Science.gov

Sample records for additional mechanistic information

  1. Informing Mechanistic Toxicology with Computational Molecular Models

    EPA Science Inventory

    Computational molecular models of chemicals interacting with biomolecular targets provides toxicologists a valuable, affordable, and sustainable source of in silico molecular level information that augments, enriches, and complements in vitro and in vivo effo...

  2. Perspectives on the Application of Mechanistic Information in Chemical Hazard and Dose-Response Assessments

    EPA Science Inventory

    This overview summarizes several EPA Assessment publications reviewing approaches for applying mechanistic information in human health risk assessment and exploring opportunities for progress in this area.

  3. Helical-Peptide-Catalyzed Enantioselective Michael Addition Reactions and Their Mechanistic Insights.

    PubMed

    Ueda, Atsushi; Umeno, Tomohiro; Doi, Mitsunobu; Akagawa, Kengo; Kudo, Kazuaki; Tanaka, Masakazu

    2016-08-01

    Helical peptide foldamer catalyzed Michael addition reactions of nitroalkane or dialkyl malonate to α,β-unsaturated ketones are reported along with the mechanistic considerations of the enantio-induction. A wide variety of α,β-unsaturated ketones, including β-aryl, β-alkyl enones, and cyclic enones, were found to be catalyzed by the helical peptide to give Michael adducts with high enantioselectivities (up to 99%). On the basis of X-ray crystallographic analysis and depsipeptide study, the amide protons, N(2)-H and N(3)-H, at the N terminus in the α-helical peptide catalyst were crucial for activating Michael donors, while the N-terminal primary amine activated Michael acceptors through the formation of iminium ion intermediates.

  4. Toward a mechanistic understanding of the effect of biochar addition on soil water retention

    NASA Astrophysics Data System (ADS)

    Yi, S.; Chang, N.; Guo, M.; Imhoff, P. T.

    2014-12-01

    Biochar (BC) is a carbon-rich product produced by thermal degradation of biomass in an oxygen-free environment, whose application to sediment is said to improve water retention. However, BC produced from different feedstocks and pyrolyzed at different temperatures have distinct properties, which may alter water retention in ways difficult to predict a priori. Our goal is to develop a mechanistic understanding of BC addition on water retention by examining the impact of BC from two feedstocks, poultry litter (PL) and hardwood (HW), on the soil-water retention curves (SWRC) of a uniform sand and a sandy loam (SL). For experiments with sand, BC and sand were sieved to the same particle size (~ 0.547 mm) to minimize effects of BC addition on particle size distribution. Experiments with SL contained the same sieved BC. PL and HW bicohars were added at 2 and 7% (w/w), and water retention was measured from 0 to -4.38 × 106 cm-H2O. Both BCs increased porosities for sand and SL, up to 39 and 13% for sand and SL, respectively, with 7% HW BC addition. The primary cause for these increases was the internal porosity of BC particles. While the matric potential for air-entry was unchanged with BC addition, BC amendment increased water retention for sand and SL in the capillary region (0 to -15,000 cm-H2O) by an average of 26 and 33 % for 7% PL and HW BC in sand, respectively, but only 7 and 14 % for 7% PL and HW BC in SL. The most dramatic influence of BC amendment on water retention occurred in the adsorption region (< -15,000 cm-H2O), where water retention increased by a factor of 11 and 22 for 7% PL and HW BC in sand, respectively, but by 140 and 190 % for 7% PL and HW BC in SL, respectively. The impact of BC on water retention in these sediments is explained primarily by the additional surface area and internal porosity of PL and HW BC particles. van Genuchten (VG) models were fitted to the water retention data. For SL where the impact of BC addition on water retention was

  5. 16 CFR 1102.16 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... PUBLICLY AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.16 Additional... in the Database any additional information it determines to be in the public interest,...

  6. 16 CFR 1102.16 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... PUBLICLY AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.16 Additional... in the Database any additional information it determines to be in the public interest,...

  7. 16 CFR 1102.16 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... PUBLICLY AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE Content Requirements § 1102.16 Additional... in the Database any additional information it determines to be in the public interest,...

  8. Mechanistic and computational studies of the atom transfer radical addition of CCl4 to styrene catalyzed by copper homoscorpionate complexes.

    PubMed

    Muñoz-Molina, José María; Sameera, W M C; Álvarez, Eleuterio; Maseras, Feliu; Belderrain, Tomás R; Pérez, Pedro J

    2011-03-21

    Experimental as well as theoretical studies have been carried out with the aim of elucidating the mechanism of the atom transfer radical addition (ATRA) of styrene and carbon tetrachloride with a Tp(x)Cu(NCMe) complex as the catalyst precursor (Tp(x) = hydrotrispyrazolyl-borate ligand). The studies shown herein demonstrate the effect of different variables in the kinetic behavior. A mechanistic proposal consistent with theoretical and experimental data is presented.

  9. 17 CFR 230.408 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Additional information. 230... RULES AND REGULATIONS, SECURITIES ACT OF 1933 General Requirements § 230.408 Additional information. (a) In addition to the information expressly required to be included in a registration statement,...

  10. 17 CFR 230.408 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Additional information. 230... RULES AND REGULATIONS, SECURITIES ACT OF 1933 General Requirements § 230.408 Additional information. (a) In addition to the information expressly required to be included in a registration statement,...

  11. 47 CFR 25.111 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Additional information. 25.111 Section 25.111... Applications and Licenses General Application Filing Requirements § 25.111 Additional information. (a) The Commission may request from any party at any time additional information concerning any application, or...

  12. 10 CFR 810.14 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Additional information. 810.14 Section 810.14 Energy DEPARTMENT OF ENERGY ASSISTANCE TO FOREIGN ATOMIC ENERGY ACTIVITIES § 810.14 Additional information. The... activity to submit additional information....

  13. 47 CFR 25.111 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Additional information. 25.111 Section 25.111... Applications and Licenses General Application Filing Requirements § 25.111 Additional information. (a) The Commission may request from any party at any time additional information concerning any application, or...

  14. 10 CFR 725.13 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Additional information. 725.13 Section 725.13 Energy DEPARTMENT OF ENERGY PERMITS FOR ACCESS TO RESTRICTED DATA Applications § 725.13 Additional information. The... and before the termination of the permit, require additional information in order to enable the...

  15. 47 CFR 25.111 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Additional information. 25.111 Section 25.111... Applications and Licenses General Application Filing Requirements § 25.111 Additional information. (a) The Commission may request from any party at any time additional information concerning any application, or...

  16. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Additional information. 80.7 Section 80.7... § 80.7 Additional information. If an issuer's or domestic concern's submission does not contain all of the information required by § 80.6, the Department of Justice may request whatever...

  17. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Additional information. 80.7 Section 80.7... § 80.7 Additional information. If an issuer's or domestic concern's submission does not contain all of the information required by § 80.6, the Department of Justice may request whatever...

  18. 16 CFR 1102.16 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... PUBLICLY AVAILABLE CONSUMER PRODUCT SAFETY INFORMATION DATABASE (Eff. Jan. 10, 2011) Content Requirements... notices, the CPSC shall include in the Database any additional information it determines to be in...

  19. 10 CFR 810.14 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Additional information. 810.14 Section 810.14 Energy DEPARTMENT OF ENERGY ASSISTANCE TO FOREIGN ATOMIC ENERGY ACTIVITIES § 810.14 Additional information. The Department of Energy may at any time require a person engaging in any generally or specifically...

  20. 10 CFR 810.14 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Additional information. 810.14 Section 810.14 Energy DEPARTMENT OF ENERGY ASSISTANCE TO FOREIGN ATOMIC ENERGY ACTIVITIES § 810.14 Additional information. The Department of Energy may at any time require a person engaging in any generally or specifically...

  1. 10 CFR 810.14 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Additional information. 810.14 Section 810.14 Energy DEPARTMENT OF ENERGY ASSISTANCE TO FOREIGN ATOMIC ENERGY ACTIVITIES § 810.14 Additional information. The Department of Energy may at any time require a person engaging in any generally or specifically...

  2. 10 CFR 810.14 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Additional information. 810.14 Section 810.14 Energy DEPARTMENT OF ENERGY ASSISTANCE TO FOREIGN ATOMIC ENERGY ACTIVITIES § 810.14 Additional information. The Department of Energy may at any time require a person engaging in any generally or specifically...

  3. 25 CFR 214.5 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Additional information. 214.5 Section 214.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS, OKLAHOMA, FOR MINING, EXCEPT OIL AND GAS § 214.5 Additional information. The officer in...

  4. 25 CFR 214.5 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Additional information. 214.5 Section 214.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS, OKLAHOMA, FOR MINING, EXCEPT OIL AND GAS § 214.5 Additional information. The officer in charge may, at...

  5. 25 CFR 214.5 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Additional information. 214.5 Section 214.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS, OKLAHOMA, FOR MINING, EXCEPT OIL AND GAS § 214.5 Additional information. The officer in...

  6. 25 CFR 214.5 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Additional information. 214.5 Section 214.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS, OKLAHOMA, FOR MINING, EXCEPT OIL AND GAS § 214.5 Additional information. The officer in...

  7. 25 CFR 214.5 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Additional information. 214.5 Section 214.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF OSAGE RESERVATION LANDS, OKLAHOMA, FOR MINING, EXCEPT OIL AND GAS § 214.5 Additional information. The officer in...

  8. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS How Grants Are Made Procedures to Make A Grant § 75.231 Additional information. After selecting an application for funding, the Secretary may require the applicant to submit additional information. (Authority: 20 U.S.C. 1221e-3 and 3474)...

  9. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS How Grants Are Made Procedures to Make A Grant § 75.231 Additional information. After selecting an application for funding, the Secretary may require the applicant to submit additional information. (Authority: 20 U.S.C. 1221e-3 and 3474)...

  10. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS How Grants Are Made Procedures to Make A Grant § 75.231 Additional information. After selecting an application for funding, the Secretary may require the applicant to submit additional information. (Authority: 20 U.S.C. 1221e-3 and 3474)...

  11. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS How Grants Are Made Procedures to Make A Grant § 75.231 Additional information. After selecting an application for funding, the Secretary may require the applicant to submit additional information. (Authority: 20 U.S.C. 1221e-3 and 3474)...

  12. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Office of the Secretary, Department of Education DIRECT GRANT PROGRAMS How Grants Are Made Procedures to Make A Grant § 75.231 Additional information. After selecting an application for funding, the Secretary may require the applicant to submit additional information. (Authority: 20 U.S.C. 1221e-3 and 3474)...

  13. Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models.

    PubMed

    Baeder, Desiree Y; Yu, Guozhi; Hozé, Nathanaël; Rolff, Jens; Regoes, Roland R

    2016-05-26

    Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'. PMID:27160596

  14. Mechanistic Aspects of Aryl-Halide Oxidative Addition, Coordination Chemistry, and Ring-Walking by Palladium.

    PubMed

    Zenkina, Olena V; Gidron, Ori; Shimon, Linda J W; Iron, Mark A; van der Boom, Milko E

    2015-11-01

    This contribution describes the reactivity of a zero-valent palladium phosphine complex with substrates that contain both an aryl halide moiety and an unsaturated carbon-carbon bond. Although η(2) -coordination of the metal center to a C=C or C≡C unit is kinetically favored, aryl halide bond activation is favored thermodynamically. These quantitative transformations proceed under mild reaction conditions in solution or in the solid state. Kinetic measurements indicate that formation of η(2) -coordination complexes are not nonproductive side-equilibria, but observable (and in several cases even isolated) intermediates en route to aryl halide bond cleavage. At the same time, DFT calculations show that the reaction with palladium may proceed through a dissociation-oxidative addition mechanism rather than through a haptotropic intramolecular process (i.e., ring walking). Furthermore, the transition state involves coordination of a third phosphine to the palladium center, which is lost during the oxidative addition as the C-halide bond is being broken. Interestingly, selective activation of aryl halides has been demonstrated by adding reactive aryl halides to the η(2) -coordination complexes. The product distribution can be controlled by the concentration of the reactants and/or the presence of excess phosphine.

  15. Determination, correlation, and mechanistic interpretation of effects of hydrogen addition on laminar flame speeds of hydrocarbon–air mixtures

    SciTech Connect

    Tang, C. L.; Huang, Z. H.; Law, C. K.

    2010-08-30

    The stretch-affected propagation speeds of expanding spherical flames of n-butane–air mixtures with hydrogen addition were measured at atmospheric pressure and subsequently processed through a nonlinear regression analysis to yield the stretch-free laminar flame speeds. Based on a hydrogen addition parameter (RH) and an effective fuel equivalence ratio (ΦF), these laminar flame speeds were found to increase almost linearly with RH, for ΦF between 0.6 and 1.4 and RHRH from 0 to 0.5, with the slope of the variation assuming a minimum around stoichiometry. These experimental results also agree well with computed values using a detailed reaction mechanism. Furthermore, a mechanistic investigation aided by sensitivity analysis identified that kinetic effects through the global activation energy, followed by thermal effects through the adiabatic flame temperature, have the most influence on the increase in the flame speeds and the associated linear variation with RH due to hydrogen addition. Nonequidiffusion effects due to the high mobility of hydrogen, through the global Lewis number, have the least influence. Further calculations for methane, ethene, and propane as the fuel showed similar behavior, leading to possible generalization of the phenomena and correlation.

  16. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Additional information. 1008.39 Section 1008.39 Public Health OFFICE OF INSPECTOR GENERAL-HEALTH CARE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OIG AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion §...

  17. Recent advances in mathematical modeling of developmental abnormalities using mechanistic information.

    PubMed

    Kavlock, R J

    1997-01-01

    During the last several years, significant changes in the risk assessment process for developmental toxicity of environmental contaminants have begun to emerge. The first of these changes is the development and beginning use of statistically based dose-response models [the benchmark dose (BMD) approach] that better utilize data derived from existing testing approaches. Accompanying this change is the greater emphasis placed on understanding and using mechanistic information to yield more accurate, reliable, and less uncertain risk assessments. The next stage in the evolution of risk assessment will be the use of biologically based dose-response (BBDR) models that begin to build into the statistically based models factors related to the underlying kinetic, biochemical, and/or physiologic processes perturbed by a toxicant. Such models are now emerging from several research laboratories. The introduction of quantitative models and the incorporation of biologic information into them has pointed to the need for even more sophisticated modifications for which we offer the term embryologically based dose-response (EBDR) models. Because these models would be based upon the understanding of normal morphogenesis, they represent a quantum leap in our thinking, but their complexity presents daunting challenges both to the developmental biologist and the developmental toxicologist. Implementation of these models will require extensive communication between developmental toxicologists, molecular embryologists, and biomathematicians. The remarkable progress in the understanding of mammalian embryonic development at the molecular level that has occurred over the last decade combined with advances in computing power and computational models should eventually enable these as yet hypothetical models to be brought into use.

  18. 47 CFR 25.111 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... information it requires for the Advance Publication, Coordination and Notification of frequency assignments..., with respect to individual administrations, by successfully completing coordination agreements. Any... terms and conditions as required to effect coordination of the frequency assignments with...

  19. INCORPORATION OF MECHANISTIC INFORMATION IN THE ARSENIC PBPK MODEL DEVELOPMENT PROCESS

    EPA Science Inventory

    INCORPORATING MECHANISTIC INSIGHTS IN A PBPK MODEL FOR ARSENIC

    Elaina M. Kenyon, Michael F. Hughes, Marina V. Evans, David J. Thomas, U.S. EPA; Miroslav Styblo, University of North Carolina; Michael Easterling, Analytical Sciences, Inc.

    A physiologically based phar...

  20. Mechanistic Insights into the Initiation Step of the Base Promoted Direct C-H Arylation of Benzene in the Presence of Additive.

    PubMed

    Patil, Mahendra

    2016-01-15

    The direct arylation of unactivated arenes is a very practical and highly convenient procedure for the construction of biaryl scaffolds. Recently, a direct arylation of unactivated benzene has been achieved in the presence of base (tBuOK or tBuONa) and organic additive such as 1,10-phenanthroline. However, details of intimate mechanism of reaction as well as the role of additive have remained elusive until date. The present work explores various mechanistic possibilities of the key electron transfer step of the reaction in order to identify a probable route for the initiation of phenyl radical from iodobenzene. A detailed DFT (M06-2X functional) investigation indicates that the reaction of additive and base can be crucial to generate an electron acceptor-donor pair that can facilitate electron transfer mechanism. This computational model provides a satisfactory explanation for experimental observations, clearly defining the roles of additive and base in the reaction.

  1. 17 CFR 240.12b-20 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Additional information. 240... Securities Exchange Act of 1934 General Requirements As to Contents § 240.12b-20 Additional information. In addition to the information expressly required to be included in a statement or report, there shall...

  2. 17 CFR 270.8b-20 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Additional information. 270.8b...) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.8b-20 Additional information. In addition to the information expressly required to be included in a registration statement or report, there...

  3. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Opportunities to submit additional information. 2570.39... Prohibited Transaction Exemption Applications § 2570.39 Opportunities to submit additional information. (a) An applicant may notify the Department of its intent to submit additional information supporting...

  4. 43 CFR 3430.4-2 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Additional information. 3430.4-2 Section... Leases § 3430.4-2 Additional information. (a) If the applicant for a preference right lease has submitted timely, some, but not all of the information required in § 3430.4-1 of this title, the authorized...

  5. 34 CFR 303.212 - Additional information and assurances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... system as required by section 427(b) of GEPA; and (b) Other information and assurances as the Secretary... 34 Education 2 2012-07-01 2012-07-01 false Additional information and assurances. 303.212 Section... Additional information and assurances. Each application must contain— (a) A description of the steps...

  6. 34 CFR 303.212 - Additional information and assurances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... system as required by section 427(b) of GEPA; and (b) Other information and assurances as the Secretary... 34 Education 2 2014-07-01 2013-07-01 true Additional information and assurances. 303.212 Section... Additional information and assurances. Each application must contain— (a) A description of the steps...

  7. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Opportunities to submit additional information. 2570.39... Processing of Prohibited Transaction Exemption Applications § 2570.39 Opportunities to submit additional information. (a) An applicant may notify the Department of its intent to submit additional...

  8. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Opportunities to submit additional information. 2570.39... Processing of Prohibited Transaction Exemption Applications § 2570.39 Opportunities to submit additional information. (a) An applicant may notify the Department of its intent to submit additional...

  9. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Opportunities to submit additional information. 2570.39... Processing of Prohibited Transaction Exemption Applications § 2570.39 Opportunities to submit additional information. (a) An applicant may notify the Department of its intent to submit additional...

  10. A Mechanistic Understanding of a Binary Additive System to Synergistically Boost Efficiency in All-Polymer Solar Cells.

    PubMed

    Kim, Yu Jin; Ahn, Sunyong; Wang, Dong Hwan; Park, Chan Eon

    2015-12-11

    All-polymer solar cells are herein presented utilizing the PBDTTT-CT donor and the P(NDI2OD-T2) acceptor with 1,8-diiodooctane (DIO) and 1-chloronaphthalene (CN) binary solvent additives. A systematic study of the polymer/polymer bulk heterojunction photovoltaic cells processed from the binary additives revealed that the microstructures and photophysics were quite different from those of a pristine system. The combination of DIO and CN with a DIO/CN ratio of 3:1 (3 vol% DIO, 1 vol% CN and 96 vol% o-DCB) led to suitable penetrating polymer networks, efficient charge generation and balanced charge transport, which were all beneficial to improving the efficiency. This improvement is attributed to increase in power conversion efficiency from 2.81% for a device without additives to 4.39% for a device with the binary processing additives. A detailed investigation indicates that the changes in the polymer:polymer interactions resulted in the formation of a percolating nasnoscale morphology upon processing with the binary additives. Depth profile measurements with a two-dimensional grazing incidence wide-angle X-ray scattering confirm this optimum phase feature. Furthermore impedance spectroscopy also finds evidence for synergistically boosting the device performance.

  11. A Mechanistic Understanding of a Binary Additive System to Synergistically Boost Efficiency in All-Polymer Solar Cells

    PubMed Central

    Kim, Yu Jin; Ahn, Sunyong; Wang, Dong Hwan; Park, Chan Eon

    2015-01-01

    All-polymer solar cells are herein presented utilizing the PBDTTT-CT donor and the P(NDI2OD-T2) acceptor with 1,8-diiodooctane (DIO) and 1-chloronaphthalene (CN) binary solvent additives. A systematic study of the polymer/polymer bulk heterojunction photovoltaic cells processed from the binary additives revealed that the microstructures and photophysics were quite different from those of a pristine system. The combination of DIO and CN with a DIO/CN ratio of 3:1 (3 vol% DIO, 1 vol% CN and 96 vol% o-DCB) led to suitable penetrating polymer networks, efficient charge generation and balanced charge transport, which were all beneficial to improving the efficiency. This improvement is attributed to increase in power conversion efficiency from 2.81% for a device without additives to 4.39% for a device with the binary processing additives. A detailed investigation indicates that the changes in the polymer:polymer interactions resulted in the formation of a percolating nasnoscale morphology upon processing with the binary additives. Depth profile measurements with a two-dimensional grazing incidence wide-angle X-ray scattering confirm this optimum phase feature. Furthermore impedance spectroscopy also finds evidence for synergistically boosting the device performance. PMID:26658472

  12. A Mechanistic Understanding of a Binary Additive System to Synergistically Boost Efficiency in All-Polymer Solar Cells.

    PubMed

    Kim, Yu Jin; Ahn, Sunyong; Wang, Dong Hwan; Park, Chan Eon

    2015-01-01

    All-polymer solar cells are herein presented utilizing the PBDTTT-CT donor and the P(NDI2OD-T2) acceptor with 1,8-diiodooctane (DIO) and 1-chloronaphthalene (CN) binary solvent additives. A systematic study of the polymer/polymer bulk heterojunction photovoltaic cells processed from the binary additives revealed that the microstructures and photophysics were quite different from those of a pristine system. The combination of DIO and CN with a DIO/CN ratio of 3:1 (3 vol% DIO, 1 vol% CN and 96 vol% o-DCB) led to suitable penetrating polymer networks, efficient charge generation and balanced charge transport, which were all beneficial to improving the efficiency. This improvement is attributed to increase in power conversion efficiency from 2.81% for a device without additives to 4.39% for a device with the binary processing additives. A detailed investigation indicates that the changes in the polymer:polymer interactions resulted in the formation of a percolating nasnoscale morphology upon processing with the binary additives. Depth profile measurements with a two-dimensional grazing incidence wide-angle X-ray scattering confirm this optimum phase feature. Furthermore impedance spectroscopy also finds evidence for synergistically boosting the device performance. PMID:26658472

  13. DETAIL OF PLAQUE WITH ADDITIONAL DESIGN AND CONSTRUCTION INFORMATION, SOUTHEAST ...

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

    DETAIL OF PLAQUE WITH ADDITIONAL DESIGN AND CONSTRUCTION INFORMATION, SOUTHEAST ABUTMENT - Connecticut Avenue Bridge, Spans Rock Creek & Potomac Parkway at Connecticut Avenue, Washington, District of Columbia, DC

  14. Combining Empirical Relationships with Data Based Mechanistic Modeling to Inform Solute Tracer Investigations across Stream Orders

    NASA Astrophysics Data System (ADS)

    Herrington, C.; Gonzalez-Pinzon, R.; Covino, T. P.; Mortensen, J.

    2015-12-01

    Solute transport studies in streams and rivers often begin with the introduction of conservative and reactive tracers into the water column. Information on the transport of these substances is then captured within tracer breakthrough curves (BTCs) and used to estimate, for instance, travel times and dissolved nutrient and carbon dynamics. Traditionally, these investigations have been limited to systems with small discharges (< 200 L/s) and with small reach lengths (< 500 m), partly due to the need for a priori information of the reach's hydraulic characteristics (e.g., channel geometry, resistance and dispersion coefficients) to predict arrival times, times to peak concentrations of the solute and mean travel times. Current techniques to acquire these channel characteristics through preliminary tracer injections become cost prohibitive at higher stream orders and the use of semi-continuous water quality sensors for collecting real-time information may be affected from erroneous readings that are masked by high turbidity (e.g., nitrate signals with SUNA instruments or fluorescence measures) and/or high total dissolved solids (e.g., making prohibitively expensive the use of salt tracers such as NaCl) in larger systems. Additionally, a successful time-of-travel study is valuable for only a single discharge and river stage. We have developed a method to predict tracer BTCs to inform sampling frequencies at small and large stream orders using empirical relationships developed from multiple tracer injections spanning several orders of magnitude in discharge and reach length. This method was successfully tested in 1st to 8th order systems along the Middle Rio Grande River Basin in New Mexico, USA.

  15. A mechanistic study of the addition of alcohol to a five-membered ring silene via a photochemical reaction.

    PubMed

    Su, Ming-Der

    2016-03-21

    The mechanism for the photochemical rearrangement of a cyclic divinyldisilane (1-Si) in its first excited state ((1)π → (1)π*) is determined using the CAS/6-311G(d) and MP2-CAS/6-311++G(3df,3pd) levels of theory. The photoproduct, a cyclic silene, reacts with various alcohols to yield a mixture of cis- and trans- adducts. The two reaction pathways are denoted as the cis- addition path (path A) and the trans-addition path (path B). These model studies demonstrate that conical intersections play a crucial role in the photo-rearrangements of cyclic divinyldisilanes. The theoretical evidence also demonstrates that the addition of alcohol to a cyclic divinyldisilane follows the reaction path: cyclic divinyldisilane → Franck-Condon region → conical intersection → photoproduct (cyclic silene) → local intermediate (with alcohol) → transition state → cis- or trans-adduct. The theoretical studies demonstrate that the steric effects as well as the concentrations of CH3OH must have a dominant role in determining the yields of the final adducts by stereochemistry. The same mechanism for the carbon derivative (1-C) is also considered in this work. However, the theoretical results indicate that 1-C does not undergo a methanol addition reaction via the photochemical reaction pathway, since its energy of conical intersection (S1/S0-CI-C) is more than that of its FC (FC-C). The reason for these phenomena could be that the atomic radius of carbon is much smaller than that of silicon (77 and 117 pm, respectively). As a result, the conformation for 1-C is more sterically congested than that for 1-Si, along the 1,3-silyl-migration pathway. PMID:26928893

  16. 19 CFR 111.60 - Request for additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Request for additional information. 111.60 Section 111.60 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT... particular language of the proposed statement of charges as to which additional information is needed. If...

  17. 40 CFR 141.154 - Required additional health information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 24 2013-07-01 2013-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk...

  18. 40 CFR 141.154 - Required additional health information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 23 2014-07-01 2014-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk...

  19. 40 CFR 141.154 - Required additional health information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 23 2011-07-01 2011-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk...

  20. 40 CFR 141.154 - Required additional health information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk...

  1. 40 CFR 141.154 - Required additional health information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 24 2012-07-01 2012-07-01 false Required additional health information... Required additional health information. (a) All reports must prominently display the following language... from their health care providers. EPA/CDC guidelines on appropriate means to lessen the risk...

  2. 10 CFR 71.39 - Requirement for additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Requirement for additional information. 71.39 Section 71.39 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PACKAGING AND TRANSPORTATION OF RADIOACTIVE MATERIAL Application for Package Approval § 71.39 Requirement for additional information. The...

  3. Fundamental Mechanistic Investigations of Silane and Chlorocarbon Addition to Low Valent Palladium Species and their Application to Catalysis

    SciTech Connect

    Fink, Mark J.

    2009-01-27

    The collaboration between Mark Fink (Tulane University) and R. Morris Bullock (Brookhaven National Laboratory, currently at PNL) is an effort to understand some of the fundamental processes involved in catalytic bond activations with low coordinate palladium species. The project involves the photochemical generation of reactive low-valent palladium species as transients using nanosecond laser flash photolysis and the subsequent investigation of their reactions with chloroarenes and hydrosilanes. In the case of Si-H activation of hydrosilanes, relatively long-lived sigma complexes are implicated. These complexes may be important models for C-H activation in hydrocarbons. The information obtained from these studies will help in the understanding of fundamental processes involved in a number of important catalytic reactions in the petrochemical and environmental areas.

  4. A Public Opinion Survey on Correctional Education: Does Additional Information on Efficacy Lead to Additional Support?

    ERIC Educational Resources Information Center

    Waterland, Keri Lynn

    2009-01-01

    Though much research has been done on the efficacy of correctional education on reducing recidivism rates for prison inmates, there is little research on the effect that information about the efficacy of correctional education has on public opinion. This study examined whether providing additional information regarding the efficacy of correctional…

  5. 21 CFR 807.26 - Additional listing information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FDA electronic device registration and listing system. Electronic submissions of such information must...) MEDICAL DEVICES ESTABLISHMENT REGISTRATION AND DEVICE LISTING FOR MANUFACTURERS AND INITIAL IMPORTERS OF DEVICES Procedures for Device Establishments § 807.26 Additional listing information. (a) Each owner...

  6. 21 CFR 807.26 - Additional listing information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FDA electronic device registration and listing system. Electronic submissions of such information must...) MEDICAL DEVICES ESTABLISHMENT REGISTRATION AND DEVICE LISTING FOR MANUFACTURERS AND INITIAL IMPORTERS OF DEVICES Procedures for Device Establishments § 807.26 Additional listing information. (a) Each owner...

  7. Value Addition in Information Technology and Literacy: An Empirical Investigation

    ERIC Educational Resources Information Center

    Sanghera, Kamaljeet K.

    2009-01-01

    The purpose of the research is to analyze the value addition in students' information communication and technology (ICT) literacy level and confidence in using technology after completing a general education information technology course at a four-year university. An online survey was created to examine students' perceptions. The findings revealed…

  8. 28 CFR 4.4 - Supporting affidavit; additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... EMPLOYEE RETIREMENT INCOME SECURITY ACT OF 1974 § 4.4 Supporting affidavit; additional information. (a... together with any other person and the amount and source of all income during the immediately preceding five calendar years plus income to date of application. (12) Any other information which the...

  9. To be or not to be butterfly: New mechanistic insights in the Aza-Michael asymmetric addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide.

    PubMed

    Nieto, Carlos T; Díez, David; Garrido, Narciso M

    2014-09-30

    The asymmetric Aza-Michael addition of homochiral lithium benzylamides to α,β-unsaturated esters represents an extended protocol to obtain enantioenriched β-amino esters. An exhaustive mechanistic revision of the originally proposed mechanism is reported, developing a quantum mechanics/molecular mechanics protocol for the asymmetric Aza-Michael reaction of homochiral lithium benzylamides. Explicit and implicit solvent schemes were considered, together with a proper account of long-range dispersion forces, evaluated through a density functional theory benchmark of different functionals. Theoretical results showed that the diastereoselectivity is mainly controlled by the N-α-methylbenzyl moiety placing, deriving a Si/Re 99:1 diastereoselective ratio, in good agreement with reported experimental results. The main transition state geometries are two transition state conformers in a "V-stacked" orientation of the amide's phenyl rings, differing in the tetrahydrofuran molecule arrangement coordinated to the metal center. Extensive conformational sampling and quantum-level refinement give reasonable good speed/accuracy results, allowing this protocol to be extended to other similar Aza-Michael reaction systems.

  10. 25 CFR 215.17 - Additional information required.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Additional information required. 215.17 Section 215.17 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEAD AND ZINC MINING... interested in lead and zinc mining leases, or land under the jurisdiction of the Quapaw Indian Agency,...

  11. 25 CFR 227.7 - Additional information from applicant.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 25 Indians 1 2012-04-01 2011-04-01 true Additional information from applicant. 227.7 Section 227.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING How to Acquire Leases §...

  12. 25 CFR 227.7 - Additional information from applicant.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 25 Indians 1 2011-04-01 2011-04-01 false Additional information from applicant. 227.7 Section 227.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING How to Acquire...

  13. 25 CFR 227.7 - Additional information from applicant.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Additional information from applicant. 227.7 Section 227.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING How to Acquire...

  14. 46 CFR 535.606 - Requests for additional information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 9 2010-10-01 2010-10-01 false Requests for additional information. 535.606 Section 535.606 Shipping FEDERAL MARITIME COMMISSION REGULATIONS AFFECTING OCEAN SHIPPING IN FOREIGN COMMERCE OCEAN COMMON CARRIER AND MARINE TERMINAL OPERATOR AGREEMENTS SUBJECT TO THE SHIPPING ACT OF 1984...

  15. 21 CFR 207.31 - Additional drug listing information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Additional drug listing information. 207.31 Section 207.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL...

  16. 25 CFR 227.7 - Additional information from applicant.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 25 Indians 1 2013-04-01 2013-04-01 false Additional information from applicant. 227.7 Section 227.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING How to Acquire...

  17. 25 CFR 227.7 - Additional information from applicant.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false Additional information from applicant. 227.7 Section 227.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEASING OF CERTAIN LANDS IN WIND RIVER INDIAN RESERVATION, WYOMING, FOR OIL AND GAS MINING How to Acquire...

  18. 21 CFR 207.31 - Additional drug listing information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Additional drug listing information. 207.31 Section 207.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL...

  19. 21 CFR 207.31 - Additional drug listing information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Additional drug listing information. 207.31 Section 207.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL...

  20. 21 CFR 207.31 - Additional drug listing information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Additional drug listing information. 207.31 Section 207.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL REGISTRATION OF PRODUCERS OF DRUGS AND LISTING OF DRUGS IN COMMERCIAL...

  1. 49 CFR 235.12 - Additional required information-prints.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OR MATERIAL MODIFICATION OF A SIGNAL SYSTEM OR RELIEF FROM THE REQUIREMENTS OF PART 236 § 235.12... application should be shown uncolored. (Approved by the Office of Management and Budget under control number... 49 Transportation 4 2010-10-01 2010-10-01 false Additional required information-prints....

  2. 38 CFR 39.3 - Decisionmakers, notifications, and additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Decisionmakers, notifications, and additional information. 39.3 Section 39.3 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID TO STATES FOR ESTABLISHMENT, EXPANSION, AND IMPROVEMENT...

  3. Progress in the experimental observation of thiamin diphosphate-bound intermediates on enzymes and mechanistic information derived from these observations.

    PubMed

    Jordan, Frank; Nemeria, Natalia S

    2014-12-01

    Thiamin diphosphate (ThDP), the vitamin B1 coenzyme is an excellent representative of coenzymes, which carry out electrophilic catalysis by forming a covalent complex with their substrates. The function of ThDP is to greatly increase the acidity of two carbon acids by stabilizing their conjugate bases, the ylide/carbene/C2-carbanion of the thiazolium ring and the C2α-carbanion/enamine, once the substrate binds to ThDP. In recent years, several ThDP-bound intermediates on such pathways have been characterized by both solution and solid-state methods. Prominent among these advances are X-ray crystallographic results identifying both oxidative and non-oxidative intermediates, rapid chemical quench followed by NMR detection of several intermediates which are stable under acidic conditions, solid-state NMR and circular dichroism detection of the states of ionization and tautomerization of the 4'-aminopyrimidine moiety of ThDP in some of the intermediates. These methods also enabled in some cases determination of the rate-limiting step in the complex series of steps. This review is an update of a review with the same title published by the authors in 2005 in this Journal. Much progress has been made in the intervening decade in the identification of the intermediates and their application to gain additional mechanistic insight.

  4. Censored data treatment using additional information in intelligent medical systems

    NASA Astrophysics Data System (ADS)

    Zenkova, Z. N.

    2015-11-01

    Statistical procedures are a very important and significant part of modern intelligent medical systems. They are used for proceeding, mining and analysis of different types of the data about patients and their diseases; help to make various decisions, regarding the diagnosis, treatment, medication or surgery, etc. In many cases the data can be censored or incomplete. It is a well-known fact that censorship considerably reduces the efficiency of statistical procedures. In this paper the author makes a brief review of the approaches which allow improvement of the procedures using additional information, and describes a modified estimation of an unknown cumulative distribution function involving additional information about a quantile which is known exactly. The additional information is used by applying a projection of a classical estimator to a set of estimators with certain properties. The Kaplan-Meier estimator is considered as an estimator of the unknown cumulative distribution function, the properties of the modified estimator are investigated for a case of a single right censorship by means of simulations.

  5. Additives

    NASA Technical Reports Server (NTRS)

    Smalheer, C. V.

    1973-01-01

    The chemistry of lubricant additives is discussed to show what the additives are chemically and what functions they perform in the lubrication of various kinds of equipment. Current theories regarding the mode of action of lubricant additives are presented. The additive groups discussed include the following: (1) detergents and dispersants, (2) corrosion inhibitors, (3) antioxidants, (4) viscosity index improvers, (5) pour point depressants, and (6) antifouling agents.

  6. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... tentative denial letter. At the same time, the applicant should indicate generally the type of information... penalty of perjury attesting to the truth and correctness of the information provided, which is dated...

  7. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color... respect to the safety of the color additive or the physical or technical effect it produces. The date...

  8. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... samples of the color additive, articles used as components thereof, or of the food, drug, or cosmetic in... additive, or articles used as components thereof, or of the food, drug, or cosmetic in which the color... respect to the safety of the color additive or the physical or technical effect it produces. The date...

  9. A Mechanistically Informed User-Friendly Model to Predict Greenhouse Gas (GHG) Fluxes and Carbon Storage from Coastal Wetlands

    NASA Astrophysics Data System (ADS)

    Abdul-Aziz, O. I.; Ishtiaq, K. S.

    2015-12-01

    We present a user-friendly modeling tool on MS Excel to predict the greenhouse gas (GHG) fluxes and estimate potential carbon sequestration from the coastal wetlands. The dominant controls of wetland GHG fluxes and their relative mechanistic linkages with various hydro-climatic, sea level, biogeochemical and ecological drivers were first determined by employing a systematic data-analytics method, including Pearson correlation matrix, principal component and factor analyses, and exploratory partial least squares regressions. The mechanistic knowledge and understanding was then utilized to develop parsimonious non-linear (power-law) models to predict wetland carbon dioxide (CO2) and methane (CH4) fluxes based on a sub-set of climatic, hydrologic and environmental drivers such as the photosynthetically active radiation, soil temperature, water depth, and soil salinity. The models were tested with field data for multiple sites and seasons (2012-13) collected from the Waquoit Bay, MA. The model estimated the annual wetland carbon storage by up-scaling the instantaneous predicted fluxes to an extended growing season (e.g., May-October) and by accounting for the net annual lateral carbon fluxes between the wetlands and estuary. The Excel Spreadsheet model is a simple ecological engineering tool for coastal carbon management and their incorporation into a potential carbon market under a changing climate, sea level and environment. Specifically, the model can help to determine appropriate GHG offset protocols and monitoring plans for projects that focus on tidal wetland restoration and maintenance.

  10. 77 FR 67655 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... Collection; Comment Request; Food Additive Petitions and Investigational Food Additive Exemptions; Extension... comment in response to the notice. This notice solicits comments on food additive petitions regarding... of information technology. Food Additive Petitions and Investigational Food Additive Exemptions,...

  11. 78 FR 51265 - 30-Day Notice of Proposed Information Collection: Application for Additional Visa Pages or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-20

    ... Notice of Proposed Information Collection: Application for Additional Visa Pages or Miscellaneous...: Title of Information Collection: Application for Additional Visa Pages or Miscellaneous Passport... applies for the addition of visa pages to that passport, the Department must confirm the...

  12. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... respect to the safety of the color additive or the physical or technical effect it produces. The date used for computing the 90-day limit for the purposes of section 721(d)(1) of the act shall be moved...

  13. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... respect to the safety of the color additive or the physical or technical effect it produces. The date used for computing the 90-day limit for the purposes of section 721(d)(1) of the act shall be moved...

  14. 34 CFR 303.212 - Additional information and assurances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... State is taking to ensure equitable access to, and equitable participation in, the part C statewide system as required by section 427(b) of GEPA; and (b) Other information and assurances as the Secretary may reasonably require. (Approved by Office of Management and Budget under control number...

  15. 78 FR 77119 - Proposed Information Collection Request; Comment Request; Regulation of Fuels and Fuel Additives...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... AGENCY Proposed Information Collection Request; Comment Request; Regulation of Fuels and Fuel Additives: 2011 Renewable Fuel Standards-- Petition for International Aggregate Compliance Approach AGENCY... to submit an information collection request (ICR), ``Regulation of Fuels and Fuel Additives:...

  16. 40 CFR Table 42 to Subpart Uuu of... - Additional Information for Initial Notification of Compliance Status

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 12 2010-07-01 2010-07-01 true Additional Information for Initial..., Table 42 Table 42 to Subpart UUU of Part 63—Additional Information for Initial Notification of... applies to you. For . . . You shall provide this additional information . . . 1. Identification...

  17. Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies.

    PubMed

    Yazici, Arife; Wille, Uta; Pyne, Stephen G

    2016-02-19

    Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,β-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,β-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs. PMID:26816207

  18. Synthesis of Bridged Heterocycles via Sequential 1,4- and 1,2-Addition Reactions to α,β-Unsaturated N-Acyliminium Ions: Mechanistic and Computational Studies.

    PubMed

    Yazici, Arife; Wille, Uta; Pyne, Stephen G

    2016-02-19

    Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,β-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,β-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs.

  19. Enhancement of antimicrobial activities of whole and sub-fractionated white tea by addition of copper (II) sulphate and vitamin C against Staphylococcus aureus; a mechanistic approach

    PubMed Central

    2011-01-01

    . Investigations to establish which WTF component/s and in what proportions additives are most effective against target organisms are warranted. PMID:22093997

  20. 16 CFR 2.20 - Petitions for review of requests for additional information or documentary material.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... or documentary material issued under 16 CFR 803.20. (b) Second request procedures—(1) Notice. Every request for additional information or documentary material issued under 16 CFR 803.20 shall inform the... additional information or documentary material. 2.20 Section 2.20 Commercial Practices FEDERAL...

  1. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Confidentiality of data and information in color... and information in color additive petitions. (a) The following data and information in a color... because of the deficiencies involved: (1) All safety and functionality data and information submitted...

  2. 42 CFR 435.955 - Additional requirements regarding information released by a Federal agency.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Additional requirements regarding information... requirements regarding information released by a Federal agency. (a) Unless waived under paragraph (d) of this section, based on information received from a computerized data match in which information on...

  3. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Additional information for Applicants not having a... Financial Assistance § 260.25 Additional information for Applicants not having a credit rating. Each application submitted by Applicants not having a recent credit rating from one or more nationally...

  4. Can metabolomics in addition to genomics add to prognostic and predictive information in breast cancer?

    PubMed

    Howell, Anthony

    2010-11-16

    Genomic data from breast cancers provide additional prognostic and predictive information that is beginning to be used for patient management. The question arises whether additional information derived from other 'omic' approaches such as metabolomics can provide additional information. In an article published this month in BMC Cancer, Borgan et al. add metabolomic information to genomic measures in breast tumours and demonstrate, for the first time, that it may be possible to further define subgroups of patients which could be of value clinically. See research article: http://www.biomedcentral.com/1471-2407/10/628.

  5. 75 FR 77645 - Agency Information Collection Activities; Proposed Collection; Comment Request; Color Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-13

    ... Collection; Comment Request; Color Additive Certification Requests and Recordkeeping AGENCY: Food and Drug... certification of color additives manufactured for use in foods, drugs, cosmetics or medical devices in the... of information technology. Color Additive Certification Requests and Recordkeeping--21 CFR Part...

  6. Mechanistic investigations of CO-photoextrusion and oxidative addition reactions of early transition-metal carbonyls: (η(5)-C5H5)M(CO)4 (M = V, Nb, Ta).

    PubMed

    Su, Shih-Hao; Su, Ming-Der

    2016-06-28

    The mechanisms for the photochemical Si-H bond activation reaction are studied theoretically using a model system of the group 5 organometallic compounds, η(5)-CpM(CO)4 (M = V, Nb, and Ta), with the M06-2X method and the Def2-SVPD basis set. Three types of reaction pathways that lead to final insertion products are identified. The structures of the intersystem crossings, which play a central role in these photo-activation reactions, are determined. The intermediates and transitional structures in either the singlet or triplet states are also calculated to provide a mechanistic explanation of the reaction pathways. All of the potential energy surfaces for the group 5 η(5)-CpM(CO)4 complexes are quite similar. In particular, the theoretical evidence suggests that after irradiation using light, η(5)-CpM(CO)4 quickly loses one CO ligand to yield two tricarbonyls, in either the singlet or the triplet states. The triplet tricarbonyl 16-electron intermediates, ([η(5)-CpM(CO)3](3)), play a key role in the formation of the final oxidative addition product, η(5)-CpM(CO)3(H)(SiMe3). However, the singlet counterparts, ([η(5)-CpM(CO)3](1)), play no role in the formation of the final product molecule, but their singlet metal centers interact weakly with solvent molecules ((Me3)SiH) to produce alkyl-solvated organometallic complexes, which are observable experimentally. This theoretical evidence is in accordance with the available experimental observations.

  7. 30 CFR 250.418 - What additional information must I submit with my APD?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must...

  8. 30 CFR 250.418 - What additional information must I submit with my APD?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must...

  9. 18 CFR 33.4 - Additional information requirements for applications involving vertical competitive impacts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Additional information requirements for applications involving vertical competitive impacts. 33.4 Section 33.4 Conservation of Power... FEDERAL POWER ACT APPLICATIONS UNDER FEDERAL POWER ACT SECTION 203 § 33.4 Additional...

  10. 18 CFR 33.4 - Additional information requirements for applications involving vertical competitive impacts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Additional information requirements for applications involving vertical competitive impacts. 33.4 Section 33.4 Conservation of Power... FEDERAL POWER ACT APPLICATIONS UNDER FEDERAL POWER ACT SECTION 203 § 33.4 Additional...

  11. "The Dose Makes the Poison": Informing Consumers About the Scientific Risk Assessment of Food Additives.

    PubMed

    Bearth, Angela; Cousin, Marie-Eve; Siegrist, Michael

    2016-01-01

    Intensive risk assessment is required before the approval of food additives. During this process, based on the toxicological principle of "the dose makes the poison,ˮ maximum usage doses are assessed. However, most consumers are not aware of these efforts to ensure the safety of food additives and are therefore sceptical, even though food additives bring certain benefits to consumers. This study investigated the effect of a short video, which explains the scientific risk assessment and regulation of food additives, on consumers' perceptions and acceptance of food additives. The primary goal of this study was to inform consumers and enable them to construct their own risk-benefit assessment and make informed decisions about food additives. The secondary goal was to investigate whether people have different perceptions of food additives of artificial (i.e., aspartame) or natural origin (i.e., steviolglycoside). To attain these research goals, an online experiment was conducted on 185 Swiss consumers. Participants were randomly assigned to either the experimental group, which was shown a video about the scientific risk assessment of food additives, or the control group, which was shown a video about a topic irrelevant to the study. After watching the video, the respondents knew significantly more, expressed more positive thoughts and feelings, had less risk perception, and more acceptance than prior to watching the video. Thus, it appears that informing consumers about complex food safety topics, such as the scientific risk assessment of food additives, is possible, and using a carefully developed information video is a successful strategy for informing consumers. PMID:25951078

  12. "The Dose Makes the Poison": Informing Consumers About the Scientific Risk Assessment of Food Additives.

