WorldWideScience

Sample records for development mechanistic studies

  1. Organometallic Reactions Development, Mechanistic Studies and Synthetic Applications

    DEFF Research Database (Denmark)

    Dam, Johan Hygum

    of the successful total synthesis of the cyclophane cavicularin, which contains a bent aromatic moiety. The pivotal step in the synthesis embodied a pyrone-alkyne Diels-Alder cycloaddition with CO2-extrusion to deliver the bent aromatic residue. The fourth project involved further development of the conditions...... previously discovered in the Madsen group for the direct coupling of alcohols and amines to amides under dihydrogen liberation. The goal was to synthesize isolatable ruthenium catalysts and two 18-electron complexes capable of performing the reaction in excellent yields were prepared and characterized...

  2. Oxide nanomaterials: synthetic developments, mechanistic studies, and technological innovations.

    Science.gov (United States)

    Patzke, Greta R; Zhou, Ying; Kontic, Roman; Conrad, Franziska

    2011-01-24

    Oxide nanomaterials are indispensable for nanotechnological innovations, because they combine an infinite variety of structural motifs and properties with manifold morphological features. Given that new oxide materials are almost reported on a daily basis, considerable synthetic and technological work remains to be done to fully exploit this ever increasing family of compounds for innovative nano-applications. This calls for reliable and scalable preparative approaches to oxide nanomaterials and their development remains a challenge for many complex nanostructured oxides. Oxide nanomaterials with special physicochemical features and unusual morphologies are still difficult to access by classic synthetic pathways. The limitless options for creating nano-oxide building blocks open up new technological perspectives with the potential to revolutionize areas ranging from data processing to biocatalysis. Oxide nanotechnology of the 21st century thus needs a strong interplay of preparative creativity, analytical skills, and new ideas for synergistic implementations. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Preparative and mechanistic studies toward the rational development of catalytic, enantioselective selenoetherification reactions.

    Science.gov (United States)

    Denmark, Scott E; Kalyani, Dipannita; Collins, William R

    2010-11-10

    A systematic investigation into the Lewis base catalyzed, asymmetric, intramolecular selenoetherification of olefins is described. A critical challenge for the development of this process was the identification and suppression of racemization pathways available to arylseleniranium ion intermediates. This report details a thorough study of the influences of the steric and electronic modulation of the arylselenenyl group on the configurational stability of enantioenriched seleniranium ions. These studies show that the 2-nitrophenyl group attached to the selenium atom significantly attenuates the racemization of seleniranium ions. A variety of achiral Lewis bases catalyze the intramolecular selenoetherification of alkenes using N-(2-nitrophenylselenenyl)succinimide as the electrophile along with a Brønsted acid. Preliminary mechanistic studies suggest the intermediacy of ionic Lewis base-selenium(II) adducts. Most importantly, a broad survey of chiral Lewis bases revealed that 1,1'-binaphthalene-2,2'-diamine (BINAM)-derived thiophosphoramides catalyze the cyclization of unsaturated alcohols in the presence of N-(2-nitrophenylselenenyl)succinimide and methanesulfonic acid. A variety of cyclic seleno ethers were produced in good chemical yields and in moderate to good enantioselectivities, which constitutes the first catalytic, enantioselective selenofunctionalization of unactivated olefins.

  4. The physicochemical process of bacterial attachment to abiotic surfaces: Challenges for mechanistic studies, predictability and the development of control strategies.

    Science.gov (United States)

    Wang, Yi; Lee, Sui Mae; Dykes, Gary

    2015-01-01

    Bacterial attachment to abiotic surfaces can be explained as a physicochemical process. Mechanisms of the process have been widely studied but are not yet well understood due to their complexity. Physicochemical processes can be influenced by various interactions and factors in attachment systems, including, but not limited to, hydrophobic interactions, electrostatic interactions and substratum surface roughness. Mechanistic models and control strategies for bacterial attachment to abiotic surfaces have been established based on the current understanding of the attachment process and the interactions involved. Due to a lack of process control and standardization in the methodologies used to study the mechanisms of bacterial attachment, however, various challenges are apparent in the development of models and control strategies. In this review, the physicochemical mechanisms, interactions and factors affecting the process of bacterial attachment to abiotic surfaces are described. Mechanistic models established based on these parameters are discussed in terms of their limitations. Currently employed methods to study these parameters and bacterial attachment are critically compared. The roles of these parameters in the development of control strategies for bacterial attachment are reviewed, and the challenges that arise in developing mechanistic models and control strategies are assessed.

  5. Mechanistic study of plasma damage to porous low-k: Process development and dielectric recovery

    Science.gov (United States)

    Shi, Hualiang

    Low-k dielectrics with porosity are being introduced to reduce the RC delay of Cu/low-k interconnect. However, during the O2 plasma ashing process, the porous low-k dielectrics tend to degrade due to methyl depletion, moisture uptake, and densification, increasing the dielectric constant and leakage current. This dissertation presents a study of the mechanisms of plasma damage and dielectric recovery. The kinetics of plasma interaction with low-k dielectrics was investigated both experimentally and theoretically. By using a gap structure, the roles of ion, photon, and radical in producing damage on low-k dielectrics were differentiated. Oxidative plasma induced damage was proportional to the oxygen radical density, enhanced by VUV photon, and increased with substrate temperature. Ion bombardment induced surface densification, blocking radical diffusion. Two analytical models were derived to quantify the plasma damage. Based on the radical diffusion, reaction, and recombination inside porous low-k dielectrics, a plasma altered layer model was derived to interpret the chemical effect in the low ion energy region. It predicted that oxidative plasma induced damage can be reduced by decreasing pore radius, substrate temperature, and oxygen radical density and increasing carbon concentration and surface recombination rate inside low-k dielectrics. The model validity was verified by experiments and Monte-Carlo simulations. This model was also extended to the patterned low-k structure. Based on the ion collision cascade process, a sputtering yield model was introduced to interpret the physical effect in the high ion energy region. The model validity was verified by checking the ion angular and energy dependences of sputtering yield using O2/He/Ar plasma, low-k dielectrics with different k values, and a Faraday cage. Low-k dielectrics and plasma process were optimized to reduce plasma damage, including increasing carbon concentration in low-k dielectrics, switching plasma

  6. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    KAUST Repository

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Nová k, Zoltá n; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2011-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

  7. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    Science.gov (United States)

    Behenna, Douglas C.; Mohr, Justin T.; Sherden, Nathaniel H.; Marinescu, Smaranda C.; Harned, Andrew M.; Tani, Kousuke; Seto, Masaki; Ma, Sandy; Novák, Zoltán; Krout, Michael R.; McFadden, Ryan M.; Roizen, Jennifer L.; Enquist, John A.; White, David E.; Levine, Samantha R.; Petrova, Krastina V.; Iwashita, Akihiko; Virgil, Scott C.; Stoltz, Brian M.

    2012-01-01

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursors: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center. PMID:22083969

  8. Enantioselective Decarboxylative Alkylation Reactions: Catalyst Development, Substrate Scope, and Mechanistic Studies

    KAUST Repository

    Behenna, Douglas C.

    2011-11-14

    α-Quaternary ketones are accessed through novel enantioselective alkylations of allyl and propargyl electrophiles by unstabilized prochiral enolate nucleophiles in the presence of palladium complexes with various phosphinooxazoline (PHOX) ligands. Excellent yields and high enantiomeric excesses are obtained from three classes of enolate precursor: enol carbonates, enol silanes, and racemic β-ketoesters. Each of these substrate classes functions with nearly identical efficiency in terms of yield and enantioselectivity. Catalyst discovery and development, the optimization of reaction conditions, the exploration of reaction scope, and applications in target-directed synthesis are reported. Experimental observations suggest that these alkylation reactions occur through an unusual inner-sphere mechanism involving binding of the prochiral enolate nucleophile directly to the palladium center.

  9. Mechanistic studies aimed at the development of single site metal alkoxide catalysts for the production of polyoxygenates from renewable resources.

    Energy Technology Data Exchange (ETDEWEB)

    Chisholm, Malcolm H. [The Ohio State Univ., Columbus, OH (United States)

    2015-12-15

    The work proposed herein follows on directly from the existing 3 year grant and the request for funding is for 12 months to allow completion of this work and graduation of current students supported by DOE. The three primary projects are as follows. 1.) A comparative study of the reactivity of LMg(OR) (solvent), where L= a β-diiminate or pyrromethene ligand, in the ring-opening of cyclic esters. 2.) The homopolymerization of expoxides, particularly propylene oxide and styrene oxide, and their copolymerizations with carbon dioxide or organic anhydrides to yield polycarbonates or polyesters, respectively. 3.) The development of well-defined bismuth (III) complexes for ring-opening polymerizations that are tolerant of both air and water. In each of these topics special emphasis is placed on developing a detailed mechanistic understanding of the ring-opening event and how this is modified by the employment of specific metal and ligand combinations. This document also provides a report on findings of the past grant period that are not yet in the public domain/published and shows how the proposed work will bring the original project to conclusion.

  10. Mechanistic Indicators of Childhood Asthma (MICA) Study

    Science.gov (United States)

    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...

  11. Mechanistic studies of carbon monoxide reduction

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Development of Improved Mechanistic Deterioration Models for Flexible Pavements

    DEFF Research Database (Denmark)

    Ullidtz, Per; Ertman, Hans Larsen

    1998-01-01

    The paper describes a pilot study in Denmark with the main objective of developing improved mechanistic deterioration models for flexible pavements based on an accelerated full scale test on an instrumented pavement in the Danish Road Tessting Machine. The study was the first in "International...... Pavement Subgrade Performance Study" sponsored by the Federal Highway Administration (FHWA), USA. The paper describes in detail the data analysis and the resulting models for rutting, roughness, and a model for the plastic strain in the subgrade.The reader will get an understanding of the work needed...

  13. Mechanistic systems modeling to guide drug discovery and development.

    Science.gov (United States)

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

    2013-02-01

    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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Advanced reach tool (ART) : Development of the mechanistic model

    NARCIS (Netherlands)

    Fransman, W.; Tongeren, M. van; Cherrie, J.W.; Tischer, M.; Schneider, T.; Schinkel, J.; Kromhout, H.; Warren, N.; Goede, H.; Tielemans, E.

    2011-01-01

    This paper describes the development of the mechanistic model within a collaborative project, referred to as the Advanced REACH Tool (ART) project, to develop a tool to model inhalation exposure for workers sharing similar operational conditions across different industries and locations in Europe.

  15. Mechanistic considerations in benzene physiological model development.

    Science.gov (United States)

    Medinsky, M A; Kenyon, E M; Seaton, M J; Schlosser, P M

    1996-12-01

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites (hydroquinone and phenol, for example) may be necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergistic effect of phenol on myeloperoxidase-mediated oxidation of hydroquinone to the reactive metabolite benzoquinone. Because benzene and its hydroxylated metabolites (phenol, hydroquinone, and catechol) are substrates for the same cytochrome P450 enzymes, competitive interactions among the metabolites are possible. In vivo data on metabolite formation by mice exposed to various benzene concentrations are consistent with competitive inhibition of phenol oxidation by benzene. In vitro studies of the metabolic oxidation of benzene, phenol, and hydroquinone are consistent with the mechanism of competitive interaction among the metabolites. The dosimetry of benzene and its metabolites in the target tissue, bone marrow, depends on the balance of activation processes such as enzymatic oxidation and deactivation processes such as conjugation and excretion. Phenol, the primary benzene metabolite, can undergo both oxidation and conjugation. Thus the potential exists for competition among various enzymes for phenol. Zonal localization of phase I and phase II enzymes in various regions of the liver acinus also impacts this competition. Biologically based dosimetry models that incorporate the important determinants of benzene flux, including interactions with other chemicals, will enable prediction of target tissue doses of benzene and metabolites at low exposure concentrations relevant for humans.

  16. Cyclic voltammetry and reduction mechanistic studies of ...

    African Journals Online (AJOL)

    styrylpyrylium perchlorates have been evaluated using cyclic voltammetry, in comparison to their non-methylated derivatives values. The reduction peak of all studied compounds remained chemically irreversible. The presence of the ...

  17. Sorption data bases and mechanistic sorption studies

    International Nuclear Information System (INIS)

    Bradbury, M.H.

    2000-01-01

    In common with many other countries with a nuclear programme, the Swiss concept for the disposal of radioactive waste is focused on deep burial in specially constructed repositories in geologically stable host rocks. Under such conditions, the most likely means whereby radionuclides might return to the biosphere involves their transport in slowly moving groundwater. The sorption of radionuclides by solid phases in the engineered barriers within the repository, and in the surrounding geological media, limits their release and retards their movement. Performance assessment studies for disposal concepts are carried out by Nagra, the National Cooperative for the Disposal of Radioactive Waste, in which various release scenarios are examined, and 'doses to man' calculated. The uptake of radionuclides by immobile phases is one of the pillars upon which the safety case rests. Hence, sorption databases are very important data sets for performance assessments. The methodology lying behind the construction of sorption databases, and some aspects of the supporting experimental work, are briefly described in this report. Flexible, long-term, focused research programmes are required to properly understand the radionuclide/rock/groundwater system, and this is an essential pre-requisite for producing robust state-of-the-art sorption databases. (author)

  18. Sorption data bases and mechanistic sorption studies

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, M.H

    2000-07-01

    In common with many other countries with a nuclear programme, the Swiss concept for the disposal of radioactive waste is focused on deep burial in specially constructed repositories in geologically stable host rocks. Under such conditions, the most likely means whereby radionuclides might return to the biosphere involves their transport in slowly moving groundwater. The sorption of radionuclides by solid phases in the engineered barriers within the repository, and in the surrounding geological media, limits their release and retards their movement. Performance assessment studies for disposal concepts are carried out by Nagra, the National Cooperative for the Disposal of Radioactive Waste, in which various release scenarios are examined, and 'doses to man' calculated. The uptake of radionuclides by immobile phases is one of the pillars upon which the safety case rests. Hence, sorption databases are very important data sets for performance assessments. The methodology lying behind the construction of sorption databases, and some aspects of the supporting experimental work, are briefly described in this report. Flexible, long-term, focused research programmes are required to properly understand the radionuclide/rock/groundwater system, and this is an essential pre-requisite for producing robust state-of-the-art sorption databases. (author)

  19. Multiscale mechanistic modeling in pharmaceutical research and development.

    Science.gov (United States)

    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.

  20. Mechanistic studies of ethylene biosynthesis in higher plants

    International Nuclear Information System (INIS)

    McGeehan, G.M.

    1986-01-01

    Ethylene is a plant hormone that elicits a wide variety of responses in plant tissue. Among these responses are the hastening of abscission, ripening and senescence. In 1979 it was discovered that 1-amino-1-cyclopropane carboxylic acid is the immediate biosynthetic precursor to ethylene. Given the obvious economic significance of ethylene production the authors concentrated their studies on the conversion of ACC to ethylene. They delved into mechanistic aspects of ACC oxidation and they studied potential inhibitors of ethylene forming enzyme (EFE). They synthesized various analogs of ACC and found that EFE shows good stereodiscrimination among alkyl substituted ACC analogs with the 1R, 2S stereoisomer being processed nine times faster than the 1S, 2R isomer in the MeACC series. They also synthesized 2-cyclopropyl ACC which is a good competitive inhibitor of EFE. This compound also causes time dependent loss of EFE activity leading us to believe it is an irreversible inhibitor of ethylene formation. The synthesis of these analogs has also allowed them to develop a spectroscopic technique to assign the relative stereochemistry of alkyl groups. 13 C NMR allows them to assign the alkyl stereochemistry based upon gamma-shielding effects on the carbonyl resonance. Lastly, they measured kinetic isotope effects on the oxidation of ACC in vivo and in vitro and found that ACC is oxidized by a rate-determining 1-electron removal from nitrogen in close accord with mechanisms for the oxidation of other alkyl amines

  1. Refined pipe theory for mechanistic modeling of wood development.

    Science.gov (United States)

    Deckmyn, Gaby; Evans, Sam P; Randle, Tim J

    2006-06-01

    We present a mechanistic model of wood tissue development in response to changes in competition, management and climate. The model is based on a refinement of the pipe theory, where the constant ratio between sapwood and leaf area (pipe theory) is replaced by a ratio between pipe conductivity and leaf area. Simulated pipe conductivity changes with age, stand density and climate in response to changes in allocation or pipe radius, or both. The central equation of the model, which calculates the ratio of carbon (C) allocated to leaves and pipes, can be parameterized to describe the contrasting stem conductivity behavior of different tree species: from constant stem conductivity (functional homeostasis hypothesis) to height-related reduction in stem conductivity with age (hydraulic limitation hypothesis). The model simulates the daily growth of pipes (vessels or tracheids), fibers and parenchyma as well as vessel size and simulates the wood density profile and the earlywood to latewood ratio from these data. Initial runs indicate the model yields realistic seasonal changes in pipe radius (decreasing pipe radius from spring to autumn) and wood density, as well as realistic differences associated with the competitive status of trees (denser wood in suppressed trees).

  2. A preliminary study of mechanistic approach in pavement design to accommodate climate change effects

    Science.gov (United States)

    Harnaeni, S. R.; Pramesti, F. P.; Budiarto, A.; Setyawan, A.

    2018-03-01

    Road damage is caused by some factors, including climate changes, overload, and inappropriate procedure for material and development process. Meanwhile, climate change is a phenomenon which cannot be avoided. The effects observed include air temperature rise, sea level rise, rainfall changes, and the intensity of extreme weather phenomena. Previous studies had shown the impacts of climate changes on road damage. Therefore, several measures to anticipate the damage should be considered during the planning and construction in order to reduce the cost of road maintenance. There are three approaches generally applied in the design of flexible pavement thickness, namely mechanistic approach, mechanistic-empirical (ME) approach and empirical approach. The advantages of applying mechanistic approach or mechanistic-empirical (ME) approaches are its efficiency and reliability in the design of flexible pavement thickness as well as its capacity to accommodate climate changes in compared to empirical approach. However, generally, the design of flexible pavement thickness in Indonesia still applies empirical approach. This preliminary study aimed to emphasize the importance of the shifting towards a mechanistic approach in the design of flexible pavement thickness.

  3. MECHANISTIC STUDY OF COLCHICINE’s ELECTROCHEMICAL OXIDATION

    International Nuclear Information System (INIS)

    Bodoki, Ede; Chira, Ruxandra; Zaharia, Valentin; Săndulescu, Robert

    2015-01-01

    Colchicine, as one of the most ancient drugs of human kind, is still in the focal point of the current research due to its multimodal mechanism of action. The elucidation of colchicine’s still unknown redox properties may play an important role in deciphering its beneficial and harmful implications over the human body. Therefore, a systematic mechanistic study of colchicine’s oxidation has been undertaken by electrochemistry coupled to mass spectrometry using two different types of electrolytic cells, in order to clarify the existing inconsistencies with respect to this topic. At around 1 V vs. Pd/H 2 , initiated by a one-electron transfer, the oxidation of colchicine sets off leading to a cation radical, whose further oxidation may evolve on several different pathways. The main product of the anodic electrochemical reaction, regardless of the carrier solution’s pH is represented by a 7-hydroxy derivative of colchicine. At more anodic potentials (above 1.4 V vs. Pd/H 2 ) compounds arising from epoxidation and/or multiple hydroxylation occur. No di- or tridemethylated quinone structures, as previously suggested in the literature for the electrolytic oxidation of colchicine, has been detected in the mass spectra.

  4. Mechanistic Models for Process Development and Optimization of Fed-batch Fermentation Systems

    DEFF Research Database (Denmark)

    Mears, Lisa; Stocks, Stuart M.; Albæk, Mads O.

    2016-01-01

    This work discusses the application of mechanistic models to pilot scale filamentous fungal fermentation systems operated at Novozymes A/S. For on-line applications, a state estimator model is developed based on a stoichiometric balance in order to predict the biomass and product concentration....... This is based on on-line gas measurements and ammonia addition flow rate measurements. Additionally, a mechanistic model is applied offline as a tool for batch planning, based on definition of the process back pressure, aeration rate and stirrer speed. This allows the batch starting fill to be planned, taking...... into account the oxygen transfer conditions, as well as the evaporation rates of the system. Mechanistic models are valuable tools which are applicable for both process development and optimization. The state estimator described will be a valuable tool for future work as part of control strategy development...

  5. Mechanistic basis of otolith formation during teleost inner ear development.

    Science.gov (United States)

    Wu, David; Freund, Jonathan B; Fraser, Scott E; Vermot, Julien

    2011-02-15

    Otoliths, which are connected to stereociliary bundles in the inner ear, serve as inertial sensors for balance. In teleostei, otolith development is critically dependent on flow forces generated by beating cilia; however, the mechanism by which flow controls otolith formation remains unclear. Here, we have developed a noninvasive flow probe using optical tweezers and a viscous flow model in order to demonstrate how the observed hydrodynamics influence otolith assembly. We show that rotational flow stirs and suppresses precursor agglomeration in the core of the cilia-driven vortex. The velocity field correlates with the shape of the otolith and we provide evidence that hydrodynamics is actively involved in controlling otolith morphogenesis. An implication of this hydrodynamic effect is that otolith self-assembly is mediated by the balance between Brownian motion and cilia-driven flow. More generally, this flow feature highlights an alternative biological strategy for controlling particle localization in solution. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Mechanistic models for cancer development after short time radiation exposure

    International Nuclear Information System (INIS)

    Kottbauer, M. M.

    1997-12-01

    In this work two biological based models were developed. First the single-hit model for solid tumors (SHM-S) and second the single-hit model for leukemia (SHM-L). These models are a further development of the Armitage-Doll model for the special case of a short time radiation exposure. The basis of the models is the multistage process of carcinogeneses. The single-hit models provide simultaneously the age-dependent cancer-rate of spontaneous and radiation induced tumors as well as the dose-effect relationships at any age after exposure. The SHM-S leads to a biological based dose-effect relationship, which is similar to the relative risk model suggested by the ICRP 60. The SHM-S describes the increased mortality rate of the bomb survivors more accurate than the relative risk model. The SHM-L results in an additive dose-effect relationship. It is shown that only small differences in the derivation of the two models lead to the two dose-effect relationships. Beside the radiation exposure the new models consider the decrease of the cancer mortality rate at higher ages (age>75) which can be traced back mainly to three causes: competitive causes of death, reduction of cell proliferation and reduction of risk groups. The single-hit models also consider children cancer, the different rates of incidence and mortality, influence of the immune system and the cell-killing effect. (author)

  7. Mechanistic study of aerosol dry deposition on vegetated canopies

    International Nuclear Information System (INIS)

    Petroff, A.

    2005-04-01

    The dry deposition of aerosols onto vegetated canopies is modelled through a mechanistic approach. The interaction between aerosols and vegetation is first formulated by using a set of parameters, which are defined at the local scale of one surface. The overall deposition is then deduced at the canopy scale through an up-scaling procedure based on the statistic distribution parameters. This model takes into account the canopy structural and morphological properties, and the main characteristics of the turbulent flow. Deposition mechanisms considered are Brownian diffusion, interception, initial and turbulent impaction, initially with coniferous branches and then with entire canopies of different roughness, such as grass, crop field and forest. (author)

  8. Utilizing Mechanistic Cross-Linking Technology to Study Protein-Protein Interactions: An Experiment Designed for an Undergraduate Biochemistry Lab

    Science.gov (United States)

    Finzel, Kara; Beld, Joris; Burkart, Michael D.; Charkoudian, Louise K.

    2017-01-01

    Over the past decade, mechanistic cross-linking probes have been used to study protein-protein interactions in natural product biosynthetic pathways. This approach is highly interdisciplinary, combining elements of protein biochemistry, organic chemistry, and computational docking. Herein, we described the development of an experiment to engage…

  9. Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Casey, Charles P

    2012-11-14

    Mechanistic Studies at the Interface Between Organometallic Chemistry and Homogeneous Catalysis Charles P. Casey, Principal Investigator Department of Chemistry, University of Wisconsin - Madison, Madison, Wisconsin 53706 Phone 608-262-0584 FAX: 608-262-7144 Email: casey@chem.wisc.edu http://www.chem.wisc.edu/main/people/faculty/casey.html Executive Summary. Our goal was to learn the intimate mechanistic details of reactions involved in homogeneous catalysis and to use the insight we gain to develop new and improved catalysts. Our work centered on the hydrogenation of polar functional groups such as aldehydes and ketones and on hydroformylation. Specifically, we concentrated on catalysts capable of simultaneously transferring hydride from a metal center and a proton from an acidic oxygen or nitrogen center to an aldehyde or ketone. An economical iron based catalyst was developed and patented. Better understanding of fundamental organometallic reactions and catalytic processes enabled design of energy and material efficient chemical processes. Our work contributed to the development of catalysts for the selective and mild hydrogenation of ketones and aldehydes; this will provide a modern green alternative to reductions by LiAlH4 and NaBH4, which require extensive work-up procedures and produce waste streams. (C5R4OH)Ru(CO)2H Hydrogenation Catalysts. Youval Shvo described a remarkable catalytic system in which the key intermediate (C5R4OH)Ru(CO)2H (1) has an electronically coupled acidic OH unit and a hydridic RuH unit. Our efforts centered on understanding and improving upon this important catalyst for reduction of aldehydes and ketones. Our mechanistic studies established that the reduction of aldehydes by 1 to produce alcohols and a diruthenium bridging hydride species occurs much more rapidly than regeneration of the ruthenium hydride from the diruthenium bridging hydride species. Our mechanistic studies require simultaneous transfer of hydride from ruthenium to

  10. Regulatory Technology Development Plan - Sodium Fast Reactor: Mechanistic Source Term - Trial Calculation

    International Nuclear Information System (INIS)

    Grabaskas, David

    2016-01-01

    The potential release of radioactive material during a plant incident, referred to as the source term, is a vital design metric and will be a major focus of advanced reactor licensing. The U.S. Nuclear Regulatory Commission has stated an expectation for advanced reactor vendors to present a mechanistic assessment of the potential source term in their license applications. The mechanistic source term presents an opportunity for vendors to realistically assess the radiological consequences of an incident, and may allow reduced emergency planning zones and smaller plant sites. However, the development of a mechanistic source term for advanced reactors is not without challenges, as there are often numerous phenomena impacting the transportation and retention of radionuclides. This project sought to evaluate U.S. capabilities regarding the mechanistic assessment of radionuclide release from core damage incidents at metal fueled, pool-type sodium fast reactors (SFRs). The purpose of the analysis was to identify, and prioritize, any gaps regarding computational tools or data necessary for the modeling of radionuclide transport and retention phenomena. To accomplish this task, a parallel-path analysis approach was utilized. One path, led by Argonne and Sandia National Laboratories, sought to perform a mechanistic source term assessment using available codes, data, and models, with the goal to identify gaps in the current knowledge base. The second path, performed by an independent contractor, performed sensitivity analyses to determine the importance of particular radionuclides and transport phenomena in regards to offsite consequences. The results of the two pathways were combined to prioritize gaps in current capabilities.

  11. Regulatory Technology Development Plan - Sodium Fast Reactor: Mechanistic Source Term – Trial Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Grabaskas, David [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Bucknor, Matthew [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Jerden, James [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Brunett, Acacia J. [Argonne National Lab. (ANL), Argonne, IL (United States). Nuclear Engineering Division; Denman, Matthew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nuclear Engineering Division; Clark, Andrew [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Nuclear Engineering Division; Denning, Richard S. [Consultant, Columbus, OH (United States)

    2016-10-01

    The potential release of radioactive material during a plant incident, referred to as the source term, is a vital design metric and will be a major focus of advanced reactor licensing. The U.S. Nuclear Regulatory Commission has stated an expectation for advanced reactor vendors to present a mechanistic assessment of the potential source term in their license applications. The mechanistic source term presents an opportunity for vendors to realistically assess the radiological consequences of an incident, and may allow reduced emergency planning zones and smaller plant sites. However, the development of a mechanistic source term for advanced reactors is not without challenges, as there are often numerous phenomena impacting the transportation and retention of radionuclides. This project sought to evaluate U.S. capabilities regarding the mechanistic assessment of radionuclide release from core damage incidents at metal fueled, pool-type sodium fast reactors (SFRs). The purpose of the analysis was to identify, and prioritize, any gaps regarding computational tools or data necessary for the modeling of radionuclide transport and retention phenomena. To accomplish this task, a parallel-path analysis approach was utilized. One path, led by Argonne and Sandia National Laboratories, sought to perform a mechanistic source term assessment using available codes, data, and models, with the goal to identify gaps in the current knowledge base. The second path, performed by an independent contractor, performed sensitivity analyses to determine the importance of particular radionuclides and transport phenomena in regards to offsite consequences. The results of the two pathways were combined to prioritize gaps in current capabilities.

  12. Mechanistic studies of copper(I)-catalyzed 1,3-halogen migration.

    Science.gov (United States)

    Van Hoveln, Ryan; Hudson, Brandi M; Wedler, Henry B; Bates, Desiree M; Le Gros, Gabriel; Tantillo, Dean J; Schomaker, Jennifer M

    2015-04-29

    An ongoing challenge in modern catalysis is to identify and understand new modes of reactivity promoted by earth-abundant and inexpensive first-row transition metals. Herein, we report a mechanistic study of an unusual copper(I)-catalyzed 1,3-migration of 2-bromostyrenes that reincorporates the bromine activating group into the final product with concomitant borylation of the aryl halide bond. A combination of experimental and computational studies indicated this reaction does not involve any oxidation state changes at copper; rather, migration occurs through a series of formal sigmatropic shifts. Insight provided from these studies will be used to expand the utility of aryl copper species in synthesis and develop new ligands for enantioselective copper-catalyzed halogenation.

  13. A holistic approach to anesthesia-induced neurotoxicity and its implications for future mechanistic studies.

    Science.gov (United States)

    Zanghi, Christine N; Jevtovic-Todorovic, Vesna

    The year 2016 marked the 15th anniversary since anesthesia-induced developmental neurotoxicity and its resulting cognitive dysfunction were first described. Since that time, multiple scientific studies have supported these original findings and investigated possible mechanisms behind anesthesia-induced neurotoxicity. This paper reviews the existing mechanistic literature on anesthesia-induced neurotoxicity in the context of a holistic approach that emphasizes the importance of both neuronal and non-neuronal cells during early postnatal development. Sections are divided into key stages in early neural development; apoptosis, neurogenesis, migration, differentiation, synaptogenesis, gliogenesis, myelination and blood brain barrier/cerebrovasculature. In addition, the authors combine the established literature in the field of anesthesia-induced neurotoxicity with literature from other related scientific fields to speculate on the potential role of non-neuronal cells and to generate new future hypotheses for understanding anesthetic toxicity and its application to the practice of pediatric anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Productivity of "Collisions Generate Heat" for Reconciling an Energy Model with Mechanistic Reasoning: A Case Study

    Science.gov (United States)

    Scherr, Rachel E.; Robertson, Amy D.

    2015-01-01

    We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a…

  15. Development of a mechanistically based computer simulation of nitrogen oxide absorption in packed towers

    International Nuclear Information System (INIS)

    Counce, R.M.

    1981-01-01

    A computer simulation for nitrogen oxide (NO/sub x/) scrubbing in packed towers was developed for use in process design and process control. This simulation implements a mechanistically based mathematical model, which was formulated from (1) an exhaustive literature review; (2) previous NO/sub x/ scrubbing experience with sieve-plate towers; and (3) comparisons of sequential sets of experiments. Nitrogen oxide scrubbing is characterized by simultaneous absorption and desorption phenomena: the model development is based on experiments designed to feature these two phenomena. The model was then successfully tested in experiments designed to put it in jeopardy

  16. A mechanistic understanding of ageing revealed by studying the young.

    Science.gov (United States)

    Crespi, Erica J

    2012-03-01

    A main focus within biomedical research is to understand how adverse environmental conditions experienced during early development affects lifelong health (Barker 1992). Within this context, extensive research in rodent models and humans has shown that intrauterine growth retardation (IUGR) caused by nutrient restriction during early development is often followed by post-natal 'catch-up' growth when access to food resources improves. However, this accelerated growth rate seems to come at a cost, as metabolic and endocrine processes that are programmed during this time cause later-life onset of diseases such as obesity, insulin resistance and cardiovascular disease (reviewed in Crespi & Denver 2005). In this issue Molecular Ecology, Geiger et al. (2012) asked what are the costs of catch-up growth in nutrient-restricted king penguin chicks (Fig. 1) by measuring lengths of telomeres, the protective DNA sequences at the end of chromosomes, before and after catch-up growth, as the amount and rate of telomere sequence loss over time has been associated with reduced lifespan in both model and nonmodel organisms (see reviews of Costantini et al. 2010; Haussmann & Marchetto 2010). Geiger et al. (2011) found that chicks entering the post-winter growth season at a smaller size exhibited increased growth rates (i.e. catch-up growth) at the cost of increased oxidative stress and reduced telomere lengths compared with the chicks entering the growth period at a larger size. Furthermore, chicks that did not survive had drastically shorter telomere lengths and reduced antioxidant capacities at the beginning of the growth period than all other chicks, thereby directly associating telomere length to mortality. These results suggest that while catch-up growth allows smaller chicks to head off into the world on equal footing with chicks that hatched at a larger size, it likely comes at the cost of a shortened lifespan. Thus, this study provides a mechanism that supports the

  17. Mechanistic studies of the agmatine deiminase from Listeria monocytogenes.

    Science.gov (United States)

    Soares, Charles A; Knuckley, Bryan

    2016-06-01

    Listeria monocytogenes is a Gram-positive food-borne pathogen that is capable of living within extreme environments (i.e. low temperatures and pH). This ability to survive in such conditions may arise, at least in part, from agmatine catabolism via the agmatine deiminase system (AgDS). This catabolic pathway utilizes an agmatine deiminase (AgD) to hydrolyse agmatine into N-carbamoylputrescine (NCP), with concomitant release of ammonia, which increases the pH, thus mitigating the ill effects of the acidic environment. Given the potential significance of this pathway for cell survival, we set out to study the catalytic mechanism of the AgD encoded by L. monocytogenes In the present paper, we describe the catalytic mechanism employed by this enzyme based on pH profiles, pKa measurements of the active site cysteine and solvent isotope effects (SIE). In addition, we report inhibition of this enzyme by two novel AgD inhibitors, i.e. N-(4-aminobutyl)-2-fluoro-ethanimidamide (ABFA) and N-(4-aminobutyl)-2-chloro-ethanimidamide (ABCA). In contrast with other orthologues, L. monocytogenes AgD does not use the reverse protonation or substrate-assisted mechanism, which requires an active site cysteine with a high pKa and has been commonly seen in other members of the guanidinium-modifying enzyme (GME) superfamily. Instead, the L. monocytogenes AgD has a low pKa cysteine in the active site leading to an alternative mechanism of catalysis. This is the first time that this mechanism has been observed in the GME superfamily and is significant because it explains why previously developed mechanism-based inactivators of AgDs are ineffective against this orthologue. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  18. Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation: Report of an FDA Public Workshop.

