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. Mechanistic information from analysis of molecular weight distributions of starch.

    PubMed

    Castro, Jeffrey V; Dumas, Céline; Chiou, Herbert; Fitzgerald, Melissa A; Gilbert, Robert G

    2005-01-01

    A methodology is developed for interpreting the molecular weight distributions of debranched amylopectin, based on techniques developed for quantitatively and qualitatively finding mechanistic information from the molecular weight distributions of synthetic polymers. If the only events occurring are random chain growth and stoppage (i.e., the rates are independent of degree of polymerization over the range in question), then the number of chains of degree of polymerization N, P(N), is linear in ln P(N) with a negative slope, where the slope gives the ratio of the stoppage and growth rates. This starting point suggests that mechanistic inferences can be made from a plot of lnP against N. Application to capillary electrophoresis data for the P(N) of debranched starch from across the major taxa, from bacteria (Escherichia coli), green algae (Chlamydomonas reinhardtii), mammals (Bos), and flowering plants (Oryza sativa, rice; Zea mays, maize; Triticum aestivum, wheat; Hordeum vulgare, barley; and Solanum tuberosum, potato), gives insights into the biosynthetic pathways, showing the differences and similarities of the alpha-1,4-glucans produced by the various species. Four characteristic regions for storage starch from the higher plants are revealed: (1) an initial increasing region corresponding to the formation of new branches, (2) a linear ln P region with negative slope, indicating random growth and stoppage, (3) a region corresponding to the formation of the crystalline lamellae and subsequent elongation of chains, and (4) a second linear ln P with negative slope region. Each region can be assigned to specific enzymatic processes in starch synthesis, including determining the ranges of degrees of polymerization which are subject to random and nonrandom processes. PMID:16004469

  4. 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. PMID:27384597

  5. 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

  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, 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,...

  8. 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,...

  9. 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...

  10. 34 CFR 75.231 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 1 2012-07-01 2012-07-01 false Additional information. 75.231 Section 75.231 Education... 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. 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... activity to submit additional information....

  12. 10 CFR 725.13 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 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...

  13. 10 CFR 725.13 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 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...

  14. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Additional information. 1010.116 Section 1010...) Reporting Requirements § 1010.116 Additional information. (a) Property Owners' Association. (1) Will there... obligation to retire the debt. (c) Violations and litigations. This information need appear only if any...

  15. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Additional information. 1710.216... § 1710.216 Additional information. (a) Property Owners' Association. (1) If the association has been..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  16. 12 CFR 1010.116 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Additional information. 1010.116 Section 1010...) Reporting Requirements § 1010.116 Additional information. (a) Property Owners' Association. (1) Will there... obligation to retire the debt. (c) Violations and litigations. This information need appear only if any...

  17. 12 CFR 1010.216 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Additional information. 1010.216 Section 1010...) Reporting Requirements § 1010.216 Additional information. (a) Property Owners' Association. (1) If the..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  18. 12 CFR 1010.216 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Additional information. 1010.216 Section 1010...) Reporting Requirements § 1010.216 Additional information. (a) Property Owners' Association. (1) If the..., information on such matters as to: (i) Whether the developer will employ his own sales force or will...

  19. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.39 Additional information. (a) If the request for an advisory opinion does not contain all of the information... advisory opinion, the OIG may, at any time, request whatever additional information or documents it...

  20. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.39 Additional information. (a) If the request for an advisory opinion does not contain all of the information... advisory opinion, the OIG may, at any time, request whatever additional information or documents it...

  1. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.39 Additional information. (a) If the request for an advisory opinion does not contain all of the information... advisory opinion, the OIG may, at any time, request whatever additional information or documents it...

  2. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.39 Additional information. (a) If the request for an advisory opinion does not contain all of the information... advisory opinion, the OIG may, at any time, request whatever additional information or documents it...

  3. 42 CFR 1008.39 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... AUTHORITIES ADVISORY OPINIONS BY THE OIG Submission of a Formal Request for an Advisory Opinion § 1008.39 Additional information. (a) If the request for an advisory opinion does not contain all of the information... advisory opinion, the OIG may, at any time, request whatever additional information or documents it...

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. 46 CFR 502.314 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 9 2011-10-01 2011-10-01 false Additional information. 502.314 Section 502.314 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Formal Procedure for Adjudication of Small Claims § 502.314 Additional information. The administrative law...

  11. 46 CFR 502.314 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 9 2014-10-01 2014-10-01 false Additional information. 502.314 Section 502.314 Shipping FEDERAL MARITIME COMMISSION GENERAL AND ADMINISTRATIVE PROVISIONS RULES OF PRACTICE AND PROCEDURE Formal Procedure for Adjudication of Small Claims § 502.314 Additional information. The administrative law...

  12. 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...

  13. 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...

  14. 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 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses General Application Filing Requirements § 25.111 Additional information. (a)...

  15. 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 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES SATELLITE COMMUNICATIONS Applications and Licenses General Application Filing Requirements § 25.111 Additional information. (a)...

  16. 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...

  17. 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 Department of Energy may at any time require a person engaging in any generally or specifically...

  18. Turbulent Flow Enhancement by Polyelectrolyte Additives: Mechanistic Implications for Drag Reduction.

    NASA Astrophysics Data System (ADS)

    Wagger, David Leonard

    1992-01-01

    The drag reduction phenomenon was experimentally studied in two pipes, of diameters 1.46 and 1.02 cm, using seven polyelectrolytic HPAM additives, with molecular weights from 1 to 20 times 10^6 g/mole and degree of backbone hydrolysis from 8 to 60%, at concentrations from 1 to 1000 wppm, in saline solutions containing from 0.3 to 0.00001 N NaCl. Both laminar and turbulent flow behavior were greatly influenced by salinity-induced changes in the initial conformation of the HPAM additives. Initially collapsed, random-coiling conformations exhibited Newtonian laminar flow and Type-A turbulent drag reduction, while initially extended conformations exhibited shear-thinning in laminar flow and Type-B turbulent drag reduction. The gross-flow physics of Type-B drag reduction were delineated. A characteristic "ladder" structure prevailed, with polymeric regime segments that were roughly parallel to, but shifted upward from, the Prandtl-Karman line. In the polymeric regime, both Type-A fan and Type -B ladder structures were essentially independent of pipe diameter, and were scaled by the wall shear stress. The wall shear stress also scaled degradation during drag reduction. New onset and slope increment correlations were presented for Type-A drag reduction by HPAM additives. In Type-B drag reduction, flow enhancement was found proportional to additive concentration, and the intrinsic slip, Sigma = S^'/(c/M _{rm w}), varied roughly as the third power of backbone chain links N_ {rm bb}. New intrinsic slip and retro-onset correlations were presented for Type-B drag reduction by HPAM additives. Analysis of Type-B literature revealed a wide range of additive efficacies, with specific slips S^'/c from 0.0001 to 4. For the most effective additives, HPAM and asbestos fibers, the additive-pervaded volume fraction per unit flow enhancement, X_{rm v} /S^' ~ 3000, implied that these additives align during drag reduction. The slip ratio R_{rm sc}, which is the relative flow enhancement

  19. 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

  20. Mechanistic investigations reveal that dibromobimane extrudes sulfur from biological sulfhydryl sources other than hydrogen sulfide† †Electronic supplementary information (ESI) available: Experimental details, pH stability data for BTE, NMR spectra. See DOI: 10.1039/c4sc01875c Click here for additional data file.

    PubMed Central

    Montoya, Leticia A.; Shen, Xinggui; McDermott, James J.

    2015-01-01

    Hydrogen sulfide (H2S) has emerged as an important biological signaling molecule in the last decade. During the growth of this field, significant controversy has arisen centered on the physiological concentrations of H2S. Recently, a monobromobimane (mBB) method has been developed for the quantification of different biologically-relevant sulfide pools. Based on the prevalence of the mBB method for sulfide quantification, we expand on this method to report the use of dibromobimane (dBB) for sulfide quantification. Reaction of H2S with dBB results in formation of highly-fluorescent bimane thioether (BTE), which is readily quantifiable by HPLC. Additionally, the reaction of sulfide with dBB to form BTE is significantly faster than the reaction of sulfide with mBB to form sulfide dibimane. Using the dBB method, BTE levels as low as 0.6 pM can be detected. Upon use of the dBB method in wild-type and CSE–/– mice, however, dBB reports significantly higher sulfide levels than those measured using mBB. Further investigation revealed that dBB is able to extract sulfur from other sulfhydryl sources including thiols. Based on mechanistic studies, we demonstrate that dBB extracts sulfur from thiols with α- or β-hydrogens, thus leading to higher BTE formation than from sulfide alone. Taken together, the dBB method is a highly sensitive method for H2S but is not compatible for use in studies in which other thiols are present. PMID:25632344

  1. A Mechanistic Study of Halogen Addition and Photoelimination from π-Conjugated Tellurophenes.

    PubMed

    Carrera, Elisa I; Lanterna, Anabel E; Lough, Alan J; Scaiano, Juan C; Seferos, Dwight S

    2016-03-01

    The ability to drive reactivity using visible light is of importance for many disciplines of chemistry and has significant implications for sustainable chemistry. Identifying photochemically active compounds and understanding photochemical mechanisms is important for the development of useful materials for synthesis and catalysis. Here we report a series of photoactive diphenyltellurophene compounds bearing electron-withdrawing and electron-donating substituents synthesized by alkyne coupling/ring closing or palladium-catalyzed ipso-arylation chemistry. The redox chemistry of these compounds was studied with respect to oxidative addition and photoelimination of bromine, which is of importance for energy storage reactions involving X2. The oxidative addition reaction mechanism was studied using density functional theory, the results of which support a three-step mechanism involving the formation of an initial η(1) association complex, a monobrominated intermediate, and finally the dibrominated product. All of the tellurophene derivatives undergo photoreduction using 430, 447, or 617 nm light depending on the absorption properties of the compound. Compounds bearing electron-withdrawing substituents have the highest photochemical quantum efficiencies in the presence of an alkene trap, with efficiencies of up to 42.4% for a pentafluorophenyl-functionalized tellurophene. The photoelimination reaction was studied in detail through bromine trapping experiments and laser flash photolysis, and a mechanism is proposed. The photoreaction, which occurs by release of bromine radicals, is competitive with intersystem crossing to the triplet state of the brominated species, as evidenced by the formation of singlet oxygen. These findings should be useful for the design of new photochemically active compounds supported by main-group elements. PMID:26853739

  2. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Additional information. 1710.116 Section 1710.116 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  3. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Additional information. 1710.116 Section 1710.116 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  4. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Additional information. 1710.116 Section 1710.116 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  5. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Additional information. 1710.216 Section 1710.216 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  6. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Additional information. 1710.116 Section 1710.116 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  7. 18 CFR 33.10 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 33.10 Section 33.10 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS UNDER FEDERAL POWER ACT SECTION 203 § 33.10 Additional information. The Director of the Office of Energy Market Regulation, or his...

  8. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Additional information. 1710.216 Section 1710.216 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  9. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Additional information. 970.2601 Section 970.2601 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED...

  10. 24 CFR 1710.216 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Additional information. 1710.216 Section 1710.216 Housing and Urban Development Regulations Relating to Housing and Urban Development... URBAN DEVELOPMENT (INTERSTATE LAND SALES REGISTRATION PROGRAM) LAND REGISTRATION Reporting...

  11. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Additional information. 970.2601 Section 970.2601 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED...

  12. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Additional information. 970.2601 Section 970.2601 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED...

  13. 15 CFR 970.2601 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Additional information. 970.2601 Section 970.2601 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE GENERAL REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED...

  14. Refining Breast Cancer Risk Stratification: Additional Genes, Additional Information.

    PubMed

    Kurian, Allison W; Antoniou, Antonis C; Domchek, Susan M

    2016-01-01

    Recent advances in genomic technology have enabled far more rapid, less expensive sequencing of multiple genes than was possible only a few years ago. Advances in bioinformatics also facilitate the interpretation of large amounts of genomic data. New strategies for cancer genetic risk assessment include multiplex sequencing panels of 5 to more than 100 genes (in which rare mutations are often associated with at least two times the average risk of developing breast cancer) and panels of common single-nucleotide polymorphisms (SNPs), combinations of which are generally associated with more modest cancer risks (more than twofold). Although these new multiple-gene panel tests are used in oncology practice, questions remain about the clinical validity and the clinical utility of their results. To translate this increasingly complex genetic information for clinical use, cancer risk prediction tools are under development that consider the joint effects of all susceptibility genes, together with other established breast cancer risk factors. Risk-adapted screening and prevention protocols are underway, with ongoing refinement as genetic knowledge grows. Priority areas for future research include the clinical validity and clinical utility of emerging genetic tests; the accuracy of developing cancer risk prediction models; and the long-term outcomes of risk-adapted screening and prevention protocols, in terms of patients' experiences and survival. PMID:27249685

  15. Sufficient dimension reduction with additional information.

    PubMed

    Hung, Hung; Liu, Chih-Yen; Horng-Shing Lu, Henry

    2016-07-01

    Sufficient dimension reduction is widely applied to help model building between the response [Formula: see text] and covariate [Formula: see text] In some situations, we also collect additional covariate [Formula: see text] that has better performance in predicting [Formula: see text], but has a higher obtaining cost, than [Formula: see text] While constructing a predictive model for [Formula: see text] based on [Formula: see text] is straightforward, this strategy is not applicable since [Formula: see text] is not available for future observations in which the constructed model is to be applied. As a result, the aim of the study is to build a predictive model for [Formula: see text] based on [Formula: see text] only, where the available data is [Formula: see text] A naive method is to conduct analysis using [Formula: see text] directly, but ignoring [Formula: see text] can cause the problem of inefficiency. On the other hand, it is not trivial to utilize the information of [Formula: see text] to infer [Formula: see text], either. In this article, we propose a two-stage dimension reduction method for [Formula: see text] that is able to utilize the information of [Formula: see text] In the breast cancer data, the risk score constructed from the two-stage method can well separate patients with different survival experiences. In the Pima data, the two-stage method requires fewer components to infer the diabetes status, while achieving higher classification accuracy than the conventional method. PMID:26704765

  16. 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... information required by the ITU Radiocommunication Bureau to advance publish, coordinate and notify...

  17. A Mechanistic Dichotomy Leading to a Ruthenium-Catalyzed cis-Addition for Stereoselective Formation of (Z)-Vinyl Bromides.

    PubMed

    Trost; Pinkerton

    2000-01-01

    Either trans- or cis-haloalkylation is possible through a three-component coupling [Eq. (1)]. The cis-bromoruthenation of an alkyne by lithium bromide and [CpRu(CH(3)CN)(3)]PF(6), catalyzed by SnBr(4), gives (Z)-vinyl bromides with high chemoselectivity. The degree of control over the sterochemistry raises intriguing mechanistic questions as well as offering practical synthetic utility. PMID:10649409

  18. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE... receipt of the opinion request, or, in the case of an incomplete response to a previous request for... requesting an FCPA Opinion must promptly provide the information requested. A request will not be...

  19. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE... receipt of the opinion request, or, in the case of an incomplete response to a previous request for... requesting an FCPA Opinion must promptly provide the information requested. A request will not be...

  20. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE... receipt of the opinion request, or, in the case of an incomplete response to a previous request for... requesting an FCPA Opinion must promptly provide the information requested. A request will not be...

  1. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE... receipt of the opinion request, or, in the case of an incomplete response to a previous request for... requesting an FCPA Opinion must promptly provide the information requested. A request will not be...

  2. 28 CFR 80.7 - Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) FOREIGN CORRUPT PRACTICES ACT OPINION PROCEDURE... receipt of the opinion request, or, in the case of an incomplete response to a previous request for... requesting an FCPA Opinion must promptly provide the information requested. A request will not be...

  3. Informed Additive Literacy Instruction for ELLs

    ERIC Educational Resources Information Center

    Bauer, Eurydice Bouchereau

    2009-01-01

    There are numerous reasons why schools struggle to provide English-language learners (ELLs) with additive literacy instruction. One reason for this is the lack of available trained bilingual teachers, mainstream teachers who have not received adequate training on how to teach ELLs, and the current political climate that appears to support an…

  4. 29 CFR 2570.39 - Opportunities to submit additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 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...

  5. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Samples; additional information. 71.4 Section 71.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS General Provisions § 71.4 Samples; additional information. The Commissioner may request samples of the color additive,...

  6. Mechanistic validation.

    PubMed

    Hartung, Thomas; Hoffmann, Sebastian; Stephens, Martin

    2013-01-01

    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

  7. 34 CFR 303.212 - Additional information and assurances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  8. 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...

  9. 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...

  10. The Value of Mechanistic Biophysical Information for Systems-Level Understanding of Complex Biological Processes Such as Cytokinesis

    PubMed Central

    Pollard, Thomas D.