    PubMed

    Bearth, Angela; Cousin, Marie-Eve; Siegrist, Michael

    2016-01-01

    Intensive risk assessment is required before the approval of food additives. During this process, based on the toxicological principle of "the dose makes the poison,ˮ maximum usage doses are assessed. However, most consumers are not aware of these efforts to ensure the safety of food additives and are therefore sceptical, even though food additives bring certain benefits to consumers. This study investigated the effect of a short video, which explains the scientific risk assessment and regulation of food additives, on consumers' perceptions and acceptance of food additives. The primary goal of this study was to inform consumers and enable them to construct their own risk-benefit assessment and make informed decisions about food additives. The secondary goal was to investigate whether people have different perceptions of food additives of artificial (i.e., aspartame) or natural origin (i.e., steviolglycoside). To attain these research goals, an online experiment was conducted on 185 Swiss consumers. Participants were randomly assigned to either the experimental group, which was shown a video about the scientific risk assessment of food additives, or the control group, which was shown a video about a topic irrelevant to the study. After watching the video, the respondents knew significantly more, expressed more positive thoughts and feelings, had less risk perception, and more acceptance than prior to watching the video. Thus, it appears that informing consumers about complex food safety topics, such as the scientific risk assessment of food additives, is possible, and using a carefully developed information video is a successful strategy for informing consumers.

  13. 38 CFR 61.15 - Capital grants-obtaining additional information and awarding capital grants.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Capital grants-obtaining additional information and awarding capital grants. 61.15 Section 61.15 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) VA HOMELESS PROVIDERS GRANT AND PER DIEM PROGRAM Capital Grants § 61.15...

  14. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Additional information shall be supplied within reasonable time. 803.21 Section 803.21 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF...

  15. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Additional information shall be supplied within reasonable time. 803.21 Section 803.21 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF...

  16. 13 CFR 126.403 - May SBA require additional information from a HUBZone SBC?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false May SBA require additional information from a HUBZone SBC? 126.403 Section 126.403 Business Credit and Assistance SMALL BUSINESS... adverse inference from the failure of a HUBZone SBC to cooperate with a program examination or...

  17. 13 CFR 126.403 - May SBA require additional information from a HUBZone SBC?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false May SBA require additional information from a HUBZone SBC? 126.403 Section 126.403 Business Credit and Assistance SMALL BUSINESS... adverse inference from the failure of a HUBZone SBC to cooperate with a program examination or...

  18. 13 CFR 126.403 - May SBA require additional information from a HUBZone SBC?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false May SBA require additional information from a HUBZone SBC? 126.403 Section 126.403 Business Credit and Assistance SMALL BUSINESS... adverse inference from the failure of a HUBZone SBC to cooperate with a program examination or...

  19. 18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Additional information... and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE... role that entry could play in mitigating adverse competitive effects of the transaction; (3)...

  20. 18 CFR 33.3 - Additional information requirements for applications involving horizontal competitive impacts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Additional information... and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE... role that entry could play in mitigating adverse competitive effects of the transaction; (3)...

  1. 18 CFR 33.4 - Additional information requirements for applications involving vertical competitive impacts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Additional information... and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE... competitive effects of the transaction. (ii) The potential for entry in the market and the role that...

  2. 18 CFR 33.4 - Additional information requirements for applications involving vertical competitive impacts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Additional information... and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE... competitive effects of the transaction. (ii) The potential for entry in the market and the role that...

  3. 18 CFR 33.4 - Additional information requirements for applications involving vertical competitive impacts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Additional information... and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE... competitive effects of the transaction. (ii) The potential for entry in the market and the role that...

  4. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Confidentiality of data and information in color additive petitions. 71.15 Section 71.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... established in § 20.61 of this chapter. (6) All records showing the Food and Drug Administration's testing...

  5. 76 FR 24854 - Proposed Information Collection; Comment Request; Additional Protocol Report Forms

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... International Atomic Energy Agency (IAEA) on a number of commercial nuclear and nuclear-related items, materials... for a nuclear weapons program. These forms provides the IAEA with information about additional aspects...; buildings on sites of facilities selected by the IAEA from the U.S. Eligible Facilities List;...

  6. 30 CFR 250.418 - What additional information must I submit with my APD?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What additional information must I submit with my APD? 250.418 Section 250.418 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND... plot if the well is to be directionally drilled; (d) A Hydrogen Sulfide Contingency Plan (see §...

  7. 30 CFR 250.418 - What additional information must I submit with my APD?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must I submit with my APD? You must include the following with the APD: (a) Rated capacities of the drilling rig and...

  8. 38 CFR 39.4 - Decision makers, notifications, and additional information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Decision makers, notifications, and additional information. 39.4 Section 39.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID TO STATES FOR ESTABLISHMENT, EXPANSION, AND IMPROVEMENT,...

  9. 38 CFR 39.4 - Decision makers, notifications, and additional information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2014-07-01 2014-07-01 false Decision makers, notifications, and additional information. 39.4 Section 39.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR...

  10. 38 CFR 39.4 - Decision makers, notifications, and additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false Decision makers, notifications, and additional information. 39.4 Section 39.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR...

  11. 38 CFR 39.4 - Decision makers, notifications, and additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false Decision makers, notifications, and additional information. 39.4 Section 39.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) AID FOR THE ESTABLISHMENT, EXPANSION, AND IMPROVEMENT, OR...

  12. 26 CFR 1.852-7 - Additional information required in returns of shareholders.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... shareholders. 1.852-7 Section 1.852-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Trusts § 1.852-7 Additional information required in returns of shareholders. Any person who fails or....852-6 requires the company to demand from its shareholders shall submit as a part of his income...

  13. Dehydrofluorination of Hydrofluorocarbons by Titanium Alkylidynes via Sequential C-H/C-F Bond Activation Reactions. A Synthetic, Structural, and Mechanistic Study of 1,2-CH Bond Addition and [beta]-Fluoride Elimination

    SciTech Connect

    Fout, A.R.; Scott, J.; Miller, D.L.; Bailey, B.C.; Pink, M.; Mindiola, D.J.

    2009-01-07

    The neopentylidene-neopentyl complex (PNP)Ti=CH{sup t}Bu(CH{sub 2}{sup t}Bu) (1); (PNP{sup -} = N[2-P(CHMe{sub 2}){sub 2}-4-methylphenyl]{sub 2}) extrudes neopentane in neat fluorobenzene under mild conditions (25 C) to generate the transient titanium alkylidyne (PNP)Ti-C{sup t}Bu (A), which subsequently undergoes regioselective 1,2-CH bond addition of a fluorobenzene across the Ti-C linkage to generate (PNP)Ti=CH{sup t}Bu(o-FC{sub 6}H{sub 4}) (2). Kinetic and mechanistic studies suggest that the C-H activation process is pseudo-first-order in titanium, with the {alpha}-hydrogen abstraction being the rate-determining step and the post-rate-determining step being the C-H bond activation of fluorobenzene. At 100 C complex 2 does not equilibrate back to A and the preference for C-H activation in benzene versus fluorobenzene is 2:3, respectively. Compound 1 also reacts readily, and in most cases cleanly, with a series of hydrofluoroarenes (HAr{sub F}), to form a family of alkylidene-arylfluoride derivatives of the type (PNP)Ti=CH{sup t}Bu(Ar{sub F}). Thermolysis of the latter compounds generates the titanium alkylidene-fluoride (PNP)Ti=CH{sup t}Bu(F) (14) by a {beta}-fluoride elimination, concurrent with formation of o-benzyne. {beta}-Fluoride elimination to yield 14 occurs from 2 under elevated temperatures with k{sub average} = 4.96(16) x 10{sup -5} s{sup -1} and with activation parameters {Delta}H{sub {-+}} = 29(1) kcal/mol and {Delta}S{sub {-+}} = -3(4) cal/mol {center_dot}K. It was found that {beta}-fluoride elimination is accelerated when electron-rich groups are adjacent to the fluoride group, thus implying that a positive charge buildup at the arylfluoride ring occurs in the activated complex of 2. The alkylidene derivative (PNP)Ti=CHSiMe{sub 3}(CH{sub 2}SiMe{sub 3}) (15) also undergoes {alpha}-hydrogen abstraction to form the putative (PNP)Ti'-CSiMe{sub 3} (B) at higher temperatures (>70 C) and dehydrofluorinates the same series of HArF when the reaction

  14. 75 FR 35119 - 60-Day Notice of Proposed Information Collection: Form DS-4085 Application for Additional Visa...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... Notice of Proposed Information Collection: Form DS-4085 Application for Additional Visa Pages or... the Paperwork Reduction Act of 1995. Title of Information Collection: Application for Additional Visa... collection: The information collected on the DS-4085 is used to facilitate the issuance of additional...

  15. 26 CFR 301.6223(c)-1 - Additional information regarding partners furnished to the Internal Revenue Service.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... shown on the partnership return, the Internal Revenue Service will use additional information as... additional information at any time by filing a written statement with the Internal Revenue Service. However...) of this section. (f) Internal Revenue Service may use other information. In addition to...

  16. Food for Thought ... Mechanistic Validation

    PubMed Central

    Hartung, Thomas; Hoffmann, Sebastian; Stephens, Martin

    2013-01-01

    Summary Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st Century, either by high-throughput testing in the ToxCast/ Tox21 project or omics-based testing in the Human Toxome Project. This article explores the mostly neglected assessment of a test's scientific basis, which moves mechanism and causality to the foreground when validating/qualifying tests. Such mechanistic validation faces the problem of establishing causality in complex systems. However, pragmatic adaptations of the Bradford Hill criteria, as well as bioinformatic tools, are emerging. As critical infrastructures of the organism are perturbed by a toxic mechanism we argue that by focusing on the target of toxicity and its vulnerability, in addition to the way it is perturbed, we can anchor the identification of the mechanism and its verification. PMID:23665802

  17. Polymyxin B hemoperfusion: a mechanistic perspective.

    PubMed

    Ronco, Claudio; Klein, David J

    2014-06-09

    Direct hemoperfusion therapy with polymyxin B immobilized fiber cartridge (PMX-DHP) is an established strategy in the treatment of septic shock in Japan and parts of Western Europe. PMX-DHP is currently the subject of a pivotal North American randomized controlled trial (EUPHRATES) in patients with septic shock and confirmed endotoxemia, as measured by the endotoxin activity assay. The major mechanism of action of this therapy is the removal of circulating endotoxin. High affinity binding of circulating endotoxin by the PMX-DHP column may decrease circulating endotoxin levels by up to 90% after two standard treatments. Basic research has shown reductions in circulating cytokine levels and in renal tubular apoptosis. Clinical research has shown that PMX-DHP therapy results in hemodynamic improvements, improvements in oxygenation, renal function, and reductions in mortality. Further research is needed to further define additional patient populations with endotoxemia that may benefit from PMX-DHP therapy as well as to further elucidate dosing, timing, and additional information on mechanisms of action. This review will present the mechanistic rationale for this targeted strategy of endotoxin removal using PMX-DHP in endotoxemic septic patients, highlighting both the specific effects of the therapy and the evidence accumulated so far of clinical improvement following this therapy in terms of recovery of organ function.

  18. PAT-1 safety analysis report addendum author responses to request for additional information.

    SciTech Connect

    Weiner, Ruth F.; Schmale, David T.; Kalan, Robert J.; Akin, Lili A.; Miller, David Russell; Knorovsky, Gerald Albert; Yoshimura, Richard Hiroyuki; Lopez, Carlos; Harding, David Cameron; Jones, Perry L.; Morrow, Charles W.

    2010-09-01

    The Plutonium Air Transportable Package, Model PAT-1, is certified under Title 10, Code of Federal Regulations Part 71 by the U.S. Nuclear Regulatory Commission (NRC) per Certificate of Compliance (CoC) USA/0361B(U)F-96 (currently Revision 9). The National Nuclear Security Administration (NNSA) submitted SAND Report SAND2009-5822 to NRC that documented the incorporation of plutonium (Pu) metal as a new payload for the PAT-1 package. NRC responded with a Request for Additional Information (RAI), identifying information needed in connection with its review of the application. The purpose of this SAND report is to provide the authors responses to each RAI. SAND Report SAND2010-6106 containing the proposed changes to the Addendum is provided separately.

  19. 20 CFR 30.518 - Can OWCP require the recipient of the overpayment to submit additional financial information?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... overpayment to submit additional financial information? 30.518 Section 30.518 Employees' Benefits OFFICE OF... OWCP require the recipient of the overpayment to submit additional financial information? (a) The recipient of the overpayment is responsible for providing information about income, expenses and assets...

  20. Emerging Technologies in the Built Environment: Geographic Information Science (GIS), 3D Printing, and Additive Manufacturing

    SciTech Connect

    New, Joshua Ryan

    2014-01-01

    Abstract 1: Geographic information systems emerged as a computer application in the late 1960s, led in part by projects at ORNL. The concept of a GIS has shifted through time in response to new applications and new technologies, and is now part of a much larger world of geospatial technology. This presentation discusses the relationship of GIS and estimating hourly and seasonal energy consumption profiles in the building sector at spatial scales down to the individual parcel. The method combines annual building energy simulations for city-specific prototypical buildings and commonly available geospatial data in a GIS framework. Abstract 2: This presentation focuses on 3D printing technologies and how they have rapidly evolved over the past couple of years. At a basic level, 3D printing produces physical models quickly and easily from 3D CAD, BIM (Building Information Models), and other digital data. Many AEC firms have adopted 3D printing as part of commercial building design development and project delivery. This presentation includes an overview of 3D printing, discusses its current use in building design, and talks about its future in relation to the HVAC industry. Abstract 3: This presentation discusses additive manufacturing and how it is revolutionizing the design of commercial and residential facilities. Additive manufacturing utilizes a broad range of direct manufacturing technologies, including electron beam melting, ultrasonic, extrusion, and laser metal deposition for rapid prototyping. While there is some overlap with the 3D printing talk, this presentation focuses on the materials aspect of additive manufacturing and also some of the more advanced technologies involved with rapid prototyping. These technologies include design of carbon fiber composites, lightweight metals processing, transient field processing, and more.

  1. Summary data of potency and parameter information from semi-mechanistic PKPD modeling of prolactin release following administration of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride in rats.

    PubMed

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R H; Danhof, Meindert; De Lange, Elizabeth C M; Proost, Johannes H

    2016-09-01

    We provide the reader with relevant data related to our recently published paper, comparing two mathematical models to describe prolactin turnover in rats following one or two doses of the dopamine D2 receptor antagonists risperidone, paliperidone and remoxipride, "A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats" (Taneja et al., 2016) [1]. All information is tabulated. Summary level data on the in vitro potencies and the physicochemical properties is presented in Table 1. Model parameters required to explore the precursor pool model are presented in Table 2. In Table 3, estimated parameter comparisons for both models are presented, when separate potencies are estimated for risperidone and paliperidone, as compared to a common potency for both drugs. In Table 4, parameter estimates are compared when the drug effect is parameterized in terms of drug concentration or receptor occupancy. PMID:27617278

  2. Systematics of the family Plectopylidae in Vietnam with additional information on Chinese taxa (Gastropoda, Pulmonata, Stylommatophora)

    PubMed Central

    Páll-Gergely, Barna; Hunyadi, András; Ablett, Jonathan; Lương, Hào Văn; Fred Naggs; Asami, Takahiro

    2015-01-01

    Abstract Vietnamese species from the family Plectopylidae are revised based on the type specimens of all known taxa, more than 600 historical non-type museum lots, and almost 200 newly-collected samples. Altogether more than 7000 specimens were investigated. The revision has revealed that species diversity of the Vietnamese Plectopylidae was previously overestimated. Overall, thirteen species names (anterides Gude, 1909, bavayi Gude, 1901, congesta Gude, 1898, fallax Gude, 1909, gouldingi Gude, 1909, hirsuta Möllendorff, 1901, jovia Mabille, 1887, moellendorffi Gude, 1901, persimilis Gude, 1901, pilsbryana Gude, 1901, soror Gude, 1908, tenuis Gude, 1901, verecunda Gude, 1909) were synonymised with other species. In addition to these, Gudeodiscus hemmeni sp. n. and Gudeodiscus messageri raheemi ssp. n. are described from north-western Vietnam. Sixteen species and two subspecies are recognized from Vietnam. The reproductive anatomy of eight taxa is described. Based on anatomical information, Halongella gen. n. is erected to include Plectopylis schlumbergeri and Plectopylis fruhstorferi. Additionally, the genus Gudeodiscus is subdivided into two subgenera (Gudeodiscus and Veludiscus subgen. n.) on the basis of the morphology of the reproductive anatomy and the radula. The Chinese Gudeodiscus phlyarius werneri Páll-Gergely, 2013 is moved to synonymy of Gudeodiscus phlyarius. A spermatophore was found in the organ situated next to the gametolytic sac in one specimen. This suggests that this organ in the Plectopylidae is a diverticulum. Statistically significant evidence is presented for the presence of calcareous hook-like granules inside the penis being associated with the absence of embryos in the uterus in four genera. This suggests that these probably play a role in mating periods before disappearing when embryos develop. Sicradiscus mansuyi is reported from China for the first time. PMID:25632253

  3. Lateralization of High-Frequency Clicks Based on Interaural Time: Additivity of Information across Frequency

    NASA Astrophysics Data System (ADS)

    Wenzel, Elizabeth Marie

    Lateralization performance based on interaural differences of time (IDTs) was measured for trains of Gaussian clicks which varied in spectral content. In the first experiment, thresholds ((DELTA)IDTs) were measured as a function of the number of clicks in the train (n = 1 to 32), the interclick interval (ICI = 2.5 or 5 ms), and the spectral content (1 vs. 2 or 4 carriers). Subjects' performance was compared to perfect statistical summation which predicts slopes of -.50 when log-(DELTA)IDT vs. long -n is plotted. The results showed that increasing the spectral content of the clicks decreased the intercepts of the log -log functions (decreased thresholds) while having little effect on their slopes. Shortening the ICIs caused the slopes of the functions to decrease in absolute value. To estimate the bandwidth of frequency-interaction in lateralization, d's were measured for clicks with constant IDTs (n = 1) with a fixed carrier (FF = 4000, 5200, 6000 or 7200 Hz), both alone and combined with a second click whose carrier (F) varied from 3500 to 8500 Hz. Performance in combined conditions was compared to independent summation of the information carried by the two frequency-bands. Performance improved as the separation between F and FF increased until the level predicted by independence was reached. The final experiment investigated the interaction of frequency content with IDT. d's were measured as a function of the IDT in clicks with carriers of 5200, 6000 or 7200 Hz, both alone and combined with a 4000-Hz click with a fixed IDT. Performance in combined conditions was again compared to independent additivity. The improvement with frequency was explained by an increase in the number of samples of the IDT reaching the binaural centers due to spread of excitation along the basilar membrane. Less than independent summation was explained by correlation between overlapping bands which reduced the amount of information exciting independent channels. The data also suggest that

  4. Mechanistic Insight in the Function of Phosphite Additives for Protection of LiNi0.5Co0.2Mn0.3O2 Cathode in High Voltage Li-Ion Cells.

    PubMed

    He, Meinan; Su, Chi-Cheung; Peebles, Cameron; Feng, Zhenxing; Connell, Justin G; Liao, Chen; Wang, Yan; Shkrob, Ilya A; Zhang, Zhengcheng

    2016-05-11

    Triethlylphosphite (TEP) and tris(2,2,2-trifluoroethyl) phosphite (TTFP) have been evaluated as electrolyte additives for high-voltage Li-ion battery cells using a Ni-rich layered cathode material LiNi0.5Co0.2Mn0.3O2 (NCM523) and the conventional carbonate electrolyte. The repeated charge/discharge cycling for cells containing 1 wt % of these additives was performed using an NCM523/graphite full cell operated at the voltage window from 3.0-4.6 V. During the initial charge process, these additives decompose on the cathode surface at a lower oxidation potential than the baseline electrolyte. Impedance spectroscopy and post-test analyses indicate the formation of protective coatings by both additives on the cathode surface that prevent oxidative breakdown of the electrolyte. However, only TTFP containing cells demonstrate the improved capacity retention and Coulombic efficiency. For TEP, the protective coating is also formed, but low Li(+) ion mobility through the interphase layer results in inferior performance. These observations are rationalized through the inhibition of electrocatalytic centers present on the cathode surface and the formation of organophosphate deposits isolating the cathode surface from the electrolyte. The difference between the two phosphites clearly originates in the different properties of the resulting phosphate coatings, which may be in Li(+) ion conductivity through such materials. PMID:27090502

  5. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... fuel additive will be sold, offered for sale, or introduced into commerce, and the fuel additive manufacturer's recommended range of concentration and purpose-in-use for each such type of fuel. (e) Such other... (e) of this section as provided in § 79.5(b). (g) Assurances that the additive manufacturer will...

  6. 41 CFR 102-75.140 - In addition to the title report, and all necessary environmental information and certifications...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 102-75.140 Public Contracts and Property Management Federal Property Management Regulations System... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false In addition to the title report, and all necessary environmental information and certifications, what information must...

  7. 41 CFR 102-79.111 - Where may Executive agencies find additional information on Integrated Workplace concepts?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Where may Executive agencies find additional information on Integrated Workplace concepts? 102-79.111 Section 102-79.111 Public... Integrated Workplace concepts? The GSA Office of Governmentwide Policy provides additional guidance in...

  8. Does the anti-prothrombin antibodies measurement provide additional information in patients with thrombosis?

    PubMed

    Bardin, Nathalie; Alessi, Marie Christine; Dignat-George, Francoise; Vague, Irene Juhan; Sampol, Jose; Harlé, Jean Robert; Sanmarco, Marielle

    2007-01-01

    The aim of this study is to get new insight into the relevance of IgG anti-prothrombin antibodies in patients with thrombosis and to determine whether human prothrombin alone (aPT) or complexed to phosphatidylserine (aPS/PT) should be preferentially used for measuring these antibodies by enzyme-linked immunosorbent assay (ELISA). To this end, prevalence of anti-prothrombin antibodies, their characteristics in terms of avidity and heterogeneity, and their relationship with anti-beta2 glycoprotein I antibodies (abeta2GPI) were studied in 152 patients with thrombosis. Patients were divided into two groups according to the presence or absence of antiphospholipid antibodies (aPL), called aPL+ or aPL-, respectively. In the aPL- group (n=90), the prevalence of anti-prothrombin antibodies was substantial (10%) but not significantly different from that of control (5%). In the aPL+ group (n=62), lupus anticoagulant (LA) or anticardiolipin antibodies (aCL) positive, 61% were positive for anti-prothrombin antibodies with no statistical difference between aPT and aPS/PT prevalence (42% vs. 55%, respectively). In the whole thrombotic population, 19% were only aPT and 34% only aPS/PT suggesting the presence of different antibodies. Absorption experiments confirmed the heterogeneity of aPT and aPS/PT. No difference in their avidity was demonstrated. From the aPL+ group, 60 were LA positive. Among them, 18% were negative for abeta2GPI and anti-prothrombin antibodies showing that the detection of these antibodies could not substitute for LA determination. In conclusion, our data show that the screening of the different anti-prothrombin antibodies is not warranted in the aPL+ group since these antibodies do not provide additional information compared to aCL, LA and/or abeta2GPI measurement. Nevertheless, the substantial prevalence of anti-prothrombin antibodies in the aPL- group should be further explored in a large prospective study. PMID:17678713

  9. CMR Quantification of Myocardial Scar Provides Additive Prognostic Information in Nonischemic Cardiomyopathy

    PubMed Central

    Neilan, Tomas G.; Coelho-Filho, Otavio R.; Danik, Stephan B.; Shah, Ravi V.; Dodson, John A.; Verdini, Daniel J.; Tokuda, Michifumi; Daly, Caroline A.; Tedrow, Usha B.; Stevenson, William G.; Jerosch-Herold, Michael; Ghoshhajra, Brian B.; Kwong, Raymond Y.

    2014-01-01

    OBJECTIVES This study sought to determine whether the extent of late gadolinium enhancement (LGE) can provide additive prognostic information in patients with a nonischemic dilated cardiomyopathy (NIDC) with an indication for implantable cardioverter-defibrillator (ICD) therapy for the primary prevention of sudden cardiac death (SCD). BACKGROUND Data suggest that the presence of LGE is a strong discriminator of events in patients with NIDC. Limited data exist on the role of LGE quantification. METHODS The extent of LGE and clinical follow-up were assessed in 162 patients with NIDC prior to ICD insertion for primary prevention of SCD. LGE extent was quantified using both the standard deviation–based (2-SD) method and the full-width half-maximum (FWHM) method. RESULTS We studied 162 patients with NIDC (65% male; mean age: 55 years; left ventricular ejection fraction [LVEF]: 26 ± 8%) and followed up for major adverse cardiac events (MACE), including cardiovascular death and appropriate ICD therapy, for a mean of 29 ± 18 months. Annual MACE rates were substantially higher in patients with LGE (24%) than in those without LGE (2%). By univariate association, the presence and the extent of LGE demonstrated the strongest associations with MACE (LGE presence, hazard ratio [HR]: 14.5 [95% confidence interval (CI): 6.1 to 32.6; p < 0.001]; LGE extent, HR: 1.15 per 1% increase in volume of LGE [95% CI: 1.12 to 1.18; p < 0.0001]). Multivariate analyses showed that LGE extent was the strongest predictor in the best overall model for MACE, and a 7-fold hazard was observed per 10% LGE extent after adjustments for patient age, sex, and LVEF (adjusted HR: 7.61; p < 0.0001). LGE quantitation by 2-SD and FWHM both demonstrated robust prognostic association, with the highest MACE rate observed in patients with LGE involving >6.1% of LV myocardium. CONCLUSIONS LGE extent may provide further risk stratification in patients with NIDC with a current indication for ICD implantation for

  10. 14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252...

  11. 14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252...

  12. 14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252...

  13. 14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252...

  14. 14 CFR 121.317 - Passenger information requirements, smoking prohibitions, and additional seat belt requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Passenger information requirements, smoking... OPERATIONS Instrument and Equipment Requirements § 121.317 Passenger information requirements, smoking... command. (c) No person may operate an airplane on a flight on which smoking is prohibited by part 252...

  15. 78 FR 27936 - Request for Extension and Revision of a Currently Approved Information Collection With Additional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF AGRICULTURE Agricultural Marketing Service Request for Extension and Revision of a Currently Approved Information... of Fresh and Processed Fruits, Vegetables and Other Products AGENCY: Agricultural Marketing...

  16. Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity

    PubMed Central

    Davis, Myrtle; Li, Jianying; Knight, Elaine; Eldridge, Sandy R.; Daniels, Kellye K.; Bushel, Pierre R.

    2015-01-01

    Combinations of anticancer agents may have synergistic anti-tumor effects, but enhanced hematological toxicity often limit their clinical use. We examined whether “microarray profiles” could be used to compare early molecular responses following a single dose of agents administered individually with that of the agents administered in a combination. We compared the mRNA responses within bone marrow of Sprague-Dawley rats after a single 30 min treatment with topotecan at 4.7 mg/kg or oxaliplatin at 15 mg/kg alone to that of sequentially administered combination therapy or vehicle control for 1, 6, and 24 h. We also examined the histopathology of the bone marrow following all treatments. Drug-related histopathological lesions were limited to bone marrow hypocellularity for animals dosed with either agent alone or in combination. Lesions had an earlier onset and higher incidence for animals given topotecan alone or in combination with oxaliplatin. Severity increased from mild to moderate when topotecan was administered prior to oxaliplatin compared with administering oxaliplatin first. Notably, six patterns of co-expressed genes were detected at the 1 h time point that indicate regulatory expression of genes that are dependent on the order of the administration. These results suggest alterations in histone biology, chromatin remodeling, DNA repair, bone regeneration, and respiratory and oxidative phosphorylation are among the prominent pathways modulated in bone marrow from animals treated with an oxaliplatin/topotecan combination. These data also demonstrate the potential for early mRNA patterns derived from target organs of toxicity to inform toxicological risk and molecular mechanisms for agents given in combination. PMID:25729387

  17. Twenty-five additional cases of trisomy 9 mosaic: Birth information, medical conditions, and developmental status.

    PubMed

    Bruns, Deborah A; Campbell, Emily

    2015-05-01

    Limited literature exists on children and adults diagnosed with the mosaic form of trisomy 9. Data from the Tracking Rare Incidence Syndromes (TRIS) project has provided physical characteristics and medical conditions for 14 individuals. This article provides TRIS Survey results of 25 additional cases at two data points (birth and survey completion) as well as developmental status. Results confirmed a number of phenotypic features and medical conditions. In addition, a number of cardiac anomalies were reported along with feeding and respiratory difficulties in the immediate postnatal period. In addition, developmental status data indicated a range in functioning level up to skills in the 36 and 48-month range. Strengths were also noted across the sample in language and communication, fine motor and social-emotional development. Implications for professionals caring for children with this genetic condition are offered. PMID:25755087

  18. Testing 1...2...3...: Additional Files Available for Test Information Online.

    ERIC Educational Resources Information Center

    Fabiano, Emily

    1984-01-01

    Reviews databases providing information on published, standardized and unpublished, non-standardized test instruments: Educational Testing Service File, Mental Measurements Yearbook Database, Dissertation Abstracts Online, ERIC, and Psychological Abstracts. Search strategies, search examples, and a summary chart of searchable fields for test…

  19. 17 CFR 229.1118 - (Item 1118) Reports and additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... transaction documents. Describe the reports or other documents provided to security holders required under the... Commission maintains an Internet site that contains reports, proxy and information statements, and other... electronically filed with, or furnished to, the Commission. (2) Disclose whether other reports to...

  20. 75 FR 68608 - Information Collection; Request for Authorization of Additional Classification and Rate, Standard...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-08

    ...(c), and 5.15 (records to be kept by employers under the Fair Labor Standards Act (FLSA), 29 CFR 516... . SUPPLEMENTARY INFORMATION: A. Purpose This regulation prescribes labor standards for federally financed and assisted construction contracts subject to the Davis-Bacon and Related Acts (DBRA), as well as...

  1. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... corresponding to those used in this section, the following information: (a) A narrative statement detailing...; and (f) A narrative description of Applicant's management team, including: (1) Rail experience of top... narrative description of Applicant's workforce and the historical rate of employee turnover....

  2. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... corresponding to those used in this section, the following information: (a) A narrative statement detailing...; and (f) A narrative description of Applicant's management team, including: (1) Rail experience of top... narrative description of Applicant's workforce and the historical rate of employee turnover....

  3. Software for Information Storage and Retrieval Tested, Evaluated and Compared: Part VI--Various Additional Programs.

    ERIC Educational Resources Information Center

    Sieverts, Eric G.; And Others

    1993-01-01

    Reports on tests evaluating nine microcomputer software packages designed for information storage and retrieval: BRS-Search, dtSearch, InfoBank, Micro-OPC, Q&A, STN-PFS, Strix, TINman, and ZYindex. Tables and narrative evaluations detail results related to security, hardware, user features, search capability, indexing, input, maintenance of files,…

  4. 78 FR 22937 - 60-Day Notice of Proposed Information Collection: Application for Additional Visa Pages or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE 60-Day... Passport Services ACTION: Notice of request for public comment. SUMMARY: The Department of State is seeking Office of Management and ] Budget (OMB) approval for the information collection described below....

  5. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... shall be made that any such ingredient list is incomplete. (5) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption... information as defined in § 20.61 of this chapter: (1) Manufacturing methods or processes, including...

  6. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... shall be made that any such ingredient list is incomplete. (5) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption... information as defined in § 20.61 of this chapter: (1) Manufacturing methods or processes, including...

  7. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... shall be made that any such ingredient list is incomplete. (5) An assay method or other analytical method, unless it serves no regulatory or compliance purpose and is shown to fall within the exemption... information as defined in § 20.61 of this chapter: (1) Manufacturing methods or processes, including...

  8. 77 FR 58911 - Additional Identifying Information for One (1) Individual Designated Pursuant to Executive Order...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... Threaten to Disrupt the Middle East Peace Process'' (the ``Order''). DATES: The addition by the Director of... sanctions on persons who threaten to disrupt the Middle East peace process. The President identified in the... Middle East peace ] process; or (2) assist in, sponsor, or provide financial, material, or...

  9. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., percentage by weight, and method of analysis of each element in the additive are required provided, however, that a percentage figure combining the percentages of carbon, hydrogen, and/or oxygen may be provided unless the breakdown into percentages for these individual elements is already known to the...

  10. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., percentage by weight, and method of analysis of each element in the additive are required provided, however, that a percentage figure combining the percentages of carbon, hydrogen, and/or oxygen may be provided unless the breakdown into percentages for these individual elements is already known to the...

  11. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., percentage by weight, and method of analysis of each element in the additive are required provided, however, that a percentage figure combining the percentages of carbon, hydrogen, and/or oxygen may be provided unless the breakdown into percentages for these individual elements is already known to the...

  12. Facing Facts: Can the Face-Name Mnemonic Strategy Accommodate Additional Factual Information?

    ERIC Educational Resources Information Center

    Carney, Russell N.; Levin, Joel R.

    2012-01-01

    In 3 experiments, undergraduates used their own best method (control) or an "imposed" face-name mnemonic strategy to associate 18 caricatured faces, names, and additional facts. On all immediate tests (prompted by the faces), and on the delayed tests of Experiments 2a and 2b combined, mnemonic students statistically outperformed control students…

  13. 75 FR 62404 - Agency Information Collection Activities; Proposed Collection; Comment Request; Additional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ...-counter (OTC) drugs as generally recognized as safe and effective and not misbranded. DATES: Submit either... additional criteria and procedures for classifying OTC drugs as generally recognized as safe and effective and not misbranded (2002 TEA final rule). The regulations in Sec. 330.14 state that OTC drug...

  14. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... 52.80 Section 52.80 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  15. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... 52.158 Section 52.158 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.158 Contents of application; additional... environmental report as required by 10 CFR 51.54. (2) If the manufacturing license application references...

  16. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... 52.80 Section 52.80 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  17. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... 52.80 Section 52.80 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  18. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... 52.80 Section 52.80 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  19. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... 52.158 Section 52.158 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.158 Contents of application; additional... environmental report as required by 10 CFR 51.54. (2) If the manufacturing license application references...

  20. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... 52.158 Section 52.158 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.158 Contents of application; additional... environmental report as required by 10 CFR 51.54. (2) If the manufacturing license application references...

  1. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... 52.80 Section 52.80 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.80 Contents of applications; additional technical... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  2. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... 52.158 Section 52.158 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Manufacturing Licenses § 52.158 Contents of application; additional... environmental report as required by 10 CFR 51.54. (2) If the manufacturing license application references...

  3. 50 CFR 23.25 - What additional information is required on a non-Party CITES document?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false What additional information is required on a non-Party CITES document? 23.25 Section 23.25 Wildlife and Fisheries UNITED STATES FISH AND..., BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) CONVENTION ON INTERNATIONAL...

  4. 50 CFR 23.25 - What additional information is required on a non-Party CITES document?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false What additional information is required on a non-Party CITES document? 23.25 Section 23.25 Wildlife and Fisheries UNITED STATES FISH AND..., BARTER, EXPORTATION, AND IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) CONVENTION ON INTERNATIONAL...

  5. 12 CFR 516.220 - If OTS requests additional information to complete my application, how will it process my...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... complete my application, how will it process my application? 516.220 Section 516.220 Banks and Banking... Standard Treatment § 516.220 If OTS requests additional information to complete my application, how will it... your response. OTS will notify you that it has extended the period before the end of the initial...

  6. 12 CFR 116.220 - If the OCC requests additional information to complete my application, how will it process my...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... complete my application, how will it process my application? 116.220 Section 116.220 Banks and Banking... Treatment § 116.220 If the OCC requests additional information to complete my application, how will it... that it has extended the period before the end of the initial 15-day period and will briefly...

  7. 12 CFR 516.220 - If OTS requests additional information to complete my application, how will it process my...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... complete my application, how will it process my application? 516.220 Section 516.220 Banks and Banking... Standard Treatment § 516.220 If OTS requests additional information to complete my application, how will it... your response. OTS will notify you that it has extended the period before the end of the initial...

  8. 12 CFR 390.128 - If the FDIC requests additional information to complete my application, how will it process my...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... complete my application, how will it process my application? 390.128 Section 390.128 Banks and Banking... additional information to complete my application, how will it process my application? (a) You may use the... will notify you that it has extended the period before the end of the initial 15-day period and...

  9. Inclusion of Additional Plant Species and Trait Information in Dynamic Vegetation Modeling of Arctic Tundra and Boreal Forest Ecosystem

    NASA Astrophysics Data System (ADS)

    Euskirchen, E. S.; Patil, V.; Roach, J.; Griffith, B.; McGuire, A. D.

    2015-12-01

    Dynamic vegetation models (DVMs) have been developed to model the ecophysiological characteristics of plant functional types in terrestrial ecosystems. They have frequently been used to answer questions pertaining to processes such as disturbance, plant succession, and community composition under historical and future climate scenarios. While DVMs have proved useful in these types of applications, it has often been questioned if additional detail, such as including plant dynamics at the species-level and/or including species-specific traits would make these models more accurate and/or broadly applicable. A sub-question associated with this issue is, 'How many species, or what degree of functional diversity, should we incorporate to sustain ecosystem function in modeled ecosystems?' Here, we focus on how the inclusion of additional plant species and trait information may strengthen dynamic vegetation modeling in applications pertaining to: (1) forage for caribou in northern Alaska, (2) above- and belowground carbon storage in the boreal forest and lake margin wetlands of interior Alaska, and (3) arctic tundra and boreal forest leaf phenology. While the inclusion of additional information generally proved valuable in these three applications, this additional detail depends on field data that may not always be available and may also result in increased computational complexity. Therefore, it is important to assess these possible limitations against the perceived need for additional plant species and trait information in the development and application of dynamic vegetation models.

  10. Tautomers of a Fluorescent G Surrogate and Their Distinct Photophysics Provide Additional Information Channels.

    PubMed

    Sholokh, Marianna; Improta, Roberto; Mori, Mattia; Sharma, Rajhans; Kenfack, Cyril; Shin, Dongwon; Voltz, Karine; Stote, Roland H; Zaporozhets, Olga A; Botta, Maurizio; Tor, Yitzhak; Mély, Yves

    2016-07-01

    Thienoguanosine ((th) G) is an isomorphic nucleoside analogue acting as a faithful fluorescent substitute of G, with respectable quantum yield in oligonucleotides. Photophysical analysis of (th) G reveals the existence of two ground-state tautomers with significantly shifted absorption and emission wavelengths, and high quantum yield in buffer. Using (TD)-DFT calculations, the tautomers were identified as the H1 and H3 keto-amino tautomers. When incorporated into the loop of (-)PBS, the (-)DNA copy of the HIV-1 primer binding site, both tautomers are observed and show differential sensitivity to protein binding. The red-shifted H1 tautomer is strongly favored in matched (-)/(+)PBS duplexes, while the relative emission of the H3 tautomer can be used to detect single nucleotide polymorphisms. These tautomers and their distinct environmental sensitivity provide unprecedented information channels for analyzing G residues in oligonucleotides and their complexes.

  11. Extracting additional risk managers information from a risk assessment of Listeria monocytogenes in deli meats.

    PubMed

    Pérez-Rodríguez, F; van Asselt, E D; Garcia-Gimeno, R M; Zurera, G; Zwietering, M H

    2007-05-01

    The risk assessment study of Listeria monocytogenes in ready-to-eat foods conducted by the U.S. Food and Drug Administration is an example of an extensive quantitative microbiological risk assessment that could be used by risk analysts and other scientists to obtain information and by managers and stakeholders to make decisions on food safety management. The present study was conducted to investigate how detailed sensitivity analysis can be used by assessors to extract more information on risk factors and how results can be communicated to managers and stakeholders in an understandable way. The extended sensitivity analysis revealed that the extremes at the right side of the dose distribution (at consumption, 9 to 11.5 log CFU per serving) were responsible for most of the cases of listeriosis simulated. For concentration at retail, values below the detection limit of 0.04 CFU/g and the often used limit for L. monocytogenes of 100 CFU/g (also at retail) were associated with a high number of annual cases of listeriosis (about 29 and 82%, respectively). This association can be explained by growth of L. monocytogenes at both average and extreme values of temperature and time, indicating that a wide distribution can lead to high risk levels. Another finding is the importance of the maximal population density (i.e., the maximum concentration of L. monocytogenes assumed at a certain temperature) for accurately estimating the risk of infection by opportunistic pathogens such as L. monocytogenes. According to the obtained results, mainly concentrations corresponding to the highest maximal population densities caused risk in the simulation. However, sensitivity analysis applied to the uncertainty parameters revealed that prevalence at retail was the most important source of uncertainty in the model.

  12. Cognitive science as an interface between rational and mechanistic explanation.

    PubMed

    Chater, Nick

    2014-04-01

    Cognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation--as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces.

  13. A new species of Neparholaspis (Acari: Parholaspididae) from Russia, with additional information on Neparholaspis evansi Krantz, 1960.

    PubMed

    Marchenko, Irina I

    2016-01-01

    Neparholaspis dubatolovi sp. nov. is described and illustrated from adult females and males collected from litter and moss in montane forest in north-eastern Sikhote-Alin Ridge in the Far East of Russia. Additional morphological information and illustrations of Neparholaspis evansi Krantz, 1960 are provided, based on examination of a paratype. A key to the world species of Neparholaspis is provided. PMID:27615851

  14. Underreliance on mechanistic models: Comment on Ferguson (2015).

    PubMed

    Tryon, Warren W

    2016-09-01

    Ferguson (see record ) proposed that our overreliance on mechanistic models is responsible for the public's negative view of psychology. On the contrary, I claim that our explanations do not actually explain because they lack mechanism information and that is why the public has a negative view of psychology. Some of the mechanism information required to move from interpretations to explanations can be found in parallel distributed processing connectionist neural network models of psychology and behavior. (PsycINFO Database Record PMID:27571530

  15. Conceptualization and analysis of mechanistic studies.

    PubMed

    Aickin, Mikel

    2007-01-01

    Much recent attention has been given to the priority for doing "mechanistic studies" of complementary and alternative medicine (CAM) modalities. A preference for such studes has been clearly indicated by the National Center for Complementary and Alternative Medicine program of funding for CAM research. It is, however, difficult to find canons by which "mechanistic" studies should be analyzed, and even harder to find a good definition of "mechanism." Social scientists have well-developed ways of approaching these issues, but their methods suffer from a fatal flaw, the ecologic mechanistic fallacy. Basic scientists fare even worse, often conducting mechanistic studies that may have no plausible mechanistic content, and that also commit the ecologic mechanistic fallacy. More methodological work on the concept of mechanism is needed at a fundamental level.

  16. HTGR Mechanistic Source Terms White Paper

    SciTech Connect

    Wayne Moe

    2010-07-01

    The primary purposes of this white paper are: (1) to describe the proposed approach for developing event specific mechanistic source terms for HTGR design and licensing, (2) to describe the technology development programs required to validate the design methods used to predict these mechanistic source terms and (3) to obtain agreement from the NRC that, subject to appropriate validation through the technology development program, the approach for developing event specific mechanistic source terms is acceptable

  17. Rational and Mechanistic Perspectives on Reinforcement Learning

    ERIC Educational Resources Information Center

    Chater, Nick

    2009-01-01

    This special issue describes important recent developments in applying reinforcement learning models to capture neural and cognitive function. But reinforcement learning, as a theoretical framework, can apply at two very different levels of description: "mechanistic" and "rational." Reinforcement learning is often viewed in mechanistic terms--as…

  18. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems

    PubMed Central

    Transtrum, Mark K.; Qiu, Peng

    2016-01-01

    The inherent complexity of biological systems gives rise to complicated mechanistic models with a large number of parameters. On the other hand, the collective behavior of these systems can often be characterized by a relatively small number of phenomenological parameters. We use the Manifold Boundary Approximation Method (MBAM) as a tool for deriving simple phenomenological models from complicated mechanistic models. The resulting models are not black boxes, but remain expressed in terms of the microscopic parameters. In this way, we explicitly connect the macroscopic and microscopic descriptions, characterize the equivalence class of distinct systems exhibiting the same range of collective behavior, and identify the combinations of components that function as tunable control knobs for the behavior. We demonstrate the procedure for adaptation behavior exhibited by the EGFR pathway. From a 48 parameter mechanistic model, the system can be effectively described by a single adaptation parameter τ characterizing the ratio of time scales for the initial response and recovery time of the system which can in turn be expressed as a combination of microscopic reaction rates, Michaelis-Menten constants, and biochemical concentrations. The situation is not unlike modeling in physics in which microscopically complex processes can often be renormalized into simple phenomenological models with only a few effective parameters. The proposed method additionally provides a mechanistic explanation for non-universal features of the behavior. PMID:27187545

  19. 43 CFR 3276.13 - What additional information must I give BLM in the monthly report for flash and dry steam...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... BLM in the monthly report for flash and dry steam facilities? 3276.13 Section 3276.13 Public Lands... What additional information must I give BLM in the monthly report for flash and dry steam facilities? In addition to the regular monthly report information required by § 3276.12, send to BLM: (a)...

  20. 43 CFR 3276.13 - What additional information must I give BLM in the monthly report for flash and dry steam...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... BLM in the monthly report for flash and dry steam facilities? 3276.13 Section 3276.13 Public Lands... What additional information must I give BLM in the monthly report for flash and dry steam facilities? In addition to the regular monthly report information required by § 3276.12, send to BLM: (a)...

  1. 43 CFR 3276.13 - What additional information must I give BLM in the monthly report for flash and dry steam...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... BLM in the monthly report for flash and dry steam facilities? 3276.13 Section 3276.13 Public Lands... What additional information must I give BLM in the monthly report for flash and dry steam facilities? In addition to the regular monthly report information required by § 3276.12, send to BLM: (a)...