    Science.gov (United States)

    Zhang, X; Duan, J; Kesisoglou, F; Novakovic, J; Amidon, G L; Jamei, M; Lukacova, V; Eissing, T; Tsakalozou, E; Zhao, L; Lionberger, R

    2017-08-01

    On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling and Simulation for Formulation Development and Bioequivalence Evaluation." The topic of mechanistic oral absorption modeling, which is one of the major applications of physiologically based pharmacokinetic (PBPK) modeling and simulation, focuses on predicting oral absorption by mechanistically integrating gastrointestinal transit, dissolution, and permeation processes, incorporating systems, active pharmaceutical ingredient (API), and the drug product information, into a systemic mathematical whole-body framework. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Atomization of bismuthane in a dielectric barrier discharge: A mechanistic study

    Czech Academy of Sciences Publication Activity Database

    Kratzer, Jan; Zelina, Ondřej; Svoboda, Milan; Sturgeon, R. E.; Mester, Z.; Dědina, Jiří

    2016-01-01

    Roč. 88, č. 3 (2016), s. 1804-1811 ISSN 0003-2700 R&D Projects: GA ČR GA14-23532S Grant - others:GA AV ČR(CZ) M200311202 Institutional support: RVO:68081715 Keywords : dielectric barrier discharge * hydride generation * mechanistic study Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 6.320, year: 2016

  1. Atomization of bismuthane in a dielectric barrier discharge: A mechanistic study

    Czech Academy of Sciences Publication Activity Database

    Kratzer, Jan; Zelina, Ondřej; Svoboda, Milan; Sturgeon, R. E.; Mester, Z.; Dědina, Jiří

    2016-01-01

    Roč. 88, č. 3 (2016), s. 1804-1811 ISSN 0003-2700 R&D Projects: GA ČR GA14-23532S Grant - others:GA AV ČR(CZ) M200311202 Institutional support: RVO:68081715 Keywords : dielectric barrier discharge * hydride generation * mechanistic study Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 6.320, year: 2016

  2. A MECHANISTIC STUDY OF RHODIUM TRI(ORTHO-TERT-BUTYLPHENYL)PHOSPHITE COMPLEXES AS HYDROFORMYLATION CATALYSTS

    NARCIS (Netherlands)

    JONGSMA, T; CHALLA, G; VANLEEUWEN, PWNM

    1991-01-01

    A mechanistic study of the hydroformylation cycle with a rhodium tri(o-t-butylphenyl)phosphite complex as catalyst is presented. Spectroscopic experiments prove that under hydroformylation conditions this complex is coordinated by only one phosphite. The complex has a high activity in the

  3. Spatially confined photoinactivation of bacteria: towards novel tools for detailed mechanistic studies

    Science.gov (United States)

    Thomsen, Hanna; James, Jeemol; Farewell, Anne; Ericson, Marica B.

    2018-02-01

    Antimicrobial resistance is a serious global threat fueling an accelerated field of research aimed at developing novel antimicrobial therapies. A particular challenge is the treatment of microbial biofilms formed upon bacterial growth and often associated with chronic infections. Biofilms comprise bacteria that have adhered to a surface and formed 3D microcolonies, and demonstrate significantly increased antimicrobial resistance compared to the planktonic counterpart. A challenge in developing novel strategies for fighting these chronic infections is a lack of mechanistic understanding of what primarily contributes to enhanced drug resistance. Tools for noninvasive study of live biofilms are necessary to begin to understand these mechanisms on both a single cell and 3D level. Herein, a method by which multiphoton microscopy is implemented to study a biofilm model of Staphylococcus epidermidis to noninvasively visualize and measure penetration of compounds in 3D biofilm structure and two photon excitation was exploited for spatially confined photoinactivation and microscopy optimized for evaluation of microbiological viability at a microscopic level. Future studies are aimed at future development of the proposed techniques for detailed studies of, e.g., quorum sensing and mechanisms contributing to antimicrobial resistance.

  4. Synthesis and mechanistic studies of phosphoraziridines as radiation sensitizers

    International Nuclear Information System (INIS)

    Perlman, M.E.

    1982-01-01

    Ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinyl carbamate (AB-132) and ethyl bis(2,2-dimethyl-1-aziridinyl)phosphinate (AB-163) are potent antitumor agents which have also been demonstrated to be radiation sensitizers in experimental and clinical studies. Monophenyl aziridines and various isomers of diphenylaziridines were utilized. Optically active 2-phenyl aziridine was also employed in order to prepare diastereomerically homogeneous compounds. Para-substituted phenylaziridines were prepared as well and converted to the corresponding phosphoraziridines in order to probe electronic effects of such substituents on biological activity and chemical reactivity. The hydrolysis of 2,2-dimethylaziridine-type compounds including AB-132 and AB-163 was studied by NMR in order to gain further insight into the hydrolytic intermediates which may be responsible for the known cholinesterase inhibition and the suspected phosphorylation of radiation-damaged DNA. Comparative reactivities of the compounds prepared in this study with p-nitrobenzylpyridine were investigated so as to provide some indication of potential alkylating activity, in the hope of obtaining a correlation with biological activity. Electron spin resonance was utilized to study the effects of radiation on phosphoraziridine crystals

  5. Process optimization and mechanistic studies of lead (II): Aspergillus ...

    African Journals Online (AJOL)

    The lead (II) accumulation potential of various biosorbent had been widely studied in the last few years, but an outstanding Pb(II) accumulating biomass still seems crucial for bringing the process to a successful application stage. This investigation describes the use of non-living biomass of Aspergillus caespitosus for ...

  6. Regulatory Technology Development Plan Sodium Fast Reactor. Mechanistic Source Term Development

    Energy Technology Data Exchange (ETDEWEB)

    Grabaskas, David S. [Argonne National Lab. (ANL), Argonne, IL (United States); Brunett, Acacia Joann [Argonne National Lab. (ANL), Argonne, IL (United States); Bucknor, Matthew D. [Argonne National Lab. (ANL), Argonne, IL (United States); Sienicki, James J. [Argonne National Lab. (ANL), Argonne, IL (United States); Sofu, Tanju [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-02-28

    Construction and operation of a nuclear power installation in the U.S. requires licensing by the U.S. Nuclear Regulatory Commission (NRC). A vital part of this licensing process and integrated safety assessment entails the analysis of a source term (or source terms) that represents the release of radionuclides during normal operation and accident sequences. Historically, nuclear plant source term analyses have utilized deterministic, bounding assessments of the radionuclides released to the environment. Significant advancements in technical capabilities and the knowledge state have enabled the development of more realistic analyses such that a mechanistic source term (MST) assessment is now expected to be a requirement of advanced reactor licensing. This report focuses on the state of development of an MST for a sodium fast reactor (SFR), with the intent of aiding in the process of MST definition by qualitatively identifying and characterizing the major sources and transport processes of radionuclides. Due to common design characteristics among current U.S. SFR vendor designs, a metal-fuel, pool-type SFR has been selected as the reference design for this work, with all phenomenological discussions geared toward this specific reactor configuration. This works also aims to identify the key gaps and uncertainties in the current knowledge state that must be addressed for SFR MST development. It is anticipated that this knowledge state assessment can enable the coordination of technology and analysis tool development discussions such that any knowledge gaps may be addressed. Sources of radionuclides considered in this report include releases originating both in-vessel and ex-vessel, including in-core fuel, primary sodium and cover gas cleanup systems, and spent fuel movement and handling. Transport phenomena affecting various release groups are identified and qualitatively discussed, including fuel pin and primary coolant retention, and behavior in the cover gas and

  7. Cyclic voltammetry and reduction mechanistic studies of styrylpyrylium perchlorates

    Directory of Open Access Journals (Sweden)

    Y. L. Bonzi-Coulibaly

    2013-04-01

    Full Text Available The reduction and oxidation potentials of methylated 4-styrylpyrylium and 6-styrylpyrylium perchlorates have been evaluated using cyclic voltammetry, in comparison to their non-methylated derivatives values. The reduction peak of all studied compounds remained chemically irreversible. The presence of the electron-donating methyl group on pyrylium ring leads to a shift of the styrylpyrylium perchlorates reduction potential towards cathodic values. Kinetic studies on platinum electrodes based on the variation of the peak potential at different scan rates and upon substrate concentrations confirm, in another way, the mechanism of electron transfer.DOI: http://dx.doi.org/10.4314/bcse.v27i1.12

  8. Mechanistic studies of neoplastic cell transformation by ionizing radiation

    International Nuclear Information System (INIS)

    Yang, T.C.; Craise, L.M.; Tobias, C.A.

    1982-01-01

    As part of the Biology and Medicine heavy-ion radiation program, we are systematically investigating the potential carcinogenic and mutagenic effects of high- and low-linear energy transfer (LET) radiation at the cellular level. From these studies, we anticipate additional insight into the molecular and cellular mechanisms of radiation carcinogenesis. Such results should provide quantitative information useful for assessing the undesirable biological effects of cosmic rays in space. Some of our recent experimental results are presented here

  9. Structural and mechanistic studies of measles virus illuminate paramyxovirus entry.

    Directory of Open Access Journals (Sweden)

    Richard K Plemper

    2011-06-01

    Full Text Available Measles virus (MeV, a member of the paramyxovirus family of enveloped RNA viruses and one of the most infectious viral pathogens identified, accounts for major pediatric morbidity and mortality worldwide although coordinated efforts to achieve global measles control are in place. Target cell entry is mediated by two viral envelope glycoproteins, the attachment (H and fusion (F proteins, which form a complex that achieves merger of the envelope with target cell membranes. Despite continually expanding knowledge of the entry strategies employed by enveloped viruses, our molecular insight into the organization of functional paramyxovirus fusion complexes and the mechanisms by which the receptor binding by the attachment protein triggers the required conformational rearrangements of the fusion protein remain incomplete. Recently reported crystal structures of the MeV attachment protein in complex with its cellular receptors CD46 or SLAM and newly developed functional assays have now illuminated some of the fundamental principles that govern cell entry by this archetype member of the paramyxovirus family. Here, we review these advances in our molecular understanding of MeV entry in the context of diverse entry strategies employed by other members of the paramyxovirus family.

  10. Silicene catalyzed reduction of nitrobenzene to aniline: A mechanistic study

    Science.gov (United States)

    Morrissey, Christopher; He, Haiying

    2018-03-01

    The reduction of nitrobenzene to aniline has broad applications in chemical and pharmaceutical industries. The high reaction temperatures and pressures and unavoidable hazardous chemicals of current metal catalysts call for more environmentally friendly non-metal catalysts. In this study, the plausibility of silicene as a potential catalyst for nitrobenzene reduction is investigated with a focus on the distinct reaction mechanism based on the density functional theory. The direct reaction pathway was shown to be distinctly different from the Haber mechanism following PhNO2∗ → PhNO∗ → PhNHO∗ → PhNH2O∗ → PhNH2∗. The hydroxyl groups remain bound to silicene after aniline is formed and acquire a high activation barrier to remove.

  11. Mechanistic studies on the reaction of 0-phthaladehyde

    International Nuclear Information System (INIS)

    Maliha, B.; Siddiqui, H.L.; Hussain, I.; Ilyas, M.

    2009-01-01

    Urea and its N-alkyl/aryl derivatives react with o-phthalaldehyde (OPT A) to yield blue to purple coloration along-with isoindoline compounds (VII a,b,c) in acidic media. The color is unstable and changes into various shades with the passage of the time. The assay of urea which entirely depends upon this color does not suggest its determination with OPTA present in biological and non-biological fluids. Moreover, it is found that compounds which enhance color stability have nothing to do with determination of urea. The structures of isoindolines (VII a,b,c) have been confirmed by IH-, 13C-NMR and mass spectrometry techniques. The absolute authenticity comes from their (VII a,b,c) X-ray crystallography. The colors resulting from the said reactions fall in between 585-595 nm in UV/VIS spectra. As the use of OPTA for urea determination is known, hence, in this study, we are presenting chemistry for urea determination with OPTA. (author)

  12. Mechanistic study on exchange between labeled cyanide and nitriles

    International Nuclear Information System (INIS)

    Hussain, Munir; Chaney, J.E.; Digenis, G.A.; Layton, W.J.

    1985-01-01

    The potential of a clean, rapid exchange between the nitrile function of mandelonitrile and cyanide was examined for the preparation of labeled mandelonitrile which could be subsequently rapidly reduced with borane to labeled phenylethanolamine (PEOH). The mandelonitrile exchange (CN-CN) was studied using [ 13 C]-NaCN with crown ethers in THF, monitoring the results with 13 C-NMR. A large increase in the intensity of the signal due to [ 13 C]-nitrile was observed. The exchange was also carried out using [ 14 C]-NaCN, and the exchanged nitrile was reduced to [ 14 C]-PEOH. The chemical yield for the reduction of [ 14 C]-mandelonitrile to [ 14 C]-PEOH was 60% and the overall radio-chemical yield of the cyanide-exchange and borane reduction (based on [ 14 C]-NaCN used) was 20%. Mechanisms are proposed which were found to be consistent with results of cyanide exchange of appropriately selected nitriles. (author)

  13. Electrochemistry and spectroelectrochemistry of bioactive hydroxyquinolines: a mechanistic study.

    Science.gov (United States)

    Sokolová, Romana; Nycz, Jacek E; Ramešová, Šárka; Fiedler, Jan; Degano, Ilaria; Szala, Marcin; Kolivoška, Viliam; Gál, Miroslav

    2015-05-21

    The oxidation mechanism of selected hydroxyquinoline carboxylic acids such as 8-hydroxyquinoline-7-carboxylic acid (1), the two positional isomers 2-methyl-8-hydroxyquinoline-7-carboxylic acid (3) and 2-methyl-5-hydroxyquinoline-6-carboxylic acid (4), as well as other hydroxyquinolines were studied in aprotic environment using cyclic voltammetry, controlled potential electrolysis, in situ UV-vis and IR spectroelectrochemistry, and HPLC-MS/MS techniques. IR spectroelectrochemistry showed that oxidation unexpectedly proceeds together with protonation of the starting compound. We proved that the nitrogen atom in the heterocycle of hydroxyquinolines is protonated during the apparent 0.7 electron oxidation process. This was rationalized by the autodeprotonation reaction by another two starting molecules of hydroxyquinoline, so that the overall oxidation mechanism involves two electrons and three starting molecules. Both the electrochemical and spectroelectrochemical results showed that the oxidation mechanism is not influenced by the presence of the carboxylic group in the chemical structure of hydroxyquinolines, as results from oxidation of 2,7-dimethyl-5-hydroxyquinoline (6). In the presence of a strong proton acceptor such as pyridine, the oxidation ECEC process involves two electrons and two protons per one molecule of the hydroxyquinoline derivative. The electron transfer efficiency of hydroxyquinolines in biosystems may be related to protonation of biocompounds containing nitrogen bases. Molecular orbital calculations support the experimental findings.

  14. Development of mechanistic sorption model and treatment of uncertainties for Ni sorption on montmorillonite/bentonite

    International Nuclear Information System (INIS)

    Ochs, Michael; Ganter, Charlotte; Tachi, Yukio; Suyama, Tadahiro; Yui, Mikazu

    2011-02-01

    Sorption and diffusion of radionuclides in buffer materials (bentonite) are the key processes in the safe geological disposal of radioactive waste, because migration of radionuclides in this barrier is expected to be diffusion-controlled and retarded by sorption processes. It is therefore necessary to understand the detailed/coupled processes of sorption and diffusion in compacted bentonite and develop mechanistic /predictive models, so that reliable parameters can be set under a variety of geochemical conditions relevant to performance assessment (PA). For this purpose, JAEA has developed the integrated sorption and diffusion (ISD) model/database in montmorillonite/bentonite systems. The main goal of the mechanistic model/database development is to provide a tool for a consistent explanation, prediction, and uncertainty assessment of K d as well as diffusion parameters needed for the quantification of radionuclide transport. The present report focuses on developing the thermodynamic sorption model (TSM) and on the quantification and handling of model uncertainties in applications, based on illustrating by example of Ni sorption on montmorillonite/bentonite. This includes 1) a summary of the present state of the art of thermodynamic sorption modeling, 2) a discussion of the selection of surface species and model design appropriate for the present purpose, 3) possible sources and representations of TSM uncertainties, and 4) details of modeling, testing and uncertainty evaluation for Ni sorption. Two fundamentally different approaches are presented and compared for representing TSM uncertainties: 1) TSM parameter uncertainties calculated by FITEQL optimization routines and some statistical procedure, 2) overall error estimated by direct comparison of modeled and experimental K d values. The overall error in K d is viewed as the best representation of model uncertainty in ISD model/database development. (author)

  15. Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.

    Science.gov (United States)

    Ainsbury, Elizabeth A; Barnard, Stephen; Bright, Scott; Dalke, Claudia; Jarrin, Miguel; Kunze, Sarah; Tanner, Rick; Dynlacht, Joseph R; Quinlan, Roy A; Graw, Jochen; Kadhim, Munira; Hamada, Nobuyuki

    The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  16. Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Metal Fuel Radionuclide Release

    International Nuclear Information System (INIS)

    Grabaskas, David; Bucknor, Matthew; Jerden, James

    2016-01-01

    The development of an accurate and defensible mechanistic source term will be vital for the future licensing efforts of metal fuel, pool-type sodium fast reactors. To assist in the creation of a comprehensive mechanistic source term, the current effort sought to estimate the release fraction of radionuclides from metal fuel pins to the primary sodium coolant during fuel pin failures at a variety of temperature conditions. These release estimates were based on the findings of an extensive literature search, which reviewed past experimentation and reactor fuel damage accidents. Data sources for each radionuclide of interest were reviewed to establish release fractions, along with possible release dependencies, and the corresponding uncertainty levels. Although the current knowledge base is substantial, and radionuclide release fractions were established for the elements deemed important for the determination of offsite consequences following a reactor accident, gaps were found pertaining to several radionuclides. First, there is uncertainty regarding the transport behavior of several radionuclides (iodine, barium, strontium, tellurium, and europium) during metal fuel irradiation to high burnup levels. The migration of these radionuclides within the fuel matrix and bond sodium region can greatly affect their release during pin failure incidents. Post-irradiation examination of existing high burnup metal fuel can likely resolve this knowledge gap. Second, data regarding the radionuclide release from molten high burnup metal fuel in sodium is sparse, which makes the assessment of radionuclide release from fuel melting accidents at high fuel burnup levels difficult. This gap could be addressed through fuel melting experimentation with samples from the existing high burnup metal fuel inventory.

  17. Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Metal Fuel Radionuclide Release

    Energy Technology Data Exchange (ETDEWEB)

    Grabaskas, David [Argonne National Lab. (ANL), Argonne, IL (United States); Bucknor, Matthew [Argonne National Lab. (ANL), Argonne, IL (United States); Jerden, James [Argonne National Lab. (ANL), Argonne, IL (United States)

    2016-02-01

    The development of an accurate and defensible mechanistic source term will be vital for the future licensing efforts of metal fuel, pool-type sodium fast reactors. To assist in the creation of a comprehensive mechanistic source term, the current effort sought to estimate the release fraction of radionuclides from metal fuel pins to the primary sodium coolant during fuel pin failures at a variety of temperature conditions. These release estimates were based on the findings of an extensive literature search, which reviewed past experimentation and reactor fuel damage accidents. Data sources for each radionuclide of interest were reviewed to establish release fractions, along with possible release dependencies, and the corresponding uncertainty levels. Although the current knowledge base is substantial, and radionuclide release fractions were established for the elements deemed important for the determination of offsite consequences following a reactor accident, gaps were found pertaining to several radionuclides. First, there is uncertainty regarding the transport behavior of several radionuclides (iodine, barium, strontium, tellurium, and europium) during metal fuel irradiation to high burnup levels. The migration of these radionuclides within the fuel matrix and bond sodium region can greatly affect their release during pin failure incidents. Post-irradiation examination of existing high burnup metal fuel can likely resolve this knowledge gap. Second, data regarding the radionuclide release from molten high burnup metal fuel in sodium is sparse, which makes the assessment of radionuclide release from fuel melting accidents at high fuel burnup levels difficult. This gap could be addressed through fuel melting experimentation with samples from the existing high burnup metal fuel inventory.

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

    Science.gov (United States)

    INCORPORATING MECHANISTIC INSIGHTS IN A PBPK MODEL FOR ARSENICElaina M. Kenyon, Michael F. Hughes, Marina V. Evans, David J. Thomas, U.S. EPA; Miroslav Styblo, University of North Carolina; Michael Easterling, Analytical Sciences, Inc.A physiologically based phar...

  19. Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.

    Science.gov (United States)

    Yadav, Rajbharan; Bulitta, Jürgen B; Schneider, Elena K; Shin, Beom Soo; Velkov, Tony; Nation, Roger L; Landersdorfer, Cornelia B

    2017-12-01

    This study aimed to systematically identify the aminoglycoside concentrations required for synergy with a carbapenem and characterize the permeabilizing effect of aminoglycosides on the outer membrane of Pseudomonas aeruginosa Monotherapies and combinations of four aminoglycosides and three carbapenems were studied for activity against P. aeruginosa strain AH298-GFP in 48-h static-concentration time-kill studies (SCTK) (inoculum: 10 7.6 CFU/ml). The outer membrane-permeabilizing effect of tobramycin alone and in combination with imipenem was characterized via electron microscopy, confocal imaging, and the nitrocefin assay. A mechanism-based model (MBM) was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by imipenem combined with each of the four aminoglycosides. Notably, 0.25 mg/liter of tobramycin, which was inactive in monotherapy, achieved synergy (i.e., ≥2-log 10 more killing than the most active monotherapy at 24 h) combined with imipenem. Electron micrographs, confocal image analyses, and the nitrocefin uptake data showed distinct outer membrane damage by tobramycin, which was more extensive for the combination with imipenem. The MBM indicated that aminoglycosides enhanced the imipenem target site concentration up to 4.27-fold. Tobramycin was the most potent aminoglycoside to permeabilize the outer membrane; tobramycin (0.216 mg/liter), gentamicin (0.739 mg/liter), amikacin (1.70 mg/liter), or streptomycin (5.19 mg/liter) was required for half-maximal permeabilization. In summary, our SCTK, mechanistic studies and MBM indicated that tobramycin was highly synergistic and displayed the maximum outer membrane disruption potential among the tested aminoglycosides. These findings support the optimization of highly promising antibiotic combination dosage regimens for critically ill patients. Copyright © 2017 American Society for Microbiology.

  20. Recognizing Mechanistic Reasoning in Student Scientific Inquiry: A Framework for Discourse Analysis Developed from Philosophy of Science

    Science.gov (United States)

    Russ, Rosemary S.; Scherr, Rachel E.; Hammer, David; Mikeska, Jamie

    2008-01-01

    Science education reform has long focused on assessing student inquiry, and there has been progress in developing tools specifically with respect to experimentation and argumentation. We suggest the need for attention to another aspect of inquiry, namely "mechanistic reasoning." Scientific inquiry focuses largely on understanding causal…

  1. Productivity of "collisions generate heat" for reconciling an energy model with mechanistic reasoning: A case study

    Science.gov (United States)

    Scherr, Rachel E.; Robertson, Amy D.

    2015-06-01

    We observe teachers in professional development courses about energy constructing mechanistic accounts of energy transformations. We analyze a case in which teachers investigating adiabatic compression develop a model of the transformation of kinetic energy to thermal energy. Among their ideas is the idea that thermal energy is generated as a byproduct of individual particle collisions, which is represented in science education research literature as an obstacle to learning. We demonstrate that in this instructional context, the idea that individual particle collisions generate thermal energy is not an obstacle to learning, but instead is productive: it initiates intellectual progress. Specifically, this idea initiates the reconciliation of the teachers' energy model with mechanistic reasoning about adiabatic compression, and leads to a canonically correct model of the transformation of kinetic energy into thermal energy. We claim that the idea's productivity is influenced by features of our particular instructional context, including the instructional goals of the course, the culture of collaborative sense making, and the use of certain representations of energy.

  2. Towards the development of mechanistically based design rules for corrosion fatigue in ductile steels

    International Nuclear Information System (INIS)

    Johnson, R.; McMinn, A.; Tomkins, B.

    1980-08-01

    Design curves for nuclear pressure vessels and off-shore structures are based on air endurance curves that have had a safety factor applied to account for effects such as corrosive environments, frequency and mean stress. These are supported by a limited number of endurance tests on actual pressure vessels, and on welded joints under service conditions. These data-based rules are limited in their ability to cope with environmental effects and as the time dependencies of fatigue and corrosion processes are so different, no sound basis exists for the extrapolation of data to long component lifetimes. The crack-growth behaviour of materials used in nuclear pressure vessels and off-shore structures is examined with a view to determining how it may be used to re-assess the design curves. Even simple integration of crack-growth laws can be seen to be within reasonable agreement with present design curves; with improved methods of stress analysis, etc. this approach could potentially improve these curves. Mechanistic studies are also seen to offer a means of examining and assessing time-dependent process interactions and so, potentially, to form the basis of new guidelines. Finally the areas where further work would be needed to substantiate any changes in design curves are indicated. (author)

  3. Ruthenium-Catalyzed Transformations of Alcohols: Mechanistic Investigations and Methodology Development

    DEFF Research Database (Denmark)

    Makarov, Ilya; Madsen, Robert; Fristrup, Peter

    with dimethoxyisopropylidene and pyridilidene ligands could be more active than RuCl2(IiPr)(p-cymene) used in the mechanistic investigation. Two analogs of the calculated complexes were synthesized but were not isolated in a pure form. The amidation reaction catalyzed by a mixture containing the N-ethyl pyridilidene...

  4. Mechanistic study of manganese-substituted glycerol dehydrogenase using a kinetic and thermodynamic analysis.

    Science.gov (United States)

    Fang, Baishan; Niu, Jin; Ren, Hong; Guo, Yingxia; Wang, Shizhen

    2014-01-01

    Mechanistic insights regarding the activity enhancement of dehydrogenase by metal ion substitution were investigated by a simple method using a kinetic and thermodynamic analysis. By profiling the binding energy of both the substrate and product, the metal ion's role in catalysis enhancement was revealed. Glycerol dehydrogenase (GDH) from Klebsiella pneumoniae sp., which demonstrated an improvement in activity by the substitution of a zinc ion with a manganese ion, was used as a model for the mechanistic study of metal ion substitution. A kinetic model based on an ordered Bi-Bi mechanism was proposed considering the noncompetitive product inhibition of dihydroxyacetone (DHA) and the competitive product inhibition of NADH. By obtaining preliminary kinetic parameters of substrate and product inhibition, the number of estimated parameters was reduced from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The simulated values of time-concentration curves fit the experimental values well, with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH, respectively. A comparison of the binding energy of enzyme ternary complex for Mn-GDH and GDH derived from kinetic parameters indicated that metal ion substitution accelerated the release of dioxyacetone. The metal ion's role in catalysis enhancement was explicated.

  5. Mechanistic study of manganese-substituted glycerol dehydrogenase using a kinetic and thermodynamic analysis.

    Directory of Open Access Journals (Sweden)

    Baishan Fang

    Full Text Available Mechanistic insights regarding the activity enhancement of dehydrogenase by metal ion substitution were investigated by a simple method using a kinetic and thermodynamic analysis. By profiling the binding energy of both the substrate and product, the metal ion's role in catalysis enhancement was revealed. Glycerol dehydrogenase (GDH from Klebsiella pneumoniae sp., which demonstrated an improvement in activity by the substitution of a zinc ion with a manganese ion, was used as a model for the mechanistic study of metal ion substitution. A kinetic model based on an ordered Bi-Bi mechanism was proposed considering the noncompetitive product inhibition of dihydroxyacetone (DHA and the competitive product inhibition of NADH. By obtaining preliminary kinetic parameters of substrate and product inhibition, the number of estimated parameters was reduced from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The simulated values of time-concentration curves fit the experimental values well, with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH, respectively. A comparison of the binding energy of enzyme ternary complex for Mn-GDH and GDH derived from kinetic parameters indicated that metal ion substitution accelerated the release of dioxyacetone. The metal ion's role in catalysis enhancement was explicated.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

    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. (paper)

  7. Antimalarial benzoheterocyclic 4-aminoquinolines: Structure-activity relationship, in vivo evaluation, mechanistic and bioactivation studies.

    Science.gov (United States)

    Ongarora, Dennis S B; Strydom, Natasha; Wicht, Kathryn; Njoroge, Mathew; Wiesner, Lubbe; Egan, Timothy J; Wittlin, Sergio; Jurva, Ulrik; Masimirembwa, Collen M; Chibale, Kelly

    2015-09-01

    A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of highly promising analogues, the most potent of which had IC50s in the nanomolar range against both strains. The compounds further demonstrated good in vitro microsomal metabolic stability while those subjected to in vivo pharmacokinetic studies had desirable pharmacokinetic profiles. In vivo antimalarial efficacy in Plasmodium berghei infected mice was evaluated for four compounds, all of which showed good activity following oral administration. In particular, compound 19 completely cured treated mice at a low multiple dose of 4×10mg/kg. Mechanistic and bioactivation studies suggest hemozoin formation inhibition and a low likelihood of forming quinone-imine reactive metabolites, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Study of n-Butyl Acrylate Self-Initiation Reaction Experimentally and via Macroscopic Mechanistic Modeling

    Directory of Open Access Journals (Sweden)

    Ahmad Arabi Shamsabadi

    2016-04-01

    Full Text Available This paper presents an experimental study of the self-initiation reaction of n-butyl acrylate (n-BA in free-radical polymerization. For the first time, the frequency factor and activation energy of the monomer self-initiation reaction are estimated from measurements of n-BA conversion in free-radical homo-polymerization initiated only by the monomer. The estimation was carried out using a macroscopic mechanistic mathematical model of the reactor. In addition to already-known reactions that contribute to the polymerization, the model considers a n-BA self-initiation reaction mechanism that is based on our previous electronic-level first-principles theoretical study of the self-initiation reaction. Reaction rate equations are derived using the method of moments. The reaction-rate parameter estimates obtained from conversion measurements agree well with estimates obtained via our purely-theoretical quantum chemical calculations.

  9. Mechanistic studies related to the safety of Li/SOCl2 cells

    Science.gov (United States)

    Carter, B. J.; Williams, R. M.; Tsay, F. D.; Rodriguez, A.; Kim, S.; Evans, M. M.; Frank, H.

    1985-01-01

    Mechanistic studies of the reactions in Li-SOCl2 cells have been undertaken to improve understanding of the safety problems of these cells. The electrochemical reduction of 1.5M LiAlCl4/SOCl2 has been investigated using gas chromatography, electron spin resonance spectroscopy, and infrared spectroscopy. Cl2 and S2Cl2 have been identified as intermediates in the reduction of SOCl2, along with a radical species (g/xx/ = 2.004, g/yy/ = 2.016, g/zz/ = 2.008) and the proposed triplet ground-state dimer of this radical. SO2 and sulfur have been identified as products. Based upon these findings, a mechanism for the electrochemical reduction of 1.5M LiAlCl4/SOCl2 has been proposed, and its implications for safety of Li-SOCl2 cells during discharge to +0.5V at 25-30 C are discussed.

  10. Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides

    Science.gov (United States)

    Strieter, Eric R.; Bhayana, Brijesh; Buchwald, Stephen L.

    2009-01-01

    The copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggest that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(I) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(I) amidates also provide insights into the mechanism of aryl halide activation. PMID:19072233

  11. Reaction of Aldehydes/Ketones with Electron-Deficient 1,3,5-Triazines Leading to Functionalized Pyrimidines as Diels-Alder/Retro-Diels-Alder Reaction Products: Reaction Development and Mechanistic Studies.

    Science.gov (United States)

    Yang, Kai; Dang, Qun; Cai, Pei-Jun; Gao, Yang; Yu, Zhi-Xiang; Bai, Xu

    2017-03-03

    Catalytic inverse electron demand Diels-Alder (IEDDA) reactions of heterocyclic aza-dienes are rarely reported since highly reactive and electron-rich dienophiles are often found not compatible with strong acids such as Lewis acids. Herein, we disclose that TFA-catalyzed reactions of electron-deficient 1,3,5-triazines and electron-deficient aldehydes/ketones can take place. These reactions led to highly functionalized pyrimidines as products in fair to good yields. The reaction mechanism was carefully studied by the combination of experimental and computational studies. The reactions involve a cascade of stepwise inverse electron demand hetero-Diels-Alder (ihDA) reactions, followed by retro-Diels-Alder (rDA) reactions and elimination of water. An acid was required for both ihDA and rDA reactions. This mechanism was further verified by comparing the relative reactivity of aldehydes/ketones and their corresponding vinyl ethers in the current reaction system.

  12. Mechanistic Physiologically Based Pharmacokinetic (PBPK) Model of the Heart Accounting for Inter-Individual Variability: Development and Performance Verification.

    Science.gov (United States)

    Tylutki, Zofia; Mendyk, Aleksander; Polak, Sebastian

    2018-04-01

    Modern model-based approaches to cardiac safety and efficacy assessment require accurate drug concentration-effect relationship establishment. Thus, knowledge of the active concentration of drugs in heart tissue is desirable along with inter-subject variability influence estimation. To that end, we developed a mechanistic physiologically based pharmacokinetic model of the heart. The models were described with literature-derived parameters and written in R, v.3.4.0. Five parameters were estimated. The model was fitted to amitriptyline and nortriptyline concentrations after an intravenous infusion of amitriptyline. The cardiac model consisted of 5 compartments representing the pericardial fluid, heart extracellular water, and epicardial intracellular, midmyocardial intracellular, and endocardial intracellular fluids. Drug cardiac metabolism, passive diffusion, active efflux, and uptake were included in the model as mechanisms involved in the drug disposition within the heart. The model accounted for inter-individual variability. The estimates of optimized parameters were within physiological ranges. The model performance was verified by simulating 5 clinical studies of amitriptyline intravenous infusion, and the simulated pharmacokinetic profiles agreed with clinical data. The results support the model feasibility. The proposed structure can be tested with the goal of improving the patient-specific model-based cardiac safety assessment and offers a framework for predicting cardiac concentrations of various xenobiotics. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies.