    2014-01-01

    This review illustrates the value of quantitative information including concentrations, kinetic constants and equilibrium constants in modeling and simulating complex biological processes. Although much has been learned about some biological systems without these parameter values, they greatly strengthen mechanistic accounts of dynamical systems. The analysis of muscle contraction is a classic example of the value of combining an inventory of the molecules, atomic structures of the molecules, kinetic constants for the reactions, reconstitutions with purified proteins and theoretical modeling to account for the contraction of whole muscles. A similar strategy is now being used to understand the mechanism of cytokinesis using fission yeast as a favorable model system. PMID:25468329

  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. 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

  13. 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.

  14. 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

  15. 43 CFR 3430.4-2 - Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) NONCOMPETITIVE LEASES Preference Right Leases § 3430.4-2 Additional information. (a) If the applicant for a preference right lease has submitted... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Additional information. 3430.4-2...

  16. 29 CFR 502.44 - Additional information, if required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Additional information, if required. 502.44 Section 502.44 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS... Administrative Law Judge's Decision § 502.44 Additional information, if required. Where the ARB has determined...

  17. 29 CFR 502.44 - Additional information, if required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Additional information, if required. 502.44 Section 502.44 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS... Administrative Law Judge's Decision § 502.44 Additional information, if required. Where the ARB has determined...

  18. 33 CFR 403.6 - Additional information. [Rule 6

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Additional information. 403.6 Section 403.6 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION RULES OF PROCEDURE OF THE JOINT TOLLS REVIEW BOARD § 403.6 Additional information. The Board...

  19. 33 CFR 403.6 - Additional information. [Rule 6

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Additional information. 403.6 Section 403.6 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION RULES OF PROCEDURE OF THE JOINT TOLLS REVIEW BOARD § 403.6 Additional information. The Board...

  20. 21 CFR 607.31 - Additional blood product listing information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Additional blood product listing information. 607... BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.31 Additional blood... following information by letter or by Federal Register notice: (1) For a particular blood product so...

  1. 21 CFR 607.31 - Additional blood product listing information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Additional blood product listing information. 607... BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.31 Additional blood... following information by letter or by Federal Register notice: (1) For a particular blood product so...

  2. 21 CFR 607.31 - Additional blood product listing information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Additional blood product listing information. 607... BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.31 Additional blood... following information by letter or by Federal Register notice: (1) For a particular blood product so...

  3. 21 CFR 607.31 - Additional blood product listing information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Additional blood product listing information. 607... BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.31 Additional blood... following information by letter or by Federal Register notice: (1) For a particular blood product so...

  4. 21 CFR 607.31 - Additional blood product listing information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Additional blood product listing information. 607... BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.31 Additional blood... following information by letter or by Federal Register notice: (1) For a particular blood product so...

  5. 29 CFR 502.44 - Additional information, if required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Additional information, if required. 502.44 Section 502.44... ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF... Administrative Law Judge's Decision § 502.44 Additional information, if required. Where the ARB has determined...

  6. 29 CFR 502.44 - Additional information, if required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Additional information, if required. 502.44 Section 502.44... ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF... Administrative Law Judge's Decision § 502.44 Additional information, if required. Where the ARB has determined...

  7. 29 CFR 501.44 - Additional information, if required.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 3 2014-07-01 2014-07-01 false Additional information, if required. 501.44 Section 501.44... ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF... Decision § 501.44 Additional information, if required. Where the ARB has determined to review such...

  8. 29 CFR 501.44 - Additional information, if required.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 3 2012-07-01 2012-07-01 false Additional information, if required. 501.44 Section 501.44... ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218 OF... Decision § 501.44 Additional information, if required. Where the ARB has determined to review such...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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... Monetary Penalty in Lieu of Suspension or Revocation § 111.60 Request for additional information. If,...

  15. 78 FR 75568 - Notice of Request for Additional Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Notice of Request for Additional Information The Commission gives notice that it has formally requested that the parties to the below listed agreement provide additional information pursuant to 46 U.S.C. 40304(d). This action prevents the...

  16. 32 CFR 1698.3 - Requests for additional information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ADVISORY OPINIONS § 1698.3 Requests for additional information. (a) The Director may request additional appropriate information from the requester for an advisory opinion. (b) The Director will forward a copy of the request by a Federal, state or municipal governmental agency for an advisory opinion to the...

  17. 32 CFR 1698.3 - Requests for additional information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ADVISORY OPINIONS § 1698.3 Requests for additional information. (a) The Director may request additional appropriate information from the requester for an advisory opinion. (b) The Director will forward a copy of the request by a Federal, state or municipal governmental agency for an advisory opinion to the...

  18. 32 CFR 1698.3 - Requests for additional information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ADVISORY OPINIONS § 1698.3 Requests for additional information. (a) The Director may request additional appropriate information from the requester for an advisory opinion. (b) The Director will forward a copy of the request by a Federal, state or municipal governmental agency for an advisory opinion to the...

  19. 32 CFR 1698.3 - Requests for additional information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ADVISORY OPINIONS § 1698.3 Requests for additional information. (a) The Director may request additional appropriate information from the requester for an advisory opinion. (b) The Director will forward a copy of the request by a Federal, state or municipal governmental agency for an advisory opinion to the...

  20. 32 CFR 1698.3 - Requests for additional information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ADVISORY OPINIONS § 1698.3 Requests for additional information. (a) The Director may request additional appropriate information from the requester for an advisory opinion. (b) The Director will forward a copy of the request by a Federal, state or municipal governmental agency for an advisory opinion to the...

  1. 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.

  2. 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…

  3. 17 CFR 229.1011 - (Item 1011) Additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false (Item 1011) Additional....1011 (Item 1011) Additional information. (a) Agreements, regulatory requirements and legal proceedings... and the relief sought. Instruction to Item 1011(a)(5): A copy of any document relating to a...

  4. 17 CFR 229.1011 - (Item 1011) Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false (Item 1011) Additional....1011 (Item 1011) Additional information. (a) Agreements, regulatory requirements and legal proceedings... and the relief sought. Instruction to Item 1011(a)(5): A copy of any document relating to a...

  5. 17 CFR 229.1011 - (Item 1011) Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 1011) Additional....1011 (Item 1011) Additional information. (a) Agreements, regulatory requirements and legal proceedings... and the relief sought. Instruction to Item 1011(a)(5): A copy of any document relating to a...

  6. 17 CFR 229.1011 - (Item 1011) Additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false (Item 1011) Additional....1011 (Item 1011) Additional information. (a) Agreements, regulatory requirements and legal proceedings... and the relief sought. Instruction to Item 1011(a)(5): A copy of any document relating to a...

  7. 17 CFR 229.1011 - (Item 1011) Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false (Item 1011) Additional....1011 (Item 1011) Additional information. (a) Agreements, regulatory requirements and legal proceedings... and the relief sought. Instruction to Item 1011(a)(5): A copy of any document relating to a...

  8. 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. PMID:25052741

  9. 29 CFR 501.44 - Additional information, if required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Additional information, if required. 501.44 Section 501.44 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218...

  10. 29 CFR 501.44 - Additional information, if required.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Additional information, if required. 501.44 Section 501.44 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS ENFORCEMENT OF CONTRACTUAL OBLIGATIONS FOR TEMPORARY ALIEN AGRICULTURAL WORKERS ADMITTED UNDER SECTION 218...

  11. 25 CFR 103.14 - Can BIA request additional information?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Can BIA request additional information? 103.14 Section 103.14 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES LOAN GUARANTY, INSURANCE, AND INTEREST SUBSIDY How a Lender Obtains a Loan Guaranty or Insurance Coverage § 103.14 Can...

  12. 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,...

  13. 12 CFR 980.7 - Examinations; requests for additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Examinations; requests for additional information. 980.7 Section 980.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD NEW FEDERAL HOME LOAN BANK... cooperative nature of the Bank System; and (v) Finance Board review of any contracts or agreements between...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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 §...

  19. 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...

  20. 21 CFR 207.31 - Additional drug listing information.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 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. 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...

  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. 43 CFR 3922.30 - Application-Additional information.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Application-Additional information. 3922.30 Section 3922.30 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL SHALE LEASING...

  4. 43 CFR 3922.30 - Application-Additional information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Application-Additional information. 3922.30 Section 3922.30 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) OIL SHALE LEASING...

  5. 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...

  6. 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...

  7. 21 CFR 807.31 - Additional listing information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Additional listing information. 807.31 Section 807.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... joint ownership and control exists, the registered establishment must provide the Food and...

  8. Progress in the Experimental Observation of Thiamin Diphosphate-bound Intermediates on Enzymes and Mechanistic Information Derived from these Observations

    PubMed Central

    Jordan, Frank; Nemeria, Natalia S.

    2014-01-01

    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 a 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. PMID:15888311

  9. 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.

  10. 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.

  11. 21 CFR 71.4 - Samples; additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  12. 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...

  13. 10 CFR 1.3 - Sources of additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... Regional Offices. In addition, NRC Functional Organization Charts, NUREG-0325, contains...

  14. 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.

  15. 7 CFR 20.11 - Additional reports and information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....11 Agriculture Office of the Secretary of Agriculture EXPORT SALES REPORTING REQUIREMENTS § 20.11... Administrator information with respect to sales of agricultural commodities as requested. Daily reports shall be... reports and information, including price data, as may be requested with respect to export sales...

  16. 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...

  17. 12 CFR 980.7 - Examinations; requests for additional information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... new business activity, nothing in this part shall limit the right of the Finance Board at any time to... business activity is consistent with the housing finance and community lending mission of the Banks and the... information. 980.7 Section 980.7 Banks and Banking FEDERAL HOUSING FINANCE BOARD NEW FEDERAL HOME LOAN...

  18. 31 CFR 26.5 - Upgrades and additional environmental information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... than a full-fledged environmental impact assessment as defined by that MDB's own procedures, the... information is insufficient to provide an adequate basis for analyzing the environmental impact of the... determine that a project would have a significant impact on the human environment, but that the level...

  19. 31 CFR 26.5 - Upgrades and additional environmental information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... than a full-fledged environmental impact assessment as defined by that MDB's own procedures, the... information is insufficient to provide an adequate basis for analyzing the environmental impact of the... determine that a project would have a significant impact on the human environment, but that the level...

  20. 31 CFR 26.5 - Upgrades and additional environmental information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... than a full-fledged environmental impact assessment as defined by that MDB's own procedures, the... information is insufficient to provide an adequate basis for analyzing the environmental impact of the... determine that a project would have a significant impact on the human environment, but that the level...

  1. 31 CFR 26.5 - Upgrades and additional environmental information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... than a full-fledged environmental impact assessment as defined by that MDB's own procedures, the... information is insufficient to provide an adequate basis for analyzing the environmental impact of the... determine that a project would have a significant impact on the human environment, but that the level...

  2. 10 CFR 1.3 - Sources of additional information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.3 Sources..., assignments of responsibility, and delegations of authority is in the Nuclear Regulatory Commission...

  3. 10 CFR 1.3 - Sources of additional information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.3 Sources..., assignments of responsibility, and delegations of authority is in the Nuclear Regulatory Commission...

  4. 10 CFR 1.3 - Sources of additional information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.3 Sources..., assignments of responsibility, and delegations of authority is in the Nuclear Regulatory Commission...

  5. 10 CFR 1.3 - Sources of additional information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .../cfr/. Final opinions made in the adjudication of cases are published in “Nuclear Regulatory Commission... NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Introduction § 1.3 Sources..., assignments of responsibility, and delegations of authority is in the Nuclear Regulatory Commission...

  6. SNP Markers as Additional Information to Resolve Complex Kinship Cases

    PubMed Central

    Pontes, M. Lurdes; Fondevila, Manuel; Laréu, Maria Victoria; Medeiros, Rui

    2015-01-01

    Summary Background DNA profiling with sets of highly polymorphic autosomal short tandem repeat (STR) markers has been applied in various aspects of human identification in forensic casework for nearly 20 years. However, in some cases of complex kinship investigation, the information provided by the conventionally used STR markers is not enough, often resulting in low likelihood ratio (LR) calculations. In these cases, it becomes necessary to increment the number of loci under analysis to reach adequate LRs. Recently, it has been proposed that single nucleotide polymorphisms (SNPs) could be used as a supportive tool to STR typing, eventually even replacing the methods/markers now employed. Methods In this work, we describe the results obtained in 7 revised complex paternity cases when applying a battery of STRs, as well as 52 human identification SNPs (SNPforID 52plex identification panel) using a SNaPshot methodology followed by capillary electrophoresis. Results Our results show that the analysis of SNPs, as complement to STR typing in forensic casework applications, would at least increase by a factor of 4 total PI values and correspondent Essen-Möller's W value. Conclusions We demonstrated that SNP genotyping could be a key complement to STR information in challenging casework of disputed paternity, such as close relative individualization or complex pedigrees subject to endogamous relations. PMID:26733770

  7. Mechanistic Modeling of Pitavastatin Disposition in Sandwich-Cultured Human Hepatocytes: A Proteomics-Informed Bottom-Up Approach.

    PubMed

    Vildhede, Anna; Mateus, André; Khan, Elin K; Lai, Yurong; Karlgren, Maria; Artursson, Per; Kjellsson, Maria C

    2016-04-01

    Isolated human hepatocytes are commonly used to predict transporter-mediated clearance in vivo. Such predictions, however, do not provide estimations of transporter contributions and consequently do not allow predictions of the outcome resulting from a change in the activity of a certain transporter, for example, by inhibition or a genetic variant with reduced function. Pitavastatin is a drug that is heavily dependent on hepatic transporters for its elimination, and it is excreted mainly as unchanged drug in the bile. For this reason, pitavastatin was used as a model drug to demonstrate the applicability of a bottom-up approach to predict transporter-mediated disposition in sandwich-cultured human hepatocytes (SCHHs), allowing for the estimation of transporter contributions. Transport experiments in transfected human embryonic kidney cells (HEK293 cell lines) and inverted membrane vesicles overexpressing each of the relevant transport proteins were used to generate parameter estimates for the mechanistic model. By adjusting for differences in transporter abundance between the in vitro systems and individual SCHH batches, the model successfully predicted time profiles of medium and intracellular accumulation. Our predictions of pitavastatin bile accumulation could not be confirmed, however, because of a very low biliary excretion of pitavastatin in relation to the hepatic uptake in our SCHHs. This study is, to our knowledge, the first to successfully simulate transporter-mediated processes in a complex system such as SCHHs at the level of individual transport proteins using a bottom-up approach. PMID:26842596

  8. 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:...

  9. 36 CFR 1290.3 - Sources of assassination records and additional records and information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... records and additional records and information. 1290.3 Section 1290.3 Parks, Forests, and Public Property... Sources of assassination records and additional records and information. Assassination records and additional records and information may be located at, or under the control of, without limitation:...

  10. 47 CFR 1.10017 - How can I submit additional information?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false How can I submit additional information? 1... International Bureau Filing System § 1.10017 How can I submit additional information? In response to an official request for information from the International Bureau, you can submit additional...

  11. Simvastatin and Dipentyl Phthalate Lower Ex Vivo Testicular Testosterone Production and Exhibit Additive Effects on Testicular Testosterone and Gene Expression Via Distinct Mechanistic Pathways in the Fetal Rat

    PubMed Central

    Beverly, Brandiese E. J.; Lambright, Christy S.; Furr, Johnathan R.; Sampson, Hunter; Wilson, Vickie S.; McIntyre, Barry S.; Foster, Paul M. D.; Travlos, Gregory; Gray, L. Earl

    2014-01-01

    Sex differentiation of the male reproductive tract in mammals is driven, in part, by fetal androgen production. In utero, some phthalate esters (PEs) alter fetal Leydig cell differentiation, reducing the expression of several genes associated with steroid synthesis/transport, and consequently, lowering fetal androgen and Insl3 hormone levels. Simvastatin (SMV) is a cholesterol-lowering drug that directly inhibits HMG-CoA reductase. SMV may also disrupt steroid biosynthesis, but through a different mode of action (MOA) than the PEs. As cholesterol is a precursor of steroid hormone biosynthesis, we hypothesized that in utero exposure to SMV during the critical period of sex differentiation would lower fetal testicular testosterone (T) production without affecting genes involved in cholesterol and androgen synthesis and transport. Secondly, we hypothesized that a mixture of SMV and a PE, which may have different MOAs, would reduce testosterone levels in an additive manner. Pregnant Sprague Dawley rats were dosed orally with SMV, dipentyl phthalate (DPeP), or SMV plus DPeP from gestational days 14-18, and fetuses were evaluated on GD18. On GD18, SMV lowered fetal T production and serum triglycerides, low density lipoprotein, high density lipoprotein, and total cholesterol levels, and downregulated two genes in the fetal testis that were different from those altered by PEs. When SMV and DPeP were administered as a mixture, fetal T production was significantly reduced in an additive manner, thus demonstrating that a mixture of chemicals can induce additive effects on fetal T production even though they display different MOAs. PMID:25055962

  12. Experimental and computational mechanistic investigation of chlorocarbene additions to bridgehead carbene-anti-Bredt systems: noradamantylcarbene-adamantene and adamantylcarbene-homoadamantene.