  2. 43 CFR 3276.13 - What additional information must I give BLM in the monthly report for flash and dry steam...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... BLM in the monthly report for flash and dry steam facilities? 3276.13 Section 3276.13 Public Lands... What additional information must I give BLM in the monthly report for flash and dry steam facilities? In addition to the regular monthly report information required by § 3276.12, send to BLM: (a)...

  3. The effects of practice on speed of information processing using the Adjusting-Paced Serial Addition Test (Adjusting-PSAT) and the Computerized Tests of Information Processing (CTIP).

    PubMed

    Baird, B J; Tombaugh, Thomas N; Francis, M

    2007-01-01

    Three experiments were conducted to determine the effects of practice on the Adjusting-Paced Serial Addition Task (Adjusting-PSAT) (Tombaugh, 1999) and the Computerized Tests of Information Processing (CTIP) (Tombaugh & Rees, 2000). The Adjusting-PSAT is a computerized modification of the Paced Auditory Serial Addition Test (PASAT) (Gronwall, 1977) that makes the interval between digits contingent on the correctness of the response. This titration procedure permits a threshold value to be derived that represents the shortest presentation interval in which a person can process the digits to produce the correct sum. The CTIP consists of three reaction time tests that are progressively more difficult. Results showed that robust practice effects occurred with the Adjusting-PSAT, with the greatest increase in performance occurring on the first retest trial. Practice effects were equally prominent regardless of whether the first retest trial occurred 20A min, 1 week, or 3 months after the first administration. These gains were maintained for periods up to 6 months and were independent of modality of presentation (visual or auditory) and type of number list (easy or hard). In contrast to the findings with the Adjusting-PSAT, only minimal practice effects were observed with the CTIP. The major clinical implication of the study is that the high reliability coefficients for the CTIP, the lack of anxiety associated with its administration, and its insensitivity to variables such as numerical and verbal ability make the CTIP ideally suited for the serial evaluation of cognitive status. These characteristics also make the CTIP a viable alternative to the Adjusting-PSAT or PASAT for measuring speed of information processing. If the Adjusting-PSAT is administered repeatedly in clinical evaluations, a "dual baseline" or "run in" procedure should be used, with the second administration serving as the baseline measurement. PMID:17523883

  4. Negative mechanistic reasoning in medical intervention assessment.

    PubMed

    Jerkert, Jesper

    2015-12-01

    Traditionally, mechanistic reasoning has been assigned a negligible role in standard EBM (evidence-based medicine) literature, although some recent authors have argued for an upgrade. Even so, the mechanistic reasoning that has received attention has almost exclusively been positive--both in an epistemic sense of claiming that there is a mechanistic chain and in a health-related sense of there being claimed benefits for the patient. Negative mechanistic reasoning has been neglected, both in the epistemic and in the health-related sense. I distinguish three main types of negative mechanistic reasoning and subsume them under a new definition of mechanistic reasoning in the context of assessing medical interventions. This definition is wider than a previous suggestion in the literature. Each negative type corresponds to a range of evidential strengths, and it is argued that there are differences with respect to typical evidential strengths. The variety of negative mechanistic reasoning should be acknowledged in EBM, and it presents a serious challenge to proponents of so-called medical hierarchies of evidence. PMID:26597869

  5. Modeling Bird Migration under Climate Change: A Mechanistic Approach

    NASA Technical Reports Server (NTRS)

    Smith, James A.

    2009-01-01

    behavior can be maintained over increasing and sustained environmental change. Also, the problem is much more complex than described by the current processes captured in our model. We have taken some important and interesting steps, and our model does demonstrate how local scale information about individual stop-over sites can be linked into the migratory flyway as a whole. We are incorporating additional, species specific, mechanistic processes to better reflect different climate change scenarios

  6. Somatodendritic dopamine release: recent mechanistic insights

    PubMed Central

    Rice, Margaret E.; Patel, Jyoti C.

    2015-01-01

    Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K+ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca2+ dependence of release and the potential role of exocytotic proteins. PMID:26009764

  7. Answering evolutionary questions: A guide for mechanistic biologists.

    PubMed

    Masel, Joanna; Promislow, Daniel E L

    2016-07-01

    The questions and methods of molecular biology and evolutionary biology are clearly distinct, yet a unified approach can lead to deep insights. Unfortunately, attempts to unify these approaches are fraught with pitfalls. In this informal series of questions and answers, we offer the mechanistically oriented biologist a set of steps to come up with evolutionarily reasonable and meaningful hypotheses. We emphasize the critical power and importance of carefully constructed null hypotheses, and we illustrate our ideas with examples representing a range of topics, from the biology of aging, to protein structure, to speciation, and more. We also stress the importance of mathematics as the lingua franca for biologists of all stripes, and encourage mechanistic biologists to seek out quantitative collaborators to build explicit mathematical models, making their assumptions explicit, and their logic clear and testable. Biologists in all realms of inquiry stand to gain from strong bridges between our disciplines. PMID:27151396

  8. 36 CFR 1281.12 - What information must be provided to NARA for its report to Congress on a change or addition to a...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... provided to NARA for its report to Congress on a change or addition to a Presidential library facility... ADMINISTRATION NARA FACILITIES PRESIDENTIAL LIBRARY FACILITIES § 1281.12 What information must be provided to NARA for its report to Congress on a change or addition to a Presidential library facility? (a)...

  9. 36 CFR 1281.12 - What information must be provided to NARA for its report to Congress on a change or addition to a...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... provided to NARA for its report to Congress on a change or addition to a Presidential library facility... ADMINISTRATION NARA FACILITIES PRESIDENTIAL LIBRARY FACILITIES § 1281.12 What information must be provided to NARA for its report to Congress on a change or addition to a Presidential library facility? (a)...

  10. 36 CFR 1281.12 - What information must be provided to NARA for its report to Congress on a change or addition to a...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... provided to NARA for its report to Congress on a change or addition to a Presidential library facility... ADMINISTRATION NARA FACILITIES PRESIDENTIAL LIBRARY FACILITIES § 1281.12 What information must be provided to NARA for its report to Congress on a change or addition to a Presidential library facility? (a)...

  11. 36 CFR 1281.12 - What information must be provided to NARA for its report to Congress on a change or addition to a...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... provided to NARA for its report to Congress on a change or addition to a Presidential library facility... ADMINISTRATION NARA FACILITIES PRESIDENTIAL LIBRARY FACILITIES § 1281.12 What information must be provided to NARA for its report to Congress on a change or addition to a Presidential library facility? (a)...

  12. 76 FR 64366 - Notice of Proposed Information Collection for Public Comment: Additional On-Site Data Collection...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-18

    ... Collection for the Housing Choice Voucher Program Administrative Fee Study AGENCY: Office of the Policy... lists the following information: Title of Proposal: Housing Choice Voucher Program Administrative...

  13. 33 CFR 148.108 - What if a Federal or State agency or other interested party requests additional information?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... impact statement or environmental assessment. MARAD will consider the request before making a final... time and effort required by the applicant in gathering the information will result in an undue delay...

  14. Mechanistic species distribution modelling as a link between physiology and conservation

    PubMed Central

    Evans, Tyler G.; Diamond, Sarah E.; Kelly, Morgan W.

    2015-01-01

    Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and

  15. Mechanistic species distribution modelling as a link between physiology and conservation.

    PubMed

    Evans, Tyler G; Diamond, Sarah E; Kelly, Morgan W

    2015-01-01

    Climate change conservation planning relies heavily on correlative species distribution models that estimate future areas of occupancy based on environmental conditions encountered in present-day ranges. The approach benefits from rapid assessment of vulnerability over a large number of organisms, but can have poor predictive power when transposed to novel environments and reveals little in the way of causal mechanisms that define changes in species distribution or abundance. Having conservation planning rely largely on this single approach also increases the risk of policy failure. Mechanistic models that are parameterized with physiological information are expected to be more robust when extrapolating distributions to future environmental conditions and can identify physiological processes that set range boundaries. Implementation of mechanistic species distribution models requires knowledge of how environmental change influences physiological performance, and because this information is currently restricted to a comparatively small number of well-studied organisms, use of mechanistic modelling in the context of climate change conservation is limited. In this review, we propose that the need to develop mechanistic models that incorporate physiological data presents an opportunity for physiologists to contribute more directly to climate change conservation and advance the field of conservation physiology. We begin by describing the prevalence of species distribution modelling in climate change conservation, highlighting the benefits and drawbacks of both mechanistic and correlative approaches. Next, we emphasize the need to expand mechanistic models and discuss potential metrics of physiological performance suitable for integration into mechanistic models. We conclude by summarizing other factors, such as the need to consider demography, limiting broader application of mechanistic models in climate change conservation. Ideally, modellers, physiologists and

  16. Mechanistic modelling and mechanistic monitoring: simulation and shadowgraph imaging of particulate dissolution in the flow-through apparatus.

    PubMed

    D'arcy, Deirdre M; Persoons, Tim

    2011-03-01

    Accurate mechanistic modelling of a complex system requires insight into the process being simulated, in addition to a theoretical 'first-principles' approach. The current work uses a numerical mechanistic model to simulate dissolution of a particulate system in the flow-through dissolution apparatus. A shadowgraph imaging method is also used to monitor the dissolution process, providing real-time estimates of particle motion, number and total dissolution time. Experimental dissolution studies of ibuprofen particles are used to assess the accuracy of the model. The numerical model adequately predicts the ibuprofen particle dissolution rate at 16 mL min(-1) . Parameter sensitivity analysis identified dissolution test circumstances requiring more, or less, accuracy in the particle size and density calculations. The shadowgraph imaging method successfully determined the total dissolution time and decreasing particle numbers over time. The images confirmed the pulsing particle motion of the numerical model but revealed some more complex velocity patterns, assisting numerical model development. Further optimisation of the sampling window is required to capture all relevant particle motion and changing particle size distribution. A mechanistic model can successfully simulate particulate dissolution in the flow-through apparatus, and when used along with shadowgraph imaging, can give valuable insight into the dissolution process mechanisms and environment. PMID:20848646

  17. 45 CFR 1351.19 - What additional information should an applicant or grantee have about a Runaway and Homeless...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Homeless Youth Program grants. These include: (1) The provisions of 45 CFR part 74 pertaining to the Administration of Grants; (2) The provisions of 45 CFR part 16, Departmental Grants Appeal Process, and the provisions of Informal Grant Appeal Procedures (Indirect Costs) in volume 45 CFR part 75; (3) The...

  18. 45 CFR 1351.19 - What additional information should an applicant or grantee have about a Runaway and Homeless...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Homeless Youth Program grants. These include: (1) The provisions of 45 CFR part 74 pertaining to the Administration of Grants; (2) The provisions of 45 CFR part 16, Departmental Grants Appeal Process, and the provisions of Informal Grant Appeal Procedures (Indirect Costs) in volume 45 CFR part 75; (3) The...

  19. 45 CFR 1351.19 - What additional information should an applicant or grantee have about a Runaway and Homeless...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Homeless Youth Program grants. These include: (1) The provisions of 45 CFR part 74 pertaining to the Administration of Grants; (2) The provisions of 45 CFR part 16, Departmental Grants Appeal Process, and the provisions of Informal Grant Appeal Procedures (Indirect Costs) in volume 45 CFR part 75; (3) The...

  20. 45 CFR 1351.19 - What additional information should an applicant or grantee have about a Runaway and Homeless...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Homeless Youth Program grants. These include: (1) The provisions of 45 CFR part 74 pertaining to the Administration of Grants; (2) The provisions of 45 CFR part 16, Departmental Grants Appeal Process, and the provisions of Informal Grant Appeal Procedures (Indirect Costs) in volume 45 CFR part 75; (3) The...

  1. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  2. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  3. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  4. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  5. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  6. Space Takes Time: Concentration Dependent Output Codes from Primary Olfactory Networks Rapidly Provide Additional Information at Defined Discrimination Thresholds.

    PubMed

    Daly, Kevin C; Bradley, Samual; Chapman, Phillip D; Staudacher, Erich M; Tiede, Regina; Schachtner, Joachim

    2015-01-01

    As odor concentration increases, primary olfactory network representations expand in spatial distribution, temporal complexity and duration. However, the direct relationship between concentration dependent odor representations and the psychophysical thresholds of detection and discrimination is poorly understood. This relationship is absolutely critical as thresholds signify transition points whereby representations become meaningful to the organism. Here, we matched stimulus protocols for psychophysical assays and intracellular recordings of antennal lobe (AL) projection neurons (PNs) in the moth Manduca sexta to directly compare psychophysical thresholds and the output representations they elicit. We first behaviorally identified odor detection and discrimination thresholds across an odor dilution series for a panel of structurally similar odors. We then characterized spatiotemporal spiking patterns across a population of individually filled and identified AL PNs in response to those odors at concentrations below, at, and above identified thresholds. Using spatial and spatiotemporal based analyses we observed that each stimulus produced unique representations, even at sub-threshold concentrations. Mean response latency did not decrease and the percent glomerular activation did not increase with concentration until undiluted odor. Furthermore, correlations between spatial patterns for odor decreased, but only significantly with undiluted odor. Using time-integrated Euclidean distance (ED) measures, we determined that added spatiotemporal information was present at the discrimination but not detection threshold. This added information was evidenced by an increase in integrated distance between the sub-detection and discrimination threshold concentrations (of the same odor) that was not present in comparison of the sub-detection and detection threshold. After consideration of delays for information to reach the AL we find that it takes ~120-140 ms for the AL to

  7. Space Takes Time: Concentration Dependent Output Codes from Primary Olfactory Networks Rapidly Provide Additional Information at Defined Discrimination Thresholds

    PubMed Central

    Daly, Kevin C.; Bradley, Samual; Chapman, Phillip D.; Staudacher, Erich M.; Tiede, Regina; Schachtner, Joachim

    2016-01-01

    As odor concentration increases, primary olfactory network representations expand in spatial distribution, temporal complexity and duration. However, the direct relationship between concentration dependent odor representations and the psychophysical thresholds of detection and discrimination is poorly understood. This relationship is absolutely critical as thresholds signify transition points whereby representations become meaningful to the organism. Here, we matched stimulus protocols for psychophysical assays and intracellular recordings of antennal lobe (AL) projection neurons (PNs) in the moth Manduca sexta to directly compare psychophysical thresholds and the output representations they elicit. We first behaviorally identified odor detection and discrimination thresholds across an odor dilution series for a panel of structurally similar odors. We then characterized spatiotemporal spiking patterns across a population of individually filled and identified AL PNs in response to those odors at concentrations below, at, and above identified thresholds. Using spatial and spatiotemporal based analyses we observed that each stimulus produced unique representations, even at sub-threshold concentrations. Mean response latency did not decrease and the percent glomerular activation did not increase with concentration until undiluted odor. Furthermore, correlations between spatial patterns for odor decreased, but only significantly with undiluted odor. Using time-integrated Euclidean distance (ED) measures, we determined that added spatiotemporal information was present at the discrimination but not detection threshold. This added information was evidenced by an increase in integrated distance between the sub-detection and discrimination threshold concentrations (of the same odor) that was not present in comparison of the sub-detection and detection threshold. After consideration of delays for information to reach the AL we find that it takes ~120–140 ms for the AL to

  8. Mechanistic studies on cyclohexanone oxygenase.

    PubMed

    Ryerson, C C; Ballou, D P; Walsh, C

    1982-05-25

    The bacterial flavoprotein monooxygenase carries out an oxygen insertion reaction on cyclohexanone, with ring expansion to form the seven-membered cyclic product epsilon-caprolactone, a transformation quite distinct from the phenol leads to catechol transformation carried out by the bacterial flavoprotein aromatic hydroxylases. Cyclohexanone oxygenase catalysis involves the four-electron of O2 at the expense of a two-electron oxidation of NADPH, concomitant with a two-electron oxidation of cyclohexanone to epsilon-caprolactone. NADPH oxidase activity is fully coupled with oxygen transfer to substrate. Steady-state kinetic assays demonstrate a ter-ter mechanism for this enzyme. Pre-steady-state kinetic assays demonstrate the participation of a 4a-hydroperoxyflavin intermediate during catalysis. In addition to its ketolactonizing activity, cyclohexanone oxygenase carries out S-oxygenation of thiane to thiane 1-oxide, a reaction which represents a nucleophilic displacement by the sulfur upon the terminal oxygen of the hydroperoxide. This is in contrast to cyclohexanone oxygenations where the flavin hydroperoxide acts as a nucleophile. In addition, a stable apoenzyme form is accessible and can be reconstituted with various FAD analogues with up to 100% recovery of enzyme activity. The accumulated results presented here support a Baeyer-Villiger rearrangement mechanism for the enzymatic oxygenation of cyclohexanone.

  9. [Mechanistic examination of organometallic electron transfer reactions: Annual report, 1989

    SciTech Connect

    Not Available

    1989-12-31

    Our mechanistic examination of electron transfer reactions between organometallic complexes has required data from our stopped-flow infrared spectrophotometer that was constructed in the first year. Our research on organometallic electron transfer reaction mechanisms was recognized by an invitation to the Symposium on Organometallic Reaction Mechanisms at the National ACS meeting in Miami. We have obtained a reasonable understanding of the electron transfer reactions between metal cations and anions and between metal carbonyl anions and metal carbonyl dimers. In addition we have begun to obtain data on the outer sphere electron transfer between metal carbonyl anions and coordination complexes and on reactions involving cluster anions.

  10. Exploring Organic Mechanistic Puzzles with Molecular Modeling

    ERIC Educational Resources Information Center

    Horowitz, Gail; Schwartz, Gary

    2004-01-01

    The molecular modeling was used to reinforce more general skills such as deducing and drawing reaction mechanisms, analyzing reaction kinetics and thermodynamics and drawing reaction coordinate energy diagrams. This modeling was done through the design of mechanistic puzzles, involving reactions not familiar to the students.

  11. The Substitution-Elimination Mechanistic Disc Method

    ERIC Educational Resources Information Center

    Buonora, Paul T.; Yu Jin Lim

    2004-01-01

    A method designed to facilitate prediction of mechanism and products by developing critical thinking skills and reducing memorization is presented. The mechanistic disc method requiring students to utilize their understanding of charge stabilization, structural organic chemistry, and the fundamental mechanisms of aliphatic substitution and…

  12. Mechanistic Indicators of Childhood Asthma (MICA) Study

    EPA Science Inventory

    The Mechanistic Indicators of Childhood Asthma (MICA) Study has been designed to incorporate state-of-the-art technologies to examine the physiological and environmental factors that interact to increase the risk of asthmatic responses. MICA is primarily a clinically-bases obser...

  13. Testing mechanistic models of growth in insects.

    PubMed

    Maino, James L; Kearney, Michael R

    2015-11-22

    Insects are typified by their small size, large numbers, impressive reproductive output and rapid growth. However, insect growth is not simply rapid; rather, insects follow a qualitatively distinct trajectory to many other animals. Here we present a mechanistic growth model for insects and show that increasing specific assimilation during the growth phase can explain the near-exponential growth trajectory of insects. The presented model is tested against growth data on 50 insects, and compared against other mechanistic growth models. Unlike the other mechanistic models, our growth model predicts energy reserves per biomass to increase with age, which implies a higher production efficiency and energy density of biomass in later instars. These predictions are tested against data compiled from the literature whereby it is confirmed that insects increase their production efficiency (by 24 percentage points) and energy density (by 4 J mg(-1)) between hatching and the attainment of full size. The model suggests that insects achieve greater production efficiencies and enhanced growth rates by increasing specific assimilation and increasing energy reserves per biomass, which are less costly to maintain than structural biomass. Our findings illustrate how the explanatory and predictive power of mechanistic growth models comes from their grounding in underlying biological processes.

  14. Evolving biosynthetic tangos negotiate mechanistic landscapes.

    PubMed

    Austin, Michael B; O'Maille, Paul E; Noel, Joseph P

    2008-04-01

    The dependence of polyketide synthase and terpene cyclase mechanistic adaptation on the chemistry of their oligomeric substrates illuminates a convergent evolutionary strategy for shaping cyclization in these otherwise disparate reactions. Evolution of these enzyme families relies on rhythmic tangos, in which the enzymes and substrates together determine product outcome by negotiating decision networks governing intrinsic and induced chemical reactivities. PMID:18347585

  15. Advanced Reach Tool (ART): development of the mechanistic model.

    PubMed

    Fransman, Wouter; Van Tongeren, Martie; Cherrie, John W; Tischer, Martin; Schneider, Thomas; Schinkel, Jody; Kromhout, Hans; Warren, Nick; Goede, Henk; Tielemans, Erik

    2011-11-01

    This paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure for workers sharing similar operational conditions across different industries and locations in Europe. The ART mechanistic model is based on a conceptual framework that adopts a source receptor approach, which describes the transport of a contaminant from the source to the receptor and defines seven independent principal modifying factors: substance emission potential, activity emission potential, localized controls, segregation, personal enclosure, surface contamination, and dispersion. ART currently differentiates between three different exposure types: vapours, mists, and dust (fumes, fibres, and gases are presently excluded). Various sources were used to assign numerical values to the multipliers to each modifying factor. The evidence used to underpin this assessment procedure was based on chemical and physical laws. In addition, empirical data obtained from literature were used. Where this was not possible, expert elicitation was applied for the assessment procedure. Multipliers for all modifying factors were peer reviewed by leading experts from industry, research institutes, and public authorities across the globe. In addition, several workshops with experts were organized to discuss the proposed exposure multipliers. The mechanistic model is a central part of the ART tool and with advancing knowledge on exposure, determinants will require updates and refinements on a continuous basis, such as the effect of worker behaviour on personal exposure, 'best practice' values that describe the maximum achievable effectiveness of control measures, the intrinsic emission potential of various solid objects (e.g. metal, glass, plastics, etc.), and extending the applicability domain to certain types of exposures (e.g. gas, fume, and fibre exposure).

  16. Additional evidence that rosacea pathogenesis may involve demodex: new information from the topical efficacy of ivermectin and praziquantel.

    PubMed

    Abokwidir, Manal; Fleischer, Alan B

    2015-09-01

    Additional evidence that Demodex folliculorum may contribute to the pathogenesis of papulopustular rosacea are new studies of two topical antiparasitic agents. Ivermectin and praziquantel have recently been shown to be effective in decreasing the severity of papulopustular rosacea. These two agents significantly differ in molecular structure, but yield similar antiparasitic mechanisms of action. Higher numbers of Demodex mites are found in the skin of patients with rosacea than in people with normal skin. If Demodex play a role in pathogenesis, then hypersensitivity to the mites, their flora, or their products could explain the observed efficacy of antidemodectic therapy. PMID:26437294

  17. EPA evaluation of the SYNERGY-1 fuel additive under Section 511 of the Motor Vehicle Information and Cost Savings Act. Technical report

    SciTech Connect

    Syria, S.L.

    1981-06-01

    This document announces the conclusions of the EPA evaluation of the 'SYNERGY-1' device under provisions of Section 511 of the Motor Vehicle Information and Cost Savings Act. This additive is intended to improve fuel economy and exhaust emission levels of two and four cycle gasoline fueled engines.

  18. Informal Reading-Thinking Inventory: An Informal Reading Inventory (IRI) with Options for Assessing Additional Elements of Higher-Order Literacy.

    ERIC Educational Resources Information Center

    Manzo, Anthony V.; And Others

    Focusing on better assessing the thinking, or meaning-making, aspects of reading that are emphasized in current views of the reading process, this book presents the Informal Reading-Thinking Inventory (IR-TI) which offers options to enhance assessment beyond assessing students' listening level, oral reading of words, and basic comprehension. The…

  19. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    PubMed

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

  20. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    PubMed Central

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  1. Observability analysis of biochemical process models as a valuable tool for the development of mechanistic soft sensors.

    PubMed

    Golabgir, Aydin; Hoch, Thomas; Zhariy, Mariya; Herwig, Christoph

    2015-01-01

    By enabling the estimation of difficult-to-measure target variables using available indirect measurements, mechanistic soft sensors have become important tools for various bioprocess monitoring and control scenarios. Despite promising higher process efficiencies and increased process understanding, widespread application of soft sensors has been stalled by uncertainty about the feasibility and reliability of their estimations given present process analytical constraints. Observability analysis can provide an indication of the possibility and reliability of soft sensor estimations by analyzing the structural properties of first-principle (mechanistic) models. In addition, it can provide a criteria for selection of suitable measurement methods with respect to their information content; thereby leading to successful implementation of soft sensors in bioprocess development and manufacturing environments. We demonstrate the utility of observability analysis for two classes of upstream bioprocesses: the processes involving growth and ethanol formation by Saccharomyces cerevisiae and the process of penicillin production by Penicillium chrysogenum. Results obtained from laboratory-scale cultivations in addition to in-silico experiments enable a comparison of theoretical aspects of observability analysis and the real-life performance of soft sensors. By taking the expected error of measurements provided to the soft sensor into account, an innovative scaling approach facilitates a higher degree of comparability of observability results among various measurement configurations and process conditions.

  2. Observability analysis of biochemical process models as a valuable tool for the development of mechanistic soft sensors.

    PubMed

    Golabgir, Aydin; Hoch, Thomas; Zhariy, Mariya; Herwig, Christoph

    2015-01-01

    By enabling the estimation of difficult-to-measure target variables using available indirect measurements, mechanistic soft sensors have become important tools for various bioprocess monitoring and control scenarios. Despite promising higher process efficiencies and increased process understanding, widespread application of soft sensors has been stalled by uncertainty about the feasibility and reliability of their estimations given present process analytical constraints. Observability analysis can provide an indication of the possibility and reliability of soft sensor estimations by analyzing the structural properties of first-principle (mechanistic) models. In addition, it can provide a criteria for selection of suitable measurement methods with respect to their information content; thereby leading to successful implementation of soft sensors in bioprocess development and manufacturing environments. We demonstrate the utility of observability analysis for two classes of upstream bioprocesses: the processes involving growth and ethanol formation by Saccharomyces cerevisiae and the process of penicillin production by Penicillium chrysogenum. Results obtained from laboratory-scale cultivations in addition to in-silico experiments enable a comparison of theoretical aspects of observability analysis and the real-life performance of soft sensors. By taking the expected error of measurements provided to the soft sensor into account, an innovative scaling approach facilitates a higher degree of comparability of observability results among various measurement configurations and process conditions. PMID:26404038

  3. Grignard Reaction of an Epoxide: A Mechanistic Study

    NASA Astrophysics Data System (ADS)

    Ciaccio, James A.; Volpi, Sabrina; Clarke, Ransford

    1996-12-01

    Addition of PhMgBr to styrene oxide (1) affords a mixture of 2,2-diphenylethanol (3) and 1,2-diphenylethanol (6) (3:6 = 1:3); reversing the order of addition inverts the ratio of 3 to 6 formed (3:6 = 2:1). Students identify 3 and 6 by TLC comparison with authentic samples which they prepare by independent synthesis (hydride reduction of the corresponding carbonyl compounds), and establish the ratios of 3 to 6 by a combination of 1H and 13C NMR spectroscopies. This undergraduate experiment serves as an interesting alternative to more traditional Grignard experiments and is an excellent vehicle for a "discovery-based" experiment in which students are introduced to epoxide chemistry, share their laboratory data and make mechanistic conclusions from their experimental results. Unlike most undergraduate Grignard experiments which are performed merely for the sake of illustrating a textbook reaction, this Grignard synthesis is performed to probe the reactivity of styrene oxide. Students are required to analyze their products by TLC and NMR spectroscopy (instead of just submitting them for a grade) in order to obtain the data necessary for making mechanistic conclusions.

  4. Mechanistic fracture criteria for the failure of human cortical bone

    SciTech Connect

    Nalla, Ravi K.; Kinney, John H.; Ritchie, Robert O.

    2002-12-13

    A mechanistic understanding of fracture in human bone is critical to predicting fracture risk associated with age and disease. Despite extensive work, a mechanistic framework for describing how the underlying microstructure affects the failure mode in bone is lacking.

  5. Mechanistic analysis of challenge-response experiments.

    PubMed

    Shotwell, M S; Drake, K J; Sidorov, V Y; Wikswo, J P

    2013-09-01

    We present an application of mechanistic modeling and nonlinear longitudinal regression in the context of biomedical response-to-challenge experiments, a field where these methods are underutilized. In this type of experiment, a system is studied by imposing an experimental challenge, and then observing its response. The combination of mechanistic modeling and nonlinear longitudinal regression has brought new insight, and revealed an unexpected opportunity for optimal design. Specifically, the mechanistic aspect of our approach enables the optimal design of experimental challenge characteristics (e.g., intensity, duration). This article lays some groundwork for this approach. We consider a series of experiments wherein an isolated rabbit heart is challenged with intermittent anoxia. The heart responds to the challenge onset, and recovers when the challenge ends. The mean response is modeled by a system of differential equations that describe a candidate mechanism for cardiac response to anoxia challenge. The cardiac system behaves more variably when challenged than when at rest. Hence, observations arising from this experiment exhibit complex heteroscedasticity and sharp changes in central tendency. We present evidence that an asymptotic statistical inference strategy may fail to adequately account for statistical uncertainty. Two alternative methods are critiqued qualitatively (i.e., for utility in the current context), and quantitatively using an innovative Monte-Carlo method. We conclude with a discussion of the exciting opportunities in optimal design of response-to-challenge experiments. PMID:23859366

  6. Does an additional structured information program during the intensive care unit stay reduce anxiety in ICU patients?: a multicenter randomized controlled trial

    PubMed Central

    2014-01-01

    Background Communication and information in order to reduce anxiety in the intensive care unit (ICU) has been described as area needing improvement. Therefore, the aim of this trial was to evaluate whether a structured information program that intensifies information given in standard care process reduces anxiety in ICU patients. Methods Multicenter, two-armed, non-blinded, parallel-group randomized controlled trial in hospitals in the cities of Marburg, Halle, and Stuttgart (Germany). The trial was performed in cardiac surgery, general surgery, and internal medicine ICUs. Two-hundred and eleven elective and non-elective ICU patients were enrolled in the study (intervention group, n = 104; control group, n = 107). The experimental intervention comprised a single episode of structured oral information that was given in addition to standard care and covered two main parts: (1) A more standardized part about predefined ICU specific aspects – mainly procedural, sensory and coping information, and (2) an individualized part about fears and questions of the patient. The control group received a non-specific episodic conversation of similar length additional to standard care. Both conversations took place at the beginning of the ICU stay and lasted 10–15 minutes. Study nurses administered both interventions. The primary outcome ICU-related anxiety (CINT-Score, 0–100 pts., higher scores indicate higher anxiety) was assessed after admission to a regular ward. Results The primary outcome could be measured in 82 intervention group participants and 90 control group participants resulting in mean values of 20.4 (SD 14.4) compared to 20.8 (SD 14.7) and a mean difference of −0.2 (CI 95% -4.5 to 4.1). Conclusions A structured information intervention additional to standard care during ICU stay had no demonstrated additional benefit compared to an unspecific communication of similar duration. Reduction of anxiety in ICU patients will probably require more continuous

  7. A mechanistic analysis of the Birch Reduction.

    PubMed

    Zimmerman, Howard E

    2012-02-21

    The Birch Reduction is one of the main reactions of organic chemistry. The reaction involves the reaction of dissolving metals in ammonia with aromatic compounds to produce 1,4-cyclohexadienes. Discovered by Arthur Birch in 1944, the reaction occupies 300 pages in Organic Reactions to describe its synthetic versatility. Thus, it is remarkable that the reaction mechanism has been so very controversial and only relatively recently has been firmly established. Perhaps this is not that surprising, since the reaction also has many unusual and esoteric mechanistic facets. Here, I provide a description of how I have applied ever-evolving levels of quantum mechanics and a novel experimental test to understand details of the mechanism and the origins of the selectivities observed in the Birch reduction. The reaction involves an initial radical anion resulting from introduction of an electron from the blue liquid ammonia solution of free electrons formed by the dissolution of Li or related metals. This radical anion is protonated by an alcohol and then further reduced to a carbanion. Finally, the carbanion is protonated using a second proton to afford a nonconjugated cyclohexadiene. The regiochemistry depends on substituents present. With 18 resonance structures in the case of anisole radical anion, prediction of the initial protonation site would seem difficult. Nevertheless, computational methods from Hückel theory through modern density functional calculations do correctly predict the site of protonation. An esoteric test established this mechanism experimentally. The nature of the carbanion also is of mechanistic interest, and the preponderance of the resonance structure shown was revealed from Hückel calculations involving variable bond orders. For the trianion from benzoic acid, parallel questions about structure are apparent, and have been answered. Some mechanistic questions are answered experimentally and some by modern computations. Recently, our mechanistic

  8. A Mechanistic Study of Arsenic (III) Rejection by Reverse Osmosis and Nanofiltration Membranes

    ERIC Educational Resources Information Center

    Suzuki, Tasuma

    2009-01-01

    Reverse osmosis/nanofiltration (RO/NF) membranes are capable to provide an effective barrier for a wide range of contaminants (including disinfection by-products precursors) in a single treatment step. However, solute rejection mechanisms by RO/NF membranes are not well understood. The lack of mechanistic information arises from experimental…

  9. MECHANISTIC DATA & CANCER RISK ASSESSMENT: THE NEED FOR QUANTITATIVE MOLECULAR ENDPOINTS

    EPA Science Inventory

    The cancer risk assessment process as currently proposed by the U.S. Environmental Protection Agency allows for the use of mechanistic data to inform the low dose tumor response in humans and in laboratory animals. The aim is to reduce the reliance on defaults that introduce a re...

  10. New web-based applications for mechanistic case diagramming

    PubMed Central

    Dee, Fred R.; Haugen, Thomas H.; Kreiter, Clarence D.

    2014-01-01

    The goal of mechanistic case diagraming (MCD) is to provide students with more in-depth understanding of cause and effect relationships and basic mechanistic pathways in medicine. This will enable them to better explain how observed clinical findings develop from preceding pathogenic and pathophysiological events. The pedagogic function of MCD is in relating risk factors, disease entities and morphology, signs and symptoms, and test and procedure findings in a specific case scenario with etiologic pathogenic and pathophysiological sequences within a flow diagram. In this paper, we describe the addition of automation and predetermined lists to further develop the original concept of MCD as described by Engelberg in 1992 and Guerrero in 2001. We demonstrate that with these modifications, MCD is effective and efficient in small group case-based teaching for second-year medical students (ratings of ~3.4 on a 4.0 scale). There was also a significant correlation with other measures of competency, with a ‘true’ score correlation of 0.54. A traditional calculation of reliability showed promising results (α =0.47) within a low stakes, ungraded environment. Further, we have demonstrated MCD's potential for use in independent learning and TBL. Future studies are needed to evaluate MCD's potential for use in medium stakes assessment or self-paced independent learning and assessment. MCD may be especially relevant in returning students to the application of basic medical science mechanisms in the clinical years. PMID:25059836

  11. Mechanistic study of a diazo dye degradation by Soybean Peroxidase

    PubMed Central

    2013-01-01

    Background Enzyme based remediation of wastewater is emerging as a novel, efficient and environmentally-friendlier approach. However, studies showing detailed mechanisms of enzyme mediated degradation of organic pollutants are not widely published. Results The present report describes a detailed study on the use of Soybean Peroxidase to efficiently degrade Trypan Blue, a diazo dye. In addition to examining various parameters that can affect the dye degradation ability of the enzyme, such as enzyme and H2O2 concentration, reaction pH and temperature, we carried out a detailed mechanistic study of Trypan Blue degradation. HPLC-DAD and LC-MS/MS studies were carried out to confirm dye degradation and analyze the intermediate metabolites and develop a detailed mechanistic dye degradation pathway. Conclusion We report that Soybean peroxidase causes Trypan Blue degradation via symmetrical azo bond cleavage and subsequent radical-initiated ring opening of the metabolites. Interestingly, our results also show that no high molecular weight polymers were produced during the peroxidase-H2O2 mediated degradation of the phenolic Trypan Blue. PMID:23711110

  12. Composite Nanomechanics: A Mechanistic Properties Prediction

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Handler, Louis M.; Manderscheid, Jane M.

    2007-01-01

    A unique mechanistic theory is described to predict the properties of nanocomposites. The theory is based on composite micromechanics with progressive substructuring down to a nanoscale slice of a nanofiber where all the governing equations are formulated. These equations hav e been programmed in a computer code. That computer code is used to predict 25 properties of a mononanofiber laminate. The results are pr esented graphically and discussed with respect to their practical sig nificance. Most of the results show smooth distributions. Results for matrix-dependent properties show bimodal through-the-thickness distr ibution with discontinuous changes from mode to mode.

  13. Composite Nanomechanics: A Mechanistic Properties Prediction

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Handler, Louis M.; Manderscheid, Jane M.

    2007-01-01

    A unique mechanistic theory is described to predict the properties of nanocomposites. The theory is based on composite micromechanics with progressive substructuring down to a nanoscale slice of a nanofiber where all the governing equations are formulated. These equations have been programmed in a computer code. That computer code is used to predict 25 properties of a mononanofiber laminate. The results are presented graphically and discussed with respect to their practical significance. Most of the results show smooth distributions. Results for matrix-dependent properties show bimodal through-the-thickness distribution with discontinuous changes from mode to mode.

  14. Mechanistic studies of carbon monoxide reduction

    SciTech Connect

    Geoffroy, G.L.

    1990-06-12

    The progress made during the current grant period (1 January 1988--1 April 1990) in three different areas of research is summarized. The research areas are: (1) oxidatively-induced double carbonylation reactions to form {alpha}-ketoacyl complexes and studies of the reactivity of the resulting compounds, (2) mechanistic studies of the carbonylation of nitroaromatics to form isocyanates, carbamates, and ureas, and (3) studies of the formation and reactivity of unusual metallacycles and alkylidene ligands supported on binuclear iron carbonyl fragments. 18 refs., 5 figs., 1 tab.

  15. Mechanistic issues concerning cancer prevention by tea catechins.

    PubMed

    Yang, Chung S; Wang, Hong

    2011-06-01

    The cancer preventive activities of tea (Camellia sinensis, Theaceae) have been demonstrated in animal models for cancers at different organ sites and suggested by some epidemiological studies. Many mechanisms for cancer prevention have been proposed based on studies in cell lines, which demonstrated the modulation of signal transduction and metabolic pathways by (-)-epigallocatechin-3-gallate (EGCG), the most abundant and active polyphenol in green tea. These molecular events may result in cellular changes, such as enhancement of apoptosis, suppression of cell proliferation, and inhibition of angiogenesis. Nevertheless, it is not known whether these are the molecular mechanisms of inhibition of carcinogenesis in animals and humans. This article discusses the key issues involved in extrapolating results from cell line studies to mechanistic information in vivo and in translating animal studies to human cancer prevention. PMID:21538856

  16. Synthetic and mechanistic aspects of titanium-mediated carbonyl olefinations

    SciTech Connect

    Petasis, N.A.; Staszewski, J.P.; Hu, Yong-Han; Lu, Shao-Po

    1995-12-31

    A new method for the olefination of carbonyl compounds with dimethyl titanocene, and other related bishydrocarbyl titanocene derivatives has been recently developed in the author`s laboratories. This process is experimentally convenient and works with various types of carbonyl compounds, including aldehydes, ketones, esters, lactones, carbonates, anhydrides, amides, imides, lactams, thioesters, selenoesters, and acylsilanes. More recent studies have focused on the scope and utility of this reaction, including mechanistic studies and synthetic applications. In addition to varying the reaction conditions, the authors have examined several mixed titanocene derivatives and have found ways for carrying out this type of olefination at room temperature, such as the use of tris(trimethylsilyl) titanacyclobutene. The authors have also employed this reaction in the modification of carbohydrates and cyclobutenediones. This olefination was also followed-up with subsequent transformations to produce carbocycles and heterocycles, including tetrahydrofurans and tetrahydropyrans.

  17. Appropriateness of mechanistic and non-mechanistic models for the application of ultrafiltration to mixed waste

    SciTech Connect

    Foust, Henry; Ghosehajra, Malay

    2007-07-01

    This study asks two questions: (1) How appropriate is the use of a basic filtration equation to the application of ultrafiltration of mixed waste, and (2) How appropriate are non-parametric models for permeate rates (volumes)? To answer these questions, mechanistic and non-mechanistic approaches are developed for permeate rates and volumes associated with an ultrafiltration/mixed waste system in dia-filtration mode. The mechanistic approach is based on a filtration equation which states that t/V vs. V is a linear relationship. The coefficients associated with this linear regression are composed of physical/chemical parameters of the system and based the mass balance equation associated with the membrane and associated developing cake layer. For several sets of data, a high correlation is shown that supports the assertion that t/V vs. V is a linear relationship. It is also shown that non-mechanistic approaches, i.e., the use of regression models to are not appropriate. One models considered is Q(p) = a*ln(Cb)+b. Regression models are inappropriate because the scale-up from a bench scale (pilot scale) study to full-scale for permeate rates (volumes) is not simply the ratio of the two membrane surface areas. (authors)

  18. Mechanistic models of biofilm growth in porous media

    NASA Astrophysics Data System (ADS)

    Jaiswal, Priyank; Al-Hadrami, Fathiya; Atekwana, Estella A.; Atekwana, Eliot A.

    2014-07-01

    Nondestructive acoustics methods can be used to monitor in situ biofilm growth in porous media. In practice, however, acoustic methods remain underutilized due to the lack of models that can translate acoustic data into rock properties in the context of biofilm. In this paper we present mechanistic models of biofilm growth in porous media. The models are used to quantitatively interpret arrival times and amplitudes recorded in the 29 day long Davis et al. (2010) physical scale biostimulation experiment in terms of biofilm morphologies and saturation. The model pivots on addressing the sediment elastic behavior using the lower Hashin-Shtrikman bounds for grain mixing and Gassmann substitution for fluid saturation. The time-lapse P wave velocity (VP; a function of arrival times) is explained by a combination of two rock models (morphologies); "load bearing" which assumes the biofilm as an additional mineral in the rock matrix and "pore filling" which assumes the biofilm as an additional fluid phase in the pores. The time-lapse attenuation (QP-1; a function of amplitudes), on the other hand, can be explained adequately in two ways; first, through squirt flow where energy is lost from relative motion between rock matrix and pore fluid, and second, through an empirical function of porosity (φ), permeability (κ), and grain size. The squirt flow model-fitting results in higher internal φ (7% versus 5%) and more oblate pores (0.33 versus 0.67 aspect ratio) for the load-bearing morphology versus the pore-filling morphology. The empirical model-fitting results in up to 10% increase in κ at the initial stages of the load-bearing morphology. The two morphologies which exhibit distinct mechanical and hydraulic behavior could be a function of pore throat size. The biofilm mechanistic models developed in this study can be used for the interpretation of seismic data critical for the evaluation of biobarriers in bioremediation, microbial enhanced oil recovery, and CO2

  19. MECHANISTIC INFORMATION ON DISINFECTION BY-PRODUCTS FOR RISK ASSESSMENT

    EPA Science Inventory

    Colon cancer is the second most common cancer in people from developed countries, and populations exposed t o 50?g/L or more of trihalomethanes for at 1east 35 years have been estimated to be 1.5 times more likely to develop colon cancer. Trihalomethanes are one of the classes ...

  20. Food additives

    PubMed Central

    Spencer, Michael

    1974-01-01

    Food additives are discussed from the food technology point of view. The reasons for their use are summarized: (1) to protect food from chemical and microbiological attack; (2) to even out seasonal supplies; (3) to improve their eating quality; (4) to improve their nutritional value. The various types of food additives are considered, e.g. colours, flavours, emulsifiers, bread and flour additives, preservatives, and nutritional additives. The paper concludes with consideration of those circumstances in which the use of additives is (a) justified and (b) unjustified. PMID:4467857

  1. Integrating mechanistic organism--environment interactions into the basic theory of community and evolutionary ecology.

    PubMed

    Baskett, Marissa L

    2012-03-15

    This paper presents an overview of how mechanistic knowledge of organism-environment interactions, including biomechanical interactions of heat, mass and momentum transfer, can be integrated into basic theoretical population biology through mechanistic functional responses that quantitatively describe how organisms respond to their physical environment. Integrating such functional responses into simple community and microevolutionary models allows scaling up of the organism-level understanding from biomechanics both ecologically and temporally. For community models, Holling-type functional responses for predator-prey interactions provide a classic example of the functional response affecting qualitative model dynamics, and recent efforts are expanding analogous models to incorporate environmental influences such as temperature. For evolutionary models, mechanistic functional responses dependent on the environment can serve as fitness functions in both quantitative genetic and game theoretic frameworks, especially those concerning function-valued traits. I present a novel comparison of a mechanistic fitness function based on thermal performance curves to a commonly used generic fitness function, which quantitatively differ in their predictions for response to environmental change. A variety of examples illustrate how mechanistic functional responses enhance model connections to biologically relevant traits and processes as well as environmental conditions and therefore have the potential to link theoretical and empirical studies. Sensitivity analysis of such models can provide biologically relevant insight into which parameters and processes are important to community and evolutionary responses to environmental change such as climate change, which can inform conservation management aimed at protecting response capacity. Overall, the distillation of detailed knowledge or organism-environment interactions into mechanistic functional responses in simple population

  2. Reaction Coordinates and Mechanistic Hypothesis Tests.

    PubMed

    Peters, Baron

    2016-05-27

    Reaction coordinates are integral to several classic rate theories that can (a) predict kinetic trends across conditions and homologous reactions, (b) extract activation parameters with a clear physical interpretation from experimental rates, and (c) enable efficient calculations of free energy barriers and rates. New trajectory-based rare events methods can provide rates directly from dynamical trajectories without a reaction coordinate. Trajectory-based frameworks can also generate ideal (but abstract) reaction coordinates such as committors and eigenfunctions of the master equation. However, rates and mechanistic insights obtained from trajectory-based methods and abstract coordinates are not readily generalized across simulation conditions or reaction families. We discuss methods for identifying physically meaningful reaction coordinates, including committor analysis, variational transition state theory, Kramers-Langer-Berezhkovskii-Szabo theory, and statistical inference methods that can use path sampling data to screen, mix, and optimize thousands of trial coordinates. Special focus is given to likelihood maximization and inertial likelihood maximization approaches.