    Science.gov (United States)

    Dear, James W; Clarke, Joanna I; Francis, Ben; Allen, Lowri; Wraight, Jonathan; Shen, Jasmine; Dargan, Paul I; Wood, David; Cooper, Jamie; Thomas, Simon H L; Jorgensen, Andrea L; Pirmohamed, Munir; Park, B Kevin; Antoine, Daniel J

    2018-02-01

    Paracetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation. Using data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction. Between June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A

  14. Can ligand addition to soil enhance Cd phytoextraction? A mechanistic model study.

    Science.gov (United States)

    Lin, Zhongbing; Schneider, André; Nguyen, Christophe; Sterckeman, Thibault

    2014-11-01

    Phytoextraction is a potential method for cleaning Cd-polluted soils. Ligand addition to soil is expected to enhance Cd phytoextraction. However, experimental results show that this addition has contradictory effects on plant Cd uptake. A mechanistic model simulating the reaction kinetics (adsorption on solid phase, complexation in solution), transport (convection, diffusion) and root absorption (symplastic, apoplastic) of Cd and its complexes in soil was developed. This was used to calculate plant Cd uptake with and without ligand addition in a great number of combinations of soil, ligand and plant characteristics, varying the parameters within defined domains. Ligand addition generally strongly reduced hydrated Cd (Cd(2+)) concentration in soil solution through Cd complexation. Dissociation of Cd complex ([Formula: see text]) could not compensate for this reduction, which greatly lowered Cd(2+) symplastic uptake by roots. The apoplastic uptake of [Formula: see text] was not sufficient to compensate for the decrease in symplastic uptake. This explained why in the majority of the cases, ligand addition resulted in the reduction of the simulated Cd phytoextraction. A few results showed an enhanced phytoextraction in very particular conditions (strong plant transpiration with high apoplastic Cd uptake capacity), but this enhancement was very limited, making chelant-enhanced phytoextraction poorly efficient for Cd.

  15. Mechanistic link between uptake of sulfonamides and bacteriostatic effect: model development and application to experimental data from two soil microorganisms.

    Science.gov (United States)

    Focks, Andreas; Klasmeier, Jörg; Matthies, Michael

    2010-07-01

    Sulfonamides (SA) are antibiotic compounds that are widely used as human and veterinary pharmaceuticals. They are not rapidly biodegradable and have been detected in various environmental compartments. Effects of sulfonamides on microbial endpoints in soil have been reported from laboratory incubation studies. Sulfonamides inhibit the growth of sensitive microorganisms by competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid production. A mathematical model was developed that relates the extracellular SA concentration to the inhibition of the relative bacterial growth rate. Two factors--the anionic accumulation factor (AAF) and the cellular affinity factor (CAF)--determine the effective concentration of an SA. The AAF describes the SA uptake into bacterial cells and varies with both the extra- and intracellular pH values and with the acidic pKa value of an SA. The CAF subsumes relevant cellular and enzyme properties, and is directly proportional to the DHPS affinity constant for an SA. Based on the model, a mechanistic dose-response relationship is developed and evaluated against previously published data, where differences in the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing medium pH values were found, most likely as a result of their diverse pH regulation. The derived dose-response relationship explains the pH and pKa dependency of mean effective concentration values (EC50) of eight SA and two soil bacteria based on AAF and CAF values. The mathematical model can be used to extrapolate sulfonamide effects to other pH values and to calculate the CAF as a pH-independent measure for the SA effects on microbial growth. Copyright (c) 2010 SETAC.

  16. Mechanistic studies of thioxanthone–carbazole as a one-component type II photoinitiator

    Energy Technology Data Exchange (ETDEWEB)

    Karaca, Nurcan; Karaca Balta, Demet; Ocal, Nuket; Arsu, Nergis, E-mail: nergisarsu@gmail.com

    2014-02-15

    A mechanistic study concerning photoinitiated free radical polymerization using Thioxanthone–Carbazole (TX–Cz) as a one-component Type II photoinitiator was performed. TX–Cz presented visible initiator characteristics with absorptions at 434 and 414 nm where the molar absorption coefficients were 2014 and 1754 L mol{sup −1} cm{sup −1}, respectively. Fluorescence and phosphorescence spectroscopy, as well as laser flash photolysis was employed to study the photophysical properties of TX–Cz. In addition, photopolymerization of methyl methacrylate (MMA) showed that TX–Cz is efficient photoinitiator. To explain the initiation mechanism of TX–Cz, fluorescence and phosphorescence emission spectra of poly (methyl methacrylate) (PMMA) were also taken to see whether the initiator covalently bonded to the polymer. The postulated mechanism is based on inter- molecular reaction of the triplet, {sup 3}(TX–Cz){sup ⁎} with the carbazole moiety at ground state, TX–Cz. The photoinitiation efficiency of TX–Cz during gelation of multifunctional acrylates was also investigated by Photo-Differential Scanning Calorimetry (Photo-DSC) technique and high polymerization rates were obtained. -- Highlights: • Thioxanthone–Carbazole was used as visible light photoinitiator for radical polymerization of meth(acrylates). • The detailed photophysical properties of TX–Cz was reported. • Fluorescence quantum yield, phosphorescence lifetime , triplet energy and triplet lifetime were determined. • Photo-DSC was used to follow photopolymerizatin kinetics of acrylates.

  17. Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

    Science.gov (United States)

    Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

    2009-01-01

    Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

  18. Isolation, characterization, and mechanistic studies of (-)-alpha-gurjunene synthase from Solidago canadensis.

    Science.gov (United States)

    Schmidt, C O; Bouwmeester, H J; Bülow, N; König, W A

    1999-04-15

    The leaves of the composite Solidago canadensis (goldenrod) were shown to contain (-)-alpha-gurjunene synthase activity. This sesquiterpene is likely to be the precursor for cyclocolorenone, a sesquiterpene ketone present in high amounts in S. canadensis leaves. (-)-alpha-Gurjunene synthase was purified to apparent homogeneity (741-fold) by anion-exchange chromatography (on several matrices), dye ligand chromatography, hydroxylapatite chromatography, and gel filtration. Chromatography on a gel filtration matrix indicated a native molecular mass of 48 kDa, and SDS-PAGE showed the enzyme to be composed of one subunit with a denatured mass of 60 kDa. Its maximum activity was observed at pH 7.8 in the presence of 10 mM Mg2+ and the KM value for the substrate farnesyl diphosphate was 5.5 microM. Over a range of purification steps (-)-alpha-gurjunene and (+)-gamma-gurjunene synthase activities copurified. In addition, the product ratio of the enzyme activity under several different assay conditions was always 91% (-)-alpha-gurjunene and 9% (+)-gamma-gurjunene. This suggests that the formation of these two structurally related products is catalyzed by one enzyme. For further confirmation, we carried out a number of mechanistic studies with (-)-alpha-gurjunene synthase, in which an enzyme preparation was incubated with deuterated substrate analogues. Based on mass spectrometry analysis of the products formed, a cyclization mechanism was postulated which makes it plausible that the synthase catalyzes the formation of both sesquiterpenes. Copyright 1999 Academic Press.

  19. Simple boron removal from seawater by using polyols as complexing agents: A computational mechanistic study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min-Kyung; Eom, Ki Heon; Lim, Jun-Heok; Lee, Jea-Keun; Lee, Ju Dong; Won, Yong Sun [Pukyong National University, Busan (Korea, Republic of)

    2015-11-15

    The complexation of boric acid (B(OH){sub 3}), the primary form of aqueous boron at moderate pH, with polyols is proposed and mechanistically studied as an efficient way to improve membrane processes such as reverse osmosis (RO) for removing boron in seawater by increasing the size of aqueous boron compounds. Computational chemistry based on the density functional theory (DFT) was used to manifest the reaction pathways of the complexation of B(OH){sub 3} with various polyols such as glycerol, xylitol, and mannitol. The reaction energies were calculated as −80.6, −98.1, and −87.2 kcal/mol for glycerol, xylitol, and mannitol, respectively, indicating that xylitol is the most thermodynamically favorable for the complexation with B(OH){sub 3}. Moreover, the 1 : 2 molar ratio of B(OH)3 to polyol was found to be more favorable than the ratio of 1 : 1 for the complexation. Meanwhile, latest lab-scale actual RO experiments successfully supported our computational prediction that 2 moles of xylitol are the most effective as the complexing agent for 1 mole of B(OH){sub 3} in aqueous solution.

  20. A DFT study on the deprotonation antioxidant mechanistic step of ortho-substituted phenolic cation radicals

    International Nuclear Information System (INIS)

    Vafiadis, Anastasios P.; Bakalbassis, Evangelos G.

    2005-01-01

    The conformers of the 2-, 3- and 4-substituted phenolic cation radicals, 2-X-, 3-X- and 4-X-ArOH ·+ , and the respective phenoxyl radicals, ArO · , the intramolecular hydrogen bond strength (ΔH intra ) estimate along with the electronic effects of five electron withdrawing (EWG) and eight electron donating groups (EDG) on the gas-phase O-H proton dissociation enthalpies, (PDEs), of the short-lived, 2-X-ArOH ·+ , (involved in the single-electron transfer antioxidant mechanism), are studied at the DFT/B3LYP level of theory. EWG result to smaller PDEs, hence to stronger acidity; EDG to weaker acidity. The deprotonation antioxidant mechanistic step is not a rate-controlling step for 2-X-ArOH to scavenge free radicals. Approximate estimations of the ΔPDEs (hence acidities as well) can be derived from calculated structural and/or vibrational frequency values. ΔH intra s correlate reasonably with geometrical parameters for the closed-shell, neutral counterparts, in contrast with previous estimates

  1. DNA damage and radical reactions: Mechanistic aspects, formation in cells and repair studies

    International Nuclear Information System (INIS)

    Cadet, J.; Ravanat, J.L.; Carell, T.; Cellai, L.; Chatgilialoglu, Ch.; Gimisis, Th.; Miranda, M.; O'Neill, P.; Robert, M.

    2008-01-01

    Several examples of oxidative and reductive reactions of DNA components that lead to single and tandem modifications are discussed in this review. These include nucleophilic addition reactions of the one-electron oxidation-mediated guanine radical cation and the one-electron reduced intermediate of 8-bromo-purine 2'-de-oxy-ribo-nucleosides that give rise to either an oxidizing guanine radical or related 5',8-cyclo-purine nucleosides. In addition, mechanistic insights into the reductive pathways involved in the photolyase induced reversal of cyclo-buta-cli-pyrimidine and pyrimidine (6-4) pyrimidone photoproducts are provided. Evidence for the occurrence and validation in cellular DNA of (OH) · radical degradation pathways of guanine that have been established in model systems has been gained from the accurate measurement of degradation products. Relevant information on biochemical aspects of the repair of single and clustered oxidatively generated damage to DNA has been gained from detailed investigations that rely on the synthesis of suitable modified probes. Thus the preparation of stable carbocyclic derivatives of purine nucleoside containing defined sequence oligonucleotides has allowed detailed crystallographic studies of the recognition step of the base damage by enzymes implicated in the base excision repair (BER) pathway. Detailed insights are provided on the BER processing of non-double strand break bi-stranded clustered damage that may consist of base lesions, a single strand break or abasic sites and represent one of the main deleterious classes of radiation-induced DNA damage. (authors)

  2. Development of a mechanistic model for prediction of CO2 capture from gas mixtures by amine solutions in porous membranes.

    Science.gov (United States)

    Ghadiri, Mehdi; Marjani, Azam; Shirazian, Saeed

    2017-06-01

    A mechanistic model was developed in order to predict capture and removal of CO 2 from air using membrane technology. The considered membrane was a hollow-fiber contactor module in which gas mixture containing CO 2 was assumed as feed while 2-amino-2-metyl-1-propanol (AMP) was used as an absorbent. The mechanistic model was developed according to transport phenomena taking into account mass transfer and chemical reaction between CO 2 and amine in the contactor module. The main aim of modeling was to track the composition and flux of CO 2 and AMP in the membrane module for process optimization. For modeling of the process, the governing equations were computed using finite element approach in which the whole model domain was discretized into small cells. To confirm the simulation findings, model outcomes were compared with experimental data and good consistency was revealed. The results showed that increasing temperature of AMP solution increases CO 2 removal in the hollow-fiber membrane contactor.

  3. SENSITIVITY ANALYSIS IN FLEXIBLE PAVEMENT PERFORMANCE USING MECHANISTIC EMPIRICAL METHOD (CASE STUDY: CIREBON–LOSARI ROAD SEGMENT, WEST JAVA

    Directory of Open Access Journals (Sweden)

    E. Samad

    2012-02-01

    Full Text Available Cirebon – Losari flexible pavement which is located on the North Coast of Java, Indonesia, is in the severe damage condition caused by overloading vehicles passing the road. The need for developing improved pavement design and analysis methods is very necessary. The increment of loads and quality of material properties can be evaluated through Mechanistic-Empirical (M-E method. M-E software like KENLAYER has been developed to facilitate the transition from empirical to mechanistic design methods. From the KENLAYER analysis, it can be concluded that the effect of overloading to the pavement structure performance is difficult to minimize even though the first two layers have relatively high modulus of elasticity. The occurrence of 150%, 200%, and 250% overloading have a very significant effect in reducing 84%, 95%, and 98% of the pavement design life, respectively. For the purpose of increasing the pavement service life, it is more effective to manage the allowable load.

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

    Science.gov (United States)

    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…

  5. Assessing Metal Levels in Children from the Mechanistic Indicators of Childhood Asthma(MICA) study

    Science.gov (United States)

    Toxic and essential metals levels can be used as health indicators. Here, we quantitatively compare and contrast toxic and essential metals levels in vacuum dust, urine, and fingernail samples of 109 children in Detroit, Michigan as part of The Mechanistic Indicators of Childhood...

  6. Copper-Catalysed Aminoboration of Vinylarenes with Hydroxylamine Esters-A Computational Mechanistic Study.

    Science.gov (United States)

    Tobisch, Sven

    2017-12-14

    An in-depth computational probe of the copper-mediated formal aminoboration of β-alkylstyrenes with bis(pinacolato)diboron B 2 pin 2 and an archetype hydroxylamine ester by a dppbz-ligated {P^P}Cu I boryl catalyst (dppbz≡{P^P}≡1,2-bis(diphenylphosphino)benzene) is presented. This first comprehensive computational study of the copper-mediated formal aminoboration utilising an electrophilic strategy has identified the most accessible pathway for productive catalysis. The mechanistic picture derived from smooth energy profiles acquired by employing a reliable computational protocol applied to a realistic catalyst model conforms to all available experimental data. The high degree of regio- and stereoselectivity achieved in syn-borylcupration and Umpolung electrophilic amination is instrumental to the exclusive generation of the (syn)-β-aminoalkylborane product. On the one hand, syn-borylcupration furnishes exclusively β-borylalkylcopper nucleophile upon boryl addition onto the vinylarene β-carbon. Its subsequent approach by the hydroxylamine electrophile to deliver the product with the release of {P^P}Cu I benzoate favours a stepwise stereoretentive S N 2-type oxidative addition/N-C bond-forming reductive elimination sequence. The copper benzoate species represents the catalyst resting state, and its transformation into the catalytically active borylcopper species upon salt metathesis with Li(OtBu) base and transmetallation with B 2 pin 2 is turnover limiting. Electronically modified β-alkylstyrenes featuring a para-CF 3 substituted phenyl ring render the borylcupration faster, and more electron-rich hydroxylamine agents decelerate the electrophilic amination. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Final Report for the DOE-BES Program Mechanistic Studies of Activated Hydrogen Release from Amine-Boranes

    Energy Technology Data Exchange (ETDEWEB)

    Larry G. Sneddon; R. Thomas Baker

    2013-01-13

    Effective storage of hydrogen presents one of the most significant technical gaps to successful implementation of the hydrogen economy, particularly for transportation applications. Amine boranes, such as ammonia borane H3NBH3 and ammonia triborane H3NB3H7, have been identified as promising, high-capacity chemical hydrogen storage media containing potentially readily released protic (N-H) and hydridic (B-H) hydrogens. At the outset of our studies, dehydrogenation of ammonia borane had been studied primarily in the solid state, but our DOE sponsored work clearly demonstrated that ionic liquids, base-initiators and/or metal-catalysts can each significantly increase both the rate and extent of hydrogen release from amine boranes under moderate conditions. Our studies also showed that depending upon the activation method, hydrogen release from amine boranes can occur by very different mechanistic steps and yield different types of spent-fuel materials. The fundamental understanding that was developed during this grant of the pathways and controlling factors for each of these hydrogen-release mechanisms is now enabling continuing discovery and optimization of new chemical-hydride based hydrogen storage systems.

  8. A quantitative approach to developing more mechanistic gas exchange models for field grown potato

    DEFF Research Database (Denmark)

    Ahmadi, Seyed Hamid; Andersen, Mathias Neumann; Poulsen, Rolf Thostrup

    2009-01-01

    In this study we introduce new gas exchange models that are developed under natural conditions of field grown potato. The new models could explain about 85% of the stomatal conductance variations, which was much higher than the well-known gas exchange models such as the Ball-Berry model [Ball...... of chemical and hydraulic signalling on stomatal conductance as exp(-β[ABA])exp(-δ|ψ|) in which [ABA] and |ψ| are xylem ABA concentration and absolute value of leaf or stem water potential. In this study we found that stem water potential could be a very reliable indicator of how plant water status affects...

  9. Development and application of a mechanistic model to estimate emission of nitrous oxide from UK agriculture

    International Nuclear Information System (INIS)

    Brown, L.; Jarvis, S.C.; Syed, B.; Goulding, K.W.T.; Li, C.

    2002-01-01

    A mechanistic model of N 2 O emission from agricultural soil (DeNitrification-DeComposition - DNDC) was modified for application to the UK, and was used as the basis of an inventory of N 2 O emission from UK agriculture in 1990. UK-specific input data were added to DNDC's database and the ability to simulate daily C and N inputs from grazing animals and applied animal waste was added to the model. The UK version of the model, UK-DNDC, simulated emissions from 18 different crop types on the 3 areally dominant soils in each county. Validation of the model at the field scale showed that predictions matched observations well. Emission factors for the inventory were calculated from estimates of N 2 O emission from UK-DNDC, in order to maintain direct comparability with the IPCC approach. These, along with activity data, were included in a transparent spreadsheet format. Using UK-DNDC, the estimate of N 2 O-N emission from UK current agricultural practice in 1990 was 50.9Gg. This total comprised 31.7Gg from the soil sector, 5.9Gg from animals and 13.2Gg from the indirect sector. The range of this estimate (using the range of soil organic C for each soil used) was 30.5-62.5Gg N. Estimates of emissions in each sector were compared to those calculated using the IPCC default methodology. Emissions from the soil and indirect sectors were smaller with the UK-DNDC approach than with the IPCC methodology, while emissions from the animal sector were larger. The model runs suggested a relatively large emission from agricultural land that was not attributable to current agricultural practices (33.8Gg in total, 27.4Gg from the soil sector). This 'background' component is partly the result of historical agricultural land use. It is not normally included in inventories of emission, but would increase the total emission of N 2 O-N from agricultural land in 1990 to 78.3Gg. (Author)

  10. Development and application of a mechanistic model to estimate emission of nitrous oxide from UK agriculture

    Energy Technology Data Exchange (ETDEWEB)

    Brown, L.; Jarvis, S.C. [Institute of Grassland and Environmental Research, Okehampton (United Kingdom); Syed, B. [Cranfield Univ., Silsoe (United Kingdom). Soil Survey and Land Research Centre; Sneath, R.W.; Phillips, V.R. [Silsoe Research Inst. (United Kingdom); Goulding, K.W.T. [Institute of Arable Crops Research, Rothamsted (United Kingdom); Li, C. [University of New Hampshire (United States). Inst. for the Study of Earth, Oceans and Space

    2002-07-01

    A mechanistic model of N{sub 2}O emission from agricultural soil (DeNitrification-DeComposition - DNDC) was modified for application to the UK, and was used as the basis of an inventory of N{sub 2}O emission from UK agriculture in 1990. UK-specific input data were added to DNDC's database and the ability to simulate daily C and N inputs from grazing animals and applied animal waste was added to the model. The UK version of the model, UK-DNDC, simulated emissions from 18 different crop types on the 3 areally dominant soils in each county. Validation of the model at the field scale showed that predictions matched observations well. Emission factors for the inventory were calculated from estimates of N{sub 2}O emission from UK-DNDC, in order to maintain direct comparability with the IPCC approach. These, along with activity data, were included in a transparent spreadsheet format. Using UK-DNDC, the estimate of N{sub 2}O-N emission from UK current agricultural practice in 1990 was 50.9Gg. This total comprised 31.7Gg from the soil sector, 5.9Gg from animals and 13.2Gg from the indirect sector. The range of this estimate (using the range of soil organic C for each soil used) was 30.5-62.5Gg N. Estimates of emissions in each sector were compared to those calculated using the IPCC default methodology. Emissions from the soil and indirect sectors were smaller with the UK-DNDC approach than with the IPCC methodology, while emissions from the animal sector were larger. The model runs suggested a relatively large emission from agricultural land that was not attributable to current agricultural practices (33.8Gg in total, 27.4Gg from the soil sector). This 'background' component is partly the result of historical agricultural land use. It is not normally included in inventories of emission, but would increase the total emission of N{sub 2}O-N from agricultural land in 1990 to 78.3Gg. (Author)

  11. Development and application of a mechanistic model to estimate emission of nitrous oxide from UK agriculture

    Science.gov (United States)

    Brown, L.; Syed, B.; Jarvis, S. C.; Sneath, R. W.; Phillips, V. R.; Goulding, K. W. T.; Li, C.

    A mechanistic model of N 2O emission from agricultural soil (DeNitrification-DeComposition—DNDC) was modified for application to the UK, and was used as the basis of an inventory of N 2O emission from UK agriculture in 1990. UK-specific input data were added to DNDC's database and the ability to simulate daily C and N inputs from grazing animals and applied animal waste was added to the model. The UK version of the model, UK-DNDC, simulated emissions from 18 different crop types on the 3 areally dominant soils in each county. Validation of the model at the field scale showed that predictions matched observations well. Emission factors for the inventory were calculated from estimates of N 2O emission from UK-DNDC, in order to maintain direct comparability with the IPCC approach. These, along with activity data, were included in a transparent spreadsheet format. Using UK-DNDC, the estimate of N 2O-N emission from UK current agricultural practice in 1990 was 50.9 Gg. This total comprised 31.7 Gg from the soil sector, 5.9 Gg from animals and 13.2 Gg from the indirect sector. The range of this estimate (using the range of soil organic C for each soil used) was 30.5-62.5 Gg N. Estimates of emissions in each sector were compared to those calculated using the IPCC default methodology. Emissions from the soil and indirect sectors were smaller with the UK-DNDC approach than with the IPCC methodology, while emissions from the animal sector were larger. The model runs suggested a relatively large emission from agricultural land that was not attributable to current agricultural practices (33.8 Gg in total, 27.4 Gg from the soil sector). This 'background' component is partly the result of historical agricultural land use. It is not normally included in inventories of emission, but would increase the total emission of N 2O-N from agricultural land in 1990 to 78.3 Gg.

  12. Mechanistic studies on the OH-initiated atmospheric oxidation of selected aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Nehr, Sascha

    2012-07-01

    Benzene, toluene, the xylenes, and the trimethylbenzenes are among the most abundant aromatic trace constituents of the atmosphere mainly originating from anthropogenic sources. The OH-initiated atmospheric photo-oxidation of aromatic hydrocarbons is the predominant removal process resulting in the formation of O{sub 3} and secondary organic aerosol. Therefore, aromatics are important trace constituents regarding air pollution in urban environments. Our understanding of aromatic photo-oxidation processes is far from being complete. This work presents novel approaches for the investigation of OH-initiated atmospheric degradation mechanisms of aromatic hydrocarbons. Firstly, pulsed kinetic studies were performed to investigate the prompt HO{sub 2} formation from OH+ aromatic hydrocarbon reactions under ambient conditions. For these studies, the existing OH reactivity instrument, based on the flash photolysis/laser-induced fluorescence (FP/LIF) technique, was extended to the detection of HO{sub 2} radicals. The experimental design allows for the determination of HO{sub 2} formation yields and kinetics. Results of the pulsed kinetic experiments complement previous product studies and help to reduce uncertainties regarding the primary oxidation steps. Secondly, experiments with aromatic hydrocarbons were performed under atmospheric conditions in the outdoor atmosphere simulation chamber SAPHIR (Simulation of Atmospheric PHotochemistry In a large Reaction chamber) located at Forschungszentrum Juelich. The experiments were aimed at the evaluation of up-to-date aromatic degradation schemes of the Master Chemical Mechanism (MCMv3.2). The unique combination of analytical instruments operated at SAPHIR allows for a detailed investigation of HO{sub x} and NO{sub x} budgets and for the determination of primary phenolic oxidation product yields. MCMv3.2 deficiencies were identified and most likely originate from shortcomings in the mechanistic representation of ring

  13. Deposition, characterization, patterning and mechanistic study of inorganic resists for next-generation nanolithography

    Science.gov (United States)

    Luo, Feixiang

    The semiconductor industry has witnessed a continuous decrease in the size of logic, memory and other computer chip components since its birth over half a century ago. The shrinking (scaling) of components has to a large extent been enabled by the development of micro- and now nano-lithographic techniques. This thesis focuses on one central component of lithography, the resist, which is essentially a thin film that when appropriately exposed enables a pattern to be printed onto a surface. Smaller features require an ever more precisely focused photon, electron or ion beam with which to expose the resist. The likely next generation source of radiation that will enable sub-20nm features to be written will employ extreme ultraviolet radiation (EUV), 92eV (13.5nm). The work discussed here involves a novel class of inorganic resists (including a solution processed Hf-based resist called HafSOx), as the organic resists that have dominated the microlithography industry for the past few decades have approached fundamental scaling limits. In order to maintain the high throughput required by high volume semiconductor manufacturing, metal oxide resists have been proposed and developed to meet the resolution and sensitivity in EUV lithography. One can think of our resists as the nano-lithographic analog to the silver halide film that dominated the photographic print industry for a century. In this thesis, we mainly describe our work on HafSOx, a "first generation" metal oxide EUV resist system. HafSOx thin films can be deposited by spin-coating a mixed solution of HfOCl2, H2O 2, and H2SO4. Various materials characterization techniques have been employed to achieve a comprehensive understanding of film composition and structure at both surface and bulk level, as well as a mechanistic understanding of the film radiation chemistry. Taking advantage of the high energy x-rays used in the XPS experiment, we developed an experiment to dynamically monitor the photochemistry within the

  14. A kinetic mechanistic study of acid-catalyzed alkylation of isobutane with C4-olefins at low temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Doshi, B.M.

    1978-01-01

    A kinetic and mechanistic study of sulfuric acid-catalyzed alkylation of isobutane with C/sub 4/-Olefins at Low Temperatures(-20/sup 0/ to 0/sup 0/C) was based on a new two-step reaction sequence in which the desired first-step reactions are between acid and olefin to form sulfates and the desired second-step reactions are between sulfates and isobutane to form mostly trimethylpentanes. Linear butenes formed stable sulfates that formed alkylates of exceptionally high quality, up to 100 Research octane, whereas isobutylene and trimethylpentene mainly polymerized during the first step, and the alkylate produced had only 90 Research octane. Trimethylpentanes and dimethylhexanes, when contacted with concentrated sulfuric acid at -10/sup 0/ to +25/sup 0/C, degraded and isomerized to form C/sub 4/-C/sub 9/ and higher isoparaffins and acid-soluble hydrocarbons (conjunct polymers). For the two-step process and the degradation and isomerization reactions, kinetic models based on reaction at the interface were developed; but for isoolefins, a polymerization-cracking sequence (via C/sub 12/- and even C/sub 16/-olefins) is the preferred route. Commercial applications of the results are proposed.

  15. Mechanistic Study of the Oxidative Coupling of Styrene with 2-Phenylpyridine Derivatives Catalyzed by Cationic Rhodium( III) via C–H Activation

    Science.gov (United States)

    Brasse, Mikaël; Cámpora, Juan; Ellman, Jonathan A.; Bergman, Robert G.

    2013-01-01

    The Rh(III) catalyzed oxidative coupling of alkenes with arenes provides a greener alternative to the classical Heck reaction for the synthesis of arene-functionalized alkenes. The present mechanistic study gives insights for the rational development of this key transformation. The catalyst resting states and the rate law of the reaction have been identified. The reaction rate is solely dependent on catalyst and alkene concentrations and the rate determining step is the migratory insertion of alkene into a Rh–C(aryl) bond. PMID:23590843

  16. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: appo@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  17. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    International Nuclear Information System (INIS)

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified

  18. Development and Implementation of Mechanistic Terry Turbine Models in RELAP-7 to Simulate RCIC Normal Operation Conditions

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Haihua [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zou, Ling [Idaho National Lab. (INL), Idaho Falls, ID (United States); Zhang, Hongbin [Idaho National Lab. (INL), Idaho Falls, ID (United States); O' Brien, James Edward [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-09-01

    As part of the efforts to understand the unexpected “self-regulating” mode of the RCIC (Reactor Core Isolation Cooling) systems in Fukushima accidents and extend BWR RCIC and PWR AFW (Auxiliary Feed Water) operational range and flexibility, mechanistic models for the Terry turbine, based on Sandia’s original work [1], have been developed and implemented in the RELAP-7 code to simulate the RCIC system. In 2016, our effort has been focused on normal working conditions of the RCIC system. More complex off-design conditions will be pursued in later years when more data are available. In the Sandia model, the turbine stator inlet velocity is provided according to a reduced-order model which was obtained from a large number of CFD (computational fluid dynamics) simulations. In this work, we propose an alternative method, using an under-expanded jet model to obtain the velocity and thermodynamic conditions for the turbine stator inlet. The models include both an adiabatic expansion process inside the nozzle and a free expansion process outside of the nozzle to ambient pressure. The combined models are able to predict the steam mass flow rate and supersonic velocity to the Terry turbine bucket entrance, which are the necessary input information for the Terry turbine rotor model. The analytical models for the nozzle were validated with experimental data and benchmarked with CFD simulations. The analytical models generally agree well with the experimental data and CFD simulations. The analytical models are suitable for implementation into a reactor system analysis code or severe accident code as part of mechanistic and dynamical models to understand the RCIC behaviors. The newly developed nozzle models and modified turbine rotor model according to the Sandia’s original work have been implemented into RELAP-7, along with the original Sandia Terry turbine model. A new pump model has also been developed and implemented to couple with the Terry turbine model. An input

  19. Comparative approaches from empirical to mechanistic simulation modelling in Land Evaluation studies

    Science.gov (United States)

    Manna, P.; Basile, A.; Bonfante, A.; Terribile, F.

    2009-04-01

    The Land Evaluation (LE) comprise the evaluation procedures to asses the attitudes of the land to a generic or specific use (e.g. biomass production). From local to regional and national scale the approach to the land use planning should requires a deep knowledge of the processes that drive the functioning of the soil-plant-atmosphere system. According to the classical approaches the assessment of attitudes is the result of a qualitative comparison between the land/soil physical properties and the land use requirements. These approaches have a quick and inexpensive applicability; however, they are based on empirical and qualitative models with a basic knowledge structure specifically built for a specific landscape and for the specific object of the evaluation (e.g. crop). The outcome from this situation is the huge difficulties in the spatial extrapolation of the LE results and the rigidity of the system. Modern techniques instead, rely on the application of mechanistic and quantitative simulation modelling that allow a dynamic characterisation of the interrelated physical and chemical processes taking place in the soil landscape. Moreover, the insertion of physical based rules in the LE procedure may make it less difficult in terms of both extending spatially the results and changing the object (e.g. crop species, nitrate dynamics, etc.) of the evaluation. On the other side these modern approaches require high quality and quantity of input data that cause a significant increase in costs. In this scenario nowadays the LE expert is asked to choose the best LE methodology considering costs, complexity of the procedure and benefits in handling a specific land evaluation. In this work we performed a forage maize land suitability study by comparing 9 different methods having increasing complexity and costs. The study area, of about 2000 ha, is located in North Italy in the Lodi plain (Po valley). The range of the 9 employed methods ranged from standard LE approaches to

  20. A mechanistic model to study the thermal ecology of a southeastern pacific dominant intertidal mussel and implications for climate change.

    Science.gov (United States)

    Finke, G R; Bozinovic, F; Navarrete, S A

    2009-01-01

    Developing mechanistic models to predict an organism's body temperature facilitates the study of physiological stresses caused by extreme climatic conditions the species might have faced in the past or making predictions about changes to come in the near future. Because the models combine empirical observation of different climatic variables with essential morphological attributes of the species, it is possible to examine specific aspects of predicted climatic changes. Here, we develop a model for the competitively dominant intertidal mussel Perumytilus purpuratus that estimates body temperature on the basis of meteorological and tidal data with an average difference (+/-SE) of 0.410 degrees +/- 0.0315 degrees C in comparison with a field-deployed temperature logger. Modeled body temperatures of P. purpuratus in central Chile regularly exceeded 30 degrees C in summer months, and values as high as 38 degrees C were found. These results suggest that the temperatures reached by mussels in the intertidal zone in central Chile are not sufficiently high to induce significant mortality on adults of this species; however, because body temperatures >40 degrees C can be lethal for this species, sublethal effects on physiological performance warrant further investigation. Body temperatures of mussels increased sigmoidally with increasing tidal height. Body temperatures of individuals from approximately 70% of the tidal range leveled off and did not increase any further with increasing tidal height. Finally, body size played an important role in determining body temperature. A hypothetical 5-cm-long mussel (only 1 cm longer than mussels found in nature) did reach potentially lethal body temperatures, suggesting that the biophysical environment may play a role in limiting the size of this small species.

  1. Regulatory Technology Development Plan - Sodium Fast Reactor. Mechanistic Source Term - Trial Calculation. Work Plan

    International Nuclear Information System (INIS)

    Grabaskas, David; Bucknor, Matthew; Jerden, James; Brunett, Acacia J.

    2016-01-01

    The overall objective of the SFR Regulatory Technology Development Plan (RTDP) effort is to identify and address potential impediments to the SFR regulatory licensing process. In FY14, an analysis by Argonne identified the development of an SFR-specific MST methodology as an existing licensing gap with high regulatory importance and a potentially long lead-time to closure. This work was followed by an initial examination of the current state-of-knowledge regarding SFR source term development (ANLART-3), which reported several potential gaps. Among these were the potential inadequacies of current computational tools to properly model and assess the transport and retention of radionuclides during a metal fuel pool-type SFR core damage incident. The objective of the current work is to determine the adequacy of existing computational tools, and the associated knowledge database, for the calculation of an SFR MST. To accomplish this task, a trial MST calculation will be performed using available computational tools to establish their limitations with regard to relevant radionuclide release/retention/transport phenomena. The application of existing modeling tools will provide a definitive test to assess their suitability for an SFR MST calculation, while also identifying potential gaps in the current knowledge base and providing insight into open issues regarding regulatory criteria/requirements. The findings of this analysis will assist in determining future research and development needs.

  2. Mechanistic study of fuel freezing, channel plugging, and continued coolability during fast reactor overpower excursions

    International Nuclear Information System (INIS)

    Wong, K.W.; Catton, I.; Kastenberg, W.E.