    PubMed

    Hare, Stephanie R; Orman, Marina; Dewan, Faizunnahar; Dalchand, Elizabeth; Buzard, Camilla; Ahmed, Sadia; Tolentino, Julia C; Sethi, Ulweena; Terlizzi, Kelly; Houferak, Camille; Stein, Aliza M; Stedronsky, Alexandra; Thamattoor, Dasan M; Tantillo, Dean J; Merrer, Dina C

    2015-05-15

    Cophotolysis of noradamantyldiazirine with the phenanthride precursor of dichlorocarbene or phenylchlorodiazirine in pentane at room temperature produces noradamantylethylenes in 11% yield with slight diastereoselectivity. Cophotolysis of adamantyldiazirine with phenylchlorodiazirine in pentane at room temperature generates adamantylethylenes in 6% yield with no diastereoselectivity. (1)H NMR showed the reaction of noradamantyldiazirine + phenylchlorodiazirine to be independent of solvent, and the rate of noradamantyldiazirine consumption correlated with the rate of ethylene formation. Laser flash photolysis showed that reaction of phenylchlorocarbene + adamantene was independent of adamantene concentration. The reaction of phenylchlorocarbene + homoadamantene produces the ethylene products with k = 9.6 × 10(5) M(-1) s(-1). Calculations at the UB3LYP/6-31+G(d,p) and UM062X/6-31+G(d,p)//UB3LYP/6-31+G(d,p) levels show the formation of exocyclic ethylenes to proceed (a) on the singlet surface via stepwise addition of phenylchlorocarbene (PhCCl) to bridgehead alkenes adamantene and homoadamantene, respectively, producing an intermediate singlet diradical in each case, or (b) via addition of PhCCl to the diazo analogues of noradamantyl- and adamantyldiazirine. Preliminary direct dynamics calculations on adamantene + PhCCl show a high degree of recrossing (68%), indicative of a flat transition state surface. Overall, 9% of the total trajectories formed noradamantylethylene product, each proceeding via the computed singlet diradical. PMID:25902301

  13. HARMONIZATION OF HUMAN AND ECOLOGICAL HEALTH ASSESSMENT: DEVELOPMENT OF BAYESIAN UPDATING TECHNIQUES TO INCORPORATE MECHANISTIC INFORMATION ACROSS SPECIES

    EPA Science Inventory

    Bayesian statistical techniques have proven useful in clinical and environmental epidemiological applications to evaluate and integrate available information, and in regulatory applications such as the National Ambient Air Quality Assessment for Nitrogen Oxides. A recent special...

  14. 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

  15. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... additive petitions. 71.15 Section 71.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS General Provisions § 71.15 Confidentiality of data and information in color additive petitions. (a) The following data and information in a...

  16. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... additive petitions. 71.15 Section 71.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS General Provisions § 71.15 Confidentiality of data and information in color additive petitions. (a) The following data and information in a...

  17. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... additive petitions. 71.15 Section 71.15 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS General Provisions § 71.15 Confidentiality of data and information in color additive petitions. (a) The following data and information in a...

  18. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... provided by the additive manufacturer. 79.21 Section 79.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGISTRATION OF FUELS AND FUEL ADDITIVES Additive Registration Procedures § 79.21 Information and assurances to be provided by the additive manufacturer....

  19. The pathogenicity of splicing defects: mechanistic insights into pre-mRNA processing inform novel therapeutic approaches.

    PubMed

    Daguenet, Elisabeth; Dujardin, Gwendal; Valcárcel, Juan

    2015-12-01

    Removal of introns from pre-mRNA precursors (pre-mRNA splicing) is a necessary step for the expression of most genes in multicellular organisms, and alternative patterns of intron removal diversify and regulate the output of genomic information. Mutation or natural variation in pre-mRNA sequences, as well as in spliceosomal components and regulatory factors, has been implicated in the etiology and progression of numerous pathologies. These range from monogenic to multifactorial genetic diseases, including metabolic syndromes, muscular dystrophies, neurodegenerative and cardiovascular diseases, and cancer. Understanding the molecular mechanisms associated with splicing-related pathologies can provide key insights into the normal function and physiological context of the complex splicing machinery and establish sound basis for novel therapeutic approaches. PMID:26566663

  20. 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 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...

  2. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 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 AND HUMAN SERVICES GENERAL COLOR ADDITIVE PETITIONS General Provisions § 71.15 Confidentiality of data and information in color...

  3. 19 CFR 141.89 - Additional information for certain classes of merchandise.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Additional information for certain classes of merchandise. 141.89 Section 141.89 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) ENTRY OF MERCHANDISE Invoices § 141.89 Additional information for certain classes of...

  4. 26 CFR 1.852-7 - Additional information required in returns of shareholders.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 9 2013-04-01 2013-04-01 false Additional information required in returns of... Investment Trusts § 1.852-7 Additional information required in returns of shareholders. Any person who fails... income tax return a statement showing, to the best of his knowledge and belief— (a) The number of...

  5. 26 CFR 1.852-7 - Additional information required in returns of shareholders.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 9 2011-04-01 2011-04-01 false Additional information required in returns of... Investment Trusts § 1.852-7 Additional information required in returns of shareholders. Any person who fails... income tax return a statement showing, to the best of his knowledge and belief— (a) The number of...

  6. 47 CFR 25.111 - Additional information and ITU cost recovery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Additional information and ITU cost recovery. 25.111 Section 25.111 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER....111 Additional information and ITU cost recovery. (a) The Commission may request from any party at...

  7. 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...

  8. 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. PMID:27265245

  9. 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...

  10. 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...

  11. 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...

  12. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Office of Foreign Assets Control Additional Identifying Information for One (1) Individual Designated... identifying information for one individual whose property and interests in property are blocked pursuant...

  13. 16 CFR 2.20 - Petitions for review of requests for additional information or documentary material.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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..., glossaries, proposed form of relief and any appendices containing only sections of statutes or...

  14. 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..., glossaries, proposed form of relief and any appendices containing only sections of statutes or...

  15. 16 CFR 2.20 - Petitions for review of requests for additional information or documentary material.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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..., glossaries, proposed form of relief and any appendices containing only sections of statutes or...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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..., glossaries, proposed form of relief and any appendices containing only sections of statutes or...

  17. 16 CFR 2.20 - Petitions for review of requests for additional information or documentary material.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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..., glossaries, proposed form of relief and any appendices containing only sections of statutes or...

  18. Multiplicative and Additive Modulation of Neuronal Tuning with Population Activity Affects Encoded Information.

    PubMed

    Arandia-Romero, Iñigo; Tanabe, Seiji; Drugowitsch, Jan; Kohn, Adam; Moreno-Bote, Rubén

    2016-03-16

    Numerous studies have shown that neuronal responses are modulated by stimulus properties and also by the state of the local network. However, little is known about how activity fluctuations of neuronal populations modulate the sensory tuning of cells and affect their encoded information. We found that fluctuations in ongoing and stimulus-evoked population activity in primate visual cortex modulate the tuning of neurons in a multiplicative and additive manner. While distributed on a continuum, neurons with stronger multiplicative effects tended to have less additive modulation and vice versa. The information encoded by multiplicatively modulated neurons increased with greater population activity, while that of additively modulated neurons decreased. These effects offset each other so that population activity had little effect on total information. Our results thus suggest that intrinsic activity fluctuations may act as a "traffic light" that determines which subset of neurons is most informative. PMID:26924437

  19. "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

  20. 45 CFR 146.122 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Additional requirements prohibiting discrimination based on genetic information. 146.122 Section 146.122 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES REQUIREMENTS RELATING TO HEALTH CARE ACCESS REQUIREMENTS FOR THE GROUP HEALTH INSURANCE MARKET Requirements Relating to Access...

  1. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Additional requirements prohibiting discrimination based on genetic information (temporary). 54.9802-3T Section 54.9802-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.9802-3T...

  2. 29 CFR 2590.702-1 - Additional requirements prohibiting discrimination based on genetic information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Additional requirements prohibiting discrimination based on genetic information. 2590.702-1 Section 2590.702-1 Labor Regulations Relating to Labor (Continued) EMPLOYEE BENEFITS SECURITY ADMINISTRATION, DEPARTMENT OF LABOR GROUP HEALTH PLANS RULES AND REGULATIONS FOR GROUP HEALTH PLANS Health...

  3. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Additional requirements prohibiting discrimination based on genetic information (temporary). 54.9802-3T Section 54.9802-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.9802-3T...

  4. 26 CFR 54.9802-3T - Additional requirements prohibiting discrimination based on genetic information (temporary).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Additional requirements prohibiting discrimination based on genetic information (temporary). 54.9802-3T Section 54.9802-3T Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES (CONTINUED) PENSION EXCISE TAXES § 54.9802-3T...

  5. 24 CFR 1710.200 - Instructions for Statement of Record, Additional Information and Documentation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Instructions for Statement of Record, Additional Information and Documentation. 1710.200 Section 1710.200 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR...

  6. 16 CFR 803.20 - Requests for additional information or documentary material.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... documentary material. 803.20 Section 803.20 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS... RULES § 803.20 Requests for additional information or documentary material. (a)(1) Persons and... documentary material relevant to the acquisition may be required from one or more persons required to...

  7. 78 FR 52803 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Additional...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... on April 9, 2013 (78 FR 21159). OMB authorization for an ICR cannot be for more than three (3) years...; Additional Information Collection Requirements for Special Dipping and Coating Operations ACTION: Notice... Requirements for Special Dipping and Coating Operations,'' to the Office of Management and Budget (OMB)...

  8. 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 §...

  9. 30 CFR 250.418 - What additional information must I submit with my APD?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., 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 I... applicable, and not previously submitted; (e) A welding plan (see §§ 250.109 to 250.113) if not...

  10. 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 requirements for applications involving vertical competitive impacts. 33.4 Section 33.4 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS...

  11. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Additional information for Applicants not having a credit rating. 260.25 Section 260.25 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS GOVERNING LOANS AND LOAN GUARANTEES UNDER THE...

  12. 75 FR 61572 - Additional Identifying Information Associated With Persons Whose Property and Interests in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ...The Treasury Department's Office of Foreign Assets Control (``OFAC'') is publishing additional identifying information associated with the eight individuals listed in the Annex to the Executive Order of September 28, 2010, ``Blocking Property of Certain Persons With Respect to Serious Human Rights Abuses by the Government of Iran and Taking Certain Other Actions,'' whose property and interests......

  13. 18 CFR 33.3 - Additional information requirements for applications involving horizontal 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 horizontal competitive impacts. 33.3 Section 33.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS...

  14. 40 CFR Table 42 to Subpart Uuu of... - Additional Information for Initial Notification of Compliance Status

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 12 2011-07-01 2009-07-01 true Additional Information for Initial Notification of Compliance Status 42 Table 42 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES...

  15. 40 CFR Table 42 to Subpart Uuu of... - Additional Information for Initial Notification of Compliance Status

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 13 2014-07-01 2014-07-01 false Additional Information for Initial Notification of Compliance Status 42 Table 42 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 13 2013-07-01 2012-07-01 true Additional Information for Initial Notification of Compliance Status 42 Table 42 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES...

  17. 40 CFR Table 42 to Subpart Uuu of... - Additional Information for Initial Notification of Compliance Status

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 13 2012-07-01 2012-07-01 false Additional Information for Initial Notification of Compliance Status 42 Table 42 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS FOR SOURCE CATEGORIES...

  18. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... credit rating. 260.25 Section 260.25 Transportation Other Regulations Relating to Transportation... 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...

  19. 49 CFR 260.25 - Additional information for Applicants not having a credit rating.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... credit rating. 260.25 Section 260.25 Transportation Other Regulations Relating to Transportation... 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...

  20. 16 CFR 803.20 - Requests for additional information or documentary material.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... documentary material. 803.20 Section 803.20 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS... RULES § 803.20 Requests for additional information or documentary material. (a)(1) Persons and... documentary material relevant to the acquisition may be required from one or more persons required to...

  1. 16 CFR 803.20 - Requests for additional information or documentary material.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... documentary material. 803.20 Section 803.20 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS... RULES § 803.20 Requests for additional information or documentary material. (a)(1) Persons and... documentary material relevant to the acquisition may be required from one or more persons required to...

  2. 16 CFR 803.20 - Requests for additional information or documentary material.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... documentary material. 803.20 Section 803.20 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS... RULES § 803.20 Requests for additional information or documentary material. (a)(1) Persons and... documentary material relevant to the acquisition may be required from one or more persons required to...

  3. 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...

  4. 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...

  5. 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...

  6. 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,...

  7. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... under 42 U.S.C. 7545(f)(4). (i) The manufacturer shall submit, or shall reference prior submissions... data and information as are specified in the designation of the additive in subpart D. (f) Assurances... the provisions of subpart F of this part....

  8. 40 CFR 79.21 - Information and assurances to be provided by the additive manufacturer.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... under 42 U.S.C. 7545(f)(4). (i) The manufacturer shall submit, or shall reference prior submissions... data and information as are specified in the designation of the additive in subpart D. (f) Assurances... the provisions of subpart F of this part....

  9. 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...

  10. 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;...

  11. 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

  12. Additional sensory information reduces body sway of individuals with anterior cruciate ligament injury.

    PubMed

    Bonfim, Thatia Regina; Grossi, Débora Bevilaqua; Paccola, Cleber Antonio Jansen; Barela, José Angelo

    2008-08-29

    The purpose of this study was to investigate whether the additional sensory information could improve postural control in individuals with unilateral anterior cruciate ligament (ACL) injury. Twenty-eight individuals with unilateral ACL injury (mean age 23.6, 26 males, 2 females) and 28 healthy young control subjects (mean age 22.1 years, 26 males, 2 females) participated in this study. Postural control was evaluated with subjects single-leg standing on a force platform with eyes closed under two sensory conditions: normal sensory information and light touch to a stationary bar (applied force below 1N). Three trials of 30s were performed in each single-leg stance and in each sensory condition. Mean sway amplitude and predominant frequency of center of pressure were calculated for both anterior-posterior and medial-lateral directions. Individuals with ACL injury showed greater mean sway amplitude than healthy control individuals even though the predominant frequency was similar for both groups. Additional sensory information improved postural control performance in individuals with ACL injury and healthy control, with a greater effect observed for the ACL group. Based on these results, we suggest that reduction in postural control performance in individuals with ACL injury would be due to the reduction of sensory information provided by the ACL, but when sensory information is enhanced, postural control performance improves. These results have implications for novel approaches to improve stability in individuals with ACL injury. PMID:18582536

  13. 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...

  14. 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

  15. Mechanistic models in computational social science

    NASA Astrophysics Data System (ADS)

    Holme, Petter; Liljeros, Fredrik

    2015-09-01

    Quantitative social science is not only about regression analysis or, in general, data inference. Computer simulations of social mechanisms have an over 60 years long history. They have been used for many different purposes—to test scenarios, to test the consistency of descriptive theories (proof-of-concept models), to explore emergent phenomena, for forecasting, etc. In this essay, we sketch these historical developments, the role of mechanistic models in the social sciences and the influences from the natural and formal sciences. We argue that mechanistic computational models form a natural common ground for social and natural sciences, and look forward to possible future information flow across the social-natural divide.

  16. 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.

  17. 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

    ... scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  18. 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

    ... in scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  19. 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

    ... in scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  20. Multiple small RNAs act additively to integrate sensory information and control quorum sensing in Vibrio harveyi

    PubMed Central

    Tu, Kimberly C.; Bassler, Bonnie L.

    2007-01-01

    Quorum sensing is a cell–cell communication mechanism that bacteria use to collectively regulate gene expression and, at a higher level, to coordinate group behavior. In the bioluminescent marine bacterium Vibrio harveyi, sensory information from three independent quorum-sensing systems converges on the shared response regulator LuxO. When LuxO is phosphorylated, it activates the expression of a putative repressor that destabilizes the mRNA encoding the master quorum-sensing transcriptional regulator LuxR. In the closely related species Vibrio cholerae, this repressor was revealed to be the RNA chaperone Hfq together with four small regulatory RNAs (sRNAs) called Qrr1–4 (quorum regulatory RNA). Here, we identify five Qrr sRNAs that control quorum sensing in V. harveyi. Mutational analysis reveals that only four of the five Qrrs are required for destabilization of the luxR mRNA. Surprisingly, unlike in V. cholerae where the sRNAs act redundantly, in V. harveyi, the Qrr sRNAs function additively to control quorum sensing. This latter mechanism produces a gradient of LuxR that, in turn, enables differential regulation of quorum-sensing target genes. Other regulators appear to be involved in control of V. harveyi qrr expression, allowing the integration of additional sensory information into the regulation of quorum-sensing gene expression. PMID:17234887

  1. 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.

  2. Climate change inferred from borehole temperatures: How to improve the solution by using additional information

    NASA Astrophysics Data System (ADS)

    Bodri, L.; Čermák, V.

    Past climate changes have caused certain perturbations in the subsurface temperature field. Their inversion yields the time variations of the ground surface temperature (GST), the solution of which however may be highly non-unique. To incorporate additional information on the behaviour of the unknown function usually helps treat the non-uniqueness. The traditionally used information imposing bounding and smoothing constraints on climate history can be further significantly extended by including stochastic properties of climate. It was shown that climatic records reveal: (1) long-term persistence of climate, and (2) high intermittency of climate variations characterized by hyperbolic decrease of probability tails. We have quantified and incorporated such information into the inversion method in the form of the covariance matrix of the unknown parameters. Inversion of almost 100 temperature-depth profiles from the Czech Republic (Bodri and Čermák, 1995, 1997) provided more meaningful climatic histories in comparison with simple inversion and increased the time span that could be resolved. In present work the effectiveness of the method is illistrated on the examples of 5 selected temperature logs.