  3. Reaction Coordinates and Mechanistic Hypothesis Tests

    NASA Astrophysics Data System (ADS)

    Peters, Baron

    2016-05-01

    Reaction coordinates are integral to several classic rate theories that can (a) predict kinetic trends across conditions and homologous reactions, (b) extract activation parameters with a clear physical interpretation from experimental rates, and (c) enable efficient calculations of free energy barriers and rates. New trajectory-based rare events methods can provide rates directly from dynamical trajectories without a reaction coordinate. Trajectory-based frameworks can also generate ideal (but abstract) reaction coordinates such as committors and eigenfunctions of the master equation. However, rates and mechanistic insights obtained from trajectory-based methods and abstract coordinates are not readily generalized across simulation conditions or reaction families. We discuss methods for identifying physically meaningful reaction coordinates, including committor analysis, variational transition state theory, Kramers-Langer-Berezhkovskii-Szabo theory, and statistical inference methods that can use path sampling data to screen, mix, and optimize thousands of trial coordinates. Special focus is given to likelihood maximization and inertial likelihood maximization approaches.

  4. No Additional Prognostic Value of Genetic Information in the Prediction of Vascular Events after Cerebral Ischemia of Arterial Origin: The PROMISe Study

    PubMed Central

    Achterberg, Sefanja; Kappelle, L. Jaap; de Bakker, Paul I. W.; Traylor, Matthew; Algra, Ale

    2015-01-01

    Background Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events. PMID:25906364

  5. Parameter and uncertainty estimation for mechanistic, spatially explicit epidemiological models

    NASA Astrophysics Data System (ADS)

    Finger, Flavio; Schaefli, Bettina; Bertuzzo, Enrico; Mari, Lorenzo; Rinaldo, Andrea

    2014-05-01

    Epidemiological models can be a crucially important tool for decision-making during disease outbreaks. The range of possible applications spans from real-time forecasting and allocation of health-care resources to testing alternative intervention mechanisms such as vaccines, antibiotics or the improvement of sanitary conditions. Our spatially explicit, mechanistic models for cholera epidemics have been successfully applied to several epidemics including, the one that struck Haiti in late 2010 and is still ongoing. Calibration and parameter estimation of such models represents a major challenge because of properties unusual in traditional geoscientific domains such as hydrology. Firstly, the epidemiological data available might be subject to high uncertainties due to error-prone diagnosis as well as manual (and possibly incomplete) data collection. Secondly, long-term time-series of epidemiological data are often unavailable. Finally, the spatially explicit character of the models requires the comparison of several time-series of model outputs with their real-world counterparts, which calls for an appropriate weighting scheme. It follows that the usual assumption of a homoscedastic Gaussian error distribution, used in combination with classical calibration techniques based on Markov chain Monte Carlo algorithms, is likely to be violated, whereas the construction of an appropriate formal likelihood function seems close to impossible. Alternative calibration methods, which allow for accurate estimation of total model uncertainty, particularly regarding the envisaged use of the models for decision-making, are thus needed. Here we present the most recent developments regarding methods for parameter and uncertainty estimation to be used with our mechanistic, spatially explicit models for cholera epidemics, based on informal measures of goodness of fit.

  6. A windows based mechanistic subsidence prediction model for longwall mining

    SciTech Connect

    Begley, R.; Beheler, P.; Khair, A.W.

    1996-12-31

    The previously developed Mechanistic Subsidence Prediction Model (MSPM) has been incorporated into the graphical interface environment of MS Windows. MSPM has the unique capability of predicting maximum subsidence, angle of draw and the subsidence profile of a longwall panel at various locations for both the transverse and longitudinal orientations. The resultant enhanced model can be operated by individuals with little knowledge of subsidence prediction theories or little computer programming experience. In addition, predictions of subsidence can be made in a matter of seconds without the need to develop input data files or use the keyboard in some cases. The predictions are based upon the following input parameters: panel width, mining height, overburden depth, rock quality designation, and percent hard rock in the immediate roof, main roof and the entire overburden. The recently developed enhanced model has the capability to compare predictions in a graphical format for one half of the predicted subsidence profile based upon changes in input parameters easily and instantly on the same screen. In addition another screen can be obtained from a pull down menu where the operator can compare predictions for the entire subsidence profiles. This paper presents the background of the subsidence prediction model and the methodology of the enhanced model development. The paper also presents comparisons of subsidence predictions for several different sets of input parameters in addition to comparisons of the subsidence predictions with actual field data.

  7. Are Mechanistic and Statistical QSAR Approaches Really Different? MLR Studies on 158 Cycloalkyl-Pyranones.

    PubMed

    Bhhatarai, Barun; Garg, Rajni; Gramatica, Paola

    2010-07-12

    Two parallel approaches for quantitative structure-activity relationships (QSAR) are predominant in literature, one guided by mechanistic methods (including read-across) and another by the use of statistical methods. To bridge the gap between these two approaches and to verify their main differences, a comparative study of mechanistically relevant and statistically relevant QSAR models, developed on a case study of 158 cycloalkyl-pyranones, biologically active on inhibition (Ki ) of HIV protease, was performed. Firstly, Multiple Linear Regression (MLR) based models were developed starting from a limited amount of molecular descriptors which were widely proven to have mechanistic interpretation. Then robust and predictive MLR models were developed on the same set using two different statistical approaches unbiased of input descriptors. Development of models based on Statistical I method was guided by stepwise addition of descriptors while Genetic Algorithm based selection of descriptors was used for the Statistical II. Internal validation, the standard error of the estimate, and Fisher's significance test were performed for both the statistical models. In addition, external validation was performed for Statistical II model, and Applicability Domain was verified as normally practiced in this approach. The relationships between the activity and the important descriptors selected in all the models were analyzed and compared. It is concluded that, despite the different type and number of input descriptors, and the applied descriptor selection tools or the algorithms used for developing the final model, the mechanistical and statistical approach are comparable to each other in terms of quality and also for mechanistic interpretability of modelling descriptors. Agreement can be observed between these two approaches and the better result could be a consensus prediction from both the models.

  8. Fuel characteristics pertinent to the design of aircraft fuel systems, Supplement I : additional information on MIL-F-7914(AER) grade JP-5 fuel and several fuel oils

    NASA Technical Reports Server (NTRS)

    Barnett, Henry C; Hibbard, Robert R

    1953-01-01

    Since the release of the first NACA publication on fuel characteristics pertinent to the design of aircraft fuel systems (NACA-RM-E53A21), additional information has become available on MIL-F7914(AER) grade JP-5 fuel and several of the current grades of fuel oils. In order to make this information available to fuel-system designers as quickly as possible, the present report has been prepared as a supplement to NACA-RM-E53A21. Although JP-5 fuel is of greater interest in current fuel-system problems than the fuel oils, the available data are not as extensive. It is believed, however, that the limited data on JP-5 are sufficient to indicate the variations in stocks that the designer must consider under a given fuel specification. The methods used in the preparation and extrapolation of data presented in the tables and figures of this supplement are the same as those used in NACA-RM-E53A21.

  9. Intriguing mechanistic labyrinths in gold(i) catalysis

    PubMed Central

    Obradors, Carla

    2014-01-01

    Many mechanistically intriguing reactions have been developed in the last decade using gold(i) as catalyst. Here we review the main mechanistic proposals in gold-catalysed activation of alkynes and allenes, in which this metal plays a central role by stabilising a variety of complex cationic intermediates. PMID:24176910

  10. Territoriality and home-range dynamics in meerkats, Suricata suricatta: a mechanistic modelling approach.

    PubMed

    Bateman, Andrew W; Lewis, Mark A; Gall, Gabriella; Manser, Marta B; Clutton-Brock, Tim H

    2015-01-01

    Multiple approaches exist to model patterns of space use across species, among them resource selection analysis, statistical home-range modelling and mechanistic movement modelling. Mechanistic home-range models combine the benefits of these approaches, describing emergent territorial patterns based on fine-scale individual- or group-movement rules and incorporating interactions with neighbours and the environment. These models have not, to date, been extended to dynamic contexts. Using mechanistic home-range models, we explore meerkat (Suricata suricatta) territorial patterns, considering scent marking, direct group interactions and habitat selection. We also extend the models to accommodate dynamic aspects of meerkat territoriality (territory development and territory shift). We fit models, representing multiple working hypotheses, to data from a long-term meerkat study in South Africa, and we compare models using Akaike's and Bayesian Information Criteria. Our results identify important features of meerkat territorial patterns. Notably, larger groups do not seem to control larger territories, and groups apparently prefer dune edges along a dry river bed. Our model extensions capture instances in which 1) a newly formed group interacts more strongly with its parent groups over time and 2) a group moves its territory core out of aversive habitat. This extends our mechanistic modelling framework in previously unexplored directions.

  11. Predictive mechanistic bioenergetics to model habitat suitability of shellfish culture in coastal lakes

    NASA Astrophysics Data System (ADS)

    Rinaldi, A.; Montalto, V.; Manganaro, A.; Mazzola, A.; Mirto, S.; Sanfilippo, M.; Sarà, G.

    2014-05-01

    Quantitative tools based on mechanistic modelling of functional traits able to enhance the sustainability of aquaculture and most other human activities (i.e. reducing the likelihood of detrimental impacts optimising productions), are especially important factors in the decision to site aquaculture facilities in coastal lakes, ponds and lagoons and, in the case of detrimental impact, to adopt mitigation measures. We tested the ability of mechanistic functional trait based models to predict life history traits of cultivable shellfish in shallow coastal lakes. Dynamic Energy Budget (DEB) models were run to generate spatially explicit predictions of Mytilus galloprovincialis life history (LH) traits (e.g. body size and fecundity). Using fortnightly data of food supply and hourly data of body temperatures, and exploiting the power of mechanistic rules, we estimated the amount of faeces ejected by a fixed quantity of organisms cultivated in two shallow Southern Mediterranean (Sicily) lakes. These differed in terms of temperature and food density, implying large differences in life history traits of mussels in the two study areas. This information could help facilitate the selection of sites where environmental conditions are more suitable for aquaculture and contextually compatible with sustainability. The validation exercise obtained by comparing the predicted and observed data was nearly consistent. Therefore, a mechanistic functional traits-based model seems able to capture the link between habitat characteristics and functional traits of organisms, delineating the fundamental portion of an ecological niche, the possibility of predicting LH traits and potential ecological applications in the management of natural coastal resources.

  12. Territoriality and home-range dynamics in meerkats, Suricata suricatta: a mechanistic modelling approach.

    PubMed

    Bateman, Andrew W; Lewis, Mark A; Gall, Gabriella; Manser, Marta B; Clutton-Brock, Tim H

    2015-01-01

    Multiple approaches exist to model patterns of space use across species, among them resource selection analysis, statistical home-range modelling and mechanistic movement modelling. Mechanistic home-range models combine the benefits of these approaches, describing emergent territorial patterns based on fine-scale individual- or group-movement rules and incorporating interactions with neighbours and the environment. These models have not, to date, been extended to dynamic contexts. Using mechanistic home-range models, we explore meerkat (Suricata suricatta) territorial patterns, considering scent marking, direct group interactions and habitat selection. We also extend the models to accommodate dynamic aspects of meerkat territoriality (territory development and territory shift). We fit models, representing multiple working hypotheses, to data from a long-term meerkat study in South Africa, and we compare models using Akaike's and Bayesian Information Criteria. Our results identify important features of meerkat territorial patterns. Notably, larger groups do not seem to control larger territories, and groups apparently prefer dune edges along a dry river bed. Our model extensions capture instances in which 1) a newly formed group interacts more strongly with its parent groups over time and 2) a group moves its territory core out of aversive habitat. This extends our mechanistic modelling framework in previously unexplored directions. PMID:24995457

  13. Mechanistic insights into type III restriction enzymes.

    PubMed

    Raghavendra, Nidhanapati K; Bheemanaik, Shivakumara; Rao, Desirazu N

    2012-01-01

    Type III restriction-modification (R-M) enzymes need to interact with two separate unmethylated DNA sequences in indirectly repeated, head-to-head orientations for efficient cleavage to occur at a defined location next to only one of the two sites. However, cleavage of sites that are not in head-to-head orientation have been observed to occur under certain reaction conditions in vitro. ATP hydrolysis is required for the long-distance communication between the sites prior to cleavage. Type III R-M enzymes comprise two subunits, Res and Mod that form a homodimeric Mod2 and a heterotetrameric Res2Mod2 complex. The Mod subunit in M2 or R2M2 complex recognizes and methylates DNA while the Res subunit in R2M2 complex is responsible for ATP hydrolysis, DNA translocation and cleavage. A vast majority of biochemical studies on Type III R-M enzymes have been undertaken using two closely related enzymes, EcoP1I and EcoP15I. Divergent opinions about how the long-distance interaction between the recognition sites exist and at least three mechanistic models based on 1D- diffusion and/or 3D- DNA looping have been proposed.

  14. Structural and mechanistic insights on nitrate reductases.

    PubMed

    Coelho, Catarina; Romão, Maria João

    2015-12-01

    Nitrate reductases (NR) belong to the DMSO reductase family of Mo-containing enzymes and perform key roles in the metabolism of the nitrogen cycle, reducing nitrate to nitrite. Due to variable cell location, structure and function, they have been divided into periplasmic (Nap), cytoplasmic, and membrane-bound (Nar) nitrate reductases. The first crystal structure obtained for a NR was that of the monomeric NapA from Desulfovibrio desulfuricans in 1999. Since then several new crystal structures were solved providing novel insights that led to the revision of the commonly accepted reaction mechanism for periplasmic nitrate reductases. The two crystal structures available for the NarGHI protein are from the same organism (Escherichia coli) and the combination with electrochemical and spectroscopic studies also lead to the proposal of a reaction mechanism for this group of enzymes. Here we present an overview on the current advances in structural and functional aspects of bacterial nitrate reductases, focusing on the mechanistic implications drawn from the crystallographic data. PMID:26362109

  15. Mechanistically based mapping of human cardiac fibrillation.

    PubMed

    Narayan, Sanjiv M; Zaman, Junaid A B

    2016-05-01

    The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper 'On dynamic equilibrium in the heart', Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms - sources in preferred cardiac regions or spatially diffuse self-sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non-uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non-coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation. PMID:26607671

  16. Mechanistically based mapping of human cardiac fibrillation

    PubMed Central

    Zaman, Junaid A. B.

    2016-01-01

    Abstract The mechanisms underpinning human cardiac fibrillation remain elusive. In his 1913 paper ‘On dynamic equilibrium in the heart’, Mines proposed that an activation wave front could propagate repeatedly in a circle, initiated by a stimulus in the vulnerable period. While the dynamics of activation and recovery are central to cardiac fibrillation, these physiological data are rarely used in clinical mapping. Fibrillation is a rapid irregular rhythm with spatiotemporal disorder resulting from two fundamental mechanisms – sources in preferred cardiac regions or spatially diffuse self‐sustaining activity, i.e. with no preferred source. On close inspection, however, this debate may also reflect mapping technique. Fibrillation is initiated from triggers by regional dispersion in repolarization, slow conduction and wavebreak, then sustained by non‐uniform interactions of these mechanisms. Notably, optical mapping of action potentials in atrial fibrillation (AF) show spiral wave sources (rotors) in nearly all studies including humans, while most traditional electrogram analyses of AF do not. Techniques may diverge in fibrillation because electrograms summate non‐coherent waves within an undefined field whereas optical maps define waves with a visually defined field. Also fibrillation operates at the limits of activation and recovery, which are well represented by action potentials while fibrillatory electrograms poorly represent repolarization. We conclude by suggesting areas for study that may be used, until such time as optical mapping is clinically feasible, to improve mechanistic understanding and therapy of human cardiac fibrillation. PMID:26607671

  17. The attention schema theory: a mechanistic account of subjective awareness.

    PubMed

    Graziano, Michael S A; Webb, Taylor W

    2015-01-01

    We recently proposed the attention schema theory, a novel way to explain the brain basis of subjective awareness in a mechanistic and scientifically testable manner. The theory begins with attention, the process by which signals compete for the brain's limited computing resources. This internal signal competition is partly under a bottom-up influence and partly under top-down control. We propose that the top-down control of attention is improved when the brain has access to a simplified model of attention itself. The brain therefore constructs a schematic model of the process of attention, the 'attention schema,' in much the same way that it constructs a schematic model of the body, the 'body schema.' The content of this internal model leads a brain to conclude that it has a subjective experience. One advantage of this theory is that it explains how awareness and attention can sometimes become dissociated; the brain's internal models are never perfect, and sometimes a model becomes dissociated from the object being modeled. A second advantage of this theory is that it explains how we can be aware of both internal and external events. The brain can apply attention to many types of information including external sensory information and internal information about emotions and cognitive states. If awareness is a model of attention, then this model should pertain to the same domains of information to which attention pertains. A third advantage of this theory is that it provides testable predictions. If awareness is the internal model of attention, used to help control attention, then without awareness, attention should still be possible but should suffer deficits in control. In this article, we review the existing literature on the relationship between attention and awareness, and suggest that at least some of the predictions of the theory are borne out by the evidence. PMID:25954242

  18. Phosphazene additives

    DOEpatents

    Harrup, Mason K; Rollins, Harry W

    2013-11-26

    An additive comprising a phosphazene compound that has at least two reactive functional groups and at least one capping functional group bonded to phosphorus atoms of the phosphazene compound. One of the at least two reactive functional groups is configured to react with cellulose and the other of the at least two reactive functional groups is configured to react with a resin, such as an amine resin of a polycarboxylic acid resin. The at least one capping functional group is selected from the group consisting of a short chain ether group, an alkoxy group, or an aryloxy group. Also disclosed are an additive-resin admixture, a method of treating a wood product, and a wood product.

  19. Potlining Additives

    SciTech Connect

    Rudolf Keller

    2004-08-10

    In this project, a concept to improve the performance of aluminum production cells by introducing potlining additives was examined and tested. Boron oxide was added to cathode blocks, and titanium was dissolved in the metal pool; this resulted in the formation of titanium diboride and caused the molten aluminum to wet the carbonaceous cathode surface. Such wetting reportedly leads to operational improvements and extended cell life. In addition, boron oxide suppresses cyanide formation. This final report presents and discusses the results of this project. Substantial economic benefits for the practical implementation of the technology are projected, especially for modern cells with graphitized blocks. For example, with an energy savings of about 5% and an increase in pot life from 1500 to 2500 days, a cost savings of $ 0.023 per pound of aluminum produced is projected for a 200 kA pot.

  20. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-08-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of a similar magnitude, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity-dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  1. Mechanistic study of secondary organic aerosol components formed from nucleophilic addition reactions of methacrylic acid epoxide

    NASA Astrophysics Data System (ADS)

    Birdsall, A. W.; Miner, C. R.; Mael, L. E.; Elrod, M. J.

    2014-12-01

    Recently, methacrylic acid epoxide (MAE) has been proposed as a precursor to an important class of isoprene-derived compounds found in secondary organic aerosol (SOA): 2-methylglyceric acid (2-MG) and a set of oligomers, nitric acid esters, and sulfuric acid esters related to 2-MG. However, the specific chemical mechanisms by which MAE could form these compounds have not been previously studied with experimental methods. In order to determine the relevance of these processes to atmospheric aerosol, MAE and 2-MG have been synthesized and a series of bulk solution-phase experiments aimed at studying the reactivity of MAE using nuclear magnetic resonance (NMR) spectroscopy have been performed. The present results indicate that the acid-catalyzed MAE reaction is more than 600 times slower than a similar reaction of an important isoprene-derived epoxide, but is still expected to be kinetically feasible in the atmosphere on more acidic SOA. The specific mechanism by which MAE leads to oligomers was identified, and the reactions of MAE with a number of atmospherically relevant nucleophiles were also investigated. Because the nucleophilic strengths of water, sulfate, alcohols (including 2-MG), and acids (including MAE and 2-MG) in their reactions with MAE were found to be of similar magnitudes, it is expected that a diverse variety of MAE + nucleophile product species may be formed on ambient SOA. Thus, the results indicate that epoxide chain reaction oligomerization will be limited by the presence of high concentrations of non-epoxide nucleophiles (such as water); this finding is consistent with previous environmental chamber investigations of the relative humidity dependence of 2-MG-derived oligomerization processes and suggests that extensive oligomerization may not be likely on ambient SOA because of other competitive MAE reaction mechanisms.

  2. Black tea polyphenols: a mechanistic treatise.

    PubMed

    Butt, M S; Imran, A; Sharif, M K; Ahmad, Rabia Shabir; Xiao, Hang; Imran, M; Rsool, H A

    2014-01-01

    Dietary interventions are among the emerging trends to curtail physiological malfunctioning like cancer, diabetes, cardiac complications, etc. The essence of phytonutrients has developed the concept of nutraceuticals at the junction of diet health linkages. In this context, theaflavin & thearubigins are the oxidized derivatives of black tea catechins during fermentation having nutraceutical potential owing to esterification of hydroxyl ring with digallate esters. Theaflavin may influence activation of transcription factors such as NFnB or AP-1 that ultimately hinder the formation of nitric oxide expression gene. Likewise, black tea contains a unique amino acid theanine acts as neurotransmitter owing to its ability to cross the blood-brain barrier. Moreover, it boasts immunity by enhancing the disease-fighting ability of gamma delta T cells. Theaflavin & thearubigins act as safeguard against oxidative stress thereby effective in the cardiac functioning. The mechanistic approach of these antioxidants is likely to be associated with inhibition of redox sensitive transcription factors & pro-oxidant enzymes such as xanthine oxidase or nitric oxide synthase. However, their involvement in antioxidative enzyme induction as in glutathione-S-transferases is also well documented. They act as curative agent against numerous pathological disorders by disrupting the electron chain thus inhibiting the progression of certain ailments. Black tea polyphenols established themselves as strong antioxidants due to their standard one-electron potential, and their vitality is dependent on the concentration of polyphenols and pH for their inclusive execution. Present review is an attempt to enrich the readers regarding the health promoting aspects of black tea polyphenols. Concomitantly, it needs core attention of researchers for the exploitations of black tea flavanols as an important dietary constituent for the vulnerable segment.

  3. Assessment of Mycobacterium tuberculosis Pantothenate Kinase Vulnerability through Target Knockdown and Mechanistically Diverse Inhibitors

    PubMed Central

    Reddy, B. K. Kishore; Landge, Sudhir; Ravishankar, Sudha; Patil, Vikas; Shinde, Vikas; Tantry, Subramanyam; Kale, Manoj; Raichurkar, Anandkumar; Menasinakai, Sreenivasaiah; Mudugal, Naina Vinay; Ambady, Anisha; Ghosh, Anirban; Tunduguru, Ragadeepthi; Kaur, Parvinder; Singh, Ragini; Kumar, Naveen; Bharath, Sowmya; Sundaram, Aishwarya; Bhat, Jyothi; Sambandamurthy, Vasan K.; Björkelid, Christofer; Jones, T. Alwyn; Das, Kaveri; Bandodkar, Balachandra; Malolanarasimhan, Krishnan; Mukherjee, Kakoli

    2014-01-01

    Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis, and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK (MtPanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis. PMID:24687493

  4. Mechanistic modeling of aberrant energy metabolism in human disease

    PubMed Central

    Sangar, Vineet; Eddy, James A.; Simeonidis, Evangelos; Price, Nathan D.

    2012-01-01

    Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell. PMID:23112774

  5. Mechanistic modelling of toxicokinetic processes within Myriophyllum spicatum.

    PubMed

    Heine, S; Schmitt, W; Schäffer, A; Görlitz, G; Buresová, H; Arts, G; Preuss, T G

    2015-02-01

    Effects of chemicals are, in most cases, caused by internal concentrations within organisms which rely on uptake and elimination kinetics. These processes might be key components for assessing the effects of time-variable exposure of chemicals which regularly occur in aquatic systems. However, the knowledge of toxicokinetic patterns caused by time-variable exposure is limited, and gaining such information is complex. In this work, a previously developed mechanistic growth model of Myriophyllum spicatum is coupled with a newly developed toxicokinetic part, providing a model that is able to predict uptake and elimination of chemicals, as well as distribution processes between plant compartments (leaves, stems, roots) of M. spicatum. It is shown, that toxicokinetic patterns, at least for most of the investigated chemicals, can be calculated in agreement with experimental observations, by only calibrating two chemical- specific parameters, the cuticular permeability and a plant/water partition coefficient. Through the model-based determination of the cuticular permeabilities of Isoproturon, Iofensulfuron, Fluridone, Imazamox and Penoxsulam, their toxicokinetic pattern can be described with the model approach. For the use of the model for predicting toxicokinetics of other chemicals, where experimental data is not available, equations are presented that are based on the log (P oct/wat) of a chemical and estimate parameters that are necessary to run the model. In general, a method is presented to analyze time-variable exposure of chemicals more in detail without conducting time and labour intensive experiments. PMID:25129053

  6. Warming will affect phytoplankton differently: evidence through a mechanistic approach

    PubMed Central

    Huertas, I. Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

    2011-01-01

    Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario. PMID:21508031

  7. Warming will affect phytoplankton differently: evidence through a mechanistic approach.

    PubMed

    Huertas, I Emma; Rouco, Mónica; López-Rodas, Victoria; Costas, Eduardo

    2011-12-01

    Although the consequences of global warming in aquatic ecosystems are only beginning to be revealed, a key to forecasting the impact on aquatic communities is an understanding of individual species' vulnerability to increased temperature. Despite their microscopic size, phytoplankton support about half of the global primary production, drive essential biogeochemical cycles and represent the basis of the aquatic food web. At present, it is known that phytoplankton are important targets and, consequently, harbingers of climate change in aquatic systems. Therefore, investigating the capacity of phytoplankton to adapt to the predicted warming has become a relevant issue. However, considering the polyphyletic complexity of the phytoplankton community, different responses to increased temperature are expected. We experimentally tested the effects of warming on 12 species of phytoplankton isolated from a variety of environments by using a mechanistic approach able to assess evolutionary adaptation (the so-called ratchet technique). We found different degrees of tolerance to temperature rises and an interspecific capacity for genetic adaptation. The thermal resistance level reached by each species is discussed in relation to their respective original habitats. Our study additionally provides evidence on the most resistant phytoplankton groups in a future warming scenario.

  8. A brief review of exercise, bipolar disorder, and mechanistic pathways

    PubMed Central

    Thomson, Daniel; Turner, Alyna; Lauder, Sue; Gigler, Margaret E.; Berk, Lesley; Singh, Ajeet B.; Pasco, Julie A.; Berk, Michael; Sylvia, Louisa

    2015-01-01

    Despite evidence that exercise has been found to be effective in the treatment of depression, it is unclear whether these data can be extrapolated to bipolar disorder. Available evidence for bipolar disorder is scant, with no existing randomized controlled trials having tested the impact of exercise on depressive, manic or hypomanic symptomatology. Although exercise is often recommended in bipolar disorder, this is based on extrapolation from the unipolar literature, theory and clinical expertise and not empirical evidence. In addition, there are currently no available empirical data on program variables, with practical implications on frequency, intensity and type of exercise derived from unipolar depression studies. The aim of the current paper is to explore the relationship between exercise and bipolar disorder and potential mechanistic pathways. Given the high rate of medical co-morbidities experienced by people with bipolar disorder, it is possible that exercise is a potentially useful and important intervention with regard to general health benefits; however, further research is required to elucidate the impact of exercise on mood symptomology. PMID:25788889

  9. Application of Mechanistic Toxicology Data to Ecological Risk Assessments

    EPA Science Inventory

    The ongoing evolution of knowledge and tools in the areas of molecular biology, bioinformatics, and systems biology holds significant promise for reducing uncertainties associated with ecological risk assessment. As our understanding of the mechanistic basis of responses of organ...

  10. Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science

    NASA Astrophysics Data System (ADS)

    Cañete-Valdeón, José M.; Wieringa, Roel; Smallbone, Kieran

    2012-12-01

    There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

  11. Mechanistic modelling of cancer: some reflections from software engineering and philosophy of science.

    PubMed

    Cañete-Valdeón, José M; Wieringa, Roel; Smallbone, Kieran

    2012-12-01

    There is a growing interest in mathematical mechanistic modelling as a promising strategy for understanding tumour progression. This approach is accompanied by a methodological change of making research, in which models help to actively generate hypotheses instead of waiting for general principles to become apparent once sufficient data are accumulated. This paper applies recent research from philosophy of science to uncover three important problems of mechanistic modelling which may compromise its mainstream application, namely: the dilemma of formal and informal descriptions, the need to express degrees of confidence and the need of an argumentation framework. We report experience and research on similar problems from software engineering and provide evidence that the solutions adopted there can be transferred to the biological domain. We hope this paper can provoke new opportunities for further and profitable interdisciplinary research in the field.

  12. The ecological impacts of nighttime light pollution: a mechanistic appraisal.

    PubMed

    Gaston, Kevin J; Bennie, Jonathan; Davies, Thomas W; Hopkins, John

    2013-11-01

    The ecological impacts of nighttime light pollution have been a longstanding source of concern, accentuated by realized and projected growth in electrical lighting. As human communities and lighting technologies develop, artificial light increasingly modifies natural light regimes by encroaching on dark refuges in space, in time, and across wavelengths. A wide variety of ecological implications of artificial light have been identified. However, the primary research to date is largely focused on the disruptive influence of nighttime light on higher vertebrates, and while comprehensive reviews have been compiled along taxonomic lines and within specific research domains, the subject is in need of synthesis within a common mechanistic framework. Here we propose such a framework that focuses on the cross-factoring of the ways in which artificial lighting alters natural light regimes (spatially, temporally, and spectrally), and the ways in which light influences biological systems, particularly the distinction between light as a resource and light as an information source. We review the evidence for each of the combinations of this cross-factoring. As artificial lighting alters natural patterns of light in space, time and across wavelengths, natural patterns of resource use and information flows may be disrupted, with downstream effects to the structure and function of ecosystems. This review highlights: (i) the potential influence of nighttime lighting at all levels of biological organisation (from cell to ecosystem); (ii) the significant impact that even low levels of nighttime light pollution can have; and (iii) the existence of major research gaps, particularly in terms of the impacts of light at population and ecosystem levels, identification of intensity thresholds, and the spatial extent of impacts in the vicinity of artificial lights.

  13. Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model.

    PubMed

    Harfoot, Michael B J; Newbold, Tim; Tittensor, Derek P; Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J; Scharlemann, Jörn P W; Purves, Drew W

    2014-04-01

    Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures.

  14. Modeling systems-level dynamics: Understanding without mechanistic explanation in integrative systems biology.

    PubMed

    MacLeod, Miles; Nersessian, Nancy J

    2015-02-01

    In this paper we draw upon rich ethnographic data of two systems biology labs to explore the roles of explanation and understanding in large-scale systems modeling. We illustrate practices that depart from the goal of dynamic mechanistic explanation for the sake of more limited modeling goals. These processes use abstract mathematical formulations of bio-molecular interactions and data fitting techniques which we call top-down abstraction to trade away accurate mechanistic accounts of large-scale systems for specific information about aspects of those systems. We characterize these practices as pragmatic responses to the constraints many modelers of large-scale systems face, which in turn generate more limited pragmatic non-mechanistic forms of understanding of systems. These forms aim at knowledge of how to predict system responses in order to manipulate and control some aspects of them. We propose that this analysis of understanding provides a way to interpret what many systems biologists are aiming for in practice when they talk about the objective of a "systems-level understanding."

  15. Simulating polar bear energetics during a seasonal fast using a mechanistic model.

    PubMed

    Mathewson, Paul D; Porter, Warren P

    2013-01-01

    In this study we tested the ability of a mechanistic model (Niche Mapper™) to accurately model adult, non-denning polar bear (Ursus maritimus) energetics while fasting during the ice-free season in the western Hudson Bay. The model uses a steady state heat balance approach, which calculates the metabolic rate that will allow an animal to maintain its core temperature in its particular microclimate conditions. Predicted weight loss for a 120 day fast typical of the 1990s was comparable to empirical studies of the population, and the model was able to reach a heat balance at the target metabolic rate for the entire fast, supporting use of the model to explore the impacts of climate change on polar bears. Niche Mapper predicted that all but the poorest condition bears would survive a 120 day fast under current climate conditions. When the fast extended to 180 days, Niche Mapper predicted mortality of up to 18% for males. Our results illustrate how environmental conditions, variation in animal properties, and thermoregulation processes may impact survival during extended fasts because polar bears were predicted to require additional energetic expenditure for thermoregulation during a 180 day fast. A uniform 3°C temperature increase reduced male mortality during a 180 day fast from 18% to 15%. Niche Mapper explicitly links an animal's energetics to environmental conditions and thus can be a valuable tool to help inform predictions of climate-related population changes. Since Niche Mapper is a generic model, it can make energetic predictions for other species threatened by climate change.

  16. Mechanistic insight into gramicidin-based detection of protein-ligand interactions via sensitized photoinactivation.

    PubMed

    Rokitskaya, Tatyana I; Macrae, Michael X; Blake, Steven; Egorova, Natalya S; Kotova, Elena A; Yang, Jerry; Antonenko, Yuri N

    2010-11-17

    Among the many challenges for the development of ion channel-based sensors is the poor understanding of how to engineer modified transmembrane pores with tailored functionality that can respond to external stimuli. Here, we use the method of sensitized photoinactivation of gramicidin A (gA) channels in planar bilayer lipid membranes to help elucidate the underlying mechanistic details for changes in macroscopic transmembrane ionic current observed upon interaction of C-terminally attached gA ligands with specific proteins in solution. Three different systems were studied: (i) carbonic anhydrase (CA) and gA-sulfonamide, (ii) PSD-95 protein (belonging to the 'PDZ domain-containing protein') and a gA analog carrying the KGGHRRSARYLESSV peptide sequence at the C-terminus, and (iii) an anti-biotin antibody and gA-biotin. The results challenge a previously proposed mechanistic hypothesis suggesting that protein-induced current suppression is due to steric blockage of the ion passage through gA channels, while they reveal new insight for consideration in alternative mechanistic models. Additionally, we demonstrate that the length of a linker between the ligand and the gA channel may be less important for gramicidin-based detection of monovalent compared to multivalent protein-ligand interactions. These studies collectively shed new light on the mechanism of protein-induced current alterations in bilayer recordings of gA derivatives, which may be important in the design of new gramicidin-based sensors.

  17. Mechanistic insight into gramicidin-based detection of protein-ligand interactions via sensitized photoinactivation

    NASA Astrophysics Data System (ADS)

    Rokitskaya, Tatyana I.; Macrae, Michael X.; Blake, Steven; Egorova, Natalya S.; Kotova, Elena A.; Yang, Jerry; Antonenko, Yuri N.

    2010-11-01

    Among the many challenges for the development of ion channel-based sensors is the poor understanding of how to engineer modified transmembrane pores with tailored functionality that can respond to external stimuli. Here, we use the method of sensitized photoinactivation of gramicidin A (gA) channels in planar bilayer lipid membranes to help elucidate the underlying mechanistic details for changes in macroscopic transmembrane ionic current observed upon interaction of C-terminally attached gA ligands with specific proteins in solution. Three different systems were studied: (i) carbonic anhydrase (CA) and gA-sulfonamide, (ii) PSD-95 protein (belonging to the 'PDZ domain-containing protein') and a gA analog carrying the KGGHRRSARYLESSV peptide sequence at the C-terminus, and (iii) an anti-biotin antibody and gA-biotin. The results challenge a previously proposed mechanistic hypothesis suggesting that protein-induced current suppression is due to steric blockage of the ion passage through gA channels, while they reveal new insight for consideration in alternative mechanistic models. Additionally, we demonstrate that the length of a linker between the ligand and the gA channel may be less important for gramicidin-based detection of monovalent compared to multivalent protein-ligand interactions. These studies collectively shed new light on the mechanism of protein-induced current alterations in bilayer recordings of gA derivatives, which may be important in the design of new gramicidin-based sensors.

  18. 36 CFR 1281.12 - What information must be provided to NARA for its report to Congress on a change or addition to a...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; and (v) A review of all critical spaces where NARA holdings will be stored, used, or exhibited, including information on life-safety, environmental, holdings storage, and other systems against...

  19. Mechanistic Enzyme Models: Pyridoxal and Metal Ions.

    ERIC Educational Resources Information Center

    Hamilton, S. E.; And Others

    1984-01-01

    Background information, procedures, and results are presented for experiments on the pyridoxal/metal ion model system. These experiments illustrate catalysis through Schiff's base formation between aldehydes/ketones and primary amines, catalysis by metal ions, and the predictable manner in which metal ions inhibit or catalyze reactions. (JN)

  20. Mechanistic Understanding of Microbial Plugging for Improved Sweep Efficiency

    SciTech Connect

    Steven Bryant; Larry Britton

    2008-09-30

    Microbial plugging has been proposed as an effective low cost method of permeability reduction. Yet there is a dearth of information on the fundamental processes of microbial growth in porous media, and there are no suitable data to model the process of microbial plugging as it relates to sweep efficiency. To optimize the field implementation, better mechanistic and volumetric understanding of biofilm growth within a porous medium is needed. In particular, the engineering design hinges upon a quantitative relationship between amount of nutrient consumption, amount of growth, and degree of permeability reduction. In this project experiments were conducted to obtain new data to elucidate this relationship. Experiments in heterogeneous (layered) beadpacks showed that microbes could grow preferentially in the high permeability layer. Ultimately this caused flow to be equally divided between high and low permeability layers, precisely the behavior needed for MEOR. Remarkably, classical models of microbial nutrient uptake in batch experiments do not explain the nutrient consumption by the same microbes in flow experiments. We propose a simple extension of classical kinetics to account for the self-limiting consumption of nutrient observed in our experiments, and we outline a modeling approach based on architecture and behavior of biofilms. Such a model would account for the changing trend of nutrient consumption by bacteria with the increasing biomass and the onset of biofilm formation. However no existing model can explain the microbial preference for growth in high permeability regions, nor is there any obvious extension of the model for this observation. An attractive conjecture is that quorum sensing is involved in the heterogeneous bead packs.

  1. Vitamins C and E: Beneficial effects from a mechanistic perspective

    PubMed Central

    Traber, Maret G.; Stevens, Jan F.

    2011-01-01

    The mechanistic properties of two dietary antioxidants that are required by humans, vitamins C and E, are discussed relative to their biological effects. Vitamin C (ascorbic acid) is an essential cofactor for α-ketoglutarate-dependent dioxygenases. Examples are prolyl hydroxylases, which play a role in the biosynthesis of collagen and in down-regulation of hypoxia-inducible factor (HIF)-1, a transcription factor that regulates many genes responsible for tumor growth, energy metabolism, and neutrophil function and apoptosis. Vitamin C-dependent inhibition of the HIF pathway may provide alternative or additional approaches for controlling tumor progression, infections and inflammation. Vitamin E (α-tocopherol) functions as an essential lipid soluble antioxidant, scavenging hydroperoxyl radicals in lipid milieu. Human symptoms of vitamin E deficiency suggest that its antioxidant properties play a major role in protecting erythrocyte membranes and nervous tissues. As an antioxidant, vitamin C provides protection against oxidative stress-induced cellular damage by scavenging of reactive oxygen species, vitamin E-dependent neutralization of lipid hydroperoxyl radicals, and by protecting proteins from alkylation by electrophilic lipid peroxidation products. These bioactivities bear relevance to inflammatory disorders. Vitamin C plays also a role in the function of endothelial nitric oxide synthase (eNOS) by recycling the eNOS cofactor, tetrahydrobiopterin, which is relevant to arterial elasticity and blood pressure regulation. Evidence from plants supports a role for vitamin C in the formation of covalent adducts with electrophilic secondary metabolites. Mechanism-based effects of vitamin C and E supplementation on biomarkers and on clinical outcomes from randomized, placebo-controlled trials are emphasized in this review. PMID:21664268

  2. Managing mechanistic and organic structure in health care organizations.

    PubMed

    Olden, Peter C

    2012-01-01

    Managers at all levels in a health care organization must organize work to achieve the organization's mission and goals. This requires managers to decide the organization structure, which involves dividing the work among jobs and departments and then coordinating them all toward the common purpose. Organization structure, which is reflected in an organization chart, may range on a continuum from very mechanistic to very organic. Managers must decide how mechanistic versus how organic to make the entire organization and each of its departments. To do this, managers should carefully consider 5 factors for the organization and for each individual department: external environment, goals, work production, size, and culture. Some factors may push toward more mechanistic structure, whereas others may push in the opposite direction toward more organic structure. Practical advice can help managers at all levels design appropriate structure for their departments and organization.

  3. Why did Jacques Monod make the choice of mechanistic determinism?

    PubMed

    Loison, Laurent

    2015-06-01

    The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions.

  4. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome.

    PubMed

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

  5. Addition of Cryoprotectant Significantly Alters the Epididymal Sperm Proteome

    PubMed Central

    Yoon, Sung-Jae; Rahman, Md Saidur; Kwon, Woo-Sung; Park, Yoo-Jin; Pang, Myung-Geol

    2016-01-01

    Although cryopreservation has been developed and optimized over the past decades, it causes various stresses, including cold shock, osmotic stress, and ice crystal formation, thereby reducing fertility. During cryopreservation, addition of cryoprotective agent (CPA) is crucial for protecting spermatozoa from freezing damage. However, the intrinsic toxicity and osmotic stress induced by CPA cause damage to spermatozoa. To identify the effects of CPA addition during cryopreservation, we assessed the motility (%), motion kinematics, capacitation status, and viability of epididymal spermatozoa using computer-assisted sperm analysis and Hoechst 33258/chlortetracycline fluorescence staining. Moreover, the effects of CPA addition were also demonstrated at the proteome level using two-dimensional electrophoresis. Our results demonstrated that CPA addition significantly reduced sperm motility (%), curvilinear velocity, viability (%), and non-capacitated spermatozoa, whereas straightness and acrosome-reacted spermatozoa increased significantly (p < 0.05). Ten proteins were differentially expressed (two decreased and eight increased) (>3 fold, p < 0.05) after CPA, whereas NADH dehydrogenase flavoprotein 2, f-actin-capping protein subunit beta, superoxide dismutase 2, and outer dense fiber protein 2 were associated with several important signaling pathways (p < 0.05). The present study provides a mechanistic basis for specific cryostresses and potential markers of CPA-induced stress. Therefore, these might provide information about the development of safe biomaterials for cryopreservation and basic ground for sperm cryopreservation. PMID:27031703

  6. Diversity Takes Shape: Understanding the Mechanistic and Adaptive Basis of Bacterial Morphology

    PubMed Central

    2016-01-01

    The modern age of metagenomics has delivered unprecedented volumes of data describing the genetic and metabolic diversity of bacterial communities, but it has failed to provide information about coincident cellular morphologies. Much like metabolic and biosynthetic capabilities, morphology comprises a critical component of bacterial fitness, molded by natural selection into the many elaborate shapes observed across the bacterial domain. In this essay, we discuss the diversity of bacterial morphology and its implications for understanding both the mechanistic and the adaptive basis of morphogenesis. We consider how best to leverage genomic data and recent experimental developments in order to advance our understanding of bacterial shape and its functional importance. PMID:27695035

  7. Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

    PubMed

    Timmins, Peter; Desai, Divyakant; Chen, Wei; Wray, Patrick; Brown, Jonathan; Hanley, Sarah

    2016-08-01

    Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed. PMID:27444495

  8. Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes

    NASA Astrophysics Data System (ADS)

    Niemeyer, Zachary L.; Milo, Anat; Hickey, David P.; Sigman, Matthew S.

    2016-06-01

    The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands.

  9. Copper/TEMPO-Catalyzed Aerobic Alcohol Oxidation: Mechanistic Assessment of Different Catalyst Systems

    PubMed Central

    Hoover, Jessica M.; Ryland, Bradford L.; Stahl, Shannon S.

    2013-01-01

    Combinations of homogeneous Cu salts and TEMPO have emerged as practical and efficient catalysts for the aerobic oxidation of alcohols. Several closely related catalyst systems have been reported, which differ in the identity of the solvent, the presence of 2,2′-bipyridine as a ligand, the identity of basic additives, and the oxidation state of the Cu source. These changes have a significant influence on the reaction rates, yields, and substrate scope. In this report, we probe the mechanistic basis for differences among four different Cu/TEMPO catalyst systems and elucidate the features that contribute to efficient oxidation of aliphatic alcohols. PMID:24558634

  10. Psychiatric Disorders, Morbidity, and Mortality: Tracing Mechanistic Pathways to Accelerated Aging.

    PubMed

    Kiecolt-Glaser, Janice K; Wilson, Stephanie J

    2016-09-01

    A meta-analysis published in this issue of Psychosomatic Medicine provides convincing evidence that certain psychiatric populations have shorter telomeres than nonpsychiatric controls, in accord with the strong evidence linking psychiatric disorders with premature mortality. After addressing the clinical significance of shorter telomeres, this editorial describes mechanistic pathways that lead to telomere shortening. Additionally, two other novel methods for measuring biological markers of accelerated aging are briefly discussed: DNA methylation and cellular senescence based on p16. These innovative approaches could be used to confirm and extend our understanding of psychiatric patients' increased health and mortality risks.

  11. Copper/TEMPO-Catalyzed Aerobic Alcohol Oxidation: Mechanistic Assessment of Different Catalyst Systems.

    PubMed

    Hoover, Jessica M; Ryland, Bradford L; Stahl, Shannon S

    2013-11-01

    Combinations of homogeneous Cu salts and TEMPO have emerged as practical and efficient catalysts for the aerobic oxidation of alcohols. Several closely related catalyst systems have been reported, which differ in the identity of the solvent, the presence of 2,2'-bipyridine as a ligand, the identity of basic additives, and the oxidation state of the Cu source. These changes have a significant influence on the reaction rates, yields, and substrate scope. In this report, we probe the mechanistic basis for differences among four different Cu/TEMPO catalyst systems and elucidate the features that contribute to efficient oxidation of aliphatic alcohols. PMID:24558634

  12. Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part II: Mechanistic Models and In Vitro-In Vivo Extrapolation.

