanethiol based highly stable self-assembled monolayers for germanium passivation

    International Nuclear Information System (INIS)

    Cai, Qi; Xu, Baojian; Ye, Lin; Di, Zengfeng; Huang, Shanluo; Du, Xiaowei; Zhang, Jishen; Jin, Qinghui; Zhao, Jianlong

    2015-01-01

    Highlights: • A simple and effective approach for higly stable germanium passivation. • 1-Dodecanethiol self-assembled monolayers for germanium oxidation resistance. • The influence factors of germanium passivation were systematically studied. • The stability of the passivated Ge was more than 10 days even in water conditions. - Abstract: As a typical semiconductor material, germanium has the potential to replace silicon for future-generation microelectronics, due to its better electrical properties. However, the lack of stable surface state has limited its extensive use for several decades. In this work, we demonstrated highly stable self-assembled monolayers (SAMs) on Ge surface to prevent oxidization for further applications. After the pretreatment in hydrochloric acid, the oxide-free and Cl-terminated Ge could be further coated with 1-dodecanethiol (NDM) SAMs. The influence factors including reaction time, solvent component and reaction temperature were optimized to obtain stable passivated monolayer for oxidation resistance. Contact angle analysis, atomic force microscopy, ellipsometer and X-ray photoelectron spectroscopy were performed to characterize the functionalized Ge surface respectively. Meanwhile, the reaction mechanism and stability of thiols SAMs on Ge (1 1 1) surface were investigated. Finally, highly stable passivated NDM SAMs on Ge surface could be formed through immersing oxide-free Ge in mixture solvent (water/ethanol, v/v = 1:1) at appropriately elevated temperature (∼80 °C) for 24 h. And the corresponding optimized passivated Ge surface was stable for more than 10 days even in water condition, which was much longer than the data reported and paved the way for the future practical applications of Ge.

  16. 1-Dodecanethiol based highly stable self-assembled monolayers for germanium passivation

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Qi [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Xu, Baojian, E-mail: xbj@mail.sim.ac.cn [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Shanghai Internet of Things Co., LTD, No. 1455, Pingcheng Road, Shanghai 201899 (China); Ye, Lin [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Di, Zengfeng [State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Huang, Shanluo; Du, Xiaowei [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); University of Chinese Academy of Sciences, No. 19A, Yuquan Road, Beijing 100049 (China); Zhang, Jishen; Jin, Qinghui [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China); Zhao, Jianlong, E-mail: jlzhao@mail.sim.ac.cn [State Key Laboratory of Transducer Technology, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, No. 865, Changning Road, Shanghai 200050 (China)

    2015-10-30

    Highlights: • A simple and effective approach for higly stable germanium passivation. • 1-Dodecanethiol self-assembled monolayers for germanium oxidation resistance. • The influence factors of germanium passivation were systematically studied. • The stability of the passivated Ge was more than 10 days even in water conditions. - Abstract: As a typical semiconductor material, germanium has the potential to replace silicon for future-generation microelectronics, due to its better electrical properties. However, the lack of stable surface state has limited its extensive use for several decades. In this work, we demonstrated highly stable self-assembled monolayers (SAMs) on Ge surface to prevent oxidization for further applications. After the pretreatment in hydrochloric acid, the oxide-free and Cl-terminated Ge could be further coated with 1-dodecanethiol (NDM) SAMs. The influence factors including reaction time, solvent component and reaction temperature were optimized to obtain stable passivated monolayer for oxidation resistance. Contact angle analysis, atomic force microscopy, ellipsometer and X-ray photoelectron spectroscopy were performed to characterize the functionalized Ge surface respectively. Meanwhile, the reaction mechanism and stability of thiols SAMs on Ge (1 1 1) surface were investigated. Finally, highly stable passivated NDM SAMs on Ge surface could be formed through immersing oxide-free Ge in mixture solvent (water/ethanol, v/v = 1:1) at appropriately elevated temperature (∼80 °C) for 24 h. And the corresponding optimized passivated Ge surface was stable for more than 10 days even in water condition, which was much longer than the data reported and paved the way for the future practical applications of Ge.

  17. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.; Buttner, Ulrich; Yi, Ying

    2016-01-01

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  18. Drug delivery device including electrolytic pump

    KAUST Repository

    Foulds, Ian G.

    2016-03-31

    Systems and methods are provided for a drug delivery device and use of the device for drug delivery. In various aspects, the drug delivery device combines a “solid drug in reservoir” (SDR) system with an electrolytic pump. In various aspects an improved electrolytic pump is provided including, in particular, an improved electrolytic pump for use with a drug delivery device, for example an implantable drug delivery device. A catalytic reformer can be incorporated in a periodically pulsed electrolytic pump to provide stable pumping performance and reduced actuation cycle.

  19. A review on proniosomal drug delivery system for targeted drug action

    OpenAIRE

    Radha, G. V.; Rani, T. Sudha; Sarvani, B.

    2013-01-01

    Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical po...

  20. Drug Revolving Fund-Based

    African Journals Online (AJOL)

    Background: The Drug Revolving Fund (DRF) was instituted in 1996 in Oyo State to ensure sustainable drug availability at primary health care level with a seed stock of drugs supplied by the Petroleum Trust Fund. This was discontinued in 1999 and replaced in January 2000, with free health service, which involves ...

  1. Harmonic operation of high gain harmonic generation free electron laser

    International Nuclear Information System (INIS)

    Deng Haixiao; Chinese Academy of Sciences, Beijing; Dai Zhimin

    2008-01-01

    In high gain harmonic generation (HGHG) free electron laser (FEL), with the right choice of parameters of the modulator undulator, the dispersive section and the seed laser, one may make the spatial bunching of the electron beam density distribution correspond to one of the harmonic frequencies of the radiator radiation, instead of the fundamental frequency of the radiator radiation in conventional HGHG, thus the radiator undulator is in harmonic operation (HO) mode. In this paper, we investigate HO of HGHG FEL. Theoretical analyses with universal method are derived and numerical simulations in ultraviolet and deep ultraviolet spectral regions are given. It shows that the power of the 3rd harmonic radiation in the HO of HGHG may be as high as 18.5% of the fundamental power level. Thus HO of HGHG FEL may obtain short wavelength by using lower beam energy. (authors)

  2. Dietary Intake, Body Composition, and Menstrual Cycle Changes during Competition Preparation and Recovery in a Drug-Free Figure Competitor: A Case Study

    Science.gov (United States)

    Halliday, Tanya M.; Loenneke, Jeremy P.; Davy, Brenda M.

    2016-01-01

    Physique competitions are events in which competitors are judged on muscular appearance and symmetry. The purpose of this retrospective case study was to describe changes in dietary intake, body mass/composition, and the menstrual cycle during the 20-week competition preparation (PREP) and 20-week post competition recovery (REC) periods of a drug-free amateur female figure competitor (age = 26–27, BMI = 19.5 kg/m2). Dietary intake (via weighed food records) and body mass were assessed daily and averaged weekly. Body composition was estimated via Dual-energy X-ray absorptiometry (DXA) and 7-site skinfold measurements. Energy intake, body mass and composition, and energy availability decreased during the 20-week PREP period (changes of ~298 kcals, 5.1 kg, 6.5% body fat, and 5.4 kcal/kg fat free mass, respectively) and returned to baseline values by end of the 20-week REC period. Menstrual cycle irregularity was reported within the first month of PREP and the last menstruation was reported at week 11 of PREP. Given the potentially adverse health outcomes associated with caloric restriction, future, prospective cohort studies on the physiological response to PREP and REC are warranted in drug-free, female physique competitors. PMID:27879627

  3. The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients

    DEFF Research Database (Denmark)

    Koefoed-Nielsen, Pernille Bundgaard; Karamperis, Nikolaos; Jørgensen, Kaj Anker

    2006-01-01

    in determining optimal doses. Forty stable renal transplant patients were investigated three times in a 6-month period. Blood samples were drawn at 0, 1, 2, 3 and 4 h after oral intake of tacrolimus (FK) or cyclosporin at days 1 and 180. At day 90, one blood sample at trough level (FK) or C2 level (cyclosporin A...... significantly different effects on calcineurin activity in renal transplant patients with stable, well-functioning grafts and that tacrolimus-treated patients can maintain good, stable graft function with minimal CaN inhibition.......Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in organ transplantation. Dosing and monitoring these drugs is based on pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin phosphatase (CaN) activity, could be a valuable supplement...

  4. Trends in the use of stable isotopes in biochemistry and pharmacology

    International Nuclear Information System (INIS)

    Matwiyoff, N.A.; Walker, T.E.

    1977-01-01

    Recent trends in the use of the stable isotopes 13 C, 15 N and 18 O in biochemistry and pharmacology are reviewed with emphasis on the studies that have employed nuclear magnetic resonance (nmr) spectroscopy and mass spectrometry as analytical techniques. Pharmacological studies with drugs and other compounds labelled with stable isotopes have developed in parallel with the rapid progress in the enhancement of sensitivity and selectivity of gas chromatography - mass spectrometric analyses, and have been directed largely to an evaluation of pharmako-kinetics and drug metabolic pathways. In these studies, illustrated with selected samples, isotopically labelled compounds have been used to advantage as internal standards for the mass spectrometric analyses and as in vivo tracers for metabolites. In the broader discipline of biochemistry, stable isotopes and isotopically labelled compounds have been used increasingly in conjuction with both nmr spectroscopy and mass spectrometry in tracer and structural studies. The more recent trends in the use of stable isotopes in these biochemical studies are discussed in the context of the improvements in analytical techniques. Specific examples will be drawn from investigations of the biosynthesis of natural products by micro-organisms; the protein, fat and carbohydrate fluxes in humans; and the structure and function of enzymes, membranes and other macro-molecular assemblages. The potential for the future development of stable isotopes in biochemistry and pharmacology are considered briefly, together with some of the problems that must be solved if their considerable potential is to be realized. (author)

  5. Layered gadolinium hydroxides for simultaneous drug delivery and imaging.

    Science.gov (United States)

    Xu, Yadong; Goyanes, Alvaro; Wang, Yuwei; Weston, Andrew J; So, Po-Wah; Geraldes, Carlos F G C; Fogg, Andrew M; Basit, Abdul W; Williams, Gareth R

    2018-02-27

    The potential of the layered gadolinium hydroxide (LGdH) [Gd 2 (OH) 5 ]Cl·yH 2 O (LGdH-Cl) for simultaneous drug delivery and magnetic resonance imaging was explored in this work. Three non-steroidal anti-inflammatory drugs (diclofenac [dic], ibuprofen [ibu], and naproxen [nap]) were intercalated into LGdH-Cl for the first time, using three different routes (ion exchange intercalation, coprecipitation, and exfoliation-self-assembly). X-ray diffraction, elemental microanalysis and IR spectroscopy confirmed successful incorporation of the drug into the interlayer spaces of the LGdH in all cases. From a comparison of the guest anion sizes and interlayer spacings, the active ingredients are believed to adopt intertwined bilayer configurations between the LGdH layers. The materials prepared by coprecipitation in general have noticeably higher drug loadings than those produced by ion exchange or self-assembly, as a result of the incorporation of some neutral drug into the composites. The LGdH-drug intercalates are stable at neutral pH, but rapidly degrade in acidic conditions to free Gd 3+ into solution. While LGdH-nap releases its drug loading into solution very rapidly (within ca. 1.5 h) at pH 7.4, LGdH-dic shows sustained release over 4 h, and LGdH-ibu extends this to 24 h. The latter composites therefore can be incorporated into enteric-coated tablets to provide sustained release in the small intestine. The drug intercalates are highly biocompatible and retain the proton relaxivity properties of the parent LGdH-Cl, with the materials most promising for use as negative contrast agents in MRI. Overall, the LGdH-drug intercalation compounds appear to have great potential for use in theranostic applications.

  6. A side-effect free method for identifying cancer drug targets.

    Science.gov (United States)

    Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

    2018-04-27

    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

  7. A Mathematical Analysis of Intravitreal Drug Transport | Avtar ...

    African Journals Online (AJOL)

    Method: A simple mathematical model for the intravitreal transport of drugs was developed ... of the equation describing the drug transport in the vitreous body was written, in which the ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  8. Evolution operators and transformation of states under uniform and an/or elastic forces into free particle states

    International Nuclear Information System (INIS)

    Dattoli, G.; Torre, A.

    1999-01-01

    In this paper are exploited the techniques, associated with the evolution operator method, to prove the existence of a one-to one correspondence between the wave function of a free particle and those of a particle ruled by a quadratic Hamiltonian [it

  9. A fast-running core prediction model based on neural networks for load-following operations in a soluble boron-free reactor

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jin-wook [Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejon 305-600 (Korea, Republic of)], E-mail: Jinwook@kaeri.re.kr; Seong, Seung-Hwan [Korea Atomic Energy Research Institute, P.O. Box 105, Yusong, Daejon 305-600 (Korea, Republic of)], E-mail: shseong@kaeri.re.kr; Lee, Un-Chul [Department of Nuclear Engineering, Seoul National University, Shinlim-Dong, Gwanak-Gu, Seoul 151-742 (Korea, Republic of)

    2007-09-15

    A fast prediction model for load-following operations in a soluble boron-free reactor has been proposed, which can predict the core status when three or more control rod groups are moved at a time. This prediction model consists of two multilayer feedforward neural network models to retrieve the axial offset and the reactivity, and compensation models to compensate for the reactivity and axial offset arising from the xenon transient. The neural network training data were generated by taking various overlaps among the control rod groups into consideration for training the neural network models, and the accuracy of the constructed neural network models was verified. Validation results of predicting load following operations for a soluble boron-free reactor show that this model has a good capability to predict the positions of the control rods for sustaining the criticality of a core during load-following operations to ensure that the tolerable axial offset band is not exceeded and it can provide enough corresponding time for the operators to take the necessary actions to prevent a deviation from the tolerable operating band.

  10. A fast-running core prediction model based on neural networks for load-following operations in a soluble boron-free reactor

    International Nuclear Information System (INIS)

    Jang, Jin-wook; Seong, Seung-Hwan; Lee, Un-Chul

    2007-01-01

    A fast prediction model for load-following operations in a soluble boron-free reactor has been proposed, which can predict the core status when three or more control rod groups are moved at a time. This prediction model consists of two multilayer feedforward neural network models to retrieve the axial offset and the reactivity, and compensation models to compensate for the reactivity and axial offset arising from the xenon transient. The neural network training data were generated by taking various overlaps among the control rod groups into consideration for training the neural network models, and the accuracy of the constructed neural network models was verified. Validation results of predicting load following operations for a soluble boron-free reactor show that this model has a good capability to predict the positions of the control rods for sustaining the criticality of a core during load-following operations to ensure that the tolerable axial offset band is not exceeded and it can provide enough corresponding time for the operators to take the necessary actions to prevent a deviation from the tolerable operating band

  11. Forming-Free One-Selector/One-Resistor Characteristics of Oxygen-Rich ITO Based Transparent Resistive Switching Memory via Defect Engineering Using the Reactive Sputtering Process.

    Science.gov (United States)

    Yun, Min Ju; Kim, Kyeong Heon; Kim, Sungho; Kim, Hee-Dong

    2018-09-01

    In recent research of resistive random access memory (RRAM), solving the degradation phenomenon induced by both a high forming voltage to form the conducting filaments (CFs) and a high reset current is one of the main issues encountered. In this study, to overcome these problems, we propose forming-free bipolar resistive switching (BRS) behaviors by employing an ITO film with abundant oxygen vacancies, instead of conventional CF based RRAM requiring a forming process, and systematically investigate the feasibility of forming free BRS behaviors and a possible switching mechanism. Compared to conventional CF based RRAM devices, it is possible for the proposed devices to achieve stable BRS properties (i.e., narrow variations of operating current and voltage, and retention) without the forming process, under an operating current of sub-nano ampere. In addition, the proposed cell shows a stable hysteresis of current-voltage curves, which is well matched with the Poole-Frenkel emission, and currents at a low voltage are limited due to a formed barrier height like Schottky diode between the active layer and electrodes.

  12. Antibiotics-free stable polyhydroxyalkanoate (PHA) production from carbon dioxide by recombinant cyanobacteria.

    Science.gov (United States)

    Akiyama, Hideo; Okuhata, Hiroshi; Onizuka, Takuo; Kanai, Shozo; Hirano, Masahiko; Tanaka, Satoshi; Sasaki, Ken; Miyasaka, Hitoshi

    2011-12-01

    A practical antibiotics-free plasmid expression system in cyanobacteria was developed by using the complementation of cyanobacterial recA null mutation with the EscherichiacolirecA gene on the plasmid. This system was applied to the production of polyhydroxyalkanoate (PHA), a biodegradable plastic, and the transgenic cyanobacteria stably maintained the pha genes for PHA production in the antibiotics-free medium, and accumulated up to 52% cell dry weight of PHA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. 21 CFR 1405.625 - Criminal drug statute.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Criminal drug statute. 1405.625 Section 1405.625 Food and Drugs OFFICE OF NATIONAL DRUG CONTROL POLICY GOVERNMENTWIDE REQUIREMENTS FOR DRUG-FREE WORKPLACE (FINANCIAL ASSISTANCE) Definitions § 1405.625 Criminal drug statute. Criminal drug statute means a...

  14. Methodological Study to Develop Standard Operational Protocol on Oral Drug Administration for Children.

    Science.gov (United States)

    Bijarania, Sunil Kumar; Saini, Sushma Kumari; Verma, Sanjay; Kaur, Sukhwinder

    2017-05-01

    To develop standard operational protocol (SOP) on oral drug administration and checklist to assess the implementation of the developed SOP. In this prospective methodological study, SOPs were developed in five phases. In the first phase, the preliminary draft of SOPs and checklists were prepared based on literature review, assessment of current practices and focus group discussion (FGD) with bedside working nurses. In the second phase, content validity was checked with the help of Delphi technique (12 experts). Total four drafts were prepared in stages and necessary modifications were made as per suggestions after each Delphi round. Fourth Delphi round was performed after conducting a pilot study. In the fourth phase, all bedside nurses were trained as per SOPs and asked to practice accordingly and observation of thirty oral drug administrations in children was done to check reliability of checklists for implementation of SOPs. In Phase-V, 7 FGDs were conducted with bedside nurses to assess the effectiveness of SOPs. The Content Validity Index (CVI) of SOP and checklists was 99.77%. Overall standardized Cronbach's alpha was calculated as 0.94. All the nurses felt that the SOP is useful. Valid and feasible SOP for drug administration to children through oral route along with valid and reliable checklist were developed. It is recommended to use this document for drug administration to children.

  15. Plasma HVA, tardive dyskinesia and psychotic symptoms in long-term drug-free inpatients with schizophrenia.

    Science.gov (United States)

    Muscettola, G; Barbato, G; de Bartolomeis, A; Monteleone, P; Pickar, D

    1990-09-01

    Plasma homovanillic acid (pHVA) levels were measured in 16 chronically ill patients with schizophrenia who also suffered from tardive dyskinesia, and in a group of 14 chronically ill patients with schizophrenia who did not have tardive dyskinesia. All patients were studied following an extensive drug-free period (mean = 32.9 months). Patients with orofacial dyskinesia had significantly lower levels of pHVA than did controls. In patients without tardive dyskinesia, pHVA levels were significantly correlated with both positive and negative symptomatology. In contrast, pHVA levels from patients with tardive dyskinesia bore neither a significant nor a nearly significant relationship to symptomatology. The implications of these findings for dopaminergic models of tardive dyskinesia are discussed.

  16. Covariance-based synaptic plasticity in an attractor network model accounts for fast adaptation in free operant learning.

    Science.gov (United States)

    Neiman, Tal; Loewenstein, Yonatan

    2013-01-23

    In free operant experiments, subjects alternate at will between targets that yield rewards stochastically. Behavior in these experiments is typically characterized by (1) an exponential distribution of stay durations, (2) matching of the relative time spent at a target to its relative share of the total number of rewards, and (3) adaptation after a change in the reward rates that can be very fast. The neural mechanism underlying these regularities is largely unknown. Moreover, current decision-making neural network models typically aim at explaining behavior in discrete-time experiments in which a single decision is made once in every trial, making these models hard to extend to the more natural case of free operant decisions. Here we show that a model based on attractor dynamics, in which transitions are induced by noise and preference is formed via covariance-based synaptic plasticity, can account for the characteristics of behavior in free operant experiments. We compare a specific instance of such a model, in which two recurrently excited populations of neurons compete for higher activity, to the behavior of rats responding on two levers for rewarding brain stimulation on a concurrent variable interval reward schedule (Gallistel et al., 2001). We show that the model is consistent with the rats' behavior, and in particular, with the observed fast adaptation to matching behavior. Further, we show that the neural model can be reduced to a behavioral model, and we use this model to deduce a novel "conservation law," which is consistent with the behavior of the rats.

  17. Formation of stable small cell number three-dimensional ovarian cancer spheroids using hanging drop arrays for preclinical drug sensitivity assays.