    1977-07-01

    A mechanistic model is presented which describes events following fuel pin failure which may lead to in-channel fuel plate-out. The thermal and hydraulic effects of the plate-out fuel are also evaluated. Given the amount and particle size of the fuel injected into the coolant channel during fuel pin failure, and the initial conditions of the interaction zone, the physical states of the fuel particles and the coolant in the interaction zone can be determined. The trajectories of the fuel particles in the coolant channel are determined by assuming a slip factor between the local tangential velocities of the coolant and the fuel particles. The time and distance after which a fuel particle hits a wire wrap are then determined and the impact stresses induced in the thin solid fuel crust can be evaluated

  3. Mechanistic study on spraying of blended biodiesel using phase Doppler anemometry

    International Nuclear Information System (INIS)

    Kamrak, Juthamas; Kongsombut, Benjapol; Grehan, Gerard; Saengkaew, Sawitree; Kim, Kyo-Seon; Charinpanitkul, Tawatchai

    2009-01-01

    Droplet size and dynamics of blended palm oil-based fatty acid methyl ester (FAME) and diesel oil spray were mechanistically investigated using a phase Doppler anemometry. A two-fluid atomizer was applied for dispersing viscous blends of blended biodiesel oil with designated flow rates. It was experimentally found that the atomizer could generate a spray with large droplets with Sauter mean diameters of ca. 30 μm at low air injection pressure. Such large droplets traveled with a low velocity along their trajectory after emerging from the nozzle tip. The viscosity of blended biodiesel could significantly affect the atomizing process, resulting in the controlled droplet size distribution. Blended biodiesel with a certain fraction of palm oil-based FAME would be consistently atomized owing to its low viscosity. However, the viscosity could exert only a small effect on the droplet velocity profile with the air injection pressure higher than 0.2 MPa.

  4. Mechanistic study on spraying of blended biodiesel using phase Doppler anemometry

    Energy Technology Data Exchange (ETDEWEB)

    Kamrak, Juthamas; Kongsombut, Benjapol; Charinpanitkul, Tawatchai [Center of Excellence in Particle Technology, Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Payathai Road, Patumwan, Bangkok 10330 (Thailand); Grehan, Gerard; Saengkaew, Sawitree [LESP/UMR CNRS6614/INSA et Universite de Rouen, BP 12, avenue de l' universite, 76801, Saint Etienne du Rouvray (France); Kim, Kyo-Seon [Department of Chemical Engineering, Faculty of Engineering, Kangwon National University, Chuncheon (Korea)

    2009-10-15

    Droplet size and dynamics of blended palm oil-based fatty acid methyl ester (FAME) and diesel oil spray were mechanistically investigated using a phase Doppler anemometry. A two-fluid atomizer was applied for dispersing viscous blends of blended biodiesel oil with designated flow rates. It was experimentally found that the atomizer could generate a spray with large droplets with Sauter mean diameters of ca. 30 {mu}m at low air injection pressure. Such large droplets traveled with a low velocity along their trajectory after emerging from the nozzle tip. The viscosity of blended biodiesel could significantly affect the atomizing process, resulting in the controlled droplet size distribution. Blended biodiesel with a certain fraction of palm oil-based FAME would be consistently atomized owing to its low viscosity. However, the viscosity could exert only a small effect on the droplet velocity profile with the air injection pressure higher than 0.2 MPa. (author)

  5. The loss of ecosystem services due to land degradation. Integration of mechanistic and probabilistic models in an Ethiopian case study

    Science.gov (United States)

    Cerretelli, Stefania; Poggio, Laura; Gimona, Alessandro; Peressotti, Alessandro; Black, Helaina

    2017-04-01

    Land and soil degradation are widespread especially in dry and developing countries such as Ethiopia. Land degradation leads to ecosystems services (ESS) degradation, because it causes the depletion and loss of several soil functions. Ethiopia's farmland faces intense degradation due to deforestation, agricultural land expansion, land overexploitation and overgrazing. In this study we modelled the impact of physical factors on ESS degradation, in particular soil erodibility, carbon storage and nutrient retention, in the Ethiopian Great Rift Valley, northwestern of Hawassa. We used models of the Sediment retention/loss, the Nutrient Retention/loss (from the software suite InVEST) and Carbon Storage. To run the models we coupled soil local data (such as soil organic carbon, soil texture) with remote sensing data as input in the parametrization phase, e.g. to derive a land use map, to calculate the aboveground and belowground carbon, the evapotraspiration coefficient and the capacity of vegetation to retain nutrient. We then used spatialised Bayesian Belief Networks (sBBNs) predicting ecosystem services degradation on the basis of the results of the three mechanistic models. The results show i) the importance of mapping of ESS degradation taking into consideration the spatial heterogeneity and the cross-correlations between impacts ii) the fundamental role of remote sensing data in monitoring and modelling in remote, data-poor areas and iii) the important role of spatial BBNs in providing spatially explicit measures of risk and uncertainty. This approach could help decision makers to identify priority areas for intervention in order to reduce land and ecosystem services degradation.

  6. Characterization of the cardiac Na+/K+ pump by development of a comprehensive and mechanistic model.

    Science.gov (United States)

    Oka, Chiaki; Cha, Chae Young; Noma, Akinori

    2010-07-07

    A large amount of experimental data on the characteristics of the cardiac Na(+)/K(+) pump have been accumulated, but it remains difficult to predict the quantitative contribution of the pump in an intact cell because most measurements have been made under non-physiological conditions. To extrapolate the experimental findings to intact cells, we have developed a comprehensive Na(+)/K(+) pump model based on the thermodynamic framework (Smith and Crampin, 2004) of the Post-Albers reaction cycle combined with access channel mechanisms. The new model explains a variety of experimental results for the Na(+)/K(+) pump current (I(NaK)), including the dependency on the concentrations of Na(+) and K(+), the membrane potential and the free energy of ATP hydrolysis. The model demonstrates that both the apparent affinity and the slope of the substrate-I(NaK) relationship measured experimentally are affected by the composition of ions in the extra- and intracellular solutions, indirectly through alteration in the probability distribution of individual enzyme intermediates. By considering the voltage dependence in the Na(+)- and K(+)-binding steps, the experimental voltage-I(NaK) relationship could be reconstructed with application of experimental ionic compositions in the model, and the view of voltage-dependent K(+) binding was supported. Re-evaluation of charge movements accompanying Na(+) and K(+) translocations gave a reasonable number for the site density of the Na(+)/K(+) pump on the membrane. The new model is relevant for simulation of cellular functions under various interventions, such as depression of energy metabolism. (c) 2010 Elsevier Ltd. All rights reserved.

  7. Development and evaluation of a dimensionless mechanistic pan coating model for the prediction of coated tablet appearance.

    Science.gov (United States)

    Niblett, Daniel; Porter, Stuart; Reynolds, Gavin; Morgan, Tomos; Greenamoyer, Jennifer; Hach, Ronald; Sido, Stephanie; Karan, Kapish; Gabbott, Ian

    2017-08-07

    A mathematical, mechanistic tablet film-coating model has been developed for pharmaceutical pan coating systems based on the mechanisms of atomisation, tablet bed movement and droplet drying with the main purpose of predicting tablet appearance quality. Two dimensionless quantities were used to characterise the product properties and operating parameters: the dimensionless Spray Flux (relating to area coverage of the spray droplets) and the Niblett Number (relating to the time available for drying of coating droplets). The Niblett Number is the ratio between the time a droplet needs to dry under given thermodynamic conditions and the time available for the droplet while on the surface of the tablet bed. The time available for drying on the tablet bed surface is critical for appearance quality. These two dimensionless quantities were used to select process parameters for a set of 22 coating experiments, performed over a wide range of multivariate process parameters. The dimensionless Regime Map created can be used to visualise the effect of interacting process parameters on overall tablet appearance quality and defects such as picking and logo bridging. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    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

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  9. Thermal tides and studies to tune the mechanistic tidal model using UARS observations

    Directory of Open Access Journals (Sweden)

    V. A. Yudin

    1997-09-01

    Full Text Available Monthly simulations of the thermal diurnal and semidiurnal tides are compared to High-Resolution Doppler Imager (HRDI and Wind Imaging Interferometer (WINDII wind and temperature measurements on the Upper-Atmosphere Research Satellite (UARS. There is encouraging agreement between the observations and the linear global mechanistic tidal model results both for the diurnal and semidiurnal components in the equatorial and mid-latitude regions. This gives us the confidence to outline the first steps of an assimilative analysis/interpretation for tides, dissipation, and mean flow using a combination of model results and the global measurements from HRDI and WINDII. The sensitivity of the proposed technique to the initial guess employed to obtain a best fit to the data by tuning model parameters is discussed for the January and March 1993 cases, when the WINDII day and night measurements of the meridional winds between 90 and 110 km are used along with the daytime HRDI measurements. Several examples for the derivation of the tidal variables and decomposition of the measured winds into tidal and mean flow components using this approach are compared with previous tidal estimates and modeling results for the migrating tides. The seasonal cycle of the derived diurnal tidal amplitudes are discussed and compared with radar observation between 80 and 100 km and 40°S and 40°N.

  10. Thermal tides and studies to tune the mechanistic tidal model using UARS observations

    Directory of Open Access Journals (Sweden)

    V. A. Yudin

    Full Text Available Monthly simulations of the thermal diurnal and semidiurnal tides are compared to High-Resolution Doppler Imager (HRDI and Wind Imaging Interferometer (WINDII wind and temperature measurements on the Upper-Atmosphere Research Satellite (UARS. There is encouraging agreement between the observations and the linear global mechanistic tidal model results both for the diurnal and semidiurnal components in the equatorial and mid-latitude regions. This gives us the confidence to outline the first steps of an assimilative analysis/interpretation for tides, dissipation, and mean flow using a combination of model results and the global measurements from HRDI and WINDII. The sensitivity of the proposed technique to the initial guess employed to obtain a best fit to the data by tuning model parameters is discussed for the January and March 1993 cases, when the WINDII day and night measurements of the meridional winds between 90 and 110 km are used along with the daytime HRDI measurements. Several examples for the derivation of the tidal variables and decomposition of the measured winds into tidal and mean flow components using this approach are compared with previous tidal estimates and modeling results for the migrating tides. The seasonal cycle of the derived diurnal tidal amplitudes are discussed and compared with radar observation between 80 and 100 km and 40°S and 40°N.

  11. A comparative kinetic and mechanistic study between tetrahydrozoline and naphazoline toward photogenerated reactive oxygen species.

    Science.gov (United States)

    Criado, Susana; García, Norman A

    2010-01-01

    Kinetic and mechanistic aspects of the vitamin B2 (riboflavin [Rf])-sensitized photo-oxidation of the imidazoline derivates (IDs) naphazoline (NPZ) and tetrahydrozoline (THZ) were investigated in aqueous solution. The process appears as important on biomedical grounds, considering that the vitamin is endogenously present in humans, and IDs are active components of ocular medicaments of topical application. Under aerobic visible light irradiation, a complex picture of competitive interactions between sensitizer, substrates and dissolved oxygen takes place: the singlet and triplet ((3)Rf*) excited states of Rf are quenched by the IDs: with IDs concentrations ca. 5.0 mM and 0.02 mM Rf, (3)Rf* is quenched by IDs, in a competitive fashion with dissolved ground state oxygen. Additionally, the reactive oxygen species: O(2)((1)Delta(g)), O(2)(*-), HO(*) and H(2)O(2), generated from (3)Rf* and Rf(*-), were detected with the employment of time-resolved methods or specific scavengers. Oxygen uptake experiments indicate that, for NPZ, only H(2)O(2) was involved in the photo-oxidation. In the case of THZ, O(2)(*-), HO(*) and H(2)O(2) were detected, whereas only HO(*) was unambiguously identified as THZ oxidative agents. Upon direct UV light irradiation NPZ and THZ generate O(2)((1)Delta(g)), with quantum yields of 0.2 (literature value, employed as a reference) and 0.08, respectively, in acetonitrile.

  12. Application of comparative vibrational spectroscopic and mechanistic studies in analysis of fisetin structure.

    Science.gov (United States)

    Dimitrić Marković, Jasmina M; Marković, Zoran S; Milenković, Dejan; Jeremić, Svetlana

    2011-12-01

    This paper addresses experimental and theoretical research in fisetin (2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one) structure by means of experimental IR and Raman spectroscopies and mechanistic calculations. Density Functional Theory calculations, with M05-2X functional and the 6-311+G (2df, p) basis set implemented in the Gaussian 09 package, are performed with the aim to support molecular structure, vibrational bands' positions and their intensities. Potential energy distribution (PED) values and the description of the largest vibrational contributions to the normal modes are calculated. The most intense bands appear in the 1650-1500 cm(-1) wavenumber region. This region involves a combination of the CO, C2C3 and C-C stretching vibrational modes. Most of the bands in the 1500-1000 cm(-1) range involve C-C stretching, O-C stretching and in-plane C-C-H, C-O-H, C-C-O and C-C-C bending vibrations of the rings. The region below 1000 cm(-1) is characteristic to the combination of in plane C-C-C-H, H-C-C-H, C-C-C-C, C-C-O-C and out of plane O-C-C-C, C-C-O-C, C-C-C-C torsional modes. The Raman spectra of baicalein and quercetin were used for qualitative comparison with fisetin spectrum and verification of band assignments. The applied detailed vibrational spectral analysis and the assignments of the bands, proposed on the basis of fundamentals, reproduced the experimental results with high degree of accuracy. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Mechanistic studies of formic acid oxidation at polycarbazole supported Pt nanoparticles

    International Nuclear Information System (INIS)

    Moghaddam, Reza B.; Pickup, Peter G.

    2013-01-01

    Highlights: •A polycarbazole support decreases the accumulation of adsorbed intermediates on Pt during formic acid oxidation. •Polycarbazole causes a bilayer of Cu to form on Pt nanoparticles during Cu underpotential deposition. •XPS suggests that both of these effects are due to electron donation from the metal (Pt or Cu) into the polymer π-system. -- Abstract: Mechanistic aspects of the promotion of formic acid oxidation at Pt nanoparticles supported on a thin layer of polycarbazole (PCZ) have been investigated by voltammetry and X-ray photoelectron spectroscopy (XPS). The Pt nanoparticles were drop coated onto a glassy carbon (GC) electrode coated with a ca. 9 nm layer of electrochemically deposited polycarbazole. After 500 s of formic acid oxidation at 0 V vs. SCE, the current at a GC/PCZ/Pt electrode was 25 times higher than at a GC/Pt electrode. Voltammetry in formic acid free H 2 SO 4 following potentiostatic oxidation of formic acid revealed that there was less accumulation of adsorbed intermediates for the polycarbazole supported Pt nanoparticles than for those deposited directly onto the glassy carbon with, 50% more Pt sites remaining available for the GC/PCZ/Pt electrode relative to the GC/Pt electrode. Independent CO stripping experiments revealed only slight differences, while Cu underpotential deposition surprisingly resulted in the deposition of a ca. two-fold excess of Cu on the polycarbazole supported particles. This observation was supported by XPS which also revealed a second Cu signal at a higher binding energy, suggesting electron donation into the conjugated π system of the polymer. Such an interaction of Pt with the polycarbazole may be responsible for its higher activity for formic acid oxidation

  14. Application of comparative vibrational spectroscopic and mechanistic studies in analysis of fisetin structure

    Science.gov (United States)

    Dimitrić Marković, Jasmina M.; Marković, Zoran S.; Milenković, Dejan; Jeremić, Svetlana

    2011-12-01

    This paper addresses experimental and theoretical research in fisetin (2-(3,4-dihydroxyphenyl)-3,7-dihydroxychromen-4-one) structure by means of experimental IR and Raman spectroscopies and mechanistic calculations. Density Functional Theory calculations, with M05-2X functional and the 6-311+G (2df, p) basis set implemented in the Gaussian 09 package, are performed with the aim to support molecular structure, vibrational bands' positions and their intensities. Potential energy distribution (PED) values and the description of the largest vibrational contributions to the normal modes are calculated. The most intense bands appear in the 1650-1500 cm -1 wavenumber region. This region involves a combination of the C dbnd O, C2 dbnd C3 and C-C stretching vibrational modes. Most of the bands in the 1500-1000 cm -1 range involve C-C stretching, O-C stretching and in-plane C-C-H, C-O-H, C-C-O and C-C-C bending vibrations of the rings. The region below 1000 cm -1 is characteristic to the combination of in plane C-C-C-H, H-C-C-H, C-C-C-C, C-C-O-C and out of plane O-C-C-C, C-C-O-C, C-C-C-C torsional modes. The Raman spectra of baicalein and quercetin were used for qualitative comparison with fisetin spectrum and verification of band assignments. The applied detailed vibrational spectral analysis and the assignments of the bands, proposed on the basis of fundamentals, reproduced the experimental results with high degree of accuracy.

  15. Bortezomib-induced painful peripheral neuropathy: an electrophysiological, behavioral, morphological and mechanistic study in the mouse.

    Directory of Open Access Journals (Sweden)

    Valentina A Carozzi

    Full Text Available Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for the treatment of relapsed/refractory multiple myeloma as well as other hematological and solid neoplasms. Peripheral neurological complications manifesting with paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception and vibratory sensitivity are among the major limiting side effects associated with bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy is clinically easy to diagnose and reliable models are available, its pathophysiology remains partly unclear. In this study we used well-characterized immune-competent and immune-compromised mouse models of bortezomib-induced painful peripheral neuropathy. To characterize the drug-induced pathological changes in the peripheral nervous system, we examined the involvement of spinal cord neuronal function in the development of neuropathic pain and investigated the relevance of the immune response in painful peripheral neuropathy induced by bortezomib. We found that bortezomib treatment induced morphological changes in the spinal cord, dorsal roots, dorsal root ganglia (DRG and peripheral nerves. Neurophysiological abnormalities and specific functional alterations in Aδ and C fibers were also observed in peripheral nerve fibers. Mice developed mechanical allodynia and functional abnormalities of wide dynamic range neurons in the dorsal horn of spinal cord. Bortezomib induced increased expression of the neuronal stress marker activating transcription factor-3 in most DRG. Moreover, the immunodeficient animals treated with bortezomib developed a painful peripheral neuropathy with the same features observed in the immunocompetent mice. In conclusion, this study extends the knowledge of the sites of damage induced in the nervous system by bortezomib administration. Moreover, a selective functional vulnerability of peripheral nerve fiber subpopulations

  16. Detailed Mechanistic Studies on Palladium-Catalyzed Selective C-H Olefination with Aliphatic Alkenes: A Significant Influence of Proton Shuttling.

    Science.gov (United States)

    Deb, Arghya; Hazra, Avijit; Peng, Qian; Paton, Robert S; Maiti, Debabrata

    2017-01-18

    Directing group-assisted regioselective C-H olefination with electronically biased olefins is well studied. However, the incorporation of unactivated olefins has remained largely unsuccessful. A proper mechanistic understanding of olefination involving unactivated alkenes is therefore essential for enhancing their usage in future. In this Article, detailed experimental and computational mechanistic studies on palladium catalyzed C-H olefination with unactivated, aliphatic alkenes are described. The isolation of Pd(II) intermediates is shown to be effective for elucidating the elementary steps involved in catalytic olefination. Reaction rate and order determination, control experiments, isotopic labeling studies, and Hammett analysis have been used to understand the reaction mechanism. The results from these experimental studies implicate β-hydride elimination as the rate-determining step and that a mechanistic switch occurs between cationic and neutral pathway. Computational studies support this interpretation of the experimental evidence and are used to uncover the origins of selectivity.

  17. Coupling machine learning with mechanistic models to study runoff production and river flow at the hillslope scale

    Science.gov (United States)

    Marçais, J.; Gupta, H. V.; De Dreuzy, J. R.; Troch, P. A. A.

    2016-12-01

    Geomorphological structure and geological heterogeneity of hillslopes are major controls on runoff responses. The diversity of hillslopes (morphological shapes and geological structures) on one hand, and the highly non linear runoff mechanism response on the other hand, make it difficult to transpose what has been learnt at one specific hillslope to another. Therefore, making reliable predictions on runoff appearance or river flow for a given hillslope is a challenge. Applying a classic model calibration (based on inverse problems technique) requires doing it for each specific hillslope and having some data available for calibration. When applied to thousands of cases it cannot always be promoted. Here we propose a novel modeling framework based on coupling process based models with data based approach. First we develop a mechanistic model, based on hillslope storage Boussinesq equations (Troch et al. 2003), able to model non linear runoff responses to rainfall at the hillslope scale. Second we set up a model database, representing thousands of non calibrated simulations. These simulations investigate different hillslope shapes (real ones obtained by analyzing 5m digital elevation model of Brittany and synthetic ones), different hillslope geological structures (i.e. different parametrizations) and different hydrologic forcing terms (i.e. different infiltration chronicles). Then, we use this model library to train a machine learning model on this physically based database. Machine learning model performance is then assessed by a classic validating phase (testing it on new hillslopes and comparing machine learning with mechanistic outputs). Finally we use this machine learning model to learn what are the hillslope properties controlling runoffs. This methodology will be further tested combining synthetic datasets with real ones.

  18. Synthesis of highly reactive polyisobutylene with FeCl3/ether complexes in hexane; kinetic and mechanistic studies

    KAUST Repository

    Kumar, Rajeev Ananda; De, Priyadarsi; Zheng, Bin; Huang, Kuo-Wei; Emert, Jack I.; Faust, Rudolf

    2015-01-01

    The kinetics and mechanism of the polymerization of isobutylene catalyzed by FeCl3·ether complexes in hexane at 0°C were investigated. The polymerization rates increased in the diisopropyl ether< 2-chloroethyl ethyl ether < bis(2-chloroethyl) ether order, attributed to electronic effects. The polymerization rates increased with increasing initiator and catalyst concentrations. The first order plots, however, deviated from the linear suggesting that the cation concentration decreases with time. The previously proposed mechanism is inadequate to explain this finding. The decrease in the polymerization rate with time is explained by the low solubility of the H+ROR′FeCl4 - complexes that precipitate during polymerization. Based on mechanistic studies the revised mechanism now also includes the equilibrium H+ROR′FeCl4 - ⇋ HCl + FeCl3·ROR′.

  19. BIOMAP A Daily Time Step, Mechanistic Model for the Study of Ecosystem Dynamics

    Science.gov (United States)

    Wells, J. R.; Neilson, R. P.; Drapek, R. J.; Pitts, B. S.

    2010-12-01

    BIOMAP simulates competition between two Plant Functional Types (PFT) at any given point in the conterminous U.S. using a time series of daily temperature (mean, minimum, maximum), precipitation, humidity, light and nutrients, with PFT-specific rooting within a multi-layer soil. The model employs a 2-layer canopy biophysics, Farquhar photosynthesis, the Beer-Lambert Law for light attenuation and a mechanistic soil hydrology. In essence, BIOMAP is a re-built version of the biogeochemistry model, BIOME-BGC, into the form of the MAPSS biogeography model. Specific enhancements are: 1) the 2-layer canopy biophysics of Dolman (1993); 2) the unique MAPSS-based hydrology, which incorporates canopy evaporation, snow dynamics, infiltration and saturated and unsaturated percolation with ‘fast’ flow and base flow and a ‘tunable aquifer’ capacity, a metaphor of D’Arcy’s Law; and, 3) a unique MAPSS-based stomatal conductance algorithm, which simultaneously incorporates vapor pressure and soil water potential constraints, based on physiological information and many other improvements. Over small domains the PFTs can be parameterized as individual species to investigate fundamental vs. potential niche theory; while, at more coarse scales the PFTs can be rendered as more general functional groups. Since all of the model processes are intrinsically leaf to plot scale (physiology to PFT competition), it essentially has no ‘intrinsic’ scale and can be implemented on a grid of any size, taking on the characteristics defined by the homogeneous climate of each grid cell. Currently, the model is implemented on the VEMAP 1/2 degree, daily grid over the conterminous U.S. Although both the thermal and water-limited ecotones are dynamic, following climate variability, the PFT distributions remain fixed. Thus, the model is currently being fitted with a ‘reproduction niche’ to allow full dynamic operation as a Dynamic General Vegetation Model (DGVM). While global simulations

  20. Development of a mechanistic model for release of radionuclides from spent fuel in brines: Salt Repository Project

    International Nuclear Information System (INIS)

    Reimus, P.W.; Windisch, C.F.

    1988-03-01

    At present there are no comprehensive mechanistic models describing the release of radionuclides from spent fuel in brine environments. This report provides a comprehensive review of the various factors that can affect radionuclide release from spent fuel, suggests a modeling approach, and discusses proposed experiments for obtaining a better mechanistic understanding of the radionuclide release processes. Factors affecting radionuclide release include the amount, location, and disposition of radionuclides in the fuel and environmental factors such as redox potential, pH, the presence of complexing anions, temperature, and radiolysis. It is concluded that a model describing the release of radionuclides from spent fuel should contain separate terms for release from the gap, grain boundaries, and grains of the fuel. Possible functional forms for these terms are discussed in the report. Experiments for assessing their validity and obtaining key model parameters are proposed. 71 refs., 4 figs., 6 tabs

  1. Mechanistic study and modeling of radionuclides retention by the hydrated calcium silicates (HCS) of cements

    International Nuclear Information System (INIS)

    Pointeau, I.

    2000-09-01

    This work attempts to investigate the modelling of radioisotopes (Cs + , Pb 2+ , Eu 3+ ) immobilization in cement matrix, in the frame of the design of engineered barrier of a deep radwaste repository. The model development concept consists of three major steps: - surface chemistry modelling of the calcium silicate hydrate CSH, used to simulate hydrated cement behaviour; - solid analysis of the batch sorption experiments: identification of the uptake mechanism; - both previous steps are used, with isotherm data, in the modelling of the radioisotopes immobilization in the CSH matrix. Final results: (all modelling are available for all the range of studied Ca/Si ratios and have been validated with predictive calculations). - A thermodynamic modelling of the CSH surface chemistry has been developed. The labile calcium and proton sorption constants on silanol sites (>SiOH) have been extracted. - Cs + is sorbed on two sites. The silanol site (weak site) has a high site density (10 sites.nm -2 ), which accounts for the CSH unsaturation in high [CS + ]. A strong site is also identified. - Pb 2+ immobilization in CSH matrix is modelled with surface equilibria and solubility equilibrium. - Eu 3+ fixation has been investigated with solid analysis: Site-Selective anti Time-Resolved Luminescence Spectroscopy, XPS and SEM-EDS. Eu 3+ thus does not precipitate in CSH water but is sorbed on the CSH surface (high hydroxylated environment). Europium is also (minority site) inserted in the CSH framework. (author)

  2. Incorporation of basic side chains into cryptolepine scaffold: structure-antimalarial activity relationships and mechanistic studies.

    Science.gov (United States)

    Lavrado, João; Cabal, Ghislain G; Prudêncio, Miguel; Mota, Maria M; Gut, Jiri; Rosenthal, Philip J; Díaz, Cecília; Guedes, Rita C; dos Santos, Daniel J V A; Bichenkova, Elena; Douglas, Kenneth T; Moreira, Rui; Paulo, Alexandra

    2011-02-10

    The synthesis of cryptolepine derivatives containing basic side-chains at the C-11 position and their evaluations for antiplasmodial and cytotoxicity properties are reported. Propyl, butyl, and cycloalkyl diamine side chains significantly increased activity against chloroquine-resistant Plasmodium falciparum strains while reducing cytotoxicity when compared with the parent compound. Localization studies inside parasite blood stages by fluorescence microscopy showed that these derivatives accumulate inside the nucleus, indicating that the incorporation of a basic side chain is not sufficient enough to promote selective accumulation in the acidic digestive vacuole of the parasite. Most of the compounds within this series showed the ability to bind to a double-stranded DNA duplex as well to monomeric hematin, suggesting that these are possible targets associated with the observed antimalarial activity. Overall, these novel cryptolepine analogues with substantially improved antiplasmodial activity and selectivity index provide a promising starting point for development of potent and highly selective agents against drug-resistant malaria parasites.

  3. Effect of Asparagus racemosus extract on transdermal delivery of carvedilol: a mechanistic study.

    Science.gov (United States)

    Sapra, Bharti; Jain, Subheet; Tiwary, Ashok K

    2009-01-01

    This study was designed for investigating the effect of Asparagus racemosus (AR) extract and chitosan (CTN) in facilitating the permeation of carvedilol (CDL) across rat epidermis. Transdermal flux of carvedilol through heat-separated rat epidermis was investigated in vitro using vertical Keshary-Chien diffusion cells. Biophysical and microscopic manifestations of epidermis treated with AR extract, CTN, and AR extract-CTN mixture were investigated by using differential scanning calorimetry, transepidermal water loss, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Biochemical estimations of cholesterol, sphingosine, and triglycerides were carried out for treated excised as well as viable rat epidermis. The antihypertensive activity of the patches in comparison with that of oral carvedilol was studied in deoxycorticosterone acetate-induced hypertensive rats. The permeation of carvedilol across excised rat epidermis was significantly higher (p vehicle as compared to propylene glycol/ethanol (7:3) mixture. Epidermis obtained after 12 h treatment of viable rat skin with AR extract-CTN mixture showed significantly higher (p space, disordered lipid structure, and corneocyte detachment as observed in SEM and TEM suggested great potential of AR extract for use as percutaneous permeation enhancer. The developed transdermal patches of CDL containing AR extract-CTN mixture exhibited better performance as compared to oral administration in controlling hypertension in rats.

  4. Integrating experimental and simulation length and time scales in mechanistic studies of friction

    International Nuclear Information System (INIS)

    Sawyer, W G; Perry, S S; Phillpot, S R; Sinnott, S B

    2008-01-01

    Friction is ubiquitous in all aspects of everyday life and has consequently been under study for centuries. Classical theories of friction have been developed and used to successfully solve numerous tribological problems. However, modern applications that involve advanced materials operating under extreme environments can lead to situations where classical theories of friction are insufficient to describe the physical responses of sliding interfaces. Here, we review integrated experimental and computational studies of atomic-scale friction and wear at solid-solid interfaces across length and time scales. The influence of structural orientation in the case of carbon nanotube bundles, and molecular orientation in the case of polymer films of polytetrafluoroethylene and polyethylene, on friction and wear are discussed. In addition, while friction in solids is generally considered to be athermal, under certain conditions thermally activated friction is observed for polymers, carbon nanotubes and graphite. The conditions under which these transitions occur, and their proposed origins, are discussed. Lastly, a discussion of future directions is presented

  5. Oxidative degradation of alternative gasoline oxygenates in aqueous solution by ultrasonic irradiation: Mechanistic study

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Duk Kyung, E-mail: dkim@aum.edu [Department of Physical Science, Auburn University Montgomery, Montgomery, AL 36117 (United States); O' Shea, Kevin E., E-mail: osheak@fiu.edu [Department of Chemistry and Biochemistry, Florida International University, University Park, Miami, FL 33199 (United States); Cooper, William J. [Department of Civil and Environmental Engineering, Urban Water Research Center, University of California Irvine, Irvine, CA 92697-2175 (United States)

    2012-07-15

    Widespread pollution has been associated with gasoline oxygenates of branched ethers methyl tert-butyl ether (MTBE), di-isopropyl ether (DIPE), ethyl tert-butyl ether (ETBE), and tert-amyl ether (TAME) which enter groundwater. The contaminated plume develops rapidly and treatment for the removal/destruction of these ethers is difficult when using conventional methods. Degradation of MTBE, with biological methods and advanced oxidation processes, are rather well known; however, fewer studies have been reported for degradation of alternative oxygenates. Degradation of alternative gasoline oxygenates (DIPE, ETBE, and TAME) by ultrasonic irradiation in aqueous oxygen saturation was investigated to elucidate degradation pathways. Detailed degradation mechanisms are proposed for each gasoline oxygenate. The common major degradation pathways are proposed to involve abstraction of {alpha}-hydrogen atoms by hydroxyl radicals generated during ultrasound cavitation and low temperature pyrolytic degradation of ETBE and TAME. Even some of the products from {beta}-H abstraction overlap with those from high temperature pyrolysis, the effect of {beta}-H abstraction was not shown clearly from product study because of possible 1,5 H-transfer inside cavitating bubbles. Formation of hydrogen peroxide and organic peroxides was also determined during sonolysis. These data provide a better understanding of the degradation pathways of gasoline oxygenates by sonolysis in aqueous solutions. The approach may also serve as a model for others interested in the details of sonolysis. - Highlights: Black-Right-Pointing-Pointer Gasoline oxygenates (ETBE, TAME, DIPE) were completely degraded after 6 hours under ultrasonic irradiation in O{sub 2} saturation. Black-Right-Pointing-Pointer The major degradation pathways were proposed to involve abstraction of {alpha}-hydrogen atoms by hydroxyl radicals and low temperature pyrolytic degradation. Black-Right-Pointing-Pointer The effect of {beta

  6. Mechanistic insights into the vascular effects of blueberries: Evidence from recent studies.

    Science.gov (United States)

    Cutler, Brett Ronald; Petersen, Chrissa; Anandh Babu, Pon Velayutham

    2017-06-01

    Cardiovascular disease is the leading cause of death in the United States. Dietary habits influence a variety of cardiovascular complications such as peripheral artery disease, heart failure, and kidney disease. We along with others have previously reported the cardiovascular beneficial effects of dietary flavonoids. Anthocyanins, one class of flavonoids widely available in berries, have recently drawn wide scientific attention because of their diverse health benefits. Epidemiological, clinical, and animal studies indicate that blueberry anthocyanins exert protection against cardiovascular complications by acting on multiple targets in the vascular system. These include activating endothelial nitric oxide synthase signaling, reducing oxidative stress, improving inflammatory pathways, and ameliorating dyslipidemia. Anthocyanins are extensively metabolized in humans suggesting that their vascular benefits are likely mediated by their circulating metabolites. However, the bioactivities of blueberry metabolites are unknown. Evaluating the bioactivities of metabolites, analyzing their structure-activity relationship, and well-designed human trials are needed to understand the potential vascular effects of blueberries and their metabolites. Understanding the vascular effects will provide a solid scientific foundation to recommend blueberries to improve vascular health. This review highlights the recent developments in the understanding of the vascular effects of blueberries with special emphasis on the molecular mechanisms involved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Toughening of nanocelluose/PLA composites via bio-epoxy interaction: Mechanistic study

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangtao [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bocharova, Vera [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tekinalp, Halil L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States); Cheng, Shiwang [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kisliuk, Alexander [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Sokolov, Alexei P. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kunc, Vlastimil [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Peter, William H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ozcan, Soydan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Univ. of Tennessee, Knoxville, TN (United States)

    2017-11-07

    While PLA possesses modest to good strength and stiffness, broader application is hindered by its brittle nature. The aim of this study was to develop strong and tough polymeric materials from renewable biomaterials and understand the underlying interactions and mechanisms. Cellulose nanofibrils (CNFs) and epoxidized soybean oil (ESO) were compounded with poly(lactic acid) (PLA) to create a PLA-CNF-ESO tertiary nanocomposite system. Tensile and dynamic mechanical analyses were performed to see how variations in ESO and CNF content affect mechanical properties such as strength, modulus, ductility, and toughness. It was found that at low CNF levels (10 wt %) the addition of ESO can improve the ductility of the nanocomposites 5- to 10-fold with only slight losses in strength and modulus, while at higher CNF levels (20 and 30 wt %), ESO exhibited little effect on mechanical properties, possibly due to percolation of CNFs in the matrix, dominating stress transfer. Therefore, it is important to optimize CNF and ESO amounts in composites to achieve materials with both high strength and high toughness. As a result, efforts have been made to understand the underlying mechanisms of the mechanical behavior of one class of these composites via thermal, dynamic mechanical, morphological, and Raman analyses.