    PubMed

    Scotcher, Daniel; Jones, Christopher; Posada, Maria; Galetin, Aleksandra; Rostami-Hodjegan, Amin

    2016-09-01

    It is envisaged that application of mechanistic models will improve prediction of changes in renal disposition due to drug-drug interactions, genetic polymorphism in enzymes and transporters and/or renal impairment. However, developing and validating mechanistic kidney models is challenging due to the number of processes that may occur (filtration, secretion, reabsorption and metabolism) in this complex organ. Prediction of human renal drug disposition from preclinical species may be hampered by species differences in the expression and activity of drug metabolising enzymes and transporters. A proposed solution is bottom-up prediction of pharmacokinetic parameters based on in vitro-in vivo extrapolation (IVIVE), mediated by recent advances in in vitro experimental techniques and application of relevant scaling factors. This review is a follow-up to the Part I of the report from the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25th-29th October 2015) which focuses on IVIVE and mechanistic prediction of renal drug disposition. It describes the various mechanistic kidney models that may be used to investigate renal drug disposition. Particular attention is given to efforts that have attempted to incorporate elements of IVIVE. In addition, the use of mechanistic models in prediction of renal drug-drug interactions and potential for application in determining suitable adjustment of dose in kidney disease are discussed. The need for suitable clinical pharmacokinetics data for the purposes of delineating mechanistic aspects of kidney models in various scenarios is highlighted. PMID:27506526

  13. A simple mechanistic model to interpret the effects of narcotics.

    PubMed

    Baas, J; Spurgeon, D; Broerse, M

    2015-01-01

    In this research we will show the advantages of using a time-independent dose metric in a mechanistic model to evaluate toxic effects for different narcotic compounds on different species. We will show how different already existing QSARs can be combined within a mechanistic framework to 1) make predictions of lethal thresholds; 2) show some limitations in the use of existing QSARs; 3) show how a mechanistic framework solves some conceptual problems in current approaches and 4) show how such a framework can be used to be of aid in an experimental setup in predicting the outcome of a survival experiment. The approach we chose is based on the simplest mechanistic model available, a scaled one-compartment model to describe uptake and elimination and hazard model to link the exposure to effects on survival. Within this theoretical framework a prediction for an internal threshold for effects on survival of 3 mmol/kg bw can be made, which should be similar for different species and independent of the partitioning characteristics of the toxicant. To demonstrate this, a threshold for 51 different species was derived, which indeed appeared to lie in a relatively small range, typically between 1 and 10 mmol/kg bw.

  14. Does Mechanistic Thinking Improve Student Success in Organic Chemistry?

    ERIC Educational Resources Information Center

    Grove, Nathaniel P.; Cooper, Melanie M.; Cox, Elizabeth L.

    2012-01-01

    The use of the curved-arrow notation to depict electron flow during mechanistic processes is one of the most important representational conventions in the organic chemistry curriculum. Our previous research documented a disturbing trend: when asked to predict the products of a series of reactions, many students do not spontaneously engage in…

  15. Rearrangements of Allylic Sulfinates to Sulfones: A Mechanistic Study

    ERIC Educational Resources Information Center

    Ball, David B.; Mollard, Paul; Voigtritter, Karl R.; Ball, Jenelle L.

    2010-01-01

    Most current organic chemistry textbooks are organized by functional groups and those of us who teach organic chemistry use functional-group organization in our courses but ask students to learn organic chemistry from a mechanistic approach. To enrich and extend the chemical understanding and knowledge of pericyclic-type reactions for chemistry…

  16. MECHANISTIC AND SOURCE UNDERSTANDING OF PCDD/F FORMATION

    EPA Science Inventory

    The paper discusses mechanistic and source understanding of polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) formation. (NOTE: Considerable research effort has been expended over the last 15-plus years to understand how combustion sources result in formation of PCDDs/F...

  17. DEVELOPMENT AND VALIDATION OF A MECHANISTIC GROUND SPRAYER MODEL

    EPA Science Inventory

    In the last ten years the Spray Drift Task Force (SDTF), U.S. Environmental Protection Agency (EPA), USDA Agricultural Research Service, and USDA Forest Service cooperated in the refinement and evaluation of a mechanistically-based aerial spray model (contained within AGDISP and ...

  18. Two new endemic species of Ameiva (Squamata: Teiidae) from the dry forest of northwestern Peru and additional information on Ameiva concolor Ruthven, 1924.

    PubMed

    Koch, Claudia; Venegas, Pablo J; Rödder, Dennis; Flecks, Morris; Böhme, Wolfgang

    2013-01-01

    We describe two new species of Ameiva Meyer, 1795 from the dry forest of the Northern Peruvian Andes. The new species Ameiva nodam sp. nov. and Ameiva aggerecusans sp. nov. share a divided frontal plate and are differentiated from each other and from their congeners based on genetic (12S and 16S rRNA genes) and morphological characteristics. A. nodam sp. nov. has dilated postbrachials, a maximum known snout-vent length of 101 mm, 10 longitudinal rows of ventral plates, 86-113 midbody granules, 25-35 lamellae under the fourth toe, and a color pattern with 5 longitudinal yellow stripes on the dorsum. Ameiva aggerecusans sp. nov. has not or only hardly dilated postbrachials, a maximum known snout-vent length of 99.3 mm, 10-12 longitudinal rows of ventral plates, 73-92 midbody granules, 31-39 lamellae under the fourth toe, and the females and juveniles of the species normally exhibit a cream-colored vertebral stripe on a dark dorsum ground color. We provide information on the intraspecific variation and distribution of A. concolor. Furthermore, we provide information on the environmental niches of the taxa and test for niche conservatism.  PMID:25113348

  19. Mechanistic Insights of Vitamin D Anticancer Effects.

    PubMed

    Ma, Yingyu; Johnson, Candace S; Trump, Donald L

    2016-01-01

    Vitamin D is a secosteroid hormone that regulates many biological functions in addition to its classical role in maintaining calcium homeostasis and bone metabolism. Vitamin D deficiency appears to predispose individuals to increased risk of developing a number of cancers. Compelling epidemiological and experimental evidence supports a role for vitamin D in cancer prevention and treatment in many types of cancers. Preclinical studies show that 1,25D3, the active metabolite of vitamin D, and its analogs have antitumor effects in vitro and in vivo through multiple mechanisms including the induction of cell cycle arrest, apoptosis, differentiation and the suppression of inflammation, angiogenesis, invasion, and metastasis. 1,25D3 also potentiates the effect of chemotherapeutic agents and other agents in the combination treatment. In this review, the antitumor effects of 1,25D3 and the potential underlying mechanisms will be discussed. The current findings support the application of 1,25D3 in cancer prevention and treatment. PMID:26827961

  20. A mechanistic view of drying suspension droplets.

    PubMed

    van der Kooij, Hanne M; van de Kerkhof, Gea T; Sprakel, Joris

    2016-03-21

    When a dispersion droplet dries, a rich variety of spatial and temporal heterogeneities emerge. Controlling these phenomena is essential for many applications yet requires a thorough understanding of the underlying mechanisms. Although the process of film formation from initially dispersed polymer particles is well documented and is known to involve three main stages - evaporation, particle deformation and coalescence - it is impossible to fully disentangle the effects of particle deformation and coalescence, as these stages are closely linked. We circumvent this problem by studying suspensions of colloidal rubber particles that are incapable of coalescing. Varying the crosslink density allows us to tune the particle deformability in a controlled manner. We develop a theoretical framework of the main regimes and stresses in drying droplets of these suspensions, and validate this framework experimentally. Specifically, we show that changing the particle modulus by less than an order of magnitude can completely alter the stress development and resulting instabilities. Scanning electron microscopy reveals that particle deformability is a key factor in stress mitigation. Our model is the suspension equivalent of the widely used Routh-Russel model for film formation in drying dispersions, with additional focus on lateral nonuniformities such as cracking and wrinkling inherent to the droplet geometry, thus adding a new dimension to the conventional view of particle deformation.

  1. Mechanistic Insights of Vitamin D Anticancer Effects.

    PubMed

    Ma, Yingyu; Johnson, Candace S; Trump, Donald L

    2016-01-01

    Vitamin D is a secosteroid hormone that regulates many biological functions in addition to its classical role in maintaining calcium homeostasis and bone metabolism. Vitamin D deficiency appears to predispose individuals to increased risk of developing a number of cancers. Compelling epidemiological and experimental evidence supports a role for vitamin D in cancer prevention and treatment in many types of cancers. Preclinical studies show that 1,25D3, the active metabolite of vitamin D, and its analogs have antitumor effects in vitro and in vivo through multiple mechanisms including the induction of cell cycle arrest, apoptosis, differentiation and the suppression of inflammation, angiogenesis, invasion, and metastasis. 1,25D3 also potentiates the effect of chemotherapeutic agents and other agents in the combination treatment. In this review, the antitumor effects of 1,25D3 and the potential underlying mechanisms will be discussed. The current findings support the application of 1,25D3 in cancer prevention and treatment.

  2. Horseradish peroxidase catalyzed hydroxylations: mechanistic studies.

    PubMed

    Dordick, J S; Klibanov, A M; Marletta, M A

    1986-05-20

    The hydroxylation of phenol to hydroquinone and catechol in the presence of dihydroxyfumaric acid and oxygen catalyzed by horseradish peroxidase was studied under conditions where the product yield was high and the side reactions were minimal. The reaction is partially uncoupled with a molar ratio of dihydroxyfumaric acid consumed to hydroxylated products of 12:1. Hydrogen peroxide does not participate in the reaction as evidenced by the lack of effect of catalase and by the direct addition of hydrogen peroxide. Conversely, superoxide and hydroxyl radicals are involved as their scavengers are potent inhibitors. Experiments were all consistent with the involvement of compound III (oxygenated ferrous complex) of peroxidase in the reaction. Compound III is stable in the presence of phenol alone but decomposes rapidly in the presence of both phenol and dihydroxyfumaric acid with the concomitant formation of product. Therefore, phenol and dihydroxyfumaric acid must be present with compound III in order for the hydroxylation reaction to occur. A mechanism consistent with the experimental results is proposed. PMID:3718931

  3. Do X-ray determined cardiac volume and signs of congestive heart failure provide additional prognostic information after myocardial infarction if the left ventricular ejection fraction is known?

    PubMed

    Rollag, A; Mangschau, A; Jonsbu, J; Aase, O; Nerdrum, H J; Erikssen, J

    1989-04-01

    Cardiac volume (CV) was measured and indices of pulmonary congestion (PCG) were judged from routine chest films taken post myocardial infarction (AMI) in a consecutive series of 477 patients (340 first and 137 recurrent AMIs). Cardiac volume (CV) and signs of PCG were compared to left ventricular ejection fraction (LVEF), measured with isotope technique, and the prognostic value of all the parameters was assessed after 1 and 5 years. The accuracy of CV and PCG in predicting impaired LVEF was low (62% and 50% respectively). Although specificity is suboptimal, however, these parameters provided valuable prognostic information. For example, patients with signs of PCG had a very high 1 and 5 years' mortality, and two-thirds of those who died during the first year of observation had enlarged CV. The independent value of LVEF determination was mainly observed in re-AMI patients. A more restricted use of this expensive procedure may therefore be recommended. PMID:2498456

  4. Carbenic vs. ionic mechanistic pathway in reaction of cyclohexanone with bromoform.

    PubMed

    Vitnik, Vesna D; Vitnik, Zeljko J; Juranić, Ivan O

    2012-10-01

    The extensive computation study was done to elucidate the mechanism of formation dibromoepoxide from cyclohexanone and bromoform. In this reaction, the formation of dihaloepoxide 2 is postulated as a key step that determines the distribution and stereochemistry of products. Two mechanistic paths of reaction were investigated: the addition of dibromocarbene to carbonyl group of ketone, and the addition of tribromomethyl carbanion to the same (C=O) group. The mechanisms for the addition reactions of dibromocarbenes and tribromomethyl carbanions with cyclohexanone have been investigated using ab initio HF/6-311++G** and MP2/6-311+G* level of theory. Solvent effects on these reactions have been explored by calculations which included a continuum polarizable conductor model (CPCM) for the solvent (H₂O). The calculations showed that both mechanisms are possible and are exothermic, but have markedly different activation energies.

  5. MECHANISTIC STUDIES OF IMPROVED FOAM EOR PROCESSES

    SciTech Connect

    William R. Rossen

    2003-01-28

    The objective of this research is to widen the application of foam to enhanced oil recovery (EOR) by investigating fundamental mechanisms of foams in porous media. This research will lay the groundwork for more applied research on foams for improved sweep efficiency in miscible gas, steam and surfactant-based EOR. Task 1 investigates the pore-scale interactions between foam bubbles and polymer molecules. Task 2 examines the mechanisms of gas trapping, and interaction between gas trapping and foam effectiveness. Task 3 investigates mechanisms of foam generation in porous media. The most significant progress during this period was made on Tasks 2 and 3. Research on Task 2 focused on simulating the effect of gas trapping on foam mobility during foam injection and during subsequent injection of liquid. Gas trapping during liquid injection is crucial both to injectivity during liquid injection in surfactant-alternating-gas foam (SAG) projects and also provides a window into trapping mechanisms that apply during foam flow. We updated our simulator for foam (Rossen et al., 1999; Cheng et al., 2000) to account explicitly for the first time for the effects of gas trapping on gas mobility in foam and in liquid injected after foam, and for the effects of pressure gradient on gas trapping. The foam model fits steady-state foam behavior in both high- and low-quality flow regimes (Alvarez et al., 2001) and steady-state liquid mobility after foam. The simulator also fits the transition period between foam and liquid injection in laboratory corefloods qualitatively with no additional adjustable parameters. Research on Task 3 focused on foam generation in homogeneous porous media. In steady gas-liquid flow in homogeneous porous media with surfactant present, there is often observed a critical injection velocity or pressure gradient {del}{sub p}{sup min} at which foam generation occurs. Earlier research on foam generation was extended with extensive data for a variety of porous

  6. Mechanistic investigation of a hemostatic keratin biomaterial

    NASA Astrophysics Data System (ADS)

    Rahmany, Maria Bahawdory

    Traumatic injury leads to more productive years lost than heart disease, cancer and stroke combined. Trauma is often accompanied and complicated by uncontrolled bleeding. Human hair keratin biomaterials have demonstrated efficacy in controlling hemorrhage in both small and large animal models; however little is known about the mechanism by which these proteins aid in blood clotting. Inspection of the amino acid sequence of known keratins shows the presence of several cellular binding motifs, suggesting a possible mechanism and potentially eliminating the need to functionalize the material's surface for cellular interaction. In addition to small animal studies, the hemostatic activity of keratin hydrogels was explored through porcine hemorrhage models representing both a high flow and low flow bleed. In both studies, keratin hydrogels appeared to lead to a significant reduction in blood loss. The promising results from these in vivo studies provided the motivation for this project. The objective of this dissertation work was to assess the mechanism of action of a hemostatic keratin biomaterial, and more broadly assess the biomaterial-cellular interaction(s). It is our hypothesis that keratin biomaterials have the capacity to specifically interact with cells and lead to propagation of intracellular signaling pathway, specifically contributing to hemostasis. Through application of biochemical and molecular tools, we demonstrate here that keratin biomaterials contribute to hemostasis through two probable mechanisms; integrin mediated platelet adhesion and increased fibrin polymerization. Platelets are the major cell type involved in coagulation both by acting as a catalytic surface for the clotting cascade and adhering to extracellular matrix (ECM) proteins providing a soft platelet plug. Because keratin biomaterials have structural and biochemical characteristics similar to ECM proteins, we utilized several adhesion assays to investigate platelet adhesion to keratin

  7. Ring Substituent Effects on the Thiol Addition and Hydrolysis Reactions of N-Arylmaleimides.

    PubMed

    Chen, Yingche; Tsao, Kelvin; De Francesco, Élise; Keillor, Jeffrey W

    2015-12-18

    Maleimide groups are used extensively in bioconjugation reactions, but limited kinetic information is available regarding their thiol addition and hydrolysis reactions. We prepared a series of fluorogenic coumarin maleimide derivatives that differ by the substituent on their maleimide C═C bond. Fluorescence-based kinetic studies of the reaction with β-mercaptoethanol (BME) yielded the second-order rate constants (k2), while pH-rate studies from pH 7 to 9 gave base-catalyzed hydrolysis rate constants (kOH). Linear free-energy relationships were studied through the correlation of log k2 and log kOH to both electronic (σ(+)) and steric (Es(norm)) parameters of the C═C substituent. These correlations revealed the thiol addition reaction is primarily sensitive to the electronic effects, while steric effects dominate the hydrolysis reaction. These mechanistic studies provide the basis for the design of novel bioconjugation reactants or fluorogenic labeling agents.

  8. Mechanistic variables can enhance predictive models of endotherm distributions: The American pika under current, past, and future climates

    USGS Publications Warehouse

    Mathewson, Paul; Moyer-Horner, Lucas; Beever, Erik; Briscoe, Natalie; Kearney, Michael T; Yahn, Jeremiah; Porter, Warren P.

    2016-01-01

    How climate constrains species’ distributions through time and space is an important question in the context of conservation planning for climate change. Despite increasing awareness of the need to incorporate mechanism into species distribution models (SDMs), mechanistic modeling of endotherm distributions remains limited in this literature. Using the American pika (Ochotona princeps) as an example, we present a framework whereby mechanism can be incorporated into endotherm SDMs. Pika distribution has repeatedly been found to be constrained by warm temperatures, so we used Niche Mapper, a mechanistic heat-balance model, to convert macroclimate data to pika-specific surface activity time in summer across the western United States. We then explored the difference between using a macroclimate predictor (summer temperature) and using a mechanistic predictor (predicted surface activity time) in SDMs. Both approaches accurately predicted pika presences in current and past climate regimes. However, the activity models predicted 8–19% less habitat loss in response to annual temperature increases of ~3–5 °C predicted in the region by 2070, suggesting that pikas may be able to buffer some climate change effects through behavioral thermoregulation that can be captured by mechanistic modeling. Incorporating mechanism added value to the modeling by providing increased confidence in areas where different modeling approaches agreed and providing a range of outcomes in areas of disagreement. It also provided a more proximate variable relating animal distribution to climate, allowing investigations into how unique habitat characteristics and intraspecific phenotypic variation may allow pikas to exist in areas outside those predicted by generic SDMs. Only a small number of easily obtainable data are required to parameterize this mechanistic model for any endotherm, and its use can improve SDM predictions by explicitly modeling a widely applicable direct physiological effect

  9. A dynamic and mechanistic model of PCB bioaccumulation in the European hake ( Merluccius merluccius)

    NASA Astrophysics Data System (ADS)

    Bodiguel, Xavier; Maury, Olivier; Mellon-Duval, Capucine; Roupsard, François; Le Guellec, Anne-Marie; Loizeau, Véronique

    2009-08-01

    Bioaccumulation is difficult to document because responses differ among chemical compounds, with environmental conditions, and physiological processes characteristic of each species. We use a mechanistic model, based on the Dynamic Energy Budget (DEB) theory, to take into account this complexity and study factors impacting accumulation of organic pollutants in fish through ontogeny. The bioaccumulation model proposed is a comprehensive approach that relates evolution of hake PCB contamination to physiological information about the fish, such as diet, metabolism, reserve and reproduction status. The species studied is the European hake ( Merluccius merluccius, L. 1758). The model is applied to study the total concentration and the lipid normalised concentration of 4 PCB congeners in male and female hakes from the Gulf of Lions (NW Mediterranean sea) and the Bay of Biscay (NE Atlantic ocean). Outputs of the model compare consistently to measurements over the life span of fish. Simulation results clearly demonstrate the relative effects of food contamination, growth and reproduction on the PCB bioaccumulation in hake. The same species living in different habitats and exposed to different PCB prey concentrations exhibit marked difference in the body accumulation of PCBs. At the adult stage, female hakes have a lower PCB concentration compared to males for a given length. We successfully simulated these sex-specific PCB concentrations by considering two mechanisms: a higher energy allocation to growth for females and a transfer of PCBs from the female to its eggs when allocating lipids from reserve to eggs. Finally, by its mechanistic description of physiological processes, the model is relevant for other species and sets the stage for a mechanistic understanding of toxicity and ecological effects of organic contaminants in marine organisms.

  10. Evolution of enzymatic activity in the tautomerase superfamily: mechanistic and structural studies of the 1,3-dichloropropene catabolic enzymes.

    PubMed

    Poelarends, Gerrit J; Whitman, Christian P

    2004-10-01

    The use of the soil fumigant Telone II, which contains a mixture of cis- and trans-1,3-dichloropropene, to control plant-parasitic nematodes is a common agricultural practice for maximizing yields of various crops. The effectiveness of Telone II is limited by the rapid turnover of the dichloropropenes in the soil due to the presence of bacterial catabolic pathways, which may be of recent origin. The characterization of three enzymes in these pathways, trans-3-chloroacrylic acid dehalogenase (CaaD), cis-3-chloroacrylic acid dehalogenase (cis-CaaD), and malonate semialdehyde decarboxylase (MSAD), has uncovered intriguing catalytic mechanisms as well as a fascinating evolutionary lineage for these proteins. Sequence comparisons and mutagenesis studies revealed that all three enzymes belong to the tautomerase superfamily. Tautomerase superfamily members with known structures are characterized by a beta-alpha-beta structural fold. Moreover, they have a conserved N-terminal proline, which plays an important catalytic role. Mechanistic, NMR, and pH rate studies of the two dehalogenases, coupled with a crystal structure of CaaD inactivated by 3-bromopropiolate, indicate that they use a general acid/base mechanism to catalyze the conversion of their respective isomer of 3-chloroacrylate to malonate semialdehyde. The reaction is initiated by the conjugate addition of water to the C-2, C-3 double bond and is followed by the loss of HCl. MSAD processes malonate semialdehyde to acetaldehyde, and is the first identified decarboxylase in the tautomerase superfamily. The catalytic mechanism is not well defined but the N-terminal proline plays a prominent role and may function as a general acid catalyst, similar to its role in CaaD and cis-CaaD. These are the first structural and mechanistic details for tautomerase superfamily members that catalyze either a hydration or a decarboxylation reaction, rather than a tautomerization reaction, in which Pro-1 serves as a general acid

  11. Mechanistic model for catalytic recombination during aerobraking maneuvers

    NASA Technical Reports Server (NTRS)

    Willey, Ronald J.

    1989-01-01

    Several mechanistic models are developed to predict recombination coefficients for use in heat shield design for reusable surface insulation (RSI) on aerobraking vehicles such as space shuttles. The models are applied over a temperature range of 300 to 1800 K and a stagnation pressure range of 0 to 3,000 Pa. A four parameter model in temperature was found to work best; however, several models (including those with atom concentrations at the surface) were also investigated. Mechanistic models developed with atom concentration terms may be applicable when sufficient data becomes available. The requirement is shown for recombination experiments in the 300 to 1000 K and 1500 to 1850 K temperature range, with deliberate concentration variations.

  12. Millifluidics for Chemical Synthesis and Time-resolved Mechanistic Studies

    PubMed Central

    Krishna, Katla Sai; Biswas, Sanchita; Navin, Chelliah V.; Yamane, Dawit G.; Miller, Jeffrey T.; Kumar, Challa S.S.R.

    2013-01-01

    Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst. PMID:24327099

  13. Millifluidics for chemical synthesis and time-resolved mechanistic studies.

    PubMed

    Krishna, Katla Sai; Biswas, Sanchita; Navin, Chelliah V; Yamane, Dawit G; Miller, Jeffrey T; Kumar, Challa S S R

    2013-01-01

    Procedures utilizing millifluidic devices for chemical synthesis and time-resolved mechanistic studies are described by taking three examples. In the first, synthesis of ultra-small copper nanoclusters is described. The second example provides their utility for investigating time resolved kinetics of chemical reactions by analyzing gold nanoparticle formation using in situ X-ray absorption spectroscopy. The final example demonstrates continuous flow catalysis of reactions inside millifluidic channel coated with nanostructured catalyst. PMID:24327099

  14. Home range analysis using a mechanistic home range model

    SciTech Connect

    Moorcroft, P.R. . Dept. of Ecology and Evolutionary Biology); Lewis, M.A. . Dept. of Mathematics) Crabtree, R.L. . Dept. of Fish and Wildlife Resources)

    1999-07-01

    The traditional models used to characterize animal home ranges have no mechanistic basis underlying their descriptions of space use, and as a result, the analysis of animal home ranges has primarily been a descriptive endeavor. In this paper, the authors characterize coyote (Canis latrans) home range patterns using partial differential equations for expected space use that are formally derived from underlying descriptions of individual movement behavior. To the authors' knowledge, this is the first time that mechanistic models have been used to characterize animal home ranges. The results provide empirical support for a model formulation of movement response to scent marks, and suggest that having relocation data for individuals in adjacent groups is necessary to capture the spatial arrangement of home range boundaries. The authors then show how the model fits can be used to obtain predictions for individual movement and scent marking behavior and to predict changes in home range patterns. More generally, the findings illustrate how mechanistic models permit the development of a predictive theory for the relationship between movement behavior and animal spatial distribution.

  15. NGSI student activities in open source information analysis in support of the training program of the U.S. DOE laboratories for the entry into force of the additional protocol

    SciTech Connect

    Sandoval, M Analisa; Uribe, Eva C; Sandoval, Marisa N; Boyer, Brian D; Stevens, Rebecca S

    2009-01-01

    In 2008 a joint team from Los Alamos National Laboratory (LANL) and Brookhaven National Laboratory (BNL) consisting of specialists in training of IAEA inspectors in the use of complementary access activities formulated a training program to prepare the U.S. Doe laboratories for the entry into force of the Additional Protocol. As a major part of the support of the activity, LANL summer interns provided open source information analysis to the LANL-BNL mock inspection team. They were a part of the Next Generation Safeguards Initiative's (NGSI) summer intern program aimed at producing the next generation of safeguards specialists. This paper describes how they used open source information to 'backstop' the LANL-BNL team's effort to construct meaningful Additional Protocol Complementary Access training scenarios for each of the three DOE laboratories, Lawrence Livermore National Laboratory, Idaho National Laboratory, and Oak Ridge National Laboratory.

  16. Bird Migration Under Climate Change - A Mechanistic Approach Using Remote Sensing

    NASA Technical Reports Server (NTRS)

    Smith, James A.; Blattner, Tim; Messmer, Peter

    2010-01-01

    The broad-scale reductions and shifts that may be expected under climate change in the availability and quality of stopover habitat for long-distance migrants is an area of increasing concern for conservation biologists. Researchers generally have taken two broad approaches to the modeling of migration behaviour to understand the impact of these changes on migratory bird populations. These include models based on causal processes and their response to environmental stimulation, "mechanistic models", or models that primarily are based on observed animal distribution patterns and the correlation of these patterns with environmental variables, i.e. "data driven" models. Investigators have applied the latter technique to forecast changes in migration patterns with changes in the environment, for example, as might be expected under climate change, by forecasting how the underlying environmental data layers upon which the relationships are built will change over time. The learned geostatstical correlations are then applied to the modified data layers.. However, this is problematic. Even if the projections of how the underlying data layers will change are correct, it is not evident that the statistical relationships will remain the same, i.e. that the animal organism may not adapt its' behaviour to the changing conditions. Mechanistic models that explicitly take into account the physical, biological, and behaviour responses of an organism as well as the underlying changes in the landscape offer an alternative to address these shortcomings. The availability of satellite remote sensing observations at multiple spatial and temporal scales, coupled with advances in climate modeling and information technologies enable the application of the mechanistic models to predict how continental bird migration patterns may change in response to environmental change. In earlier work, we simulated the impact of effects of wetland loss and inter-annual variability on the fitness of

  17. Accessing N-Stereogenicity through a Double Aza-Michael Reaction: Mechanistic Insights.

    PubMed

    Kohrt, Sonja; Santschi, Nico; Cvengroš, Ján

    2016-01-01

    Further development of the chemistry and applications of chiral compounds that possess configurationally stable stereogenic nitrogen atoms is hampered by the lack of efficient strategies to access such compounds in an enantiomerically pure form. Esters of propiolic acid and chiral alcohols were evaluated as cheap and readily available Michael acceptors in a diastereoselective synthesis of N-stereogenic compounds by means of a double aza-Michael conjugate addition. Diastereomeric ratios of up to 74:26 and high yields were achieved with (-)-menthyl propiolate as a substrate. Furthermore, a detailed mechanistic investigation was undertaken to shed some light on the course of this domino transformation. Kinetic studies revealed that the protic-solvent additive acts as a Brønsted acid and activates the ester toward the initial attack of the tetrahydrodiazocine partner. Conversely, acidic conditions proved unfavorable during the final cyclization step that provides the product.

  18. Water-soluble NHC-Cu catalysts: applications in click chemistry, bioconjugation and mechanistic analysis.

    PubMed

    Díaz Velázquez, Heriberto; Ruiz García, Yara; Vandichel, Matthias; Madder, Annemieke; Verpoort, Francis

    2014-12-14

    Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and terminal alkynes (CuAAC), better known as "click" reaction, has triggered the use of 1,2,3-triazoles in bioconjugation, drug discovery, materials science and combinatorial chemistry. Here we report a new series of water-soluble catalysts based on N-heterocyclic carbene (NHC)-Cu complexes which are additionally functionalized with a sulfonate group. The complexes show superior activity towards CuAAC reactions and display a high versatility, enabling the production of triazoles with different substitution patterns. Additionally, successful application of these complexes in bioconjugation using unprotected peptides acting as DNA binding domains was achieved for the first time. Mechanistic insight into the reaction mechanism is obtained by means of state-of-the-art first principles calculations.

  19. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    PubMed

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses.

  20. Elucidation of arctigenin pharmacokinetics after intravenous and oral administrations in rats: integration of in vitro and in vivo findings via semi-mechanistic pharmacokinetic modeling.

    PubMed

    Gao, Qiong; Zhang, Yufeng; Wo, Siukwan; Zuo, Zhong

    2014-11-01

    Although arctigenin (AR) has attracted substantial research interests due to its promising and diverse therapeutic effects, studies regarding its biotransformation were limited. The current study aims to provide information regarding the pharmacokinetic properties of AR via various in vitro and in vivo experiments as well as semi-mechanistic pharmacokinetic modeling. Our in vitro rat microsome incubation studies revealed that glucuronidation was the main intestinal and liver metabolic pathway of AR, which occurred with V max, K m, and Clint of 47.5 ± 3.4 nmol/min/mg, 204 ± 22 μM, and 233 ± 9 μl/min/mg with intestinal microsomes and 2.92 ± 0.07 nmol/min/mg, 22.7 ± 1.2 μM, and 129 ± 4 μl/min/mg with liver microsomes, respectively. In addition, demethylation and hydrolysis of AR occurred with liver microsomes but not with intestinal microsomes. In vitro incubation of AR and its metabolites in intestinal content demonstrated that glucuronides of AR excreted in bile could be further hydrolyzed back to the parent compound, suggesting its potential enterohepatic circulation. Furthermore, rapid formation followed by fast elimination of arctigenic acid (AA) and arctigenin-4'-O-glucuronide (AG) was observed after both intravenous (IV) and oral administrations of AR in rats. Linear pharmacokinetics was observed at three different doses for AR, AA, and AG after IV administration of AR (0.48-2.4 mg/kg, r (2) > 0.99). Finally, an integrated semi-mechanistic pharmacokinetic model using in vitro enzyme kinetic and in vivo pharmacokinetic parameters was successfully developed to describe plasma concentrations of AR, AA, and AG after both IV and oral administration of AR at all tested doses. PMID:25274606

  1. Unravelling the Relationship between Body Mass Index and Polychlorinated Biphenyl Concentrations Using a Mechanistic Model.

    PubMed

    Wood, Stephen A; Xu, Feng; Armitage, James M; Wania, Frank

    2016-09-20

    Human biomonitoring (HBM) often reveals statistical associations between persistent organic pollutant (POP) concentrations and body mass index (BMI). Both negative and positive associations have been observed, which has been hypothesized to reflect variable toxicokinetics in lean and obese individuals during times of increasing and decreasing exposure. We examined this hypothesis and assessed the influence of the obesity epidemic on time trends in human exposure to polychlorinated biphenyls (PCB) at the population level using a mechanistic modeling approach and data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Using model results for PCB-153, we simulated cross-sectional body burden versus BMI trends (CBBTs), as well as population level body burden versus time trends. Negative associations between PCB-153 concentrations and BMI are predicted for all birth cohorts in HBM studies conducted in the 1990s, while for future cross-sectional studies, we predict negative or positive relationships depending on the age group sampled. At the population level, demographic changes such as the obesity epidemic and population aging had only marginal influence on the simulated rate of decline in PCB-153 concentrations between 1980 and 2010. Mechanistic bioaccumulation models can help unravel relationships between age, BMI, and POP concentrations, informing efforts to understand potential obesogenic effects of POPs. PMID:27616073

  2. The autism puzzle: challenging a mechanistic model on conceptual and historical grounds

    PubMed Central

    2013-01-01

    Although clinicians and researchers working in the field of autism are generally not concerned with philosophical categories of kinds, a model for understanding the nature of autism is important for guiding research and clinical practice. Contemporary research in the field of autism is guided by the depiction of autism as a scientific object that can be identified with systematic neuroscientific investigation. This image of autism is compatible with a permissive account of natural kinds: the mechanistic property cluster (MPC) account of natural kinds, recently proposed as the model for understanding psychiatric disorders. Despite the heterogeneity, multicausality and fuzzy boundaries that complicate autism research, a permissive account of natural kinds (MPC kinds) provides prescriptive guidance for the investigation of objective causal mechanisms that should inform nosologists in their attempt to carve autism’s boundaries at its natural joints. However, this essay will argue that a mechanistic model of autism is limited since it disregards the way in which autism relates to ideas about what kind of behavior is abnormal. As historical studies and definitions of autism show, normative issues concerning disability, impairment and societal needs have been and still are inextricably linked to how we recognize and understand autism. The current search for autism’s unity in neurobiological mechanisms ignores the values, social norms and various perspectives on mental pathology that play a significant role in 'the thing called autism’. Autism research needs to engage with these issues in order to achieve more success in the effort to become clinically valuable. PMID:24207065

  3. Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link.

    PubMed

    Hursting, Stephen D; Lashinger, Laura M; Wheatley, Karrie W; Rogers, Connie J; Colbert, Lisa H; Nunez, Nomeli P; Perkins, Susan N

    2008-08-01

    The prevalence of obesity, an established epidemiologic risk factor for many cancers, has risen steadily for the past several decades in the US. The increasing rates of obesity among children are especially alarming and suggest continuing increases in the rates of obesity-related cancers for many years to come. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood. In particular, the effects on the carcinogenesis process and mechanistic targets of interventions that modulate energy balance, such as reduced-calorie diets and physical activity, have not been well characterized. The purpose of this review is to provide a strong foundation for the translation of mechanism-based research in this area by describing key animal and human studies of energy balance modulations involving diet or physical activity and by focusing on the interrelated pathways affected by alterations in energy balance. Particular attention is placed on signaling through the insulin and insulin-like growth factor-1 receptors, including components of the Akt and mammalian target of rapamycin (mTOR) signaling pathways downstream of these growth factor receptors. These pathways have emerged as potential targets for disrupting the obesity-cancer link. The ultimate goal of this work is to provide the missing mechanistic information necessary to identify targets for the prevention and control of cancers related to or caused by excess body weight.

  4. Combining solvent isotope effects with substrate isotope effects in mechanistic studies of alcohol and amine oxidation by enzymes.

    PubMed

    Fitzpatrick, Paul F

    2015-11-01

    Oxidation of alcohols and amines is catalyzed by multiple families of flavin- and pyridine nucleotide-dependent enzymes. Measurement of solvent isotope effects provides a unique mechanistic probe of the timing of the cleavage of the OH and NH bonds, necessary information for a complete description of the catalytic mechanism. The inherent ambiguities in interpretation of solvent isotope effects can be significantly decreased if isotope effects arising from isotopically labeled substrates are measured in combination with solvent isotope effects. The application of combined solvent and substrate (mainly deuterium) isotope effects to multiple enzymes is described here to illustrate the range of mechanistic insights that such an approach can provide. This article is part of a Special Issue entitled: Enzyme Transition States from Theory and Experiment.

  5. Mechanistic sediment quality guidelines based on contaminant bioavailability: equilibrium partitioning sediment benchmarks.

    PubMed

    Burgess, Robert M; Berry, Walter J; Mount, David R; Di Toro, Dominic M

    2013-01-01

    Globally, estimated costs to manage (i.e., remediate and monitor) contaminated sediments are in the billions of U.S. dollars. Biologically based approaches for assessing the contaminated sediments which pose the greatest ecological risk range from toxicity testing to benthic community analysis. In addition, chemically based sediment quality guidelines (SQGs) provide a relatively inexpensive line of evidence for supporting these assessments. The present study summarizes a mechanistic SQG based on equilibrium partitioning (EqP), which uses the dissolved concentrations of contaminants in sediment interstitial waters as a surrogate for bioavailable contaminant concentrations. The EqP-based mechanistic SQGs are called equilibrium partitioning sediment benchmarks (ESBs). Sediment concentrations less than or equal to the ESB values are not expected to result in adverse effects and benthic organisms should be protected, while sediment concentrations above the ESB values may result in adverse effects to benthic organisms. In the present study, ESB values are reported for 34 polycyclic aromatic hydrocarbon, 32 other organic contaminants, and seven metals (cadmium, chromium, copper, nickel, lead, silver, zinc). Also included is an overview of EqP theory, ESB derivation, examples of applying ESB values, and considerations when using ESBs. The ESBs are intended as a complement to existing sediment-assessment tools, to assist in determining the extent of sediment contamination, to help identify chemicals causing toxicity, and to serve as targets for pollutant loading control measures.

  6. Mechanistic micro-structural theory of soft tissues growth and remodeling: tissues with unidirectional fibers.

    PubMed

    Lanir, Yoram

    2015-04-01

    A new mechanistic theory was developed for soft tissues growth and remodeling (G&R). The theory considers tissues with unidirectional fibers. It is based on the loading-dependent local turnover events of each constituent and on the resulting evolution of the tissue micro-structure, the tissue dimensions and its mechanical properties. The theory incorporates the specific mechanical properties and turnover kinetics of each constituent, thereby establishing a general framework which can serve for future integration of additional mechanisms involved in G&R. The feasibility of the theory was examined by considering a specific realization of tissues with one fibrous constituent (collagen fibers), assuming a specific loading-dependent first-order fiber's turnover kinetics and the fiber's deposition characteristics. The tissue was subjected to a continuous constant rate growth. Model parameters were adopted from available data. The resulting predictions show qualitative agreement with a number of well-known features of tissues including the fibers' non-uniform recruitment density distribution, the associated tissue convex nonlinear stress-stretch relationship, and the development of tissue pre-stretch and pre-stress states. These results show that mechanistic micro-structural modeling of soft tissue G&R based on first principles can successfully capture the evolution of observed tissues' structure and size, and of their associated mechanical properties.

  7. A tissue-engineered gastric cancer model for mechanistic study of anti-tumor drugs.

    PubMed

    Gao, Ming; Cai, Yiting; Wu, Wei; Shi, Yazhou; Fei, Zhewei

    2013-08-01

    The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24(+) and CD44(+) cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44(+) subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells. PMID:23715169

  8. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous §...

  9. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous §...

  10. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous §...

  11. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous §...

  12. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Miscellaneous §...

  13. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... developer exercise, or have the right to exercise, any control over the Association because of voting rights... there any functions or services that the developer now provides at no charge for which the association... to a purchaser? If the taxes are to paid to the developer, include a statement that “Should we...

  14. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., when will it be formed? Who is responsible for its formation? (2) Does the developer exercise, or have... or services that the developer now provides at no charge for which the association may be required to... taxes are to paid to the developer, include a statement that “Should we not forward the tax funds to...

  15. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a copy of the charter or certificate of incorporation. (2) If the developer exercises any control... developer or any affiliate or principal of the developer. If there have been, briefly summarize the terms of... to reimburse the developer, its affiliates or successors for any attorney's fees or costs...

  16. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., when will it be formed? Who is responsible for its formation? (2) Does the developer exercise, or have... or services that the developer now provides at no charge for which the association may be required to... taxes are to paid to the developer, include a statement that “Should we not forward the tax funds to...

  17. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., when will it be formed? Who is responsible for its formation? (2) Does the developer exercise, or have... or services that the developer now provides at no charge for which the association may be required to... taxes are to paid to the developer, include a statement that “Should we not forward the tax funds to...

  18. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....116 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION LAND REGISTRATION (REGULATION J..., financial obligations including operating costs, maintenance and repair costs and reserves for replacement... environment, land sales, securities sales, construction or sale of homes or home improvements, consumer...

  19. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....116 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION LAND REGISTRATION (REGULATION J..., financial obligations including operating costs, maintenance and repair costs and reserves for replacement... environment, land sales, securities sales, construction or sale of homes or home improvements, consumer...

  20. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... is voluntary, you may be required to pay a disproportionate share of the association costs or it may... including operating costs, maintenance and repair costs and reserves for replacement? If not, how will any... it valid and what is its cost? (3) Time sharing. (i) How is title to be conveyed? How many...

  1. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting Requirements... violation of a Federal, state or local law concerned with the environment, land sales, securities sales... owner of the land or any of their principals, officers, directors, parent corporation, subsidiaries...

  2. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting Requirements... supporting documents, including copies of any laws which restrict the ownership of land by aliens, shall...

  3. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting Requirements... supporting documents, including copies of any laws which restrict the ownership of land by aliens, shall...

  4. Ferritin Diversity: Mechanistic Studies, Disease Implications, and Materials Chemistry

    NASA Astrophysics Data System (ADS)

    Hilton, Robert J.

    2011-07-01

    The study of ferritin includes a rich history of discoveries and scientific progress. Initially, the composition of ferritin was determined. Soon, it was shown that ferritin is a spherical, hollow protein. Eventually, over several decades of research, the structure and some function of this interesting protein was elucidated. However, the ferritin field was not completely satisfied. Today, for example, researchers are interested in refining the details of ferritin function, in discovering the role of ferritin in a variety of diseases, and in using ferritin for materials chemistry applications. The work presented in this dissertation highlights the progress that we have made in each of these three areas: (1) Mechanistic studies: The buffer used during horse spleen ferritin iron loading significantly influences the mineralization process and the quantity of iron deposited in ferritin. The ferrihydrite core of ferritin is crystalline and ordered when iron is loaded into ferritin in the presence of imidazole buffer. On the other hand, when iron is loaded into ferritin in the presence of MOPS buffer, the ferrihydrite core is less crystalline and less ordered, and a smaller amount of total iron is loaded in ferritin. We also show that iron can be released from the ferritin core in a non-reductive manner. The rate of Fe3+ release from horse spleen ferritin was measured using the Fe3+-specific chelator desferoxamine. We show that iron release occurs by three kinetic events. (2) Disease studies: In order to better understand iron disruption during disease states, we performed in vitro assays that mimicked chronic kidney disease. We tested the hypothesis that elevated levels of serum phosphate interrupted normal iron binding by transferrin and ferritin. Results show that phosphate competes for iron, forming an iron(III)-phosphate complex that is inaccessible to either transferrin or ferritin. Ferritin samples separated from the iron(III)-phosphate complex shows that as the

  5. Opioid receptors: Structural and mechanistic insights into pharmacology and signaling.

    PubMed

    Shang, Yi; Filizola, Marta

    2015-09-15

    Opioid receptors are important drug targets for pain management, addiction, and mood disorders. Although substantial research on these important subtypes of G protein-coupled receptors has been conducted over the past two decades to discover ligands with higher specificity and diminished side effects, currently used opioid therapeutics remain suboptimal. Luckily, recent advances in structural biology of opioid receptors provide unprecedented insights into opioid receptor pharmacology and signaling. We review here a few recent studies that have used the crystal structures of opioid receptors as a basis for revealing mechanistic details of signal transduction mediated by these receptors, and for the purpose of drug discovery.

  6. A mechanistic, stochastic, population model of egg production.

    PubMed

    Johnston, S A; Gous, R M

    2007-04-01

    1. A mechanistic, stochastic egg production model is presented. Mean age at first egg may be predicted from the lighting programme applied during rearing, using the Bristol-Reading model (Lewis et al., 2002). 2. Rate of ovulation is determined by an amended version of the mathematical model of the ovulatory cycle, originally proposed by Etches and Schoch (1984). 3. Oviposition times are estimated from ovulation times. 4. Yolk, albumen and shell weights are calculated using allometric functions. 5. The model predicts egg production of a theoretical flock of laying hens for a full laying year, including random occurrences of double-yolked and soft-shelled eggs and internal ovulations.

  7. Improving Predictive Modeling in Pediatric Drug Development: Pharmacokinetics, Pharmacodynamics, and Mechanistic Modeling

    SciTech Connect

    Slikker, William; Young, John F.; Corley, Rick A.; Dorman, David C.; Conolly, Rory B.; Knudsen, Thomas; Erstad, Brian L.; Luecke, Richard H.; Faustman, Elaine M.; Timchalk, Chuck; Mattison, Donald R.

    2005-07-26

    A workshop was conducted on November 18?19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adultlike in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human.

  8. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality.

    PubMed

    Warnecke, Lisa; Turner, James M; Bollinger, Trent K; Misra, Vikram; Cryan, Paul M; Blehert, David S; Wibbelt, Gudrun; Willis, Craig K R

    2013-08-23

    White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid-base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid-base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality. PMID:23720520

  9. Mechanistic principles of antisense targets for the treatment of spinal muscular atrophy.

    PubMed

    Singh, Natalia N; Lee, Brian M; DiDonato, Christine J; Singh, Ravindra N

    2015-01-01

    Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the SMN1 gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under Phase III clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on ISS-N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here, the authors summarize the mechanistic principles behind various antisense targets currently available for SMA therapy.

  10. Mechanistic principles of antisense targets for the treatment of Spinal Muscular Atrophy

    PubMed Central

    Singh, Natalia N.; Lee, Brian M.; DiDonato, Christine J.; Singh, Ravindra N.

    2015-01-01

    Spinal muscular atrophy (SMA) is a major neurodegenerative disorder of children and infants. SMA is primarily caused by low levels of SMN protein owing to deletions or mutations of the survival motor neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of the production of the functional SMN protein due to predominant skipping of exon 7. Several compounds, including antisense oligonucleotides (ASOs) that elevate SMN protein from SMN2 hold the promise for treatment. An ASO-based drug currently under phase 3 clinical trial employs intronic splicing silencer N1 (ISS-N1) as its target. Cumulative studies on the ISS-N1 reveal a wealth of information with significance to the overall therapeutic development for SMA. Here we summarize the mechanistic principles behind various antisense targets currently available for SMA therapy. PMID:26381381

  11. Pathophysiology of white-nose syndrome in bats: a mechanistic model linking wing damage to mortality

    USGS Publications Warehouse

    Warnecke, Lisa; Turner, James M.; Bollinger, Trent K.; Misra, Vikram; Cryan, Paul M.; Blehert, David S.; Wibbelt, Gudrun; Willis, Craig K.R.