    Science.gov (United States)

    Raghavan, Shreya; Ward, Maria R; Rowley, Katelyn R; Wold, Rachel M; Takayama, Shuichi; Buckanovich, Ronald J; Mehta, Geeta

    2015-07-01

    Ovarian cancer grows and metastasizes from multicellular spheroidal aggregates within the ascites fluid. Multicellular tumor spheroids are therefore physiologically significant 3D in vitro models for ovarian cancer research. Conventional hanging drop cultures require high starting cell numbers, and are tedious for long-term maintenance. In this study, we generate stable, uniform multicellular spheroids using very small number of ovarian cancer cells in a novel 384 well hanging drop array platform. We used novel tumor spheroid platform and two ovarian cancer cell lines (A2780 and OVCAR3) to demonstrate the stable incorporation of as few as 10 cells into a single spheroid. Spheroids had uniform geometry, with projected areas (42.60×10(3)μm-475.22×10(3)μm(2) for A2780 spheroids and 37.24×10(3)μm(2)-281.01×10(3)μm(2) for OVCAR3 spheroids) that varied as a function of the initial cell seeding density. Phalloidin and nuclear stains indicated cells formed tightly packed spheroids with demarcated boundaries and cell-cell interaction within spheroids. Cells within spheroids demonstrated over 85% viability. 3D tumor spheroids demonstrated greater resistance (70-80% viability) to cisplatin chemotherapy compared to 2D cultures (30-50% viability). Ovarian cancer spheroids can be generated from limited cell numbers in high throughput 384 well plates with high viability. Spheroids demonstrate therapeutic resistance relative to cells in traditional 2D culture. Stable incorporation of low cell numbers is advantageous when translating this research to rare patient-derived cells. This system can be used to understand ovarian cancer spheroid biology, as well as carry out preclinical drug sensitivity assays. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity

    DEFF Research Database (Denmark)

    Fonnes, Siv; Holzknecht, Barbara Juliane; Gasbjerg, Lærke Smidt

    2017-01-01

    to the antibacterial effects of fosfomycin and metronidazole alone. CONCLUSION: The drug combination had neutral and stable pH, was iso-osmotic, and had stable concentrations during 24 h of storage. The antibacterial effect of fosfomycin and metronidazole were not altered when the drugs were mixed....

  19. Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

    Science.gov (United States)

    Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

    2018-05-31

    Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

  20. Physics of increased edge electron temperature and density turbulence during ELM-free QH-mode operation on DIII-D

    Science.gov (United States)

    Sung, C.; Rhodes, T. L.; Staebler, G. M.; Yan, Z.; McKee, G. R.; Smith, S. P.; Osborne, T. H.; Peebles, W. A.

    2018-05-01

    For the first time, we report increased edge electron temperature and density turbulence levels ( T˜ e and n˜ e) in Edge Localized Mode free Quiescent H-mode (ELM-free QH-mode) plasmas as compared to the ELMing time period. ELMs can severely damage plasma facing components in fusion plasma devices due to their large transient energy transport, making ELM-free operation a highly sought after goal. The QH-mode is a candidate for this goal as it is ELM-free for times limited only by hardware constraints. It is found that the driving gradients decrease during the QH-mode compared to the ELMing phase, however, a significant decrease in the ExB shearing rate is also observed that taken together is consistent with the increased turbulence. These results are significant as the prediction and control of ELM-free H-mode regimes are crucial for the operation of future fusion devices such as ITER. The changes in the linear growth rates calculated by CGYRO [Candy et al., J. Comput. Phys. 324, 73 (2016)] and the measured ExB shearing rate between ELMing and QH-mode phases are qualitatively consistent with these turbulence changes. Comparison with ELMing and 3D fields ELM suppressed H-mode finds a similar increase in T˜ e and n˜ e, however, with distinctly different origins, the increased driving gradients rather than the changes in the ExB shearing rate in 3D fields ELM suppressed the H-mode. However, linear gyrokinetic calculation results are generally consistent with the increased turbulence in both ELM-controlled discharges.

  1. Reversible anaesthesia of free-ranging lions (Panthera leo in Zimbabwe

    Directory of Open Access Journals (Sweden)

    A. Fahlman

    2005-06-01

    Full Text Available The combination of medetomidine-zolazepam-tiletamine with subsequent antagonism by atipamezole was evaluated for reversible anaesthesia of free-ranging lions (Panthera leo. Twenty-one anaesthetic events of 17 free-ranging lions (5 males and 12 females, body weight 105-211 kg were studied in Zimbabwe. Medetomidine at 0.027-0.055 mg / kg (total dose 4-11 mg and zolazepam-tiletamine at 0.38-1.32 mg / kg (total dose 50-275 mg were administered i.m. by dart injection. The doses were gradually decreased to improve recovery. Respiratory and heart rates, rectal temperature and relative haemoglobin oxygen saturation (SpO2 were recorded every 15 min. Arterial blood samples were collected from 5 lions for analysis of blood gases and acid-base status. For anaesthetic reversal, atipamezole was administered i.m. at 2.5 or 5 times the medetomidine dose. Induction was smooth and all lions were anaesthetised with good muscle relaxation within 3.4-9.5 min after darting. The predictable working time was a minimum of 1 h and no additional drug doses were needed. Respiratory and heart rates and SpO2 were stable throughout anaesthesia, whereas rectal temperature changed significantly over time. Atipamezole at 2.5 times the medetomidine dose was sufficient for reversal and recoveries were smooth and calm in all lions independent of the atipamezole dose. First sign of recovery was observed 3-27 min after reversal. The animals were up walking 8-26 min after reversal when zolazepamtiletamine doses <1 mg / kg were used. In practice, a total dose of 6 mg medetomidine and 80 mg zolazepam-tiletamine and reversal with 15 mg atipamezole can be used for either sex of an adult or subadult lion. The drugs and doses used in this study provided a reliable, safe and reversible anaesthesia protocol for free-ranging lions.

  2. Cell-free expression and stable isotope labelling strategies for membrane proteins

    International Nuclear Information System (INIS)

    Sobhanifar, Solmaz; Reckel, Sina; Junge, Friederike; Schwarz, Daniel; Kai, Lei; Karbyshev, Mikhail; Loehr, Frank; Bernhard, Frank; Doetsch, Volker

    2010-01-01

    Membrane proteins are highly underrepresented in the structural data-base and remain one of the most challenging targets for functional and structural elucidation. Their roles in transport and cellular communication, furthermore, often make over-expression toxic to their host, and their hydrophobicity and structural complexity make isolation and reconstitution a complicated task, especially in cases where proteins are targeted to inclusion bodies. The development of cell-free expression systems provides a very interesting alternative to cell-based systems, since it circumvents many problems such as toxicity or necessity for the transportation of the synthesized protein to the membrane, and constitutes the only system that allows for direct production of membrane proteins in membrane-mimetic environments which may be suitable for liquid state NMR measurements. The unique advantages of the cell-free expression system, including strong expression yields as well as the direct incorporation of almost any combination of amino acids with very little metabolic scrambling, has allowed for the development of a wide-array of isotope labelling techniques which facilitate structural investigations of proteins whose spectral congestion and broad line-widths may have earlier rendered them beyond the scope of NMR. Here we explore various labelling strategies in conjunction with cell-free developments, with a particular focus on α-helical transmembrane proteins which benefit most from such methods.

  3. Operation of the multigap resistive plate chamber using a gas mixture free of flammable components

    CERN Document Server

    Akindinov, A; Antonioli, P; Arcelli, S; Basile, M; Cara Romeo, G; Cifarelli, Luisa; Cindolo, F; De Caro, A; De Pasquale, S; Di Bartolomeo, A; Fusco-Girard, M; Golovine, V; Guida, M; Hatzifotiadou, D; Kaidalov, A B; Kim, D H; Kim, D W; Kisselev, S M; Laurenti, G; Lee, K; Lee, S C; Lioublev, E; Luvisetto, M L; Margotti, A; Martemyanov, A N; Nania, R; Noferini, F; Otiougova, P; Pesci, A; Pinazza, O; Polozov, P A; Scapparone, E; Scioli, G; Sellitto, S B; Semeria, F; Smirnitsky, A V; Tchoumakov, M M; Usenko, E; Valenti, G; Voloshin, K G; Williams, M C S; Zagreev, B V; Zampolli, C; Zichichi, A

    2004-01-01

    We have investigated the operation of the multigap resistive plate chamber (MRPC) for the ALICE-TOF system with a gas mixture free of flammable components. Two different gas mixtures, with and without iso-C//4H//1//0 have been used to measure the performance of the MRPC. The efficiency, time resolution, total charge, and the fast to total charge ratio have been found to be comparable.

  4. Local Search Approaches in Stable Matching Problems

    Directory of Open Access Journals (Sweden)

    Toby Walsh

    2013-10-01

    Full Text Available The stable marriage (SM problem has a wide variety of practical applications, ranging from matching resident doctors to hospitals, to matching students to schools or, more generally, to any two-sided market. In the classical formulation, n men and n women express their preferences (via a strict total order over the members of the other sex. Solving an SM problem means finding a stable marriage where stability is an envy-free notion: no man and woman who are not married to each other would both prefer each other to their partners or to being single. We consider both the classical stable marriage problem and one of its useful variations (denoted SMTI (Stable Marriage with Ties and Incomplete lists where the men and women express their preferences in the form of an incomplete preference list with ties over a subset of the members of the other sex. Matchings are permitted only with people who appear in these preference lists, and we try to find a stable matching that marries as many people as possible. Whilst the SM problem is polynomial to solve, the SMTI problem is NP-hard. We propose to tackle both problems via a local search approach, which exploits properties of the problems to reduce the size of the neighborhood and to make local moves efficiently. We empirically evaluate our algorithm for SM problems by measuring its runtime behavior and its ability to sample the lattice of all possible stable marriages. We evaluate our algorithm for SMTI problems in terms of both its runtime behavior and its ability to find a maximum cardinality stable marriage. Experimental results suggest that for SM problems, the number of steps of our algorithm grows only as O(n log(n, and that it samples very well the set of all stable marriages. It is thus a fair and efficient approach to generate stable marriages. Furthermore, our approach for SMTI problems is able to solve large problems, quickly returning stable matchings of large and often optimal size, despite the

  5. Protein-based stable isotope probing.

    Science.gov (United States)

    Jehmlich, Nico; Schmidt, Frank; Taubert, Martin; Seifert, Jana; Bastida, Felipe; von Bergen, Martin; Richnow, Hans-Hermann; Vogt, Carsten

    2010-12-01

    We describe a stable isotope probing (SIP) technique that was developed to link microbe-specific metabolic function to phylogenetic information. Carbon ((13)C)- or nitrogen ((15)N)-labeled substrates (typically with >98% heavy label) were used in cultivation experiments and the heavy isotope incorporation into proteins (protein-SIP) on growth was determined. The amount of incorporation provides a measure for assimilation of a substrate, and the sequence information from peptide analysis obtained by mass spectrometry delivers phylogenetic information about the microorganisms responsible for the metabolism of the particular substrate. In this article, we provide guidelines for incubating microbial cultures with labeled substrates and a protocol for protein-SIP. The protocol guides readers through the proteomics pipeline, including protein extraction, gel-free and gel-based protein separation, the subsequent mass spectrometric analysis of peptides and the calculation of the incorporation of stable isotopes into peptides. Extraction of proteins and the mass fingerprint measurements of unlabeled and labeled fractions can be performed in 2-3 d.

  6. Crystal engineering of stable temozolomide cocrystals.

    Science.gov (United States)

    Babu, N Jagadeesh; Sanphui, Palash; Nangia, Ashwini

    2012-10-01

    The antitumor prodrug temozolomide (TMZ) decomposes in aqueous medium of pH≥7 but is relatively stable under acidic conditions. Pure TMZ is obtained as a white powder but turns pink and then brown, which is indicative of chemical degradation. Pharmaceutical cocrystals of TMZ were engineered with safe coformers such as oxalic acid, succinic acid, salicylic acid, d,l-malic acid, and d,l-tartaric acid, to stabilize the drug as a cocrystal. All cocrystals were characterized by powder X-ray diffraction (PXRD), single crystal X-ray diffraction, and FT-IR as well as FT-Raman spectroscopy. Temozolomide cocrystals with organic acids (pK(a) 2-6) were found to be more stable than the reference drug under physiological conditions. The half-life (T(1/2)) of TMZ-oxalic and TMZ-salicylic acid measured by UV/Vis spectroscopy in pH 7 buffer is two times longer than that of TMZ (3.5 h and 3.6 h vs. 1.7 h); TMZ-succinic acid, TMZ-tartaric acid, and TMZ-malic acid also exhibited a longer half-life (2.3, 2.5, and 2.8 h, respectively). Stability studies at 40 °C and 75 % relative humidity (ICH conditions) showed that hydrolytic degradation of temozolomide in the solid state started after one week, as determined by PXRD, whereas its cocrystals with succinic acid and oxalic acid were intact at 28 weeks, thus confirming the greater stability of cocrystals compared to the reference drug. The intrinsic dissolution rate (IDR) profile of TMZ-oxalic acid and TMZ-succinic acid cocrystals in buffer of pH 7 is comparable to that of temozolomide. Among the temozolomide cocrystals examined, those with succinic acid and oxalic acid exhibited both an improved stability and a comparable dissolution rate to the reference drug. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. High peak current operation of x-ray free-electron laser multiple beam lines by suppressing coherent synchrotron radiation effects

    Science.gov (United States)

    Hara, Toru; Kondo, Chikara; Inagaki, Takahiro; Togawa, Kazuaki; Fukami, Kenji; Nakazawa, Shingo; Hasegawa, Taichi; Morimoto, Osamu; Yoshioka, Masamichi; Maesaka, Hirokazu; Otake, Yuji; Tanaka, Hitoshi

    2018-04-01

    The parallel operation of multiple beam lines is an important means to expand the opportunity of user experiments at x-ray free-electron laser (XFEL) facilities. At SPring-8 Angstrom free-electron laser (SACLA), the multi-beam-line operation had been tested using two beam lines, but transverse coherent synchrotron radiation (CSR) effects at a dogleg beam transport severely limited the laser performance. To suppress the CSR effects, a new beam optics based on two double bend achromat (DBA) structures was introduced for the dogleg. After the replacement of the beam optics, high peak current bunches of more than 10 kA are now stably transported through the dogleg and the laser pulse output is increased by a factor of 2-3. In the multi-beam-line operation of SACLA, the electron beam parameters, such as the beam energy and peak current, can be adjusted independently for each beam line. Thus the laser output can be optimized and wide spectral tunability is ensured for all beam lines.

  8. Preparation of thermally stable nanocrystalline hydroxyapatite by hydrothermal method.

    Science.gov (United States)

    Prakash Parthiban, S; Elayaraja, K; Girija, E K; Yokogawa, Y; Kesavamoorthy, R; Palanichamy, M; Asokan, K; Narayana Kalkura, S

    2009-12-01

    Thermally stable hydroxyapatite (HAp) was synthesized by hydrothermal method in the presence of malic acid. X-ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), Raman spectroscopy, scanning electron microscopy (SEM), differential thermal analysis (DTA), thermogravimetric analysis (TGA) was done on the synthesized powders. These analyses confirmed the sample to be free from impurities and other phases of calcium phosphates, and were of rhombus morphology along with nanosized particles. IR and Raman analyses indicated the adsorption of malic acid on HAp. Thermal stability of the synthesized HAp was confirmed by DTA and TGA. The synthesized powders were thermally stable upto 1,400 degrees C and showed no phase change. The proposed method might be useful for producing thermally stable HAp which is a necessity for high temperature coating applications.

  9. Stable Asymptotically Free Extensions (SAFEs) of the Standard Model

    International Nuclear Information System (INIS)

    Holdom, Bob; Ren, Jing; Zhang, Chen

    2015-01-01

    We consider possible extensions of the standard model that are not only completely asymptotically free, but are such that the UV fixed point is completely UV attractive. All couplings flow towards a set of fixed ratios in the UV. Motivated by low scale unification, semi-simple gauge groups with elementary scalars in various representations are explored. The simplest model is a version of the Pati-Salam model. The Higgs boson is truly elementary but dynamical symmetry breaking from strong interactions may be needed at the unification scale. A hierarchy problem, much reduced from grand unified theories, is still in need of a solution.

  10. A review on proniosomal drug delivery system for targeted drug action.

    Science.gov (United States)

    Radha, G V; Rani, T Sudha; Sarvani, B

    2013-03-01

    Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of proniosomes in targeted drug action.

  11. Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior in Indomethacin-Eudragit E Amorphous Solid Dispersions.

    Science.gov (United States)

    Lubach, Joseph W; Hau, Jonathan

    2018-02-20

    To investigate the nature of drug-excipient interactions between indomethacin (IMC) and methacrylate copolymer Eudragit® E (EE) in the amorphous state, and evaluate the effects on formulation and stability of these amorphous systems. Amorphous solid dispersions containing IMC and EE were spray dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous nature of the dispersions, and DSC was used to measure glass transition temperatures (T g ). 13 C and 15 N solid-state NMR was utilized to investigate changes in local structure and protonation state, while 1 H T 1 and T 1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. T g values for IMC-EE solid dispersions showed significant positive deviations from predicted values in the drug loading range of 40-90%, indicating a relatively strong drug-excipient interaction. 15 N solid-state NMR exhibited a change in protonation state of the EE basic amine, with two distinct populations for the EE amine at -360.7 ppm (unprotonated) and -344.4 ppm (protonated). Additionally, 1 H relaxation measurements showed phase separation at high drug load, indicating an amorphous ionic complex and free IMC-rich phase. PXRD data showed all ASDs up to 90% drug load remained physically stable after 2 years. 15 N solid-state NMR experiments show a change in protonation state of EE, indicating that an ionic complex indeed forms between IMC and EE in amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale phase separation at high drug load between the amorphous ionic complex and excess free IMC.

  12. Closed-Cycle, Frequency-Stable CO2 Laser Technology

    Science.gov (United States)

    Batten, Carmen E. (Editor); Miller, Irvin M. (Editor); Wood, George M., Jr. (Editor); Willetts, David V. (Editor)

    1987-01-01

    These proceedings contain a collection of papers and comments presented at a workshop on technology associated with long-duration closed-cycle operation of frequency-stable, pulsed carbon dioxide lasers. This workshop was held at the NASA Langley Research Center June 10 to 12, 1986. The workshop, jointly sponsored by the National Aeronautics and Space Administration (NASA) and the Royal Signals and Radar Establishment (RSRE), was attended by 63 engineers and scientists from the United States and the United Kingdom. During the 2 1/2 days of the workshop, a number of issues relating to obtaining frequency-stable operation and to the catalytic control of laser gas chemistry were discussed, and specific recommendations concerning future activities were drafted.

  13. Polymer-Free Drug-Coated Coronary Stents Are Cost-Effective in Patients at High Bleeding Risk: Economic Evaluation of the LEADERS FREE Trial.

    Science.gov (United States)

    Filipovic-Pierucci, Antoine; Durand-Zaleski, Isabelle; Butel, Thibault; Greene, Samantha; Hovasse, Thomas; Iñiguez, Andres; Nazzaro, Marco Stefano; Oldroyd, Keith G; Talwar, Suneel; Richardt, Gert; Windhovel, Ute; Urban, Philip; Morice, Marie-Claude

    2018-02-20

    In patients at high risk of bleeding who undergo PCI the biolimus A9 polymer-free drug coated stent (DCS) has superior efficacy and safety compared to a bare metal stent (BMS). We estimated the cost effectiveness of DCS vs. BMS. The Leaders FREE-based economic evaluation estimated service use and quality of life data collected prospectively. The entire trial population was analysed using cost-weights from England, France, Germany, Italy, Scotland and Spain. Country-specific QALYs were derived from EQ-5D scores. We estimated cost per event averted and per QALY gained. DCS use resulted in -0.095 cardiac deaths, target vessel MI, stent thrombosis and revascularization per patient (0.152 vs. 0.237;pcosts for the index admission were similar between groups. One-year costs using cost-weights from each of the 6 countries, including the additional €300 per DCS stent, ranged from €4,664-8,593 for DCS and €4,845-9,742 for BMS and were lower in the DCS group (England:€-428, France:€-137, Germany:€-33, Italy:€-522, Scotland:€-298, Spain:€-854). The probability that DCS dominated BMS was >50% in all countries. At a threshold of €10,000 per event averted DCS had a 98% probability of being cost-effective in all 6 countries.

  14. Implementability of two-qubit unitary operations over the butterfly network and the ladder network with free classical communication

    Energy Technology Data Exchange (ETDEWEB)

    Akibue, Seiseki [Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo (Japan); Murao, Mio [Department of Physics, Graduate School of Science, The University of Tokyo, Tokyo, Japan and NanoQuine, The University of Tokyo, Tokyo (Japan)

    2014-12-04

    We investigate distributed implementation of two-qubit unitary operations over two primitive networks, the butterfly network and the ladder network, as a first step to apply network coding for quantum computation. By classifying two-qubit unitary operations in terms of the Kraus-Cirac number, the number of non-zero parameters describing the global part of two-qubit unitary operations, we analyze which class of two-qubit unitary operations is implementable over these networks with free classical communication. For the butterfly network, we show that two classes of two-qubit unitary operations, which contain all Clifford, controlled-unitary and matchgate operations, are implementable over the network. For the ladder network, we show that two-qubit unitary operations are implementable over the network if and only if their Kraus-Cirac number do not exceed the number of the bridges of the ladder.