  8. Mechanistic study of the toxicity of ionizing radiation in Daphnia magna

    Energy Technology Data Exchange (ETDEWEB)

    Parisot, F.; Alonzo, F. [Institut de Radioprotection et de Surete Nucleaire, IRSN/PRP-ENV/SERIS/LECO, Laboratoire d' Ecotoxicologie des Radionucleides, Cadarache (France); Bourdineaud, J.P. [UMR CNRS 5805 EPOC - OASU Station Marine d' Arcachon Universite Bordeaux 1, Arcachon (France); Poggiale, J.C. [Mediterranean Institute of Oceanography - MIO - UMR 7294 Pytheas Institute - OSU, Aix-Marseille University, Marseille (France)

    2014-07-01

    In the last decade, the ecological impact of ionizing radiation has emerged as a growing scientific concern for ecosystems protection. However, the assessment of potential radiological effects on the environment is hampered by both a gap of available scientific data and a lack in proven methods. Understanding how ionizing radiation affects wildlife at biologically and ecologically relevant scales is a major issue in environmental protection. This issue is one of the objectives of the Strategic Research Agenda (SRA) developed in the framework of the European program STAR (Strategy for Allied Radioecology). In this context, the present PhD project aims to evaluate chronic effects of external Cs-137 gamma radiation at low doses on a representative species of aquatic ecosystems, the cladoceran crustacean Daphnia magna. More precisely, the objectives of this study are to evaluate multi-generational effects of irradiation on: (i) genotoxic effects and their potential consequences on survival, somatic growth and fecundity, (ii) the energy budget and (iii) the population dynamics of Daphnia. An experimental design was developed to expose daphnids to low doses of ionizing radiation ranging from 0,008 to 32 mGy.h{sup -1} across 3 successive generations (75 days). DNA damages were assessed using random amplified polymorphic DNA and real time PCR (RAPD - PCR). Effects on survival, somatic growth and fecundity were monitored for 21-25 days in each generation, from hatching to release of brood 5. Our aim is to: examine a potential correlation between molecular (DNA) damage and effects observed at the individual level (survival, somatic growth and fecundity) across generations and test the suitability of DNA damage as an early indice of future trans-generational effects. As a future perspective, individual and molecular effects data will be analysed using a DEBtox model (Dynamic Energy Budget Applied to Toxicology) in order to identify the metabolic modes of action of ionizing

  9. Chemical Reductive Transformations of Synthetic Organic Compounds. Probe Compound Studies and Mechanistic Modeling

    National Research Council Canada - National Science Library

    Peyton, Gary

    2001-01-01

    .... A kinetic model that was previously developed to describe the results of batch AOP treatment by H2O2/UV did not give satisfactory predictive results obtained when extended to describe flow experiments...

  10. Conceptual models for waste tank mechanistic analysis

    International Nuclear Information System (INIS)

    Allemann, R.T.; Antoniak, Z.I.; Eyler, L.L.; Liljegren, L.M.; Roberts, J.S.

    1992-02-01

    Pacific Northwest Laboratory (PNL) is conducting a study for Westinghouse Hanford Company (Westinghouse Hanford), a contractor for the US Department of Energy (DOE). The purpose of the work is to study possible mechanisms and fluid dynamics contributing to the periodic release of gases from double-shell waste storage tanks at the Hanford Site in Richland, Washington. This interim report emphasizing the modeling work follows two other interim reports, Mechanistic Analysis of Double-Shell Tank Gas Release Progress Report -- November 1990 and Collection and Analysis of Existing Data for Waste Tank Mechanistic Analysis Progress Report -- December 1990, that emphasized data correlation and mechanisms. The approach in this study has been to assemble and compile data that are pertinent to the mechanisms, analyze the data, evaluate physical properties and parameters, evaluate hypothetical mechanisms, and develop mathematical models of mechanisms

  11. Toward mechanistic classification of enzyme functions.

    Science.gov (United States)

    Almonacid, Daniel E; Babbitt, Patricia C

    2011-06-01

    Classification of enzyme function should be quantitative, computationally accessible, and informed by sequences and structures to enable use of genomic information for functional inference and other applications. Large-scale studies have established that divergently evolved enzymes share conserved elements of structure and common mechanistic steps and that convergently evolved enzymes often converge to similar mechanisms too, suggesting that reaction mechanisms could be used to develop finer-grained functional descriptions than provided by the Enzyme Commission (EC) system currently in use. Here we describe how evolution informs these structure-function mappings and review the databases that store mechanisms of enzyme reactions along with recent developments to measure ligand and mechanistic similarities. Together, these provide a foundation for new classifications of enzyme function. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Foust, Henry; Ghosehajra, Malay

    2007-01-01

    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)

  13. IRIS Toxicological Review of Hexavalent Chromium Part 2: Human, Toxicokinetic, and Mechanistic Studies (Preliminary Assessment Materials)

    Science.gov (United States)

    In August 2014, EPA released the second part of draft literature searches and associated search strategies, evidence tables, and exposure response arrays for Cr(VI) to obtain input from stakeholders and the public prior to developing the draft IRIS assessment. Specifically, EPA w...

  14. Mechanistic studies on long peptide-based vaccines for the use in cancer therapy

    NARCIS (Netherlands)

    Bijker, Martijn Sander

    2007-01-01

    Synthetic peptide vaccines aiming at the induction of a protective CD8+ T-cell response against infectious or malignant diseases are widely used in the clinic but, despite their success in animal models, they do not yet live up to their promise in humans. This thesis assesses the development of

  15. Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

    Science.gov (United States)

    Lau, Cia-Hin; Suh, Yousin

    2017-01-01

    The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

  16. Mechanistic Study of Magnesium Carbonate Semibatch Reactive Crystallization with Magnesium Hydroxide and CO2

    DEFF Research Database (Denmark)

    Han, B.; Qu, H. Y.; Niemi, H.

    2014-01-01

    This work investigates semibatch precipitation of magnesium carbonate at ambient temperature and pressure using Mg(OH)(2) and CO2 as starting materials. A thermal analysis method was developed that reflects the dissolution rate of Mg(OH)(2) and the formation of magnesium carbonate. The method...... the liquid and solid phases. A stirring rate of 650 rpm was found to be the optimum speed as the flow rate of CO2 was 1 L/min. Precipitation rate increased with gas flow rate, which indicates that mass transfer of CO2 plays a critical role in this precipitation case. Magnesium carbonate trihydrate...

  17. Mechanistic study of the isotopic-exchange reaction between gaseous hydrogen and palladium hydride powder

    International Nuclear Information System (INIS)

    Outka, D.A.; Foltz, G.W.

    1991-01-01

    A detailed mechanism for the isotopic-exchange reaction between gaseous hydrogen and solid palladium hydride is developed which extends previous model for this reaction by specifically including surface reactions. The modeling indicates that there are two surface-related processes that contribute to the overall rate of exchange: the desorption of hydrogen from the surface and the exchange between surface hydrogen and bulk hydrogen. This conclusion is based upon measurements examining the effect of small concentrations of carbon monoxide were helpful in elucidating the mechanism. Carbon monoxide reversibly inhibits certain steps in the exchange; this slows the overall rate of exchange and changes the distribution of products from the reactor

  18. Recent Advances in the Mechanistic Studies of Alkylaromatic Conversions over Zeolite Catalysts

    International Nuclear Information System (INIS)

    Min, Hyung-Ki; Hong, Suk Bong

    2013-01-01

    The transformation of alkylaromatic hydrocarbons using zeolite catalysts play big part in the current petrochemical industry. Here we review recent advances in the understanding of the reaction mechanisms of various alkylaromatic conversions with respect to the structural and physicochemical properties of zeolite catalysts employed. Indeed, the shape-selective nature of zeolite catalysts determines the type of reaction intermediates and hence the prevailing reaction mechanism together with the product distribution. The prospect of zeolite catalysis in the development of more efficient petrochemical processes is also described

  19. Mechanistic Studies of Hafnium-Pyridyl Amido-Catalyzed 1-Octene Polymerization and Chain Transfer Using Quench-Labeling Methods.

    Science.gov (United States)

    Cueny, Eric S; Johnson, Heather C; Anding, Bernie J; Landis, Clark R

    2017-08-30

    Chromophore quench-labeling applied to 1-octene polymerization as catalyzed by hafnium-pyridyl amido precursors enables quantification of the amount of active catalyst and observation of the molecular weight distribution (MWD) of Hf-bound polymers via UV-GPC analysis. Comparison of the UV-detected MWD with the MWD of the "bulk" (all polymers, from RI-GPC analysis) provides important mechanistic information. The time evolution of the dual-detection GPC data, concentration of active catalyst, and monomer consumption suggests optimal activation conditions for the Hf pre-catalyst in the presence of the activator [Ph 3 C][B(C 6 F 5 ) 4 ]. The chromophore quench-labeling agents do not react with the chain-transfer agent ZnEt 2 under the reaction conditions. Thus, Hf-bound polymeryls are selectively labeled in the presence of zinc-polymeryls. Quench-labeling studies in the presence of ZnEt 2 reveal that ZnEt 2 does not influence the rate of propagation at the Hf center, and chain transfer of Hf-bound polymers to ZnEt 2 is fast and quasi-irreversible. The quench-label techniques represent a means to study commercial polymerization catalysts that operate with high efficiency at low catalyst concentrations without the need for specialized equipment.

  20. Improving the International Agency for Research on Cancer's consideration of mechanistic evidence

    International Nuclear Information System (INIS)

    Goodman, Julie; Lynch, Heather

    2017-01-01

    Background: The International Agency for Research on Cancer (IARC) recently developed a framework for evaluating mechanistic evidence that includes a list of 10 key characteristics of carcinogens. This framework is useful for identifying and organizing large bodies of literature on carcinogenic mechanisms, but it lacks sufficient guidance for conducting evaluations that fully integrate mechanistic evidence into hazard assessments. Objectives: We summarize the framework, and suggest approaches to strengthen the evaluation of mechanistic evidence using this framework. Discussion: While the framework is useful for organizing mechanistic evidence, its lack of guidance for implementation limits its utility for understanding human carcinogenic potential. Specifically, it does not include explicit guidance for evaluating the biological significance of mechanistic endpoints, inter- and intra-individual variability, or study quality and relevance. It also does not explicitly address how mechanistic evidence should be integrated with other realms of evidence. Because mechanistic evidence is critical to understanding human cancer hazards, we recommend that IARC develop transparent and systematic guidelines for the use of this framework so that mechanistic evidence will be evaluated and integrated in a robust manner, and concurrently with other realms of evidence, to reach a final human cancer hazard conclusion. Conclusions: IARC does not currently provide a standardized approach to evaluating mechanistic evidence. Incorporating the recommendations discussed here will make IARC analyses of mechanistic evidence more transparent, and lead to assessments of cancer hazards that reflect the weight of the scientific evidence and allow for scientifically defensible decision-making. - Highlights: • IARC has a revised framework for evaluating literature on carcinogenic mechanisms. • The framework is based on 10 key characteristics of carcinogens. • IARC should develop transparent

  1. Improving the International Agency for Research on Cancer's consideration of mechanistic evidence

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, Julie, E-mail: jgoodman@gradientcorp.com; Lynch, Heather

    2017-03-15

    Background: The International Agency for Research on Cancer (IARC) recently developed a framework for evaluating mechanistic evidence that includes a list of 10 key characteristics of carcinogens. This framework is useful for identifying and organizing large bodies of literature on carcinogenic mechanisms, but it lacks sufficient guidance for conducting evaluations that fully integrate mechanistic evidence into hazard assessments. Objectives: We summarize the framework, and suggest approaches to strengthen the evaluation of mechanistic evidence using this framework. Discussion: While the framework is useful for organizing mechanistic evidence, its lack of guidance for implementation limits its utility for understanding human carcinogenic potential. Specifically, it does not include explicit guidance for evaluating the biological significance of mechanistic endpoints, inter- and intra-individual variability, or study quality and relevance. It also does not explicitly address how mechanistic evidence should be integrated with other realms of evidence. Because mechanistic evidence is critical to understanding human cancer hazards, we recommend that IARC develop transparent and systematic guidelines for the use of this framework so that mechanistic evidence will be evaluated and integrated in a robust manner, and concurrently with other realms of evidence, to reach a final human cancer hazard conclusion. Conclusions: IARC does not currently provide a standardized approach to evaluating mechanistic evidence. Incorporating the recommendations discussed here will make IARC analyses of mechanistic evidence more transparent, and lead to assessments of cancer hazards that reflect the weight of the scientific evidence and allow for scientifically defensible decision-making. - Highlights: • IARC has a revised framework for evaluating literature on carcinogenic mechanisms. • The framework is based on 10 key characteristics of carcinogens. • IARC should develop transparent

  2. The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis.

    Science.gov (United States)

    Mirabello, Lisa; Clarke, Megan A; Nelson, Chase W; Dean, Michael; Wentzensen, Nicolas; Yeager, Meredith; Cullen, Michael; Boland, Joseph F; Schiffman, Mark; Burk, Robert D

    2018-02-13

    Of the ~60 human papillomavirus (HPV) genotypes that infect the cervicovaginal epithelium, only 12-13 "high-risk" types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral-host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

  3. The Intersection of HPV Epidemiology, Genomics and Mechanistic Studies of HPV-Mediated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lisa Mirabello

    2018-02-01

    Full Text Available Of the ~60 human papillomavirus (HPV genotypes that infect the cervicovaginal epithelium, only 12–13 “high-risk” types are well-established as causing cervical cancer, with HPV16 accounting for over half of all cases worldwide. While HPV16 is the most important carcinogenic type, variants of HPV16 can differ in their carcinogenicity by 10-fold or more in epidemiologic studies. Strong genotype-phenotype associations embedded in the small 8-kb HPV16 genome motivate molecular studies to understand the underlying molecular mechanisms. Understanding the mechanisms of HPV genomic findings is complicated by the linkage of HPV genome variants. A panel of experts in various disciplines gathered on 21 November 2016 to discuss the interdisciplinary science of HPV oncogenesis. Here, we summarize the discussion of the complexity of the viral–host interaction and highlight important next steps for selected applied basic laboratory studies guided by epidemiological genomic findings.

  4. TIMES-SS - A mechanistic evaluation of an external validation study using reaction chemistry principles

    DEFF Research Database (Denmark)

    Roberts, David W.; Patlewicz, Grace; Dimitrov, Sabcho D.

    2007-01-01

    The TImes MEtabolism Simulator platform used for predicting skin sensitization (TIMES-SS) is a hybrid expert system that was developed at Bourgas University using funding and data from a consortium comprised of industry and regulators. TIMES-SS encodes structure-toxicity and structure...... chemicals in the murine local lymph node assay (LLNA) and then compared with predictions made by TIMES-SS. The results were promising with an overall good concordance (83%) between experimental and predicted values. The LLNA results were evaluated with respect to reaction chemistry principles...... for sensitization. Additional testing on a further four chemicals was carried out to explore some of the specific reaction chemistry findings in more detail. Improvements for TIMES-SS, where appropriate, were put forward together with proposals for further research work. TIMES-SS is a promising tool to aid...

  5. A mechanistic study on the oxidative coupling of methane over lithium doped magnesium oxide catalysts

    NARCIS (Netherlands)

    Geerts, J.W.M.H.; Kasteren, van J.M.N.; Wiele, van der K.; Imarisio, G.; Frias, M.; Berntgen, J.M.

    1988-01-01

    To elucidate the importance of various reaction steps in the oxidative convers ion of methane, experiments were carried out with three reaction products: ethane, ethylene and carbon monoxide. These products were studied seperately, in oxidation experiments with and without a catalyst. Moreover , the

  6. Mindfulness & Self-Compassion Meditation for Combat Posttraumatic Stress Disorder: Randomized Controlled Trial and Mechanistic Study

    Science.gov (United States)

    2013-10-01

    PTSD and depression symptoms in adult survivors of childhoods sexual abuse (Kimbrough, Magyari, Langenberg, Chesney, & Berman, 2010). Our pilot... neuropsychological / attention measures (Attention Network Task, “ANT”)  Additional training and preparation of logistic and human subject...MBSR) found acceptability and decreased PTSD symptoms in adult survivors of childhood sexual abuse. We conducted a pilot study of MBCT adapted for PTSD

  7. A Mechanistic Study of Hydroboration of 1-Octene with 1,3,2 ...

    African Journals Online (AJOL)

    dithiaborinane in their ground states have been studied using density functional theory (DFT) at the B3LYP/3-21+G and B3LYP/6-31+G(d) levels. Hydroboration and disproportionation transition states have been determined and activation energies ...

  8. Mechanistic study of ruthenium (III) catalysed oxidation of L-lysine by ...

    Indian Academy of Sciences (India)

    Administrator

    MS received 15 April 2008; revised 2 July 2008. Abstract. The kinetics of Ru(III) catalysed oxidation of L-lysine by diperiodatoargentate (III) (DPA) in alkaline medium at 298 K and a constant ionic strength of 0⋅50 mol dm. –3 was studied spectrophotometri- cally. The oxidation products are aldehyde (5-aminopentanal) and ...

  9. Alcohol in moderation, cardioprotection, and neuroprotection: epidemiological considerations and mechanistic studies.

    Science.gov (United States)

    Collins, Michael A; Neafsey, Edward J; Mukamal, Kenneth J; Gray, Mary O; Parks, Dale A; Das, Dipak K; Korthuis, Ronald J

    2009-02-01

    In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol

  10. Mechanistic studies of ocular peptide absorption and its enhancement by various penetration enhancers

    International Nuclear Information System (INIS)

    Rojanasakul, Y.

    1989-01-01

    Two major aspects of corneal peptide absorption, namely the transport mechanisms and the promoting effect of some penetration enhancers, were investigated. Studies on transport mechanisms involve (a) identification of transport pathways of peptides across the cornea, (b) determination of rate-limiting barrier(s) for peptide absorption, and (c) permselective properties of the cornea. To study the transport pathways of peptides, four model peptides differing in molecular size and charge were either fluorescently or radioactively labeled and their movement across the cornea was detected by laser scanning confocal microscopy and autoradiography. Results from these studies indicate that peptides can penetrate the cornea via different pathways, depending on the physicochemical properties and membrane specificity of the peptides. In all cases, the outermost layer of the corneal epithelium presents the rate-limiting barrier for peptide absorption. The results also indicate a charge discrimination effect to transport of negatively charged peptides. In permselectivity studies, it has been shown that the cornea, due to the presence of ionizable charged groups, is amphoteric and exhibits dual selective characteristics to transport of charged molecules. At pH's above the isoelectric point, 3.2, the cornea carries a net negative charge and is selective to positively-charged molecules. Below the isoelectric pH, the reverse is valid. The promoting mechanisms of penetration enhancers were studied microscopically using confocal fluorescence microscopy with the aid of a specific fluorescent membrane probe (3,3'-dioctadecyloxacarbocyanine) and a non-permeating polar tracer. All enhancers, including chelators, non-ionic surfactants, bile salts, and cytoskeleton-active agents, significantly increase membrane permeability depending on concentration and exposure time

  11. Rational and Mechanistic Perspectives on Reinforcement Learning

    Science.gov (United States)

    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…

  12. The reaction of nitromethane with hydrogen and deuterium atoms in the gas phase. A mechanistic study

    DEFF Research Database (Denmark)

    Lund Thomsen, E.; Nielsen, O.J.; Egsgaard, H.

    1993-01-01

    The mechanism of the reaction between H and CH3NO2, has been studied in a discharge flow system using electron paramagnetic resonance and modulated molecular beam mass spectrometry for the detection of reactants and products. Deuterium atoms have, in addition to CD3NO2, been used to support...... the proposed reaction mechanism. The reaction was studied with the atomic reactant in slight excess at 298 K and a total pressure of 2 Torr. Two concurrent reaction channels: (1a) H+CH3NO2-->HONO+.CH3 and (1b) H+CH3NO2-->CH3NO+.OH were observed. The branching ratio, k1a/(k1a+k1b), is 0.7+/-0.2....

  13. Rapid tissue regeneration induced by intracellular ATP delivery-A preliminary mechanistic study.

    Directory of Open Access Journals (Sweden)

    Harshini Sarojini

    Full Text Available We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery-extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold

  14. A combined mechanistic and computational study of the gold(I)-catalyzed formation of substituted indenes.

    Science.gov (United States)

    Nun, Pierrick; Gaillard, Sylvain; Poater, Albert; Cavallo, Luigi; Nolan, Steven P

    2011-01-07

    Substituted indenes can be prepared after a sequence [1,3] O-acyl shift-hydroarylation-[1,3] O-acyl shift. Each step is catalyzed by a cationic NHC-Gold(I) species generated in situ after reaction between [(IPr)AuOH] and HBF(4)·OEt(2). This interesting silver-free way is fully supported by a computational study justifying the formation of each intermediate.

  15. Alcohol in Moderation, Cardioprotection and Neuroprotection: Epidemiological Considerations and Mechanistic Studies

    OpenAIRE

    Collins, Michael A.; Neafsey, Edward J.; Mukamal, Kenneth J.; Gray, Mary O.; Parks, Dale A.; Das, Dipak K.; Korthuis, Ronald J.

    2008-01-01

    In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating beneficial effects of light-moderate, non-binge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alco...

  16. Kinetic and mechanistic study of microcystin-LR degradation by nitrous acid under ultraviolet irradiation

    International Nuclear Information System (INIS)

    Ma, Qingwei; Ren, Jing; Huang, Honghui; Wang, Shoubing; Wang, Xiangrong; Fan, Zhengqiu

    2012-01-01

    Highlights: ► For the first time, degradation of MC-LR by nitrous acid under UV 365 nm was discovered. ► The effects of factors on MC-LR degradation were analyzed based on kinetic study. ► Mass spectrometry was applied for identification of intermediates and products. ► Special intermediates involved in this study were identified. ► Degradation mechanisms were proposed according to the results of LC–MS analysis. - Abstract: Degradation of microcystin-LR (MC-LR) in the presence of nitrous acid (HNO 2 ) under irradiation of 365 nm ultraviolet (UV) was studied for the first time. The influence of initial conditions including pH value, NaNO 2 concentration, MC-LR concentration and UV intensity were studied. MC-LR was degraded in the presence of HNO 2 ; enhanced degradation of MC-LR was observed with 365 nm UV irradiation, caused by the generation of hydroxyl radicals through the photolysis of HNO 2 . The degradation processes of MC-LR could well fit the pseudo-first-order kinetics. Mass spectrometry was applied for identification of the byproducts and the analysis of degradation mechanisms. Major degradation pathways were proposed according to the results of LC–MS analysis. The degradation of MC-LR was initiated via three major pathways: attack of hydroxyl radicals on the conjugated carbon double bonds of Adda, attack of hydroxyl radicals on the benzene ring of Adda, and attack of nitrosonium ion on the benzene ring of Adda.

  17. Kinetic and mechanistic study of microcystin-LR degradation by nitrous acid under ultraviolet irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Qingwei; Ren, Jing [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China); Huang, Honghui [Key Laboratory of Fisheries Ecology Environment, Ministry of Agriculture, Guangzhou 510300 (China); Wang, Shoubing [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China); Wang, Xiangrong, E-mail: xrxrwang@vip.sina.com [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China); Fan, Zhengqiu, E-mail: zhqfan@fudan.edu.cn [Department of Environmental Science and Engineering, Fudan University, Shanghai 200433 (China)

    2012-05-15

    Highlights: Black-Right-Pointing-Pointer For the first time, degradation of MC-LR by nitrous acid under UV 365 nm was discovered. Black-Right-Pointing-Pointer The effects of factors on MC-LR degradation were analyzed based on kinetic study. Black-Right-Pointing-Pointer Mass spectrometry was applied for identification of intermediates and products. Black-Right-Pointing-Pointer Special intermediates involved in this study were identified. Black-Right-Pointing-Pointer Degradation mechanisms were proposed according to the results of LC-MS analysis. - Abstract: Degradation of microcystin-LR (MC-LR) in the presence of nitrous acid (HNO{sub 2}) under irradiation of 365 nm ultraviolet (UV) was studied for the first time. The influence of initial conditions including pH value, NaNO{sub 2} concentration, MC-LR concentration and UV intensity were studied. MC-LR was degraded in the presence of HNO{sub 2}; enhanced degradation of MC-LR was observed with 365 nm UV irradiation, caused by the generation of hydroxyl radicals through the photolysis of HNO{sub 2}. The degradation processes of MC-LR could well fit the pseudo-first-order kinetics. Mass spectrometry was applied for identification of the byproducts and the analysis of degradation mechanisms. Major degradation pathways were proposed according to the results of LC-MS analysis. The degradation of MC-LR was initiated via three major pathways: attack of hydroxyl radicals on the conjugated carbon double bonds of Adda, attack of hydroxyl radicals on the benzene ring of Adda, and attack of nitrosonium ion on the benzene ring of Adda.

  18. Mechanistic interaction study of thin oxide dielectric with conducting organic electrode

    International Nuclear Information System (INIS)

    Sharma, Himani; Sethi, Kanika; Raj, P. Markondeya; Gerhardt, R.A.; Tummala, Rao

    2012-01-01

    Highlights: ► Thin film-oxide dielectric-organic electrode interface studies for investigating the leakage mechanism. ► XPS to elucidate chemical-structural changes on dielectric oxide surface. ► Correlates structural characterization data with capacitor leakage current and impedance spectroscopy characteristics. - Abstract: This paper aims at understanding the interaction of intrinsic conducting polymer, PEDT, with ALD-deposited Al 2 O 3 and thermally oxidized Ta 2 O 5 dielectrics, and the underlying mechanisms for increase in leakage currents in PEDT-based capacitors. Conducting polymers offer several advantages as electrodes for high surface area capacitors because of their lower resistance, self-healing and enhanced conformality. However, capacitors with in situ polymerized PEDT show poor electrical properties that are attributed to the interfacial interaction between the organic electrode and the oxide dielectric. This study focuses on characterizing these interactions. A combination of compositional, structural and electrical characterization techniques was applied to polymer-solid-state-capacitor to understand the interfacial chemical behavior and dielectric property deterioration of alumina and tantalum-oxide films. XPS and impedance studies were employed to understand the stiochiometric and compositional changes that occur in the dielectric film on interaction with in situ deposited PEDT. Based on the observations from several complimentary techniques, it is concluded that tantalum-pentoxide has more resistance towards chemical interaction with in situ polymerized PEDT. The thermally oxidized Ta 2 O 5 -PEDT system showed leakage current of 280 nA μF −1 at 3 V with a breakdown voltage of 30 V. On the other hand, Al 2 O 3 -PEDT capacitor showed leakage current of 50 μA μF −1 and a breakdown voltage of 40 V. The study reports direct evidence for the mechanism of resistivity drop in alumina dielectric with in situ polymerized PEDT electrode.

  19. First-principles mechanistic studies of ammonia-related industrial processes

    OpenAIRE

    Gómez Díaz, Jaime

    2011-01-01

    In this dissertation, the mechanisms that govern four essential industrial processes have been studied by means of Density Functional Theory (DFT). The processes are the following: Ostwald (HNO3 production), Degussa and Andrussow (HCN production) and MacArthurForrest (gold recovery). In these processes, ammonia is the main raw material or a precursor of it.The KohnSham equations that describe the model systems have been solved by means of VASP and GPAW using the RPBE functional. These package...

  20. β-Elemene: Mechanistic Studies on Cancer Cell Interaction and Its Chemosensitization Effect

    Science.gov (United States)

    Jiang, Ziyu; Jacob, Joe A.; Loganathachetti, Dinesh S.; Nainangu, Prasannabalaji; Chen, Baoan

    2017-01-01

    Over the past decade, screening and identifying novel compounds for their biomedical applications has become an upcoming area of research. Identifying the molecular mechanisms of these compounds has become an integral part of anticancer research. β-elemene, a sesquiterpene, is renowned for its anticancer activity against a variety of cell lines. Recent studies on β-elemene have elucidated that it possesses anti-proliferative effect on cancer cells by creating an apoptotic trigger. Interestingly, it also induces protective autophagy in some cancerous cell lines and is less cytotoxic compared to other widely accepted chemotherapeutic agents. This provides an edge with the perception of limited toxicity to normal cells. This mini-review precisely focuses on the studies performed to identify the mechanism of anticancer activity of β-elemene against cancer cells of multiple origin. In accordance to the evaluation made by the studies mentioned, apoptosis has been identified to be most possible reason behind anticancer activity exerted by β-elemene against a variety of cancer cell lines. Cell cycle arrest and necrosis have been credited to be possible alternate mechanisms for the anticancer effect of β-elemene. PMID:28337141

  1. Mechanistic study of the azithromycin dosage-form-dependent food effect.

    Science.gov (United States)

    Curatolo, William; Foulds, George; Labadie, Robert

    2010-07-01

    Azithromycin capsules are known to exhibit a negative food effect, manifest as a decrease in azithromycin bioavailability in the fed state. Azithromycin tablets are known to be bioequivalent to capsules in the fasted state, but do not exhibit a food effect. In the present study, the involvement of gastric degradation of azithromycin to des-cladinose azithromycin (DCA) has been investigated as a possible mechanism for the observed capsule food effect. Healthy volunteers were dosed with azithromycin tablets and capsules, fasted and fed, in a four-way randomized crossover study. Serum levels of DCA were measured as a function of time post-dose. Natural log-transformed PK parameters were statistically analyzed using an ANOVA model appropriate for the study design. When capsules were dosed to fed subjects, the systemic AUC for DCA was 243% of the value observed after fasted-state dosing, and the DCA C(max) was 270% of the value observed after fasted-state dosing. When azithromycin tablets were dosed in the fasted and fed states, there was no significant difference in systemic DCA. Gastric degradation of azithromycin to DCA is the likely mechanism for the observed negative food effect observed for azithromycin capsules. This effect is not observed for tablets. These observations suggest that azithromycin capsules exhibit slow and/or delayed disintegration in the fed stomach, resulting in extended gastric residence and degradation of a portion of the gastrically retained azithromycin.

  2. Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15.

    Science.gov (United States)

    Rajebahadur, Minal; Zia, Hossein; Nues, Anthony; Lee, Chong

    2006-01-01

    The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.

  3. Mechanistic Studies of Metal-Oxo Cubane Catalysts for Lightweight Solar Fuels Storage

    Science.gov (United States)

    2013-03-01

    13692. 4 “ Single - crystal growth, crystal and electronic structure of NaCoO2.” Takahashi, Y.; Gotoh, Y.; Akimoto, J. J. Sol. State Chem. 2003, 172, 22...bond formation by the Co–OEC catalysts. 2. A penetrating study of Co3 +|Co4+ self-exchange kinetics of Co4O4 cubanes and a detailed understanding of...construct the artificial leaf described in (7). 4. The examination of Co2+| Co3 + self-exchange in a faithful structural molecular analog of the 7

  4. Empirical Force Fields for Mechanistic Studies of Chemical Reactions in Proteins.

    Science.gov (United States)

    Das, A K; Meuwly, M

    2016-01-01

    Following chemical reactions in atomistic detail is one of the most challenging aspects of current computational approaches to chemistry. In this chapter the application of adiabatic reactive MD (ARMD) and its multistate version (MS-ARMD) are discussed. Both methods allow to study bond-breaking and bond-forming processes in chemical and biological processes. Particular emphasis is put on practical aspects for applying the methods to investigate the dynamics of chemical reactions. The chapter closes with an outlook of possible generalizations of the methods discussed. © 2016 Elsevier Inc. All rights reserved.

  5. Oxidation of Methionine by Tripropylammonium Fluorochromate-A Kinetic and Mechanistic Study

    Directory of Open Access Journals (Sweden)

    S. Sheik Mansoor

    2011-01-01

    Full Text Available The kinetics of oxidation of methionine (Met by tripropylammonium fluorochromate (TriPAFC has been studied in the presence of chloroacetic acid in aqueous acetic acid medium. The reaction is first order with respect to methionine, TriPAFC and acid. The reaction rate has been determined at different temperatures and activation parameters calculated. With an increase in the amount of acetic acid in its aqueous mixture, the rate increases. The reaction does not induce polymerization of acrylonitrile. A suitable mechanism has been proposed.

  6. Cationic Pd(II-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

    Directory of Open Access Journals (Sweden)

    Takashi Nishikata

    2016-05-01

    Full Text Available Cationic palladium(II complexes have been found to be highly reactive towards aromatic C–H activation of arylureas at room temperature. A commercially available catalyst [Pd(MeCN4](BF42 or a nitrile-free cationic palladium(II complex generated in situ from the reaction of Pd(OAc2 and HBF4, effectively catalyzes C–H activation/cross-coupling reactions between aryl iodides, arylboronic acids and acrylates under milder conditions than those previously reported. The nature of the directing group was found to be critical for achieving room temperature conditions, with the urea moiety the most effective in promoting facile coupling reactions at an ortho C–H position. This methodology has been utilized in a streamlined and efficient synthesis of boscalid, an agent produced on the kiloton scale annually and used to control a range of plant pathogens in broadacre and horticultural crops. Mechanistic investigations led to a proposed catalytic cycle involving three steps: (1 C–H activation to generate a cationic palladacycle; (2 reaction of the cationic palladacycle with an aryl iodide, arylboronic acid or acrylate, and (3 regeneration of the active cationic palladium catalyst. The reaction between a cationic palladium(II complex and arylurea allowed the formation and isolation of the corresponding palladacycle intermediate, characterized by X-ray analysis. Roles of various additives in the stepwise process have also been studied.