    2013-01-01

    White-nose syndrome is devastating North American bat populations but we lack basic information on disease mechanisms. Altered blood physiology owing to epidermal invasion by the fungal pathogen Geomyces destructans (Gd) has been hypothesized as a cause of disrupted torpor patterns of affected hibernating bats, leading to mortality. Here, we present data on blood electrolyte concentration, haematology and acid–base balance of hibernating little brown bats, Myotis lucifugus, following experimental inoculation with Gd. Compared with controls, infected bats showed electrolyte depletion (i.e. lower plasma sodium), changes in haematology (i.e. increased haematocrit and decreased glucose) and disrupted acid–base balance (i.e. lower CO2 partial pressure and bicarbonate). These findings indicate hypotonic dehydration, hypovolaemia and metabolic acidosis. We propose a mechanistic model linking tissue damage to altered homeostasis and morbidity/mortality.

  12. Supramolecular polymerisation in water; elucidating the role of hydrophobic and hydrogen-bond interactions† †Electronic supplementary information (ESI) available: Experimental details, characterization by IR and UV spectroscopy and dynamic light scattering, video files of optical microscopy imaging. See DOI: 10.1039/c5sm02843d Click here for additional data file. Click here for additional data file. Click here for additional data file. Click here for additional data file.

    PubMed Central

    Leenders, Christianus M. A.; Baker, Matthew B.; Pijpers, Imke A. B.; Lafleur, René P. M.; Albertazzi, Lorenzo

    2016-01-01

    Understanding the self-assembly of small molecules in water is crucial for the development of responsive, biocompatible soft materials. Here, a family of benzene-1,3,5-tricarboxamide (BTA) derivatives that comprise a BTA moiety connected to an amphiphilic chain is synthesised with the aim to elucidate the role of hydrophobic and hydrogen-bonding interactions in the self-assembly of these BTAs. The amphiphilic chain consists of an alkyl chain with a length of 10, 11, or 12 methylene units, connected to a tetraethylene glycol (at the periphery). The results show that an undecyl spacer is the minimum length required for these BTAs to self-assemble into supramolecular polymers. Interestingly, exchange studies reveal only minor differences in exchange rates between BTAs containing undecyl or dodecyl spacers. Additionally, IR spectroscopy provides the first experimental evidence that hydrogen-bonding is operative and contributes to the stabilisation of the supramolecular polymers in water. PMID:26892482

  13. Combating Pathogenic Microorganisms Using Plant-Derived Antimicrobials: A Minireview of the Mechanistic Basis

    PubMed Central

    Upadhyaya, Indu; Kollanoor-Johny, Anup

    2014-01-01

    The emergence of antibiotic resistance in pathogenic bacteria has led to renewed interest in exploring the potential of plant-derived antimicrobials (PDAs) as an alternative therapeutic strategy to combat microbial infections. Historically, plant extracts have been used as a safe, effective, and natural remedy for ailments and diseases in traditional medicine. Extensive research in the last two decades has identified a plethora of PDAs with a wide spectrum of activity against a variety of fungal and bacterial pathogens causing infections in humans and animals. Active components of many plant extracts have been characterized and are commercially available; however, research delineating the mechanistic basis of their antimicrobial action is scanty. This review highlights the potential of various plant-derived compounds to control pathogenic bacteria, especially the diverse effects exerted by plant compounds on various virulence factors that are critical for pathogenicity inside the host. In addition, the potential effect of PDAs on gut microbiota is discussed. PMID:25298964

  14. A Three-Stage Mechanistic Model for Ammonia Borane Dehydrogenation by Shvo’s Catalyst

    PubMed Central

    Lu, Zhiyao; Conley, Brian L.; Williams, Travis J.

    2012-01-01

    We propose a mechanistic model for three-stage dehydrogenation of ammonia borane (AB) catalyzed by Shvo’s cyclopentadienone-ligated ruthenium complex. We provide evidence for a plausible mechanism for catalyst deactivation, the transition from fast catalysis to slow catalysis, and relate those findings to the invention of a second-generation catalyst that does not suffer from the same deactivation chemistry. The primary mechanism of catalyst deactivation is borazine-mediated hydroboration of the ruthenium species that is the active oxidant in the fast catalysis case. This transition is characterized by a change in the rate law for the reaction and changes in the apparent resting state of the catalyst. Also, in this slow catalysis situation, we see an additional intermediate in the sequence of boron, nitrogen species, aminodiborane. This occurs with concurrent generation of NH3, which itself does not strongly affect the rate of AB dehydrogenation. PMID:23335832

  15. A Three-Stage Mechanistic Model for Ammonia Borane Dehydrogenation by Shvo's Catalyst.

    PubMed

    Lu, Zhiyao; Conley, Brian L; Williams, Travis J

    2012-10-01

    We propose a mechanistic model for three-stage dehydrogenation of ammonia borane (AB) catalyzed by Shvo's cyclopentadienone-ligated ruthenium complex. We provide evidence for a plausible mechanism for catalyst deactivation, the transition from fast catalysis to slow catalysis, and relate those findings to the invention of a second-generation catalyst that does not suffer from the same deactivation chemistry.The primary mechanism of catalyst deactivation is borazine-mediated hydroboration of the ruthenium species that is the active oxidant in the fast catalysis case. This transition is characterized by a change in the rate law for the reaction and changes in the apparent resting state of the catalyst. Also, in this slow catalysis situation, we see an additional intermediate in the sequence of boron, nitrogen species, aminodiborane. This occurs with concurrent generation of NH(3), which itself does not strongly affect the rate of AB dehydrogenation. PMID:23335832

  16. Descriptive vs. mechanistic network models in plant development in the post-genomic era.

    PubMed

    Davila-Velderrain, J; Martinez-Garcia, J C; Alvarez-Buylla, E R

    2015-01-01

    Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals. PMID:25757787

  17. Discerning mechanistically rewired biological pathways by cumulative interaction heterogeneity statistics.

    PubMed

    Cotton, Travis B; Nguyen, Hien H; Said, Joseph I; Ouyang, Zhengyu; Zhang, Jinfa; Song, Mingzhou

    2015-01-01

    Changes in response of a biological pathway could be a consequence of either pathway rewiring, changed input, or a combination of both. Most pathway analysis methods are not designed for mechanistic rewiring such as regulatory element variations. This limits our understanding of biological pathway evolution. Here we present a Q-method to discern whether changed pathway response is caused by mechanistic rewiring of pathways due to evolution. The main innovation is a cumulative pathway interaction heterogeneity statistic accounting for rewiring-specific effects on the rate of change of each molecular variable across conditions. The Q-method remarkably outperformed differential-correlation based approaches on data from diverse biological processes. Strikingly, it also worked well in differentiating rewired chaotic systems, whose dynamics are notoriously difficult to predict. Applying the Q-method on transcriptome data of four yeasts, we show that pathway interaction heterogeneity for known metabolic and signaling pathways is indeed a predictor of interspecies genetic rewiring due to unbalanced TATA box-containing genes among the yeasts. The demonstrated effectiveness of the Q-method paves the way to understanding network evolution at the resolution of functional biological pathways. PMID:25921728

  18. Modeling of batch sorber system: kinetic, mechanistic, and thermodynamic modeling

    NASA Astrophysics Data System (ADS)

    Mishra, Vishal

    2016-09-01

    The present investigation has dealt with the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase. Various rate models were evaluated to elucidate the kinetics of copper and zinc biosorptions, and the results indicated that the pseudo-second-order model was more appropriate than the pseudo-first-order model. The curve of the initial sorption rate versus the initial concentration of copper and zinc ions also complemented the results of the pseudo-second-order model. Models used for the mechanistic modeling were the intra-particle model of pore diffusion and Bangham's model of film diffusion. The results of the mechanistic modeling together with the values of pore and film diffusivities indicated that the preferential mode of the biosorption of copper and zinc ions on the surface of egg-shell particles in the liquid phase was film diffusion. The results of the intra-particle model showed that the biosorption of the copper and zinc ions was not dominated by the pore diffusion, which was due to macro-pores with open-void spaces present on the surface of egg-shell particles. The thermodynamic modeling reproduced the fact that the sorption of copper and zinc was spontaneous, exothermic with the increased order of the randomness at the solid-liquid interface.

  19. From Data Patterns to Mechanistic Models in Acute Critical Illness

    PubMed Central

    Aerts, Jean-Marie; Haddad, Wassim M.; An, Gary; Vodovotz, Yoram

    2014-01-01

    The complexity of the physiologic and inflammatory response in acute critical illness has stymied the accurate diagnosis and development of therapies. The Society for Complex Acute Illness was formed a decade ago with the goal of leveraging multiple complex systems approaches in order to address this unmet need. Two main paths of development have characterized the Society’s approach: i) data pattern analysis, either defining the diagnostic/prognostic utility of complexity metrics of physiological signals or multivariate analyses of molecular and genetic data, and ii) mechanistic mathematical and computational modeling, all being performed with an explicit translational goal. Here, we summarize the progress to date on each of these approaches, along with pitfalls inherent in the use of each approach alone. We suggest that the next decade holds the potential to merge these approaches, connecting patient diagnosis to treatment via mechanism-based dynamical system modeling and feedback control, and allowing extrapolation from physiologic signals to biomarkers to novel drug candidates. As a predicate example, we focus on the role of data-driven and mechanistic models in neuroscience, and the impact that merging these modeling approaches can have on general anesthesia. PMID:24768566

  20. Water on hydrophobic surfaces: Mechanistic modeling of hydrophobic interaction chromatography.

    PubMed

    Wang, Gang; Hahn, Tobias; Hubbuch, Jürgen

    2016-09-23

    Mechanistic models are successfully used for protein purification process development as shown for ion-exchange column chromatography (IEX). Modeling and simulation of hydrophobic interaction chromatography (HIC) in the column mode has been seldom reported. As a combination of these two techniques is often encountered in biopharmaceutical purification steps, accurate modeling of protein adsorption in HIC is a core issue for applying holistic model-based process development, especially in the light of the Quality by Design (QbD) approach. In this work, a new mechanistic isotherm model for HIC is derived by consideration of an equilibrium between well-ordered water molecules and bulk-like ordered water molecules on the hydrophobic surfaces of protein and ligand. The model's capability of describing column chromatography experiments is demonstrated with glucose oxidase, bovine serum albumin (BSA), and lysozyme on Capto™ Phenyl (high sub) as model system. After model calibration from chromatograms of bind-and-elute experiments, results were validated with batch isotherms and prediction of further gradient elution chromatograms. PMID:27575919

  1. Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

    PubMed Central

    2013-01-01

    Summary The copper-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  2. Advancements in the mechanistic understanding of the copper-catalyzed azide-alkyne cycloaddition.

    PubMed

    Berg, Regina; Straub, Bernd F

    2013-01-01

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I) alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC's catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I) catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates. PMID:24367437

  3. p53 and rapamycin are additive

    PubMed Central

    Campisi, Judith; Huang, Jing; Jones, Diane; Dodds, Sherry G.; Williams, Charnae; Hubbard, Gene; Livi, Carolina B.; Gao, Xiaoli; Weintraub, Susan; Curiel, Tyler; Sharp, Z. Dave; Hasty, Paul

    2015-01-01

    Mechanistic target of rapamycin (mTOR) is a kinase found in a complex (mTORC1) that enables macromolecular synthesis and cell growth and is implicated in cancer etiology. The rapamycin-FK506 binding protein 12 (FKBP12) complex allosterically inhibits mTORC1. In response to stress, p53 inhibits mTORC1 through a separate pathway involving cell signaling and amino acid sensing. Thus, these different mechanisms could be additive. Here we show that p53 improved the ability of rapamycin to: 1) extend mouse life span, 2) suppress ionizing radiation (IR)-induced senescence-associated secretory phenotype (SASP) and 3) increase the levels of amino acids and citric acid in mouse embryonic stem (ES) cells. This additive effect could have implications for cancer treatment since rapamycin and p53 are anti-oncogenic. PMID:26158292

  4. Palladium(0)/NHC-Catalyzed Reductive Heck Reaction of Enones: A Detailed Mechanistic Study.

    PubMed

    Raoufmoghaddam, Saeed; Mannathan, Subramaniyan; Minnaard, Adriaan J; de Vries, Johannes G; Reek, Joost N H

    2015-12-14

    We have studied the mechanism of the palladium-catalyzed reductive Heck reaction of para-substituted enones with 4-iodoanisole by using N,N-diisopropylethylamine (DIPEA) as the reductant. Kinetic studies and in situ spectroscopic analysis have provided a detailed insight into the reaction. Progress kinetic analysis demonstrated that neither catalyst decomposition nor product inhibition occurred during the catalysis. The reaction is first order in the palladium and aryl iodide, and zero order in the activated alkene, N-heterocyclic carbene (NHC) ligand, and DIPEA. The experiments with deuterated solvent ([D7]DMF) and deuterated base ([D15]Et3N) supported the role of the amine as a reductant in the reaction. The palladium complex [Pd(0)(NHC)(1)] has been identified as the resting state. The kinetic experiments by stopped-flow UV/Vis also revealed that the presence of the second substrate, benzylideneacetone 1, slows down the oxidative addition of 4-iodoanisole through its competing coordination to the palladium center. The kinetic and mechanistic studies indicated that the oxidative addition of the aryl iodide is the rate-determining step. Various scenarios for the oxidative addition step have been analyzed by using DFT calculations (bp86/def2-TZVP) that supported the inhibiting effect of substrate 1 by formation of resting state [Pd(0)(NHC)(1)] species at the cost of further increase in the energy barrier of the oxidative addition step. PMID:26561034

  5. A new mechanistic framework to predict OCS fluxes in soils

    NASA Astrophysics Data System (ADS)

    Sauze, Joana; Ogee, Jérôme; Launois, Thomas; Kesselmeier, Jürgen; Van Diest, Heidi; Wingate, Lisa

    2015-04-01

    A better description of the amplitude of photosynthetic and respiratory gross CO2 fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulfide (COS) is the most abundant sulphur gas in the atmosphere and has been proposed as a new tracer of gross photosynthesis, as the uptake of COS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. However, soils also exchange COS with the atmosphere and there is growing evidence that this flux must also be accounted for in atmospheric budgets. In this context a new mechanistic description of soil-atmosphere COS exchange is clearly needed. Soils can take up COS from the atmosphere as the soil biota also contain CA, and COS emissions from soils have also been reported in agricultural fields or anoxic soils. Previous studies have also shown that soil COS fluxes present an optimum soil water content and soil temperature. Here we propose a new mechanistic framework to predict the fluxes of COS between the soils and the atmosphere. We describe the COS soil budget by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of COS by CA is total and irreversible. To describe COS diffusion through the soil matrix, we use different formulations of soil air-filled pore space and temperature, depending on the turbulence level above the soil surface. Using this model we are able to explain the observed presence of an optimum temperature for soil COS uptake and show how this optimum can shift to cooler temperatures in the presence of soil COS emissions. Our model can also explain the observed optimum with soil moisture content previously described in the literature (e.g. Van Diest & Kesselmeier, 2008) as a result of diffusional constraints on COS hydrolysis. These diffusional constraints are also responsible for the response of COS uptake to soil

  6. Conservative or reactive? Mechanistic chemical perspectives on organic matter stability

    NASA Astrophysics Data System (ADS)

    Koch, Boris

    2016-04-01

    Carbon fixation by terrestrial and marine primary production has a fundamental seasonal effect on the atmospheric carbon content and it profoundly contributes to long-term carbon storage in form of organic matter (OM) in soils, water, and sediments. The efficacy of this sequestration process strongly depends on the degree of OM persistence. Therefore, one of the key issues in dissolved and particulate OM research is to assess the stability of reservoirs and to quantify their contribution to global carbon fluxes. Incubation experiments are helpful to assess OM stability during the first, early diagenetic turnover induced by sunlight or microbes. However, net carbon fluxes within the global carbon cycle also act on much longer time scales, which are not amenable in experiments. It is therefore critical to improve our mechanistic understanding to be able to assess potential future changes in the organic matter cycle. This session contribution highlights some achievements and open questions in the field. An improved mechanistic understanding of OM turnover particularly depends on the molecular characterization of biogeochemical processes and their kinetics: (i) in soils and sediments, aggregation/disaggregation of OM is primarily controlled by its molecular composition. Hence, the chemical composition determines the transfer of organic carbon from the large particulate to the small dissolved organic matter reservoir - an important substrate for microbial metabolism. (ii) In estuaries, dissolved organic carbon gradients usually suggest conservative behavior, whereas molecular-level studies reveal a substantial chemical modification of terrestrial DOM along the land-ocean interface. (iii) In the ocean, previous studies have shown that the recalcitrance of OM depends on bulk concentration and energy yield. However, ultrahigh resolution mass spectrometry in combination with radiocarbon analyses also emphasized that stability is tightly connected to molecular composition

  7. Mechanistic models of plant seed dispersal by wind in heterogeneous landscapes

    NASA Astrophysics Data System (ADS)

    Trakhtenbrot, A.; Katul, G. G.; Nathan, R.

    2010-12-01

    Seed dispersal, and especially long-distance dispersal (LDD), is a key process in plant population survival, colonization, and gene flow. Its importance is amplified by the man-induced habitat fragmentation, climate change and invasions of exotic species. Mechanistic seed dispersal models are central to quantitative prediction of dispersal patterns and understanding their underlying mechanisms. For wind dispersal, most current mechanistic models assume homogenous environment. Although both topography and sharp transitions in vegetation stature profoundly affect wind flow, accounting for these effects via simplified models remains a vexing research problem. Such simplified models are needed to inform ecosystem managers about consequences of landscape fragmentation. We modified the Coupled Eulerian-Lagrangian closure (CELC) mechanistic dispersal model to represent scenarios of wind flow over a sharp transition from short to tall vegetation or over forested hilly terrain, and predicted the resulting dispersal distances and direction. We parameterized the wind and vegetation factors using measurements taken on a hill with short height Mediterranean shrubland and pine forest vegetation at Mt. Pithulim, Israel. For the short-to-tall vegetation transition scenario, the main feature of the modeled wind field is an exponential decay of the mean horizontal wind velocity, assuming that the mean momentum equation simplifies to a balance between the advective acceleration and the drag force terms. As a consequence of the incompressibility condition, this exponential decay leads to strong upward mean vertical velocity component. We found that for seed release downwind of the edge, the simulated median (short) and 99-th percentile (long) distances were longer than those for the homogeneous tall vegetation scenario. For seed release upwind of the edge the effect on dispersal distance was more complex and depended on the release height and he seed terminal velocity of the seeds

  8. Backtracking behaviour in lost ants: an additional strategy in their navigational toolkit.

    PubMed

    Wystrach, Antoine; Schwarz, Sebastian; Baniel, Alice; Cheng, Ken

    2013-10-22

    Ants use multiple sources of information to navigate, but do not integrate all this information into a unified representation of the world. Rather, the available information appears to serve three distinct main navigational systems: path integration, systematic search and the use of learnt information--mainly via vision. Here, we report on an additional behaviour that suggests a supplemental system in the ant's navigational toolkit: 'backtracking'. Homing ants, having almost reached their nest but, suddenly displaced to unfamiliar areas, did not show the characteristic undirected headings of systematic searches. Instead, these ants backtracked in the compass direction opposite to the path that they had just travelled. The ecological function of this behaviour is clear as we show it increases the chances of returning to familiar terrain. Importantly, the mechanistic implications of this behaviour stress an extra level of cognitive complexity in ant navigation. Our results imply: (i) the presence of a type of 'memory of the current trip' allowing lost ants to take into account the familiar view recently experienced, and (ii) direct sharing of information across different navigational systems. We propose a revised architecture of the ant's navigational toolkit illustrating how the different systems may interact to produce adaptive behaviours.

  9. A mechanistic interpretation of the resonant wave-particle interaction

    NASA Astrophysics Data System (ADS)

    Chim, Chi Yung; O'Neil, Thomas M.

    2016-05-01

    This paper provides a simple mechanistic interpretation of the resonant wave-particle interaction of Landau. For the simple case of a Langmuir wave in a Vlasov plasma, the non-resonant electrons satisfy an oscillator equation that is driven resonantly by the bare electric field from the resonant electrons, and in the case of wave damping, this complex driver field is of a phase to reduce the oscillation amplitude. The wave-particle resonant interaction also occurs in waves governed by 2D E × B drift dynamics, such as a diocotron wave. In this case, the bare electric field from the resonant electrons causes E × B drift motion back in the core plasma, reducing the amplitude of the wave.

  10. Atrial Fibrillation and Hypertension: Mechanistic, Epidemiologic, and Treatment Parallels

    PubMed Central

    Ogunsua, Adedotun A.; Shaikh, Amir Y.; Ahmed, Mohamed; McManus, David D.

    2015-01-01

    Atrial fibrillation (AF) is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and hypertension (HTN). Of all the risk factors, HTN is the most commonly encountered condition in patients with incident AF. Hypertension is associated with a 1.8-fold increase in the risk of developing new-onset AF and a 1.5-fold increase in the risk of progression to permanent AF. Hypertension predisposes to cardiac structural changes that influence the development of AF such as atrial remodeling. The renin angiotensin aldosterone system has been demonstrated to be a common mechanistic link in the pathogenesis of HTN and AF. Importantly, HTN is one of the few modifiable AF risk factors, and guideline-directed management of HTN may reduce the incidence of AF. PMID:27057292

  11. Mechanistic insights into selective autophagy pathways: lessons from yeast.

    PubMed

    Farré, Jean-Claude; Subramani, Suresh

    2016-09-01

    Autophagy has burgeoned rapidly as a field of study because of its evolutionary conservation, the diversity of intracellular cargoes degraded and recycled by this machinery, the mechanisms involved, as well as its physiological relevance to human health and disease. This self-eating process was initially viewed as a non-selective mechanism used by eukaryotic cells to degrade and recycle macromolecules in response to stress; we now know that various cellular constituents, as well as pathogens, can also undergo selective autophagy. In contrast to non-selective autophagy, selective autophagy pathways rely on a plethora of selective autophagy receptors (SARs) that recognize and direct intracellular protein aggregates, organelles and pathogens for specific degradation. Although SARs themselves are not highly conserved, their modes of action and the signalling cascades that activate and regulate them are. Recent yeast studies have provided novel mechanistic insights into selective autophagy pathways, revealing principles of how various cargoes can be marked and targeted for selective degradation. PMID:27381245

  12. Mechanistic characterization of chloride interferences in electrothermal atomization systems

    USGS Publications Warehouse

    Shekiro, J.M.; Skogerboe, R.K.; Taylor, H.E.

    1988-01-01

    A computer-controlled spectrometer with a photodiode array detector has been used for wavelength and temperature resolved characterization of the vapor produced by an electrothermal atomizer. The system has been used to study the chloride matrix interference on the atomic absorption spectrometric determination of manganese and copper. The suppression of manganese and copper atom populations by matrix chlorides such as those of calcium and magnesium is due to the gas-phase formation of an analyte chloride species followed by the diffusion of significant fractions of these species from the atom cell prior to completion of the atomization process. The analyte chloride species cannot be formed when matrix chlorides with metal-chloride bond dissociation energies above those of the analyte chlorides are the principal entitles present. The results indicate that multiple wavelength spectrometry used to obtain temperature-resolved spectra is a viable tool in the mechanistic characterization of interference effects observed with electrothermal atomization systems. ?? 1988 American Chemical Society.

  13. Atrial Fibrillation and Hypertension: Mechanistic, Epidemiologic, and Treatment Parallels.

    PubMed

    Ogunsua, Adedotun A; Shaikh, Amir Y; Ahmed, Mohamed; McManus, David D

    2015-01-01

    Atrial fibrillation (AF) is an increasingly prevalent condition and the most common sustained arrhythmia encountered in ambulatory and hospital practice. Several clinical risk factors for AF include age, sex, valvular heart disease, obesity, sleep apnea, heart failure, and hypertension (HTN). Of all the risk factors, HTN is the most commonly encountered condition in patients with incident AF. Hypertension is associated with a 1.8-fold increase in the risk of developing new-onset AF and a 1.5-fold increase in the risk of progression to permanent AF. Hypertension predisposes to cardiac structural changes that influence the development of AF such as atrial remodeling. The renin angiotensin aldosterone system has been demonstrated to be a common mechanistic link in the pathogenesis of HTN and AF. Importantly, HTN is one of the few modifiable AF risk factors, and guideline-directed management of HTN may reduce the incidence of AF. PMID:27057292

  14. Mechanistic model for void distribution in flashing flow

    SciTech Connect

    Riznic, J.; Ishii, M.; Afgan, N.

    1987-01-01

    A problem of discharging of an initially subcooled liquid from a high pressure condition into a low pressure environment is quite important in several industrial systems such as nuclear reactors and chemical reactors. A new model for the flashing process is proposed here based on the wall nucleation theory, bubble growth model and drift-flux bubble transport model. In order to calculate the bubble number density, the bubble number transport equation with a distributed source from the wall nucleation sites is used. The model predictions in terms of the void fraction are compared to Moby Dick and BNL experimental data. It shows that satisfactory agreements could be obtained from the present model without any floating parameter to be adjusted with data. This result indicates that, at least for the experimental conditions considered here, the mechanistic prediction of the flashing phenomenon is possible based on the present wall nucleation based model. 43 refs., 4 figs.

  15. Mechanistic model for void distribution in flashing flow

    NASA Astrophysics Data System (ADS)

    Riznic, J.; Ishii, M.; Afgan, N.

    A problem of discharging of an initially subcooled liquid from a high pressure condition into a low pressure environment is quite important in several industrial systems such as nuclear reactors and chemical reactors. A new model for the flashing process is proposed here based on the wall nucleation theory, bubble growth model and drift-flux bubble transport model. In order to calculate the bubble number density, the bubble number transport equation with a distributed source from the wall nucleation sites is used. The model predictions in terms of the void fraction are compared to Moby Dick and BNL experimental data. It shows that satisfactory agreements could be obtained from the present model without any floating parameter to be adjusted with data. This result indicates that, at least for the experimental conditions considered here, the mechanistic prediction of the flashing phenomenon is possible based on the present wall nucleation based model.

  16. Calorie restriction and cancer prevention: a mechanistic perspective

    PubMed Central

    2013-01-01

    Calorie restriction (CR) is one of the most potent broadly acting dietary interventions for inducing weight loss and for inhibiting cancer in experimental models. Translation of the mechanistic lessons learned from research on CR to cancer prevention strategies in human beings is important given the high prevalence of excess energy intake, obesity, and metabolic syndrome in many parts of the world and the established links between obesity-associated metabolic perturbations and increased risk or progression of many types of cancer. This review synthesizes findings on the biological mechanisms underlying many of the anticancer effects of CR, with emphasis on the impact of CR on growth factor signaling pathways, inflammation, cellular and systemic energy homeostasis pathways, vascular perturbations, and the tumor microenvironment. These CR-responsive pathways and processes represent targets for translating CR research into effective cancer prevention strategies in human beings. PMID:24280167

  17. Mechanistic modeling confronts the complexity of molecular cell biology.

    PubMed

    Phair, Robert D

    2014-11-01

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  18. Mechanistic failure mode investigation and resolution of parvovirus retentive filters.

    PubMed

    LaCasse, Daniel; Lute, Scott; Fiadeiro, Marcus; Basha, Jonida; Stork, Matthew; Brorson, Kurt; Godavarti, Ranga; Gallo, Chris

    2016-07-01

    Virus retentive filters are a key product safety measure for biopharmaceuticals. A simplistic perception is that they function solely based on a size-based particle removal mechanism of mechanical sieving and retention of particles based on their hydrodynamic size. Recent observations have revealed a more nuanced picture, indicating that changes in viral particle retention can result from process pressure and/or flow interruptions. In this study, a mechanistic investigation was performed to help identify a potential mechanism leading to the reported reduced particle retention in small virus filters. Permeate flow rate or permeate driving force were varied and analyzed for their impact on particle retention in three commercially available small virus retentive filters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:959-970, 2016.

  19. Obesity, energy balance, and cancer: a mechanistic perspective.

    PubMed

    Hursting, Stephen D

    2014-01-01

    Nearly 36 % of adults and 20 % of children in the USA are obese, defined as a body mass index (BMI) ≥30 kg/m(2). Obesity, which is accompanied by metabolic dysregulation often manifesting in the metabolic syndrome, is an established risk factor for many cancers. Within the growth-promoting, proinflammatory environment of the obese state, cross talk between macrophages, adipocytes, and epithelial cells occurs via obesity-associated hormones, cytokines, and other mediators that may enhance cancer risk and/or progression. This chapter synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on obesity-associated enhancements in growth factor signaling, inflammation, and vascular integrity processes, as well as obesity-dependent microenvironmental perturbations, including the epithelial-to-mesenchymal transition. These interrelated pathways represent possible mechanistic targets for disrupting the obesity-cancer link.

  20. Mechanistic modeling confronts the complexity of molecular cell biology

    PubMed Central

    Phair, Robert D.

    2014-01-01

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist–electrical engineer–systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build—and subject to exhaustive experimental tests—models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set. PMID:25368428

  1. Antiproliferative naphthopyrans: biological activity, mechanistic studies and therapeutic potential.

    PubMed

    Dell, C P

    1998-06-01

    This article will firstly briefly review the newer generation of immunosuppressant drugs, focusing mainly on tacrolimus (FK-506), sirolimus (rapamycin), mycophenolate mofetil (RS-61443) and leflunomide (HWA 486) and then describe work carried out at the Lilly Research Centre on analogues of leflunomide and subsequent diversion into a structurally distinct series of compounds, the naphthopyrans. A clear structure activity relationship exists within this series and selected data from a Concanavalin A stimulated T-cell proliferation assay are presented to illustrate this. Although the compounds proved to possess little in vivo activity in our rheumatoid arthritis program, examination of the compounds in in vitro and in vivo models within the diabetic complications group showed the compounds behaved as would be anticipated for inhibitors of protein kinase C, although this direct mode of action was clearly not correct. Mechanistic investigations revealed that the favoured compound 290181 blocks phorbol 12,13-dibutyrate-induced binding of transcription factor proteins to the PEA3/TRE sequence of the promoter region of the urokinase plasminogen activator gene. The compounds also showed antiproliferative effects on vascular smooth muscle cells, an in vitro activity that translated into in vivo efficacy in a rat model of restenosis. Mechanistic studies here demonstrated that 290181 blocks proliferation in the G2/M phase of the cell cycle by binding directly to a novel site on tubulin. Finally the compounds were shown to inhibit the release of neutral proteases from interleukin-1 stimulated articular chondrocytes, this activity having implications in the degenerative aspects of osteoarthritis. PMID:9562601

  2. Assembly Line Polyketide Synthases: Mechanistic Insights and Unsolved Problems

    PubMed Central

    2015-01-01

    Two hallmarks of assembly line polyketide synthases have motivated an interest in these unusual multienzyme systems, their stereospecificity and their capacity for directional biosynthesis. In this review, we summarize the state of knowledge regarding the mechanistic origins of these two remarkable features, using the 6-deoxyerythronolide B synthase as a prototype. Of the 10 stereocenters in 6-deoxyerythronolide B, the stereochemistry of nine carbon atoms is directly set by ketoreductase domains, which catalyze epimerization and/or diastereospecific reduction reactions. The 10th stereocenter is established by the sequential action of three enzymatic domains. Thus, the problem has been reduced to a challenge in mainstream enzymology, where fundamental gaps remain in our understanding of the structural basis for this exquisite stereochemical control by relatively well-defined active sites. In contrast, testable mechanistic hypotheses for the phenomenon of vectorial biosynthesis are only just beginning to emerge. Starting from an elegant theoretical framework for understanding coupled vectorial processes in biology [Jencks, W. P. (1980) Adv. Enzymol. Relat. Areas Mol. Biol. 51, 75–106], we present a simple model that can explain assembly line polyketide biosynthesis as a coupled vectorial process. Our model, which highlights the important role of domain–domain interactions, not only is consistent with recent observations but also is amenable to further experimental verification and refinement. Ultimately, a definitive view of the coordinated motions within and between polyketide synthase modules will require a combination of structural, kinetic, spectroscopic, and computational tools and could be one of the most exciting frontiers in 21st Century enzymology. PMID:24779441

  3. Toxic neuropathies: Mechanistic insights based on a chemical perspective.

    PubMed

    LoPachin, Richard M; Gavin, Terrence

    2015-06-01

    2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies.

  4. Mechanistic diversity of the van Leusen reaction applied to 6-ketomorphinans and synthetic potential of the resulting acrylonitrile substructures.

    PubMed

    Schütz, Johannes; Windisch, Petra; Kristeva, Elka; Wurst, Klaus; Ongania, Karl-Hans; Horvath, Ulrike E I; Schottenberger, Herwig; Laus, Gerhard; Schmidhammer, Helmut

    2005-06-24

    Tosylmethyl isocyanide was used to convert 7,8-didehydro-6-ketomorphinans to 6,7-didehydromorphinan-6-carbonitriles with retainment of the 4,5-epoxy ring. However, ring opening occurred in the presence of NaH giving 5,6,7,8-tetradehydromorphinan-6-carbonitriles. Addition of nucleophiles such as Li diisopropylamide or Grignard reagents to the acrylonitrile substructure yielded ring-opened 5,6-didehydro products. Seven products were characterized by X-ray crystal structure analysis and revealed insight into the mechanistic diversity of the van Leusen reaction.

  5. Simvastatin and dipentyl phthalate lower testosterone production and exhibit dose additive effects on the fetal testis via distinct mechanistic pathways

    EPA Science Inventory

    Sex differentiation of the mammalian reproductive tract is a highly regulated process that is driven, in part, by fetal testosterone (T) production. In utero exposure to phthalate esters (PE) during sex differentiation can result in reproductive tract malformations in rats. PE al...

  6. Randomized pilot study and qualitative evaluation of a clinical decision support system for brain tumour diagnosis based on SV ¹H MRS: evaluation as an additional information procedure for novice radiologists.

    PubMed

    Sáez, Carlos; Martí-Bonmatí, Luis; Alberich-Bayarri, Angel; Robles, Montserrat; García-Gómez, Juan M

    2014-02-01

    The results of a randomized pilot study and qualitative evaluation of the clinical decision support system Curiam BT are reported. We evaluated the system's feasibility and potential value as a radiological information procedure complementary to magnetic resonance (MR) imaging to assist novice radiologists in diagnosing brain tumours using MR spectroscopy (1.5 and 3.0T). Fifty-five cases were analysed at three hospitals according to four non-exclusive diagnostic questions. Our results show that Curiam BT improved the diagnostic accuracy in all the four questions. Additionally, we discuss the findings of the users' feedback about the system, and the further work to optimize it for real environments and to conduct a large clinical trial. PMID:24480160

  7. Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study.

    PubMed

    Laurell Nash, Anna; Hertzberg, Robin; Wen, Ye-Qian; Dahlgren, Björn; Brinck, Tore; Moberg, Christina

    2016-03-01

    A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.

  8. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    SciTech Connect

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-04-15

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  9. Backtracking behaviour in lost ants: an additional strategy in their navigational toolkit

    PubMed Central

    Wystrach, Antoine; Schwarz, Sebastian; Baniel, Alice; Cheng, Ken

    2013-01-01

    Ants use multiple sources of information to navigate, but do not integrate all this information into a unified representation of the world. Rather, the available information appears to serve three distinct main navigational systems: path integration, systematic search and the use of learnt information—mainly via vision. Here, we report on an additional behaviour that suggests a supplemental system in the ant's navigational toolkit: ‘backtracking’. Homing ants, having almost reached their nest but, suddenly displaced to unfamiliar areas, did not show the characteristic undirected headings of systematic searches. Instead, these ants backtracked in the compass direction opposite to the path that they had just travelled. The ecological function of this behaviour is clear as we show it increases the chances of returning to familiar terrain. Importantly, the mechanistic implications of this behaviour stress an extra level of cognitive complexity in ant navigation. Our results imply: (i) the presence of a type of ‘memory of the current trip’ allowing lost ants to take into account the familiar view recently experienced, and (ii) direct sharing of information across different navigational systems. We propose a revised architecture of the ant's navigational toolkit illustrating how the different systems may interact to produce adaptive behaviours. PMID:23966644

  10. Development of a mechanistic model for forced convection subcooled boiling

    NASA Astrophysics Data System (ADS)

    Shaver, Dillon R.

    The focus of this work is on the formulation, implementation, and testing of a mechanistic model of subcooled boiling. Subcooled boiling is the process of vapor generation on a heated wall when the bulk liquid temperature is still below saturation. This is part of a larger effort by the US DoE's CASL project to apply advanced computational tools to the simulation of light water reactors. To support this effort, the formulation of the dispersed field model is described and a complete model of interfacial forces is formulated. The model has been implemented in the NPHASE-CMFD computer code with a K-epsilon model of turbulence. The interfacial force models are built on extensive work by other authors, and include novel formulations of the turbulent dispersion and lift forces. The complete model of interfacial forces is compared to experiments for adiabatic bubbly flows, including both steady-state and unsteady conditions. The same model is then applied to a transient gas/liquid flow in a complex geometry of fuel channels in a sodium fast reactor. Building on the foundation of the interfacial force model, a mechanistic model of forced-convection subcooled boiling is proposed. This model uses the heat flux partitioning concept and accounts for condensation of bubbles attached to the wall. This allows the model to capture the enhanced heat transfer associated with boiling before the point of net generation of vapor, a phenomenon consistent with existing experimental observations. The model is compared to four different experiments encompassing flows of light water, heavy water, and R12 at different pressures, in cylindrical channels, an internally heated annulus, and a rectangular channel. The experimental data includes axial and radial profiles of both liquid temperature and vapor volume fraction, and the agreement can be considered quite good. The complete model is then applied to simulations of subcooled boiling in nuclear reactor subchannels consistent with the

  11. A new mechanistic framework to predict OCS fluxes from soils

    NASA Astrophysics Data System (ADS)

    Ogée, Jérôme; Sauze, Joana; Kesselmeier, Jürgen; Genty, Bernard; Van Diest, Heidi; Launois, Thomas; Wingate, Lisa

    2016-04-01

    Estimates of photosynthetic and respiratory fluxes at large scales are needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulfide (OCS) is the most abundant sulfur gas in the atmosphere and has been proposed as a new tracer of photosynthetic gross primary productivity (GPP), as the uptake of OCS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. However soils also exchange OCS with the atmosphere, which complicates the retrieval of GPP from atmospheric budgets. Indeed soils can take up large amounts of OCS from the atmosphere as soil microorganisms also contain CA, and OCS emissions from soils have been reported in agricultural fields or anoxic soils. To date no mechanistic framework exists to describe this exchange of OCS between soils and the atmosphere, but empirical results, once upscaled to the global scale, indicate that OCS consumption by soils dominates OCS emission and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, also with a large uncertainty. Here, we propose a new mechanistic model of the exchange of OCS between soils and the atmosphere that builds on our knowledge of soil CA activity from CO2 oxygen isotopes. In this model the OCS soil budget is described by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of OCS by CA is total and irreversible. Using this model we are able to explain the observed presence of an optimum temperature for soil OCS uptake and show how this optimum can shift to cooler temperatures in the presence of soil OCS emission. Our model can also explain the observed optimum with soil moisture content previously described in the literature as a result of diffusional constraints on OCS hydrolysis. These diffusional constraints are also responsible for the response of OCS uptake to soil weight and

  12. A new mechanistic framework to predict OCS fluxes from soils

    NASA Astrophysics Data System (ADS)

    Ogee, J.; Sauze, J.; Kesselmeier, J.; Genty, B.; Whelan, M.; Launois, T.; Wingate, L.

    2015-12-01

    A better description of the amplitude of photosynthetic and respiratory gross CO2 fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulphide (OCS) has been proposed as a new tracer of gross photosynthesis (GPP), as the uptake of OCS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. But soils also exchange OCS with the atmosphere which complicates the retrieval of GPP from atmospheric budgets. Indeed soils can take up large amounts of OCS from the atmosphere as soil microorganisms also contain CA, and OCS emissions from soils have been reported in agricultural or anoxic soils. To date no mechanistic framework exists to describe this exchange of OCS between soils and the atmosphere but empirical results, once up-scaled to the global scale, indicate that OCS consumption by soils dominates over production and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, with also a large uncertainty. Here, we propose a new mechanistic model of the exchange of OCS between soils and the atmosphere that builds on our knowledge of soil CA activity from CO2 oxygen isotopes. In this model the OCS soil budget is described by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of OCS by CA is total and irreversible. Using this model we are able to explain the observed presence of an optimum temperature for soil OCS uptake and show how this optimum can shift to cooler temperatures in the presence of soil OCS emissions. Our model can also explain the observed optimum with soil moisture content previously described in the literature as a result of diffusional constraints on OCS hydrolysis. In order to simulate the exact OCS uptake rates and patterns observed on several soils collected from a range of biomes, different CA activities

  13. A new mechanistic framework to predict OCS fluxes from soils

    NASA Astrophysics Data System (ADS)

    Ogée, J.; Sauze, J.; Kesselmeier, J.; Genty, B.; Van Diest, H.; Launois, T.; Wingate, L.

    2015-09-01

    Estimates of photosynthetic and respiratory fluxes at large scales is needed to improve our predictions of the current and future global CO2 cycle. Carbonyl sulphide (OCS) is the most abundant sulphur gas in the atmosphere and has been proposed as a new tracer of photosynthesis (GPP), as the uptake of OCS from the atmosphere is dominated by the activity of carbonic anhydrase (CA), an enzyme abundant in leaves that also catalyses CO2 hydration during photosynthesis. But soils also exchange OCS with the atmosphere which complicates the retrieval of GPP from atmospheric budgets. Indeed soils can take up large amounts of OCS from the atmosphere as soil microorganisms also contain CA, and OCS emissions from soils have been reported in agricultural fields or anoxic soils. To date no mechanistic framework exists to describe this exchange of OCS between soils and the atmosphere but empirical results, once upscaled to the global scale, indicate that OCS consumption by soils dominates over production and its contribution to the atmospheric budget is large, at about one third of the OCS uptake by vegetation, with also a large uncertainty. Here, we propose a new mechanistic model of the exchange of OCS between soils and the atmosphere that builds on our knowledge of soil CA activity from CO2 oxygen isotopes. In this model the OCS soil budget is described by a first-order reaction-diffusion-production equation, assuming that the hydrolysis of OCS by CA is total and irreversible. Using this model we are able to explain the observed presence of an optimum temperature for soil OCS uptake and show how this optimum can shift to cooler temperatures in the presence of soil OCS emissions. Our model can also explain the observed optimum with soil moisture content previously described in the literature as a result of diffusional constraints on OCS hydrolysis. These diffusional constraints are also responsible for the response of OCS uptake to soil weight and depth observed previously. In

  14. Station Blackout: A case study in the interaction of mechanistic and probabilistic safety analysis

    SciTech Connect

    Curtis Smith; Diego Mandelli; Cristian Rabiti

    2013-11-01

    The ability to better characterize and quantify safety margins is important to improved decision making about nuclear power plant design, operation, and plant life extension. As research and development (R&D) in the light-water reactor (LWR) Sustainability (LWRS) Program and other collaborative efforts yield new data, sensors, and improved scientific understanding of physical processes that govern the aging and degradation of plant SSCs needs and opportunities to better optimize plant safety and performance will become known. The purpose of the Risk Informed Safety Margin Characterization (RISMC) Pathway R&D is to support plant decisions for risk-informed margin management with the aim to improve economics, reliability, and sustain safety of current NPPs. In this paper, we describe the RISMC analysis process illustrating how mechanistic and probabilistic approaches are combined in order to estimate a safety margin. We use the scenario of a “station blackout” wherein offsite power and onsite power is lost, thereby causing a challenge to plant safety systems. We describe the RISMC approach, illustrate the station blackout modeling, and contrast this with traditional risk analysis modeling for this type of accident scenario.

  15. Exploring novel mechanistic insights in Alzheimer’s disease by assessing reliability of protein interactions

    PubMed Central

    Malhotra, Ashutosh; Younesi, Erfan; Sahadevan, Sudeep; Zimmermann, Joerg; Hofmann-Apitius, Martin

    2015-01-01

    Protein interaction networks are widely used in computational biology as a graphical means of representing higher-level systemic functions in a computable form. Although, many algorithms exist that seamlessly collect and measure protein interaction information in network models, they often do not provide novel mechanistic insights using quantitative criteria. Measuring information content and knowledge representation in network models about disease mechanisms becomes crucial particularly when exploring new target candidates in a well-defined functional context of a potential disease mechanism. To this end, we have developed a knowledge-based scoring approach that uses literature-derived protein interaction features to quantify protein interaction confidence. Thereby, we introduce the novel concept of knowledge cliffs, regions of the interaction network where a significant gap between high scoring and low scoring interactions is observed, representing a divide between established and emerging knowledge on disease mechanism. To show the application of this approach, we constructed and assessed reliability of a protein-protein interaction model specific to Alzheimer’s disease, which led to screening, and prioritization of four novel protein candidates. Evaluation of the identified candidates showed that two of them are already followed in clinical trials for testing potential AD drugs. PMID:26346705

  16. 27 CFR 5.33 - Additional requirements.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... English, and for products bottled for consumption within Puerto Rico the required information may be... cannot be removed without thorough application of water or other solvents. (f) Additional information...

  17. 27 CFR 5.33 - Additional requirements.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... English, and for products bottled for consumption within Puerto Rico the required information may be... cannot be removed without thorough application of water or other solvents. (f) Additional information...

  18. 27 CFR 5.33 - Additional requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... English, and for products bottled for consumption within Puerto Rico the required information may be... cannot be removed without thorough application of water or other solvents. (f) Additional information...

  19. 27 CFR 5.33 - Additional requirements.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... English, and for products bottled for consumption within Puerto Rico the required information may be... cannot be removed without thorough application of water or other solvents. (f) Additional information...