  15. Implementability of two-qubit unitary operations over the butterfly network and the ladder network with free classical communication

    International Nuclear Information System (INIS)

    Akibue, Seiseki; Murao, Mio

    2014-01-01

    We investigate distributed implementation of two-qubit unitary operations over two primitive networks, the butterfly network and the ladder network, as a first step to apply network coding for quantum computation. By classifying two-qubit unitary operations in terms of the Kraus-Cirac number, the number of non-zero parameters describing the global part of two-qubit unitary operations, we analyze which class of two-qubit unitary operations is implementable over these networks with free classical communication. For the butterfly network, we show that two classes of two-qubit unitary operations, which contain all Clifford, controlled-unitary and matchgate operations, are implementable over the network. For the ladder network, we show that two-qubit unitary operations are implementable over the network if and only if their Kraus-Cirac number do not exceed the number of the bridges of the ladder

  16. Cold starting characteristics analysis of hydraulic free piston engine

    International Nuclear Information System (INIS)

    Zhang, Shuanlu; Zhao, Zhenfeng; Zhao, Changlu; Zhang, Fujun; Wang, Shan

    2017-01-01

    The cold start characteristic of hydraulic free piston diesel engine may affect its stable operation. Therefore the specific cold start characteristics, such as BDC or TDC positions, pressure in-cylinder, heat release rate, should be investigated in detail. These parameters fluctuate in some regularity in the cod start process. With the development of the free piston engine prototype and the establishment of test bench, the results are obtained. For the dynamic results, the fluctuation range of TDC and BDC positions is 8 mm and decreases with time. The thermodynamic results show that the combustion process is not stable and the pressure in-cylinder fluctuates largely in the cold start process. In addition, the combustion is rapid and knock happens inevitably. In order to investigate the reasons, a CFD model is established for temperature analysis in-cylinder and heat transfer conditions. It is found that higher start wall temperature will lead to more uniform temperature distribution. The delay period may decreases and heat release will move forward. This reason is analyzed by thermodynamic derivation based on the first law of thermodynamics. Finally, the improvement suggestions of cold start strategy are proposed. - Highlights: • The cold start behaviors of HFPE are investigated in detail. • CFD method is used for simulating temperature distribution in start process. • Thermodynamic derivation uncovers the compression temperature distribution. • The improvement suggestions of cold start strategy are proposed.

  17. [Application of operant conditioning techniques to forensic toxicology: experimental studies on alcohol and abusable drugs].

    Science.gov (United States)

    Hishida, S

    1996-10-01

    This paper describes some experiments that apply the operant conditioning techniques to forensic toxicological research. These techniques may be useful in investigating the mechanisms of action, toxic symptoms, legal competence and drug metabolism associated with substance abuse such as abuse of alcohol, psychotropic drugs, narcotics, stimulants, and organic solvents. 1) Genetic research on alcohol preference in rats. We applied operant conditioning to investigate alcohol preference in rats and constructed an apparatus for the measurement of discriminated operate responses for water or alcohol reinforcement in rat. This apparatus is a modified Skinner box with a one-lever two-liquid system. Fixed ratio-10 (FR-10) schedules of reinforcement are used to increase the work of the rat before it obtains the reinforcement. The voluntary choice of water or 10% ethanol by the rat can be assessed quantitatively by measuring the lever-pushing responses. It is an extremely useful method for measuring the real alcohol preference of rats. A rat was kept in a Skinner box overnight. The numbers of responses and reinforcement for water and ethanol and the volumes of the two liquids consumed were recorded. The ratio of ethanol reinforcement was defined as the number of ethanol reinforcement to the total number of ethanol and water reinforcement. The ratio of ethanol intake was defined as the volume of ethanol consumed to the volume of water and ethanol consumed. Ethanol consumption per g body weight was calculated from the volume of ethanol consumed by the rat. We used this apparatus to investigate alcohol preference of more than 300 Wistar Albino Rats, and divided them into a high alcohol preference (HAP) group and a low alcohol preference (LAP) group. Inbreeding between littermates was conducted in each of the HAP and LAP groups. The liver tissue of each offspring was obtained and the cytosol fraction was collected and subjected to isoelectric focusing using polyacrylamide gel

  18. Deflection of jets discharged into a reservoir with a free surface

    International Nuclear Information System (INIS)

    Wada, Akihiro; Ishikawa, Keizo; Mizushima, Jiro; Akinaga, Takeshi

    2011-01-01

    Deflections of jets discharged into a reservoir with a free surface are investigated numerically. The jets are known to deflect towards either side of the free surface or the bottom, whose direction is not determined uniquely in some experimental conditions, i.e. there are multiple stable states realizable in the same condition. The origin of the multiple stable states is explored by utilizing homotopy transformations in which the top boundary of the reservoir is transformed from a rigid to a free boundary and also the location of the outlet throat is continuously moved from mid-height to the top. We depicted bifurcation diagrams of the flow compiling the data of numerical simulations, from which we identified the origin as an imperfect pitchfork bifurcation, and obtained an insight into the mechanism for the direction to be determined. The parameter region where such multiple stable states are possible is also delimited.

  19. Livestock-Associated Methicillin and Multidrug Resistant Staphylococcus aureus Is Present among Industrial, Not Antibiotic-Free Livestock Operation Workers in North Carolina

    Science.gov (United States)

    Wing, Steve; Hall, Devon; Baron, Dothula; Price, Lance B.; Larsen, Jesper; Stegger, Marc; Stewart, Jill; Heaney, Christopher D.

    2013-01-01

    Objectives Administration of antibiotics to food animals may select for drug-resistant pathogens of clinical significance, such as methicillin-resistant Staphylococcus aureus (MRSA). In the United States, studies have examined prevalence of MRSA carriage among individuals exposed to livestock, but prevalence of multidrug-resistant S. aureus (MDRSA) carriage and the association with livestock raised with versus without antibiotic selective pressure remains unclear. We aimed to examine prevalence, antibiotic susceptibility, and molecular characteristics of S. aureus among industrial livestock operation (ILO) and antibiotic-free livestock operation (AFLO) workers and household members in North Carolina. Methods Participants in this cross-sectional study were interviewed and provided a nasal swab for S. aureus analysis. Resulting S. aureus isolates were assessed for antibiotic susceptibility, multi-locus sequence type, and absence of the scn gene (a marker of livestock association). Results Among 99 ILO and 105 AFLO participants, S. aureus nasal carriage prevalence was 41% and 40%, respectively. Among ILO and AFLO S. aureus carriers, MRSA was detected in 7% (3/41) and 7% (3/42), respectively. Thirty seven percent of 41 ILO versus 19% of 42 AFLO S. aureus-positive participants carried MDRSA. S. aureus clonal complex (CC) 398 was observed only among workers and predominated among ILO (13/34) compared with AFLO (1/35) S. aureus-positive workers. Only ILO workers carried scn-negative MRSA CC398 (2/34) and scn-negative MDRSA CC398 (6/34), and all of these isolates were tetracycline resistant. Conclusions Despite similar S. aureus and MRSA prevalence among ILO and AFLO-exposed individuals, livestock-associated MRSA and MDRSA (tetracycline-resistant, CC398, scn-negative) were only present among ILO-exposed individuals. These findings support growing concern about antibiotics use and confinement in livestock production, raising questions about the potential for occupational

  20. Livestock-associated methicillin and multidrug resistant Staphylococcus aureus is present among industrial, not antibiotic-free livestock operation workers in North Carolina.

    Directory of Open Access Journals (Sweden)

    Jessica L Rinsky

    Full Text Available OBJECTIVES: Administration of antibiotics to food animals may select for drug-resistant pathogens of clinical significance, such as methicillin-resistant Staphylococcus aureus (MRSA. In the United States, studies have examined prevalence of MRSA carriage among individuals exposed to livestock, but prevalence of multidrug-resistant S. aureus (MDRSA carriage and the association with livestock raised with versus without antibiotic selective pressure remains unclear. We aimed to examine prevalence, antibiotic susceptibility, and molecular characteristics of S. aureus among industrial livestock operation (ILO and antibiotic-free livestock operation (AFLO workers and household members in North Carolina. METHODS: Participants in this cross-sectional study were interviewed and provided a nasal swab for S. aureus analysis. Resulting S. aureus isolates were assessed for antibiotic susceptibility, multi-locus sequence type, and absence of the scn gene (a marker of livestock association. RESULTS: Among 99 ILO and 105 AFLO participants, S. aureus nasal carriage prevalence was 41% and 40%, respectively. Among ILO and AFLO S. aureus carriers, MRSA was detected in 7% (3/41 and 7% (3/42, respectively. Thirty seven percent of 41 ILO versus 19% of 42 AFLO S. aureus-positive participants carried MDRSA. S. aureus clonal complex (CC 398 was observed only among workers and predominated among ILO (13/34 compared with AFLO (1/35 S. aureus-positive workers. Only ILO workers carried scn-negative MRSA CC398 (2/34 and scn-negative MDRSA CC398 (6/34, and all of these isolates were tetracycline resistant. CONCLUSIONS: Despite similar S. aureus and MRSA prevalence among ILO and AFLO-exposed individuals, livestock-associated MRSA and MDRSA (tetracycline-resistant, CC398, scn-negative were only present among ILO-exposed individuals. These findings support growing concern about antibiotics use and confinement in livestock production, raising questions about the potential for

  1. Development and validation of a free-piston engine generator numerical model

    International Nuclear Information System (INIS)

    Jia, Boru; Zuo, Zhengxing; Tian, Guohong; Feng, Huihua; Roskilly, A.P.

    2015-01-01

    Highlights: • Detailed numerical model of free-piston engine generator is presented. • Sub models for both starting process and steady operation are derived. • Simulation results show good agreement with prototype test data. • Engine performance with different starting motor force and varied loads are simulated. • The efficiency of the prototype is estimated to be 31.5% at a power output of 4 kW under full load. - Abstract: This paper focuses on the numerical modelling of a spark ignited free-piston engine generator and the model validation with test results. Detailed sub-models for both starting process and steady operation were derived. The compression and expansion processes were not regarded as ideal gas isentropic processes; both heat transfer and air leakage were taken into consideration. The simulation results show good agreement with the prototype test data for both the starting process and steady operation. During the starting process, the difference of the in-cylinder gas pressure can be controlled within 1 bar for every running cycle. For the steady operation process, the difference was less than 5% and the areas enclosed on the pressure–volume diagram were similar, indicating that the power produced by the engine and the engine efficiency could be predicted by this model. Based on this model, the starting process with different starting motor forces and the combustion process with various throttle openings were simulated. The engine performance during stable operation at 100% engine load was predicted, and the efficiency of the prototype was estimated to be 31.5% at power output of 4 kW

  2. Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

    Science.gov (United States)

    van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2017-01-01

    Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. THE OPERATIONS OF THE MEXICAN ARMY AGAINST DRUG TRAFFICKING, REVIEW AND PRESENT SITUATION

    Directory of Open Access Journals (Sweden)

    Alma Palom Mendoza Cortés

    2017-12-01

    Full Text Available legal po ers, responsibilities and impact across space and time. This paper is a report of the MA thesis “The Mexican Secretariat of National Defense SEDENA , organizational changes: 1937C2010”. The object of this article is to propose a descriptive analysis and conduct a revie of the increase of the Mexican military operations background and history, from the moment drug trafficking as conceived as a Mexico s national security threat. This derived in the fact of the deployment of the Army nation ide to perform high impact military operations to counter it, under an internal security environment characterized by the lack of strong and not corrupt internal security institutions that finally ended endorsing the military intervention and alongside the negative consequences for the civilCmilitary relations.

  4. Stable production of the antimalarial drug artemisinin in the moss Physcomitrella patens

    DEFF Research Database (Denmark)

    Binti Khairul Ikram, Nur Kusaira; Kashkooli, Arman Beyraghdar; Peramuna, Anantha Vithakshana

    2017-01-01

    study shows that P. patens can be a sustainable and efficient production platform of artemisinin that without further modifications allow for industrial scale production. A stable supply of artemisinin will lower the price of artemisinin-based treatments, hence become more affordable to the lower income...

  5. Decoupling Design and Verification of a Free-Piston Linear Generator

    Directory of Open Access Journals (Sweden)

    Peng Sun

    2016-12-01

    Full Text Available This paper proposes a decoupling design approach for a free-piston linear generator (FPLG constituted of three key components, including a combustion chamber, a linear generator and a gas spring serving as rebounding device. The approach is based on the distribution of the system power and efficiency, which provides a theoretical design method from the viewpoint of the overall power and efficiency demands. The energy flow and conversion processes of the FPLG are analyzed, and the power and efficiency demands of the thermal-mechanical and mechanical-electrical energy conversion are confirmed. The energy and efficiency distributions of the expansion and compression strokes within a single stable operation cycle are analyzed and determined. Detailed design methodologies of crucial geometric dimensions and operational parameters of each key component are described. The feasibility of the proposed decoupling design approach is validated through several design examples with different output power.

  6. Modeling the structure and operation of drug supply chains: The case of cocaine and heroin in Italy and Slovenia.

    Science.gov (United States)

    Caulkins, Jonathan P; Disley, Emma; Tzvetkova, Marina; Pardal, Mafalda; Shah, Hemali; Zhang, Xiaoke

    2016-05-01

    Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible

  7. Retrieval-travel-time model for free-fall-flow-rack automated storage and retrieval system

    Science.gov (United States)

    Metahri, Dhiyaeddine; Hachemi, Khalid

    2018-03-01

    Automated storage and retrieval systems (AS/RSs) are material handling systems that are frequently used in manufacturing and distribution centers. The modelling of the retrieval-travel time of an AS/RS (expected product delivery time) is practically important, because it allows us to evaluate and improve the system throughput. The free-fall-flow-rack AS/RS has emerged as a new technology for drug distribution. This system is a new variation of flow-rack AS/RS that uses an operator or a single machine for storage operations, and uses a combination between the free-fall movement and a transport conveyor for retrieval operations. The main contribution of this paper is to develop an analytical model of the expected retrieval-travel time for the free-fall flow-rack under a dedicated storage assignment policy. The proposed model, which is based on a continuous approach, is compared for accuracy, via simulation, with discrete model. The obtained results show that the maximum deviation between the continuous model and the simulation is less than 5%, which shows the accuracy of our model to estimate the retrieval time. The analytical model is useful to optimise the dimensions of the rack, assess the system throughput, and evaluate different storage policies.

  8. The effects of FreeSurfer version, workstation type, and Macintosh operating system version on anatomical volume and cortical thickness measurements.

    Science.gov (United States)

    Gronenschild, Ed H B M; Habets, Petra; Jacobs, Heidi I L; Mengelers, Ron; Rozendaal, Nico; van Os, Jim; Marcelis, Machteld

    2012-01-01

    FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8 ± 6.6% (range 1.3-64.0%) (volume) and 2.8 ± 1.3% (1.1-7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies.The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable.

  9. The effects of FreeSurfer version, workstation type, and Macintosh operating system version on anatomical volume and cortical thickness measurements.

    Directory of Open Access Journals (Sweden)

    Ed H B M Gronenschild

    Full Text Available FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0, workstation (Macintosh and Hewlett-Packard, and Macintosh operating system version (OSX 10.5 and OSX 10.6. Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8 ± 6.6% (range 1.3-64.0% (volume and 2.8 ± 1.3% (1.1-7.7% (cortical thickness. About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies.The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable.

  10. Nanoparticle-neural stem cells for targeted ovarian cancer treatment: optimization of silica nanoparticles for efficient drug loading

    Science.gov (United States)

    Patel, Z.; Berlin, J.; Abidi, W.

    2018-02-01

    One of the drugs used to treat ovarian cancer is cisplatin. However, cisplatin kills normal surrounding tissue in addition to cancer cells. To improve tumor targeting efficiency, our lab uses neural stem cells (NSCs), which migrate directly to ovarian tumors. If free cisplatin is loaded into NSCs for targeted drug delivery, it will kill the NSCs. To prevent the drug cisplatin from killing both the NSCs and normal surrounding tissue, our lab synthesizes silica nanoparticles (SiNPs) that act as a protective carrier. The big picture here is to maximize efficiency of tumor targeting using NSCs and minimize toxicity to these NSCs using SiNPs. The goal of this project is to optimize the stability of SiNPs, which is important for efficient drug loading. To do this, the concentration of tetraethyl orthosilicate (TEOS), one of the main components of SiNPs, was varied. We hypothesized that more TEOS equates to more stable SiNPs because TEOS contributes carbon to SiNPs, and thus a tightly-packed chemical structure results in a stable particle. Then, the stability of the SiNPs were checked in cell media and phosphate buffered saline (PBS). Lastly, the SiNPs were analyzed for their porosity using the transmission electron microscope (TEM). TEM imaging showed white spots in the 200-800 μL TEOS batches and no white spots in the 1000-1800 μL TEOS batches. The white spots were pores, which indicate instability. We concluded that the ultimate factor that determines the stability of SiNPs (100 nm) is the concentration of organic substance.

  11. Orfeo Toolbox: A Free And Open Source Solution For Research And Operational Remote Sensing Projects

    Science.gov (United States)

    Savinaud, Mickael; OTB-CS Team

    2013-12-01

    The free and open source solution, Orfeo ToolBox (OTB), offers the possibility to deal with large data processing. This library designed by CNES in the frame of the ORFEO accompaniment program to promote use of Pleiades data and other VHR data offers now a larger number of applications designed to end users. Due to its modular design, OTB is now used in different context from R&D studies to operational chain.

  12. Phase Stable RF-over-fiber Transmission using Heterodyne Interferometry

    International Nuclear Information System (INIS)

    Wilcox, R.; Byrd, J.M.; Doolittle, L.; Huang, G.; Staples, J.W.

    2010-01-01

    New scientific applications require phase-stabilized RF distribution to multiple remote locations. These include phased-array radio telescopes and short pulse free electron lasers. RF modulated onto a CW optical carrier and transmitted via fiber is capable of low noise, but commercially available systems aren't long term stable enough for these applications. Typical requirements are for less than 50fs long term temporal stability between receivers, which is 0.05 degrees at 3GHz. Good results have been demonstrated for RF distribution schemes based on transmission of short pulses, but these require specialized free-space optics and high stability mechanical infrastructure. We report a method which uses only standard telecom optical and RF components, and achieves less than 20fs RMS error over 300m of standard single-mode fiber. We demonstrate stable transmission of 3GHz over 300m of fiber with less than 0.017 degree (17fs) RMS phase error. An interferometer measures optical phase delay, providing information to a feed-forward correction of RF phase.

  13. Free fatty acids-sensing G protein-coupled receptors in drug targeting and therapeutics.

    Science.gov (United States)

    Yonezawa, Tomo; Kurata, Riho; Yoshida, Kaori; Murayama, Masanori A; Cui, Xiaofeng; Hasegawa, Akihiko

    2013-01-01

    G protein-coupled receptor (GPCR) (also known as seven-transmembrane domain receptor) superfamily represents the largest protein family in the human genome. These receptors respond to various physiological ligands such as photons, odors, pheromones, hormones, ions, and small molecules including amines, amino acids to large peptides and steroids. Thus, GPCRs are involved in many diseases and the target of around half of all conventional drugs. The physiological roles of free fatty acids (FFAs), in particular, long-chain FFAs, are important for the development of many metabolic disease including obesity, diabetes, and atherosclerosis. In the past half decade, deorphanization of several GPCRs has revealed that GPR40, GPR41, GPR43, GPR84 and GPR120 sense concentration of extracellular FFAs with various carbon chain lengths. GPR40 and GPR120 are activated by medium- and long-chain FFAs. GPR84 is activated by medium- chain, but not long-chain, FFAs. GPR41 and GPR43 are activated by short-chain FFAs. GPR40 is highly expressed in pancreatic beta cells and plays a crucial role in FFAs-induced insulin secretion. GPR120 is mainly expressed in enteroendocrine cells and plays an important role for FFAs-induced glucagon-like peptide-1. GPR43 is abundant in leukocytes and adipose tissue, whilst GPR41 is highly expressed in adipose tissue, the pancreas and leukocytes. GPR84 is expressed in leukocytes and monocyte/macrophage. This review aims to shed light on the physiological roles and development of drugs targeting these receptors.

  14. STUDIES ON HIGH SOLID CONTENT AND STABLE EMULSIFIER—FREE EMULSION POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    TangGuangliang; HaoGuangjie; 等

    1998-01-01

    In this article,AHPS(3-allyloxy-2-hydroxy-1-propanesulfonate salt) was synthesized to use in emulsifier-free emulsion polymerization of BA/BMA/MMA system for high solid content latexes.Storage stability,flow behavior of the latexes,morphology of the obtained latex particles,dynamic viscoelastic behavior,tensile strength and water resistance properties of the resulted copolymers were investigated.The experimental results show that with the addition of AHPS,stability of the emulsion is greatly improved that there appears no apparent precipitation during the polymerization and storage at room temperature for 6 months and at -10℃ for four months.Flow of the latexes follows the Bingham body laws,diameter of the latex particles is about 0.6μm,of which is larger than that of by conventional emulsion polymerization(0.12μm).In addition,not only water resistance of the copolymers obtained by emulsifier-free emulstion polymerization is greatly improved,but also tensile strength is obviously enhanced.