  7. Dopant-induced ignition of helium nanoplasmas—a mechanistic study

    Science.gov (United States)

    Heidenreich, Andreas; Schomas, Dominik; Mudrich, Marcel

    2017-12-01

    Helium (He) nanodroplets irradiated by intense near-infrared laser pulses form a nanoplasma by avalanche-like electron impact ionizations (EIIs) even at lower laser intensities where He is not directly field ionized, provided that the droplets contain a few dopant atoms which provide seed electrons for the EII avalanche. In this theoretical paper on calcium and xenon doped He droplets we elucidate the mechanism which induces ionization avalanches, termed ignition. We find that the partial loss of seed electrons from the activated droplets starkly assists ignition, as the Coulomb barrier for ionization of helium is lowered by the electric field of the dopant cations, and this deshielding of the cation charges enhances their electric field. In addition, the dopant ions assist the acceleration of the seed electrons (slingshot effect) by the laser field, supporting EIIs of He and also causing electron loss by catapulting electrons away. The dopants’ ability to lower the Coulomb barriers at He as well as the slingshot effect decrease with the spatial expansion of the dopant, causing a dependence of the dopants’ ignition capability on the dopant mass. Here, we develop criteria (impact count functions) to assess the ignition capability of dopants, based on (i) the spatial overlap of the seed electron cloud with the He atoms and (ii) the overlap of their kinetic energy distribution with the distribution of Coulomb barrier heights at He. The relatively long time delays between the instants of dopant ionization and ignition (incubation times) for calcium doped droplets are determined to a large extent by the time it takes to deshield the dopant ions.

  8. A mechanistic study on the simultaneous elimination of soot and nitric oxide from engine exhaust

    KAUST Repository

    Raj, Abhijeet; Zainuddin, Zakwan; Sander, Markus; Kraft, Markus

    2011-01-01

    The non-catalytic interaction between soot and nitric oxide (NO) resulting in their simultaneous elimination was studied on different types of reactive site present on soot. The reaction mechanism proposed previously was extended by including seven new reaction pathways for which the reaction energetics and kinetics were studied using density functional theory and transition state theory. This has led to the calculation of a new rate for the removal of carbon monoxide (CO) from soot. The new pathways have been added to our polycyclic aromatic hydrocarbon (PAH) growth model and used to simulate the NO-soot interaction to form CO, N2 and N2O. The simulation results show satisfactory agreement with experiment for the new CO removal rate. The NO-soot reaction was found to depend strongly on the soot site type and temperature. For a set of temperatures, computed PAH structures were analysed to determine the functional groups responsible for the decrease in the reactivity of soot with NO with increasing reaction time. In isothermal conditions, it was found that as temperature is increased, the number of oxygen atoms remaining on the soot surface decreases, while the number of nitrogen atoms increases for a given reaction time. © 2010 Elsevier Ltd. All rights reserved.

  9. A mechanistic study on the simultaneous elimination of soot and nitric oxide from engine exhaust

    KAUST Repository

    Raj, Abhijeet

    2011-04-01

    The non-catalytic interaction between soot and nitric oxide (NO) resulting in their simultaneous elimination was studied on different types of reactive site present on soot. The reaction mechanism proposed previously was extended by including seven new reaction pathways for which the reaction energetics and kinetics were studied using density functional theory and transition state theory. This has led to the calculation of a new rate for the removal of carbon monoxide (CO) from soot. The new pathways have been added to our polycyclic aromatic hydrocarbon (PAH) growth model and used to simulate the NO-soot interaction to form CO, N2 and N2O. The simulation results show satisfactory agreement with experiment for the new CO removal rate. The NO-soot reaction was found to depend strongly on the soot site type and temperature. For a set of temperatures, computed PAH structures were analysed to determine the functional groups responsible for the decrease in the reactivity of soot with NO with increasing reaction time. In isothermal conditions, it was found that as temperature is increased, the number of oxygen atoms remaining on the soot surface decreases, while the number of nitrogen atoms increases for a given reaction time. © 2010 Elsevier Ltd. All rights reserved.

  10. A mechanistic study of cigarette smoke and cyclooxygenase-2 on proliferation of gastric cancer cells

    International Nuclear Information System (INIS)

    Shin, Vivian Y.; Liu, Edgar S.L.; Ye, Yi-Ne; Koo, Marcel W.L.; Chu, K.-M.; Cho, C.-H.

    2004-01-01

    Cigarette smoke has been shown to cause gastric cancer. Overexpression of cyclooxygenase-2 (COX-2) is a common characteristic in gastric malignancy. The present study aimed to explore the correlation between cigarette smoke and COX-2 in the promotion of tumorigenesis in human gastric cancer cells (AGS). We further studied the action of COX-2 on other proto-oncogenes on gastric tumor growth. Results showed that chloroform extract (CE) and ethanol extract (EE) from cigarette smoke dose-dependently stimulated gastric cancer cell proliferation, which was accompanied with an activation of ornithine decarboxylase (ODC) activity, COX-2, and c-myc expressions. Both antisense of c-myc and α-difluoromethylornithine (DFMO, specific ODC inhibitor) inhibited cell proliferation without affecting COX-2 expression in response to cigarette smoke extracts (CSE). However, selective COX-2 inhibitor (SC-236) not only blocked the proliferative activity but also the ODC activity and c-myc protein expression by CSE in gastric cancer cells. Further, supplementation of exogenous prostaglandin (PG) E 2 reversed all the inhibitory actions of SC-236. Our results underline the importance of COX-2 in the cancer-promoting effect of CSE and its modulation on its downstream growth-related genes, such as c-myc and ODC in cancer cell proliferation. These results reveal that CSE-induced gastric carcinogenesis is via the COX-2/c-myc/ODC and PGE 2 -dependent pathway. Hence, selective COX-2 inhibitor could be an effective therapeutic agent for gastric cancer in smokers

  11. Kinetic and mechanistic study of microcystin-LR degradation by nitrous acid under ultraviolet irradiation.

    Science.gov (United States)

    Ma, Qingwei; Ren, Jing; Huang, Honghui; Wang, Shoubing; Wang, Xiangrong; Fan, Zhengqiu

    2012-05-15

    Degradation of microcystin-LR (MC-LR) in the presence of nitrous acid (HNO(2)) under irradiation of 365nm ultraviolet (UV) was studied for the first time. The influence of initial conditions including pH value, NaNO(2) concentration, MC-LR concentration and UV intensity were studied. MC-LR was degraded in the presence of HNO(2); enhanced degradation of MC-LR was observed with 365nm UV irradiation, caused by the generation of hydroxyl radicals through the photolysis of HNO(2). The degradation processes of MC-LR could well fit the pseudo-first-order kinetics. Mass spectrometry was applied for identification of the byproducts and the analysis of degradation mechanisms. Major degradation pathways were proposed according to the results of LC-MS analysis. The degradation of MC-LR was initiated via three major pathways: attack of hydroxyl radicals on the conjugated carbon double bonds of Adda, attack of hydroxyl radicals on the benzene ring of Adda, and attack of nitrosonium ion on the benzene ring of Adda. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.

    Science.gov (United States)

    Hu, Hailong; Li, Li; Guo, Qian; Jin, Sanli; Zhou, Ying; Oh, Yuri; Feng, Yujie; Wu, Qiong; Gu, Ning

    2016-09-01

    Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Mechanistic study of the interaction of uranyl ions with zirconium oxide and zirconium silicate

    International Nuclear Information System (INIS)

    Lomenech, C.

    2002-04-01

    This work deals with structural and thermodynamic studies of the sorption of uranyl species on zircon and zirconia. After determination of the specific areas, of the pH of the isoelectric points, and of the sorption site numbers, thermodynamic data were obtained using alpha spectrometry, for different uranyl concentrations, different background electrolytes (NaClO 4 or KNO 3 ) and different ionic strengths. The structural identification of the surface complexes and sorption sites was carried out using several spectroscopies: XPS spectroscopy allowed a determination of the nature of the sorption sites (≡Zr-O- on zirconia and ≡Si-O- on zircon). Whereas fluorescence decay measurements gave the number of surface species, the combined use of XPS spectroscopy and laser spectro-fluorimetry enabled us to correlate differences in bonding energies and emission wavelengths with differences in the nature of the background electrolyte or in the pH of sorption; DRIFT spectroscopy was a powerful tool for the determination of the presence of sorbed uranyl nitrate species. EXAFS results clearly showed a splitting of the equatorial oxygen atoms in two shells, corresponding to a polydentate, inner-sphere complex. EXAFS results also indicated strong similarities between dry samples and in situ experiments, which confirms the validity of all the spectroscopic measurements. Macroscopic thermodynamic data were then modeled using a surface complexation model (2 pK and constant capacitance models), the results of the structural study being used as constraints for the simulation code FITEQL. (author)

  14. Mechanistic Study of Delamination Fracture in Al-Li Alloy C458 (2099)

    Science.gov (United States)

    Tayon, W. A.; Crooks, R. E.; Domack, M. S.; Wagner, J. A.; Beaudoin, A. J.; McDonald, R. J.

    2009-01-01

    Delamination fracture has limited the use of lightweight Al-Li alloys. In the present study, electron backscattered diffraction (EBSD) methods were used to characterize crack paths in Al-Li alloy C458 (2099). Secondary delamination cracks in fracture toughness samples showed a pronounced tendency for fracture between grain variants of the same deformation texture component. These results were analyzed by EBSD mapping methods and simulated with finite element analyses. Simulation procedures include a description of material anisotropy, local grain orientations, and fracture utilizing crystal plasticity and cohesive zone elements. Taylor factors computed for each grain orientation subjected to normal and shear stresses indicated that grain pairs with the largest Taylor factor differences were adjacent to boundaries that failed by delamination. Examination of matching delamination fracture surface pairs revealed pronounced slip bands in only one of the grains bordering the delamination. These results, along with EBSD studies, plasticity simulations, and Auger electron spectroscopy observations support a hypothesis that delamination fracture occurs due to poor slip accommodation along boundaries between grains with greatly differing plastic response.

  15. α-Mangostin from Cratoxylum arborescens (Vahl Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study

    Directory of Open Access Journals (Sweden)

    Heyam M. A. Sidahmed

    2013-01-01

    Full Text Available Cratoxylum arborescens (Vahl Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s of α-mangostin (AM in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation of C. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH, malondialdehyde (MDA, nitric oxide (NO, and nonprotein sulfhydryl groups (NP-SH were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2 inhibitory effect, and antioxidant activity of AM were also investigated in vitro. AM (10 and 30 mg/kg inhibited significantly (P<0.05 ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC of AM showed an effective in vitro anti-H. pylori activity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity of α-mangostin.

  16. Radical Initiated Hydrosilylation on Silicon Nanocrystal Surfaces: An Evaluation of Functional Group Tolerance and Mechanistic Study.

    Science.gov (United States)

    Yang, Zhenyu; Gonzalez, Christina M; Purkait, Tapas K; Iqbal, Muhammad; Meldrum, Al; Veinot, Jonathan G C

    2015-09-29

    Hydrosilylation is among the most common methods used for modifying silicon surface chemistry. It provides a wide range of surface functionalities and effective passivation of surface sites. Herein, we report a systematic study of radical initiated hydrosilylation of silicon nanocrystal (SiNC) surfaces using two common radical initiators (i.e., 2,2'-azobis(2-methylpropionitrile) and benzoyl peroxide). Compared to other widely applied hydrosilylation methods (e.g., thermal, photochemical, and catalytic), the radical initiator based approach is particle size independent, requires comparatively low reaction temperatures, and yields monolayer surface passivation after short reaction times. The effects of differing functional groups (i.e., alkene, alkyne, carboxylic acid, and ester) on the radical initiated hydrosilylation are also explored. The results indicate functionalization occurs and results in the formation of monolayer passivated surfaces.

  17. Oxidation behaviour of zirconium alloys and their precipitates – A mechanistic study

    International Nuclear Information System (INIS)

    Proff, C.; Abolhassani, S.; Lemaignan, C.

    2013-01-01

    The precipitate oxidation behaviour of binary zirconium alloys containing 1 wt.% Fe, Ni, Cr or 0.6 wt.% Nb was characterised in TEM on FIB prepared transverse sections of the oxide and reported in previous studies [1,2]. In the present study the following alloys: Zr1%Cu, Zr0.5%Cu0.5%Mo and pure Zr are analysed to add to the available information. In all cases, the observed precipitate oxidation behaviour in the oxide close to the metal-oxide interface could be described either with delayed oxidation with respect to the matrix or simultaneous oxidation as the surrounding zirconium matrix. Attempt was made to explain these observations, with different parameters such as precipitate size and structure, composition and thermodynamic properties. It was concluded that the thermodynamics with the new approach presented could explain most precisely their behaviour, considering the precipitate stoichiometry and the free energy of oxidation of the constituting elements. The surface topography of the oxidised materials, as well as the microstructure of the oxide presenting microcracks have been examined. A systematic presence of microcracks above the precipitates exhibiting delayed oxidation has been found; the height of these crack calculated using the Pilling–Bedworth ratios of different phases present, can explain their origin. The protrusions at the surface in the case of materials containing large precipitates can be unambiguously correlated to the presence of these latter, and the height can be correlated to the Pilling–Bedworth ratios of the phases present as well as the diffusion of the alloying elements to the surface and their subsequent oxidation. This latter behaviour was much more considerable in the case of Fe and Cu with Fe showing systematically diffusion to the outer surface.

  18. Mechanistic studies of the genetically encoded fluorescent protein voltage probe ArcLight.

    Directory of Open Access Journals (Sweden)

    Zhou Han

    Full Text Available ArcLight, a genetically encoded fluorescent protein voltage probe with a large ΔF/ΔV, is a fusion between the voltage sensing domain of the Ciona instestinalis voltage sensitive phosphatase and super ecliptic pHluorin carrying a single mutation (A227D in the fluorescent protein. Without this mutation the probe produces only a very small change in fluorescence in response to voltage deflections (∼ 1%. The large signal afforded by this mutation allows optical detection of action potentials and sub-threshold electrical events in single-trials in vitro and in vivo. However, it is unclear how this single mutation produces a probe with such a large modulation of its fluorescence output with changes in membrane potential. In this study, we identified which residues in super ecliptic pHluorin (vs eGFP are critical for the ArcLight response, as a similarly constructed probe based on eGFP also exhibits large response amplitude if it carries these critical residues. We found that D147 is responsible for determining the pH sensitivity of the fluorescent protein used in these probes but by itself does not result in a voltage probe with a large signal. We also provide evidence that the voltage dependent signal of ArcLight is not simply sensing environmental pH changes. A two-photon polarization microscopy study showed that ArcLight's response to changes in membrane potential includes a reorientation of the super ecliptic pHluorin. We also explored different changes including modification of linker length, deletion of non-essential amino acids in the super ecliptic pHluorin, adding a farnesylation site, using tandem fluorescent proteins and other pH sensitive fluorescent proteins.

  19. Mechanistic and kinetic studies on the OH-initiated atmospheric oxidation of fluoranthene

    International Nuclear Information System (INIS)

    Dang, Juan; Shi, Xiangli; Zhang, Qingzhu; Hu, Jingtian; Chen, Jianmin; Wang, Wenxing

    2014-01-01

    The atmospheric oxidation of polycyclic aromatic hydrocarbons (PAHs) can generate toxic derivatives which contribute to the carcinogenic potential of particulate organic matter. In this work, the mechanism of the OH-initiated atmospheric oxidation of fluoranthene (Flu) was investigated by using high-accuracy molecular orbital calculations. All of the possible oxidation pathways were discussed, and the theoretical results were compared with the available experimental observation. The rate constants of the crucial elementary reactions were evaluated by the Rice–Ramsperger–Kassel–Marcus (RRKM) theory. The main oxidation products are a range of ring-retaining and ring-opening chemicals containing fluoranthols, fluoranthones, fluoranthenequinones, nitro-fluoranthenes, dialdehydes and epoxides. The overall rate constant of the OH addition reaction is 1.72 × 10 −11 cm 3 molecule −1 s −1 at 298 K and 1 atm. The atmospheric lifetime of Flu determined by OH radicals is about 0.69 days. This work provides a comprehensive investigation of the OH-initiated oxidation of Flu and should help to clarify its atmospheric conversion. - Highlights: • We studied a comprehensive mechanism of OH-initiated oxidation of fluoranthene. • We reported the formation pathways of fluoranthone, fluoranthenequinone and epoxide. • The rate constants of the crucial elementary steps were evaluated

  20. Mechanistic studies on the bovine liver mitochondrial dihydroorotate dehydrogenase using kinetic deuterium isotope effects

    International Nuclear Information System (INIS)

    Hines, V.; Johnston, M.

    1989-01-01

    Dihydroorotates deuteriated at both C 5 and C 6 have been prepared and used to probe the mechanism of the bovine liver mitochondrial dihydroorotate dehydrogenase. Primary deuterium isotope effects on k cat are observed with both (6RS)-[5(S)- 2 H]- and (6RS)-[6- 2 H]dihydroorotates (3 and 6, respectively); these effects are maximal at low pH. At pH 6.6, D V = 3.4 for the C 5 -deuteriated dihydroorotate (3), and D V = 2.3 for the C 6 -deuteriated compound (6). The isotope effects approach unity at pH 8.8. Analysis of the pH dependence of the isotope effects on k cat reveals a shift in the rate-determining step of the enzyme mechanism as a function of pH. Dihydroorotate oxidation appears to require general base catalysis; this step is completely rate-determining at low pH and isotopically sensitive. Reduction of the cosubstrate, coenzyme Q 6 , is rate-limiting at high pH and is isotopically insensitive; this step appears to require general acid catalysis. The results of double isotope substitution studies and analysis for substrate isotope exchange with solvent point toward a concerted mechanism for oxidation of dihydroorotate. This finding serves to distinguish further the mammalian dehydrogenase from its parasitic cognate, which catalyzes a stepwise oxidation reaction

  1. Mechanistic studies on reactivities of organometallic macrocyclic complexes of chromium and cobalt

    International Nuclear Information System (INIS)

    Shi, Shu.

    1990-01-01

    Reaction pathways leading to the formation and cleavage of a transition metal-carbon bond at various oxidation states of the metal occupy a central position in understanding many enzymatic reactions and designing catalysts. The report is divided into six parts that (1) focus on the homolysis vs heterolysis of a C-Cr(III) bond, (2) describes a unique chain reaction and a S E 2 reaction I 2 and RCrL 2+ , (3) concerns the oxidation of organochromium(III) complexes by dihalide and pseudo-dihalide radical anions generated by pulse radiolysis, (4) concentrates on the oxidation mechanism of RCr(H 2 O) 2+ and the fate of RCr(H 2 O) 3+ as well as the corresponding reduction potentials, (5) extends study of organocobalt complexes with attention to reduction induced cleavages of a transition metal-carbon bond, and (6) describes the crystallization of [(CH 3 ) 4 N][Co(dmgBF 2 ) 2 py] and reports its molecular structure as determined by x-ray diffraction. 182 refs., 25 figs., 16 tabs. (BM)

  2. Mechanistic studies on reactivities of organometallic macrocyclic complexes of chromium and cobalt

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Shu.

    1990-12-10

    Reaction pathways leading to the formation and cleavage of a transition metal-carbon bond at various oxidation states of the metal occupy a central position in understanding many enzymatic reactions and designing catalysts. The report is divided into six parts that (1) focus on the homolysis vs heterolysis of a C-Cr(III) bond, (2) describes a unique chain reaction and a S{sub E}2 reaction I{sub 2} and RCrL{sup 2+}, (3) concerns the oxidation of organochromium(III) complexes by dihalide and pseudo-dihalide radical anions generated by pulse radiolysis, (4) concentrates on the oxidation mechanism of RCr(H{sub 2}O){sup 2+} and the fate of RCr(H{sub 2}O){sup 3+} as well as the corresponding reduction potentials, (5) extends study of organocobalt complexes with attention to reduction induced cleavages of a transition metal-carbon bond, and (6) describes the crystallization of ((CH{sub 3}){sub 4}N)(Co(dmgBF{sub 2}){sub 2}py) and reports its molecular structure as determined by x-ray diffraction. 182 refs., 25 figs., 16 tabs. (BM)

  3. Mechanistic studies on the conjugation of methyl isocyanate with N-Acetyl-Cysteine in rats

    International Nuclear Information System (INIS)

    Hu, P.; Davis, M.R.; Baillie, T.A.

    1996-01-01

    In order to investigate the utility of selected thiols as scavengers of MIC, we first assessed the chemical stability of SMG, AMCC and SMC by measuring their rates of reaction in vitro with thiorphan. The initial rates of carbamoylation of thiorpan (0.5 mM) by the above conjugates (0.5 mM) in aqeous buffer at pH 7.4 and 37 deg C were 2.51, 0.76 and 8.47 μmol L -1 min -1 , repectively, indicating that the mercapturate AMCC was the most stable of the three MIC conjugates. In light of these results, studies were conducted to examine the effect of pretreatment with N-acetyl-L-cysteine (L-NAC; 500 mg kg -1 , i.p.) on the urinary elimination of AMCC in rats dosed with MIC (15 mg kg -1 , i.p.). In separate experiments, groups of rats were pretreated with either N-acetyl-D-cysteine (D-NAC) or N-trideuteroacetyl-L-cysteine (d 3 -L-NAC) in order to explore the mechanism by which MIC undergoes conjugation to AMCC in vivo. The results indicated that exogenous NAC effectively enhancess the urinary excretion of MIC in the form of AMCC, and that it does so lagerly by direct conjugation with the isocyanate, rather than via biosynthesis to GSH. (author). 9 refs., 5 figs

  4. A mechanistic investigation on the formation and rearrangement of silaspiropentane: A theoretical study.

    Science.gov (United States)

    Yildiz, Cem Burak; Azizoglu, Akin

    2016-07-01

    The formation of silaspiropentane from addition of singlet silacyclopropylidene 1 and silacyclopropylidenoid 8 to ethylene has been investigated separately at the B3LYP, X3LYP, WB97XD, and M05-2X theories using the 6-31+G(d,p) basis set. The silacycloproylidenoid addition follows a stepwise route. In contrast, a concerted mechanism occurs for silacyclopropylidene addition. Moreover, the intramolecular rearrangements of silaspiropentane 9 to methylenesilacyclobutane 11 and 2-silaallene + ethylene 12 have been studied extensively. The required energy barrier for the isomerization of 9 to 10 was determined to be 44.0 kcal mol(-1) at the B3LYP/6-31+G(d,p) level. After formation of 10, the rearrangement to methylenesilacyclobutane 12 is highly exergonic by -15.9 kcal mol(-1), which makes this reaction promising. However, the conversion of 9 to 11 is calculated to be quite endergonic, by 26.5 kcal mol(-1).

  5. Design and mechanistic study of a novel gold nanocluster-based drug delivery system.

    Science.gov (United States)

    Li, Qinzhen; Pan, Yiting; Chen, Tiankai; Du, Yuanxin; Ge, Honghua; Zhang, Buchang; Xie, Jianping; Yu, Haizhu; Zhu, Manzhou

    2018-05-22

    Chemically-triggered drug delivery systems (DDSs) have been extensively studied as they do not require specialized equipment to deliver the drug and can deeply penetrate human tissue. However, their syntheses are complicated and they tend to be cytotoxic, which restricts their clinical utility. In this work, the self-regulated drug loading and release capabilities of peptide-protected gold nanoclusters (Pep-Au NCs) are investigated using vancomycin (Van) as the model drug. Gold nanoclusters (Au NCs) coated with a custom-designed pentapeptide are synthesized as drug delivery nanocarriers and loaded with Van - a spontaneous process reliant on the specific binding between Van and the custom-designed peptide. The Van-loaded Au NCs show comparable antimicrobial activity with Van on its own, and the number of Van released by the Pep-Au NCs is found to be proportional to the amount of bacteria present. The controlled nature of the Van release is very encouraging, and predominantly due to the stronger binding affinity of Van with bacteria than that with Au NCs. In addition, these fluorescent Au NCs could also be used to construct temperature sensors, which enable the in vitro and in vivo bioimaging.

  6. Mechanistic and kinetic studies on the OH-initiated atmospheric oxidation of fluoranthene

    Energy Technology Data Exchange (ETDEWEB)

    Dang, Juan; Shi, Xiangli; Zhang, Qingzhu, E-mail: zqz@sdu.edu.cn; Hu, Jingtian; Chen, Jianmin; Wang, Wenxing

    2014-08-15

    The atmospheric oxidation of polycyclic aromatic hydrocarbons (PAHs) can generate toxic derivatives which contribute to the carcinogenic potential of particulate organic matter. In this work, the mechanism of the OH-initiated atmospheric oxidation of fluoranthene (Flu) was investigated by using high-accuracy molecular orbital calculations. All of the possible oxidation pathways were discussed, and the theoretical results were compared with the available experimental observation. The rate constants of the crucial elementary reactions were evaluated by the Rice–Ramsperger–Kassel–Marcus (RRKM) theory. The main oxidation products are a range of ring-retaining and ring-opening chemicals containing fluoranthols, fluoranthones, fluoranthenequinones, nitro-fluoranthenes, dialdehydes and epoxides. The overall rate constant of the OH addition reaction is 1.72 × 10{sup −11} cm{sup 3} molecule{sup −1} s{sup −1} at 298 K and 1 atm. The atmospheric lifetime of Flu determined by OH radicals is about 0.69 days. This work provides a comprehensive investigation of the OH-initiated oxidation of Flu and should help to clarify its atmospheric conversion. - Highlights: • We studied a comprehensive mechanism of OH-initiated oxidation of fluoranthene. • We reported the formation pathways of fluoranthone, fluoranthenequinone and epoxide. • The rate constants of the crucial elementary steps were evaluated.

  7. A mechanistic study of the uniform corrosion of copper in compacted clay-sand soil

    International Nuclear Information System (INIS)

    Litke, C.D.; Ryan, S.R.; King, F.

    1992-08-01

    The results of a study of the mechanism of uniform corrosion of copper under simulated nuclear fuel waste disposal conditions are presented. Evidence is given that suggests that the rate-controlling process is the transport of copper corrosion products away from the corroding surface. In the experiments described here, the copper diffused through a column of compacted clay-sand buffer. The properties of the buffer material, especially its ability to sorb copper species, are significant in determining the rate of uniform corrosion of copper. The evidence that copper diffusion is rate-controlling stems from the effect of γ-radiation on the tests. In the presence of γ-radiation, copper diffused farther along the column of compacted buffer material than in the unirradiated tests, but the corrosion rate was lower. These two effects can be best explained in terms of a slow copper-diffusion process. Irradiation is thought to reduce the extent of sorption of copper by the clay component of the buffer. This results in a more mobile copper species and a smaller interfacial flux of copper (i.e., a lower corrosion rate)

  8. Mechanistic Study of the Inhibitory Effect of Kaempferol on Uterine Fibroids In Vitro.

    Science.gov (United States)

    Li, Yanxia; Ding, Zhaoxia; Wu, Chuanzhong

    2016-12-08

    BACKGROUND This study examined the effect of kaempferol on uterine fibroids in vitro and the underlying mechanism, and investigated the potential of kaempferol as a clinical drug for the treatment of uterine fibroids. MATERIAL AND METHODS Uterine fibroid tissue and surrounding smooth muscle tissue were collected for primary culture. Different concentrations of kaempferol (12 μM, 24 μM, and 48 μM) were used to treat the cells for 24, 48, and 72 hours. Ethanol was used in the control group. A CCK-8 colorimetric assay was used to detect cell proliferation. Real-time PCR and immunoblot were used to detect estrogen receptor (ER), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF) levels in mRNA and protein. RESULTS The differences in proliferation at different time points and concentrations of kaempferol were statistically significant. The inhibitory effect of kaempferol on mRNA levels of ER and IGF, and protein levels of ER, VEGF, and IGF-1 were positively correlated with kaempferol concentration. Changes in kaempferol concentration showed no effect on VEGF mRNA expression. Treatment with kaempferol significantly lowered myocardin levels in uterine fibroid tissue compared to normal uterine smooth muscle (PKaempferol might be used for clinical treatment of uterine fibroids due to its inhibitory effect on the proliferation of uterine fibroids cells.

  9. Synthesis of nickel nanoparticles by hydrazine reduction: mechanistic study and continuous flow synthesis

    International Nuclear Information System (INIS)

    Eluri, Ravi; Paul, Brian

    2012-01-01

    The continuous synthesis of nickel nanoparticles (NiNPs) in a static microchannel T-mixer by the reduction of NiCl 2 ·6H 2 O in the presence of ethylene glycol without a stabilizing/capping agent was investigated. The nanoparticles were formed in accordance with the modified polyol process with hydrazine used as a reducing agent and NaOH as a catalyst for nanoparticle formation. The reaction mechanism for NiNP formation was investigated in batch with the help of Fourier transform infrared spectroscopy and X-ray diffraction (XRD) techniques. Parameters were found for reducing reaction times from 60 to 1 min. The effects of temperature (60–120 °C) and NaOH concentration (0.1 and 0.5 M) on batch-processed particle characteristics were also studied using XRD, transmission electron microscope and electron microprobe analysis. Average particle size was reduced from 9.2 ± 2.9 to 5.4 ± 0.9 nm at higher temperature and NaOH concentration. Adaptation of this chemistry to a static microchannel T-mixer for continuous synthesis resulted in smooth, spherical particles. Increases in the reaction temperature from 120 to 130 °C resulted in a narrow size distribution of 5.3 ± 1 nm and also resulted in magnetic properties of 5.1 emu/g (saturation magnetization), 1.1 emu/g (remanent magnetization), and 62 Oe (coercivity).

  10. Mechanistic and kinetic study on the catalytic hydrolysis of COS in small clusters of sulfuric acid.

    Science.gov (United States)

    Li, Kai; Song, Xin; Zhu, Tingting; Wang, Chi; Sun, Xin; Ning, Ping; Tang, Lihong

    2018-01-01

    The catalytic hydrolysis of carbonyl sulfide (COS) and the effect of small clusters of H 2 O and H 2 SO 4 have been studied by theoretical calculations. The addition of H 2 SO 4 could increase the enthalpy change (ΔHhydrolysis reaction changed from an endothermic reaction to an exothermic reaction. Further, H 2 SO 4 decreases the energy barrier by 5.25 kcal/mol, and it enhances the catalytic hydrolysis through the hydrogen transfer effect. The (COS + H 2 SO 4 -H 2 O) reaction has the lowest energy barrier of 29.97 kcal/mol. Although an excess addition of H 2 O and H 2 SO 4 increases the energy barrier, decreases the catalytic hydrolysis, which is consistent with experimental observations. The order of the energy barriers for the three reactions from low to high are as follows: COS + H 2 SO 4 -H 2 O hydrolysis of COS both kinetically and thermodynamically. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans

    International Nuclear Information System (INIS)

    Baillie, T.A.; Adams, W.J.; Kaiser, D.G.; Olanoff, L.S.; Halstead, G.W.; Harpootlian, H.; Van Giessen, G.J.

    1989-01-01

    The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: (1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; (2) chiral inversion of R-(-)-[2H3]ibuprofen is not subject to a discernible deuterium isotope effect; and (3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence

  12. Mechanistic studies with solubilized rat liver steroid 5 alpha-reductase: Elucidation of the kinetic mechanism

    International Nuclear Information System (INIS)

    Levy, M.A.; Brandt, M.; Greway, A.T.

    1990-01-01

    A solubilized preparation of steroid 5 alpha-reductase from rat liver has been used in studies focused toward an understanding of the kinetic mechanism associated with enzyme catalysis. From the results of analyses with product and dead-end inhibitors, a preferentially ordered binding of substrates and release of products from the surface of the enzyme is proposed. The observations from these experiments were identical with those using the steroid 5 alpha-reductase activity associated with rat liver microsomes. The primary isotope effects on steady-state kinetic parameters when [4S-2H]NADPH was used also were consistent with an ordered kinetic mechanism. Normal isotope effects were observed for all three kinetic parameters (Vm/Km for both testosterone and NADPH and Vm) at all substrate concentrations used experimentally. Upon extrapolation to infinite concentration of testosterone, the isotope effect on Vm/Km for NADPH approached unity, indicating that the nicotinamide dinucleotide phosphate is the first substrate binding to and the second product released from the enzyme. The isotope effects on Vm/Km for testosterone at infinite concentration of cofactor and on Vm were 3.8 +/- 0.5 and 3.3 +/- 0.4, respectively. Data from the pH profiles of these three steady-state parameters and the inhibition constants (1/Ki) of competitive inhibitors versus both substrates indicate that the binding of nicotinamide dinucleotide phosphate involves coordination of its anionic 2'-phosphate to a protonated enzyme-associated base with an apparent pK near 8.0. From these results, relative limits have been placed on several of the internal rate constants used to describe the ordered mechanism of the rat liver steroid 5 alpha-reductase

  13. Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells

    International Nuclear Information System (INIS)

    Papa, Anne-Laure; Basu, Sudipta; Sengupta, Poulomi; Banerjee, Deboshri; Sengupta, Shiladitya; Harfouche, Rania

    2012-01-01

    Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell penetrance. A new paradigm to improve Gemcitabine’s therapeutic index is to administer it in nanoparticles, which favour its delivery to cells when under 500 nm in diameter. Although promising, this approach still suffers from major limitations, as the choice of nanovector used as well as its effects on Gemcitabine intracellular trafficking inside pancreatic cancer cells remain unknown. A proper elucidation of these mechanisms would allow for the elaboration of better strategies to engineer more potent Gemcitabine nanotherapeutics against pancreatic cancer. Gemcitabine was encapsulated in two types of commonly used nanovectors, namely poly(lactic-co-glycolic acid) (PLGA) and cholesterol-based liposomes, and their physico-chemical parameters assessed in vitro. Their mechanisms of action in human pancreatic cells were compared with those of the free drug, and with each others, using cytotoxity, apoptosis and ultrastructural analyses. Physico-chemical analyses of both drugs showed high loading efficiencies and sizes of less than 200 nm, as assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with a drug release profile of at least one week. These profiles translated to significant cytotoxicity and apoptosis, as well as distinct intracellular trafficking mechanisms, which were most pronounced in the case of PLGem showing significant mitochondrial, cytosolic and endoplasmic reticulum stresses. Our study demonstrates how the choice of nanovector affects the mechanisms of drug action and is a crucial determinant of Gemcitabine intracellular trafficking and potency in pancreatic cancer settings

  14. Transcranial direct current stimulation to lessen neuropathic pain after spinal cord injury: a mechanistic PET study.

    Science.gov (United States)

    Yoon, Eun Jin; Kim, Yu Kyeong; Kim, Hye-Ri; Kim, Sang Eun; Lee, Youngjo; Shin, Hyung Ik

    2014-01-01

    It is suggested that transcranial direct current stimulation (tDCS) can produce lasting changes in corticospinal excitability and can potentially be used for the treatment of neuropathic pain. However, the detailed mechanisms underlying the effects of tDCS are unknown. We investigated the underlying neural mechanisms of tDCS for chronic pain relief using [(18)F]-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET). Sixteen patients with neuropathic pain (mean age 44.1 ± 8.6 years, 4 females) due to traumatic spinal cord injury received sham or active anodal stimulation of the motor cortex using tDCS for 10 days (20 minutes, 2 mA, twice a day). The effect of tDCS on regional cerebral glucose metabolism was evaluated by [(18)F]FDG-PET before and after tDCS sessions. There was a significant decrease in the numeric rating scale scores for pain, from 7.6 ± 0.5 at baseline to 5.9 ± 1.8 after active tDCS (P = .016). We found increased metabolism in the medulla and decreased metabolism in the left dorsolateral prefrontal cortex after active tDCS treatment compared with the changes induced by sham tDCS. Additionally, an increase in metabolism after active tDCS was observed in the subgenual anterior cingulate cortex and insula. The results of this study suggest that anodal stimulation of the motor cortex using tDCS can modulate emotional and cognitive components of pain and normalize excessive attention to pain and pain-related information.