  20. Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades

    PubMed Central

    Liu, Zhichao; Wang, Yuping; Borlak, Jürgen; Tong, Weida

    2016-01-01

    Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades. PMID:27045805

  1. Cobalt-Catalyzed C(sp(2))-H Borylation: Mechanistic Insights Inspire Catalyst Design.

    PubMed

    Obligacion, Jennifer V; Semproni, Scott P; Pappas, Iraklis; Chirik, Paul J

    2016-08-24

    A comprehensive study into the mechanism of bis(phosphino)pyridine (PNP) cobalt-catalyzed C-H borylation of 2,6-lutidine using B2Pin2 (Pin = pinacolate) has been conducted. The experimentally observed rate law, deuterium kinetic isotope effects, and identification of the catalyst resting state support turnover limiting C-H activation from a fully characterized cobalt(I) boryl intermediate. Monitoring the catalytic reaction as a function of time revealed that borylation of the 4-position of the pincer in the cobalt catalyst was faster than arene borylation. Cyclic voltammetry established the electron withdrawing influence of 4-BPin, which slows the rate of C-H oxidative addition and hence overall catalytic turnover. This mechanistic insight inspired the next generation of 4-substituted PNP cobalt catalysts with electron donating and sterically blocking methyl and pyrrolidinyl substituents that exhibited increased activity for the C-H borylation of unactivated arenes. The rationally designed catalysts promote effective turnover with stoichiometric quantities of arene substrate and B2Pin2. Kinetic studies on the improved catalyst, 4-(H)2BPin, established a change in turnover limiting step from C-H oxidative addition to C-B reductive elimination. The iridium congener of the optimized cobalt catalyst, 6-(H)2BPin, was prepared and crystallographically characterized and proved inactive for C-H borylation, a result of the high kinetic barrier for reductive elimination from octahedral Ir(III) complexes. PMID:27476954

  2. Mechanistic solutions to the opening of the Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Schouten, Hans; Klitgord, Kim D.

    1994-06-01

    Two mechanistic models—which are unlike the traditional plate-tectonic landfill models used for most proposed Pangea reconstructions of the Yucatán block—relate the Mesozoic opening of the Gulf of Mexico directly to the movement of the North and South American plates: (1) a previous piggyback model in which Yucatán moves with South America out of the western gulf and (2) a new edge-driven model in which the motion of the Yucatán block is caused by forces applied to its margins by the movement of the North and South American plates. In the second model, Yucatán moves out of the northern Gulf of Mexico as a gear or roller bearing. On the basis of magnetic edge anomalies around the gulf, this edge-driven model predicts that from the Bathonian to Tithonian (˜170 to ˜150 Ma), Yucatán was rotated ˜60° counterclockwise as a rigid block between North and South America with rift propagation and extension occurring simultaneously in the Gulf of Mexico and Yucatan Basin.

  3. Mechanistic Features of Nanodiamonds in the Lapping of Magnetic Heads

    PubMed Central

    Jiang, Xionghua; Chen, Zhenxing; Wolfram, Joy; Yang, Zhizhou

    2014-01-01

    Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p0 = (3/2)·(W/πa2) and the indentation depth satisfies δ=k1P/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES) were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm·min−1) can be obtained with 100 nm diamonds embedded in the plate. PMID:25045730

  4. Equation-free mechanistic ecosystem forecasting using empirical dynamic modeling.

    PubMed

    Ye, Hao; Beamish, Richard J; Glaser, Sarah M; Grant, Sue C H; Hsieh, Chih-Hao; Richards, Laura J; Schnute, Jon T; Sugihara, George

    2015-03-31

    It is well known that current equilibrium-based models fall short as predictive descriptions of natural ecosystems, and particularly of fisheries systems that exhibit nonlinear dynamics. For example, model parameters assumed to be fixed constants may actually vary in time, models may fit well to existing data but lack out-of-sample predictive skill, and key driving variables may be misidentified due to transient (mirage) correlations that are common in nonlinear systems. With these frailties, it is somewhat surprising that static equilibrium models continue to be widely used. Here, we examine empirical dynamic modeling (EDM) as an alternative to imposed model equations and that accommodates both nonequilibrium dynamics and nonlinearity. Using time series from nine stocks of sockeye salmon (Oncorhynchus nerka) from the Fraser River system in British Columbia, Canada, we perform, for the the first time to our knowledge, real-data comparison of contemporary fisheries models with equivalent EDM formulations that explicitly use spawning stock and environmental variables to forecast recruitment. We find that EDM models produce more accurate and precise forecasts, and unlike extensions of the classic Ricker spawner-recruit equation, they show significant improvements when environmental factors are included. Our analysis demonstrates the strategic utility of EDM for incorporating environmental influences into fisheries forecasts and, more generally, for providing insight into how environmental factors can operate in forecast models, thus paving the way for equation-free mechanistic forecasting to be applied in management contexts.

  5. Anti-fibro-hepatocarcinogenic Chinese herbal medicines: A mechanistic overview

    PubMed Central

    Boye, Alex; Yang, Yan; Asenso, James; Wei, Wei

    2016-01-01

    Chinese herbal medicine (CHM) is an integral component of complementary/alternative medicine and it is increasingly becoming the preferred therapeutic modality for the treatment of liver fibrosis and hepatocellular carcinoma (HCC) worldwide. Accordingly, the World Health Organization (WHO) has attested to the popularity and efficacy of indigenous herbal therapies including CHM as a first line of treatment for some diseases including liver disorders. However, the WHO and drug discovery experts have always recommended that use of indigenous herbal remedies must go hand-in-hand with the requisite mechanistic elucidation so as to constitute a system of verification of efficacy within the ethnobotanical context of use. Although many CHM experts have advanced knowledge on CHM, nonetheless, more enlightenment is needed, particularly mechanisms of action of CHMs on fibro-hepato-carcinogenesis. We, herein, provide in-depth mechanisms of the action of CHMs which have demonstrated anti-fibro-hepatocarcinogenic effects, in pre-clinical and clinical studies as published in PubMed and other major scientific databases. Specifically, the review brings out the important signaling pathways, and their downstream targets which are modulated at multi-level by various anti-fibro-hepatocarcinogenic CHMs. PMID:27366355

  6. Thermal hydrogen-atom transfer from methane: A mechanistic exercise

    NASA Astrophysics Data System (ADS)

    Schwarz, Helmut

    2015-06-01

    Hydrogen-atom transfer (HAT) constitutes a key process in a broad range of chemical transformations as it covers heterogeneous, homogeneous, and enzymatic reactions. While open-shell metal oxo species [MO]rad are no longer regarded as being involved in the heterogeneously catalyzed oxidative coupling of methane (2CH4 + → C2H6 + H2O), these reagents are rather versatile in bringing about (gas-phase) hydrogen-atom transfer, even from methane at ambient conditions. In this mini-review, various mechanistic scenarios will be presented, and it will be demonstrated how these are affected by the composition of the metal-oxide cluster ions. Examples will be discussed, how 'doping' the clusters permits the control of the charge and spin situation at the active site and, thus, the course of the reaction. Also, the interplay between supposedly inert support material and the active site - the so-called 'aristocratic atoms' - of the gas-phase catalyst will be addressed. Finally, gas-phase HAT from methane will be analyzed in the broader context of thermal activation of inert Csbnd H bonds by metal-oxo species.

  7. Spectroscopic and Mechanistic Investigations of Dehaloperoxidase B from Amphitrite ornata†

    PubMed Central

    D’Antonio, Jennifer; D’Antonio, Edward L.; Thompson, Matthew K.; Bowden, Edmond F.; Franzen, Stefan; Smirnova, Tatyana; Ghiladi, Reza A.

    2010-01-01

    Dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a bifunctional enzyme that possesses both hemoglobin and peroxidase activities. Of the two DHP isoenzymes identified to date, much of the recent focus has been on DHP A, whereas very little is known pertaining to the activity, substrate specificity, mechanism of function, or spectroscopic properties of DHP B. Herein, we report the recombinant expression and purification of DHP B, as well as the details of our investigations into its catalytic cycle using biochemical assays, stopped-flow UV-visible, resonance Raman and rapid-freeze-quench electron paramagnetic resonance spectroscopies, and spectroelectrochemistry. Our experimental design reveals mechanistic insights and kinetic descriptions of the dehaloperoxidase mechanism which have not been previously reported for isoenzyme A. Namely, we demonstrate a novel reaction pathway in which the products of the oxidative dehalogenation of trihalophenols (dihaloquinones) are themselves capable of inducing formation of oxyferrous DHP B, and an updated catalytic cycle for DHP is proposed. We further demonstrate that unlike the traditional monofunctional peroxidases, the oxyferrous state in DHP is a peroxidase competent starting species, which suggests that the ferric oxidation state may not be an obligatory starting point for the enzyme. The data presented herein provide a link between the peroxidase and oxygen transport activities which furthers our understanding of how this bifunctional enzyme is able to unite its two inherent functions in one system. PMID:20545299

  8. A mechanistic stochastic framework for regulating bacterial cell division

    PubMed Central

    Ghusinga, Khem Raj; Vargas-Garcia, Cesar A.; Singh, Abhyudai

    2016-01-01

    How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size. PMID:27456660

  9. Mechanistic understanding of monosaccharide-air flow battery electrochemistry

    NASA Astrophysics Data System (ADS)

    Scott, Daniel M.; Tsang, Tsz Ho; Chetty, Leticia; Aloi, Sekotilani; Liaw, Bor Yann

    Recently, an inexpensive monosaccharide-air flow battery configuration has been demonstrated to utilize a strong base and a mediator redox dye to harness electrical power from the partial oxidation of glucose. Here the mechanistic understanding of glucose oxidation in this unique glucose-air power source is further explored by acid-base titration experiments, 13C NMR, and comparison of results from chemically different redox mediators (indigo carmine vs. methyl viologen) and sugars (fructose vs. glucose) via studies using electrochemical techniques. Titration results indicate that gluconic acid is the main product of the cell reaction, as supported by evidence in the 13C NMR spectra. Using indigo carmine as the mediator dye and fructose as the energy source, an abiotic cell configuration generates a power density of 1.66 mW cm -2, which is greater than that produced from glucose under similar conditions (ca. 1.28 mW cm -2). A faster transition from fructose into the ene-diol intermediate than from glucose likely contributed to this difference in power density.

  10. Mechanistic modeling of destratification in cryogenic storage tanks using ultrasonics.

    PubMed

    Jagannathan, T K; Mohanan, Srijith; Nagarajan, R

    2014-01-01

    Stratification is one of the main causes for vaporization of cryogens and increase of tank pressure during cryogenic storage. This leads subsequent problems such as cavitation in cryo-pumps, reduced length of storage time. Hence, it is vital to prevent stratification to improve the cost efficiency of storage systems. If stratified layers exist inside the tank, they have to be removed by suitable methods without venting the vapor. Sonication is one such method capable of keeping fluid layers mixed. In the present work, a mechanistic model for ultrasonic destratification is proposed and validated with destratification experiments done in water. Then, the same model is used to predict the destratification characteristics of cryogenic liquids such as liquid nitrogen (LN₂), liquid hydrogen (LH₂) and liquid ammonia (LNH₃). The destratification parameters are analysed for different frequencies of ultrasound and storage pressures by considering continuous and pulsed modes of ultrasonic operation. From the results, it is determined that use of high frequency ultrasound (low-power/continuous; high-power/pulsing) or low frequency ultrasound (continuous operation with moderate power) can both be effective in removing stratification. PMID:23810463

  11. Mechanistic basis of infertility of mouse intersubspecific hybrids.

    PubMed

    Bhattacharyya, Tanmoy; Gregorova, Sona; Mihola, Ondrej; Anger, Martin; Sebestova, Jaroslava; Denny, Paul; Simecek, Petr; Forejt, Jiri

    2013-02-01

    According to the Dobzhansky-Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit.

  12. A mechanistic compartmental model for total antibody uptake in tumors.

    PubMed

    Thurber, Greg M; Dane Wittrup, K

    2012-12-01

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. PMID:22974563

  13. A mechanistic compartmental model for total antibody uptake in tumors

    PubMed Central

    Thurber, Greg M.; Dane Wittrup, K.

    2012-01-01

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. PMID:22974563

  14. Circadian rhythms and addiction: Mechanistic insights and future directions

    PubMed Central

    Logan, Ryan W.; Williams, Wilbur P.; McClung, Colleen A.

    2014-01-01

    Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction. PMID:24731209

  15. A global scale mechanistic model of the photosynthetic capacity

    NASA Astrophysics Data System (ADS)

    Xu, C.; Ali, A. A.; Fisher, R.; Wullschleger, S. D.; Rogers, A.; McDowell, N. G.; Wilson, C. J.

    2015-12-01

    Although plant photosynthetic capacity as determined by the maximum carboxylation rate (i.e., Vc,max25) and the maximum electron transport rate (i.e., Jmax25) at a reference temperature (generally 25oC) is known to vary substantially in space and time in response to environmental conditions, it is typically parameterized in Earth system models (ESMs) with tabulated values associated to plant functional types. In this study, we developed a mechanistic model of leaf utilization of nitrogen for assimilation (LUNA V1.0) to predict the photosynthetic capacity at the global scale under different environmental conditions, based on the optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The LUNA model was able to reasonably well capture the observed patterns of photosynthetic capacity in view that it explained approximately 55% of the variation in observed Vc,max25 and 65% of the variation in observed Jmax25 across the globe. Our model simulations under current and future climate conditions indicated that Vc,max25 could be most affected in high-latitude regions under a warming climate and that ESMs using a fixed Vc,max25 or Jmax25 by plant functional types were likely to substantially overestimate future global photosynthesis.

  16. Air pollution, inflammation and preterm birth: a potential mechanistic link.

    PubMed

    Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

    2014-02-01

    Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

  17. Mechanistic studies of malonic acid-mediated in situ acylation.

    PubMed

    Chandra, Koushik; Naoum, Johnny N; Roy, Tapta Kanchan; Gilon, Chaim; Gerber, R Benny; Friedler, Assaf

    2015-09-01

    We have previously introduced an easy to perform, cost-effective and highly efficient acetylation technique for solid phase synthesis (SPPS). Malonic acid is used as a precursor and the reaction proceeds via a reactive ketene that acetylates the target amine. Here we present a detailed mechanistic study of the malonic acid-mediated acylation. The influence of reaction conditions, peptide sequence and reagents was systematically studied. Our results show that the methodology can be successfully applied to different types of peptides and nonpeptidic molecules irrespective of their structure, sequence, or conformation. Using alkyl, phenyl, and benzyl malonic acid, we synthesized various acyl peptides with almost quantitative yields. The ketenes obtained from the different malonic acid derived precursors were characterized by in situ (1) H-NMR. The reaction proceeded in short reaction times and resulted in excellent yields when using uronium-based coupling agents, DIPEA as a base, DMF/DMSO/NMP as solvents, Rink amide/Wang/Merrifield resins, temperature of 20°C, pH 8-12 and 5 min preactivation at inert atmosphere. The reaction was unaffected by Lewis acids, transition metal ions, surfactants, or salt. DFT studies support the kinetically favorable concerted mechanism for CO2 and ketene formation that leads to the thermodynamically stable acylated products. We conclude that the malonic acid-mediated acylation is a general method applicable to various target molecules. PMID:25846609

  18. A Mechanistic Stochastic Ricker Model: Analytical and Numerical Investigations

    NASA Astrophysics Data System (ADS)

    Gadrich, Tamar; Katriel, Guy

    The Ricker model is one of the simplest and most widely-used ecological models displaying complex nonlinear dynamics. We study a discrete-time population model, which is derived from simple assumptions concerning individual organisms’ behavior, using the “site-based” approach, developed by Brännström, Broomhead, Johansson and Sumpter. In the large-population limit the model converges to the Ricker model, and can thus be considered a mechanistic version of the Ricker model, derived from basic ecological principles, and taking into account the demographic stochasticity inherent to finite populations. We employ several analytical and precise numerical methods to study the model, showing how each approach contributes to understanding the model’s dynamics. Expressing the model as a Markov chain, we employ the concept of quasi-stationary distributions, which are computed numerically, and used to examine the interaction between complex deterministic dynamics and demographic stochasticity, as well as to calculate mean times to extinction. A Gaussian Markov chain approximation is used to obtain quantitative asymptotic approximations for the size of fluctuations of the stochastic model’s time series around the deterministic trajectory, and for the correlations between successive fluctuations. Results of these approximations are compared to results obtained from quasi-stationary distributions and from direct simulations, and are shown to be in good agreement.

  19. AIR POLLUTION, INFLAMMATION AND PRETERM BIRTH: A POTENTIAL MECHANISTIC LINK

    PubMed Central

    Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A.; Sánchez, Brisa N.; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G.; O´Neill, Marie S.

    2014-01-01

    Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth. PMID:24382337

  20. Physical activity and its mechanistic effects on prostate cancer.

    PubMed

    Wekesa, A; Harrison, M; Watson, R W

    2015-09-01

    Beneficial effects of physical activity have been illustrated in numerous aspects of health. With the increasing incidence of prostate cancer and changes in physical activity of men, understanding the link between the two has important implications for changing this cancer burden. Both positive and negative associations between physical activity and prostate cancer have been previously demonstrated in observational epidemiological studies. Elucidating the biological mechanisms would lead to a better understanding of how physical activity influences the progression of prostate cancer. This review was undertaken to: (1) identify evidence in literature that demonstrates the effects of physical activity on skeletal muscle secretomes, (2) indicate the plausible signaling pathways these proteins might activate, and (3) identify evidence in literature that demonstrates the roles of the signaling pathways in prostate cancer progression and regression. We also discuss proposed biological mechanisms and signaling pathways by which physical activity may prevent the development and progression of prostate cancer. We discuss proteins involved in the normal and aberrant growth and development of the prostate gland that may be affected by physical activity. We further identify future directions for research, including a better understanding of the biological mechanisms, the need to standardize physical activity and identify mechanistic end points of physical activity that can then be correlated with outcomes.

  1. Mechanistic insight into sonochemical biodiesel synthesis using heterogeneous base catalyst.

    PubMed

    Choudhury, Hanif A; Chakma, Sankar; Moholkar, Vijayanand S

    2014-01-01

    The beneficial effect of ultrasound on transesterification reaction is well known. Heterogeneous (or solid) catalysts for biodiesel synthesis have merit that they do not contaminate the byproduct of glycerol. In this paper, we have attempted to identify the mechanistic features of ultrasound-enhanced biodiesel synthesis with the base-catalyst of CaO. A statistical design of experiments (Box-Behnken) was used to identify the influence of temperature, alcohol to oil molar ratio and catalyst loading on transesterification yield. The optimum values of these parameters for the highest yield were identified through Response Surface Method (with a quadratic model) and ANOVA. These values are: temperature=62 °C, molar ratio=10:1 and catalyst loading=6 wt.%. The activation energy was determined as 82.3 kJ/mol, which is higher than that for homogeneous catalyzed system (for both acidic and basic catalyst). The experimental results have been analyzed vis-à-vis simulations of cavitation bubble dynamics. Due to 3-phase heterogeneity of the system, the yield was dominated by intrinsic kinetics, and the optimum temperature for the highest yield was close to boiling point of methanol. At this temperature, the influence of cavitation bubbles (in terms of both sonochemical and sonophysical effect) is negligible, and ultrasonic micro-streaming provided necessary convection in the system. The influence of all parameters on the reaction system was found to be strongly inter-dependent. PMID:23742888

  2. Mechanistic insight into sonochemical biodiesel synthesis using heterogeneous base catalyst.

    PubMed

    Choudhury, Hanif A; Chakma, Sankar; Moholkar, Vijayanand S

    2014-01-01

    The beneficial effect of ultrasound on transesterification reaction is well known. Heterogeneous (or solid) catalysts for biodiesel synthesis have merit that they do not contaminate the byproduct of glycerol. In this paper, we have attempted to identify the mechanistic features of ultrasound-enhanced biodiesel synthesis with the base-catalyst of CaO. A statistical design of experiments (Box-Behnken) was used to identify the influence of temperature, alcohol to oil molar ratio and catalyst loading on transesterification yield. The optimum values of these parameters for the highest yield were identified through Response Surface Method (with a quadratic model) and ANOVA. These values are: temperature=62 °C, molar ratio=10:1 and catalyst loading=6 wt.%. The activation energy was determined as 82.3 kJ/mol, which is higher than that for homogeneous catalyzed system (for both acidic and basic catalyst). The experimental results have been analyzed vis-à-vis simulations of cavitation bubble dynamics. Due to 3-phase heterogeneity of the system, the yield was dominated by intrinsic kinetics, and the optimum temperature for the highest yield was close to boiling point of methanol. At this temperature, the influence of cavitation bubbles (in terms of both sonochemical and sonophysical effect) is negligible, and ultrasonic micro-streaming provided necessary convection in the system. The influence of all parameters on the reaction system was found to be strongly inter-dependent.

  3. Mechanistic modeling of destratification in cryogenic storage tanks using ultrasonics.

    PubMed

    Jagannathan, T K; Mohanan, Srijith; Nagarajan, R

    2014-01-01

    Stratification is one of the main causes for vaporization of cryogens and increase of tank pressure during cryogenic storage. This leads subsequent problems such as cavitation in cryo-pumps, reduced length of storage time. Hence, it is vital to prevent stratification to improve the cost efficiency of storage systems. If stratified layers exist inside the tank, they have to be removed by suitable methods without venting the vapor. Sonication is one such method capable of keeping fluid layers mixed. In the present work, a mechanistic model for ultrasonic destratification is proposed and validated with destratification experiments done in water. Then, the same model is used to predict the destratification characteristics of cryogenic liquids such as liquid nitrogen (LN₂), liquid hydrogen (LH₂) and liquid ammonia (LNH₃). The destratification parameters are analysed for different frequencies of ultrasound and storage pressures by considering continuous and pulsed modes of ultrasonic operation. From the results, it is determined that use of high frequency ultrasound (low-power/continuous; high-power/pulsing) or low frequency ultrasound (continuous operation with moderate power) can both be effective in removing stratification.

  4. Mechanistic Enzymology of the Radical SAM Enzyme DesII

    PubMed Central

    2016-01-01

    DesII is a member of the radical SAM family of enzymes that catalyzes radical-mediated transformations of TDP-4-amino-4,6-didexoy-D-glucose as well as other sugar nucleotide diphosphates. Like nearly all radical SAM enzymes, the reactions begin with the reductive homolysis of SAM to produce a 5′-deoxyadenosyl radical which is followed by regiospecific hydrogen atom abstraction from the substrate. What happens next, however, depends on the nature of the substrate radical so produced. In the case of the biosynthetically relevant substrate, a radical-mediated deamination ensues; however, when this amino group is replaced with a hydroxyl, one instead observes dehydrogenation. The factors that govern the fate of the initially generated substrate radical as well as the mechanistic details underlying these transformations have been a key focus of research into the chemistry of DesII. This review will discuss recent discoveries pertaining to the enzymology of DesII, how it may relate to understanding other radical-mediated lyases and dehydrogenases and the working hypotheses currently being investigated regarding the mechanism of DesII catalysis.

  5. Mechanistic aspects of photooxidation of polyhydroxylated molecules on metal oxides.

    SciTech Connect

    Shkrob, I. A.; Marin, T. M.; Sevilla, M. D.; Chemerisov, S.

    2011-03-24

    Polyhydroxylated molecules, including natural carbohydrates, are known to undergo photooxidation on wide-gap transition-metal oxides irradiated by ultraviolet light. In this study, we examine mechanistic aspects of this photoreaction on aqueous TiO{sub 2}, {alpha}-FeOOH, and {alpha}-Fe{sub 2}O{sub 3} particles using electron paramagnetic resonance (EPR) spectroscopy and site-selective deuteration. We demonstrate that the carbohydrates are oxidized at sites involved in the formation of oxo bridges between the chemisorbed carbohydrate molecule and metal ions at the oxide surface. This bridging inhibits the loss of water (which is the typical reaction of the analogous free radicals in bulk solvent) promoting instead a rearrangement that leads to elimination of the formyl radical. For natural carbohydrates, the latter reaction mainly involves carbon-1, whereas the main radical products of the oxidation are radical arising from H atom loss centered on carbon-1, -2, and -3 sites. Photoexcited TiO{sub 2} oxidizes all of the carbohydrates and polyols, whereas {alpha}-FeOOH oxidizes some of the carbohydrates, and {alpha}-Fe{sub 2}O{sub 3} is unreactive. These results serve as a stepping stone for understanding the photochemistry on mineral surfaces of more complex biomolecules such as nucleic acids.

  6. Mechanistic overview of immune modulatory effects of environmental toxicants.

    PubMed

    Bahadar, Haji; Abdollahi, Mohammad; Maqbool, Faheem; Baeeri, Maryam; Niaz, Kamal

    2015-01-01

    The immune system is an integrated organization, comprising of specific organs, cells and molecules playing a crucial role in the maintenance of health. The purpose of this paper is to give a mechanistic overview of toxic effects of various chemicals and pharmacological agents, and their interaction with the various components of the immune system that leads to modulation of the immune responses. Studies suggest that many chemical agents present in the environment like; heavy metals, agrochemicals, and various types of hydrocarbons possess immune toxicity and cause either structural, functional or compositional changes in various components of the immune system that alters immune response. There is present a complex bidirectional relationship between central nervous system (CNS) and the immune system. And receptors for neuropeptides, neurotransmitters, and hormones are located on lymphoid organs. Therefore, we are of the opinion that Endocrine Disrupting Chemicals (EDCs) present in our environment may be indirectly involved in causing immune toxicity via neuroendocrine channels, and vice versa many neurological disorders may be associated with environmental pollutants utilizing immuno-neuroendocrine pathways.

  7. Functional and mechanistic diversity of distal transcription enhancers

    PubMed Central

    Bulger, Michael; Groudine, Mark

    2013-01-01

    Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

  8. Equation-free mechanistic ecosystem forecasting using empirical dynamic modeling.

    PubMed

    Ye, Hao; Beamish, Richard J; Glaser, Sarah M; Grant, Sue C H; Hsieh, Chih-Hao; Richards, Laura J; Schnute, Jon T; Sugihara, George

    2015-03-31

    It is well known that current equilibrium-based models fall short as predictive descriptions of natural ecosystems, and particularly of fisheries systems that exhibit nonlinear dynamics. For example, model parameters assumed to be fixed constants may actually vary in time, models may fit well to existing data but lack out-of-sample predictive skill, and key driving variables may be misidentified due to transient (mirage) correlations that are common in nonlinear systems. With these frailties, it is somewhat surprising that static equilibrium models continue to be widely used. Here, we examine empirical dynamic modeling (EDM) as an alternative to imposed model equations and that accommodates both nonequilibrium dynamics and nonlinearity. Using time series from nine stocks of sockeye salmon (Oncorhynchus nerka) from the Fraser River system in British Columbia, Canada, we perform, for the the first time to our knowledge, real-data comparison of contemporary fisheries models with equivalent EDM formulations that explicitly use spawning stock and environmental variables to forecast recruitment. We find that EDM models produce more accurate and precise forecasts, and unlike extensions of the classic Ricker spawner-recruit equation, they show significant improvements when environmental factors are included. Our analysis demonstrates the strategic utility of EDM for incorporating environmental influences into fisheries forecasts and, more generally, for providing insight into how environmental factors can operate in forecast models, thus paving the way for equation-free mechanistic forecasting to be applied in management contexts. PMID:25733874

  9. A mechanistic stochastic framework for regulating bacterial cell division.

    PubMed

    Ghusinga, Khem Raj; Vargas-Garcia, Cesar A; Singh, Abhyudai

    2016-01-01

    How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size. PMID:27456660

  10. Ancient Chinese medicine and mechanistic evidence of acupuncture physiology.

    PubMed

    Yang, Edward S; Li, Pei-Wen; Nilius, Bernd; Li, Geng

    2011-11-01

    Acupuncture has been widely used in China for three millennia as an art of healing. Yet, its physiology is not yet understood. The current interest in acupuncture started in 1971. Soon afterward, extensive research led to the concept of neural signaling with possible involvement of opioid peptides, glutamate, adenosine and identifying responsive parts in the central nervous system. In the last decade scientists began investigating the subject with anatomical and molecular imaging. It was found that mechanical movements of the needle, ignored in the past, appear to be central to the method and intracellular calcium ions may play a pivotal role. In this review, we trace the technique of clinical treatment from the first written record about 2,200 years ago to the modern time. The ancient texts have been used to introduce the concepts of yin, yang, qi, de qi, and meridians, the traditional foundation of acupuncture. We explore the sequence of the physiological process, from the turning of the needle, the mechanical wave activation of calcium ion channel to beta-endorphin secretion. By using modern terminology to re-interpret the ancient texts, we have found that the 2nd century B.C.: physiologists were meticulous investigators and their explanation fits well with the mechanistic model derived from magnetic resonance imaging (MRI) and confocal microscopy. In conclusion, the ancient model appears to have withstood the test of time surprisingly well confirming the popular axiom that the old wine is better than the new.

  11. Mechanistic aspects of photooxidation of polyhydroxylated molecules on metal oxides

    PubMed Central

    Shkrob, Ilya A.; Marin, Timothy M.; Chemerisov, Sergey D.; Sevilla, Michael D.

    2011-01-01

    Polyhydroxylated molecules, including natural carbohydrates, are known to undergo photooxidation on wide-gap transition metal oxides irradiated by ultraviolet light. In this study, we examine mechanistic aspects of this photoreaction on aqueous TiO2, α-FeOOH, and α-Fe2O3 particles using electron paramagnetic resonance (EPR) spectroscopy and site-selective deuteration. We demonstrate that the carbohydrates are oxidized at sites involved in the formation of oxo-bridges between the chemisorbed carbohydrate molecule and metal ions at the oxide surface. This bridging inhibits the loss of water (which is the typical reaction of the analogous free radicals in bulk solvent) promoting instead a rearrangement that leads to elimination of the formyl radical. For natural carbohydrates, the latter reaction mainly involves carbon-1, whereas the main radical products of the oxidation are radical arising from H atom loss centered on carbon-1, -2, and -3 sites. Photoexcited TiO2 oxidizes all of the carbohydrates and polyols, whereas α-FeOOH oxidizes some of the carbohydrates, and α-Fe2O3 is unreactive. These results serve as a stepping stone for understanding the photochemistry on mineral surfaces of more complex biomolecules such as nucleic acids. PMID:21532934

  12. Anti-fibro-hepatocarcinogenic Chinese herbal medicines: A mechanistic overview.

    PubMed

    Boye, Alex; Yang, Yan; Asenso, James; Wei, Wei

    2016-01-01

    Chinese herbal medicine (CHM) is an integral component of complementary/alternative medicine and it is increasingly becoming the preferred therapeutic modality for the treatment of liver fibrosis and hepatocellular carcinoma (HCC) worldwide. Accordingly, the World Health Organization (WHO) has attested to the popularity and efficacy of indigenous herbal therapies including CHM as a first line of treatment for some diseases including liver disorders. However, the WHO and drug discovery experts have always recommended that use of indigenous herbal remedies must go hand-in-hand with the requisite mechanistic elucidation so as to constitute a system of verification of efficacy within the ethnobotanical context of use. Although many CHM experts have advanced knowledge on CHM, nonetheless, more enlightenment is needed, particularly mechanisms of action of CHMs on fibro-hepato-carcinogenesis. We, herein, provide in-depth mechanisms of the action of CHMs which have demonstrated anti-fibro-hepatocarcinogenic effects, in pre-clinical and clinical studies as published in PubMed and other major scientific databases. Specifically, the review brings out the important signaling pathways, and their downstream targets which are modulated at multi-level by various anti-fibro-hepatocarcinogenic CHMs. PMID:27366355

  13. Mechanistic insight into the photosensory versatility of DXCF cyanobacteriochromes.

    PubMed

    Rockwell, Nathan C; Martin, Shelley S; Lagarias, J Clark

    2012-05-01

    Cyanobacteriochromes (CBCRs) are photosensory proteins related to the red/far-red phytochromes. Like phytochromes, CBCRs use linear tetrapyrrole (bilin) chromophores covalently attached via a thioether linkage to a conserved Cys residue also found in plant and cyanobacterial phytochromes. Unlike almost all phytochromes, CBCRs require only an isolated GAF domain to undergo efficient, reversible photocycles that are responsible for their broad light sensing range, spanning the visible to the near ultraviolet (UV). Sensing of blue, violet, and near-UV light by CBCRs requires another Cys residue proposed to form a second linkage to the bilin precursor. Light triggers 15,16-double bond isomerization as in phytochromes. After photoisomerization, elimination of the second linkage frequently occurs, thus yielding a large red shift of the stable photoproducts. Here we examine this process for representative DXCF CBCRs, a large subfamily named for the conserved Asp-Xaa-Cys-Phe motif that contains their second Cys residue. DXCF CBCRs with such dual-Cys photocycles yield a wide diversity of photoproducts absorbing teal, green, or orange light. Using a combination of CD spectroscopy, chemical modification, and bilin substitution experiments with recombinant CBCRs from Thermosynechococcus elongatus and Nostoc punctiforme expressed in Escherichia coli, we establish that second-linkage elimination is required for all of these photocycles. We also identify deconjugation of the D-ring as the mechanism for specific detection of teal light, at approximately 500 nm. Our studies thus provide new mechanistic insight into the photosensory versatility of this important family of photosensory proteins.

  14. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

    PubMed Central

    Yap, Wei Hsum; Lim, Yang Mooi

    2015-01-01

    Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs) are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX) enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS). The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB)/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli. PMID:26491566

  15. A mechanistic stochastic framework for regulating bacterial cell division.

    PubMed

    Ghusinga, Khem Raj; Vargas-Garcia, Cesar A; Singh, Abhyudai

    2016-07-26

    How exponentially growing cells maintain size homeostasis is an important fundamental problem. Recent single-cell studies in prokaryotes have uncovered the adder principle, where cells add a fixed size (volume) from birth to division, irrespective of their size at birth. To mechanistically explain the adder principle, we consider a timekeeper protein that begins to get stochastically expressed after cell birth at a rate proportional to the volume. Cell-division time is formulated as the first-passage time for protein copy numbers to hit a fixed threshold. Consistent with data, the model predicts that the noise in division timing increases with size at birth. Intriguingly, our results show that the distribution of the volume added between successive cell-division events is independent of the newborn cell size. This was dramatically seen in experimental studies, where histograms of the added volume corresponding to different newborn sizes collapsed on top of each other. The model provides further insights consistent with experimental observations: the distribution of the added volume when scaled by its mean becomes invariant of the growth rate. In summary, our simple yet elegant model explains key experimental findings and suggests a mechanism for regulating both the mean and fluctuations in cell-division timing for controlling size.

  16. Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone.

    PubMed

    Kundu, Juthika; Chun, Kyung-Soo; Aruoma, Okezie I; Kundu, Joydeb Kumar

    2014-10-01

    The bioactive natural products (plant secondary metabolites) are widely known to possess therapeutic value for the prevention and treatment of various chronic diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone; TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic pharmacological activities including antioxidant, anti-inflammatory, antidiabetic and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of animal models and has been shown to arrest the growth of various cancer cells in culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity and oxidative damage of cellular macromolecules, attenuation of inflammation, induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor angiogenesis, and suppression of migration, invasion and metastasis of cancer cells. TQ shows synergistic and/or potentiating anticancer effects when combined with clinically used chemotherapeutic agents. At the molecular level, TQ targets various components of intracellular signaling pathways, particularly a variety of upstream kinases and transcription factors, which are aberrantly activated during the course of tumorigenesis. PMID:25847385

  17. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems

    PubMed Central

    Lomnitz, Jason G.; Savageau, Michael A.

    2016-01-01

    An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values. PMID:27578053

  18. Equation-free mechanistic ecosystem forecasting using empirical dynamic modeling

    PubMed Central

    Ye, Hao; Beamish, Richard J.; Glaser, Sarah M.; Grant, Sue C. H.; Hsieh, Chih-hao; Richards, Laura J.; Schnute, Jon T.; Sugihara, George

    2015-01-01

    It is well known that current equilibrium-based models fall short as predictive descriptions of natural ecosystems, and particularly of fisheries systems that exhibit nonlinear dynamics. For example, model parameters assumed to be fixed constants may actually vary in time, models may fit well to existing data but lack out-of-sample predictive skill, and key driving variables may be misidentified due to transient (mirage) correlations that are common in nonlinear systems. With these frailties, it is somewhat surprising that static equilibrium models continue to be widely used. Here, we examine empirical dynamic modeling (EDM) as an alternative to imposed model equations and that accommodates both nonequilibrium dynamics and nonlinearity. Using time series from nine stocks of sockeye salmon (Oncorhynchus nerka) from the Fraser River system in British Columbia, Canada, we perform, for the the first time to our knowledge, real-data comparison of contemporary fisheries models with equivalent EDM formulations that explicitly use spawning stock and environmental variables to forecast recruitment. We find that EDM models produce more accurate and precise forecasts, and unlike extensions of the classic Ricker spawner–recruit equation, they show significant improvements when environmental factors are included. Our analysis demonstrates the strategic utility of EDM for incorporating environmental influences into fisheries forecasts and, more generally, for providing insight into how environmental factors can operate in forecast models, thus paving the way for equation-free mechanistic forecasting to be applied in management contexts. PMID:25733874

  19. The road to advanced glycation end products: a mechanistic perspective.

    PubMed

    Cho, S-J; Roman, G; Yeboah, F; Konishi, Y

    2007-01-01

    Protein glycation is a slow natural process involving the chemical modification of the reactive amino and guanidine functions in amino acids by sugars and carbohydrates-derived reactive carbonyls. Its deleterious consequences are obvious in the case of long-lived proteins in aged people and are exacerbated by the high blood concentration of sugars in diabetic patients. The non-enzymatic glycation of proteins occurs through a wide range of concurrent processes comprising condensation, rearrangement, fragmentation, and oxidation reactions. Using a few well established intermediates such as Schiff base, Amadori product and reactive a-dicarbonyls as milestones and the results of in vitro glycation investigations, an overall detailed mechanistic analysis of protein glycation is presented for the first time. The pathways leading to several advanced glycation end products (AGEs) such as (carboxymethyl)lysine, pentosidine, and glucosepane are outlined, whereas other AGEs useful as potential biomarkers of glycation are only briefly mentioned. The current stage of the development of glycation inhibitors has been reviewed with an emphasis on their mechanism of action.

  20. Air pollution, inflammation and preterm birth: a potential mechanistic link.

    PubMed

    Vadillo-Ortega, Felipe; Osornio-Vargas, Alvaro; Buxton, Miatta A; Sánchez, Brisa N; Rojas-Bracho, Leonora; Viveros-Alcaráz, Martin; Castillo-Castrejón, Marisol; Beltrán-Montoya, Jorge; Brown, Daniel G; O'Neill, Marie S

    2014-02-01

    Preterm birth is a public health issue of global significance, which may result in mortality during the perinatal period or may lead to major health and financial consequences due to lifelong impacts. Even though several risk factors for preterm birth have been identified, prevention efforts have failed to halt the increasing rates of preterm birth. Epidemiological studies have identified air pollution as an emerging potential risk factor for preterm birth. However, many studies were limited by study design and inadequate exposure assessment. Due to the ubiquitous nature of ambient air pollution and the potential public health significance of any role in causing preterm birth, a novel focus investigating possible causal mechanisms influenced by air pollution is therefore a global health priority. We hypothesize that air pollution may act together with other biological factors to induce systemic inflammation and influence the duration of pregnancy. Evaluation and testing of this hypothesis is currently being conducted in a prospective cohort study in Mexico City and will provide an understanding of the pathways that mediate the effects of air pollution on preterm birth. The important public health implication is that crucial steps in this mechanistic pathway can potentially be acted on early in pregnancy to reduce the risk of preterm birth.

  1. Mechanistic solutions to the opening of the Gulf of Mexico

    USGS Publications Warehouse

    Schouten, Hans; Klitgord, Kim D.

    1994-01-01

    Two mechanistic models-which are unlike the traditional plate-tectonic landfill models used for most proposed Pangea reconstructions of the Yucatán block-relate the Mesozoic opening of the Gulf of Mexico directly to the movement of the North and South American plates: (1) a previous piggyback model in which Yucatán moves with South America out of the western gulf and (2) a new edge-driven model in which the motion of the Yucatán block is caused by forces applied to its margins by the movement of the North and South American plates. In the second model, Yucatán moves out of the northern Gulf of Mexico as a gear or roller bearing. On the basis of magnetic edge anomalies around the gulf, this edge-driven model predicts that from the Bathonian to Tithonian (~170 to ~50 Ma), Yucatán was rotated ~60° counterclockwise as a rigid block between North and South America with rift propagation and extension occurring simultaneously in the Gulf of Mexico and Yucatán Basin.

  2. A mechanistic model for permeability evolution in fractured sorbing media

    NASA Astrophysics Data System (ADS)

    Wang, Shugang; Elsworth, Derek; Liu, Jishan

    2012-06-01

    A mechanistic model is presented to represent the evolution of permeability in fractured sorbing media such as coal beds and organic-rich shales. This model accommodates key competing processes of poromechanical dilation and sorption-induced swelling. We show that the significant difference in stiffness between fracture and matrix transforms the composite system from globally unconstrained to locally constrained by the development of a virtual "stiff shell" that envelops the perimeter of a representative elementary volume containing a fracture. It is this transformation that results in swelling-induced permeability reduction at low (sorbing) gas pressures and self consistently allows competitive dilation of the fracture as gas pressures are increased. Importantly, net dilation is shown to require a mismatch in the Biot coefficients of fracture and matrix with the coefficient for the fracture exceeding that for the matrix—a condition that is logically met. Permeability evolution is cast in terms of series and parallel models with the series model better replicating observational data. The model may be cast in terms of nondimensional parameters representing sorptive and poromechanical effects and modulated by the sensitivity of the fracture network to dilation or compaction of the individual fractures. This latter parameter encapsulates the effects of fracture spacing and initial permeability and scale changes in permeability driven by either sorption or poromechanical effects. This model is applied to well-controlled observational data for different ranks of coals and different gases (He, CO2) and satisfactory agreement is obtained.

  3. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems.

    PubMed

    Lomnitz, Jason G; Savageau, Michael A

    2016-01-01

    An overarching goal in molecular biology is to gain an understanding of the mechanistic basis underlying biochemical systems. Success is critical if we are to predict effectively the outcome of drug treatments and the development of abnormal phenotypes. However, data from most experimental studies is typically noisy and sparse. This allows multiple potential mechanisms to account for experimental observations, and often devising experiments to test each is not feasible. Here, we introduce a novel strategy that discriminates among putative models based on their repertoire of qualitatively distinct phenotypes, without relying on knowledge of specific values for rate constants and binding constants. As an illustration, we apply this strategy to two synthetic gene circuits exhibiting anomalous behaviors. Our results show that the conventional models, based on their well-characterized components, cannot account for the experimental observations. We examine a total of 40 alternative hypotheses and show that only 5 have the potential to reproduce the experimental data, and one can do so with biologically relevant parameter values. PMID:27578053

  4. A Mechanistic Link between Olfaction and Autism Spectrum Disorder.

    PubMed

    Rozenkrantz, Liron; Zachor, Ditza; Heller, Iris; Plotkin, Anton; Weissbrod, Aharon; Snitz, Kobi; Secundo, Lavi; Sobel, Noam

    2015-07-20

    Internal action models (IAMs) are brain templates for sensory-motor coordination underlying diverse behaviors. An emerging theory suggests that impaired IAMs are a common theme in autism spectrum disorder (ASD). However, whether impaired IAMs occur across sensory systems and how they relate to the major phenotype of ASD, namely impaired social communication, remains unclear. Olfaction relies on an IAM known as the sniff response, where sniff magnitude is automatically modulated to account for odor valence. To test the failed IAM theory in olfaction, we precisely measured the non-verbal non-task-dependent sniff response concurrent with pleasant and unpleasant odors in 36 children--18 with ASD and 18 matched typically developing (TD) controls. We found that whereas TD children generated a typical adult-like sniff response within 305 ms of odor onset, ASD children had a profoundly altered sniff response, sniffing equally regardless of odor valance. This difference persisted despite equal reported odor perception and allowed for 81% correct ASD classification based on the sniff response alone (binomial, p < 0.001). Moreover, increasingly aberrant sniffing was associated with increasingly severe ASD (r = -0.75, p < 0.001), specifically with social (r = -0.72, p < 0.001), but not motor (r < -0.38, p > 0.18), impairment. These results uncover a novel ASD marker implying a mechanistic link between the underpinnings of olfaction and ASD and directly linking an impaired IAM with impaired social abilities.

  5. Diffusion theory in biology: a relic of mechanistic materialism.

    PubMed

    Agutter, P S; Malone, P C; Wheatley, D N

    2000-01-01

    Diffusion theory explains in physical terms how materials move through a medium, e.g. water or a biological fluid. There are strong and widely acknowledged grounds for doubting the applicability of this theory in biology, although it continues to be accepted almost uncritically and taught as a basis of both biology and medicine. Our principal aim is to explore how this situation arose and has been allowed to continue seemingly unchallenged for more than 150 years. The main shortcomings of diffusion theory will be briefly reviewed to show that the entrenchment of this theory in the corpus of biological knowledge needs to be explained, especially as there are equally valid historical grounds for presuming that bulk fluid movement powered by the energy of cell metabolism plays a prominent note in the transport of molecules in the living body. First, the theory's evolution, notably from its origins in connection with the mechanistic materialist philosophy of mid nineteenth century physiology, is discussed. Following this, the entrenchment of the theory in twentieth century biology is analyzed in relation to three situations: the mechanism of oxygen transport between air and mammalian tissues; the structure and function of cell membranes; and the nature of the intermediary metalbolism, with its implicit presumptions about the intracellular organization and the movement of molecules within it. In our final section, we consider several historically based alternatives to diffusion theory, all of which have their precursors in nineteenth and twentieth century philosophy of science.

  6. Ozonation of piperidine, piperazine and morpholine: Kinetics, stoichiometry, product formation and mechanistic considerations.

    PubMed

    Tekle-Röttering, Agnes; Jewell, Kevin S; Reisz, Erika; Lutze, Holger V; Ternes, Thomas A; Schmidt, Winfried; Schmidt, Torsten C

    2016-01-01

    Piperidine, piperazine and morpholine as archetypes for secondary heterocyclic amines, a structural unit that is often present in pharmaceuticals (e.g., ritalin, cetirizine, timolol, ciprofloxacin) were investigated in their reaction with ozone. In principle the investigated compounds can be degraded with ozone in a reasonable time, based on their high reaction rate constants with respect to ozone (1.9 × 10(4)-2.4 × 10(5) M(-1) s(-1)). However, transformation is insufficient (13-16%), most likely due to a chain reaction, which decomposes ozone. This conclusion is based on OH scavenging experiments, leading to increased compound transformation (18-27%). The investigated target compounds are similar in their kinetic and stoichiometric characteristics. However, the mechanistic considerations based on product formation indicate various reaction pathways. Piperidine reacts with ozone via a nonradical addition reaction to N-hydroxypiperidine (yield: 92% with and 94% without scavenging, with respect to compound transformation). However, piperazine degradation with ozone does not lead to N-hydroxypiperazine. In the morpholine/ozone reaction, N-hydroxymorpholine was identified. Additional oxidation pathways in all cases involved the formation of OH with high yields. One important pathway of piperazine and morpholine by ozonation could be the formation of C-centered radicals after ozone or OH radical attack. Subsequently, O2 addition forms unstable peroxyl radicals, which in one pathway loose superoxide radicals by generating a carbon-centered cation. Subsequent hydrolysis of the carbon-centered cation leads to formaldehyde, whereby ozonation of the N-hydroxy products can proceed in the same way and in addition give rise to hydroxylamine. A second pathway of the short-lived peroxyl radicals could be a dimerization to form short-lived tetraoxides, which cleave by forming hydrogen peroxide. All three products have been found. PMID:26624229

  7. [Food additives and healthiness].