  15. 21 CFR 862.1730 - Free tyrosine test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Free tyrosine test system. 862.1730 Section 862....1730 Free tyrosine test system. (a) Identification. A free tyrosine test system is a device intended to measure free tyrosine (an amono acid) in serum and urine. Measurements obtained by this device are used in...

  16. Protein labelling with stable isotopes: strategies

    International Nuclear Information System (INIS)

    Lirsac, P.N.; Gilles, N.; Jamin, N.; Toma, F.; Gabrielsen, O.; Boulain, J.C.; Menez, A.

    1994-01-01

    A protein labelling technique with stable isotopes has been developed at the CEA: a labelled complete medium has been developed, performing as well as the Luria medium, but differing from it because it contains not only free aminated acids and peptides, but also sugars (96% of D-glucopyrannose) and labelled nucleosides. These precursors are produced from a labelled photosynthetic micro-organisms biomass, obtained with micro-algae having incorporated carbon 13, nitrogen 15 and deuterium during their culture. Labelling costs are reduced. 1 fig., 1 tab., 3 refs

  17. Emulsifiers' composition modulates venous irritation of the nanoemulsions as a lipophilic and venous irritant drug delivery system.

    Science.gov (United States)

    Mao, Chengwen; Wan, Jiangling; Chen, Huabing; Xu, Huibi; Yang, Xiangliang

    2009-01-01

    In this study, a nanoemulsion (NE) system was investigated for intravenous delivery of lipophilic and venous irritant drugs. NEs were prepared to deliver diallyl trisulfide (DT) for systemic therapy of bacterial and fungal infection, egg phospholipid was chosen as the main emulsifier, and two co-emulsifiers were also incorporated, including Poloxamer 188 (P188) and Solutol HS 15 (S15). Soybean oil was used as the dispersed phases, forming stable DT NEs with small particle sizes. The venous irritation of DT NEs was evaluated by in vitro human umbilical cord endothelial cells (CRL 1730) compatibility model with the intracellular adenosine triphosphate (ATP) and guanosine triphosphate (GTP) concentrations as the indices. The intracellular ATP and GTP reduction changed with the incorporation of a variety of co-emulsifiers, which varied in a free DT concentration-dependent manner. It was deduced that the free DT concentrations of NEs containing co-emulsifiers were determined by the partition coefficient of DT between oil and surfactant buffer solution. In conclusion, NE was an appropriate delivery system for lipophilic and venous irritant drug, and optimization of the composition of emulsifiers was an effective method to alleviate the venous irritation of DT NEs.

  18. The social construction of drug-related death.

    Science.gov (United States)

    Cruts

    2000-12-01

    This article invites you to a social constructionist view on the issue of drug-related death. Social constructionism is often misunderstood for denying plain facts. It sure is a fact that there are deadly doses of legal and illegal substances. In this sense it is a truism that drugs kill people. Nonetheless, it is argued that reducing the causes of death to a certain drug as the essential underlying cause of death is a social construction. A case is discussed to demonstrate that a drug-related death can just as well be seen as a free-market death. Free markets kill people at least as much as drugs do. It is argued that drug-related death is a social construction, because attributing a death to a drug is based on unfalsifiable counterfactual thinking. Counterfactual thoughts about what the world would look like if there were no drugs, are seen as expressing one's view of life.

  19. Sulfur poisoning of Ni/Gadolinium-doped ceria anodes: A long-term study outlining stable solid oxide fuel cell operation

    Science.gov (United States)

    Riegraf, Matthias; Zekri, Atef; Knipper, Martin; Costa, Rémi; Schiller, Günter; Friedrich, K. Andreas

    2018-03-01

    This work presents an analysis of the long-term behavior of nickel/gadolinium-doped ceria (CGO) anode-based solid oxide fuel cells (SOFC) under sulfur poisoning conditions. A parameter study of sulfur-induced irreversible long-term degradation of commercial, high-performance single cells was carried out at 900 °C for different H2/N2/H2S fuel gas atmospheres, current densities and Ni/CGO anodes. The poisoning periods of the cells varied from 200 to 1500 h. The possibility of stable long-term Ni/CGO anode operation under sulfur exposure is established and the critical operating regime is outlined. Depending on the operating conditions, two degradation phenomena can be observed. Small degradation of the ohmic resistance was witnessed for sulfur exposure times of approximately 1000 h. Moreover, degradation of the anode charge transfer resistance was observed to be triggered by the combination of a small anodic potential step and high sulfur coverage on Ni. The microstructural evolution of altered Ni/CGO anodes was examined post-mortem by means of SEM and FIB/SEM, and is correlated to the anode performance degradation under critical operating conditions, establishing Ni depletion, porosity increase and a tripe phase boundary density decrease in the anode functional layer. It is shown that short-term sulfur poisoning behavior can be used to assess long-term stability.

  20. ASSESSMENT OF AWARENESS LEVEL OF OWN DISEASE IN PATIENTS WITH STABLE ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    G. F. Andreeva

    2005-01-01

    Full Text Available Arterial hypertension (AH is the most frequent risk factor of cardiovascular diseases and related mortality in all developed countries. Altough therapy with antihypertensive drugs significantly reduces this risk, patients with stable mild hypertension have poor compliance with the treatment. The reasons and levels of inadequacy of antihypertensive therapy in this group of patients are well-known.Aim. To evaluate the awareness level of own disease, adequacy of therapy only in those patients with stable mild arterial hypertension, who are complied with recommendations of physicians concerning AH treatment and changing of mode of life. It was also planned to reveal possible grounds for inadequate secondary prevention of cardiovascular disease.Materials and methods. 76 patiens with stable mild arterial hypertension were included into study. They didn’t have any serious concomitant diseases and were complied with the recommendations of physicians concerning secondary prevention of cardiovascular disease. Questionnaire of State Research Center for Preventive Medicine “Assessment of awareness level of own disease in patients with stable arterial hypertension” was used in the study.Results. It was revealed, that the majority of patients, invoved in the study, were nonsmokers and regularly took antihypertensive drugs. 70% of questioned patients reached the target arterial blood pressure levels, while patients with arterial hypertension in general Russia population received regular and efficient treatment in less than 30-20%. Drugs treatment of questioned patients almost didn’t differ from that, which received patients in out-patient clinics of Moscow: in both cases ACE inhibitors were preferred. Only 29% of questioned patients knew their lipid levels in blood and none of the patients took drugs, reducing levels of lipids in blood. Half of the patients, that took part in our study, had increased level of body mass index.Conclusions. Inadequate

  1. Stable Amplification and High Current Drop Bistable Switching in Supercritical GaAs Tills

    DEFF Research Database (Denmark)

    Izadpanah, S.H; Jeppsson, B; Jeppesen, Palle

    1974-01-01

    Bistable switching with current drops of 40% and switching times of 100 ps are obtained in pulsed operation of 10¿m supercritically doped n+ nn+ GaAs Transferred Electron Devices (TEDs). When CW-operated the same devices exhibit a 5-17 GHz bandwidth for the stable negative resistance.......Bistable switching with current drops of 40% and switching times of 100 ps are obtained in pulsed operation of 10¿m supercritically doped n+ nn+ GaAs Transferred Electron Devices (TEDs). When CW-operated the same devices exhibit a 5-17 GHz bandwidth for the stable negative resistance....

  2. Recombinant Amphiphilic Protein Micelles for Drug Delivery

    OpenAIRE

    Kim, Wookhyun; Xiao, Jiantao; Chaikof, Elliot L.

    2011-01-01

    Amphiphilic block polypeptides can self-assemble into a range of nanostructures in solution, including micelles and vesicles. Our group has recently described the capacity of recombinant amphiphilic diblock copolypeptides to form highly stable micelles. In this report, we demonstrate the utility of protein nanoparticles to serve as a vehicle for controlled drug delivery. Drug-loaded micelles were produced by encapsulating dipyridamole as a model hydrophobic drug with anti-inflammatory activit...

  3. Dynamic analysis of Free-Piston Stirling Engine/Linear Alternator-load system-experimentally validated

    Science.gov (United States)

    Kankam, M. David; Rauch, Jeffrey S.; Santiago, Walter

    1992-01-01

    This paper discusses the effects of variations in system parameters on the dynamic behavior of the Free-Piston Stirling Engine/Linear Alternator (FPSE/LA)-load system. The mathematical formulations incorporate both the mechanical and thermodynamic properties of the FPSE, as well as the electrical equations of the connected load. A state-space technique in the frequency domain is applied to the resulting system of equations to facilitate the evaluation of parametric impacts on the system dynamic stability. Also included is a discussion on the system transient stability as affected by sudden changes in some key operating conditions. Some representative results are correlated with experimental data to verify the model and analytic formulation accuracies. Guidelines are given for ranges of the system parameters which will ensure an overall stable operation.

  4. Free electron lifetime achievements in Liquid Argon Imaging TPC

    CERN Document Server

    Baibussinov, B; Calligarich, E; Centro, S; Cieslik, K; Farnese, C; Fava, A; Gibin, D; Guglielmi, A; Meng, G; Pietropaolo, F; Rubbia, C; Varanini, F; Ventura, S

    2010-01-01

    A key feature for the success of the Liquid Argon TPC technology is the industrial purification against electro-negative impurities, especially Oxygen and Nitrogen remnants, which have to be initially and continuously kept at an exceptional purity. New purification techniques have been applied to a 120 litres LAr-TPC test facility in the INFN-LNL laboratory. Through-going muon tracks have been used to monitor the LAr purity. The short path length used (30 cm) is compensated by the high accuracy in the observation of the specific ionization of cosmic rays muons at sea level. A free electron lifetime of (21.4+7.3-4.3) ms, namely > 15.8 ms at 90 % C.L. has been observed under stable conditions over several weeks, corresponding to about 15 ppt (part per trillion) of Oxygen equivalent. At 500 V/cm, where the electron speed is approximately of 1.5 mm/us, the free electron lifetime >15 ms corresponds to an attenuation <15 % for a drift path of 5 m, opening the way to reliable operation of LAr TPC for exceptionall...

  5. Computer-designed surgical guide template compared with free-hand operation for mesiodens extraction in premaxilla using “trapdoor” method

    Science.gov (United States)

    Hu, Ying Kai; Xie, Qian Yang; Yang, Chi; Xu, Guang Zhou

    2017-01-01

    Abstract The aim of this study was to introduce a novel method of mesiodens extraction using a vascularized pedicled bone flap by piezosurgery and to compare the differences between a computer-aided design surgical guide template and free-hand operation. A total of 8 patients with mesiodens, 4 with a surgical guide (group I), and 4 without it (group II) were included in the study. The surgical design was to construct a trapdoor pedicle on the superior mucoperiosteal attachment with application of piezosurgery. The bone lid was repositioned after mesiodens extraction. Group I patients underwent surgeries based on the preoperative planning with surgical guide templates, while group II patients underwent free-hand operation. The outcome variables were success rate, intraoperative time, anterior nasal spine (ANS) position, changes of nasolabial angle (NLA), and major complications. Data from the 2 groups were compared by SPSS 17.0, using Wilcoxon test. The operative time was significantly shorter in group I patients. All the mesiodentes were extracted successfully and no obvious differences of preoperative and postoperative ANS position and NLA value were found in both groups. The patients were all recovered uneventfully. Surgical guide templates can enhance clinical accuracy and reduce operative time by facilitating accurate osteotomies. PMID:28658139

  6. Why Are Drugs So Hard to Quit?

    Medline Plus

    Full Text Available ... it free Find out why Close Why Are Drugs So Hard to Quit? National Institute on Drug Abuse (NIDA/NIH) Loading... Unsubscribe from National Institute on Drug Abuse (NIDA/NIH)? Cancel Unsubscribe Working... Subscribe Subscribed ...

  7. A drug's life: the pathway to drug approval.

    Science.gov (United States)

    Keng, Michael K; Wenzell, Candice M; Sekeres, Mikkael A

    2013-10-01

    In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process-specifically the orphan drug designation and accelerated approval process-and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs-axitinib (Inlyta, Pfizer) and tivozanib-that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

  8. Meta-analysis of acupuncture therapy for the treatment of stable angina pectoris.

    Science.gov (United States)

    Zhang, Ze; Chen, Min; Zhang, Li; Zhang, Zhe; Wu, Wensheng; Liu, Jun; Yan, Jun; Yang, Guanlin

    2015-01-01

    Angina pectoris is a common symptom imperiling patients' life quality. The aim of this study is to evaluate the efficacy and safety of acupuncture for stable angina pectoris. Clinical randomized-controlled trials (RCTs) comparing the efficacy of acupuncture to conventional drugs in patients with stable angina pectoris were searched using the following database of PubMed, Medline, Wanfang and CNKI. Overall odds ratio (ORs) and weighted mean difference (MD) with their 95% confidence intervals (CI) were calculated by using fixed- or random-effect models depending on the heterogeneity of the included trials. Total 8 RCTs, including 640 angina pectoris cases with 372 patients received acupuncture therapy and 268 patients received conventional drugs, were included. Overall, our result showed that acupuncture significantly increased the clinical curative effects in the relief of angina symptoms (OR=2.89, 95% CI=1.87-4.47, Pacupuncture therapy was superior to conventional drugs. Although there was no significant difference in overall effective rate relating reduction of nitroglycerin between two groups (OR=2.13, 95% CI=0.90-5.07, P=0.09), a significant reduction on nitroglycerin consumption in acupuncture group was found (MD=-0.44, 95% CI=-0.64, -0.24, Pacupuncture therapy than for traditional medicines (MD=2.44, 95% CI=1.64-3.24, Pacupuncture therapy were found. Acupuncture may be an effective therapy for stable angina pectoris. More clinical trials are needed to systematically assess the role of acupuncture in angina pectoris.

  9. Drugs as instruments: a new framework for non-addictive psychoactive drug use.

    Science.gov (United States)

    Müller, Christian P; Schumann, Gunter

    2011-12-01

    Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a "necessary" prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of "drug instrumentalization." Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific "instrumentalization goals" and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future.

  10. Towards an Entropy Stable Spectral Element Framework for Computational Fluid Dynamics

    KAUST Repository

    Carpenter, Mark H.

    2016-01-04

    Nonlinearly stable finite element methods of arbitrary type and order, are currently unavailable for discretizations of the compressible Navier-Stokes equations. Summation-by-parts (SBP) entropy stability analysis provides a means of constructing nonlinearly stable discrete operators of arbitrary order, but is currently limited to simple element types. Herein, recent progress is reported, on developing entropy-stable (SS) discontinuous spectral collocation formulations for hexahedral elements. Two complementary efforts are discussed. The first effort generalizes previous SS spectral collocation work to extend the applicable set of points from tensor product, Legendre-Gauss-Lobatto (LGL) to tensor product Legendre-Gauss (LG) points. The LG and LGL point formulations are compared on a series of test problems. Both the LGL and LG operators are of comparable efficiency and robustness, as is demonstrated using test problems for which conventional FEM techniques suffer instability. The second effort extends previous work on entropy stability to include p-refinement at nonconforming interfaces. A generalization of existing entropy stability theory is required to accommodate the nuances of fully multidimensional SBP operators. The entropy stability of the compressible Euler equations on nonconforming interfaces is demonstrated using the newly developed LG operators and multidimensional interface interpolation operators. Preliminary studies suggest design order accuracy at nonconforming interfaces.

  11. Funnel metadynamics as accurate binding free-energy method

    Science.gov (United States)

    Limongelli, Vittorio; Bonomi, Massimiliano; Parrinello, Michele

    2013-01-01

    A detailed description of the events ruling ligand/protein interaction and an accurate estimation of the drug affinity to its target is of great help in speeding drug discovery strategies. We have developed a metadynamics-based approach, named funnel metadynamics, that allows the ligand to enhance the sampling of the target binding sites and its solvated states. This method leads to an efficient characterization of the binding free-energy surface and an accurate calculation of the absolute protein–ligand binding free energy. We illustrate our protocol in two systems, benzamidine/trypsin and SC-558/cyclooxygenase 2. In both cases, the X-ray conformation has been found as the lowest free-energy pose, and the computed protein–ligand binding free energy in good agreement with experiments. Furthermore, funnel metadynamics unveils important information about the binding process, such as the presence of alternative binding modes and the role of waters. The results achieved at an affordable computational cost make funnel metadynamics a valuable method for drug discovery and for dealing with a variety of problems in chemistry, physics, and material science. PMID:23553839

  12. Stable convergence and stable limit theorems

    CERN Document Server

    Häusler, Erich

    2015-01-01

    The authors present a concise but complete exposition of the mathematical theory of stable convergence and give various applications in different areas of probability theory and mathematical statistics to illustrate the usefulness of this concept. Stable convergence holds in many limit theorems of probability theory and statistics – such as the classical central limit theorem – which are usually formulated in terms of convergence in distribution. Originated by Alfred Rényi, the notion of stable convergence is stronger than the classical weak convergence of probability measures. A variety of methods is described which can be used to establish this stronger stable convergence in many limit theorems which were originally formulated only in terms of weak convergence. Naturally, these stronger limit theorems have new and stronger consequences which should not be missed by neglecting the notion of stable convergence. The presentation will be accessible to researchers and advanced students at the master's level...

  13. Self-adjusting entropy-stable scheme for compressible Euler equations

    Institute of Scientific and Technical Information of China (English)

    程晓晗; 聂玉峰; 封建湖; LuoXiao-Yu; 蔡力

    2015-01-01

    In this work, a self-adjusting entropy-stable scheme is proposed for solving compressible Euler equations. The entropy-stable scheme is constructed by combining the entropy conservative flux with a suitable diffusion operator. The entropy has to be preserved in smooth solutions and be dissipated at shocks. To achieve this, a switch function, based on entropy variables, is employed to make the numerical diffusion term added around discontinuities automatically. The resulting scheme is still entropy-stable. A number of numerical experiments illustrating the robustness and accuracy of the scheme are presented. From these numerical results, we observe a remarkable gain in accuracy.

  14. New stable phase in binary Fe-Nd

    International Nuclear Information System (INIS)

    Schneider, G.; Landgraf, F.J.G.; Villas-Boas, V.; Bezerra, G.H.; Missell, F.P.; Ray, A.E.

    1992-01-01

    An investigation of binary Fe-Nd alloys revealed the existence of an oxygen-free, stable Fe-rich phase A 2 , formed peritecticly in the range 750-800 deg C. EPMA shows this phase to contain 22.8 atomic percent Nd. This ferromagnetic phase has T c = 230 de C, but is magnetically soft. The X-ray diffraction pattern can be indexed using a hexagonal cell with a = 2.021 nm. and c = 1.235 nm. (author)

  15. XMM-Newton operations beyond the design lifetime

    Science.gov (United States)

    Parmar, Arvind N.; Kirsch, Marcus G. F.; Muñoz, J. Ramon; Santos-Lleo, Maria; Schartel, Norbert

    2012-09-01

    After more than twelve years in orbit and two years beyond the design lifetime, XMM-Newton continues its near faultless operations providing the worldwide astronomical community with an unprecedented combination of imaging and spectroscopic X-ray capabilities together with simultaneous optical and ultra-violet monitoring. The interest from the scientific community in observing with XMM-Newton remains extremely high with the last annual Announcement of Observing Opportunity (AO-11) attracting proposals requesting 6.7 times more observing time than was available. Following recovery from a communications problem in 2008, all elements of the mission are stable and largely trouble free. The operational lifetime if currently limited by the amount of available hydrazine fuel. XMM-Newton normally uses reaction wheels for attitude control and fuel is only used when offsetting reaction wheel speed away from limiting values and for emergency Sun acquisition following an anomaly. Currently, the hydrazine is predicted to last until around 2020. However, ESA is investigating the possibility of making changes to the operations concept and the onboard software that would enable lower fuel consumption. This could allow operations to well beyond 2026.

  16. Differential speciation of ferriprotoporphyrin IX in the presence of free base and diprotic 4-aminoquinoline antimalarial drugs

    Science.gov (United States)

    Gildenhuys, Johandie; Müller, Ronel; le Roex, Tanya; de Villiers, Katherine A.