  3. 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

  4. 17 CFR 230.496 - Contents of prospectus and statement of additional information used after nine months.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Contents of prospectus and statement of additional information used after nine months. 230.496 Section 230.496 Commodity and Securities... statement of additional information used after nine months. In the case of a registration statement filed...

  5. 17 CFR 230.496 - Contents of prospectus and statement of additional information used after nine months.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Contents of prospectus and statement of additional information used after nine months. 230.496 Section 230.496 Commodity and Securities... statement of additional information used after nine months. In the case of a registration statement filed...

  6. 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... Space Integrated Workplace § 102-79.111 Where may Executive agencies find additional information...

  7. 77 FR 67655 - Agency Information Collection Activities; Proposed Collection; Comment Request; Food Additive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ...) Moderate Category: For a food additive petition without complex chemistry, manufacturing, efficacy, or...) Complex Category: For a food additive petition with complex chemistry, manufacturing, efficacy, and/or... investigational food additive file without complex chemistry, manufacturing, efficacy, or safety issues,...

  8. 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

  9. 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

  10. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... information or documentary material requested pursuant to section 7A(e) and § 803.20 (or, if such request is not fully complied with, the information or documentary material submitted and a statement of...

  11. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... information or documentary material requested pursuant to section 7A(e) and § 803.20 (or, if such request is not fully complied with, the information or documentary material submitted and a statement of...

  12. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... information or documentary material requested pursuant to section 7A(e) and § 803.20 (or, if such request is not fully complied with, the information or documentary material submitted and a statement of...

  13. 16 CFR 803.21 - Additional information shall be supplied within reasonable time.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... information or documentary material requested pursuant to section 7A(e) and § 803.20 (or, if such request is not fully complied with, the information or documentary material submitted and a statement of...

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

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... information or documentary material requested pursuant to section 7A(e) and § 803.20 (or, if such request is not fully complied with, the information or documentary material submitted and a statement of...

  15. 50 CFR 23.25 - What additional information is required on a non-Party CITES document?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....25 What additional information is required on a non-Party CITES document? (a) Purpose. Under Article... Certification (1) Export (i) For Appendix-I and -II specimens, the Scientific Authority has advised that...

  16. 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...

  17. 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

  18. 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

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  3. 21 CFR 803.12 - Where and how do I submit reports and additional information?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES MEDICAL DEVICE REPORTING General Provisions § 803.12 Where and how do... information required under this part to FDA, CDRH, Medical Device Reporting, P.O. Box 3002, Rockville,...

  4. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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...

  5. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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...

  6. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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...

  7. 10 CFR 52.158 - Contents of application; additional technical information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  8. 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

  9. 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

  10. 17 CFR 229.1118 - (Item 1118) Reports and additional information.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Commission maintains an Internet site that contains reports, proxy and information statements, and other... electronic or paper copies of those filings and other reports free of charge upon request. ... (http://www.sec.gov). (c) Web site access to reports. (1) State whether the issuing entity's...

  11. 17 CFR 229.1118 - (Item 1118) Reports and additional information.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Commission maintains an Internet site that contains reports, proxy and information statements, and other... electronic or paper copies of those filings and other reports free of charge upon request. ... (http://www.sec.gov). (c) Web site access to reports. (1) State whether the issuing entity's...

  12. 17 CFR 229.1118 - (Item 1118) Reports and additional information.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Commission maintains an Internet site that contains reports, proxy and information statements, and other... electronic or paper copies of those filings and other reports free of charge upon request. ... (http://www.sec.gov). (c) Web site access to reports. (1) State whether the issuing entity's...

  13. 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,…

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... under 10 CFR 50.10 be issued before issuance of the combined license, the application must include the information otherwise required by 10 CFR 50.10, in accordance with either 10 CFR 2.101(a)(1) through (a)(4... environmental report, either in accordance with 10 CFR 51.50(c) if a limited work authorization under 10 CFR...

  15. 77 FR 31068 - Additional Identifying Information Associated With Persons Whose Property and Interests in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... and Suspending Entry Into the United States of Certain Persons With Respect to Grave Human Rights... Property and Suspending Entry Into the United States of Certain Persons With Respect to Grave Human Rights... Rights Abuses by Governments of Iran and Syria via Information Technology AGENCY: Office of...

  16. 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

    ..., certification and auditing services for fresh and processed fruits, vegetables, and other products on a ``user... provides a nationwide inspection, grading, and auditing service for fresh and processed fruits, vegetables... inspection, grading, or auditing services. Such information includes; the name and location of the person...

  17. 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…

  18. 21 CFR 71.15 - Confidentiality of data and information in color additive petitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... additive petition are available for public disclosure, unless extraordinary circumstances are shown, after... § 20.61 of this chapter. (3) Adverse reaction reports, product experience reports, consumer complaints... particular ingredient or group of ingredients shall be deleted from any such list prior to public...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... the horizontal Competitive Analysis Screen. (3) The applicant may use a computer model to complete one... requirements for applications involving horizontal competitive impacts. 33.3 Section 33.3 Conservation of Power... FEDERAL POWER ACT APPLICATIONS UNDER FEDERAL POWER ACT SECTION 203 § 33.3 Additional...

  20. 30 CFR 75.1200-1 - Additional information on mine map.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Maps § 75.1200-1 Additional... symbols; (g) The location of railroad tracks and public highways leading to the mine, and mine buildings... permanent base line points coordinated with the underground and surface mine traverses, and the location...

  1. 30 CFR 75.1200-1 - Additional information on mine map.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Maps § 75.1200-1 Additional... symbols; (g) The location of railroad tracks and public highways leading to the mine, and mine buildings... permanent base line points coordinated with the underground and surface mine traverses, and the location...

  2. 30 CFR 75.1200-1 - Additional information on mine map.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Maps § 75.1200-1 Additional... symbols; (g) The location of railroad tracks and public highways leading to the mine, and mine buildings... permanent base line points coordinated with the underground and surface mine traverses, and the location...

  3. 30 CFR 75.1200-1 - Additional information on mine map.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SAFETY AND HEALTH MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Maps § 75.1200-1 Additional... symbols; (g) The location of railroad tracks and public highways leading to the mine, and mine buildings... permanent base line points coordinated with the underground and surface mine traverses, and the location...

  4. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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 50... under 10 CFR 50.10 be issued before issuance of the combined license, the application must include...

  5. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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 50... under 10 CFR 50.10 be issued before issuance of the combined license, the application must include...

  6. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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 50... under 10 CFR 50.10 be issued before issuance of the combined license, the application must include...

  7. 10 CFR 52.80 - Contents of applications; additional technical information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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 50... under 10 CFR 50.10 be issued before issuance of the combined license, the application must include...

  8. 14 CFR 11.77 - Is there any additional information I must include in my petition for designating airspace?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Is there any additional information I must include in my petition for designating airspace? 11.77 Section 11.77 Aeronautics and Space FEDERAL... of the agency, office, facility, or person who would have authority to permit the use of the...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. Estimating additive and dominance variances for complex traits in pigs combining genomic and pedigree information.

    PubMed

    Costa, E V; Diniz, D B; Veroneze, R; Resende, M D V; Azevedo, C F; Guimaraes, S E F; Silva, F F; Lopes, P S

    2015-01-01

    Knowledge of dominance effects should improve ge-netic evaluations, provide the accurate selection of purebred animals, and enable better breeding strategies, including the exploitation of het-erosis in crossbreeds. In this study, we combined genomic and pedi-gree data to study the relative importance of additive and dominance genetic variation in growth and carcass traits in an F2 pig population. Two GBLUP models were used, a model without a polygenic effect (ADM) and a model with a polygenic effect (ADMP). Additive effects played a greater role in the control of growth and carcass traits than did dominance effects. However, dominance effects were important for all traits, particularly in backfat thickness. The narrow-sense and broad-sense heritability estimates for growth (0.06 to 0.42, and 0.10 to 0.51, respectively) and carcass traits (0.07 to 0.37, and 0.10 to 0.76, respec-tively) exhibited a wide variation. The inclusion of a polygenic effect in the ADMP model changed the broad-sense heritability estimates only for birth weight and weight at 21 days of age. PMID:26125833

  14. 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.

  15. 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. PMID:27273741

  16. Getting the most out of additional guidance information in deformable image registration by leveraging multi-objective optimization

    NASA Astrophysics Data System (ADS)

    Alderliesten, Tanja; Bosman, Peter A. N.; Bel, Arjan

    2015-03-01

    Incorporating additional guidance information, e.g., landmark/contour correspondence, in deformable image registration is often desirable and is typically done by adding constraints or cost terms to the optimization function. Commonly, deciding between a "hard" constraint and a "soft" additional cost term as well as the weighting of cost terms in the optimization function is done on a trial-and-error basis. The aim of this study is to investigate the advantages of exploiting guidance information by taking a multi-objective optimization perspective. Hereto, next to objectives related to match quality and amount of deformation, we define a third objective related to guidance information. Multi-objective optimization eliminates the need to a-priori tune a weighting of objectives in a single optimization function or the strict requirement of fulfilling hard guidance constraints. Instead, Pareto-efficient trade-offs between all objectives are found, effectively making the introduction of guidance information straightforward, independent of its type or scale. Further, since complete Pareto fronts also contain less interesting parts (i.e., solutions with near-zero deformation effort), we study how adaptive steering mechanisms can be incorporated to automatically focus more on solutions of interest. We performed experiments on artificial and real clinical data with large differences, including disappearing structures. Results show the substantial benefit of using additional guidance information. Moreover, compared to the 2-objective case, additional computational cost is negligible. Finally, with the same computational budget, use of the adaptive steering mechanism provides superior solutions in the area of interest.

  17. 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

  18. THYROID FOLLICULAR CELL CARCINOGENESIS: MECHANISTIC AND SCIENCE POLICY CONSIDERATIONS

    EPA Science Inventory

    EPA's Guidelines for Carcinogen Risk Assessment call for use of mechanistic and other relevant information in making choices about the models to be used in extrapolating hazard estimates from high to low exposures. The Forum report on thyroid neoplasia proposes that, under clearl...

  19. Explanation and inference: mechanistic and functional explanations guide property generalization

    PubMed Central

    Lombrozo, Tania; Gwynne, Nicholas Z.

    2014-01-01

    The ability to generalize from the known to the unknown is central to learning and inference. Two experiments explore the relationship between how a property is explained and how that property is generalized to novel species and artifacts. The experiments contrast the consequences of explaining a property mechanistically, by appeal to parts and processes, with the consequences of explaining the property functionally, by appeal to functions and goals. The findings suggest that properties that are explained functionally are more likely to be generalized on the basis of shared functions, with a weaker relationship between mechanistic explanations and generalization on the basis of shared parts and processes. The influence of explanation type on generalization holds even though all participants are provided with the same mechanistic and functional information, and whether an explanation type is freely generated (Experiment 1), experimentally provided (Experiment 2), or experimentally induced (Experiment 2). The experiments also demonstrate that explanations and generalizations of a particular type (mechanistic or functional) can be experimentally induced by providing sample explanations of that type, with a comparable effect when the sample explanations come from the same domain or from a different domains. These results suggest that explanations serve as a guide to generalization, and contribute to a growing body of work supporting the value of distinguishing mechanistic and functional explanations. PMID:25309384

  20. Mechanistic investigations of shuttle glow

    NASA Technical Reports Server (NTRS)

    Caledonia, G. E.; Holtzclaw, K. W.; Krech, R. H.; Sonnenfroh, D. M.; Leone, A.; Blumberg, W. A. M.

    1993-01-01

    A series of laboratory measurements have been performed in order to provide a mechanistic interpretation for the visible shuttle glow. These studies involved interactions of an 8 km/s oxygen atom beam with both contaminant dosed surfaces and gaseous targets. We conclude that visible shuttle glow arises from surface mediated O + NO recombination via a Langmuir-Hinshelwood mechanism and that the gas-phase exchange reaction O + N2 - NO + N provides a viable source of precursor NO above surfaces oriented in the ram direction.

  1. Mechanistic investigations of shuttle glow

    SciTech Connect

    Caledonia, G.E.; Holtzclaw, K.W.; Krech, R.H.; Sonnenfroh, D.M. ); Leone, A. ); Blumber, W.A.M. )

    1993-03-01

    A series of laboratory measurements have been performed in order to provide a mechanistic interpretation for the visible shuttle glow. These studies involved interactions in an 8 km/s oxygen atom beam with both contaminant dosed surfaces and gaseous targets. The authors conclude that visible shuttle glow arises from surface mediated O + NO recombination via a Langmuir-Hinshelwood mechanism and that the gas-phase exchange reaction O + N[sub 2] [r arrow] NO + N provides a viable source of precursor NO above surfaces oriented in the ram direction. 35 refs., 4 figs.

  2. 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

  3. Review of information on the radiation chemistry of materials around waste canisters in salt and assessment of the need for additional experimental information

    SciTech Connect

    Jenks, G.H.; Baes, C.F. Jr.

    1980-03-01

    The brines, vapors, and salts precipitated from the brines will be exposed to gamma rays and to elevated temperatures in the regions close to a waste package in the salt. Accordingly, they will be subject to changes in composition brought about by reactions induced by the radiations and heat. This report reviews the status of information on the radiation chemistry of brines, gases, and solids which might be present around a waste package in salt and to assess the need for additional laboratory investigations on the radiation chemistry of these materials. The basic aspects of the radiation chemistry of water and aqueous solutions, including concentrated salt solutions, were reviewed briefly and found to be substantially unchanged from those presented in Jenks's 1972 review of radiolysis and hydrolysis in salt-mine brines. Some additional information pertaining to the radiolytic yields and reactions in brine solutions has become available since the previous review, and this information will be useful in the eventual, complete elucidation of the radiation chemistry of the salt-mine brines. 53 references.

  4. 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

  5. Natural selection and mechanistic regularity.

    PubMed

    DesAutels, Lane

    2016-06-01

    In this article, I address the question of whether natural selection operates regularly enough to qualify as a mechanism of the sort characterized by Machamer, Darden, and Craver (2000). Contrary to an influential critique by Skipper and Millstein (2005), I argue that natural selection can be seen to be regular enough to qualify as an MDC mechanism just fine-as long as we pay careful attention to some important distinctions regarding mechanistic regularity and abstraction. Specifically, I suggest that when we distinguish between process vs. product regularity, mechanism-internal vs. mechanism-external sources of irregularity, and abstract vs. concrete regularity, we can see that natural selection is only irregular in senses that are unthreatening to its status as an MDC mechanism. PMID:26921876

  6. 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…

  7. 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

  8. Bridging Mechanistic and Phenomenological Models of Complex Biological Systems.

    PubMed

    Transtrum, Mark K; Qiu, Peng

    2016-05-01

    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

  9. 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

  10. Data graphs and mechanistic explanation.

    PubMed

    Burnston, Daniel C

    2016-06-01

    It is a widespread assumption in philosophy of science that representations of data are not explanatory-that they are mere stepping stones towards an explanation, such as a representation of a mechanism. I draw on instances of representational and explanatory practice from mammalian chronobiology to suggest that this assumption is unsustainable. In many instances, biologists employ representations of data in explanatory ways that are not reducible to constraints on or evidence for representations of mechanisms. Data graphs are used to represent relationships between quantities across conditions, and often these representations are necessary for explaining particular aspects of the phenomena under study. The benefit of the analysis is two-fold. First, it provides a more accurate account of explanatory practice in broadly mechanistic investigation in biology. Second, it suggests that there is not an explanatorily "fundamental" type of representation in biology. Rather, the practice of explanation consists in the construction of different types of representations and their employment for distinct explanatory purposes. PMID:26871740

  11. On the additional information content of hyperspectral remote sensing data for estimating ecosystem carbon dioxde and energy exchange

    NASA Astrophysics Data System (ADS)

    Wohlfahrt, Georg; Hammerle, Albin; Tomelleri, Enrico

    2015-04-01

    Radiation reflected back from an ecosystem carries a spectral signature resulting from the interaction of radiation with the vegetation canopy and the underlying soil and thus allows drawing conclusions about the structure and functioning of an ecosystem. When this information is linked to a model of the leaf CO2 exchange, the ecosystem-scale CO2 exchange can be simulated. A well-known and very simplistic example for this approach is the light-use efficiency (LUE) model proposed by Monteith which links the flux of absorbed photosynthetically active radiation times a LUE parameter, both of which may be estimated based on remote sensing data, to predict the ecosystem gross photosynthesis. Here we explore the ability of a more elaborate approach by using near-surface remote sensing of hyperspectral reflected radiation, eddy covariance CO2 and energy flux measurements and a coupled radiative transfer and soil-vegetation-atmosphere-transfer (SVAT) model. Our main objective is to understand to what degree the joint assimilation of hyperspectral reflected radiation and eddy covariance flux measurements into the model helps to better constrain model parameters. To this end we use the SCOPE model, a combination of the well-known PROSAIL model and a SVAT model, and the Bayesian inversion algorithm DREAM. In order to explicitly link reflectance in the visible light and the leaf CO2 exchange, a novel parameterisation of the maximum carboxylation capacity parameter (Vcmax) on the leaf a+b chlorophyll content parameter of PROSAIL is introduced. Results are discussed with respect to the additional information content the hyperspectral data yield for simulating canopy photosynthesis.