    PubMed

    Heinonen, Marina

    2014-01-01

    Additives are used for improving food structure or preventing its spoilage, for example. Many substances used as additives are also naturally present in food. The safety of additives is evaluated according to commonly agreed principles. If high concentrations of an additive cause adverse health effects for humans, a limit of acceptable daily intake (ADI) is set for it. An additive is a risk only when ADI is exceeded. The healthiness of food is measured on the basis of nutrient density and scientifically proven effects.

  8. Mechanistic analysis of cavitation assisted transesterification on biodiesel characteristics.

    PubMed

    Sajjadi, Baharak; Abdul Aziz, A R; Ibrahim, Shaliza

    2015-01-01

    The influence of sonoluminescence transesterification on biodiesel physicochemical properties was investigated and the results were compared to those of traditional mechanical stirring. This study was conducted to identify the mechanistic features of ultrasonication by coupling statistical analysis of the experiments into the simulation of cavitation bubble. Different combinations of operational variables were employed for alkali-catalysis transesterification of palm oil. The experimental results showed that transesterification with ultrasound irradiation could change the biodiesel density by about 0.3kg/m(3); the viscosity by 0.12mm(2)/s; the pour point by about 1-2°C and the flash point by 5°C compared to the traditional method. Furthermore, 93.84% of yield with alcohol to oil molar ratio of 6:1 could be achieved through ultrasound assisted transesterification within only 20min. However, only 89.09% of reaction yield was obtained by traditional macro mixing/heating under the same condition. Based on the simulated oscillation velocity value, the cavitation phenomenon significantly contributed to generation of fine micro emulsion and was able to overcome mass transfer restriction. It was found that the sonoluminescence bubbles reached the temperature of 758-713K, pressure of 235.5-159.55bar, oscillation velocity of 3.5-6.5cm/s, and equilibrium radius of 17.9-13.7 times greater than its initial size under the ambient temperature of 50-64°C at the moment of collapse. This showed that the sonoluminescence bubbles were in the condition in which the decomposition phenomena were activated and the reaction rate was accelerated together with a change in the biodiesel properties.

  9. Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics

    SciTech Connect

    Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D; Wilson, Cathy; Cai, Michael; McDowell, Nathan

    2012-01-01

    Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO{sub 2} concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO{sub 2} concentration, temperature, and radiation when evaluated against published data of V{sub c,max} (maximum carboxylation rate) and J{sub max} (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO{sub 2} concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions

  10. Common Mechanistic Themes for the Powerstroke of Kinesin-14 motors

    PubMed Central

    Gonzalez, Miguel A.; Cope, Julia; Rank, Katherine C.; Chen, Chun Ju; Tittmann, Peter; Rayment, Ivan; Gilbert, Susan P.; Hoenger, Andreas

    2013-01-01

    Kar3Cik1 is a heterodimeric kinesin-14 from Saccharomyces cerevisiae involved in spindle formation during mitosis and karyogamy in mating cells. Kar3 represents a canonical kinesin motor domain that interacts with microtubules under the control of ATP-hydrolysis. In vivo, the localization and function of Kar3 is differentially regulated by its interacting stoichiometrically with either Cik1 or Vik1, two closely related motor homology domains that lack the nucleotide-binding site. Indeed, Vik1 structurally resembles the core of a kinesin head. Despite being closely related, Kar3Cik1 and Kar3Vik1 are each responsible for a distinct set of functions in vivo and also display different biochemical behavior in vitro. To determine a structural basis for their distinct functional abilities, we used cryo-electron microscopy and helical reconstruction to investigate the 3-D structure of Kar3Cik1 complexed to microtubules in various nucleotide states and compared our 3-D data of Kar3Cik1 with that of Kar3Vik1 and the homodimeric kinesin-14 Ncd from Drosophila melanogaster. Due to the lack of an X-ray crystal structure of the Cik1 motor homology domain, we predicted the structure of this Cik1 domain based on sequence similarity to its relatives Vik1, Kar3 and Ncd. By molecular docking into our 3-D maps, we produced a detailed near-atomic model of Kar3Cik1 complexed to microtubules in two distinct nucleotide states, a nucleotide-free state and an ATP-bound state. Our data show that despite their functional differences, heterodimeric Kar3Cik1 and Kar3Vik1 and homodimeric Ncd, all share striking structural similarities at distinct nucleotide states indicating a common mechanistic theme within the kinesin-14 family. PMID:24099757

  11. Metabolic diseases and pro- and prebiotics: Mechanistic insights

    PubMed Central

    2012-01-01

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual’s behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases. PMID:22713169

  12. Toward a mechanistic understanding and prediction of biotic homogenization.

    PubMed

    Olden, Julian D; Poff, N LeRoy

    2003-10-01

    The widespread replacement of native species with cosmopolitan, nonnative species is homogenizing the global fauna and flora. While the empirical study of biotic homogenization is substantial and growing, theoretical aspects have yet to be explored. Consequently, the breadth of possible ecological mechanisms that can shape current and future patterns and rates of homogenization remain largely unknown. Here, we develop a conceptual model that describes 14 potential scenarios by which species invasions and/or extinctions can lead to various trajectories of biotic homogenization (increased community similarity) or differentiation (decreased community similarity); we then use a simulation approach to explore the model's predictions. We found changes in community similarity to vary with the type and number of nonnative and native species, the historical degree of similarity among the communities, and, to a lesser degree, the richness of the recipient communities. Homogenization is greatest when similar species invade communities, causing either no extinction or differential extinction of native species. The model predictions are consistent with current empirical data for fish, bird, and plant communities and therefore may represent the dominant mechanisms of contemporary homogenization. We present a unifying model illustrating how the balance between invading and extinct species dictates the outcome of biotic homogenization. We conclude by discussing a number of critical but largely unrecognized issues that bear on the empirical study of biotic homogenization, including the importance of spatial scale, temporal scale, and data resolution. We argue that the study of biotic homogenization needs to be placed in a more mechanistic and predictive framework in order for studies to provide adequate guidance in conservation efforts to maintain regional distinctness of the global biota. PMID:14582007

  13. Mechanistic analysis of cavitation assisted transesterification on biodiesel characteristics.

    PubMed

    Sajjadi, Baharak; Abdul Aziz, A R; Ibrahim, Shaliza

    2015-01-01

    The influence of sonoluminescence transesterification on biodiesel physicochemical properties was investigated and the results were compared to those of traditional mechanical stirring. This study was conducted to identify the mechanistic features of ultrasonication by coupling statistical analysis of the experiments into the simulation of cavitation bubble. Different combinations of operational variables were employed for alkali-catalysis transesterification of palm oil. The experimental results showed that transesterification with ultrasound irradiation could change the biodiesel density by about 0.3kg/m(3); the viscosity by 0.12mm(2)/s; the pour point by about 1-2°C and the flash point by 5°C compared to the traditional method. Furthermore, 93.84% of yield with alcohol to oil molar ratio of 6:1 could be achieved through ultrasound assisted transesterification within only 20min. However, only 89.09% of reaction yield was obtained by traditional macro mixing/heating under the same condition. Based on the simulated oscillation velocity value, the cavitation phenomenon significantly contributed to generation of fine micro emulsion and was able to overcome mass transfer restriction. It was found that the sonoluminescence bubbles reached the temperature of 758-713K, pressure of 235.5-159.55bar, oscillation velocity of 3.5-6.5cm/s, and equilibrium radius of 17.9-13.7 times greater than its initial size under the ambient temperature of 50-64°C at the moment of collapse. This showed that the sonoluminescence bubbles were in the condition in which the decomposition phenomena were activated and the reaction rate was accelerated together with a change in the biodiesel properties. PMID:24981808

  14. Mechanistic basis for overcoming platinum resistance using copper chelating agents.

    PubMed

    Liang, Zheng D; Long, Yan; Tsai, Wen-Bin; Fu, Siqing; Kurzrock, Razelle; Gagea-Iurascu, Mihai; Zhang, Fan; Chen, Helen H W; Hennessy, Bryan T; Mills, Gordon B; Savaraj, Niramol; Kuo, Macus Tien

    2012-11-01

    Platinum-based antitumor agents are widely used in cancer chemotherapy. Drug resistance is a major obstacle to the successful use of these agents because once drug resistance develops, other effective treatment options are limited. Recently, we conducted a clinical trial using a copper-lowering agent to overcome platinum drug resistance in ovarian cancer patients and the preliminary results are encouraging. In supporting this clinical study, using three pairs of cisplatin (cDDP)-resistant cell lines and two ovarian cancer cell lines derived from patients who had failed in platinum-based chemotherapy, we showed that cDDP resistance associated with reduced expression of the high-affinity copper transporter (hCtr1), which is also a cDDP transporter, can be preferentially resensitized by copper-lowering agents because of enhanced hCtr1 expression, as compared with their drug-sensitive counterparts. Such a preferential induction of hCtr1 expression in cDDP-resistant variants by copper chelation can be explained by the mammalian copper homeostasis regulatory mechanism. Enhanced cell-killing efficacy by a copper-lowering agent was also observed in animal xenografts bearing cDDP-resistant cells. Finally, by analyzing a public gene expression dataset, we found that ovarian cancer patients with elevated levels of hCtr1 in their tumors, but not ATP7A and ATP7B, had more favorable outcomes after platinum drug treatment than those expressing low hCtr1 levels. This study reveals the mechanistic basis for using copper chelation to overcome cDDP resistance in clinical investigations.

  15. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    PubMed Central

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  16. Conceptualising population health: from mechanistic thinking to complexity science.

    PubMed

    Jayasinghe, Saroj

    2011-01-20

    The mechanistic interpretation of reality can be traced to the influential work by René Descartes and Sir Isaac Newton. Their theories were able to accurately predict most physical phenomena relating to motion, optics and gravity. This paradigm had at least three principles and approaches: reductionism, linearity and hierarchy. These ideas appear to have influenced social scientists and the discourse on population health. In contrast, Complexity Science takes a more holistic view of systems. It views natural systems as being 'open', with fuzzy borders, constantly adapting to cope with pressures from the environment. These are called Complex Adaptive Systems (CAS). The sub-systems within it lack stable hierarchies, and the roles of agency keep changing. The interactions with the environment and among sub-systems are non-linear interactions and lead to self-organisation and emergent properties. Theoretical frameworks such as epi+demos+cracy and the ecosocial approach to health have implicitly used some of these concepts of interacting dynamic sub-systems. Using Complexity Science we can view population health outcomes as an emergent property of CAS, which has numerous dynamic non-linear interactions among its interconnected sub-systems or agents. In order to appreciate these sub-systems and determinants, one should acquire a basic knowledge of diverse disciplines and interact with experts from different disciplines. Strategies to improve health should be multi-pronged, and take into account the diversity of actors, determinants and contexts. The dynamic nature of the system requires that the interventions are constantly monitored to provide early feedback to a flexible system that takes quick corrections.

  17. Mechanistic Insights into Homogeneous and Heterogeneous Asymmetric Iron Catalysis

    NASA Astrophysics Data System (ADS)

    Sonnenberg, Jessica

    Our group has been focused on replacing toxic and expensive precious metal catalysts with iron for the synthesis of enantiopure compounds for industrial applications. During an investigation into the mechanism of asymmetric transfer hydrogenation with our first generation iron-(P-N-N-P) catalysts we found substantial evidence for zero-valent iron nanoparticles coated in chiral ligand acting as the active site. Extensive experimental and computational experiments were undertaken which included NMR, DFT, reaction profile analysis, substoichiometric poisoning, electron microscope imaging, XPS and multiphasic analysis, all of which supported the fact that NPs were the active species in catalysis. Reversibility of this asymmetric reaction on the nanoparticle surface was then probed using oxidative kinetic resolution of racemic alcohols, yielding modest enantiopurity and high turnover frequencies (TOF) for a range of aromatic alcohols. Efficient dehydrogenation of ammonia-borane for hydrogen evolution and the formation of B-N oligomers was also shown using the NP system, yielding highly active systems, with a maximum TOF of 3.66 H2/s-1 . We have also begun to focus on the development of iron catalysts for asymmetric direct hydrogenation of ketones using hydrogen gas. New chiral iron-(P-N-P) catalysts were developed and shown to be quite active and selective for a wide range of substrates. Mechanistic investigations primarily using NMR and DFT indicated that a highly active trans-dihydride species was being formed during catalyst activation. Lastly, a new library of chiral P-N-P and P-NH-P ligands were developed, as well as their corresponding iron complexes, some of which show promise for the development of future generations of active asymmetric direct hydrogenation catalysts.

  18. A partial mechanistic understanding of the North American monsoon

    NASA Astrophysics Data System (ADS)

    Erfani, Ehsan; Mitchell, David

    2014-12-01

    An understanding of the major governing processes of North American monsoon (NAM) is necessary to guide improvement in global and regional climate modeling of the NAM, as well as NAM's impacts on the summer circulation, precipitation, and drought over North America. A mechanistic understanding of the NAM is suggested by incorporating local- and synoptic-scale processes. The local-scale mechanism describes the effect of the temperature inversion over the Gulf of California (GC) on controlling low-level moisture during the 2004 NAM. The strong low-level inversion inhibits the exchange between the moist air in the marine boundary layer (MBL) and the overlying dry air. This inversion weakens with increasing sea surface temperatures (SSTs) in GC and generally disappears once SSTs exceed 29.5°C, allowing the moist air, trapped in the MBL, to mix with free tropospheric air. This leads to a deep, moist layer that can be transported by across-gulf (along-gulf) flow toward the NAM core region (southwestern U.S.) to form thunderstorms. On the synoptic scale, climatologies from 1983 to 2010 exhibit a temporal correspondence between coastal warm tropical surface water, NAM deep convection, NAM anticyclone center, and NAM-induced strong descent. A hypothesis is proposed to explain this correspondence, based on limited soundings at the GC entrance (suggesting this local mechanism may also be active in that region), the climatologies, and the relevant literature. The warmest SSTs moving up the coast may initiate NAM convection and atmospheric heating, advancing the position of the anticyclone and the region of descent northward.

  19. Mechanistic Study of Plasma Damage of Low k Dielectric Surfaces

    SciTech Connect

    Bao Junjing; Shi Hualiang; Huang Huai; Ho, P. S.; Liu Junjun; Goodner, M. D.; Moinpour, M.; Kloster, G. M.

    2007-10-31

    Plasma damage to low k dielectric materials was investigated from a mechanistic point of view. Low k dielectric films were treated by plasma Ar, O{sub 2}, N{sub 2}/H{sub 2}, N{sub 2} and H{sub 2} in a standard RIE chamber and the damage was characterized by Angle Resolved X-ray Photoelectron Spectroscopy (ARXPS), X-Ray Reflectivity (XRR), Fourier Transform Infrared Spectroscopy (FTIR) and Contact Angle measurements. Both carbon depletion and surface densification were observed on the top surface of damaged low k materials while the bulk remained largely unaffected. Plasma damage was found to be a complicated phenomenon involving both chemical and physical effects, depending on chemical reactivity and the energy and mass of the plasma species. A downstream hybrid plasma source with separate ions and atomic radicals was employed to study their respective roles in the plasma damage process. Ions were found to play a more important role in the plasma damage process. The dielectric constant of low k materials can increase up to 20% due to plasma damage and we attributed this to the removal of the methyl group making the low k surface hydrophilic. Annealing was generally effective in mitigating moisture uptake to restore the k value but the recovery was less complete for higher energy plasmas. Quantum chemistry calculation confirmed that physisorbed water in low k materials induces the largest increase of dipole moments in comparison with changes of surface bonding configurations, and is primarily responsible for the dielectric constant increase.

  20. Mechanistic basis of infertility of mouse intersubspecific hybrids

    PubMed Central

    Bhattacharyya, Tanmoy; Gregorova, Sona; Mihola, Ondrej; Anger, Martin; Sebestova, Jaroslava; Denny, Paul; Simecek, Petr; Forejt, Jiri

    2013-01-01

    According to the Dobzhansky–Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than the rest of the genome. Here we propose that asynapsis of heterospecific chromosomes in meiotic prophase provides a recurrently evolving trigger for the meiotic arrest of interspecific F1 hybrids. We observed extensive asynapsis of chromosomes and disturbance of the sex body in >95% of pachynemas of Mus m. musculus × Mus m. domesticus sterile F1 males. Asynapsis was not preceded by a failure of double-strand break induction, and the rate of meiotic crossing over was not affected in synapsed chromosomes. DNA double-strand break repair was delayed or failed in unsynapsed autosomes, and misexpression of chromosome X and chromosome Y genes was detected in single pachynemas and by genome-wide expression profiling. Oocytes of F1 hybrid females showed the same kind of synaptic problems but with the incidence reduced to half. Most of the oocytes with pachytene asynapsis were eliminated before birth. We propose the heterospecific pairing of homologous chromosomes as a preexisting condition of asynapsis in interspecific hybrids. The asynapsis may represent a universal mechanistic basis of F1 hybrid sterility manifested by pachytene arrest. It is tempting to speculate that a fast-evolving subset of the noncoding genomic sequence important for chromosome pairing and synapsis may be the culprit. PMID:23329330

  1. Mechanistic Insight into DNA-Guided Control of Nanoparticle Morphologies.

    PubMed

    Tan, Li Huey; Yue, Yuan; Satyavolu, Nitya Sai Reddy; Ali, Arzeena Sultana; Wang, Zidong; Wu, Yuqing; Lu, Yi

    2015-11-18

    Although shapes and surface characteristics of nanoparticles are known to play important roles in defining their properties, it remains challenging to fine-tune the morphologies systematically and predictably. Recently, we have shown that DNA molecules can serve as programmable ligands to fine-tune the morphologies of nanomaterials. Despite this discovery, the mechanism of how the morphology can be controlled and the roles of the DNA molecules in contributing to such control are not understood. We herein report mechanistic investigation of DNA-mediated morphological evolution of gold nanoprism seeds into nonagon, hexagon, and six-pointed stars, some of which display rough surfaces, in the presence of homo-oligomeric T30, G20, C30, and A30. The growth, elucidated through various analytical methods including UV-vis, SEM, TEM, zeta potential, fluorescence, and cyclic voltammetry, is found to occur in two stages: control of shape, followed by control of thickness. A careful analysis of diffraction patterns of the nanoprism seeds as well as the resulting intermediate shapes by TEM allowed us to deduce the exact sequence of shape evolution. Through systematic comparison of the nanoparticle growth process, the DNA molecules were found to play important roles by influencing diffusion of the Au precursor to the seed and modulating the growth through differences in DNA desorption, density, and mobility on the seed surface. These insights into the mechanism of DNA-guided control of nanomaterial morphologies provide deeper understanding of the interactions between the DNA and nanomaterials and will allow better control of the shapes and surface properties of many nanomaterials. PMID:26492515

  2. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Bennett, Charles L.; Kim, Benjamin; Zakarija, Anaadriana; Bandarenko, Nicholas; Pandey, Dilip K.; Buffie, Charlie G.; McKoy, June M.; Tevar, Amul D.; Cursio, John F.; Yarnold, Paul R.; Kwaan, Hau C.; De Masi, Davide; Sarode, Ravindra; Raife, Thomas J.; Kiss, Joseph E.; Raisch, Dennis W.; Davidson, Charles; Sadler, J. Evan; Ortel, Thomas L.; Zheng, X. Long; Kato, Seiji; Matsumoto, Masanori; Uemura, Masahito; Fujimura, Yoshihiro

    2011-01-01

    Objectives We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID:17868804

  3. A mechanistic accounting of SOM speciation and kinetics in soils

    NASA Astrophysics Data System (ADS)

    Maggi, F.; Riley, W. J.; Guerry, N.; Torn, M. S.; Kleber, M.

    2012-12-01

    The nature and dynamics of soil organic matter (SOM) are arguably far from being understood and accurately represented in current site, regional, and global land use and climate models. Whereas consolidated models make use of aggregated pools describing SOM with characteristic turnover times such as inert, passive, slow cycling, and fast cycling, or linking the turnover time to the molecular weight of the compound, recent analyses of SOM below the top soil suggest that those approaches only partially capture SOM dynamics, and that SOM stability may largely be determined by biological and chemical protection as well as other environmental factors rather than the molecular structure of the compound and its molecular weight. We introduce here a new paradigm of SOM speciation and kinetics that explicitly decouples the assumed recalcitrance and turnover time from the SOM molecular density and structure in favour of a mechanistic accounting of microbially mediated processes and chemo-physical interactions among the various SOM species and soil environment. These processes include microbial assimilation, respiration and C recycling; depolymerization of solid litter, root exudates, and dead cells into various decomposed SOM groups; and incorporation of soluble SOM species into a protected phase not available to chemical and biological agents. SOM was described by means of functional compounds including mono- and polysaccharides, lignin, amino compounds, organic acids, nucleic acids, lipids, and phenols, each being accounted for by one or more representative species in the model. Fungal and bacterial microbial functional groups were used to characterize depolymerization and respiration rates. The SOM reaction network and characteristics, its mathematical inclusion within the TOUGHREACT framework, and some preliminary results of modeling grasslands and forested ecosystems are presented here. Biogeochemical reaction network of SOC pathways. Steady state vertical contentration

  4. Transcriptional Profiling of Dibenzo[def,p]chrysene-induced Spleen Atrophy Provides Mechanistic Insights into its Immunotoxicity in MutaMouse.

    PubMed

    Chepelev, Nikolai L; Long, Alexandra S; Williams, Andrew; Kuo, Byron; Gagné, Rémi; Kennedy, Dean A; Phillips, David H; Arlt, Volker M; White, Paul A; Yauk, Carole L

    2016-01-01

    Dibenzo[def,p]chrysene (DBC) is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) examined to date. We investigated the immunotoxicity of DBC, manifested as spleen atrophy, following acute exposure of adult MutaMouse males by oral gavage. Mice were exposed to 0, 2.0, 6.2, or 20.0 mg DBC /kg-bw per day, for 3 days. Genotoxic endpoints (DBC-DNA adducts and lacZ mutant frequency in spleen and bone marrow, and red blood cell micronucleus frequency) and global gene expression changes were measured. All of the genotoxicity measures increased in a dose-dependent manner in spleen and bone marrow. Gene expression analysis showed that DBC activates p53 signaling pathways related to cellular growth and proliferation, which was evident even at the low dose. Strikingly, the expression profiles of DBC exposed mouse spleens were highly inversely correlated with the expression profiles of the only published toxicogenomics dataset of enlarged mouse spleen. This analysis suggested a central role for Bnip3l, a pro-apoptotic protein involved in negative regulation of erythroid maturation. RT-PCR confirmed expression changes in several genes related to apoptosis, iron metabolism, and aryl hydrocarbon receptor signaling that are regulated in the opposite direction during spleen atrophy versus benzo[a]pyrene-mediated splenomegaly. In addition, benchmark dose modeling of toxicogenomics data yielded toxicity estimates that are very close to traditional toxicity endpoints. This work illustrates the power of toxicogenomics to reveal rich mechanistic information for immunotoxic compounds and its ability to provide information that is quantitatively similar to that derived from standard toxicity methods in health risk assessment.

  5. Transcriptional Profiling of Dibenzo[def,p]chrysene-induced Spleen Atrophy Provides Mechanistic Insights into its Immunotoxicity in MutaMouse.

    PubMed

    Chepelev, Nikolai L; Long, Alexandra S; Williams, Andrew; Kuo, Byron; Gagné, Rémi; Kennedy, Dean A; Phillips, David H; Arlt, Volker M; White, Paul A; Yauk, Carole L

    2016-01-01

    Dibenzo[def,p]chrysene (DBC) is the most carcinogenic polycyclic aromatic hydrocarbon (PAH) examined to date. We investigated the immunotoxicity of DBC, manifested as spleen atrophy, following acute exposure of adult MutaMouse males by oral gavage. Mice were exposed to 0, 2.0, 6.2, or 20.0 mg DBC /kg-bw per day, for 3 days. Genotoxic endpoints (DBC-DNA adducts and lacZ mutant frequency in spleen and bone marrow, and red blood cell micronucleus frequency) and global gene expression changes were measured. All of the genotoxicity measures increased in a dose-dependent manner in spleen and bone marrow. Gene expression analysis showed that DBC activates p53 signaling pathways related to cellular growth and proliferation, which was evident even at the low dose. Strikingly, the expression profiles of DBC exposed mouse spleens were highly inversely correlated with the expression profiles of the only published toxicogenomics dataset of enlarged mouse spleen. This analysis suggested a central role for Bnip3l, a pro-apoptotic protein involved in negative regulation of erythroid maturation. RT-PCR confirmed expression changes in several genes related to apoptosis, iron metabolism, and aryl hydrocarbon receptor signaling that are regulated in the opposite direction during spleen atrophy versus benzo[a]pyrene-mediated splenomegaly. In addition, benchmark dose modeling of toxicogenomics data yielded toxicity estimates that are very close to traditional toxicity endpoints. This work illustrates the power of toxicogenomics to reveal rich mechanistic information for immunotoxic compounds and its ability to provide information that is quantitatively similar to that derived from standard toxicity methods in health risk assessment. PMID:26496743

  6. Photochemical ozone creation potentials for oxygenated volatile organic compounds: sensitivity to variations in kinetic and mechanistic parameters

    NASA Astrophysics Data System (ADS)

    Jenkin, Michael E.; Hayman, Garry D.

    The sensitivity of Photochemical Ozone Creation Potentials (POCP) to a series of systematic variations in the rates and products of reactions of radical intermediates and oxygenated products is investigated for the C 4 alcohols, 1-butanol ( n-butanol) and 2-methyl-1-propanol ( i-butanol), using the recently developed Master Chemical Mechanism (MCM) as the base case. The POCP values are determined from the calculated formation of ozone in the boundary layer over a period of approximately five days along an idealised straight line trajectory, using a photochemical trajectory model and methodology described in detail previously. The results allow the relative impacts on calculated ozone formation of various classes of chemical reaction within the degradation chemistry to be assessed. The calculated POCP is found to be very insensitive to many of the changes investigated. However, it is found to be sensitive to variations in the rate coefficient for the initiating reaction with OH ( kOH), although the sensitivity decreases with increasing kOH. The POCP appears to vary approximately linearly with kOH at low values (i.e. kOH less than ca. 4×10 -13 cm 3 molecule -1 s -1), whereas at high reactivities (i.e. kOH greater than ca. 4×10 -11 cm 3 molecule -1 s -1), the calculated POCP value is comparatively insensitive to the precise value of kOH. The POCP is also very sensitive to mechanistic changes which influence the yields of unreactive oxygenated products (i.e. those with OH reactivities below ca. 10 -12 cm 3 molecule -1 s -1), for example acetone. The propensity of the organic compound to produce organic nitrates (which act as comparatively unreactive reservoirs for free radicals and NO x) also appears to have a notable influence on the calculated POCP. Recently reported information relevant to the degradation of oxygenated VOCs is then used to update the chemical schemes for the 17 alcohols and glycols, 10 ethers and glycol ethers, and 8 esters included in the MCM

  7. A mechanistic modeling system for estimating large scale emissions and transport of pollen and co-allergens.

    PubMed

    Efstathiou, Christos; Isukapalli, Sastry; Georgopoulos, Panos

    2011-04-01

    . For the case of ragweed pollen, the model was able to capture the patterns observed during September 2002, but did not predict an early peak; this can be associated with a wider species pollination window and inadequate spatial information in current land cover databases. An additional sensitivity simulation was performed to comparatively evaluate the dispersion patterns predicted by CMAQ-pollen with those predicted by the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model, which is used extensively in aerobiological studies. The CMAQ estimated concentration plumes matched the equivalent pollen scenario modeled with HYSPLIT. The novel pollen modeling approach presented here allows simultaneous estimation of multiple airborne allergens and other air pollutants, and is being developed as a central component of an integrated population exposure modeling system, the Modeling Environment for Total Risk studies (MENTOR) for multiple, co-occurring contaminants that include aeroallergens and irritants.

  8. Investigation of intervertebral disc degeneration using multivariate FTIR spectroscopic imaging† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5fd00160a Click here for additional data file.

    PubMed Central

    Peeters, Mirte; Detiger, Suzanne E. L.; Helder, Marco N.; Smit, Theo H.; Le Maitre, Christine L.; Sammon, Chris

    2016-01-01

    Traditionally tissue samples are analysed using protein or enzyme specific stains on serial sections to build up a picture of the distribution of components contained within them. In this study we investigated the potential of multivariate curve resolution-alternating least squares (MCR-ALS) to deconvolute 2nd derivative spectra of Fourier transform infrared (FTIR) microscopic images measured in transflectance mode of goat and human paraffin embedded intervertebral disc (IVD) tissue sections, to see if this methodology can provide analogous information to that provided by immunohistochemical stains and bioassays but from a single section. MCR-ALS analysis of non-degenerate and enzymatically in vivo degenerated goat IVDs reveals five matrix components displaying distribution maps matching histological stains for collagen, elastin and proteoglycan (PG), as well as immunohistochemical stains for collagen type I and II. Interestingly, two components exhibiting characteristic spectral and distribution profiles of proteoglycans were found, and relative component/tissue maps of these components (labelled PG1 and PG2) showed distinct distributions in non-degenerate versus mildly degenerate goat samples. MCR-ALS analysis of human IVD sections resulted in comparable spectral profiles to those observed in the goat samples, highlighting the inter species transferability of the presented methodology. Multivariate FTIR image analysis of a set of 43 goat IVD sections allowed the extraction of semi-quantitative information from component/tissue gradients taken across the IVD width of collagen type I, collagen type II, PG1 and PG2. Regional component/tissue parameters were calculated and significant correlations were found between histological grades of degeneration and PG parameters (PG1: p = 0.0003, PG2: p < 0.0001); glycosaminoglycan (GAG) content and PGs (PG1: p = 0.0055, PG2: p = 0.0001); and MRI T2* measurements and PGs (PG1: p = 0.0021, PG2: p < 0.0001). Additionally

  9. The effect of zinc on amyloid β-protein assembly and toxicity: A mechanistic investigation

    NASA Astrophysics Data System (ADS)

    Solomonov, Inna; Sagi, Irit

    2014-10-01

    Neurotoxic assemblies of amyloid β-protein (Aβ) are widely believed to be the cause for Alzheimer's disease (AD). Therefore, understanding the factors and mechanisms that control, modulate, and inhibit formation of these assemblies is crucial for the development of therapeutic intervention of AD. This information also can contribute significantly to our understanding of the mechanisms of other amyloidosis diseases, such as Parkinson's disease, Huntington's disease, type 2 diabetes, amyotrophic lateral sclerosis (Lou Gehrig's disease) and prion diseases (e.g. Mad Cow disease). We have developed a multidisciplinary experimental strategy to study structural and dynamic mechanistic aspects that underlie the Aβ assembly process. Utilizing this strategy, we explored the molecular basis leading to the perturbation of the Aβ assembly process by divalent metal ions, mainly Zn2+ ions. Using Zn2+ as reaction physiological relevant probes, it was demonstrated that Zn2+ rapidly (milliseconds) induce self-assembly of Aβ aggregates and stabilize them in a manner that prevents formation of Aβ fibrils. Importantly, the early-formed intermediates are substantially more neurotoxic than fibrils. Our results suggest that relevant Aβ modulators should be targeted against the rapidly evolved intermediate states of Aβ assembly. The design of such modulators is challenging, as they have to compete with different natural mediators (such as Zn2+) of Aβ aggregation, which diverse Aβ assemblies in both specific and nonspecific manners.

  10. Kinetic and mechanistic studies of free-radical reactions in combustion

    SciTech Connect

    Tully, F.P.

    1993-12-01

    Combustion is driven by energy-releasing chemical reactions. Free radicals that participate in chain reactions carry the combustion process from reactants to products. Research in chemical kinetics enables us to understand the microscopic mechanisms involved in individual chemical reactions as well as to determine the rates at which they proceed. Both types of information are required for an understanding of how flames burn, why engines knock, how to minimize the production of pollutants, and many other important questions in combustion. In this program the authors emphasize accurate measurements over wide temperature ranges of the rates at which ubiquitous free radicals react with stable molecules. The authors investigate a variety of OH, CN, and CH + stable molecule reactions important to fuel conversion, emphasizing application of the extraordinarily precise technique of laser photolysis/continuous-wave laser-induced fluorescence (LP/cwLIF). This precision enables kinetic measurements to serve as mechanistic probes. Since considerable effort is required to study each individual reaction, prudent selection is critical. Two factors encourage selection of a specific reaction: (1) the rates and mechanisms of the subject reaction are required input to a combustion model; and (2) the reaction is a chemical prototype which, upon characterization, will provide fundamental insight into chemical reactivity, facilitate estimation of kinetic parameters for similar reactions, and constrain and test the computational limits of reaction-rate theory. Most studies performed in this project satisfy both conditions.

  11. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    NASA Astrophysics Data System (ADS)

    Stites, Edward C.

    2013-04-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients.

  12. Rational design of transcranial current stimulation (TCS) through mechanistic insights into cortical network dynamics.

    PubMed

    Fröhlich, Flavio; Schmidt, Stephen L

    2013-01-01

    Transcranial current stimulation (TCS) is a promising method of non-invasive brain stimulation to modulate cortical network dynamics. Preliminary studies have demonstrated the ability of TCS to enhance cognition and reduce symptoms in both neurological and psychiatric illnesses. Despite the encouraging results of these studies, the mechanisms by which TCS and endogenous network dynamics interact remain poorly understood. Here, we propose that the development of the next generation of TCS paradigms with increased efficacy requires such mechanistic understanding of how weak electric fields (EFs) imposed by TCS interact with the nonlinear dynamics of large-scale cortical networks. We highlight key recent advances in the study of the interaction dynamics between TCS and cortical network activity. In particular, we illustrate an interdisciplinary approach that bridges neurobiology and electrical engineering. We discuss the use of (1) hybrid biological-electronic experimental approaches to disentangle feedback interactions; (2) large-scale computer simulations for the study of weak global perturbations imposed by TCS; and (3) optogenetic manipulations informed by dynamic systems theory to probe network dynamics. Together, we here provide the foundation for the use of rational design for the development of the next generation of TCS neurotherapeutics. PMID:24324427

  13. Parameter determination and validation for a mechanistic model of the enzymatic saccharification of cellulose-Iβ.

    PubMed

    Nag, Ambarish; Sprague, Michael A; Griggs, Andrew J; Lischeske, James J; Stickel, Jonathan J; Mittal, Ashutosh; Wang, Wei; Johnson, David K

    2015-01-01

    Cost-effective production of fuels and chemicals from lignocellulosic biomass often involves enzymatic saccharification, which has been the subject of intense research and development. Recently, a mechanistic model for the enzymatic saccharification of cellulose has been developed that accounts for distribution of cellulose chain lengths, the accessibility of insoluble cellulose to enzymes, and the distinct modes of action of the component cellulases [Griggs et al. (2012) Biotechnol. Bioeng., 109(3):665-675; Griggs et al. (2012) Biotechnol. Bioeng., 109(3):676-685]. However, determining appropriate values for the adsorption, inhibition, and rate parameters required further experimental investigation. In this work, we performed several sets of experiments to aid in parameter estimation and to quantitatively validate the model. Cellulosic materials differing in degrees of polymerization and crystallinity (α-cellulose-Iβ and highly crystalline cellulose-Iβ ) were digested by component enzymes (EGI/CBHI/βG) and by mixtures of these enzymes. Based on information from the literature and the results from these experiments, a single set of model parameters was determined, and the model simulation results using this set of parameters were compared with the experimental data of total glucan conversion, chain-length distribution, and crystallinity. Model simulations show significant agreement with the experimentally derived glucan conversion and chain-length distribution curves and provide interesting insights into multiple complex and interacting physico-chemical phenomena involved in enzymatic hydrolysis, including enzyme synergism, substrate accessibility, cellulose chain length distribution and crystallinity, and inhibition of cellulases by soluble sugars.

  14. Predicting Ecosystem Responses with AQUATOX, a Mechanistic Fate and Effects Model

    NASA Astrophysics Data System (ADS)

    Park, R. A.; Wellman, M. C.

    2005-05-01

    AQUATOX, a mechanistic fate and effects model, simulates the significant physical, chemical, and biological processes affecting aquatic biota. The user can represent the food web with as little or as much complexity as desired. Generality is balanced with site specificity. The parameters governing the biological processes are designed to be as general as possible, such that a parameter set for a group of organisms should transfer from site to site with little or no recalibration. For example, maximum photosynthetic rates for specific plants should be "global," but the predicted time-varying site photosynthetic rates change with temperature, nutrients, light, and toxic chemicals. AQUATOX also contains informative analytical tools. Control and Perturbed simulations isolate the effects of the differences due to a particular stressor, much like a controlled laboratory experiment. The predicted in situ rates due to ecological processes (such as consumption, mortality, and reproduction) and limitations on photosynthesis can be saved and graphed, enabling the analyst to identify the important processes and environmental controls operating at any given time. Built-in uncertainty analysis allows the user to test which driving variables and parameters are most important to the particular endpoints of interest. Examples of simulations of stream ecosystems will be given.

  15. Mechanistic and therapeutic overview of glycosaminoglycans: the unsung heroes of biomolecular signaling.

    PubMed

    Gulati, Khushboo; Poluri, Krishna Mohan

    2016-02-01

    Immune regulation is a complex biological signaling pathway in which several classes of biomolecules and small molecules play a complacent role to mediate this process. Glycoimmunology is a rapidly evolving research area that deals with the structure, binding interactions and immunological functions of glycans. Great deal of information regarding proteins and nucleic acids in molecular recognition events have been established owing to their well-established structural features and straight forward replication, transcription and translation principles. However considering the complexities of template free synthesis and structural heterogeneity, role of carbohydrates in immune regulation are still unsung to a large extent. In the current review, we illuminate the canonical structural features, emerging and significant pathophysiological functions of glycosaminoglycans (GAGs), the negatively charged linear carbohydrate molecules that are primarily present on all types of cell surfaces and extra cellular matrix. A snap shot of their association with protein counterparts of diversified protein families has been updated exclusively to provide mechanistic insights into their cellular signaling functions. Eventually, this review throws light on the recent biomedical/biotechnological advances of GAG based biomarkers, nutraceuticals, therapeutics, and nanocomposites for inflammatory, immune disorders and their invaluable contribution in tissue engineering.

  16. Indole-3- carbinol enhances sorafenib cytotoxicity in hepatocellular carcinoma cells: A mechanistic study

    NASA Astrophysics Data System (ADS)

    Abdelmageed, Mai M.; El-Naga, Reem N.; El-Demerdash, Ebtehal; Elmazar, Mohamed M.

    2016-09-01

    Sorafenib is the only chemotherapeutic agent currently approved for unresectable hepatocellular carcinoma (HCC). However, poor response rates have been widely reported. Indole-3-carbinol (I3C) is a potential chemopreventive phytochemical. The present study aimed to explore the potential chemomodulatory effects of I3C on sorafenib in HCC cells as well as the possible underlying mechanisms. I3C exhibited a greater cytotoxicity in HepG2 cells compared to Huh-7 cells (p < 0.0001). Moreover, the co-treatment of HepG2 cells with I3C and sorafenib was more effective (p = 0.002). Accordingly, subsequent mechanistic studies were carried on HepG2 cells. The results show that the ability of I3C to enhance sorafenib cytotoxicity in HCC cells could be partially attributed to increasing the apoptotic activity and decreasing the angiogenic potentials. The combination had a negative effect on epithelial-mesenchymal transition (EMT). Increased NOX-1 expression was also observed which may indicate the involvement of NOX-1 in I3C chemomodulatory effects. Additionally, the combination induced cell cycle arrest at the G0/G1 phase. In conclusion, these findings provide evidence that I3C enhances sorafenib anti-cancer activity in HCC cells.

  17. Immunosuppressive potency of mechanistic target of rapamycin inhibitors in solid-organ transplantation

    PubMed Central

    Baroja-Mazo, Alberto; Revilla-Nuin, Beatriz; Ramírez, Pablo; Pons, José A

    2016-01-01

    Mammalian target of rapamycin, also known as mechanistic target of rapamycin (mTOR) is a protein kinase that belongs to the PI3K/AKT/mTOR signaling pathway, which is involved in several fundamental cellular functions such as cell growth, proliferation, and survival. This protein and its associated pathway have been implicated in cancer development and the regulation of immune responses, including the rejection response generated following allograft transplantation. Inhibitors of mTOR (mTORi) such as rapamycin and its derivative everolimus are potent immunosuppressive drugs that both maintain similar rates of efficacy and could optimize the renal function and diminish the side effects compared with calcineurin inhibitors. These drugs are used in solid-organ transplantationtoinduceimmunosuppression while also promoting the expansion of CD4+CD25+FOXP3+ regulatory T-cells that could favor a scenery of immunological tolerance. In this review, we describe the mechanisms by which inhibitors of mTOR induce suppression by regulation of these pathways at different levels of the immune response. In addition, we particularly emphasize about the main methods that are used to assess the potency of immunosuppressive drugs, highlighting the studies carried out about immunosuppressive potency of inhibitors of mTOR. PMID:27011916

  18. A mechanistic treatment of the dominant soil nitrogen cycling processes: Model development, testing, and application

    NASA Astrophysics Data System (ADS)

    Maggi, F.; Gu, C.; Riley, W. J.; Hornberger, G. M.; Venterea, R. T.; Xu, T.; Spycher, N.; Steefel, C.; Miller, N. L.; Oldenburg, C. M.

    2008-06-01

    The development and initial application of a mechanistic model (TOUGHREACT-N) designed to characterize soil nitrogen (N) cycling and losses are described. The model couples advective and diffusive nutrient transport, multiple microbial biomass dynamics, and equilibrium and kinetic chemical reactions. TOUGHREACT-N was calibrated and tested against field measurements to assess pathways of N loss as either gas emission or solute leachate following fertilization and irrigation in a Central Valley, California, agricultural field as functions of fertilizer application rate and depth, and irrigation water volume. Our results, relative to the period before plants emerge, show that an increase in fertilizer rate produced a nonlinear response in terms of N losses. An increase of irrigation volume produced NO2- and NO3- leaching, whereas an increase in fertilization depth mainly increased leaching of all N solutes. In addition, nitrifying bacteria largely increased in mass with increasing fertilizer rate. Increases in water application caused nitrifiers and denitrifiers to decrease and increase their mass, respectively, while nitrifiers and denitrifiers reversed their spatial stratification when fertilizer was applied below 15 cm depth. Coupling aqueous advection and diffusion, and gaseous diffusion with biological processes, closely captured actual conditions and, in the system explored here, significantly clarified interpretation of field measurements.

  19. A comparative kinetic and mechanistic study between tetrahydrozoline and naphazoline toward photogenerated reactive oxygen species.

    PubMed

    Criado, Susana; García, Norman A

    2010-01-01

    Kinetic and mechanistic aspects of the vitamin B2 (riboflavin [Rf])-sensitized photo-oxidation of the imidazoline derivates (IDs) naphazoline (NPZ) and tetrahydrozoline (THZ) were investigated in aqueous solution. The process appears as important on biomedical grounds, considering that the vitamin is endogenously present in humans, and IDs are active components of ocular medicaments of topical application. Under aerobic visible light irradiation, a complex picture of competitive interactions between sensitizer, substrates and dissolved oxygen takes place: the singlet and triplet ((3)Rf*) excited states of Rf are quenched by the IDs: with IDs concentrations ca. 5.0 mM and 0.02 mM Rf, (3)Rf* is quenched by IDs, in a competitive fashion with dissolved ground state oxygen. Additionally, the reactive oxygen species: O(2)((1)Delta(g)), O(2)(*-), HO(*) and H(2)O(2), generated from (3)Rf* and Rf(*-), were detected with the employment of time-resolved methods or specific scavengers. Oxygen uptake experiments indicate that, for NPZ, only H(2)O(2) was involved in the photo-oxidation. In the case of THZ, O(2)(*-), HO(*) and H(2)O(2) were detected, whereas only HO(*) was unambiguously identified as THZ oxidative agents. Upon direct UV light irradiation NPZ and THZ generate O(2)((1)Delta(g)), with quantum yields of 0.2 (literature value, employed as a reference) and 0.08, respectively, in acetonitrile.

  20. A Mechanistic Treatment of the Dominant Soil Nitrogen Cycling Processes: Model Development, Testing, and Application

    SciTech Connect

    Riley, William; Maggi, F.; Gu, C.; Riley, W.J.; Hornberger, G.M.; Venterea, R.T.; Xu, T.; Spycher, N.; Steefel, C.; Miller, N.L.; Oldenburg, C.M.

    2008-05-01

    The development and initial application of a mechanistic model (TOUGHREACT-N) designed to characterize soil nitrogen (N) cycling and losses are described. The model couples advective and diffusive nutrient transport, multiple microbial biomass dynamics, and equilibrium and kinetic chemical reactions. TOUGHREACT-N was calibrated and tested against field measurements to assess pathways of N loss as either gas emission or solute leachate following fertilization and irrigation in a Central Valley, California, agricultural field as functions of fertilizer application rate and depth, and irrigation water volume. Our results, relative to the period before plants emerge, show that an increase in fertilizer rate produced a nonlinear response in terms of N losses. An increase of irrigation volume produced NO{sub 2}{sup -} and NO{sub 3}{sup -} leaching, whereas an increase in fertilization depth mainly increased leaching of all N solutes. In addition, nitrifying bacteria largely increased in mass with increasing fertilizer rate. Increases in water application caused nitrifiers and denitrifiers to decrease and increase their mass, respectively, while nitrifiers and denitrifiers reversed their spatial stratification when fertilizer was applied below 15 cm depth. Coupling aqueous advection and diffusion, and gaseous diffusion with biological processes, closely captured actual conditions and, in the system explored here, significantly clarified interpretation of field measurements.