    2017-03-01

    The crystal structures of the μ-propionato dimer and π-π dimer of ferriprotoporphyrin IX (Fe(III)PPIX) have been determined by single crystal X-ray diffraction (SCD). Both species were obtained in the presence of the synthetic 4-aminoquinoline antimalarial drug, amodiaquine (AQ). The solution that afforded the μ-propionato dimer contained AQ as a free base (i.e. with both quinoline and terminal amine nitrogen atoms neutral). On the other hand, when the diprotic salt of AQ was included in the crystallization medium, the Fe(III)PPIX π-π dimer was obtained. The structure of the μ-propionato dimer, which is the discrete structural unit that constitutes haemozoin (malaria pigment), is identical to that obtained previously in presence of chloroquine free base. We suspect that the drug, via its two available basic sites, facilitates dissociation of one of the two Fe(III)PPIX propionic acid groups to yield a propionate group that is required for reciprocal coordination of the metal centre to form the centrosymmetric dimer. On the other hand, this proton transfer is not possible when the drug is present as a diprotic salt. In this case, the π-π dimer of Fe(III)PPIX is obtained. In the current study, the π-π dimer of haemin (chloro-Fe(III)PPIX) was obtained as a DMF solvate from non-aqueous aprotic solution (dimethyl formamide and chloroform), however the π-π dimer is also known to exist in aqueous solution (as aqua- or hydroxo-Fe(III)PPIX), where it is purportedly involved in the nucleation of haemozoin. We have been able to unambiguously determine the positions of all non-hydrogen atoms, as well as locate or assign all hydrogen atoms in the structure of the π-π dimer, which was not possible in the SCD structure of haemin reported by Koenig in 1965 owing to disorder in the vinyl and methyl substituents. Interestingly, no disorder in the methyl and vinyl groups is observed in the current structure. Both the π-π and μ-propionato dimers of Fe(III)PPIX are

  17. Extension of operation regimes and investigation of three-dimensional current-less plasmas in the Large Helical Device

    International Nuclear Information System (INIS)

    Kaneko, O.

    2012-11-01

    The Large Helical Device (LHD) has shown the advantages of heliotron plasma for fusion reactor from operational point of view not only such as disruption free and steady state operation, but also as high density and stable high beta operation. Since the last Fusion Energy Conference in Daejon in 2010 (Yamada, 2011 Nucl. Fusion 51 094021), physical understanding as well as parameter improvement of net-current free helical plasmas has progressed successively. The current efforts are focused on optimization of plasma edge condition to extend the operation regime towards higher ion temperature and more stable high density. In LHD a part of open helical divertors are being modified to the baffle-structured closed ones to aim at active control of the edge plasma. It has been demonstrated that the neutral pressure in the closed helical divertor was more than 10 times higher than that in the open helical divertor. The central ion temperature has exceeded 7 keV. This high-T i plasma was obtained by a carbon pellet injection and the kinetic-energy confinement was improved by a factor of 1.5. Transport analysis of the high-T i plasmas has shown that the ion-thermal conductivity and the viscosity reduced after the pellet injection. Study of physics in 3-D geometry is highlighted in the topics of the response to Resonant Magnetic Perturbation such as ELM mitigation and divertor detachment. Novel approaches of non-local and non-diffusive transport have also been advanced. In this paper, highlighted results in these two years are overviewed. (author)

  18. Problems Associated With Substandard And Counterfeit Drugs In ...

    African Journals Online (AJOL)

    Problems Associated With Substandard And Counterfeit Drugs In Developing Countries: A Review Article On Global Implications Of Counterfeit Drugs In The Era Of Anti-Retroviral (ARVS) Drugs In A Free Market Economy.

  19. Formation of stable radicals during perfluoroalkane radiolysis

    International Nuclear Information System (INIS)

    Allayarov, S.R.; Demidov, S.V.; Kiryukhin, D.P.; Mikhajlov, A.I.; Barkalov, I.M.

    1984-01-01

    Accumulation and stabilization kinetics of perfluoroalkyls during α-radiolysis ( 60 Co) of perfluoralkanes (PFA) in a wide temperature range for different PFA fractions differing in the average molecular weight, is investigated. It is noted that low temperature (PFA) radiolysis (77 K) is of a linear nature of accumulation of stabilized radicals up to doses of approximately 700 KGy. In the case of PFA radiolysis at 300 K radiation yields of stable radicals are somewhat lower than at 47 K and at doses of 200-300 KGy, their accumulation ceases. It is shown that kinetics of formation and accumulation of stable radicals does not depend on molecular mass and PFA fraction viscosity. Perfluoroalkyl stability is explained by intra molecular conformation spheric insulation of the free valency. Perfluoroalkyl stability in different PFA fractions in a wide time range in different media is investigated

  20. Limiting stable states of high-Tc superconductors in the alternating current modes

    International Nuclear Information System (INIS)

    Romanovskii, V.R.; Watanabe, K.; Awaji, S.

    2014-01-01

    The limiting current-carrying capacity of high-T c superconductor and superconducting tape has been studied in the alternating current states. The features that are responsible for their stable formation have been investigated under the conduction-cooled conditions when the operating peak values of the electric field and the current may essentially exceed the corresponding critical values of superconductor. Besides, it has been proved that these peak values are higher than the values of the electric field and the current, which lead to the thermal runaway phenomenon when the current instability onset occurs in the operating modes with direct current. As a result, the stable extremely high heat generation exists in these operating states, which can be called as overloaded states. The limiting stable peak values of charged currents and stability conditions have been determined taking into account the flux creep states of superconductors. The analysis performed has revealed that there exist characteristic times defining the corresponding time windows in the stable development of overloaded states of the alternating current. In order to explain their existence, the basic thermo-electrodynamics mechanisms have been formulated, which have allowed to explain the high stable values of the temperature and the induced electric field before the onset of alternating current instability. In general, it has been shown that the high-T c superconductors may stably operate in the overloaded alternating current states even under the not intensive cooling conditions at a very high level of heat generation, which is not considered in the existing theory of losses. (authors)

  1. Lead-free, air-stable all-inorganic cesium bismuth halide perovskite nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bin; Hong, Feng; Mao, Xin; Li, Yajuan [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science (China); University of the Chinese Academy of Sciences, Beijing (China); Chen, Junsheng [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science (China); Department of Chemical Physics and NanoLund, Chemical Center, Lund University (Sweden); Zheng, Kaibo; Pullerits, Tonu [Department of Chemical Physics and NanoLund, Chemical Center, Lund University (Sweden); Yang, Songqiu; Deng, Weiqiao; Han, Keli [State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science (China)

    2017-10-02

    Lead-based perovskite nanocrystals (NCs) have outstanding optical properties and cheap synthesis conferring them a tremendous potential in the field of optoelectronic devices. However, two critical problems are still unresolved and hindering their commercial applications: one is the fact of being lead-based and the other is the poor stability. Lead-free all-inorganic perovskite Cs{sub 3}Bi{sub 2}X{sub 9} (X=Cl, Br, I) NCs are synthesized with emission wavelength ranging from 400 to 560 nm synthesized by a facile room temperature reaction. The ligand-free Cs{sub 3}Bi{sub 2}Br{sub 9} NCs exhibit blue emission with photoluminescence quantum efficiency (PLQE) about 0.2 %. The PLQE can be increased to 4.5 % when extra surfactant (oleic acid) is added during the synthesis processes. This improvement stems from passivation of the fast trapping process (2-20 ps). Notably, the trap states can also be passivated under humid conditions, and the NCs exhibited high stability towards air exposure exceeding 30 days. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  2. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    LENUS (Irish Health Repository)

    Toomey, David

    2009-01-01

    BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins\\/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and\\/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY\\/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i) homologous to previously crystallized proteins or (ii) targets of known drugs, but are (iii) not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS\\/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under \\'change-of-application\\' patents.

  3. Genomes2Drugs: identifies target proteins and lead drugs from proteome data.

    Directory of Open Access Journals (Sweden)

    David Toomey

    Full Text Available BACKGROUND: Genome sequencing and bioinformatics have provided the full hypothetical proteome of many pathogenic organisms. Advances in microarray and mass spectrometry have also yielded large output datasets of possible target proteins/genes. However, the challenge remains to identify new targets for drug discovery from this wealth of information. Further analysis includes bioinformatics and/or molecular biology tools to validate the findings. This is time consuming and expensive, and could fail to yield novel drugs if protein purification and crystallography is impossible. To pre-empt this, a researcher may want to rapidly filter the output datasets for proteins that show good homology to proteins that have already been structurally characterised or proteins that are already targets for known drugs. Critically, those researchers developing novel antibiotics need to select out the proteins that show close homology to any human proteins, as future inhibitors are likely to cross-react with the host protein, causing off-target toxicity effects later in clinical trials. METHODOLOGY/PRINCIPAL FINDINGS: To solve many of these issues, we have developed a free online resource called Genomes2Drugs which ranks sequences to identify proteins that are (i homologous to previously crystallized proteins or (ii targets of known drugs, but are (iii not homologous to human proteins. When tested using the Plasmodium falciparum malarial genome the program correctly enriched the ranked list of proteins with known drug target proteins. CONCLUSIONS/SIGNIFICANCE: Genomes2Drugs rapidly identifies proteins that are likely to succeed in drug discovery pipelines. This free online resource helps in the identification of potential drug targets. Importantly, the program further highlights proteins that are likely to be inhibited by FDA-approved drugs. These drugs can then be rapidly moved into Phase IV clinical studies under 'change-of-application' patents.

  4. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

    Directory of Open Access Journals (Sweden)

    Francesca Selmin

    2015-01-01

    Full Text Available This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C. By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE, suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%. Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs.

  5. Teens in Action. Creating a Drug-Free Future for America's Youth.

    Science.gov (United States)

    Adams, Tom; Resnik, Hank

    This book on drug abuse prevention is addressed to teenagers and covers five main areas where drug use can be prevented: schools, communities, media, the social scene, and the family. The first chapter on school programs briefly discusses peer-led alcohol and drug education, peer counseling, creating a positive school climate, and developing…

  6. The design and implementation of the FreeBSD operating system

    CERN Document Server

    McKusick, Marshall Kirk; Watson, Robert N M

    2015-01-01

    The most complete, authoritative technical guide to the FreeBSD kernel's internal structure has now been extensively updated to cover all major improvements between Versions 5 and 11. Approximately one-third of this edition's content is completely new, and another one-third has been extensively rewritten. Three long-time FreeBSD project leaders begin with a concise overview of the FreeBSD kernel's current design and implementation. Next, they cover the FreeBSD kernel from the system-call level down-from the interface to the kernel to the hardware. Explaining key design decisions, they detail the concepts, data structures, and algorithms used in implementing each significant system facility, including process management, security, virtual memory, the I/O system, filesystems, socket IPC, and networking. This Second Edition * Explains highly scalable and lightweight virtualization using FreeBSD jails, and virtual-machine acceleration with Xen and Virtio device paravirtualization * Describes new security features...

  7. Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine.

    Science.gov (United States)

    Shahba, Ahmad Abdul-Wahhab; Ahmed, Abid Riaz; Alanazi, Fars Kaed; Mohsin, Kazi; Abdel-Rahman, Sayed Ibrahim

    2018-04-25

    Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.

  8. Changing effects of direct-to-consumer broadcast drug advertising information sources on prescription drug requests.

    Science.gov (United States)

    Lee, Annisa Lai

    2009-06-01

    This study tracks the changes of the effects of 4 information sources for direct-to-consumer drug advertising on patients' requests for prescription drugs from physicians since the inception of the "Guidance for Industry about Consumer-directed Broadcast Advertisements." The Guidance advises pharmaceuticals to use four information sources for consumers to seek further information to supplement broadcast drug advertisements: small-print information, the Internet, a toll-free number, and health-care providers (nurses, doctors, and pharmacists). Logistic models were created by using survey data collected by the Food and Drug Administration in 1999 and 2002. Results show that throughout the years, health-care providers remain the most used and strongest means associated with patients' direct requests for nonspecific and specific prescription drugs from doctors. The small-print information source gains power and changes from an indirect means associated with patients' discussing drugs with health-care providers to a direct means associated with patients' asking about nonspecific and specific drugs from their doctors. The Internet is not directly related to drug requests, but the effect of its association with patients seeking information from health-care providers grew 11-fold over the course of the study. The toll-free number lost its power altogether for both direct request for a prescription drug and further discussion with health-care providers. Patient demographics will be considered for specific policy implications.

  9. Phased mission modelling of systems with maintenance-free operating periods using simulated Petri nets

    Energy Technology Data Exchange (ETDEWEB)

    Chew, S.P.; Dunnett, S.J. [Department of Aeronautical and Automotive Engineering, Loughborough University, Loughborough, Leics (United Kingdom); Andrews, J.D. [Department of Aeronautical and Automotive Engineering, Loughborough University, Loughborough, Leics (United Kingdom)], E-mail: j.d.andrews@lboro.ac.uk

    2008-07-15

    A common scenario in engineering is that of a system which operates throughout several sequential and distinct periods of time, during which the modes and consequences of failure differ from one another. This type of operation is known as a phased mission, and for the mission to be a success the system must successfully operate throughout all of the phases. Examples include a rocket launch and an aeroplane flight. Component or sub-system failures may occur at any time during the mission, yet not affect the system performance until the phase in which their condition is critical. This may mean that the transition from one phase to the next is a critical event that leads to phase and mission failure, with the root cause being a component failure in a previous phase. A series of phased missions with no maintenance may be considered as a maintenance-free operating period (MFOP). This paper describes the use of a Petri net (PN) to model the reliability of the MFOP and phased missions scenario. The model uses Monte-Carlo simulation to obtain its results, and due to the modelling power of PNs, can consider complexities such as component failure rate interdependencies and mission abandonment. The model operates three different types of PN which interact to provide the overall system reliability modelling. The model is demonstrated and validated by considering two simple examples that can be solved analytically.

  10. Phased mission modelling of systems with maintenance-free operating periods using simulated Petri nets

    International Nuclear Information System (INIS)

    Chew, S.P.; Dunnett, S.J.; Andrews, J.D.

    2008-01-01

    A common scenario in engineering is that of a system which operates throughout several sequential and distinct periods of time, during which the modes and consequences of failure differ from one another. This type of operation is known as a phased mission, and for the mission to be a success the system must successfully operate throughout all of the phases. Examples include a rocket launch and an aeroplane flight. Component or sub-system failures may occur at any time during the mission, yet not affect the system performance until the phase in which their condition is critical. This may mean that the transition from one phase to the next is a critical event that leads to phase and mission failure, with the root cause being a component failure in a previous phase. A series of phased missions with no maintenance may be considered as a maintenance-free operating period (MFOP). This paper describes the use of a Petri net (PN) to model the reliability of the MFOP and phased missions scenario. The model uses Monte-Carlo simulation to obtain its results, and due to the modelling power of PNs, can consider complexities such as component failure rate interdependencies and mission abandonment. The model operates three different types of PN which interact to provide the overall system reliability modelling. The model is demonstrated and validated by considering two simple examples that can be solved analytically

  11. Self nano-emulsifying drug delivery system for Embelin: Design, characterization and in-vitro studies

    Directory of Open Access Journals (Sweden)

    Komal Parmar

    2015-10-01

    Full Text Available CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS containing Capryol-90 as oil phase for the delivery of Embelin, a poorly water soluble herbal active ingredient. Box-Behnken experimental design was employed to optimise the formulation variables, X1 (amount of oil; Capryol 90, X2 (amount of surfactant; Acrysol EL 135 and X3 (amount of co-surfactant; PEG 400. Systems were appraised for visual characteristics for self emulsifying time, globule size and drug release. Optimised liquid formulations were formulated into free flowing granules (S-SNEDDS by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into tablet. In vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the drug. FT-IR data revealed no physicochemical interaction between drug and excipients. Solid state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution studies. TEM analysis exhibited spherical globules. Further, the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical properties. Thus, the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient, Embelin.

  12. A micromachined electrochemical sensor for free chlorine monitoring in drinking water.

    Science.gov (United States)

    Mehta, A; Shekhar, H; Hyun, S H; Hong, S; Cho, H J

    2006-01-01

    In this work, we designed, fabricated and tested a disposable, flow-through amperometric sensor for free chlorine determination in water. The sensor is based on the principle of an electrochemical cell. The substrate, as well as the top microfluidic layer, is made up of a polymer material. The advantages include; (a) disposability from low cost; (b) stable operation range from three-electrode design; (c) fluidic interconnections that provide on line testing capabilities; and (d) transparent substrate which provides for future integration of on-chip optics. The sensor showed a good response and linearity in the chlorine concentration ranging from 0.3 to 1.6 ppm, which applies to common chlorination process for drinking water purification.

  13. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system

    International Nuclear Information System (INIS)

    Gao Lei; Zhang Dianrui; Chen Minghui

    2008-01-01

    Formulation of poorly soluble drugs is a general intractable problem in pharmaceutical field, especially those compounds poorly soluble in both aqueous and organic media. It is difficult to resolve this problem using conventional formulation approaches, so many drugs are abandoned early in discovery. Nanocrystals, a new carrier-free colloidal drug delivery system with a particle size ranging from 100 to 1000 nm, is thought as a viable drug delivery strategy to develop the poorly soluble drugs, because of their simplicity in preparation and general applicability. In this article, the product techniques of the nanocrystals were reviewed and compared, the special features of drug nanocrystals were discussed. The researches on the application of the drug nanocrystals to various administration routes were described in detail. In addition, as introduced later, the nanocrystals could be easily scaled up, which was the prerequisite to the development of a delivery system as a market product

  14. A high-power diode-laser-pumped CW Nd:YAG laser using a stable-unstable resonator

    International Nuclear Information System (INIS)

    Mudge, M.; Ostermeyer, P.; Veitch, J.; Munch, J.; Hamilton, M.W.

    2000-01-01

    Full text: The design and operation of a power-scalable diode-laser-pumped CW Nd:YAG zigzag slab laser that uses a stable-unstable resonator with a graded reflectivity mirror as an output coupler is described. We demonstrate control of the thermal lens strength in the unstable plane and weak thermal lensing in the stable plane that is independent of pump power, vital for efficient scalability. This enabled CW operation of the stable-unstable resonator with excellent near- and far-field beam quality

  15. Drug-use pattern, comorbid psychosis and mortality in people with a history of opioid addiction

    DEFF Research Database (Denmark)

    Sørensen, H J; Jepsen, P W; Haastrup, S

    2005-01-01

    OBJECTIVE: To compare the 15-year mortality of people with a history of opioid dependence that had achieved stable abstinence, with the mortality associated with continued drug use. Another objective was to study the influence of hospitalization with comorbid psychosis on the 15-year mortality. M...... at lower risk of premature death than people with continued drug use. A residual observed excess mortality in people who had apparently achieved stable abstinence from drug use is consistent with the view of drug addiction as a chronic disease....

  16. Self-plied and twist-stable carbon nanotube yarn artificial muscles driven by organic solvent adsorption.

    Science.gov (United States)

    Jin, Kaiyun; Zhang, Silan; Zhou, Susheng; Qiao, Jian; Song, Yanhui; Di, Jiangtao; Zhang, Dengsong; Li, Qingwen

    2018-05-03

    Artificial yarn/fiber muscles have recently attracted considerable interest for various applications. These muscles can provide large-stroke tensile and torsional actuations, resulting from inserted twists. However, tensional tethering of twisted muscles is generally needed to avoid muscle snarling and untwisting. In this paper a carbon nanotube (CNT) yarn muscle that is tethering-free and twist-stable is reported. The yarn muscle is prepared by allowing the self-plying of a coiled CNT yarn. When driven by acetone adsorption, this muscle shows decoupled actuations, which provide fast and reversible ∼13.3% contraction strain against a constant stress corresponding to ∼38 000 times the muscle weight but almost zero torsional strokes. The cycling test shows that the self-plied muscle has very good structural stability and actuation reversibility. Applied joule heating can help increase the desorption of acetone and increase the operation frequency of the self-plied muscle. Furthermore, by controlling the coupling between the joule heating and acetone adsorption/desorption, tensile actuations from negative to positive have been achieved. This twist-stable feature could considerably facilitate the practical applications of such muscle.

  17. A multiple free-radical scavenging (MULTIS) study on the antioxidant capacity of a neuroprotective drug, edaravone as compared with uric acid, glutathione, and trolox.

    Science.gov (United States)

    Kamogawa, Erisa; Sueishi, Yoshimi

    2014-03-01

    Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) is a neuroprotective drug that has been used for brain ischemia injury treatment. Because its activity is speculated to be due to free radical scavenging activity, we carried out a quantitative determination of edaravone's free radical scavenging activity against multiple free radical species. Electron spin resonance (ESR) spin trapping-based multiple free-radical scavenging (MULTIS) method was employed, where target free radicals were hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen. Edaravone showed relatively high scavenging abilities against hydroxyl radical (scavenging rate constant k=2.98×10(11) M(-1) s(-1)), singlet oxygen (k=2.75×10(7) M(-1) s(-1)), and methyl radical (k=3.00×10(7) M(-1) s(-1)). Overall, edaravone's scavenging activity against multiple free radical species is as robust as other known potent antioxidant such as uric acid, glutathione, and trolox. A radar chart illustration of the MULTIS activity relative to uric acid, glutathione, and trolox indicates that edaravone has a high and balanced antioxidant activity with low specificity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Free probability and random matrices

    CERN Document Server

    Mingo, James A

    2017-01-01

    This volume opens the world of free probability to a wide variety of readers. From its roots in the theory of operator algebras, free probability has intertwined with non-crossing partitions, random matrices, applications in wireless communications, representation theory of large groups, quantum groups, the invariant subspace problem, large deviations, subfactors, and beyond. This book puts a special emphasis on the relation of free probability to random matrices, but also touches upon the operator algebraic, combinatorial, and analytic aspects of the theory. The book serves as a combination textbook/research monograph, with self-contained chapters, exercises scattered throughout the text, and coverage of important ongoing progress of the theory. It will appeal to graduate students and all mathematicians interested in random matrices and free probability from the point of view of operator algebras, combinatorics, analytic functions, or applications in engineering and statistical physics.