  12. 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

  13. 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

  14. Mechanistic chemical perspective of hydrogen sulfide signaling.

    PubMed

    Nagy, Péter

    2015-01-01

    Hydrogen sulfide is now a well-appreciated master regulator in a diverse array of physiological processes. However, as a consequence of the rapid growth of the area, sulfide biology suffers from an increasing number of controversial observations and interpretations. A better understanding of the underlying molecular pathways of sulfide's actions is key to reconcile controversial issues, which calls for rigorous chemical/biochemical investigations. Protein sulfhydration and coordination/redox chemical interactions of sulfide with heme proteins are the two most extensively studied pathways in sulfide biochemistry. These pathways are important mediators of protein functions, generate bioactive sulfide metabolites, contribute to sulfide storage/trafficking and carry antioxidant functions. In addition, inorganic polysulfides, which are oxidative sulfide metabolites, are increasingly recognized as important players in sulfide biology. This chapter provides an overview of our mechanistic perspective on the reactions that govern (i) sulfide's bioavailability (including the delicate enzyme machineries that orchestrate sulfide production and consumption and the roles of the large sulfide-storing pools as biological buffers), (ii) biological significance and mechanisms of persulfide formation (including the reduction of disulfides, condensation with sulfenic acids, oxidation of thiols with polysulfides and radical-mediated pathways), (iii) coordination and redox chemical interactions of sulfide with heme proteins (including cytochrome c oxidase, hemoglobins, myoglobins and peroxidases), and (iv) the chemistry of polysulfides. PMID:25725513

  15. Somatodendritic dopamine release: recent mechanistic insights.

    PubMed

    Rice, Margaret E; Patel, Jyoti C

    2015-07-01

    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 Ca(2+) dependence of release and the potential role of exocytotic proteins. PMID:26009764

  16. MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA)

    EPA Science Inventory

    The US Environmental Protection Agency (EPA) is interested in the interplay of environmental and genetic factors on the development and exacerbation of asthma. The Mechanistic Indicators of Childhood Asthma (MICA) study will use exposure measurements and markers of environmental ...

  17. 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

  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, 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)...

  19. 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)...

  20. 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

    ... 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)...

  1. 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)...

  2. A framework for recognizing mechanistic reasoning in student scientific inquiry

    NASA Astrophysics Data System (ADS)

    Russ, Rosemary S.

    A central ambition of science education reform is to help students develop abilities for scientific inquiry. Education research is thus rightly focused on defining what constitutes "inquiry" and developing tools for assessing it. There has been progress with respect to particular aspects of inquiry, namely student abilities for controlled experimentation and scientific argumentation. However, we suggest that in addition to these frameworks for assessing the structure of inquiry we need frameworks for analyzing the substance of that inquiry. In this work we draw attention to and evaluate the substance of student mechanistic reasoning. Both within the history and philosophy of science and within science education research, scientific inquiry is characterized in part as understanding the causal mechanisms that underlie natural phenomena. The challenge for science education, however, is that there has not been the same progress with respect to making explicit what constitutes mechanistic reasoning as there has been in making explicit other aspects of inquiry. This dissertation attempts to address this challenge. We adapt an account of mechanism in professional research science to develop a framework for reliably recognizing mechanistic reasoning in student discourse. The coding scheme articulates seven specific aspects of mechanistic reasoning and can be used to systematically analyze narrative data for patterns in student thinking. It provides a tool for detecting quality reasoning that may be overlooked by more traditional assessments. We apply the mechanism coding scheme to video and written data from a range of student inquiries, from large group discussions among first grade students to the individual problem solving of graduate students. While the primary result of this work is the coding scheme itself and the finding that it provides a reliable means of analyzing transcript data for evidence of mechanistic thinking, the rich descriptions we develop in each case

  3. 41 CFR 102-75.140 - In addition to the title report, and all necessary environmental information and certifications...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 40 CFR part 761, if requested by the disposal agency. If the property does contain any equipment subject to EPA regulation under 40 CFR part 761, the certification must include the landholding agency's... report, and all necessary environmental information and certifications, what information must...

  4. 41 CFR 102-75.140 - In addition to the title report, and all necessary environmental information and certifications...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 40 CFR part 761, if requested by the disposal agency. If the property does contain any equipment subject to EPA regulation under 40 CFR part 761, the certification must include the landholding agency's... report, and all necessary environmental information and certifications, what information must...

  5. 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

  6. 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

  7. Processing time of addition or withdrawal of single or combined balance-stabilizing haptic and visual information.

    PubMed

    Honeine, Jean-Louis; Crisafulli, Oscar; Sozzi, Stefania; Schieppati, Marco

    2015-12-01

    We investigated the integration time of haptic and visual input and their interaction during stance stabilization. Eleven subjects performed four tandem-stance conditions (60 trials each). Vision, touch, and both vision and touch were added and withdrawn. Furthermore, vision was replaced with touch and vice versa. Body sway, tibialis anterior, and peroneus longus activity were measured. Following addition or withdrawal of vision or touch, an integration time period elapsed before the earliest changes in sway were observed. Thereafter, sway varied exponentially to a new steady-state while reweighting occurred. Latencies of sway changes on sensory addition ranged from 0.6 to 1.5 s across subjects, consistently longer for touch than vision, and were regularly preceded by changes in muscle activity. Addition of vision and touch simultaneously shortened the latencies with respect to vision or touch separately, suggesting cooperation between sensory modalities. Latencies following withdrawal of vision or touch or both simultaneously were shorter than following addition. When vision was replaced with touch or vice versa, adding one modality did not interfere with the effect of withdrawal of the other, suggesting that integration of withdrawal and addition were performed in parallel. The time course of the reweighting process to reach the new steady-state was also shorter on withdrawal than addition. The effects of different sensory inputs on posture stabilization illustrate the operation of a time-consuming, possibly supraspinal process that integrates and fuses modalities for accurate balance control. This study also shows the facilitatory interaction of visual and haptic inputs in integration and reweighting of stance-stabilizing inputs. PMID:26334013

  8. 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...

  9. 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...

  10. 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...

  11. 45 CFR 1351.19 - What additional information should an applicant or grantee have about a Runaway and Homeless...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 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...

  12. 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...

  13. 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...

  14. 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

  15. Mechanistic systems modeling to guide drug discovery and development

    PubMed Central

    Schmidt, Brian J.; Papin, Jason A.; Musante, Cynthia J.

    2013-01-01

    A crucial question that must be addressed in the drug development process is whether the proposed therapeutic target will yield the desired effect in the clinical population. Pharmaceutical and biotechnology companies place a large investment on research and development, long before confirmatory data are available from human trials. Basic science has greatly expanded the computable knowledge of disease processes, both through the generation of large omics data sets and a compendium of studies assessing cellular and systemic responses to physiologic and pathophysiologic stimuli. Given inherent uncertainties in drug development, mechanistic systems models can better inform target selection and the decision process for advancing compounds through preclinical and clinical research. PMID:22999913

  16. (Mechanistic examination of organometallic electron transfer reactions: Annual report, 1989)

    SciTech Connect

    Not Available

    1989-01-01

    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.

  17. [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.

  18. 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. PMID:26609084

  19. 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.

  20. 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...

  1. 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

  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, 2014 CFR

    2014-10-01

    ... flow into the turbine in klbs; for dual flash facilities, you must separate the steam flow into high... 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...

  3. 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

    ... flow into the turbine in klbs; for dual flash facilities, you must separate the steam flow into high... 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...

  4. 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

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false What additional information must I give BLM in the monthly report for flash and dry steam facilities? 3276.13 Section 3276.13 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000)...

  5. 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

    ... flow into the turbine in klbs; for dual flash facilities, you must separate the steam flow into high... 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...

  6. 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.

  7. Highly informative Y-chromosomal haplotypes by the addition of three new STRs DYS437, DYS438 and DYS439.

    PubMed

    Grignani, P; Peloso, G; Fattorini, P; Previderè, C

    2000-01-01

    The Y chromosome STRs DYS437, DYS438 and DYS439 were selected from publicly available genome databases and used to analyse an Italian population sample. A tetraplex PCR reaction including the highly informative DYS385 locus, was set up and used for the analysis of 131 male samples to determine allele frequencies and STR diversity values. The number of different haplotypes and the haplotype diversity value found from the analysis of the STRs included in the tetraplex reaction were very similar to those found from the analysis of the basic set of 7 Y-STRs (DYS19, DYS389I/II, DYS390, DYS391, DYS392 and DYS393) previously carried out on the same population sample. By combining the allelic states of the 11 Y-chromosomal STRs we could construct highly informative haplotypes that allowed the discrimination of 93.8% (120 out of 128) of the samples tested. This approach represents a very powerful tool for individual identification and paternity testing in forensic medicine. PMID:11197619

  8. 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

  9. 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

  10. Randomised Controlled Feasibility Trial of an Evidence-Informed Behavioural Intervention for Obese Adults with Additional Risk Factors

    PubMed Central

    Sniehotta, Falko F.; Dombrowski, Stephan U.; Avenell, Alison; Johnston, Marie; McDonald, Suzanne; Murchie, Peter; Ramsay, Craig R.; Robertson, Kim; Araujo-Soares, Vera

    2011-01-01

    Background Interventions for dietary and physical activity changes in obese adults may be less effective for participants with additional obesity-related risk factors and co-morbidities than for otherwise healthy individuals. This study aimed to test the feasibility and acceptability of the recruitment, allocation, measurement, retention and intervention procedures of a randomised controlled trial of an intervention to improve physical activity and dietary practices amongst obese adults with additional obesity related risk factors. Method Pilot single centre open-labelled outcome assessor-blinded randomised controlled trial of obese (Body Mass Index (BMI)≥30 kg/m2) adults (age≥18 y) with obesity related co-morbidities such as type 2 diabetes, impaired glucose tolerance or hypertension. Participants were randomly allocated to a manual-based group intervention or a leaflet control condition in accordance to a 2∶1 allocation ratio. Primary outcome was acceptability and feasibility of trial procedures, secondary outcomes included measures of body composition, physical activity, food intake and psychological process measures. Results Out of 806 potentially eligible individuals identified through list searches in two primary care general medical practices N = 81 participants (63% female; mean-age = 56.56(11.44); mean-BMI = 36.73(6.06)) with 2.35(1.47) co-morbidities were randomised. Scottish Index of Multiple Deprivation (SIMD) was the only significant predictor of providing consent to take part in the study (higher chances of consent for invitees with lower levels of deprivation). Participant flowcharts, qualitative and quantitative feedback suggested good acceptance and feasibility of intervention procedures but 34.6% of randomised participants were lost to follow-up due to overly high measurement burden and sub-optimal retention procedures. Participants in the intervention group showed positive trends for most psychological, behavioural and body

  11. 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.

  12. 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

  13. 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…

  14. 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

  15. A mechanistic detachment rate model to predict soil erodibility due to fluvial and seepage forces

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The erosion rate of cohesive soils is typically computed using an excess shear stress model based on the applied fluvial shear stress. However, no mechanistic approaches are available for incorporating additional forces such as localized groundwater seepage forces into the excess shear stress model...

  16. Performance modeling of the Ballard Mark IV solid polymer electrolyte fuel cell. 1: Mechanistic model development

    SciTech Connect

    Amphlett, J.C.; Baumert, R.M.; Mann, R.F.; Peppley, B.A.; Roberge, P.R. ); Harris, T.J. )

    1995-01-01

    A parametric model predicting the performance of a solid polymer electrolyte, proton exchange membrane (PEM) fuel cell has been developed using a combination of mechanistic and empirical modeling techniques. This paper details the mechanistic model development. Mass transport properties are considered in the mechanistic development via Stefan-Maxwell equations. Thermodynamic equilibrium potentials are defined using the Nernst equation. Activation overvoltages are defined via a Tafel equation, and internal resistance are defined via the Nernst-Planck equation, leading to a definition of ohmic overvoltage via an Ohm's law equation. The mechanistic model cannot adequately model fuel cell performance, since several simplifying approximations have been used in order to facilitate model development. Additionally, certain properties likely to be observed in operational fuel cells, such as thermal gradients, have not been considered. Nonetheless, the insights gained from the mechanistic assessment of fuel cell processes were found to give the resulting empirical model a firmer theoretical basis than many of the models presently available in the literature. Correlation of the empirical model to actual experimental data was very good.

  17. Mechanistic similarity and diversity among the guanidine-modifying members of the pentein superfamily

    PubMed Central

    Linsky, Thomas; Fast, Walter

    2014-01-01

    The pentein superfamily is a mechanistically diverse superfamily encompassing both noncatalytic proteins and enzymes that catalyze hydrolase, dihydrolase and amidinotransfer reactions on guanidine substrates. Despite generally low sequence identity, they possess a conserved structural fold and display common mechanistic themes in catalysis. The structurally characterized catalytic penteins possess a conserved core of residues that include a Cys, His and two polar, guanidine-binding residues. All known catalytic penteins use the core Cys to attack the substrate’s guanidine moiety to form a covalent thiouronium adduct and all cleave one or more of the guanidine C–N bonds. The mechanistic information compiled to date supports the hypothesis that this superfamily may have evolved divergently from a catalytically promiscuous ancestor. PMID:20654741

  18. Mechanistic bases for modelling space radiation risk and planning radiation protection of astronauts.

    PubMed

    Ottolenghi, A; Ballarini, F; Biaggi, M

    2001-01-01

    The approaches generally adopted for planning radiation protection in ground-based facilities cannot be applied straightforward for astronaut protection in space. Indeed in such extreme conditions, modelling methods and shielding design must be based on a detailed mechanistic knowledge of the peculiar astronauts irradiation conditions. Great help can derive from mechanistic modelling, generally aimed to better understand the intermediate steps leading from the initial energy depositions to different biological endpoints, up to organ and organism level. In the present work, criteria will be illustrated for using mechanistic approaches in developing practical tools for astronauts radioprotection, once the external field and the interaction cross sections with the spacecraft walls are known; particular attention will be given to the treatment of mixed fields. Techniques for integrating into condensed-history codes stochastic information provided by event-by-event simulations will be presented. PMID:11780618

  19. MECHANISTIC STUDIES OF IMPROVED FOAM EOR PROCESSES

    SciTech Connect

    William R. Rossen

    2003-03-31

    . We find that such behavior is consistent with earlier models of foam viscosity in tubes, and a modified model for the low-quality regime can account for this behavior. It is not yet clear why this new regime appears in some cases and not in others. Simple modeling suggests that the answer may have to do with the sensitivity of gas trapping to pressure gradient. Research on Task 3 continued to focus on foam generation at limited pressure gradient in sandpacks. We investigated the effects of permeability, surfactant concentration and liquid injection rates on foam generation. In addition, a careful review of published studies showed that repeated snap-off is not a plausible mechanism of foam generation in homogeneous porous media beyond the stage of initial drainage from a fully liquid-saturated state. Snap-off has been the focus of much research on foam generation and is incorporated into most mechanistic foam simulators. This finding should force a reconsideration of its role in foam generation and properties in porous media.

  20. Mechanistic facility safety and source term analysis

    SciTech Connect

    PLYS, M.G.

    1999-06-09

    A PC-based computer program was created for facility safety and source term analysis at Hanford The program has been successfully applied to mechanistic prediction of source terms from chemical reactions in underground storage tanks, hydrogen combustion in double contained receiver tanks, and proccss evaluation including the potential for runaway reactions in spent nuclear fuel processing. Model features include user-defined facility room, flow path geometry, and heat conductors, user-defined non-ideal vapor and aerosol species, pressure- and density-driven gas flows, aerosol transport and deposition, and structure to accommodate facility-specific source terms. Example applications are presented here.

  1. 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.

  2. 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.

  3. 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.

  4. Mechanistic Investigations into the Application of Sulfoxides in Carbohydrate Synthesis

    PubMed Central

    Brabham, Robin

    2016-01-01

    Abstract The utility of sulfoxides in a diverse range of transformations in the field of carbohydrate chemistry has seen rapid growth since the first introduction of a sulfoxide as a glycosyl donor in 1989. Sulfoxides have since developed into more than just anomeric leaving groups, and today have multiple roles in glycosylation reactions. These include as activators for thioglycosides, hemiacetals, and glycals, and as precursors to glycosyl triflates, which are essential for stereoselective β‐mannoside synthesis, and bicyclic sulfonium ions that facilitate the stereoselective synthesis of α‐glycosides. In this review we highlight the mechanistic investigations undertaken in this area, often outlining strategies employed to differentiate between multiple proposed reaction pathways, and how the conclusions of these investigations have and continue to inform upon the development of more efficient transformations in sulfoxide‐based carbohydrate synthesis. PMID:26744250

  5. Food additives

    MedlinePlus

    Food additives are substances that become part of a food product when they are added during the processing or making of that food. "Direct" food additives are often added during processing to: Add nutrients ...