  15. Combining Solvent Isotope Effects with Substrate Isotope Effects in Mechanistic Studies of Alcohol and Amine Oxidation by Enzymes*

    Science.gov (United States)

    Fitzpatrick, Paul F.

    2014-01-01

    Oxidation of alcohols and amines is catalyzed by multiple families of flavin-and pyridine nucleotide-dependent enzymes. Measurement of solvent isotope effects provides a unique mechanistic probe of the timing of the cleavage of the OH and NH bonds, necessary information for a complete description of the catalytic mechanism. The inherent ambiguities in interpretation of solvent isotope effects can be significantly decreased if isotope effects arising from isotopically labeled substrates are measured in combination with solvent isotope effects. The application of combined solvent and substrate (mainly deuterium) isotope effects to multiple enzymes is described here to illustrate the range of mechanistic insights that such an approach can provide. PMID:25448013

  16. Mathematical Description and Mechanistic Reasoning: A Pathway toward STEM Integration

    Science.gov (United States)

    Weinberg, Paul J.

    2017-01-01

    Because reasoning about mechanism is critical to disciplined inquiry in science, technology, engineering, and mathematics (STEM) domains, this study focuses on ways to support the development of this form of reasoning. This study attends to how mechanistic reasoning is constituted through mathematical description. This study draws upon Smith's…

  17. Polyester Textiles as a Source of Microplastics from Households: A Mechanistic Study to Understand Microfiber Release During Washing.

    Science.gov (United States)

    Hernandez, Edgar; Nowack, Bernd; Mitrano, Denise M

    2017-06-20

    Microplastic fibers make up a large proportion of microplastics found in the environment, especially in urban areas. There is good reason to consider synthetic textiles a major source of microplastic fibers, and it will not diminish since the use of synthetic fabrics, especially polyester, continues to increase. In this study we provide quantitative data regarding the size and mass of microplastic fibers released from synthetic (polyester) textiles during simulated home washing under controlled laboratory conditions. Consideration of fabric structure and washing conditions (use of detergents, temperature, wash duration, and sequential washings) allowed us to study the propensity of fiber shedding in a mechanistic way. Thousands of individual fibers were measured (number, length) from each wash solution to provide a robust data set on which to draw conclusions. Among all the variables tested, the use of detergent appeared to affect the total mass of fibers released the most, yet the detergent composition (liquid or powder) or overdosing of detergent did not significantly influence microplastic release. Despite different release quantities due to the addition of a surfactant (approximately 0.025 and 0.1 mg fibers/g textile washed, without and with detergent, respectively), the overall microplastic fiber length profile remained similar regardless of wash condition or fabric structure, with the vast majority of fibers ranging between 100 and 800 μm in length irrespective of wash cycle number. This indicates that the fiber staple length and/or debris encapsulated inside the fabric from the yarn spinning could be directly responsible for releasing stray fibers. This study serves as a first look toward understanding the physical properties of the textile itself to better understand the mechanisms of fiber shedding in the context of microplastic fiber release into laundry wash water.

  18. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Tolosa, Laia [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Gómez-Lechón, M. José [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Jiménez, Nuria [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Hervás, David [Biostatistics Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); Jover, Ramiro [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain); Donato, M. Teresa, E-mail: donato_mte@gva.es [Unidad de Hepatología Experimental, Instituto de Investigación Sanitaria La Fe, Valencia 46026 (Spain); CIBERehd, FIS, Barcelona 08036 (Spain); Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Valencia 46010 (Spain)

    2016-07-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  19. Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis

    International Nuclear Information System (INIS)

    Tolosa, Laia; Gómez-Lechón, M. José; Jiménez, Nuria; Hervás, David; Jover, Ramiro; Donato, M. Teresa

    2016-01-01

    Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis. - Highlights: • HepaRG cells were explored as an in vitro model to detect steatogenic potential. • Multiple toxicity-related endpoints were analysed by HCS. • HepaRG showed a greater sensitivity to drug-induced steatosis than HepG2 cells. • Changes in the expression of genes related to lipid metabolism were revealed. • HepaRG allow mechanistic understanding of liver damage induced by steatogenic drugs.

  20. Why did high-dose rosuvastatin not improve cardiac remodeling in chronic heart failure? Mechanistic insights from the UNIVERSE study.

    Science.gov (United States)

    Ashton, Emma; Windebank, Emma; Skiba, Marina; Reid, Christopher; Schneider, Hans; Rosenfeldt, Franklin; Tonkin, Andrew; Krum, Henry

    2011-02-03

    Statins are often prescribed for prevention of atherosclerotic outcomes in patients who have chronic heart failure (CHF), if this has an ischaemic etiology. These agents may also possess additional properties, independent of effects on blood lipid levels, which may have an effect on cardiac remodeling. However, beneficial effects were not observed in the recent UNIVERSE trial. We prospectively planned a sub-study of UNIVERSE to explore relevant mechanistic effects of rosuvastatin, including effects on collagen turnover and plasma coenzyme Q10 (CoQ) levels. Additionally, CoQ levels in CHF patients receiving chronic statin therapy were measured. CoQ levels were significantly reduced after 26 weeks of rosuvastatin statin therapy (n = 32), compared to placebo (n = 37) in CHF patients in UNIVERSE trial. Patients with CHF (n = 56) matched for age, gender and severity of disease who had been taking statins for 12 months or longer had CoQ levels of 847 ± 344 nmol/L, significantly lower than 1065.4 ± 394 nmol/L in UNIVERSE patients at baseline (p = 0.0001). Serum types I and III N-terminal procollagen peptide (PINP and PIIINP), measures of collagen turnover which can contribute to cardiac fibrosis were significantly increased in the rosuvastatin group compared to baseline in UNIVERSE patients (PINP: p = 0.03, PIIINP: p = 0.001). In conclusion putative beneficial effects of statin therapy on cardiac remodeling in UNIVERSE may have been negated by increases in collagen turnover markers as well as a reduction in plasma CoQ levels in these patients with CHF. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Unraveling molecular mechanistic differences in liver metabolism between lean and fat lines of Pekin duck (Anas platyrhynchos domestica): a proteomic study.

    Science.gov (United States)

    Zheng, Aijuan; Chang, Wenhuan; Hou, Shuisheng; Zhang, Shu; Cai, Huiyi; Chen, Guilan; Lou, Ruiying; Liu, Guohua

    2014-02-26

    Duck is one of the major poultry meat sources for human consumption. To satisfy different eating habits, lean and fat strains of Pekin ducks have been developed. The objective of this study was to determine the molecular mechanistic differences in liver metabolism between two duck strains. The liver proteome of the Pekin duck lines was compared on days 1, 14, 28, and 42 posthatching using 2-DE based proteomics. There was a different abundance of 76 proteins in the livers of the two duck lines. Fat ducks strongly expressed proteins related to pathways of glycolysis, ATP synthesis, and protein catabolism, suggesting enhanced fat deposition rather than protein retention. In contrast, highly expressed proteins in lean ducks improved protein anabolism and reduced protein catabolism, resulting in an enhancement of lean meat deposition. Along with the decrease in fat deposition, the immune system of the lean duck strain may be enhanced by enhanced expression of proteins involved in stress response, immune defense, and antioxidant functions. These results indicate that selection pressure has shaped the two duck lines differently resulting in different liver metabolic capacities. These observed variations between the two strains at the molecular level are matched with physiological changes in growth performance and meat production. This information may have beneficial impacts in areas such as genetic modification through the manipulation of target proteins or genes in specific pathways to improve the efficiency of duck meat production. The objective of this study was to unravel molecular mechanistic differences in liver metabolism between lean and fat Pekin duck (Anas platyrhynchos domestica) strains. There was a different abundance of 76 proteins in the livers of the two duck lines. Enhanced protein expression in the fat ducks related to pathways of glycolysis, ATP synthesis and protein catabolism suggesting increased fat deposition rather than protein retention. In

  2. Mechanistic study on lung cancer mortality after radon exposure in the Wismut cohort supports important role of clonal expansion in lung carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zaballa, I.; Eidemueller, M. [Helmholtz Zentrum Muenchen, Institute of Radiation Protection, Neuherberg (Germany)

    2016-08-15

    Lung cancer mortality after radon exposure in the Wismut cohort was analyzed using the two-stage clonal expansion (TSCE) model. A total of 2996 lung cancer deaths among the 58,695 male workers were observed during the follow-up period between 1946 and 2003. Adjustment to silica exposure was performed to find a more accurate estimation of the risk of radon exposure. An additional analysis with the descriptive excess relative risk (ERR) model was carried out for comparison. The TSCE model that best describes the data is nonlinear in the clonal expansion with radon exposure and has a saturation level at an exposure rate of d{sub r} ≅ 100 WLM/yr. The excess relative risk decreases with age and shows an inverse exposure rate effect. In comparison with the ERR model, the TSCE model predicts a considerably larger risk for low exposures rates below 50 WLM/yr. Comparison to other mechanistic studies of lung cancer after exposure to alpha particles using the TSCE model reveals an extraordinary consistency in the main features of the exposure response, given the diversity in the characteristics of the cohorts and the exposure across different studies. This suggests that a nonlinear response mechanism in the clonal expansion, with some level of saturation at large exposure rates, may be playing a crucial role in the development of lung cancer after alpha particle irradiation. (orig.)

  3. Assessing the ability of mechanistic volatilization models to simulate soil surface conditions: a study with the Volt'Air model.

    Science.gov (United States)

    Garcia, L; Bedos, C; Génermont, S; Braud, I; Cellier, P

    2011-09-01

    Ammonia and pesticide volatilization in the field is a surface phenomenon involving physical and chemical processes that depend on the soil surface temperature and water content. The water transfer, heat transfer and energy budget sub models of volatilization models are adapted from the most commonly accepted formalisms and parameterizations. They are less detailed than the dedicated models describing water and heat transfers and surface status. The aim of this work was to assess the ability of one of the available mechanistic volatilization models, Volt'Air, to accurately describe the pedo-climatic conditions of a soil surface at the required time and space resolution. The assessment involves: (i) a sensitivity analysis, (ii) an evaluation of Volt'Air outputs in the light of outputs from a reference Soil-Vegetation-Atmosphere Transfer model (SiSPAT) and three experimental datasets, and (iii) the study of three tests based on modifications of SiSPAT to establish the potential impact of the simplifying assumptions used in Volt'Air. The analysis confirmed that a 5 mm surface layer was well suited, and that Volt'Air surface temperature correlated well with the experimental measurements as well as with SiSPAT outputs. In terms of liquid water transfers, Volt'Air was overall consistent with SiSPAT, with discrepancies only during major rainfall events and dry weather conditions. The tests enabled us to identify the main source of the discrepancies between Volt'Air and SiSPAT: the lack of gaseous water transfer description in Volt'Air. They also helped to explain why neither Volt'Air nor SiSPAT was able to represent lower values of surface water content: current classical water retention and hydraulic conductivity models are not yet adapted to cases of very dry conditions. Given the outcomes of this study, we discuss to what extent the volatilization models can be improved and the questions they pose for current research in water transfer modeling and parameterization

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

    Science.gov (United States)

    Loison, Laurent

    2015-06-01

    The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions. Copyright © 2015 Académie des sciences. Published by Elsevier SAS. All rights reserved.

  5. Supporting Mechanistic Reasoning in Domain-Specific Contexts

    Science.gov (United States)

    Weinberg, Paul J.

    2017-01-01

    Mechanistic reasoning is an epistemic practice central within science, technology, engineering, and mathematics disciplines. Although there has been some work on mechanistic reasoning in the research literature and standards documents, much of this work targets domain-general characterizations of mechanistic reasoning; this study provides…

  6. Kinetic and mechanistic studies of reactive intermediates in photochemical and transition metal-assisted oxidation, decarboxylation and alkyl transfer reactions

    Energy Technology Data Exchange (ETDEWEB)

    Carraher, Jack McCaslin [Iowa State Univ., Ames, IA (United States)

    2014-01-01

    Reactive species like high-valent metal-oxo complexes and carbon and oxygen centered radicals are important intermediates in enzymatic systems, atmospheric chemistry, and industrial processes. Understanding the pathways by which these intermediates form, their relative reactivity, and their fate after reactions is of the utmost importance. Herein are described the mechanistic detail for the generation of several reactive intermediates, synthesis of precursors, characterization of precursors, and methods to direct the chemistry to more desirable outcomes yielding ‘greener’ sources of commodity chemicals and fuels.

  7. Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells.

    Science.gov (United States)

    Saneja, Ankit; Nayak, Debasis; Srinivas, M; Kumar, Amit; Khare, Vaibhav; Katoch, Archana; Goswami, Anindya; Vishwakarma, Ram A; Sawant, Sanghapal D; Gupta, Prem N

    2017-01-15

    The overexpression of CD44 in cancer cells reroutes number of oncogenic pathways including the central Pi3K/Akt/NF-kB pathway leading to cancer progression and malignancy. Herein, we developed hyaluronic acid-modified poly(dl-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles (PLGA-PEG-HA NPs) for targeted delivery of TTQ (thio-tetrazolyl analog of a clinical candidate, IC87114) to CD44 overexpressing cancer cells. The PLGA-PEG co-polymer was synthesized and characterized by NMR and FTIR. The co-polymer based nanoparticles were prepared by solvent evaporation method and hyaluronic acid (HA) was conjugated on to the nanoparticle surface via EDC/NHS chemistry. The PLGA-PEG-HA NPs had a desirable particle size (AFM). In vitro cytotoxicity and cellular uptake studies demonstrated higher cytotoxicity and enhanced intracellular accumulation of PLGA-PEG-HA NPs compared to PLGA-PEG NPs in high CD44 expressing MiaPaca-2 cells compared to MDA-MB-231 and MCF7 cells. At the molecular level, the PLGA-PEG-HA NPs were found to be inducing premature senescence with increase in senescence associated β-galactosidase activity and senescence specific marker p21 expression through modulation of Pi3K/Akt/NF-kB signaling pathway in MiaPaca-2 cells. These findings collectively indicated that HA-modified nanoparticles might serve as a promising nanocarrier for site-specific drug delivery, and can be explored further to increase the therapeutic efficacy of anticancer drugs via targeting to CD44 over-expressing cancer cells. Copyright © 2016. Published by Elsevier B.V.

  8. How to use mechanistic effect models in environmental risk assessment of pesticides: Case studies and recommendations from the SETAC workshop MODELINK.

    Science.gov (United States)

    Hommen, Udo; Forbes, Valery; Grimm, Volker; Preuss, Thomas G; Thorbek, Pernille; Ducrot, Virginie

    2016-01-01

    Mechanistic effect models (MEMs) are useful tools for ecological risk assessment of chemicals to complement experimentation. However, currently no recommendations exist for how to use them in risk assessments. Therefore, the Society of Environmental Toxicology and Chemistry (SETAC) MODELINK workshop aimed at providing guidance for when and how to apply MEMs in regulatory risk assessments. The workshop focused on risk assessment of plant protection products under Regulation (EC) No 1107/2009 using MEMs at the organism and population levels. Realistic applications of MEMs were demonstrated in 6 case studies covering assessments for plants, invertebrates, and vertebrates in aquatic and terrestrial habitats. From the case studies and their evaluation, 12 recommendations on the future use of MEMs were formulated, addressing the issues of how to translate specific protection goals into workable questions, how to select species and scenarios to be modeled, and where and how to fit MEMs into current and future risk assessment schemes. The most important recommendations are that protection goals should be made more quantitative; the species to be modeled must be vulnerable not only regarding toxic effects but also regarding their life history and dispersal traits; the models should be as realistic as possible for a specific risk assessment question, and the level of conservatism required for a specific risk assessment should be reached by designing appropriately conservative environmental and exposure scenarios; scenarios should include different regions of the European Union (EU) and different crops; in the long run, generic MEMs covering relevant species based on representative scenarios should be developed, which will require EU-level joint initiatives of all stakeholders involved. The main conclusion from the MODELINK workshop is that the considerable effort required for making MEMs an integral part of environmental risk assessment of pesticides is worthwhile, because

  9. Development of boiling transition analysis code TCAPE-INS/B based on mechanistic methods for BWR fuel bundles. Models and validations with boiling transition experimental data

    International Nuclear Information System (INIS)

    Ishida, Naoyuki; Utsuno, Hideaki; Kasahara, Fumio

    2003-01-01

    The Boiling Transition (BT) analysis code TCAPE-INS/B based on the mechanistic methods coupled with subchannel analysis has been developed for the evaluation of the integrity of Boiling Water Reactor (BWR) fuel rod bundles under abnormal operations. Objective of the development is the evaluation of the BT without using empirical BT and rewetting correlations needed for different bundle designs in the current analysis methods. TCAPE-INS/B consisted mainly of the drift-flux model, the film flow model, the cross-flow model, the thermal conductivity model and the heat transfer correlations. These models were validated systematically with the experimental data. The accuracy of the prediction for the steady-state Critical Heat Flux (CHF) and the transient temperature of the fuel rod surface after the occurrence of BT were evaluated on the validations. The calculations for the experiments with the single tube and bundles were carried out for the validations of the models incorporated in the code. The results showed that the steady-state CHF was predicted within about 6% average error. In the transient calculations, BT timing and temperature of the fuel rod surface gradient agreed well with experimental results, but rewetting was predicted lately. So, modeling of heat transfer phenomena during post-BT is under modification. (author)

  10. Opening the black box—Development, testing and documentation of a mechanistically rich agent-based model

    DEFF Research Database (Denmark)

    Topping, Chris J.; Høye, Toke; Olesen, Carsten Riis

    2010-01-01

    Although increasingly widely used in biology, complex adaptive simulation models such as agent-based models have been criticised for being difficult to communicate and test. This study demonstrates the application of pattern-oriented model testing, and a novel documentation procedure to present...... accessible description of the processes included in the model. Application of the model to a comprehensive historical data set supported the hypothesis that interference competition is the primary population regulating factor in the absence of mammal predators in the brown hare, and that the effect works...

  11. Plasma-based water treatment: development of a general mechanistic model to estimate the treatability of different types of contaminants

    International Nuclear Information System (INIS)

    Mededovic Thagard, Selma; Stratton, Gunnar R; Paek, Eunsu; Dai, Fei; Holsen, Thomas M; Bellona, Christopher L; Bohl, Douglas G; Dickenson, Eric R V

    2017-01-01

    To determine the types of applications for which plasma-based water treatment (PWT) is best suited, the treatability of 23 environmental contaminants was assessed through treatment in a gas discharge reactor with argon bubbling, termed the enhanced-contact reactor. The contaminants were treated in a mixture to normalize reaction conditions and convective transport limitations. Treatability was compared in terms of the observed removal rate constant ( k obs ). To characterize the influence of interfacial processes on k obs , a model was developed that accurately predicts k obs for each compound, as well as the contributions to k obs from each of the three general degradation mechanisms thought to occur at or near the gas–liquid interface: ‘sub-surface’, ‘surface’ and ‘above-surface’. Sub-surface reactions occur just underneath the gas–liquid interface between the contaminants and dissolved plasma-generated radicals, contributing significantly to the removal of compounds that lack surfactant-like properties and so are not highly concentrated at the interface. Surface reactions occur at the interface between the contaminants and dissolved radicals, contributing significantly to the removal of surfactant-like compounds that have high interfacial concentrations. The contaminants’ interfacial concentrations were calculated using surface-activity parameters determined through surface tension measurements. Above-surface reactions are proposed to take place in the plasma interior between highly energetic plasma species and exposed portions of compounds that extend out of the interface. This mechanism largely accounts for the degradation of surfactant-like contaminants that contain highly hydrophobic perfluorocarbon groups, which are most likely to protrude from the interface. For a few compounds, the degree of exposure to the plasma interior was supported by new and previously reported molecular dynamics simulations results. By reviewing the predicted

  12. Plasma-based water treatment: development of a general mechanistic model to estimate the treatability of different types of contaminants

    Science.gov (United States)

    Mededovic Thagard, Selma; Stratton, Gunnar R.; Dai, Fei; Bellona, Christopher L.; Holsen, Thomas M.; Bohl, Douglas G.; Paek, Eunsu; Dickenson, Eric R. V.

    2017-01-01

    To determine the types of applications for which plasma-based water treatment (PWT) is best suited, the treatability of 23 environmental contaminants was assessed through treatment in a gas discharge reactor with argon bubbling, termed the enhanced-contact reactor. The contaminants were treated in a mixture to normalize reaction conditions and convective transport limitations. Treatability was compared in terms of the observed removal rate constant (k obs). To characterize the influence of interfacial processes on k obs, a model was developed that accurately predicts k obs for each compound, as well as the contributions to k obs from each of the three general degradation mechanisms thought to occur at or near the gas-liquid interface: ‘sub-surface’, ‘surface’ and ‘above-surface’. Sub-surface reactions occur just underneath the gas-liquid interface between the contaminants and dissolved plasma-generated radicals, contributing significantly to the removal of compounds that lack surfactant-like properties and so are not highly concentrated at the interface. Surface reactions occur at the interface between the contaminants and dissolved radicals, contributing significantly to the removal of surfactant-like compounds that have high interfacial concentrations. The contaminants’ interfacial concentrations were calculated using surface-activity parameters determined through surface tension measurements. Above-surface reactions are proposed to take place in the plasma interior between highly energetic plasma species and exposed portions of compounds that extend out of the interface. This mechanism largely accounts for the degradation of surfactant-like contaminants that contain highly hydrophobic perfluorocarbon groups, which are most likely to protrude from the interface. For a few compounds, the degree of exposure to the plasma interior was supported by new and previously reported molecular dynamics simulations results. By reviewing the predicted

  13. Development and Validation of a Biodynamic Model for Mechanistically Predicting Metal Accumulation in Fish-Parasite Systems.

    Directory of Open Access Journals (Sweden)

    T T Yen Le

    Full Text Available Because of different reported effects of parasitism on the accumulation of metals in fish, it is important to consider parasites while interpreting bioaccumulation data from biomonitoring programmes. Accordingly, the first step is to take parasitism into consideration when simulating metal bioaccumulation in the fish host under laboratory conditions. In the present study, the accumulation of metals in fish-parasite systems was simulated by a one-compartment toxicokinetic model and compared to uninfected conspecifics. As such, metal accumulation in fish was assumed to result from a balance of different uptake and loss processes depending on the infection status. The uptake by parasites was considered an efflux from the fish host, similar to elimination. Physiological rate constants for the uninfected fish were parameterised based on the covalent index and the species weight while the parameterisation for the infected fish was carried out based on the reported effects of parasites on the uptake kinetics of the fish host. The model was then validated for the system of the chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis following 36-day exposure to waterborne Pb. The dissolved concentration of Pb in the exposure tank water fluctuated during the exposure, ranging from 40 to 120 μg/L. Generally, the present study shows that the one-compartment model can be an effective method for simulating the accumulation of metals in fish, taking into account effects of parasitism. In particular, the predicted concentrations of Cu, Fe, Zn, and Pb in the uninfected chub as well as in the infected chub and the acanthocephalans were within one order of magnitude of the measurements. The variation in the absorption efficiency and the elimination rate constant of the uninfected chub resulted in variations of about one order of magnitude in the predicted concentrations of Pb. Inclusion of further assumptions for simulating metal accumulation

  14. A Study of Electrocyclic Reactions in a Molecular Junction: Mechanistic and Energetic Requirements for Switching in the Coulomb Blockade Regime.

    Science.gov (United States)

    Olsen, Stine T; Brøndsted Nielsen, Mogens; Hansen, Thorsten; Ratner, Mark A; Mikkelsen, Kurt V

    2017-06-20

    Molecular photoswitches incorporated in molecular junctions yield the possibility of light-controlled switching of conductance due to the electronic difference of the photoisomers. Another isomerization mechanism, dark photoswitching, promoted by a voltage stimulus rather than by light, can be operative in the Coulomb blockade regime for a specific charge state of the molecule. Here we elucidate theoretically the mechanistic and thermodynamic restrictions for this dark photoswitching for donor-acceptor substituted 4n and 4n+2 π-electron open-chain oligoenes (1,3-butadiene and 1,3,5-hexatriene) by considering the molecular energies and orbitals of the molecules placed in a junction. For an electrocyclic ring closure reaction to occur for these compounds, we put forward two requirements: a) the closed stereoisomer (cis or trans form) must be of lower energy than the open form, and b) the reaction pathway must be in accordance to the orbital symmetry rules expressed by the Woodward-Hoffmann rules (when the electrodes do not significantly alter the molecular orbital appearances). We find these two requirements to be valid for the dianion of (1E,3Z,5E)-hexa-1,3,5-triene-1,6-diamine, and the Coulomb blockade diamonds were therefore modeled for this compound to elucidate how a dark photoswitching event would manifest itself in the stability plot. From this modeling of conductance as a function of gate and bias potentials, we predict a collapse in Coulomb diamond size, that is, a decrease in the height of the island of zero conductance. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation.

    Science.gov (United States)

    Franek, F; Jarlfors, A; Larsen, F; Holm, P; Steffansen, B

    2015-09-18

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq(®), an extended release formulation (ERF). Semi-mechanistic models of desvenlafaxine were built (using SimCyp(®)) by combining in vitro data on dissolution and permeation (mechanistic part of model) with clinical data (obtained from literature) on distribution and clearance (non-mechanistic part of model). The model predictions of desvenlafaxine pharmacokinetics after IRF and ERF administration were compared with published clinical data from 14 trials. Desvenlafaxine in vivo dissolution from the IRF and ERF was predicted from in vitro solubility studies and biorelevant dissolution studies (using the USP3 dissolution apparatus), respectively. Desvenlafaxine apparent permeability (Papp) at varying apical pH was investigated using the Caco-2 cell line and extrapolated to effective intestinal permeability (Peff) in human duodenum, jejunum, ileum and colon. Desvenlafaxine pKa-values and octanol-water partition coefficients (Do:w) were determined experimentally. Due to predicted rapid dissolution after IRF administration, desvenlafaxine was predicted to be available for permeation in the duodenum. Desvenlafaxine Do:w and Papp increased approximately 13-fold when increasing apical pH from 5.5 to 7.4. Desvenlafaxine Peff thus increased with pH down the small intestine. Consequently, desvenlafaxine absorption from an IRF appears rate-limited by low Peff in the upper small intestine, which "delays" the predicted

  16. CF3CH(ONO)CF3: Synthesis, IR spectrum, and use as OH radical source for kinetic and mechanistic studies

    DEFF Research Database (Denmark)

    Andersen, Mads Peter Sulbæk; Hurley, MD; Ball, JC

    2003-01-01

    The synthesis, IR spectrum, and first-principles characterization of CF3CH(ONO)CF3 as well as its use as an OH radical source in kinetic and mechanistic studies are reported. CF3CH(ONO)CF3 exists in two conformers corresponding to rotation about the RCO-NO bond. The more prevalent trans conformer......C(O)CF3 and, by implication, OH radicals in 100% yield. CF3CH(ONO)CF3 photolysis is a convenient source of OH radicals in the studies of the yields of CO, CO2, HCHO, and HC(O)OH products which can be difficult to measure using more conventional OH radical sources (e.g., CH3ONO photolysis). CF3CH...

  17. Oxidation of alginate and pectate biopolymers by cerium(IV) in perchloric and sulfuric acid solutions: A comparative kinetic and mechanistic study.

    Science.gov (United States)

    Fawzy, Ahmed

    2016-03-15

    The kinetics of oxidation of alginate (Alg) and pectate (Pec) carbohydrate biopolymers was studied by spectrophotometry in aqueous perchloric and sulfuric acid solutions at fixed ionic strengths and temperature. In both acids, the reactions showed a first order dependence on [Ce(IV)], whereas the orders with respect to biopolymer concentrations are less than unity. In perchloric acid, the reactions exhibited less than unit orders with respect to [H(+)] whereas those proceeded in sulfuric acid showed negative fractional-first order dependences on [H(+)]. The effect of ionic strength and dielectric constant was studied. Probable mechanistic schemes for oxidation reactions were proposed. In both acids, the final oxidation products were characterized as mono-keto derivatives of both biopolymers. The activation parameters with respect to the slow step of the mechanisms were computed and discussed. The rate laws were derived and the reaction constants involved in the different steps of the mechanisms were calculated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Mechanistic Studies Investigating the Role of Organophosphate Insecticide Exposure in the Development and Exacerbation of Asthma

    National Research Council Canada - National Science Library

    Spannhake, Ernst

    2004-01-01

    ...) with a low does of the organophosphate chlorpyrifos sc. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals treated with chlorpyrifos...

  19. Mechanistic Studies Investigating the Role of Organophosphate Insecticide Exposure in the Development and Exacerbation of Asthma

    National Research Council Canada - National Science Library

    Fryer, Allison

    2003-01-01

    ...) with a low dose of the organophosphate,chlorpyrifos sc. Electrical stimulation of the vagus nerves caused frequency-dependent bronchoconstriction that was significantly potentiated in animals treated with chlorpyrifos...

  20. SUPERCRITICAL-PHASE ALKYLATION REACTION ON SOLID ACID CATALYSTS: MECHANISTIC STUDY AND CATALYST DEVELOPMENT. (R824729)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  1. Mechanistic Study of Electrolyte Additives to Stabilize High-Voltage Cathode–Electrolyte Interface in Lithium-Ion Batteries

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Han [Chemical; Maglia, Filippo [BMW Group, Munich 80788, Germany; Lamp, Peter [BMW Group, Munich 80788, Germany; Amine, Khalil [Chemical; Chen, Zonghai [Chemical

    2017-12-13

    Current developments of electrolyte additives to stabilize electrode-electrolyte interface in Li-ion batteries highly rely on a trial-and-error search, which involves repetitive testing and intensive amount of resources. The lack of understandings on the fundamental protection mechanisms of the additives significantly increases the difficulty for the transformational development of new additives. In this study, we investigated two types of individual protection routes to build a robust cathode-electrolyte interphase at high potentials: (i) a direct reduction in the catalytic decomposition of the electrolyte solvent; and (ii) formation of a “corrosion inhibitor film” that prevents severely attack and passivation from protons that generated from the solvent oxidation, even the decomposition of solvent cannot not mitigated. Effect of three exemplary electrolyte additives: (i) lithium difluoro(oxalato)borate (LiDFOB); (ii) 3-hexylthiophene (3HT); and (iii) tris(hexafluoro-iso-propyl)phosphate (HFiP), on LiNi0.6Mn0.2Co0.2O2 (NMC 622) cathode were investigated to validate our hypothesis. It is demonstrated that understandings of both electrolyte additives and solvent are essential and careful balance between the cathode protection mechanism of additives and their side effects is critical to obtain optimum results. More importantly, this study opens up new directions of rational design of functional electrolyte additives for the next generation high-energy density lithium-ion chemistries.

  2. Gold-catalyzed tandem hydroamination/formal aza-Diels-Alder reaction of homopropargyl amino esters: a combined computational and experimental mechanistic study.

    Science.gov (United States)

    Miró, Javier; Sánchez-Roselló, María; González, Javier; del Pozo, Carlos; Fustero, Santos

    2015-03-27

    A tandem gold-catalyzed hydroamination/formal aza-Diels-Alder reaction is described. This process, which employs quaternary homopropargyl amino ester substrates, leads to the formation of an intrincate tetracyclic framework and involves the generation of four bonds and five stereocenters in a highly diastereoselective manner. Theoretical calculations have allowed us to propose a suitable mechanistic rationalization for the tandem protocol. Additionally, by studying the influence of the ligands on the rate of the gold-catalyzed reactions, it was possible to establish optimum conditions in which to perform the process with a variety of substituents on the amino ester substrates. Notably, the asymmetric version of the tandem reaction was also evaluated. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Geothermal area detection using Landsat ETM+ thermal infrared data and its mechanistic analysis—A case study in Tengchong, China

    Science.gov (United States)

    Qin, Qiming; Zhang, Ning; Nan, Peng; Chai, Leilei

    2011-08-01

    Thermal infrared (TIR) remote sensing is an important technique in the exploration of geothermal resources. In this study, a geothermal survey is conducted in Tengchong area of Yunnan province in China using TIR data from Landsat-7 Enhanced Thematic Mapper Plus (ETM+) sensor. Based on radiometric calibration, atmospheric correction and emissivity calculation, a simple but efficient single channel algorithm with acceptable precision is applied to retrieve the land surface temperature (LST) of study area. The LST anomalous areas with temperature about 4-10 K higher than background area are discovered. Four geothermal areas are identified with the discussion of geothermal mechanism and the further analysis of regional geologic structure. The research reveals that the distribution of geothermal areas is consistent with the fault development in study area. Magmatism contributes abundant thermal source to study area and the faults provide thermal channels for heat transfer from interior earth to land surface and facilitate the present of geothermal anomalies. Finally, we conclude that TIR remote sensing is a cost-effective technique to detect LST anomalies. Combining TIR remote sensing with geological analysis and the understanding of geothermal mechanism is an accurate and efficient approach to geothermal area detection.

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

    Science.gov (United States)

    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

  5. Assessing uncertainty in mechanistic models

    Science.gov (United States)

    Edwin J. Green; David W. MacFarlane; Harry T. Valentine

    2000-01-01

    Concern over potential global change has led to increased interest in the use of mechanistic models for predicting forest growth. The rationale for this interest is that empirical models may be of limited usefulness if environmental conditions change. Intuitively, we expect that mechanistic models, grounded as far as possible in an understanding of the biology of tree...

  6. A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

    Science.gov (United States)

    Mahmood, Abda; Roberts, Ian; Shakur, Haleema

    2017-07-17

    Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage

  7. Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms.