  19. Short and long-term safety and efficacy of polymer-free vs. durable polymer drug-eluting stents. A comprehensive meta-analysis of randomized trials including 6178 patients

    NARCIS (Netherlands)

    Navarese, E.P.; Kowalewski, M.; Cortese, B.; Kandzari, D.; Dias, S.; Wojakowski, W.; Buffon, A.; Lansky, A.; Angelini, P.; Torguson, R.; Kubica, J.; Kelm, M.; Boer, M.J. de; Waksman, R.; Suryapranata, H.

    2014-01-01

    BACKGROUND: The efficacy and safety of polymer-free drug-eluting stents (DESs) in clinical practice is currently subject of debate; randomized trials (RCTs) conducted so far provided conflicting results or were underpowered to definitively address this question; we aimed to investigate the efficacy

  20. Exhaustive and stable electromembrane extraction of acidic drugs from human plasma

    DEFF Research Database (Denmark)

    Huang, Chuixiu; Gjelstad, Astrid; Seip, Knut Fredrik

    2015-01-01

    The first part of the current work systematically described the screening of different types of organic solvents as the supported liquid membrane (SLM) for electromembrane extraction (EME) of acidic drugs, including different alcohols, ketones, and ethers. Seven acidic drugs with a wide logP rang......). With this SLM, exhaustive EME was performed from diluted human plasma, and the recoveries of five out of seven analytes were over 91% after 10min EME. This approach was evaluated using HPLC-UV, and the evaluation data were found to be satisfactory...... to increasing viscosity and decreasing α and π* values. The system-current during EME was found to be dependent on the type and the volume of the SLM. In contact with human plasma, an SLM of pure 1-heptanol was unstable, and to improve stability, 1-heptanol was mixed with 2-nitrophenyl octyl ether (NPOE...

  1. A Stable, Non-Cesiated III-Nitride Photocathode for Ultraviolet Astronomy Application

    Science.gov (United States)

    Bell, Lloyd

    In this effort, we propose to develop a new type of cesium-free photocathode using III-nitride (III-N) materials (GaN, AlN, and their alloys) and to achieve highly efficient, solar blind, and stable UV response. Currently, detectors used in UV instruments utilize a photocathode to convert UV photons into electrons that are subsequently detected by microchannel plate or CCD. The performance of these detectors critically depends on the efficiency and stability of their photocathodes. In particular, photocathode instability is responsible for many of the fabrication difficulties commonly experienced with this class of detectors. In recent years, III-N (in particular GaN) photocathodes have been demonstrated with very high QE (>50%) in parts of UV spectral range. Moreover, due to the wide bandgaps of III-nitride materials, photocathode response can be tailored to be intrinsically solar-blind. However, these photocathodes still rely on cesiation for activation, necessitating all-vacuum fabrication and sealed-tube operation. The proposed photocathode structure will achieve activation through methods for band structure engineering such as delta-doping and polarization field engineering. Compared to the current state-of-the-art in flight-ready microchannel plate sealed tubes, photocathodes based on III-N materials will yield high QE and significantly enhance both fabrication yield and reliability, since they do not require cesium or other highly reactive materials for activation. This performance will enable a ~4 meter medium class UV spectroscopic and imaging mission that is of high scientific priority for NASA. This work will build on the success of our previous APRA-funded effort. In that work, we demonstrated III-nitride photocathode operation without the use of cesium and stable response with respect to time. These accomplishments represent major improvements to the state-of-the-art for photocathode technologies. In the proposed effort, we will implement III

  2. Drug release, preclinical and clinical pharmacokinetics relationships of alginate pellets prepared by melt technology.

    Science.gov (United States)

    Bose, Anirbandeep; Harjoh, Nurulaini; Pal, Tapan Kumar; Dan, Shubhasis; Wong, Tin Wui

    2016-01-01

    Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure. This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets. Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug. A fast in situ calcium acetate dissolution in pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate fragments and drug dissolution retardation at pH 1.2, which were not found in other pellet types. The preclinical drug absorption rate was lower with calcium acetate loaded than calcium-free alginate pellets. In human subjects, however, the extent and the rate of drug absorption were higher from calcium acetate-loaded pellets than calcium-free alginate pellets. The fine, dispersible and weakly gastric mucoadhesive calcium alginate pellets underwent fast human gastrointestinal transit. They released the drug at a greater rate than calcium-free pellets in the intestine, thereby promoting drug bioavailability. Calcium acetate was required as a disintegrant more than as a crosslinking agent clinically to promote pellet fragmentation, fast gastrointestinal transit and drug release in intestinal medium, and intestinal-specific drug bioavailability.

  3. Hyperactivity, drugs and attention deficit.

    Science.gov (United States)

    Pozzi, M; Hartley, L

    1984-09-01

    Thirty-two hyperactive children who were under imipramine or methylphenidate medication took part in the experiment. The children were asked to learn a set of paired associate pictures containing a salient, central, figure and a secondary figure below. Free recall of all pictures was scored both immediately and seven days later. The children were subdivided into four groups according to the classical state-dependent learning paradigm. Group 1 was withdrawn from medication on both trials, groups 2 and 3 were withdrawn from medication on the first or second trial and group 4 received medication on both trials. No drug effects were found in immediate total recall. Delayed free recall was improved when original learning was under the drug state. This result was related to the proposal that arousing words are better remembered in delayed recall. Delayed recall of the secondary stimuli was particularly improved by the drugs during learning. Drug state dependency of the children's memory was also shown.

  4. Modelling the complete operation of a free-piston shock tunnel for a low enthalpy condition

    Science.gov (United States)

    McGilvray, M.; Dann, A. G.; Jacobs, P. A.

    2013-07-01

    Only a limited number of free-stream flow properties can be measured in hypersonic impulse facilities at the nozzle exit. This poses challenges for experimenters when subsequently analysing experimental data obtained from these facilities. Typically in a reflected shock tunnel, a simple analysis that requires small amounts of computational resources is used to calculate quasi-steady gas properties. This simple analysis requires initial fill conditions and experimental measurements in analytical calculations of each major flow process, using forward coupling with minor corrections to include processes that are not directly modeled. However, this simplistic approach leads to an unknown level of discrepancy to the true flow properties. To explore the simple modelling techniques accuracy, this paper details the use of transient one and two-dimensional numerical simulations of a complete facility to obtain more refined free-stream flow properties from a free-piston reflected shock tunnel operating at low-enthalpy conditions. These calculations were verified by comparison to experimental data obtained from the facility. For the condition and facility investigated, the test conditions at nozzle exit produced with the simple modelling technique agree with the time and space averaged results from the complete facility calculations to within the accuracy of the experimental measurements.

  5. Self-adjusting entropy-stable scheme for compressible Euler equations

    International Nuclear Information System (INIS)

    Cheng Xiao-Han; Nie Yu-Feng; Cai Li; Feng Jian-Hu; Luo Xiao-Yu

    2015-01-01

    In this work, a self-adjusting entropy-stable scheme is proposed for solving compressible Euler equations. The entropy-stable scheme is constructed by combining the entropy conservative flux with a suitable diffusion operator. The entropy has to be preserved in smooth solutions and be dissipated at shocks. To achieve this, a switch function, which is based on entropy variables, is employed to make the numerical diffusion term be automatically added around discontinuities. The resulting scheme is still entropy-stable. A number of numerical experiments illustrating the robustness and accuracy of the scheme are presented. From these numerical results, we observe a remarkable gain in accuracy. (paper)

  6. Modified Extraction-Free Ion-Pair Methods for the Determination of Flunarizine Dihydrochloride in Bulk Drug, Tablets, and Human Urine

    Science.gov (United States)

    Prashanth, K. N.; Basavaiah, K.

    2018-01-01

    Two simple and sensitive extraction-free spectrophotometric methods are described for the determination of flunarizine dihydrochloride. The methods are based on the ion-pair complex formation between the nitrogenous compound flunarizine (FNZ), converted from flunarizine dihydrochloride (FNH), and the acidic dye phenol red (PR), in which experimental variables were circumvented. The first method (method A) is based on the formation of a yellow-colored ion-pair complex (1:1 drug:dye) between FNZ and PR in chloroform, which is measured at 415 nm. In the second method (method B), the formed drug-dye ion-pair complex is treated with ethanolic potassium hydroxide in an ethanolic medium, and the resulting base form of the dye is measured at 580 nm. The stoichiometry of the formed ion-pair complex between the drug and dye (1:1) is determined by Job's continuous variations method, and the stability constant of the complex is also calculated. These methods quantify FNZ over the concentration ranges 5.0-70.0 in method A and 0.5-7.0 μg/mL in method B. The calculated molar absorptivities are 6.17 × 103 and 5.5 × 104 L/mol·cm-1 for method A and method B, respectively, with corresponding Sandell sensitivity values of 0.0655 and 0.0074 μg/cm2. The methods are applied to the determination of FNZ in pure drug and human urine.

  7. Non-destructive measurement of Xe filling pressure in mercury-free metal halide lamp

    International Nuclear Information System (INIS)

    Motomura, Hideki; Enoki, Kyosuke; Jinno, Masafumi

    2010-01-01

    Mercury-free metal halide lamps (MHLs) for automotive purposes have been developing in the market. When mercury is not used, the electric and emission characteristics of the lamp strongly depend on the xenon filling pressure. Therefore a non-destructive gas pressure estimation technique is required to obtain stable performance of the lamps as commercial products. The authors have developed an estimation method by which the gas pressure is estimated from the current peak value at the initial stage of ignition under pulsed operation. It is shown that accuracy of the order of ±(0.1-0.3) atm is obtained using an empirical formula.

  8. 14 CFR 91.19 - Carriage of narcotic drugs, marihuana, and depressant or stimulant drugs or substances.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Carriage of narcotic drugs, marihuana, and... OPERATING AND FLIGHT RULES General § 91.19 Carriage of narcotic drugs, marihuana, and depressant or... operate a civil aircraft within the United States with knowledge that narcotic drugs, marihuana, and...

  9. Adenovirus dodecahedron, as a drug delivery vector.

    Directory of Open Access Journals (Sweden)

    Monika Zochowska

    Full Text Available BACKGROUND: Bleomycin (BLM is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad dodecahedron base (DB is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. PRINCIPAL FINDINGS: Dodecahedron (Dd structure is preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. CONCLUSIONS/SIGNIFICANCE: Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.

  10. Freedom: a transient fission-product release model for radioactive and stable species

    International Nuclear Information System (INIS)

    Macdonald, L.D.; Lewis, B.J.; Iglesias, F.C.

    1989-05-01

    A microstructure-dependent fission-gas release and swelling model (FREEDOM) has been developed for UO 2 fuel. The model describes the transient release behaviour for both the radioactive and stable fission-product species. The model can be applied over the full range of operating conditions, as well as for accident conditions that result in high fuel temperatures. The model accounts for lattice diffusion and grain-boundary sweeping of fusion products to the grain boundaries, where the fission gases accumulate in grain-face bubbles as a result of vacancy diffusion. Release of fission-gas to the free void of the fuel element occurs through the interlinkage of bubbles and cracks on the grain boundaries. This treatment also accounts for radioactive chain decay and neutron-induced transmutation effects. These phenomena are described by mass balance equations which are numerically solved using a moving-boundary, finite-element method with mesh refinement. The effects of grain-face bubbles on fuel swelling and fuel thermal conductivity are included in the ELESIM fuel performance code. FREEDOM has an accuracy of better than 1% when assessed against an analytic solution for diffusional release. The code is being evaluated against a fuel performance database for stable gas release, and against sweep-gas and in-cell fission-product release experiments at Chalk River for active species

  11. A model for a stable coronal loop

    International Nuclear Information System (INIS)

    Hoven, G.V.; Chiuderi, C.; Giachetti, R.

    1977-01-01

    We present here a new plasma-physics model of a stable active-region arch which corresponds to the structure observed in the EUV. Pressure gradients are seen, so that the equilibrium magnetic field must depart from the force-free form valid in the surrounding corona. We take advantage of the data and of the approximate cylindrical symmetry to develop a modified form of the commonly assumed sheared-spiral structure. The dynamic MHD behavior of this new pressure/field model is then evaluated by the Newcomb criterion, taken from controlled-fusion physics, and the results show short-wavelength stability in a specific parameter range. Thus we demonstrate the possibility, for pressure profiles with widths of the order of the magnetic-field scale, that such arches can persist for reasonable periods. Finally, the spatial proportions and magnetic fields of a characteristic stable coronal loop are described

  12. Mapping in vivo target interaction profiles of covalent inhibitors using chemical proteomics with label-free quantification.

    Science.gov (United States)

    van Rooden, Eva J; Florea, Bogdan I; Deng, Hui; Baggelaar, Marc P; van Esbroeck, Annelot C M; Zhou, Juan; Overkleeft, Herman S; van der Stelt, Mario

    2018-04-01

    Activity-based protein profiling (ABPP) has emerged as a valuable chemical proteomics method to guide the therapeutic development of covalent drugs by assessing their on-target engagement and off-target activity. We recently used ABPP to determine the serine hydrolase interaction landscape of the experimental drug BIA 10-2474, thereby providing a potential explanation for the adverse side effects observed with this compound. ABPP allows mapping of protein interaction landscapes of inhibitors in cells, tissues and animal models. Whereas our previous protocol described quantification of proteasome activity using stable-isotope labeling, this protocol describes the procedures for identifying the in vivo selectivity profile of covalent inhibitors with label-free quantitative proteomics. The optimization of our protocol for label-free quantification methods results in high proteome coverage and allows the comparison of multiple biological samples. We demonstrate our protocol by assessing the protein interaction landscape of the diacylglycerol lipase inhibitor DH376 in mouse brain, liver, kidney and testes. The stages of the protocol include tissue lysis, probe incubation, target enrichment, sample preparation, liquid chromatography-mass spectrometry (LC-MS) measurement, data processing and analysis. This approach can be used to study target engagement in a native proteome and to identify potential off targets for the inhibitor under investigation. The entire protocol takes at least 4 d, depending on the number of samples.

  13. Strategi Hubungan Indonesia Dengan Malaysia Dalam Mewujudkan Drug Free ASEAN 2015

    OpenAIRE

    Istiqomah, Ratih Nur; Hanura, Marten; Susiatiningsih, Hermini

    2016-01-01

    Drugs trafficking is one of the most salient transnational crimes threateningASEAN member states especially Indonesia and Malaysia. The bilateralcooperation between both countries against transnational drugs trafficking isone of the efforts in combating drug issues happening in those countries.However, the implementation of the cooperation has not effectively reduced thedrugs problem between Indonesia and Malaysia particularly in the years of2009/2010 and 2013/2014. This research aims to obse...

  14. Long term thermal energy storage with stable supercooled sodium acetate trihydrate

    DEFF Research Database (Denmark)

    Dannemand, Mark; Schultz, Jørgen M.; Johansen, Jakob Berg

    2015-01-01

    Utilizing stable supercooling of sodium acetate trihydrate makes it possible to store thermal energy partly loss free. This principle makes seasonal heat storage in compact systems possible. To keep high and stable energy content and cycling stability phase separation of the storage material must...... it expands and will cause a pressure built up in a closed chamber which might compromise stability of the supercooling. This can be avoided by having an air volume above the phase change material connected to an external pressure less expansion tank. Supercooled sodium acetate trihydrate at 20 °C stores up...

  15. Operation of the high-brightness linac for the advanced free-electron laser initiative at Los Alamos

    International Nuclear Information System (INIS)

    Sheffield, R.L.; Austin, R.H.; Chan, K.C.D.; Gierman, S.M.; Kinross-Wright, J.M.; Kong, S.H.; Nguyen, D.C.; Russell, S.J.; Timmer, C.A.

    1993-01-01

    Free-electron lasers and high-energy physics accelerators have increased the demand for very high-brightness beam sources. This paper describes the design of an accelerator which has produced beams of 2.1 π mm-mrad at 1 nC and emittances of 3.7 and 6.5 π mm-mrad for 2 and 3 nC, respectively. The accelerator has been operated between 10 and 18 MeV. The beam emittance growth in the accelerator is minimized by using a photoinjector electron source integrated into the design of the linac, a focusing solenoid to correct the emittance growth caused by space charge, and a special design of the coupling slots between accelerator cavities to minimize quadrupole effects. The FEL has recently operated at 5 microns

  16. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    Science.gov (United States)

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi

    2015-05-01

    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  17. Identifying Drug–Drug Interactions by Data Mining

    DEFF Research Database (Denmark)

    Hansen, Peter Wæde; Clemmensen, Line Katrine Harder; Sehested, Thomas S.G.

    2016-01-01

    Background—Knowledge about drug–drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug–drug interactions were discoverable without prior hypotheses using data mining. We focused...... registries. Additionally, we discovered a few potentially novel interactions. This opens up for the use of data mining to discover unknown drug–drug interactions in cardiovascular medicine....... on warfarin–drug interactions as the prototype. Methods and Results—We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation. Data sets were retrieved...

  18. The Effects of FreeSurfer Version, Workstation Type, and Macintosh Operating System Version on Anatomical Volume and Cortical Thickness Measurements

    OpenAIRE

    Gronenschild, Ed H. B. M.; Habets, Petra; Jacobs, Heidi I. L.; Mengelers, Ron; Rozendaal, Nico; van Os, Jim; Marcelis, Machteld

    2012-01-01

    FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). S...

  19. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Science.gov (United States)

    Nunn, Amy S; Fonseca, Elize M; Bastos, Francisco I; Gruskin, Sofia; Salomon, Joshua A

    2007-11-13

    Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART) for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs), procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005. We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r) have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs: patented lopinavir

  20. Evolution of antiretroviral drug costs in Brazil in the context of free and universal access to AIDS treatment.

    Directory of Open Access Journals (Sweden)

    Amy S Nunn

    2007-11-01

    Full Text Available Little is known about the long-term drug costs associated with treating AIDS in developing countries. Brazil's AIDS treatment program has been cited widely as the developing world's largest and most successful AIDS treatment program. The program guarantees free access to highly active antiretroviral therapy (HAART for all people living with HIV/AIDS in need of treatment. Brazil produces non-patented generic antiretroviral drugs (ARVs, procures many patented ARVs with negotiated price reductions, and recently issued a compulsory license to import one patented ARV. In this study, we investigate the drivers of recent ARV cost trends in Brazil through analysis of drug-specific prices and expenditures between 2001 and 2005.We compared Brazil's ARV prices to those in other low- and middle-income countries. We analyzed trends in drug expenditures for HAART in Brazil from 2001 to 2005 on the basis of cost data disaggregated by each ARV purchased by the Brazilian program. We decomposed the overall changes in expenditures to compare the relative impacts of changes in drug prices and drug purchase quantities. We also estimated the excess costs attributable to the difference between prices for generics in Brazil and the lowest global prices for these drugs. Finally, we estimated the savings attributable to Brazil's reduced prices for patented drugs. Negotiated drug prices in Brazil are lowest for patented ARVs for which generic competition is emerging. In recent years, the prices for efavirenz and lopinavir-ritonavir (lopinavir/r have been lower in Brazil than in other middle-income countries. In contrast, the price of tenofovir is US$200 higher per patient per year than that reported in other middle-income countries. Despite precipitous price declines for four patented ARVs, total Brazilian drug expenditures doubled, to reach US$414 million in 2005. We find that the major driver of cost increases was increased purchase quantities of six specific drugs

  1. Enriching stable isotopes: Alternative use for Urenco technology

    International Nuclear Information System (INIS)

    Rakhorst, H.; de Jong, P.G.T.; Dawson, P.D.

    1996-01-01

    The International Urenco Group utilizes a technologically advanced centrifuge process to enrich uranium in the fissionable isotope 235 U. The group operates plants in the United Kingdom, the Netherlands, and Germany and currently holds a 10% share of the multibillion dollar world enrichment market. In the early 1990s, Urenco embarked on a strategy of building on the company's uniquely advanced centrifuge process and laser isotope separation (LIS) experience to enrich nonradioactive isotopes colloquially known as stable isotopes. This paper summarizes the present status of Urenco's stable isotopes business

  2. Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats.

    Directory of Open Access Journals (Sweden)

    Fulvio ePlescia

    2013-06-01

    Full Text Available Increasing evidence focuses on acetaldehyde (ACD as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking and relapse behaviour. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioural equivalent of compulsive drug use despite adverse consequences.The aim of this study was thus to characterize ACD motivational and rewarding properties employing an operant-conflict paradigm in which rats, trained to lever press in order to get ACD solution (0.9%, undergo extinction, reinstatement and conflict sessions, according to a modified Geller-Seifter procedur. Furthermore the role played by CB1 receptor system in modulating ACD-induced effects were investigated through the administration of CB1 receptor antagonist, AM281 (1 mg/kg, i.p. during the extinction-, relapse- and conflict experiments.Our results indicate that ACD is able to induce and maintain an operant behaviour, a high number of responses during extinction, an increase in the lever presses during the reinstatement phase, and a higher emission of punished responses during the conflict experiments, when compared to controls.The administration of AM281 is able to decrease ACD-seeking behaviour during extinction, the number of lever presses during reinstatement and to strongly decrease the punished responses for ACD. Our data strengthen the idea that ACD may be responsible for the central effects of ethanol, and pinpoint at the CB1 system as one of the neural substrates underlying its addictive properties.