  6. 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)

  7. 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

  8. 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

  9. 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

  10. 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 ...

  11. 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. PMID:27090846

  12. 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.

  13. 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.

  14. 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.

  15. Dynamic, mechanistic, molecular-level modelling of cyanobacteria: Anabaena and nitrogen interaction.

    PubMed

    Hellweger, Ferdi L; Fredrick, Neil D; McCarthy, Mark J; Gardner, Wayne S; Wilhelm, Steven W; Paerl, Hans W

    2016-09-01

    Phytoplankton (eutrophication, biogeochemical) models are important tools for ecosystem research and management, but they generally have not been updated to include modern biology. Here, we present a dynamic, mechanistic, molecular-level (i.e. gene, transcript, protein, metabolite) model of Anabaena - nitrogen interaction. The model was developed using the pattern-oriented approach to model definition and parameterization of complex agent-based models. It simulates individual filaments, each with individual cells, each with genes that are expressed to yield transcripts and proteins. Cells metabolize various forms of N, grow and divide, and differentiate heterocysts when fixed N is depleted. The model is informed by observations from 269 laboratory experiments from 55 papers published from 1942 to 2014. Within this database, we identified 331 emerging patterns, and, excluding inconsistencies in observations, the model reproduces 94% of them. To explore a practical application, we used the model to simulate nutrient reduction scenarios for a hypothetical lake. For a 50% N only loading reduction, the model predicts that N fixation increases, but this fixed N does not compensate for the loading reduction, and the chlorophyll a concentration decreases substantially (by 33%). When N is reduced along with P, the model predicts an additional 8% reduction (compared to P only). PMID:27059435

  16. 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.

  17. 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

  18. Food additives.

    PubMed

    Berglund, F

    1978-01-01

    The use of additives to food fulfils many purposes, as shown by the index issued by the Codex Committee on Food Additives: Acids, bases and salts; Preservatives, Antioxidants and antioxidant synergists; Anticaking agents; Colours; Emulfifiers; Thickening agents; Flour-treatment agents; Extraction solvents; Carrier solvents; Flavours (synthetic); Flavour enhancers; Non-nutritive sweeteners; Processing aids; Enzyme preparations. Many additives occur naturally in foods, but this does not exclude toxicity at higher levels. Some food additives are nutrients, or even essential nutritents, e.g. NaCl. Examples are known of food additives causing toxicity in man even when used according to regulations, e.g. cobalt in beer. In other instances, poisoning has been due to carry-over, e.g. by nitrate in cheese whey - when used for artificial feed for infants. Poisonings also occur as the result of the permitted substance being added at too high levels, by accident or carelessness, e.g. nitrite in fish. Finally, there are examples of hypersensitivity to food additives, e.g. to tartrazine and other food colours. The toxicological evaluation, based on animal feeding studies, may be complicated by impurities, e.g. orthotoluene-sulfonamide in saccharin; by transformation or disappearance of the additive in food processing in storage, e.g. bisulfite in raisins; by reaction products with food constituents, e.g. formation of ethylurethane from diethyl pyrocarbonate; by metabolic transformation products, e.g. formation in the gut of cyclohexylamine from cyclamate. Metabolic end products may differ in experimental animals and in man: guanylic acid and inosinic acid are metabolized to allantoin in the rat but to uric acid in man. The magnitude of the safety margin in man of the Acceptable Daily Intake (ADI) is not identical to the "safety factor" used when calculating the ADI. The symptoms of Chinese Restaurant Syndrome, although not hazardous, furthermore illustrate that the whole ADI

  19. Multiscale mechanistic modeling in pharmaceutical research and development.

    PubMed

    Kuepfer, Lars; Lippert, Jörg; Eissing, Thomas

    2012-01-01

    Discontinuation of drug development projects due to lack of efficacy or adverse events is one of the main cost drivers in pharmaceutical research and development (R&D). Investments have to be written-off and contribute to the total costs of a successful drug candidate receiving marketing authorization and allowing return on invest. A vital risk for pharmaceutical innovator companies is late stage clinical failure since costs for individual clinical trials may exceed the one billion Euro threshold. To guide investment decisions and to safeguard maximum medical benefit and safety for patients recruited in clinical trials, it is therefore essential to understand the clinical consequences of all information and data generated. The complexity of the physiological and pathophysiological processes and the sheer amount of information available overcharge the mental capacity of any human being and prevent a prediction of the success in clinical development. A rigorous integration of knowledge, assumption, and experimental data into computational models promises a significant improvement of the rationalization of decision making in pharmaceutical industry. We here give an overview of the current status of modeling and simulation in pharmaceutical R&D and outline the perspectives of more recent developments in mechanistic modeling. Specific modeling approaches for different biological scales ranging from intracellular processes to whole organism physiology are introduced and an example for integrative multiscale modeling of therapeutic efficiency in clinical oncology trials is showcased. PMID:22161351

  20. Structural and Mechanistic Aspects of Copper Catalyzed Atom Transfer Radical Polymerization

    NASA Astrophysics Data System (ADS)

    Pintauer, Tomislav; Matyjaszewski, Krzysztof

    During the past decade, atom transfer radical polymerization (ATRP) has had a tremendous impact on the synthesis of macromolecules with well-defined compositions, architectures, and functionalities. Structural features of copper(I) and copper(II) complexes with bidentate, tridentate, tetradentate, and multidentate nitrogen-based ligands commonly utilized in ATRP are reviewed and discussed. Additionally, recent advances in mechanistic understanding of copper-mediated ATRP are outlined.

  1. Multiparametric PET/CT-perfusion does not add significant additional information for initial staging in lung cancer compared with standard PET/CT

    PubMed Central

    2014-01-01

    Background The purpose of this study was to assess the relationship of CT-perfusion (CTP), 18F-FDG-PET/CT and histological parameters, and the possible added value of CTP to FDG-PET/CT in the initial staging of lung cancer. Methods Fifty-four consecutive patients (median age 65 years, 15 females, 39 males) with suspected lung cancer were evaluated prospectively by CT-perfusion scan and 18F-FDG-PET/CT scan. Overall, 46 tumors were identified. CTP parameters blood flow (BF), blood volume (BV), and mean transit time (MTT) of the tumor tissue were calculated. Intratumoral microvessel density (MVD) was assessed quantitatively. Differences in CTP parameters concerning tumor type, location, PET positivity of lymph nodes, TNM status, and UICC stage were analyzed. Spearman correlation analyses between CTP and 18F-FDG-PET/CT parameters (SUVmax, SUVmean, PETvol, and TLG), MVD, tumor size, and tumor stage were performed. Results The mean BF (mL/100 mL min-1), BV (mL/100 mL), and MTT (s) was 35.5, 8.4, and 14.2, respectively. The BF and BV were lower in tumors with PET-positive lymph nodes (p = 0.02). However, the CTP values were not significantly different among the N stages. The CTP values were not different, depending on tumor size and location. No significant correlation was found between CTP parameters and MVD. Conclusions Overall, the CTP information showed only little additional information for the initial staging compared with standard FDG-PET/CT. Low perfusion in lung tumors might possibly be associated with metabolically active regional lymph nodes. Apart from that, both CTP and 18F-FDG-PET/CT parameter sets may reflect different pathophysiological mechanisms in lung cancer. PMID:24450990

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Phosphazene additives

    SciTech Connect

    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.

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

    PubMed Central

    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

  8. BPI-ANCA Provides Additional Clinical Information to Anti-Pseudomonas Serology: Results from a Cohort of 117 Swedish Cystic Fibrosis Patients.

    PubMed

    Lindberg, Ulrika; Carlsson, Malin; Hellmark, Thomas; Segelmark, Mårten

    2015-01-01

    Patients with cystic fibrosis (CF) colonized with Pseudomonas aeruginosa (P. aeruginosa) have worse prognosis compared with patients who are not. BPI-ANCA is an anti-neutrophil cytoplasmic antibody against BPI (bactericidal/permeability increasing protein) correlating with P. aeruginosa colonization and adverse long time prognosis. Whether it provides additional information as compared to standard anti-P. aeruginosa serology tests is not known. 117 nontransplanted CF patients at the CF centre in Lund, Sweden, were followed prospectively for ten years. Bacterial colonisation was classified according to the Leeds criteria. IgA BPI-ANCA was compared with assays for antibodies against alkaline protease (AP), Elastase (ELA), and Exotoxin A (ExoA). Lung function and patient outcome, alive, lung transplanted, or dead, were registered. BPI-ANCA showed the highest correlation with lung function impairment with an r-value of 0.44. Forty-eight of the 117 patients were chronically colonized with P. aeruginosa. Twenty of these patients experienced an adverse outcome. Receiver operator curve (ROC) analysis revealed that this could be predicted by BPI-ANCA (AUC = 0.77), (p = 0.002) to a better degree compared with serology tests. BPI-ANCA correlates better with lung function impairment and long time prognosis than anti-P. aeruginosa serology and has similar ability to identify patients with chronic P. aeruginosa. PMID:26273683

  9. 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.

  10. 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.

  11. 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. PMID:24499118

  12. Predictive toxicodynamics: Empirical/mechanistic approaches.

    PubMed

    Frazier, J M

    1997-10-01

    A major objective of the toxicological sciences is to predict the in vivo toxicological consequences of human exposure to pure chemicals, complex mixtures and commercial formulations. Historically, the experimental approach to this goal has been to investigate toxicological processes in whole animal models and extrapolate the results obtained to predict human risk using various extrapolation procedures (high-dose/low-dose extrapolation, interspecies extrapolation and route-to-route extrapolation). Can in vitro methods be more widely employed in quantitative risk assessment? One major limitation to the broader application of in vitro toxicity testing methods is the lack of validated techniques for the extrapolation of in vitro-derived toxicodynamic data to the in vivo situation. The objective of this paper is to describe some approaches to the development of techniques to extrapolate in vitro toxicity testing data to predict in vivo toxicological responses. An empirical approach within the context of a mechanistic framework is explored. The basic hypothesis is that the in vivo response can be constructed from a cellular toxicity factor that accounts for the cellular response and a toxicodynamic factor that relates toxicological events at the cellular level to the observable in vivo responses. A predictive paradigm to describe the in vivo acute target organ toxicity (hepatotoxicity) of a model chemical (cadmium) is discussed. The cellular toxicity factor is derived from in vitro toxicity testing studies using isolated rat hepatocytes. The toxicodynamic factor is derived through Biologically-Based Response (BBR) modelling techniques to predict target organ toxicity markers (i.e. plasma hepatic enzyme levels as markers for acute hepatotoxicity). The ultimate goal is to develop validated extrapolation procedures that can be applied to predicting target organ toxicity quantitatively in human populations based on in vitro toxicity studies using human cellular models. PMID

  13. 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

  14. 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

  15. Stem cell guidance through the mechanistic target of rapamycin

    PubMed Central

    Maiese, Kenneth

    2015-01-01

    Stem cells offer great promise for the treatment of multiple disorders throughout the body. Critical to this premise is the ability to govern stem cell pluripotency, proliferation, and differentiation. The mechanistic target of rapamycin (mTOR), 289-kDa serine/threonine protein kinase, that is a vital component of mTOR Complex 1 and mTOR Complex 2 represents a critical pathway for the oversight of stem cell maintenance. mTOR can control the programmed cell death pathways of autophagy and apoptosis that can yield variable outcomes in stem cell survival and be reliant upon proliferative pathways that include Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1), silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), and trophic factors. mTOR also is a necessary component for the early development and establishment of stem cells as well as having a significant impact in the regulation of the maturation of specific cell phenotypes. Yet, as a proliferative agent, mTOR can not only foster cancer stem cell development and tumorigenesis, but also mediate cell senescence under certain conditions to limit invasive cancer growth. mTOR offers an exciting target for the oversight of stem cell therapies but requires careful consideration of the diverse clinical outcomes that can be fueled by mTOR signaling pathways. PMID:26328016

  16. Microneedle/nanoencapsulation-mediated transdermal delivery: Mechanistic insights

    PubMed Central

    Gomaa, Yasmine A.; Garland, Martin J.; McInnes, Fiona J.; Donnelly, Ryan F.; El-Khordagui, Labiba K.; Wilson, Clive G.

    2014-01-01

    A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array. Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes. Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs. Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation. Data were verified using confocal laser scanning microscopy imaging. Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs. Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics. Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents. PMID:23461860

  17. Serum Total Bilirubin Levels Provide Additive Risk Information over the Framingham Risk Score for Identifying Asymptomatic Diabetic Patients at Higher Risk for Coronary Artery Stenosis

    PubMed Central

    Leem, Jaechan; Koh, Eun Hee; Jang, Jung Eun; Woo, Chang-Yun; Oh, Jin Sun; Lee, Min Jung; Kang, Joon-Won; Lim, Tae-Hwan; Jung, Chang Hee; Lee, Woo Je; Park, Joong-Yeol

    2015-01-01

    Background The diagnosis of coronary artery disease (CAD) is often delayed in patients with type 2 diabetes. Serum total bilirubin levels are inversely associated with CAD. However, no studies have examined whether this can be used as a biochemical marker for identifying asymptomatic diabetic patients at higher risk for having obstructive CAD. Methods We performed a cross-sectional study of 460 consecutive asymptomatic patients with type 2 diabetes. All patients underwent coronary computed tomographic angiography, and their serum total bilirubin levels were measured. Obstructive CAD was defined as ≥50% diameter stenosis in at least one coronary artery. Results Serum total bilirubin tertiles showed an inverse association with the prevalence of obstructive CAD. In multivariate logistic regression analysis, the odds ratio for the highest versus the lowest tertile of total bilirubin was 0.227 (95% confidence interval [CI], 0.130 to 0.398), and an increment of 1 µmol/L in serum total bilirubin level was associated with a 14.6% decrease in obstructive CAD after adjustment for confounding variables. Receiver operating characteristic curve analysis showed that the area under the curve for the Framingham Risk Score (FRS) plus serum total bilirubin level was 0.712 (95% CI, 0.668 to 0.753), which is significantly greater than that of the FRS alone (P=0.0028). Conclusion Serum total bilirubin level is inversely associated with obstructive CAD and provides additive risk information over the FRS. Serum total bilirubin may be helpful for identifying asymptomatic patients with type 2 diabetes who are at higher risk for obstructive CAD. PMID:26566499

  18. 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

  19. 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

  20. Mechanistic Studies in Friction and Wear of Bulk Materials

    NASA Astrophysics Data System (ADS)

    Sawyer, W. Gregory; Argibay, Nicolas; Burris, David L.; Krick, Brandon A.

    2014-07-01

    From the context of a contemporary understanding of the phenomenological origins of friction and wear of materials, we review insightful contributions from recent experimental investigations of three classes of materials that exhibit uniquely contrasting tribological behaviors: metals, polymers, and ionic solids. We focus on the past decade of research by the community to better understand the correlations between environment parameters, materials properties, and tribological behavior in systems of increasingly greater complexity utilizing novel synthesis and in situ experimental techniques. In addition to such review, and a half-century after seminal publications on the subject, we present recently acquired evidence linking anisotropy in friction response with anisotropy in wear behavior of crystalline ionic solids as a function of crystallographic orientation. Although the tribological behaviors of metals, polymers, and ionic solids differ widely, it is increasingly more evident that the mechanistic origins (such as fatigue, corrosion, abrasion, and adhesion) are essentially the same. However, we hope to present a clear and compelling argument favoring the prominent and irreplaceable role of in situ experimental techniques as a bridge between fundamental atomistic and molecular processes and emergent behaviors governing tribological contacts.

  1. 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...

  2. MECHANISTIC DOSIMETRY MODELS OF NANOMATERIAL DEPOSITION IN THE RESPIRATORY TRACT

    EPA Science Inventory

    Accurate health risk assessments of inhalation exposure to nanomaterials will require dosimetry models that account for interspecies differences in dose delivered to the respiratory tract. Mechanistic models offer the advantage to interspecies extrapolation that physicochemica...

  3. 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. PMID:23149931

  4. 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.

  5. Substrate inhibition in the heterogeneous catalyzed aldol condensation: A mechanistic study of supported organocatalysts

    SciTech Connect

    Kandel, Kapil; Althaus, Stacey M.; Peeraphatdit, Chorthip; Kobayashi, Takeshi; Trewyn, Brian G.; Pruski, Marek; Slowing, Igor I.

    2012-05-23

    In this study, we demonstrate how materials science can be combined with the established methods of organic chemistry to find mechanistic bottlenecks and redesign heterogeneous catalysts for improved performance. By using solid-state NMR, infrared spectroscopy, surface and kinetic analysis, we prove the existence of a substrate inhibition in the aldol condensation catalyzed by heterogeneous amines. We show that modifying the structure of the supported amines according to the proposed mechanism dramatically enhances the activity of the heterogeneous catalyst. We also provide evidence that the reaction benefits significantly from the surface chemistry of the silica support, which plays the role of a co-catalyst, giving activities up to two orders of magnitude larger than those of homogeneous amines. This study confirms that the optimization of a heterogeneous catalyst depends as much on obtaining organic mechanistic information as it does on controlling the structure of the support.