  3. Renewal after the punishment of free operant behavior.

    Science.gov (United States)

    Bouton, Mark E; Schepers, Scott T

    2015-01-01

    Three experiments examined the role of context in punishment learning. In Experiment 1, rats were trained to lever press for food in Context A and then punished for responding in Context B (by presenting response-contingent footshock). Punishment led to complete suppression of the response. However, when responding was tested (in extinction) in Contexts A and B, a strong renewal of responding occurred in Context A. In Experiment 2, renewal also occurred when initial reinforcement occurred in Context A, punishment occurred in Context B, and testing occurred in a new context (Context C). In both experiments, behavioral suppression and renewal were not observed in groups that received noncontingent (yoked) footshocks in Context B. In Experiment 3, 2 responses (lever press and chain pull) were separately reinforced in Contexts A and B and then punished in the opposite context. Although the procedure equated the contexts on their association with reinforcement and punishment, renewal of each response was observed when it was tested in its nonpunished context. The contexts also influenced response choice. Overall, the results suggest that punishment is specific to the context in which it is learned, and establish that its context-specificity does not depend on a simple association between the context and shock. Like extinction, punishment may involve learning to inhibit a specific response in a specific context. Implications for theories of punishment and for understanding the cessation of problematic operant behavior (e.g., drug abuse) are discussed. PsycINFO Database Record (c) 2015 APA, all rights reserved.

  4. Payment for antiretroviral drugs is associated with a higher rate of patients lost to follow-up than those offered free-of-charge therapy in Nairobi, Kenya

    NARCIS (Netherlands)

    Zachariah, R.; van Engelgem, I.; Massaquoi, M.; Kocholla, L.; Manzi, M.; Suleh, A.; Phillips, M.; Borgdorff, M.

    2008-01-01

    This retrospective analysis of routine programme data from Mbagathi District Hospital, Nairobi, Kenya shows the difference in rates of loss to follow-up between a cohort that paid 500 shillings/month (approximately US$7) for antiretroviral drugs (ART) and one that received medication free of charge.

  5. On the molecular basis of the activity of the antimalarial drug chloroquine: EXAFS-assisted DFT evidence of a direct Fe–N bond with free heme in solution

    International Nuclear Information System (INIS)

    Macetti, Giovanni; Rizzato, Silvia; Beghi, Fabio; Presti, Leonardo Lo; Silvestrini, Lucia

    2016-01-01

    4-aminoquinoline antiplasmodials interfere with the biocrystallization of the malaria pigment, a key step of the malaria parasite metabolism. It is commonly believed that these drugs set stacking π···π interactions with the Fe-protoporphyrin scaffold of the free heme, even though the details of the heme:drug recognition process remain elusive. In this work, the local coordination of Fe(III) ions in acidic solutions of hematin at room temperature was investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy in the 4.0–5.5 pH range, both in the presence and in the absence of the antimalarial drug chloroquine. EXAFS results were complemented by DFT simulations in polarizable continuum media to model solvent effects. We found evidence that a complex where the drug quinoline nitrogen is coordinated with the iron center might coexist with formerly proposed adduct geometries, based on stacking interactions. Charge-assisted hydrogen bonds among lateral chains of the two molecules play a crucial role in stabilizing this complex, whose formation is favored by the presence of lipid micelles. The direct Fe–N bond could reversibly block the axial position in the Fe 1st coordination shell in free heme, acting as an inhibitor for the crystallization of the malaria pigment without permanently hampering the catalytic activity of the redox center. These findings are discussed in the light of possible implications on the engineering of drugs able to thwart the adaptability of the malaria parasite against classical aminoquinoline-based therapies. (invited comment)

  6. On the molecular basis of the activity of the antimalarial drug chloroquine: EXAFS-assisted DFT evidence of a direct Fe-N bond with free heme in solution

    Science.gov (United States)

    Macetti, Giovanni; Rizzato, Silvia; Beghi, Fabio; Silvestrini, Lucia; Lo Presti, Leonardo

    2016-02-01

    4-aminoquinoline antiplasmodials interfere with the biocrystallization of the malaria pigment, a key step of the malaria parasite metabolism. It is commonly believed that these drugs set stacking π···π interactions with the Fe-protoporphyrin scaffold of the free heme, even though the details of the heme:drug recognition process remain elusive. In this work, the local coordination of Fe(III) ions in acidic solutions of hematin at room temperature was investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy in the 4.0-5.5 pH range, both in the presence and in the absence of the antimalarial drug chloroquine. EXAFS results were complemented by DFT simulations in polarizable continuum media to model solvent effects. We found evidence that a complex where the drug quinoline nitrogen is coordinated with the iron center might coexist with formerly proposed adduct geometries, based on stacking interactions. Charge-assisted hydrogen bonds among lateral chains of the two molecules play a crucial role in stabilizing this complex, whose formation is favored by the presence of lipid micelles. The direct Fe-N bond could reversibly block the axial position in the Fe 1st coordination shell in free heme, acting as an inhibitor for the crystallization of the malaria pigment without permanently hampering the catalytic activity of the redox center. These findings are discussed in the light of possible implications on the engineering of drugs able to thwart the adaptability of the malaria parasite against classical aminoquinoline-based therapies.

  7. The free radical process for the polymer surface treated by radio frequency plasma

    International Nuclear Information System (INIS)

    Ma Yuguang; Yang Meiling; Shen Jiacong; Zheng Yingguang

    1992-01-01

    The formation and translation of the free radicals on the polymer surface treated by plasmas were studied and observed by ESR measurement. The results show that C-C bond split was main reaction in the process of the polymer irradiated by plasma, by which a stable alkyl free radical was formed. When alkyl free radical contacted with air, they translate into peroxide radical instantaneously. The peroxide radical was not as stable as radical in vacuum, they can react each other to form some polar-groups on polymer surface. The interaction between the peroxide free radical and polymer chain was correlative not only to the structure of polymer but also to the molecular motion of the polymer chain. The nature of plasma treating polymer surface was that the peroxide radicals were led onto polymer surface

  8. Model-Free Coordinated Control for MHTGR-Based Nuclear Steam Supply Systems

    Directory of Open Access Journals (Sweden)

    Zhe Dong

    2016-01-01

    Full Text Available The modular high temperature gas-cooled reactor (MHTGR is a typical small modular reactor (SMR that offers simpler, standardized and safer modular design by being factory built, requiring smaller initial capital investment, and having a shorter construction period. Thanks to its small size, the MHTGRs could be beneficial in providing electric power to remote areas that are deficient in transmission or distribution and in generating local power for large population centers. Based on the multi-modular operation scheme, the inherent safety feature of the MHTGRs can be applicable to large nuclear plants of any desired power rating. The MHTGR-based nuclear steam supplying system (NSSS is constituted by an MHTGR, a side-by-side arranged helical-coil once-through steam generator (OTSG and some connecting pipes. Due to the side-by-side arrangement, there is a tight coupling effect between the MHTGR and OTSG. Moreover, there always exists the parameter perturbation of the NSSSs. Thus, it is meaningful to study the model-free coordinated control of MHTGR-based NSSSs for safe, stable, robust and efficient operation. In this paper, a new model-free coordinated control strategy that regulates the nuclear power, MHTGR outlet helium temperature and OTSG outlet overheated steam temperature by properly adjusting the control rod position, helium flowrate and feed-water flowrate is established for the MHTGR-based NSSSs. Sufficient conditions for the globally asymptotic closed-loop stability is given. Finally, numerical simulation results in the cases of large range power decrease and increase illustrate the satisfactory performance of this newly-developed model-free coordinated NSSS control law.

  9. Age-related patterns of drug use initiation among polydrug using regular psychostimulant users.

    Science.gov (United States)

    Darke, Shane; Kaye, Sharlene; Torok, Michelle

    2012-09-01

    To determine age-related patterns of drug use initiation, drug sequencing and treatment entry among regular psychostimulant users. Cross-sectional study of 269 regular psychostimulant users, administered a structured interview examining onset of use for major licit and illicit drugs. The mean age at first intoxication was not associated with age or gender. In contrast, younger age was associated with earlier ages of onset for all of the illicit drug classes. Each additional year of age was associated with a 4 month increase in onset age for methamphetamine, and 3 months for heroin. By the age of 17, those born prior to 1961 had, on average, used only tobacco and alcohol, whereas those born between 1986 and 1990 had used nine different drug classes. The period between initial use and the transition to regular use, however, was stable. Age was also negatively correlated with both age at initial injection and regular injecting. Onset sequences, however, remained stable. Consistent with the age-related patterns of drug use, each additional year of age associated with a 0.47 year increase in the age at first treatment. While the age at first intoxication appeared stable, the trajectory through illicit drug use was substantially truncated. The data indicate that, at least among those who progress to regular illicit drug use, younger users are likely to be exposed to far broader polydrug use in their teens than has previously been the case. © 2012 Australasian Professional Society on Alcohol and other Drugs.

  10. Use of hands-free technique among operating room nurses in the Republic of Korea.

    Science.gov (United States)

    Jeong, Ihn Sook; Park, Sunmi

    2009-03-01

    The recently introduced concept of hands-free technique (HFT) currently has no recommendations or formal educational program for use in the Republic of Korea. This study evaluated the level of HFT use and investigated factors related to HFT use among Korean operating room nurses. Data were obtained through a self-administered questionnaire from 158 operating room nurses in 7 general hospitals in Busan, Republic of Korea, in April and May 2006. The questionnaire elicited information on demographics, exposure to education on HFT, attitude toward the need for HFT, concerns about exposure to bloodborne pathogens, and experience with HTF use. Multilevel multiple logistic regression analysis with generalized estimating equations was used, and adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. We found that 56% of the participants had used HFT, and 50% had received education on HFT. The use of HFT had a significant association with both education on HFT (OR = 12.02; 95% CI = 7.50 to 19.25) and attitude toward the need for HFT (OR = 4.22; 95% CI = 2.43 to 7.35). Increasing education about HFT could be the most important approach to increasing the use of HFT among Korean operating room nurses. Thus, routine teaching about HFT should be provided to these nurses.

  11. Partially polymerized liposomes: stable against leakage yet capable of instantaneous release for remote controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Qin Guoting; Li Zheng; Xia Rongmin; Li Feng; O' Neill, Brian E; Li, King C [Department of Radiology, The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Goodwin, Jessica T; Khant, Htet A; Chiu, Wah, E-mail: zli@tmhs.org, E-mail: kli@tmhs.org [National Center for Macromolecular Imaging, Baylor College of Medicine, Houston, TX 77030 (United States)

    2011-04-15

    A critical issue for current liposomal carriers in clinical applications is their leakage of the encapsulated drugs that are cytotoxic to non-target tissues. We have developed partially polymerized liposomes composed of polydiacetylene lipids and saturated lipids. Cross-linking of the diacetylene lipids prevents the drug leakage even at 40 deg. C for days. These inactivated drug carriers are non-cytotoxic. Significantly, more than 70% of the encapsulated drug can be instantaneously released by a laser that matches the plasmon resonance of the tethered gold nanoparticles on the liposomes, and the therapeutic effect was observed in cancer cells. The remote activation feature of this novel drug delivery system allows for precise temporal and spatial control of drug release.

  12. Stable statistical representations facilitate visual search.

    Science.gov (United States)

    Corbett, Jennifer E; Melcher, David

    2014-10-01

    Observers represent the average properties of object ensembles even when they cannot identify individual elements. To investigate the functional role of ensemble statistics, we examined how modulating statistical stability affects visual search. We varied the mean and/or individual sizes of an array of Gabor patches while observers searched for a tilted target. In "stable" blocks, the mean and/or local sizes of the Gabors were constant over successive displays, whereas in "unstable" baseline blocks they changed from trial to trial. Although there was no relationship between the context and the spatial location of the target, observers found targets faster (as indexed by faster correct responses and fewer saccades) as the global mean size became stable over several displays. Building statistical stability also facilitated scanning the scene, as measured by larger saccadic amplitudes, faster saccadic reaction times, and shorter fixation durations. These findings suggest a central role for peripheral visual information, creating context to free resources for detailed processing of salient targets and maintaining the illusion of visual stability.

  13. Effects of D-cycloserine on the extinction of appetitive operant learning.

    Science.gov (United States)

    Vurbic, Drina; Gold, Benjamin; Bouton, Mark E

    2011-08-01

    Four experiments with rat subjects examined whether D-cycloserine (DCS), a partial NMDA agonist, facilitates the extinction of operant lever-pressing reinforced by food. Previous research has demonstrated that DCS facilitates extinction learning with methods that involve Pavlovian extinction. In the current experiments, operant conditioning occurred in Context A, extinction in Context B, and then testing occurred in both the extinction and conditioning contexts. Experiments 1A and 1B tested the effects of three doses of DCS (5, 15, and 30 mg/kg) on the extinction of lever pressing trained as a free operant. Experiment 2 examined their effects when extinction of the free operant was conducted in the presence of nonresponse-contingent deliveries of the reinforcer (that theoretically reduced the role of generalization decrement in suppressing responding). Experiment 3 examined their effects on extinction of a discriminated operant, that is, one that had been reinforced in the presence of a discriminative stimulus, but not in its absence. A strong ABA renewal effect was observed in all four experiments during testing. However, despite the use of DCS doses and a drug administration procedure that facilitates the extinction of Pavlovian learning, there was no evidence in any experiment that DCS facilitated operant extinction learning assessed in either the extinction or the conditioning context. DCS may primarily facilitate learning processes that underlie Pavlovian, rather than purely operant, extinction. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  14. Sustainable medication: Microtechnology for personalizing drug treatment

    DEFF Research Database (Denmark)

    Faralli, Adele; Melander, Fredrik; Andresen, Thomas Lars

    2014-01-01

    drug dosing” using light-­‐polymerizable polymer hydrogels as carriers for free or nanoparticle-­‐encapsulated drugs. The total dose is simply controlled by the volume of drug-­‐loaded cross-­‐ linked hydrogel defined by patterned light from a standard projector (Fig. 1). The concept enables simple...

  15. Ferrite-free high power electrodeless fluorescent lamp operated at a frequency of 160-1000 kHz

    International Nuclear Information System (INIS)

    Popov, Oleg A; Chandler, Robert

    2002-01-01

    An electrodeless ferrite-free fluorescent lamp of a closed-loop type ('tokamak') was studied at a driving frequency, f = 160-1000 kHz, and power of 100-250 W. The inductive discharge was ignited in the mercury-argon mixture with the help of an induction coil of several (7-15) turns made from multiple-strand (Litz) wire. The discharge parameters - current, resistance, and electric field - were calculated using the transformer model of an RF inductive discharge. They were found to be close to those measured in a plasma of a 'tokamak'-type lamp operated at the same frequency and RF power but with the use of the ferrite cores. The ferrite-free lamp had high luminous efficacy as high as 85 LPW at a frequency, f>200 kHz, and power of 100-200 W. Such a high efficacy is attributed to low coil power losses ( 90%

  16. Robust and Stable Disturbance Observer of Servo System for Low Speed Operation Using the Radial Basis Function Network

    DEFF Research Database (Denmark)

    Lee, Kyo-Beum; Blaabjerg, Frede

    2005-01-01

    A new scheme to estimate the moment of inertia in the servo motor drive system in very low speed is proposed in this paper. The speed estimation scheme in most servo drive systems for low speed operation is sensitive to the variation of machine parameter, especially the moment of inertia....... To estimate the motor inertia value, the observer using the Radial Basis Function Network (RBFN) is applied. A control law for stabilizing the system and adaptive laws for updating both of the weights in the RBFN and a bounding constant are established so that the whole closed-loop system is stable...... in the sense of Lyapunov. The effectiveness of the proposed inertia estimation is verified by simulations and experiments. It is concluded that the speed control performance in low speed region is improved with the proposed disturbance observer using RBFN....

  17. Drug-free gel containing ultra-deformable phospholipid vesicles (TDT 064) as topical therapy for the treatment of pain associated with osteoarthritis: a review of clinical efficacy and safety.

    Science.gov (United States)

    Conaghan, Philip G; Bijlsma, Johannes W; Kneer, Werner; Wise, Elspeth; Kvien, Tore K; Rother, Matthias

    2014-04-01

    Many patients with osteoarthritis (OA) experience side effects with available systemic therapies, some of which can be life threatening. The widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs), often without prescription, is concerning given their potential risks. New treatments for OA are therefore required. This review discusses evidence supporting the use of TDT 064, a drug-free, topical gel containing ultra-deformable phospholipid vesicles (Sequessome * vesicles), for OA-associated pain. Preclinical and clinical studies investigating TDT 064 in patients with OA-associated knee pain were identified in searches of PubMed and congress abstracts. The ultra-deformable phospholipid vesicles (sequessome vesicles) in TDT 064 pass through the skin intact to reach the synovial space within the joint. The mechanism of action is not yet certain, but the phospholipid-based structure of these ultra-deformable phospholipid vesicles, and the observation that they localize to the cartilage surface, support biolubrication as a possible mechanism of action of TDT 064. Data from randomized, phase III studies in OA knee pain in which TDT 064 was used as the drug-free vehicle control for IDEA-033 (ketoprofen in ultra-deformable phospholipid vesicles) demonstrate a marked and consistent response to TDT 064 in terms of pain, stiffness, and function. In a 12 week study of >1300 patients, the effects of TDT 064 on pain and function were statistically noninferior to those of oral celecoxib, and superior to oral placebo. TDT 064 was well tolerated in all studies, and adverse events were typically mild-to-moderate effects on the skin. Evidence from clinical studies supports the use of TDT 064 as a drug-free topical treatment for patients with OA. Further experience with TDT 064, particularly among patients with comorbidities or NSAID contraindications, will provide more information on its potential use.

  18. Free energies of stable and metastable pores in lipid membranes under tension

    NARCIS (Netherlands)

    den Otter, Wouter K.

    2009-01-01

    The free energy profile of pore formation in a lipid membrane, covering the entire range from a density fluctuation in an intact bilayer to a large tension-stabilized pore, has been calculated by molecular dynamics simulations with a coarse-grained lipid model. Several fixed elongations are used to

  19. 14 CFR 120.31 - Prohibited drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Prohibited drugs. 120.31 Section 120.31... AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS DRUG AND ALCOHOL TESTING PROGRAM... Under § 91.147 of This Chapter and Safety-Sensitive Employees § 120.31 Prohibited drugs. (a) Each...

  20. Drug Enforcement Administration

    Science.gov (United States)

    ... de informacin confidencial --> DEA NEWS The Drug Enforcement Administration and Discovery Education name grand winner of Operation ... JUN 15 (Washington) The United States Drug Enforcement Administration, DEA Educational Foundation and Discovery Education awarded Porter ...

  1. Dynamics and control of twisting bi-stable structures

    Science.gov (United States)

    Arrieta, Andres F.; van Gemmeren, Valentin; Anderson, Aaron J.; Weaver, Paul M.

    2018-02-01

    Compliance-based morphing structures have the potential to offer large shape adaptation, high stiffness and low weight, while reducing complexity, friction, and scalability problems of mechanism based systems. A promising class of structure that enables these characteristics are multi-stable structures given their ability to exhibit large deflections and rotations without the expensive need for continuous actuation, with the latter only required intermittently. Furthermore, multi-stable structures exhibit inherently fast response due to the snap-through instability governing changes between stable states, enabling rapid configuration switching between the discrete number of programmed shapes of the structure. In this paper, the design and utilisation of the inherent nonlinear dynamics of bi-stable twisting I-beam structures for actuation with low strain piezoelectric materials is presented. The I-beam structure consists of three compliant components assembled into a monolithic single element, free of moving parts, and showing large deflections between two stable states. Finite element analysis is utilised to uncover the distribution of strain across the width of the flange, guiding the choice of positioning for piezoelectric actuators. In addition, the actuation authority is maximised by calculating the generalised coupling coefficient for different positions of the piezoelectric actuators. The results obtained are employed to tailor and test I-beam designs exhibiting desired large deflection between stable states, while still enabling the activation of snap-through with the low strain piezoelectric actuators. To this end, the dynamic response of the I-beams to piezoelectric excitation is investigated, revealing that resonant excitations are insufficient to dynamically trigger snap-through. A novel bang-bang control strategy, which exploits the nonlinear dynamics of the structure successfully triggers both single and constant snap-through between the stable states

  2. Building a virtual ligand screening pipeline using free software: a survey.

    Science.gov (United States)

    Glaab, Enrico

    2016-03-01

    Virtual screening, the search for bioactive compounds via computational methods, provides a wide range of opportunities to speed up drug development and reduce the associated risks and costs. While virtual screening is already a standard practice in pharmaceutical companies, its applications in preclinical academic research still remain under-exploited, in spite of an increasing availability of dedicated free databases and software tools. In this survey, an overview of recent developments in this field is presented, focusing on free software and data repositories for screening as alternatives to their commercial counterparts, and outlining how available resources can be interlinked into a comprehensive virtual screening pipeline using typical academic computing facilities. Finally, to facilitate the set-up of corresponding pipelines, a downloadable software system is provided, using platform virtualization to integrate pre-installed screening tools and scripts for reproducible application across different operating systems. © The Author 2015. Published by Oxford University Press.