  6. Bridging paradigms: hybrid mechanistic-discriminative predictive models.

    PubMed

    Doyle, Orla M; Tsaneva-Atansaova, Krasimira; Harte, James; Tiffin, Paul A; Tino, Peter; Díaz-Zuccarini, Vanessa

    2013-03-01

    Many disease processes are extremely complex and characterized by multiple stochastic processes interacting simultaneously. Current analytical approaches have included mechanistic models and machine learning (ML), which are often treated as orthogonal viewpoints. However, to facilitate truly personalized medicine, new perspectives may be required. This paper reviews the use of both mechanistic models and ML in healthcare as well as emerging hybrid methods, which are an exciting and promising approach for biologically based, yet data-driven advanced intelligent systems. PMID:23392334

  7. 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. PMID:23565807

  8. Reproductive toxicity and meiotic dysfunction following exposure to the pesticides Maneb, Diazinon and Fenarimol† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4tx00141a Click here for additional data file. Click here for additional data file. Click here for additional data file.

    PubMed Central

    Daniela A, Parodi; Jasmine, Sjarif; Yichang, Chen

    2015-01-01

    The comprehensive identification and mechanistic analysis of reproductive toxicants constitutes one of the major hurdles in the toxicological assessment of chemicals originating from the large number of chemicals to be tested and the difficulty in examining germ cells at various stages of their development. We previously described the development of an assay in the roundworm Caenorhabditis elegans that allows the detection of chemicals bearing aneugenic activity and that could be used for the detection of germline toxicity. We present here new evidence for the reproductive toxicity of three pesticides identified in our germline toxicity assay: Maneb, Diazinon and Fenarimol. We show that all three pesticides cause an acute germline nuclear loss in exposed nematodes in a dose-dependent fashion. The loss of germline nuclei coincides with the meiotic stage of pachytene during Prophase I and is dependent on the germline apoptotic machinery suggesting activation of a meiotic checkpoint. Further investigation revealed a profound dysregulation of the meiotic program as evidenced by (1) an alteration of the kinetics of double strand repair, (2) the disruption of the process of chromosome morphogenesis at the end of Prophase I and (3) the reorganization of the meiotic differentiation gradient inherent to the C. elegans germline following exposure to Maneb and Diazinon. These defects correlate with a significant increase in embryonic lethality and a corresponding decrease in the number of progeny. These results therefore provide strong evidence for the reproductive toxicity of Maneb, Diazinon and Fenarimol rooted in the alteration of early steps of germ cell differentiation. PMID:25984295

  9. MECHANISTIC CONSIDERATIONS FOR HUMAN RELEVANCE OF CANCER HAZARD OF DI(2-ETHYLHEXYL) PHTHALATE

    PubMed Central

    Rusyn, Ivan; Corton, J. Christopher

    2012-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a peroxisome proliferator agent that is widely used as a plasticizer to soften polyvinylchloride plastics and non-polymers. Both occupational (e.g., by inhalation during its manufacture and use as a plasticizer of polyvinylchloride) and environmental (medical devices, contamination of food, or intake from air, water and soil) routes of exposure to DEHP are of concern for human health. There is sufficient evidence for carcinogenicity of DEHP in the liver in both rats and mice; however, there is little epidemiological evidence on possible associations between exposure to DEHP and liver cancer in humans. Data are available to suggest that liver is not the only target tissue for DEHP-associated toxicity and carcinogenicity in both humans and rodents. The debate regarding human relevance of the findings in rats or mice has been informed by studies on the mechanisms of carcinogenesis of the peroxisome proliferator class of chemicals, including DEHP. Important additional mechanistic information became available in the past decade, including, but not limited to, sub-acute, sub-chronic and chronic studies with DEHP in peroxisome proliferator-activated receptor (PPAR) α-null mice, as well as experiments utilizing several transgenic mouse lines. Activation of PPARα and the subsequent downstream events mediated by this transcription factor represent an important mechanism of action for DEHP in rats and mice. However, additional data from animal models and studies in humans exposed to DEHP from the environment suggest that multiple molecular signals and pathways in several cell types in the liver, rather than a single molecular event, contribute to the cancer in rats and mice. In addition, the toxic and carcinogenic effects of DEHP are not limited to liver. The International Agency for Research on Cancer working group concluded that the human relevance of the molecular events leading to cancer elicited by DEHP in several target tissues (e

  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, 2010 CFR

    2010-07-01

    ... must submit a report to Congress on a proposed physical or material change or addition to an existing... advance of the anticipated date that work will begin on the physical or material change or addition to the... standards. (2) A statement of the estimated total cost of the proposed physical or material change...

  11. Emergent Global Patterns of Ecosystem Structure and Function from a Mechanistic General Ecosystem Model

    PubMed Central

    Emmott, Stephen; Hutton, Jon; Lyutsarev, Vassily; Smith, Matthew J.; Scharlemann, Jörn P. W.; Purves, Drew W.

    2014-01-01

    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. PMID:24756001

  12. 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." PMID:25462871

  13. 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.

  14. 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. PMID:21339605

  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. PMID:24019883

  16. Simulating Polar Bear Energetics during a Seasonal Fast Using a Mechanistic Model

    PubMed Central

    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. PMID:24019883

  17. Quantitative assessment of biological impact using transcriptomic data and mechanistic network models

    SciTech Connect

    Thomson, Ty M.; Sewer, Alain; Martin, Florian; Belcastro, Vincenzo; Frushour, Brian P.; Gebel, Stephan; Park, Jennifer; Schlage, Walter K.; Talikka, Marja; Vasilyev, Dmitry M.; Westra, Jurjen W.; Hoeng, Julia; Peitsch, Manuel C.

    2013-11-01

    Exposure to biologically active substances such as therapeutic drugs or environmental toxicants can impact biological systems at various levels, affecting individual molecules, signaling pathways, and overall cellular processes. The ability to derive mechanistic insights from the resulting system responses requires the integration of experimental measures with a priori knowledge about the system and the interacting molecules therein. We developed a novel systems biology-based methodology that leverages mechanistic network models and transcriptomic data to quantitatively assess the biological impact of exposures to active substances. Hierarchically organized network models were first constructed to provide a coherent framework for investigating the impact of exposures at the molecular, pathway and process levels. We then validated our methodology using novel and previously published experiments. For both in vitro systems with simple exposure and in vivo systems with complex exposures, our methodology was able to recapitulate known biological responses matching expected or measured phenotypes. In addition, the quantitative results were in agreement with experimental endpoint data for many of the mechanistic effects that were assessed, providing further objective confirmation of the approach. We conclude that our methodology evaluates the biological impact of exposures in an objective, systematic, and quantifiable manner, enabling the computation of a systems-wide and pan-mechanistic biological impact measure for a given active substance or mixture. Our results suggest that various fields of human disease research, from drug development to consumer product testing and environmental impact analysis, could benefit from using this methodology. - Highlights: • The impact of biologically active substances is quantified at multiple levels. • The systems-level impact integrates the perturbations of individual networks. • The networks capture the relationships between

  18. From formamide to purine: an energetically viable mechanistic reaction pathway.

    PubMed

    Wang, Jing; Gu, Jiande; Nguyen, Minh Tho; Springsteen, Greg; Leszczynski, Jerzy

    2013-02-28

    A step-by-step mechanistic pathway following the transformation of formamide to purine through a five-membered ring intermediate has been explored by density functional theory computations. The highlight of the mechanistic route detailed here is that the proposed pathway represents the simplest reaction pathway. All necessary reactants are generated from a single starting compound, formamide, through energetically viable reactions. Several important reaction steps are involved in this mechanistic route: formylation-dehydration, Leuckart reduction, five- and six-membered ring-closure, and deamination. On the basis of the study of noncatalytic pathways, catalytic water has been found to provide energetically viable step-by-step mechanistic pathways. Among these reaction steps, five-member ring-closure is the rate-determining step. The energy barrier (ca. 42 kcal/mol) of this rate-control step is somewhat lower than the rate-determining step (ca. 44 kcal/mol) for a pyrimidine-based pathway reported previously. The mechanistic pathway reported herein is less energetically demanding than for previously proposed routes to adenine. PMID:23347082

  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. 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

  3. 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

  4. Additive usage levels.

    PubMed

    Langlais, R

    1996-01-01

    With the adoption of the European Parliament and Council Directives on sweeteners, colours and miscellaneous additives the Commission is now embarking on the project of coordinating the activities of the European Union Member States in the collection of the data that are to make up the report on food additive intake requested by the European Parliament. This presentation looks at the inventory of available sources on additive use levels and concludes that for the time being national legislation is still the best source of information considering that the directives have yet to be transposed into national legislation. Furthermore, this presentation covers the correlation of the food categories as found in the additives directives with those used by national consumption surveys and finds that in a number of instances this correlation still leaves a lot to be desired. The intake of additives via food ingestion and the intake of substances which are chemically identical to additives but which occur naturally in fruits and vegetables is found in a number of cases to be higher than the intake of additives added during the manufacture of foodstuffs. While the difficulties are recognized in contributing to the compilation of food additive intake data, industry as a whole, i.e. the food manufacturing and food additive manufacturing industries, are confident that in a concerted effort, use data on food additives by industry can be made available. Lastly, the paper points out that with the transportation of the additives directives into national legislation and the time by which the food industry will be able to make use of the new food legislative environment several years will still go by; food additives use data by the food industry will thus have to be reviewed at the beginning of the next century. PMID:8792135

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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 ...

  10. 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...

  11. MECHANISTIC-BASED DISINFECTION AND DISINFECTION BYPRODUCT MODELS

    EPA Science Inventory

    We propose developing a mechanistic-based numerical model for chlorine decay and regulated DBP (THM and HAA) formation derived from (free) chlorination; the model framework will allow future modifications for other DBPs and chloramination. Predicted chlorine residual and DBP r...

  12. 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…

  13. Mechanistically Consistent Reduced Models of Synthetic Gene Networks

    PubMed Central

    Mier-y-Terán-Romero, Luis; Silber, Mary; Hatzimanikatis, Vassily

    2013-01-01

    Designing genetic networks with desired functionalities requires an accurate mathematical framework that accounts for the essential mechanistic details of the system. Here, we formulate a time-delay model of protein translation and mRNA degradation by systematically reducing a detailed mechanistic model that explicitly accounts for the ribosomal dynamics and the cleaving of mRNA by endonucleases. We exploit various technical and conceptual advantages that our time-delay model offers over the mechanistic model to probe the behavior of a self-repressing gene over wide regions of parameter space. We show that a heuristic time-delay model of protein synthesis of a commonly used form yields a notably different prediction for the parameter region where sustained oscillations occur. This suggests that such heuristics can lead to erroneous results. The functional forms that arise from our systematic reduction can be used for every system that involves transcription and translation and they could replace the commonly used heuristic time-delay models for these processes. The results from our analysis have important implications for the design of synthetic gene networks and stress that such design must be guided by a combination of heuristic models and mechanistic models that include all relevant details of the process. PMID:23663853

  14. 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…

  15. Biotelemetry: a mechanistic approach to ecology.

    PubMed

    Cooke, Steven J; Hinch, Scott G; Wikelski, Martin; Andrews, Russel D; Kuchel, Louise J; Wolcott, Thomas G; Butler, Patrick J

    2004-06-01

    Remote measurement of the physiology, behaviour and energetic status of free-living animals is made possible by a variety of techniques that we refer to collectively as 'biotelemetry'. This set of tools ranges from transmitters that send their signals to receivers up to a few kilometers away to those that send data to orbiting satellites and, more frequently, to devices that log data. They enable researchers to document, for long uninterrupted periods, how undisturbed organisms interact with each other and their environment in real time. In spite of advances enabling the monitoring of many physiological and behavioural variables across a range of taxa of various sizes, these devices have yet to be embraced widely by the ecological community. Our review suggests that this technology has immense potential for research in basic and applied animal ecology. Efforts to incorporate biotelemetry into broader ecological research programs should yield novel information that has been challenging to collect historically from free-ranging animals in their natural environments. Examples of research that would benefit from biotelemetry include the assessment of animal responses to different anthropogenic perturbations and the development of life-time energy budgets. PMID:16701280

  16. Additives in plastics.

    PubMed Central

    Deanin, R D

    1975-01-01

    The polymers used in plastics are generally harmless. However, they are rarely used in pure form. In almost all commercial plastics, they are "compounded" with monomeric ingredients to improve their processing and end-use performance. In order of total volume used, these monomeric additives may be classified as follows: reinforcing fibers, fillers, and coupling agents; plasticizers; colorants; stabilizers (halogen stabilizers, antioxidants, ultraviolet absorbers, and biological preservatives); processing aids (lubricants, others, and flow controls); flame retardants, peroxides; and antistats. Some information is already available, and much more is needed, on potential toxicity and safe handling of these additives during processing and manufacture of plastics products. PMID:1175566

  17. 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. PMID:26843025

  18. 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

  19. 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

  20. MECHANISTIC STUDIES OF IMPROVED FOAM EOR PROCESSES

    SciTech Connect

    William R. Rossen

    2004-06-14

    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. Significant progress was made during this period on all three Tasks. Regarding Task 1, we continued comparisons of foam behavior in sandpacks with and without polymer and oil. As in our previous results, decane was moderately destabilizing to foam. Xanthan polymer did not stabilize foam in the presence of decane in this case. Rather, it appears to have destabilized foam, so that pressure gradient decreased in spite of the increase in aqueous-phase viscosity. Research on Task 2 included the first shake-down experiments with our new apparatus for gas-phase tracer tests for direct measurement of trapped-gas saturation with foam. In addition, we began to analyze CT images of gas-phase tracer in foam displacements, which offers an independent measure of trapped-gas fraction and insights into the roles of convection of tracer in flowing gas and diffusion into trapped gas. Research on Task 3 included foam generation experiments in heterogeneous sandpacks and beadpacks and modeling of discontinuous changes in state such as foam generation. The experiments found the same three regimes (coarse foam, strong foam, and intermediate regime) in heterogeneous sandpacks previously identified in homogeneous porous media. One implication is that there may be a minimum flow rate required for foam generation in even heterogeneous porous media. The dynamics in SAG foam processes in heterogeneous media are complex

  1. 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

  2. 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.

  3. Validating Mechanistic Sorption Model Parameters and Processes for Reactive Transport in Alluvium

    SciTech Connect

    Zavarin, M; Roberts, S K; Rose, T P; Phinney, D L

    2002-05-02

    The laboratory batch and flow-through experiments presented in this report provide a basis for validating the mechanistic surface complexation and ion exchange model we use in our hydrologic source term (HST) simulations. Batch sorption experiments were used to examine the effect of solution composition on sorption. Flow-through experiments provided for an analysis of the transport behavior of sorbing elements and tracers which includes dispersion and fluid accessibility effects. Analysis of downstream flow-through column fluids allowed for evaluation of weakly-sorbing element transport. Secondary Ion Mass Spectrometry (SIMS) analysis of the core after completion of the flow-through experiments permitted the evaluation of transport of strongly sorbing elements. A comparison between these data and model predictions provides additional constraints to our model and improves our confidence in near-field HST model parameters. In general, cesium, strontium, samarium, europium, neptunium, and uranium behavior could be accurately predicted using our mechanistic approach but only after some adjustment was made to the model parameters. The required adjustments included a reduction in strontium affinity for smectite, an increase in cesium affinity for smectite and illite, a reduction in iron oxide and calcite reactive surface area, and a change in clinoptilolite reaction constants to reflect a more recently published set of data. In general, these adjustments are justifiable because they fall within a range consistent with our understanding of the parameter uncertainties. These modeling results suggest that the uncertainty in the sorption model parameters must be accounted for to validate the mechanistic approach. The uncertainties in predicting the sorptive behavior of U-1a and UE-5n alluvium also suggest that these uncertainties must be propagated to nearfield HST and large-scale corrective action unit (CAU) models.

  4. 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.

  5. 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

  6. 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

  7. Mechanistic model and analysis of doxorubicin release from liposomal formulations.

    PubMed

    Fugit, Kyle D; Xiang, Tian-Xiang; Choi, Du H; Kangarlou, Sogol; Csuhai, Eva; Bummer, Paul M; Anderson, Bradley D

    2015-11-10

    Reliable and predictive models of drug release kinetics in vitro and in vivo are still lacking for liposomal formulations. Developing robust, predictive release models requires systematic, quantitative characterization of these complex drug delivery systems with respect to the physicochemical properties governing the driving force for release. These models must also incorporate changes in release due to the dissolution media and methods employed to monitor release. This paper demonstrates the successful development and application of a mathematical mechanistic model capable of predicting doxorubicin (DXR) release kinetics from liposomal formulations resembling the FDA-approved nanoformulation DOXIL® using dynamic dialysis. The model accounts for DXR equilibria (e.g. self-association, precipitation, ionization), the change in intravesicular pH due to ammonia release, and dialysis membrane transport of DXR. The model was tested using a Box-Behnken experimental design in which release conditions including extravesicular pH, ammonia concentration in the release medium, and the dilution of the formulation (i.e. suspension concentration) were varied. Mechanistic model predictions agreed with observed DXR release up to 19h. The predictions were similar to a computer fit of the release data using an empirical model often employed for analyzing data generated from this type of experimental design. Unlike the empirical model, the mechanistic model was also able to provide reasonable predictions of release outside the tested design space. These results illustrate the usefulness of mechanistic modeling to predict drug release from liposomal formulations in vitro and its potential for future development of in vitro - in vivo correlations for complex nanoformulations. PMID:26310713

  8. 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.