  3. NEBIVOLOL IN TREATMENT OF STABLE EXERTIONAL ANGINA PECTORIS

    Directory of Open Access Journals (Sweden)

    Y. V. Gavrilov

    2015-12-01

    Full Text Available Aim. To evaluate antianginal and antiischemic efficiency of nebivolol in patients with stable angina pectoris.Material and methods. 100 patients with ischemic heart disease showing stable exertional angina pectoris and having no contraindications to beta-blockers were studied. After 5-7 days of control period 50 randomly selected patients began to take nebivolol in initial dose of 5mg once daily and 50 patients started to take metoprolol in initial dose of 50 mg twice daily. Duration of treatment was 8 weeks. Efficiency of treatment was assessed according to the results of control treadmill assessment and control daily ECG monitoring.Results. 56-day therapy with nebivolol at a dose of 7,5 mg per day results in increase in duration of treadmill test before angina or ST depression (p<0.05. Antianginal and antiischemic effect of nebivolol 7.5 mg once daily is rather similar with that of metoprolol in average daily dose of 175 mg. Nebivolol compared to metoprolol significantly (p<0.05 more effectively reduces the number of silent myocardial ischemia.Conclusion. Nebivolol is an efficient antianginal and antiischemic drug for patients with stable exertional angina pectoris.

  4. The efficacy of trimetazidine on stable angina pectoris: a meta-analysis of randomized clinical trials.

    Science.gov (United States)

    Peng, Song; Zhao, Min; Wan, Jing; Fang, Qi; Fang, Dong; Li, Kaiyong

    2014-12-20

    This meta-analysis aimed to evaluate the efficacy of trimetazidine in combination with other anti-anginal drugs versus other anti-anginal drugs in the treatment of stable angina pectoris (SAP). Randomized controlled trials (RCTs) published in English and Chinese were retrieved from computerized databases: Embase, PubMed, and CNKI. Primary outcomes consist of clinical parameters (numbers of weekly angina attacks and nitroglycerin use) and ergometric parameters (time to 1mm ST-segment depression, and total work (in Mets) and exercise duration (in seconds) at peak exercise) in stable angina pectoris treated by trimetazidine or not. The quality of studies was evaluated using Jadad score. Data analysis of 13 studies was performed using Stata 12.0 software. Results showed that treatment of trimetazidine and other anti-anginal drugs was associated with a smaller weekly mean number of angina attacks (WMD=-0.95, 95%CI: -1.30 to -0.61, Z=5.39, Pangina pectoris. Sensitivity analysis was performed. Sub-group analysis showed that treatment duration was not a significant moderator and patients treated within 8 weeks and above 12 weeks had no difference in the outcomes addressed in this meta-analysis. No publish bias was detected. This meta-analysis confirms the efficacy of trimetazidine in the treatment of stable angina pectoris, in comparison with conventional antianginal agents, regardless of treatment duration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. A mesh-free approach to acoustic scattering from multiple spheres nested inside a large sphere by using diagonal translation operators.

    Science.gov (United States)

    Hesford, Andrew J; Astheimer, Jeffrey P; Greengard, Leslie F; Waag, Robert C

    2010-02-01

    A multiple-scattering approach is presented to compute the solution of the Helmholtz equation when a number of spherical scatterers are nested in the interior of an acoustically large enclosing sphere. The solution is represented in terms of partial-wave expansions, and a linear system of equations is derived to enforce continuity of pressure and normal particle velocity across all material interfaces. This approach yields high-order accuracy and avoids some of the difficulties encountered when using integral equations that apply to surfaces of arbitrary shape. Calculations are accelerated by using diagonal translation operators to compute the interactions between spheres when the operators are numerically stable. Numerical results are presented to demonstrate the accuracy and efficiency of the method.

  6. Why Are Drugs So Hard to Quit?

    Medline Plus

    Full Text Available ... Autoplay When autoplay is enabled, a suggested video will automatically play next. Up next Drugs: Shatter The ... Nora Volkow on Addiction: A Disease of Free Will - Duration: 21:12. National Institute on Drug Abuse ( ...

  7. Newly developed dope-free coatings help improve running operations in remote protected areas

    Energy Technology Data Exchange (ETDEWEB)

    Santi, Nestor J.; Gallo, Ernesto A. [TENARIS (Brazil)

    2008-07-01

    The Oil and Gas industry has been evolving in a permanent way to reach new sources of energy or to produce in the existing ones in a more efficient way, triggering in such a way the development of new drilling, completion and production techniques, equipment and processes; among these equipment, pipes and connections are not the exception, and the requirements on material and connections performance and reliability have been increased as well. The complexity of the new wells is not only related to the architecture of the well but also to the type of environments that are being found such as H2S, CO2, high pressure and/or high temperature; therefore, for these cases, connections have to be special premium connections threaded in most of the cases on highly alloyed materials (Ni-Cr alloys). Additionally, most of the regions under exploration are offshore and/or in remote areas of the planet which are considered untouchable due to economic reasons (fishing) or preservation (endangered flora and fauna) for instance Alaska, North Atlantic, North Sea, etc. For these areas, new environmental restrictions are applied which make it difficult for the operators to use standard practices. Among the recent solutions developed for Oil and Gas industry aiming to help with the protection of the environment are the dope-free coatings. These coatings are applied on tubing and casing connections providing a real greener alternative to traditional thread compounds, while maintaining the performance of the connections, for different materials as carbon steels, 13Cr and Corrosion Resistance Alloys (Ni, Cr). In spite of being a technically sound solution, the elimination of thread compounds may lead to potential operational problems such as galling, difficulties in making-up due to low temperature, etc. In addition, it is also necessary to evaluate the interaction between the dry coatings and the different connections to be used, as the designs have to be able to allocate the coating

  8. 14 CFR 120.35 - Testing for prohibited drugs.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Testing for prohibited drugs. 120.35... (CONTINUED) AIR CARRIERS AND OPERATORS FOR COMPENSATION OR HIRE: CERTIFICATION AND OPERATIONS DRUG AND... for prohibited drugs. (a) Each certificate holder or operator shall test each of its employees who...

  9. Investigation of the binding free energies of FDA approved drugs against subtype B and C-SA HIV PR: ONIOM approach.

    Science.gov (United States)

    Sanusi, Z K; Govender, T; Maguire, G E M; Maseko, S B; Lin, J; Kruger, H G; Honarparvar, B

    2017-09-01

    Human immune virus subtype C is the most widely spread HIV subtype in Sub-Sahara Africa and South Africa. A profound structural insight on finding potential lead compounds is therefore necessary for drug discovery. The focus of this study is to rationalize the nine Food and Drugs Administration (FDA) HIV antiviral drugs complexed to subtype B and C-SA PR using ONIOM approach. To achieve this, an integrated two-layered ONIOM model was used to optimize the geometrics of the FDA approved HIV-1 PR inhibitors for subtype B. In our hybrid ONIOM model, the HIV-1 PR inhibitors as well as the ASP 25/25' catalytic active residues were treated at high level quantum mechanics (QM) theory using B3LYP/6-31G(d), and the remaining HIV PR residues were considered using the AMBER force field. The experimental binding energies of the PR inhibitors were compared to the ONIOM calculated results. The theoretical binding free energies (?G bind ) for subtype B follow a similar trend to the experimental results, with one exemption. The computational model was less suitable for C-SA PR. Analysis of the results provided valuable information about the shortcomings of this approach. Future studies will focus on the improvement of the computational model by considering explicit water molecules in the active pocket. We believe that this approach has the potential to provide much improved binding energies for complex enzyme drug interactions. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Prisoners' views about the drugs problem in prisons, and the new Prison Service drug strategy.

    Science.gov (United States)

    Gore, S M; Bird, A G; Cassidy, J

    1999-09-01

    Three hundred and seventy-five out of 575 prisoners (222/299 drug users and 153/267 non-users) who responded to a self-completion health care questionnaire at two prisons in 1997 commented on drugs in prisons. One hundred and forty-eight out of 176 responses expressed negative opinions about mandatory drugs testing (MDT), and 107 said that MDT promoted switching to or increased use of heroin/hard drugs'. Sixty-two prisoners suggested that more help/counselling was needed for drug users, 52 segregation of drug users/drug-free wings, and 50 more security on visits/in corridors after medication. The new Prison Service drug strategy has revised random MDT. It targets those who supply drugs, and supports those who want to stop using drugs, and accords with prisoners' views about the heroin problem in prisons.

  11. Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

    Science.gov (United States)

    Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

    2016-04-01

    Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability

  12. A liposomal steroid nano-drug for treating systemic lupus erythematosus.

    Science.gov (United States)

    Moallem, E; Koren, E; Ulmansky, R; Pizov, G; Barlev, M; Barenholz, Y; Naparstek, Y

    2016-10-01

    Glucocorticoids have been known for years to be the most effective therapy in systemic lupus erythematosus. Their use, however, is limited by the need for high doses due to their unfavorable pharmacokinetics and biodistribution. We have previously developed a novel liposome-based steroidal (methylprednisolone hemisuccinate (MPS)) nano-drug and demonstrated its specific accumulation in inflamed tissues, as well as its superior therapeutic efficacy over that of free glucocorticoids (non-liposomal) in the autoimmune diseases, including the adjuvant arthritis rat model and the experimental autoimmune encephalomyelitis mouse model. In the present work we have evaluated the therapeutic effect of the above liposome-based steroidal (MPS) nano-drug in the MRL-lpr/lpr murine model of SLE and compared it with similar doses of the free MPS. MRL-lpr/lpr mice were treated with daily injections of free MPS or weekly injections of 10% dextrose, empty nano-liposomes or the steroidal nano-drug and the course of their disease was followed up to the age of 24 weeks. Treatment with the steroidal nano-drug was found to be significantly superior to the free MPS in suppressing anti-dsDNA antibody levels, proliferation of lymphoid tissue and renal damage, and in prolonging survival of animals. This significant superiority of our liposome based steroidal nano-drug administered weekly compared with daily injections of free methylprednisolone hemisuccinate in suppressing murine lupus indicates this glucocorticoid nano-drug formulation may be a good candidate for the treatment of human SLE. © The Author(s) 2016.

  13. Free random variables

    CERN Document Server

    Voiculescu, Dan; Nica, Alexandru

    1992-01-01

    This book presents the first comprehensive introduction to free probability theory, a highly noncommutative probability theory with independence based on free products instead of tensor products. Basic examples of this kind of theory are provided by convolution operators on free groups and by the asymptotic behavior of large Gaussian random matrices. The probabilistic approach to free products has led to a recent surge of new results on the von Neumann algebras of free groups. The book is ideally suited as a textbook for an advanced graduate course and could also provide material for a seminar. In addition to researchers and graduate students in mathematics, this book will be of interest to physicists and others who use random matrices.

  14. Polypeptide nanogels with hydrophobic moieties in the cross-linked ionic cores: Synthesis, characterization and implications for anticancer drug delivery

    Science.gov (United States)

    Kim, Jong Oh; Oberoi, Hardeep S.; Desale, Swapnil; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Polymer nanogels have gained considerable attention as a potential platform for drug delivery applications. Here we describe the design and synthesis of novel polypeptide-based nanogels with hydrophobic moieties in the cross-linked ionic cores. Diblock copolymer, poly(ethylene glycol)-b-poly(L-glutamic acid), hydrophobically modified with L-phenylalanine methyl ester moieties was used for controlled template synthesis of nanogels with small size (ca. 70 nm in diameter) and narrow particle size distribution. Steady-state and time-resolved fluorescence studies using coumarin C153 indicated the existence of hydrophobic domains in the ionic cores of the nanogels. Stable doxorubicin-loaded nanogels were prepared at high drug capacity (30 w/w%). We show that nanogels are enzymatically-degradable leading to accelerated drug release under simulated lysosomal acidic pH. Furthermore, we demonstrate that the nanogel-based formulation of doxorubicin is well tolerated and exhibit an improved antitumor activity compared to a free doxorubicin in an ovarian tumor xenograft mouse model. Our results signify the point to a potential of these biodegradable nanogels as attractive carriers for delivery of chemotherapeutics. PMID:23998716

  15. Highly stable and degradable multifunctional microgel for self-regulated insulin delivery under physiological conditions

    Science.gov (United States)

    Zhang, Xinjie; Lü, Shaoyu; Gao, Chunmei; Chen, Chen; Zhang, Xuan; Liu, Mingzhu

    2013-06-01

    The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size distribution (~250 nm) is suitable for diabetes because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM), control the release of preloaded insulin and is highly stable under physiological conditions (pH 7.4, 0.15 M NaCl, 37 °C). When synthesized multifunctional microgels regulate drug delivery, they gradually degrade as time passes and, as a result, show enhanced biocompatibility. This exhibits a new proof-of-concept for diabetes treatment that takes advantage of the properties of each building block from a multifunctional micro-object. These highly stable and versatile multifunctional microgels have the potential to be used for self-regulated therapy and monitoring of the response to treatment, or even simultaneous diagnosis as nanobiosensors.The response to glucose, pH and temperature, high drug loading capacity, self-regulated drug delivery and degradation in vivo are simultaneously probable by applying a multifunctional microgel under a rational design in a colloid chemistry method. Such multifunctional microgels are fabricated with N-isopropylacrylamide (NIPAAm), (2-dimethylamino)ethyl methacrylate (DMAEMA) and 3-acrylamidephenylboronic acid (AAPBA) through a precipitation emulsion method and cross-linked by reductive degradable N,N'-bis(arcyloyl)cystamine (BAC). This novel kind of microgel with a narrow size

  16. First operation of a wiggler-focused, sheet beam free electron laser amplifier

    International Nuclear Information System (INIS)

    Destler, W.W.; Cheng, S.; Zhang, Z.X.; Antonsen, T.M. Jr.; Granatstein, V.L.; Levush, B.; Rodgers, J.

    1994-01-01

    A wiggler-focused, sheet beam free electron laser (FEL) amplifier utilizing a short-period wiggler magnet has been proposed as a millimeter-wave source for current profile modification and/or electron cyclotron resonance heating of tokamak plasmas. As proposed, such an amplifier would operate at a frequency of approximately 100--200 GHz with an output power of 1--10 MW CW. Electron beam energy would be in the range 500--1000 keV. To test important aspects of this concept, an initial sheet beam FEL amplifier experiment has been performed using a 1 mmx2 cm sheet beam produced by a pulse line accelerator with a pulse duration of 100 ns. The 500--570 keV, 4--18 A sheet beam is propagated through a 56 period uniform wiggler (λ w =9.6 mm) with a peak wiggler amplitude of 2--5 kG. Linear amplification of a 5--10 W, 94 GHz signal injected in the TE 01 rectangular mode is observed. All features of the amplified signal, including pulse shape and duration, are in accordance with the predictions of numerical simulation. Amplified signal gain has been measured as a function of injected beam energy, current, and wiggler field amplitude and is also in good agreement with simulation results. Continuation of this experiment will involve studying nonlinear amplifier operation and adding a section of tapered wiggler

  17. LED surgical lighting system with multiple free-form surfaces for highly sterile operating theater application.

    Science.gov (United States)

    Liu, Peng; Zhang, Yaqin; Zheng, Zhenrong; Li, Haifeng; Liu, Xu

    2014-06-01

    Although the ventilation system is widely employed in the operating theater, a strictly sterile surgical environment still cannot be ensured because of laminar disturbance, which is mainly caused by the surgical lighting system. Abandoning traditional products, we propose an LED surgical lighting system, which can alleviate the laminar disturbance and provide an appropriate lighting condition for surgery. It contains a certain amount of LED lens units, which are embedded in the ceiling and arranged around the air supply smallpox. The LED lens unit integrated with an LED light source and a free-form lens is required to produce a uniform circular illumination with a large tolerance to the change of lighting distance. To achieve such a dedicated lens, two free-form refractive surfaces, which are converted into two ordinary differential equations by the design method presented in this paper, are used to deflect the rays. The results show that the LED surgical lighting system can provide an excellent illumination environment for surgery, and, apparently, the laminar disturbance also can be relieved.

  18. A remotely operated drug delivery system with dose control

    KAUST Repository

    Yi, Ying

    2017-05-08

    “On demand” implantable drug delivery systems can provide optimized treatments, due to their ability to provide targeted, flexible and precise dose release. However, two important issues that need to be carefully considered in a mature device include an effective actuation stimulus and a controllable dose release mechanism. This work focuses on remotely powering an implantable drug delivery system and providing a high degree of control over the released dose. This is accomplished by integration of a resonance-based wireless power transfer system, a constant voltage control circuit and an electrolytic pump. Upon the activation of the wireless power transfer system, the electrolytic actuator is remotely powered by a constant voltage regardless of movements of the device within an effective range of translation and rotation. This in turn contributes to a predictable dose release rate and greater flexibility in the positioning of external powering source. We have conducted proof-of-concept drug delivery studies using the liquid drug in reservoir approach and the solid drug in reservoir approach, respectively. Our experimental results demonstrate that the range of flow rate is mainly determined by the voltage controlled with a Zener diode and the resistance of the implantable device. The latter can be adjusted by connecting different resistors, providing control over the flow rate to meet different clinical needs. The flow rate can be maintained at a constant level within the effective movement range. When using a solid drug substitute with a low solubility, solvent blue 38, the dose release can be kept at 2.36μg/cycle within the effective movement range by using an input voltage of 10Vpp and a load of 1.5 kΩ, which indicates the feasibility and controllability of our system without any complicated closed-loop sensor.

  19. [Random clinical comparative trial between free and directed exercise in post-operative complications of breast cancer].

    Science.gov (United States)

    Rezende, Laura Ferreira de; Beletti, Patricia Odila; Franco, Ricardo Laier; Moraes, Sirlei Siani; Gurgel, Maria Salete Costa

    2006-01-01

    The objective of this study was to evaluate the association among physiotherapy exercises performed--directed or free--in case of post-operative complications in women who underwent radical mastectomy or quadrantectomy with axillary dissection. Sixty women were randomized. The directed group performed physiotherapy following a regimen of 19 exercises. The free group performed the exercises following the biomechanical physiological movements of the shoulder without a previously defined sequence or number of repetitions, exercises were done to the rhythm of music. In the average, the directed group remained 12.17 + 2.96 days with the drain, while the free group remained 11.96 + 2.32 days, with no significant difference between groups. The amount of secretion drained during the permanence of the drain also revealed resemblance between groups, with an average of 1308.71 + 562.6 ml in the directed group and of 1391.62 + 644.65 ml in the group of free exercises. Incidences of seroma and dehiscence of the surgical wound did not seem to be influenced by the type of exercise at any of the times evaluated. In the directed group, 7.4% and 3.4% of the women presented with seroma on the 28th and 42nd days, respectively, while at the same moments of evaluation the free group presented respectively. 3.6% and 3.6%. Incidence of dehiscence of the surgical wound also was similar in the two groups, in the directed group it was of 20% on the 14th day, 31% on the 28th day and 10.3% on the 42nd day of postoperative. In the free group the incidence was of 23.3% on the 14th day, of 33.3% on the 28th day and of 22.2% on the 42nd day of postoperative. The statistical difference observed in the averages of the hand and arm circumferences does not translate into clinical differences. The complications were not influenced f by the physiotherapy exercises performed.

  20. Performance of Lead-Free versus Lead-Based Hunting Ammunition in Ballistic Soap

    Science.gov (United States)

    Gremse, Felix; Krone, Oliver; Thamm, Mirko; Kiessling, Fabian; Tolba, René Hany; Rieger, Siegfried; Gremse, Carl

    2014-01-01

    Background Lead-free hunting bullets are an alternative to lead-containing bullets which cause health risks for humans and endangered scavenging raptors through lead ingestion. However, doubts concerning the effectiveness of lead-free hunting bullets hinder the wide-spread acceptance in the hunting and wildlife management community. Methods We performed terminal ballistic experiments under standardized conditions with ballistic soap as surrogate for game animal tissue to characterize dimensionally stable, partially fragmenting, and deforming lead-free bullets and one commonly used lead-containing bullet. The permanent cavities created in soap blocks are used as a measure for the potential wound damage. The soap blocks were imaged using computed tomography to assess the volume and shape of the cavity and the number of fragments. Shots were performed at different impact speeds, covering a realistic shooting range. Using 3D image segmentation, cavity volume, metal fragment count, deflection angle, and depth of maximum damage were determined. Shots were repeated to investigate the reproducibility of ballistic soap experiments. Results All bullets showed an increasing cavity volume with increasing deposited energy. The dimensionally stable and fragmenting lead-free bullets achieved a constant conversion ratio while the deforming copper and lead-containing bullets showed a ratio, which increases linearly with the total deposited energy. The lead-containing bullet created hundreds of fragments and significantly more fragments than the lead-free bullets. The deflection angle was significantly higher for the dimensionally stable bullet due to its tumbling behavior and was similarly low for the other bullets. The deforming bullets achieved higher reproducibility than the fragmenting and dimensionally stable bullets. Conclusion The deforming lead-free bullet closely resembled the deforming lead-containing bullet in terms of energy conversion, deflection angle, cavity shape