  9. 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.

  10. Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer's disease, Parkinson's disease, and related disorders.

    PubMed

    Ramanan, Vijay K; Saykin, Andrew J

    2013-01-01

    The discovery of causative genetic mutations in affected family members has historically dominated our understanding of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). Nevertheless, most cases of neurodegenerative disease are not explained by Mendelian inheritance of known genetic variants, but instead are thought to have a complex etiology with numerous genetic and environmental factors contributing to susceptibility. Although unbiased genome-wide association studies (GWAS) have identified novel associations to neurodegenerative diseases, most of these hits explain only modest fractions of disease heritability. In addition, despite the substantial overlap of clinical and pathologic features among major neurodegenerative diseases, surprisingly few GWAS-implicated variants appear to exhibit cross-disease association. These realities suggest limitations of the focus on individual genetic variants and create challenges for the development of diagnostic and therapeutic strategies, which traditionally target an isolated molecule or mechanistic step. Recently, GWAS of complex diseases and traits have focused less on individual susceptibility variants and instead have emphasized the biological pathways and networks revealed by genetic associations. This new paradigm draws on the hypothesis that fundamental disease processes may be influenced on a personalized basis by a combination of variants - some common and others rare, some protective and others deleterious - in key genes and pathways. Here, we review and synthesize the major pathways implicated in neurodegeneration, focusing on GWAS from the most prevalent neurodegenerative disorders, AD and PD. Using literature mining, we also discover a novel regulatory network that is enriched with AD- and PD-associated genes and centered on the SP1 and AP-1 (Jun/Fos) transcription factors. Overall, this pathway- and

  11. 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. PMID:25251642

  12. 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

  13. 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

  14. Using mechanistic Bayesian networks to identify downstream targets of the Sonic Hedgehog pathway

    PubMed Central

    2009-01-01

    Background The topology of a biological pathway provides clues as to how a pathway operates, but rationally using this topology information with observed gene expression data remains a challenge. Results We introduce a new general-purpose analytic method called Mechanistic Bayesian Networks (MBNs) that allows for the integration of gene expression data and known constraints within a signal or regulatory pathway to predict new downstream pathway targets. The MBN framework is implemented in an open-source Bayesian network learning package, the Python Environment for Bayesian Learning (PEBL). We demonstrate how MBNs can be used by modeling the early steps of the sonic hedgehog pathway using gene expression data from different developmental stages and genetic backgrounds in mouse. Using the MBN approach we are able to automatically identify many of the known downstream targets of the hedgehog pathway such as Gas1 and Gli1, along with a short list of likely targets such as Mig12. Conclusions The MBN approach shown here can easily be extended to other pathways and data types to yield a more mechanistic framework for learning genetic regulatory models. PMID:20021670

  15. 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

  16. Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions

    PubMed Central

    Betts, Matthew J.; Lu, Qianhao; Jiang, YingYing; Drusko, Armin; Wichmann, Oliver; Utz, Mathias; Valtierra-Gutiérrez, Ilse A.; Schlesner, Matthias; Jaeger, Natalie; Jones, David T.; Pfister, Stefan; Lichter, Peter; Eils, Roland; Siebert, Reiner; Bork, Peer; Apic, Gordana; Gavin, Anne-Claude; Russell, Robert B.

    2015-01-01

    Systematic interrogation of mutation or protein modification data is important to identify sites with functional consequences and to deduce global consequences from large data sets. Mechismo (mechismo.russellab.org) enables simultaneous consideration of thousands of 3D structures and biomolecular interactions to predict rapidly mechanistic consequences for mutations and modifications. As useful functional information often only comes from homologous proteins, we benchmarked the accuracy of predictions as a function of protein/structure sequence similarity, which permits the use of relatively weak sequence similarities with an appropriate confidence measure. For protein–protein, protein–nucleic acid and a subset of protein–chemical interactions, we also developed and benchmarked a measure of whether modifications are likely to enhance or diminish the interactions, which can assist the detection of modifications with specific effects. Analysis of high-throughput sequencing data shows that the approach can identify interesting differences between cancers, and application to proteomics data finds potential mechanistic insights for how post-translational modifications can alter biomolecular interactions. PMID:25392414

  17. 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

  18. Isocyano Enones: Addition-Cyclization Cascade to Oxazoles.

    PubMed

    Chao, Allen; Lujan-Montelongo, J Armando; Fleming, Fraser F

    2016-07-01

    Copper iodide catalyzes the conjugate addition of organometallic and heteroatom nucleophiles to isocyano enones to afford oxazoles. A range of enolates, metalated nitriles, amines, and thiols undergo catalyzed conjugate addition to cyclic and acyclic oxoalkene isocyanides. Mechanistic studies suggest that copper complexation facilitates the nucleophilic attack on the isocyano enone to generate an enolate that cyclizes onto the isocyanide leading to a variety of substituted acyclic or ring-fused oxazoles. PMID:27282173

  19. Oxidative addition of carbon-carbon bonds to gold.

    PubMed

    Joost, Maximilian; Estévez, Laura; Miqueu, Karinne; Amgoune, Abderrahmane; Bourissou, Didier

    2015-04-20

    The oxidative addition of strained CC bonds (biphenylene, benzocyclobutenone) to DPCb (diphosphino-carborane) gold(I) complexes is reported. The resulting cationic organogold(III) complexes have been isolated and fully characterized. Experimental conditions can be adjusted to obtain selectively acyl gold(III) complexes resulting from oxidative addition of either the C(aryl)C(O) or C(alkyl)C(O) bond of benzocyclobutenone. DFT calculations provide mechanistic insight into this unprecedented transformation. PMID:25727203

  20. 24 CFR 1710.116 - Additional information.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... the right to exercise, any control over the Association because of voting rights or placement of... buyers; the developer's right of first refusal; membership requirements)? If so, briefly explain the...) Must an alien obtain a permit or license to own land, build a home, live, work or do business in...

  1. Mechanistically Driven Development of Iridium Catalysts for Asymmetric Allylic Substitution

    PubMed Central

    Hartwig, John F.; Stanley, Levi M.

    2010-01-01

    , with high branched-to-linear ratios and high enantioselectivities. Parallel mechanistic studies had revealed the metallacyclic structure of the active catalyst, and subsequent experiments with the purposefully formed metallacycle increased the reaction scope dramatically. Aromatic amines, azoles, ammonia, and amides and carbamates as ammonia equivalents all reacted with high selectivities and yields. Moreover, weakly basic enolates (such as silyl enol ethers) and enolate equivalents (such as enamines) also reacted, and other research groups have used this catalyst to conduct reactions of stabilized carbon nucleophiles in the absence of additional base. One hallmark of the reactions catalyzed by this iridium system is the invariably high enantioselectivity, which reflects a high stereoselectivity for formation of the allyl intermediate. Enantioselectivity typically exceeds 95%, regioselectivity for formation of branched over linear products is usually near 20:1, and yields generally exceed 75% and are often greater than 90%. Thus, the development of iridium catalysts for enantioselective allylic substitution shows how studies of reaction mechanism can lead to a particularly active and a remarkably general system for an enantioselective process. In this case, a readily accessible catalyst effects allylic substitution, with high enantioselectivity and regioselectivity complementary to that of the venerable palladium systems. PMID:20873839

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. Structural and mechanistic aspects of 3C proteases from the Picornavirus family.

    PubMed

    Arad, D; Kreisberg, R; Shokhen, M

    1993-01-01

    Picornavirus 3C proteases are prime targets for rational drug design. This viral protease appears in a large number of viruses from the Picornavirus family that cause serious disease syndromes, and it has an important role in the life cycle of the virus, processing the translation product of the Picornavirus genome by progressive co- and posttranslational cleavages. It is, therefore, important to gain structural and mechanistic information about this family of enzymes. We concentrate in this paper on the specific features of the 3C; particularly, we are trying to show that the 3C constitute a new family to enzymes which is neither a serine- nor a cysteine-type protease. General basic theory on the behavior of sulfur nucleophile vs the behavior of oxygen nucleophile regarding the nucleophilic attack on carbonyl compounds and the possible determinants in the structure of 3C viral proteases of rhinovirus 1A are being discussed. PMID:8320292

  8. 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

  9. Synthetic and Mechanistic Studies of Strained Heterocycle Opening Reactions Mediated by Zirconium(IV) Imido Complexes

    PubMed Central

    Blum, Suzanne A.; Rivera, Vicki A.; Ruck, Rebecca T.; Michael, Forrest E.; Bergman, Robert G.

    2005-01-01

    The reactions of the bis(cyclopentadienyl)(tert-butylimido)zirconium complex (Cp2Zr=N-t-Bu)(THF) (1) with epoxides, aziridines, and episulfides were investigated. Heterocycles without accessible β-hydrogens undergo insertion/protonation of the C–X bond to produce 1,2-amino alcohols (X = O) and 1,2-diamines (X = NR), whereas heterocycles with accessible β-hydrogens undergo elimination/protonation to produce allylic alcohols (X = O) and allylic sulfides (X = S). Mechanistic investigations support a stepwise pathway with zwitterionic intermediates for the first reaction class and a concerted pathway for the second reaction class. Additionally, the feasibility of chirality transfer from the planar-chiral ebthi (ebthi = ethylenebis(tetrahydroindenyl)) ligand was demonstrated with a chiral analogue, (ebthi)-Zr=NAr(THF) (Ar = 2,6-dimethylphenyl), 2, through the diastereoselective ring opening of meso epoxides. PMID:16508693

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

    PubMed

    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. PMID:27219707

  11. 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

  12. 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

  13. 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

  14. Surgery for malignant gliomas: mechanistic reasoning and slippery statistics.

    PubMed

    Mitchell, Patrick; Ellison, David W; Mendelow, A David

    2005-07-01

    Current surgical treatment of malignant gliomas largely depends on mechanistic reasoning and data collected in non-randomised studies. Technological advance has enabled more accurate resection of tumours and preservation of eloquent brain areas but ethical considerations have restricted randomised trials on the efficacy of surgery to one small trial that found a 3 month survival advantage for patients over age 65 years who received surgery and interim analysis of a larger trial. There is an argument for surgery as a palliative measure in patients with symptoms caused by mechanisms that are surgically remediable. Whether there is any survival advantage from surgery in patients other than those with immediately life-threatening, surgically remediable complications, such as raised intracranial pressure, is unclear. The available data show that if such an advantage does exist, it is modest at best. Adjuvant treatments given surgically are being studied. Chemotherapy wafers are the most prominent of the adjuvant treatments but the evidence available is insufficient to recommend their use in routine practice. In this review we examine the prevailing mechanistic model and observational data; we assess how these are applied and the priorities they indicate for future research. PMID:15963444

  15. From data patterns to mechanistic models in acute critical illness.

    PubMed

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

    2014-08-01

    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 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 physiologic 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

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

    PubMed Central

    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

  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. 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

  19. 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

  20. Stereochemistry of enzymatic water addition to C=C bonds.

    PubMed

    Chen, Bi-Shuang; Otten, Linda G; Hanefeld, Ulf

    2015-01-01

    Water addition to carbon-carbon double bonds using hydratases is attracting great interest in biochemistry. Most of the known hydratases are involved in primary metabolism and to a lesser extent in secondary metabolism. New hydratases have recently been added to the toolbox, both from natural sources or artificial metalloenzymes. In order to comprehensively understand how the hydratases are able to catalyse the water addition to carbon-carbon double bonds, this review will highlight the mechanistic and stereochemical studies of the enzymatic water addition to carbon-carbon double bonds, focusing on the syn/anti-addition and stereochemistry of the reaction. PMID:25640045

  1. 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

  2. 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

  3. 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. PMID:23966644

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Mechanistic views on aromatic substitution reactions by gaseous cations.

    PubMed

    Fornarini, S

    1996-01-01

    Recent advances in the understanding of the gas-phase reaction of aromatics with cationic electrophiles in a thermally equilibrated domain are described. The overall substitution reaction is analyzed in terms of its elementary steps. Their contribution to the overall reactivity pattern is dissected by the use of selected systems, which allowed one to highlight the kinetic role of single elementary events. Mechanistic studies have focused on the structure and reactivity of covalent and non-covalent ionic intermediates, which display a rich chemistry and provide benchmark reactivity models. Particular interest has been devoted to proton transfer reactions, which may occur in either an intra- or intermolecular fashion in arenium intermediates. A quantitative study of their rates and associated kinetic isotope effects is reported. © 1997 John Wiley & Sons, Inc. Mass Spectrom Rev 15(6), 365-389, 1997. PMID:27082944

  10. 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. PMID:27160325

  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. The unique enzymatic and mechanistic properties of plant myosins.

    PubMed

    Henn, Arnon; Sadot, Einat

    2014-12-01

    Myosins are molecular motors that move along actin-filament tracks. Plants express two main classes of myosins, myosin VIII and myosin XI. Along with their relatively conserved sequence and functions, plant myosins have acquired some unique features. Myosin VIII has the enzymatic characteristics of a tension sensor and/or a tension generator, similar to functions found in other eukaryotes. Interestingly, class XI plant myosins have gained a novel function that consists of propelling the exceptionally rapid cytoplasmic streaming. This specific class includes the fastest known translocating molecular motors, which can reach an extremely high velocity of about 60μms(-1). However, the enzymatic properties and mechanistic basis for these remarkable manifestations are not yet fully understood. Here we review recent progress in understanding the uniqueness of plant myosins, while emphasizing the unanswered questions. PMID:25435181

  13. 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. PMID:25368428

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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...

  19. 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. PMID:26592522

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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...

  7. 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...

  8. 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.

  9. Exploring novel mechanistic insights in Alzheimer's disease by assessing reliability of protein interactions.

    PubMed

    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

  10. 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

  11. 78 FR 73504 - Procurement List; Proposed Additions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... Type/Location: Custodial Service, Directorate of Contracting Procurement Logistics Support Detachment... Contracting Procurement Logistics Support Detachment, Fort Belvoir, VA. * Additional Information:...

  12. 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

  13. 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

  14. Mechanistic constraints from the substrate concentration dependence of enzymatic fluctuations

    PubMed Central

    Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos

    2010-01-01

    The time it takes an enzyme to complete its reaction is a stochastic quantity governed by thermal fluctuations. With the advent of high-resolution methods of single-molecule manipulation and detection, it is now possible to observe directly this natural variation in the enzymatic cycle completion time and extract kinetic information from the statistics of its fluctuations. To this end, the inverse of the squared coefficient of variation, which we term nmin, is a useful measure of fluctuations because it places a strict lower limit on the number of kinetic states in the enzymatic mechanism. Here we show that there is a single general expression for the substrate dependence of nmin for a wide range of kinetic models. This expression is governed by three kinetic parameters, which we term NL, NS, and α. These parameters have simple geometric interpretations and provide clear constraints on possible kinetic mechanisms. As a demonstration of this analysis, we fit the fluctuations in the dwell times of the packaging motor of the bacteriophage φ29, revealing additional features of the nucleotide loading process in this motor. Because a diverse set of kinetic models display the same substrate dependence for their fluctuations, the expression for this general dependence may prove of use in the characterization and study of the dynamics of a wide range of enzymes. PMID:20729471

  15. 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

  16. 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

  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. Ultrasound enhanced ethanol production from Parthenium hysterophorus: A mechanistic investigation.

    PubMed

    Singh, Shuchi; Sarma, Shyamali; Agarwal, Mayank; Goyal, Arun; Moholkar, Vijayanand S

    2015-01-01

    This study presents mechanistic investigations in ultrasound-assisted bioethanol fermentation using Parthenium hysterophorus biomass. Ultrasound (35 kHz, 10% duty cycle) has been used for sonication. Experimental results were fitted to mathematical model; the kinetic and physiological parameters in the model were obtained using Genetic Algorithm (GA) based optimization. In control experiments (mechanical shaking), maximum ethanol titer of 10.93 g/L and cell mass concentration of 5.26 g/L was obtained after 18 h. In test experiments (mechanical shaking and intermittent sonication), ethanol titer of 12.14 g/L and cell mass concentration of 5.7 g/L was obtained in 10h. This indicated ∼ 2 × enhanced productivity of ethanol and cell mass with sonication. Trends in model parameters obtained after fitting of model to experimental data essentially revealed that beneficial influence of ultrasound on fermentation is a manifestation of enhanced trans-membrane transportation and dilution of toxic substances due to strong micro-convection induced by ultrasound. PMID:25555927

  19. 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

  20. 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