    Directory of Open Access Journals (Sweden)

    Yan Hu

    Full Text Available Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms.To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK, which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A. ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A. ceylanicum hookworm burdens from infected hamsters, in the process eliminating hookworm egg shedding in feces and protecting infected hamsters from blood loss. Anthelmintic activity is increased about 3-fold, eliminating >97% of the parasites with a single 3 mg dose (∼30 mg/kg, by incorporating a simple formulation to help prevent digestion in the acidic stomach of the host mammal.These studies advance the development of Cry5B protein as a potent, safe single-dose anthelmintic for hookworm therapy and make available the information of how

  8. A protocol of histone modification-based mechanistic study of acupuncture in patients with stable angina pectoris.

    Science.gov (United States)

    Wang, Ning; Lu, Sheng-Feng; Chen, Hui; Wang, Jian-Fei; Fu, Shu-Ping; Hu, Chen-Jun; Yang, Yi; Liang, Fan-Rong; Zhu, Bing-Mei

    2015-04-30

    Angina pectoris (Angina) is a medical condition related to myocardial ischemia. Although acupuncture has been widely accepted as a clinical approach for angina, there is no sufficient evidence of its effectiveness against this syndrome, and its mechanisms have not yet been well elucidated. We develop this protocol to confirm the clinical efficacy of electro-acupuncture on stable angina pectoris by needling on acupoint Neiguan (PC6). Furthermore, we employ high-throughput sequencing technology to investigate the gene expression profiling and determine involvement of histone modifications in the regulation of genes after electro-acupuncture treatment. A randomized, controlled, double-blinded (assessor and patients) trial will be carried out. Sixty participants will be randomly assigned to two acupuncture treatment groups and one control group in a 1:1:1 ratio. Participants in acupuncture groups will receive 12 sessions of electro-acupuncture treatment across 4 weeks, followed by a 12-week randomization period. The acupuncture groups are divided into Neiguan (PC6) on Pericardium Meridian of Hand-jueyin or a non-acupoint. The primary clinical measure of effect is the frequency of angina attacks between these groups for four weeks after randomization. RNAs are extracted from peripheral neutrophils collected from all participants on day 0, day 30, and week 16, and are processed to RNA-Seq. We then investigate profiles of histone modifications by ChIP-Seq, for H3 Lysine 4 (H3K4me) and acetylation of H3 Lysine 27 (H3K27ac), in the presence or absence of acupuncture treatment. This study determines the efficacy and mechanisms of electro-acupuncture on stable angina pectoris. We focus on effectiveness of acupuncture on alleviating symptoms of myocardial ischemia and the gene regulation and the chromatin remodeling marks, including H3K4me1, H3K4me2, and H3K27ac, which could be key factors for regulating gene expressions caused by electro-acupuncture treatment at Neiguan. This

  9. Numerical simulation in steam injection process by a mechanistic approach

    Energy Technology Data Exchange (ETDEWEB)

    De Souza, J.C.Jr.; Campos, W.; Lopes, D.; Moura, L.S.S. [Petrobras, Rio de Janeiro (Brazil)

    2008-10-15

    Steam injection is a common thermal recovery method used in very viscous oil reservoirs. The method involves the injection of heat to reduce viscosity and mobilize oil. A steam generation and injection system consists primarily of a steam source, distribution lines, injection wells and a discarding tank. In order to optimize injection and improve the oil recovery factor, one must determine the parameters of steam flow such as pressure, temperature and steam quality. This study focused on developing a unified mathematical model by means of a mechanistic approach for two-phase steam flow in pipelines and wells. The hydrodynamic and heat transfer mechanistic model was implemented in a computer simulator to model the parameters of steam injection while trying to avoid the use of empirical correlations. A marching algorithm was used to determine the distribution of pressure and temperature along the pipelines and wellbores. The mathematical model for steam flow in injection systems, developed by a mechanistic approach (VapMec) performed well when the simulated values of pressures and temperatures were compared with the values measured during field tests. The newly developed VapMec model was incorporated in the LinVap-3 simulator that constitutes an engineering supporting tool for steam injection wells operated by Petrobras. 23 refs., 7 tabs., 6 figs.

  10. Clarified Açaí (Euterpe oleracea Juice as an Anticonvulsant Agent: In Vitro Mechanistic Study of GABAergic Targets

    Directory of Open Access Journals (Sweden)

    Gabriela P. F. Arrifano

    2018-01-01

    Full Text Available Seizures affect about 50 million people around the world. Approximately 30% of seizures are refractory to the current pharmacological arsenal, so, the pursuit of new therapeutic alternatives is essential. Clarified Euterpe oleracea (EO juice showed anticonvulsant properties similar to diazepam in an in vivo model with pentylenetetrazol, a GABAA receptor blocker. This study investigated the effects of EO on the main GABAergic targets for anticonvulsant drugs, analyzing the effect on the GABA receptor’s benzodiazepine and picrotoxinin binding sites and the GABA uptake. Primary cultures of cortical neurons and astrocytes were treated with EO (0–25% for up to 90 min. [3H]Flunitrazepam and [3H]TBOB binding, [3H]GABA uptake, cell viability, and morphology were assayed. Nonlethal concentrations of EO increased agonist binding and decreased antagonist binding in cortical neurons. Low concentrations significantly inhibited GABA uptake, especially in astrocytes, suggesting an accumulation of endogenous GABA in the synaptic cleft. The results demonstrate, for the first time, that EO can improve GABAergic neurotransmission via interactions with GABAA receptor and modulation of GABA uptake. Understanding these molecular mechanisms will help in the treatment of seizures and epilepsy, especially in developing countries where geographic isolation and low purchasing power are the main barriers to access to adequate treatment.

  11. Kinetic and mechanistic studies of reactive intermediates in photochemical and transition metal-assisted oxidation, decarboxylation and alkyl transfer reactions

    Science.gov (United States)

    Carraher, Jack McCaslin

    Reactive species like high-valent metal-oxo complexes and carbon and oxygen centered radicals are important intermediates in enzymatic systems, atmospheric chemistry, and industrial processes. Understanding the pathways by which these intermediates form, their relative reactivity, and their fate after reactions is of the utmost importance. Herein are described the mechanistic detail for the generation of several reactive intermediates, synthesis of precursors, characterization of precursors, and methods to direct the chemistry to more desirable outcomes yielding 'greener' sources of commodity chemicals and fuels. High-valent Chromium from Hydroperoxido-Chromium(III). The decomposition of pentaaquahydroperoxido chromium(III) ion (hereafter Cr aqOOH2+) in acidic aqueous solutions is kinetically complex and generates mixtures of products (Craq3+, HCrO 4-, H2O2, and O2). The yield of high-valent chromium products (known carcinogens) increased from a few percent at pH 1 to 70 % at pH 5.5 (near biological pH). Yields of H 2O2 increased with acid concentration. The reproducibility of the kinetic data was poor, but became simplified in the presence of H2O2 or 2,2‧-azinobis(3-ethylbenzothiazoline-6-sulfonate) dianion (ABTS2-). Both are capable of scavenging strongly oxidizing intermediates). The observed rate constants (pH 1, [O2] ≤ 0.03 mM) in the presence of these scavengers are independent of [scavenger] and within the error are the same (k,ABTS2- = (4.9 +/- 0.2) x 10-4 s-1 and kH2O2 = (5.3 +/- 0.7) x 10-4 s-1); indicating involvement of the scavengers in post-rate determining steps. In the presence of either scavenger, decomposition of CrOOH2+ obeyed a two-term rate law, k obs / s-1 = (6.7 +/- 0.7) x 10-4 + (7.6 +/- 1.1) x 10-4 [H+]. Effect of [H+] on the kinetics and the product distribution, cleaner kinetics in the presence of scavengers, and independence of kobs on [scavenger] suggest a dual-pathway mechanism for the decay of Craq OOH2+. The H+-catalyzed path

  12. Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry.

    Science.gov (United States)

    Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

    2016-01-01

    We report a reaction apparatus developed to monitor singlet oxygen ((1)O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. (1)O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. (1)O2 concentrations in solution were linearly related to the emission intensities of airborne (1)O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an (1)O2 trapping agent. Products from (1)O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of (1)O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. (1)O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with (1)O2, evolution of methionine oxidation pathways at different ionization states and in different media is described.

  13. A mechanistic study of Toxoplasma gondii ROP18 inhibiting differentiation of C17.2 neural stem cells

    Directory of Open Access Journals (Sweden)

    Xian Zhang

    2017-11-01

    Full Text Available Abstract Background Congenital infection of Toxoplasma gondii is an important factor causing birth defects. The neural stem cells (NSCs are found to be one of the target cells for the parasite during development of the brain. As a key virulence factor of the parasite that hijacks host cellular functions, ROP18 has been demonstrated to mediate the inhibition of host innate and adaptive immune responses through specific binding different host immunity related molecules. However, its pathogenic actions in NSCs remain elusive. Results In the present study, ROP18 recombinant adenovirus (Ad-ROP18 was constructed and used to infect C17.2 NSCs. After 3d- or 5d–culture in differentiation medium, the differentiation of C17.2 NSCs and the activity of the Wnt/β-catenin signaling pathway were detected. The results showed that the protein level of βIII-tubulin, a marker of neurons, in the Ad-ROP18-transfected C17.2 NSCs was significantly decreased, indicating that the differentiation of C17.2 NSCs was inhibited by the ROP18. The β-catenin level in the Ad-ROP18-transfected C17.2 NSCs was found to be lower than that in the Ad group. Also, neurogenin1 (Ngn1 and neurogenin2 (Ngn2 were downregulated significantly (P < 0.05 in the Ad-ROP18-transfected C17.2 NSCs compared to the Ad group. Accordingly, the TOP flash/FOP flash dual-luciferase report system showed that the transfection of Ad-ROP18 decreased the Wnt/β-catenin pathway activity in the C17.2 NSCs. Conclusions The inhibition effect of the ROP18 from T. gondii (TgROP18 on the neuronal differentiation of C17.2 NSCs was at least partly mediated through inhibiting the activity of the Wnt/β-catenin signaling pathway, eventually resulting in the downregulation of Ngn1 and Ngn2. The findings help to better understand potential mechanisms of brain pathology induced by TgROP18.

  14. Mechanistic aspects of ionic reactions in flames

    DEFF Research Database (Denmark)

    Egsgaard, H.; Carlsen, L.

    1993-01-01

    Some fundamentals of the ion chemistry of flames are summarized. Mechanistic aspects of ionic reactions in flames have been studied using a VG PlasmaQuad, the ICP-system being substituted by a simple quartz burner. Simple hydrocarbon flames as well as sulfur-containing flames have been investigated...

  15. Mechanistic investigation of the gold-catalyzed aerobic oxidation of aldehydes: added insight from Hammett studies and isotopic labelling experiments

    DEFF Research Database (Denmark)

    Fristrup, Peter; Johansen, Louise Bahn; Christensen, Claus Hviid

    2008-01-01

    The gold-catalyzed aerobic oxidation of aldehydes proceeds through development of a partial negative charge and has a significant kinetic isotope effect (k(H)/k(D) = 2.8-2.9), which illustrates that activation of the C-H bond takes place in the rate-determining step.......The gold-catalyzed aerobic oxidation of aldehydes proceeds through development of a partial negative charge and has a significant kinetic isotope effect (k(H)/k(D) = 2.8-2.9), which illustrates that activation of the C-H bond takes place in the rate-determining step....

  16. Palladium(II)-catalyzed desulfitative synthesis of aryl ketones from sodium arylsulfinates and nitriles: scope, limitations, and mechanistic studies.

    Science.gov (United States)

    Skillinghaug, Bobo; Sköld, Christian; Rydfjord, Jonas; Svensson, Fredrik; Behrends, Malte; Sävmarker, Jonas; Sjöberg, Per J R; Larhed, Mats

    2014-12-19

    A fast and efficient protocol for the palladium(II)-catalyzed production of aryl ketones from sodium arylsulfinates and various organic nitriles under controlled microwave irradiation has been developed. The wide scope of the reaction has been demonstrated by combining 14 sodium arylsulfinates and 21 nitriles to give 55 examples of aryl ketones. One additional example illustrated that, through the choice of the nitrile reactant, benzofurans are also accessible. The reaction mechanism was investigated by electrospray ionization mass spectrometry and DFT calculations. The desulfitative synthesis of aryl ketones from nitriles was also compared to the corresponding transformation starting from benzoic acids. Comparison of the energy profiles indicates that the free energy requirement for decarboxylation of 2,6-dimethoxybenzoic acid and especially benzoic acid is higher than the corresponding desulfitative process for generating the key aryl palladium intermediate. The palladium(II) intermediates detected by ESI-MS and the DFT calculations provide a detailed understanding of the catalytic cycle.

  17. Intermanual Transfer Effect in Young Children After Training in a Complex Skill : Mechanistic, Pseudorandomized, Pretest-Posttest Study

    NARCIS (Netherlands)

    Romkema, Sietske; Bongers, Raoul M.; van der Sluis, Corry K.

    Background. Intermanual transfer implies that motor skills learned on one side of the body transfer to the untrained side. This effect was previously noted in adults practicing with a prosthesis simulator. Objective. The study objective was to determine whether intermanual transfer is present in

  18. Ni adsorption and Ni-Al LDH precipitation in a sandy aquifer: An experimental and mechanistic modeling study

    NARCIS (Netherlands)

    Regelink, I.C.; Temminghoff, E.J.M.

    2011-01-01

    Mining activities and industries have created nickel (Ni) contaminations in many parts of the world. The objective of this study is to increase our understanding of Ni adsorption and Nickel-Aluminium Layered Double Hydroxide (Ni-Al LDH) precipitation to reduce Ni mobility in a sandy soil aquifer. At

  19. MECHANISTIC STUDIES OF SURFACE CATALYZED H2O2 DECOMPOSITION AND CONTAMINANT DEGRADATION IN THE PRESENCE OF SAND. (R823402)

    Science.gov (United States)

    This study examined the mechanism and kinetics of surface catalyzed hydrogen peroxide decomposition and degradation of contaminants in the presence of sand collected from an aquifer and a riverbed. Batch experiments were conducted using variable sand concentrations (0.2 to 1.0&nb...

  20. A mechanistic study of Ni-catalyzed carbon dioxide coupling with ethylene towards the manufacture of acrylic acid

    NARCIS (Netherlands)

    Yang, G.; Schäffner, B.; Blug, M.; Hensen, E.J.M.; Pidko, E.A.

    2014-01-01

    The reaction mechanism of CO2 coupling with C2H4 by homogeneous Ni-complexes bearing bidentate phosphorous ligands was studied by means of density functional theory calculations. The reaction is initiated by sequential coordination of C2H4 and CO2 to the Ni center, followed by a facile coupling

  1. Mechanistic Aspects of the Reversible Binding of SO2 on Arylplatinum Complexes: Experimental and ab Initio Studies

    NARCIS (Netherlands)

    Koten, G. van; Albrecht, M.A.; Gossage, R.A.; Frey, H.; Ehlers, A.W.; Baerends, E.J.; Merbach, A.E.

    2001-01-01

    The detailed mechanism of the reversible binding and fast exchange of SO2 on the organoplatinum(II) complex [PtI(NCN)], 1, has been studied experimentally in solution (C2F4Br2) using low-temperature NMR spectroscopy and theoretically by ab initio calculations. Direct bonding of SO2 and formation of

  2. Adhesion of nano-sized particles to the surface of bacteria: mechanistic study with the extended DLVO theory.

    Science.gov (United States)

    Hwang, Geelsu; Ahn, Ik-Sung; Mhin, Byung Jin; Kim, Ju-Young

    2012-09-01

    Due to the increasing production and application of nanoparticles, their release into the environment would be inevitable, which requires a better understanding of their fate in the environment. When considering their toxic behavior or biodegradation as their fate, their adhesion to the cell surface must be the first step to be thoroughly studied. In this study, nano-sized polymeric particles of urethane acrylate with various hydrophobicity and ionic properties were synthesized as model nanoparticles, and their adhesion to Pseudomonas putida strains was monitored. The higher hydrophobicity and positive charge density on the particle surface exhibited the larger adhesion to the bacteria, whereas negative charge density on the particle hindered their adhesion to the bacteria, albeit high hydrophobicity of particle. These observations were successfully explained with the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. Chelated Nitrogen-Sulphur-Codoped TiO2: Synthesis, Characterization, Mechanistic, and UV/Visible Photocatalytic Studies

    Directory of Open Access Journals (Sweden)

    Hayat Khan

    2017-01-01

    Full Text Available This study presents in detail the physicochemical, photoluminescent, and photocatalytic properties of carboxylic acid chelated nitrogen-sulphur-codoped TiO2. From the Fourier transform infrared spectroscopic study, it was revealed that the formate group formed bidentate bridging linkage while the acetate group coordinated in a bidentate chelating mode with a titanium precursor. In compliance with X-ray diffraction data, the anatase to rutile transformation temperature was extended due to carboxylic acid chelation and NS codoping. Raman analysis indicated four Raman peaks at 146, 392, 512, and 632 cm−1 for the precalcined chelated TiO2; on incorporation with NS dopants, an increase in Raman intensity for these peaks was recorded, indicating the structure stability of the anatase phase. Furthermore, X-ray photoelectron spectroscopic study revealed the presence of anionic doping of nitrogen and cationic doping of sulphur in the lattice of TiO2. When evaluating the UV-visible photodegradation rate of 4-chlorophenol, the modified TiO2 (NS0.06-TFA showed the highest photocatalytic activity. In connection with the activity tests, several scavenger agents were employed to elucidate the significance of the different reactive oxidizing species during the photocatalytic process. Moreover, the transfer pathways of photogenerated carriers and the photocatalytic reaction mechanism of modified TiO2 were also explained in detail.

  4. A mechanistic study on the effect of dexamethasone in moderating cell death in Chinese Hamster Ovary cell cultures.

    Science.gov (United States)

    Jing, Ying; Qian, Yueming; Ghandi, Mahmoud; He, Aiqing; Borys, Michael C; Pan, Shih-Hsie; Li, Zheng Jian

    2012-01-01

    Dexamethasone (DEX) was previously shown (Jing et al., Biotechnol Bioeng. 2010;107:488-496) to play a dual role in increasing sialylation of recombinant glycoproteins produced by Chinese Hamster Ovary (CHO) cells. DEX addition increased sialic acid levels of a recombinant fusion protein through increased expression of α2,3-sialyltransferase and β1,4-galactosyltransferase, but also decreased the sialidase-mediated, extracellular degradation of sialic acid through slowing cell death at the end of the culture period. This study examines the underlying mechanism for this cytoprotective action by studying the transcriptional response of the CHO cell genome upon DEX treatment using DNA microarrays and gene ontology term analysis. Many of those genes showing a significant transcriptional response were associated with the regulation of programmed cell death. The gene with the highest change in expression level, as validated by Quantitative PCR assays with TaqMan® probes and confirmed by Western Blot analysis, was the antiapoptotic gene Tsc22d3, also referred to as GILZ (glucocorticoid-induced leucine zipper). The pathway by which DEX suppressed cell death towards the end of the culture period was also confirmed by showing involvement of glucocorticoid receptors and GILZ through studies using the glucocorticoid antagonist mifepristone (RU-486). These findings advance the understanding of the mechanism by which DEX suppresses cell death in CHO cells and provide a rationale for the application of glucocorticoids in CHO cell culture processes. Copyright © 2011 American Institute of Chemical Engineers (AIChE).

  5. Kinetics and mechanistic study of n-alkane hydroisomerization reaction on Pt-doped γ-alumina catalyst

    Directory of Open Access Journals (Sweden)

    Abhishek Dhar

    2017-12-01

    Full Text Available The catalysts γ-alumina (GA, the reference catalyst and Pt doped γ-alumina (PGA-s were synthesized using a simple sol-gel technique, in which at first preparation of porous base (GA, then impregnation of platinum salt over the base and finally reduction of platinum in the surface of the support were done. These catalysts prepared in different mole ratios of Pt:Al as 2:1, 1:1 and 1:2 are named as PGA-1, PGA-2 and PGA-3 respectively. The isomerization of n-alkanes (n-hexane, n-heptane and n-octane were investigated over the synthesized catalysts. The 2-methyl pentane (2-MP, 2,2-dimethyl pentane (2,2-DMP and 2,3-dimethyl hexane (2,3-DMH are the major products of respective isomerization of n-hexane, n-heptane and n-octane, besides a small amount of other branched isomers are also produced. The product distribution is comparable to that reported for Pt based other catalysts. The optimal mole ratios of Pt:Al is 1:1 (PGA-2 gives quite good catalytic activity for isomerization of n-alkane. Even through in reusability study, PGA-2 gives better performance than others. We have mainly focused on kinetic study, reaction mechanism behind isomerization and calculated the order of reactions and activation energies of the isomerization reactions in the present work. Keywords: Isomerization, n-alkanes, Catalyst, Reaction mechanism, Kinetics study, Activation energy

  6. Use of deuterium n. m. r. spectroscopy in mechanistic studies of exchange reactions of ethers on supported metal catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, J.A.; Kemball, Charles; McDougall, G.S.

    1987-10-01

    Exchange reactions of diethyl ether (DEE) and tetrahydrofuran (THF) with deuterium have been studied over supported nickel, palladium, platinum, and rhodium catalysts. Products from most of the systems were analysed by deuterium n.m.r. spectroscopy (55.28 MHz) which gave quantitative results about the distribution of deuterium in the exchanged ethers. The results confirm earlier conclusions about the mechanism of the exchange of DEE and provide new evidence about the reactions of THF. Some hydrogenolysis occurred simultaneously with exchange of THF over both nickel and platinum.

  7. Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage of Carbon-Carbon Bonds in Ketones

    DEFF Research Database (Denmark)

    Mazziotta, Andrea; Makarov, Ilya S.; Fristrup, Peter

    2017-01-01

    The hydroxide-mediated cleavage of ketones into alkanes and carboxylic acids has been reinvestigated and the substrate scope extended to benzyl carbonyl compounds. The transformation is performed with a 0.05 M ketone solution in refluxing xylene in the presence of 10 equiv of potassium hydroxide....... The studies were complemented by a theoretical investigation where two possible pathways were characterized by DFT/M06-2X. The calculations showed that the scission takes place by nucleophilic attack of hydroxide on the ketone followed by fragmentation of the resulting oxyanion into the carboxylic acid...

  8. Mechanistic Study of Utilization of Water-Insoluble Saccharomyces cerevisiae Glucans by Bifidobacterium breve Strain JCM1192.

    Science.gov (United States)

    Keung, Hoi Yee; Li, Tsz Kai; Sham, Lok To; Cheung, Man Kit; Cheung, Peter Chi Keung; Kwan, Hoi Shan

    2017-04-01

    Bifidobacteria exert beneficial effects on hosts and are extensively used as probiotics. However, due to the genetic inaccessibility of these bacteria, little is known about their mechanisms of carbohydrate utilization and regulation. Bifidobacterium breve strain JCM1192 can grow on water-insoluble yeast ( Saccharomyces cerevisiae ) cell wall glucans (YCWG), which were recently considered as potential prebiotics. According to the results of 1 H nuclear magnetic resonance (NMR) spectrometry, the YCWG were composed of highly branched (1→3,1→6)-β-glucans and (1→4,1→6)-α-glucans. Although the YCWG were composed of 78.3% β-glucans and 21.7% α-glucans, only α-glucans were consumed by the B. breve strain. The ABC transporter ( malEFG1 ) and pullulanase ( aapA ) genes were transcriptionally upregulated in the metabolism of insoluble yeast glucans, suggesting their potential involvement in the process. A nonsense mutation identified in the gene encoding an ABC transporter ATP-binding protein (MalK) led to growth failure of an ethyl methanesulfonate-generated mutant with yeast glucans. Coculture of the wild-type strain and the mutant showed that this protein was responsible for the import of yeast glucans or their breakdown products, rather than the export of α-glucan-catabolizing enzymes. Further characterization of the carbohydrate utilization of the mutant and three of its revertants indicated that this mutation was pleiotropic: the mutant could not grow with maltose, glycogen, dextrin, raffinose, cellobiose, melibiose, or turanose. We propose that insoluble yeast α-glucans are hydrolyzed by extracellular pullulanase into maltose and/or maltooligosaccharides, which are then transported into the cell by the ABC transport system composed of MalEFG1 and MalK. The mechanism elucidated here will facilitate the development of B. breve and water-insoluble yeast glucans as novel synbiotics. IMPORTANCE In general, Bifidobacterium strains are genetically intractable

  9. Kinetic and Mechanistic Study of the pH-Dependent Activation (Epoxidation) of Prodrug Treosulfan Including the Reaction Inhibition in a Borate Buffer.

    Science.gov (United States)

    Romański, Michał; Ratajczak, Whitney; Główka, Franciszek

    2017-07-01

    A prodrug treosulfan (T) undergoes a pH-dependent activation to epoxide derivatives. The process seems to involve an intramolecular Williamson reaction (IWR) but clear kinetic evidence is lacking. Moreover, a cis-diol system present in the T structure is expected to promote complexation with boric acid. As a result, the prodrug epoxidation would be inhibited; however, this phenomenon has not been investigated. In this article, the effect of pH on the kinetics of T conversion to its monoepoxide was studied from a mechanistic point of view. Also, the influence of boric acid on the reaction kinetics was examined. The rate constants observed for the activation of T (k obs ) in acetate, phosphate, and carbonate buffers satisfied the equation logk obs  = -7.48 + 0.96 pH. The reaction was inhibited in the excess of boric acid over T, and the k obs decreased with increasing borate buffer concentration. The experimental results were consistent with the inhibition model that included the formation of a tetrahedral, anionic T-boric acid monoester. To conclude, in nonborate buffers, the T activation to (2S,3S)-1,2-epoxybutane-3,4-diol 4-methanesulfonate follows IWR mechanism. A borate buffer changes the reaction kinetics and complicates kinetic analysis. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Modelling the active site of NiFe hydrogenases: new catalysts for the electro-production of H2 and mechanistic studies

    International Nuclear Information System (INIS)

    Canaguier, S.

    2009-01-01

    NiFe hydrogenases are unique metalloenzymes that catalyze H + /H 2 interconversion with remarkable efficiency close to the thermodynamic potential. Their active site consists of a hetero-bimetallic complex containing a nickel ion in a sulphur-rich environment connected by two thiolate bridges to an organometallic cyano-carbonyl iron moiety. In order to improve the understanding of the enzymatic mechanism and to obtain new base-metal electrocatalysts for H 2 production, we synthesized a series of bio-inspired low molecular weight model complexes with the butterfly structure Ni(μ-S 2 )M (M= Ru, Mn and Fe). All these compounds displayed a catalytic activity of hydrogen production. Modulating the electronic and steric properties of the ruthenium center allowed optimizing the catalytic performances of these compounds in terms of stability, catalytic rate and overpotential. Mechanistic studies of the catalytic cycle of the Ni-Ru complexes have also been carried out. They allowed us to suggest a bio-relevant bridging hydride as the catalytic intermediate. Finally, we synthesized one of the first Ni-Fe complexes that is both a structural and a functional model of NiFe hydrogenase. (author) [fr

  11. Economical recycling process for spent lithium-ion batteries and macro- and micro-scale mechanistic study

    Science.gov (United States)

    Li, Li; Bian, Yifan; Zhang, Xiaoxiao; Xue, Qing; Fan, Ersha; Wu, Feng; Chen, Renjie

    2018-02-01

    An economical effective method is developed for recycling spent LiNi1/3Co1/3Mn1/3O2 cathodes, where more than 98% Li, Co, Ni and Mn can be leached out with different organic acids, and resynthesized to LiNi1/3Co1/3Mn1/3O2. The leaching mechanism is investigated at macro- and micro-scales. The particles undergo a loosening-breaking-shrinking change for two acids, while the FTIR and UV-vis spectra indicate different coordination reactions. The performance of LiNi1/3Co1/3Mn1/3O2 resynthesized from the leachate of the acetic acid leaching (NCM-Ac) and maleic acid leaching (NCM-Ma) are compared. The first discharge capacity of NCM-Ma and NCM-Ac at 0.2C are 151.6 and 115.0 mA h g-1, respectively. The much better performance of NCM-Ma than NCM-Ac results from the different coordination of the two acids in the sol-gel process, where the maleic acid can esterify to establish a stable network to chelate metal ions, while the weak chelation of acetic acid leads to the formation of impurities. The economics analysis including the cost of leaching acid and energy consumption shows that the price of organic acids and reducing agents, short leaching time, low temperature and high-valued products are the effective way to increase recycling and environmental benefits, which shows advantages in terms of resources cost and added value.

  12. Experimental and Computational Mechanistic Studies Guiding the Rational Design of Molecular Electrocatalysts for Production and Oxidation of Hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Raugei, Simone [Center for Molecular Electrocatalysis,; Helm, Monte L. [Center for Molecular Electrocatalysis,; Hammes-Schiffer, Sharon [Department of Chemistry, University of Illinois at Urbana—Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, United States; Appel, Aaron M. [Center for Molecular Electrocatalysis,; O’Hagan, Molly [Center for Molecular Electrocatalysis,; Wiedner, Eric S. [Center for Molecular Electrocatalysis,; Bullock, R. Morris [Center for Molecular Electrocatalysis,

    2015-11-25

    Understanding how to control the movement of protons and electrons is crucial to the design of fast, efficient electrocatalysts for H2 production and oxidation based on earth-abundant metals. Our work seeks to address fundamental questions about proton movement. We have demonstrated that incorporating a pendant amine functioning as a proton relay in the second coordination sphere of a metal complex helps proton mobility, resulting in faster and more energy-efficient catalysts. Proton-transfer reactions can be rate-limiting and are influenced by several factors, such as pKa values, steric effects, hydrogen bonding, and solvation/desolvation of the exogenous base and acid employed. The presence of multiple protonation sites introduces branching points along the catalytic cycle, making less productive pathways accessible or leading to the formation of stable off-cycle species. Using ligands with only one pendant amine mitigates this problem and results in catalysts with high rates for production of H2, although generally at higher overpotentials. For H2 oxidation catalysts, iron complexes with a high H2 binding affinity were developed. However, these iron complexes had a pKa mismatch between the protonated metal center and the protonated pendant amine, and consequently intramolecular proton movement was slow. Taken altogether, our results demonstrate the necessity of optimizing the entire catalytic cycle because optimization of a specific catalytic step can negatively influence another step and not necessarily lead to a better catalytic performance. We discuss a general procedure, based on thermodynamic arguments, which allows the simultaneous minimization of the free-energy change of each catalytic step, yielding a nearly flat free-energy surface, with no large barriers due to energy mismatches from either high- or low-energy intermediates.

  13. Experimental and Computational Mechanistic Studies Guiding the Rational Design of Molecular Electrocatalysts for Production and Oxidation of Hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Raugei, Simone; Helm, Monte L.; Hammes-Schiffer, Sharon; Appel, Aaron M.; O’Hagan, Molly; Wiedner, Eric S.; Bullock, R. Morris

    2016-01-19

    Understanding how to control the movement of protons and electrons is crucial to the design of fast, efficient electrocatalysts for H2 production and oxidation based on earth-abundant metals. Our work seeks to address fundamental questions about proton movement. We have demonstrated that incorporating a pendant amine functioning as a proton relay in the second coordination sphere of a metal complex helps proton mobility, resulting in faster and more energy-efficient catalysts. Proton-transfer reactions can be rate-limiting and are influenced by several factors, such as pKa values, steric effects, hydrogen bonding, and solvation/desolvation of the exogenous base and acid employed. The presence of multiple protonation sites introduces branching points along the catalytic cycle, making less productive pathways accessible or leading to the formation of stable off-cycle species. Using ligands with only one pendant amine mitigates this problem and results in catalysts with high rates for production of H2, although generally at higher overpotentials. For H2 oxidation catalysts, iron complexes with a high H2 binding affinity were developed. However, these iron complexes had a pKa mismatch between the protonated metal center and the protonated pendant amine, and consequently intramolecular proton movement was slow. Taken altogether, our results demonstrate the necessity of optimizing the entire catalytic cycle because optimization of a specific catalytic step can negatively influence another step and not necessarily lead to a better catalytic performance. We discuss a general procedure, based on thermodynamic arguments, which allows the simultaneous minimization of the free-energy change of each catalytic step, yielding a nearly flat free-energy surface, with no large barriers due to energy mismatches from either high- or low-energy intermediates.

  14. Temperature-dependent spectroscopic evidences of curcumin in aqueous medium: a mechanistic study of its solubility and stability.

    Science.gov (United States)

    Jagannathan, Ramya; Abraham, Priya Mary; Poddar, Pankaj

    2012-12-20

    In curcumin, keto-enol-enolate equilibrium of the heptadiene-dione moiety determines its physiochemical and antioxidant properties. However, its poor solubility in water at neutral pH and room temperature decreases its bioavailability. Potential therapeutic applications have triggered an interest in manipulating the solubility of curcumin in water as its stability and solubility in water remains poorly understood. Here, the mechanism behind its solubility at various temperatures and the influence of interplay of temperature, intramolecular H-bonding, and intermolecular forces is reported, which leads to aggregation-disaggregation at various temperatures. Remarkable change is observed in temperature-dependent electronic transition behavior of curcumin, however, the absorption spectra after cooling and heating cycles remain unchanged, hinting much better thermal stability of curcumin in water than previously thought. This study indicates that it is perhaps the breaking of intramolecular hydrogen bonding which leads to exposure of polar groups and hence responsible for the dissolution of curcumin at higher temperature. The formation of intermolecular aggregates might be responsible behind a better room temperature stability of the molecules after cooling its aqueous suspension from 90 to 25 °C. These curcumin solubility studies have great application in biological research with reference to bioavailability and to understand target oriented mode of action of curcumin.

  15. Kinetic and Mechanistic Studies of Oxidation of an Antiallergic Drug with Bromamine-T in Acid and Alkaline Media

    International Nuclear Information System (INIS)

    Puttaswamy; Anu Sukhdev

    2012-01-01

    Cetrizine dihydrochloride (CTZH) is widely used as an anti-allergic drug. Sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) is the bromine analogue of chloramine-T (CAT) and is found to be a better oxidizing agent than CAT. In the present research, the kinetics of oxidation of CTZH with BAT in acid and alkaline media was studied at 313 K. The experimental rate laws obtained are: -d[BAT]/dt = k[BAT] [CTZH] 0.80 [H + ] -0.48 in acid medium and -d[BAT]/dt = k[BAT][CTZH] 0.48 [OH - ] 0.52 [PTS] -0.40 in alkaline medium where PTS is p-toluenesulfonamide. Activation parameters and reaction constants were evaluated. The solvent isotope effect was studied using D 2 O. The dielectric effect is positive. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as 4-chlorobenzophenone and (2-piperazin-1-yl-ethoxy)-acetic acid in both media. The rate of oxidation of CTZH is faster in acid medium. Suitable mechanisms and related rate laws have been worked out

  16. Studies of extractant molecules in solution and at liquid-liquid interfaces: structural and mechanistic aspects of synergy effects

    International Nuclear Information System (INIS)

    Baaden, Marc

    2000-01-01

    Molecular dynamics simulations reported herein provide new important insights into cation recognition and complexation in solution as well as liquid-liquid extraction, with a particular focus on the microscopic events taking place at the interface between two immiscible liquids. Preliminary studies concerned the representation of the trivalent rare earth cations La 3+ , Eu 3+ and Yb 3+ in force field simulations, probing structural and energetic features on an experimentally characterized model system based on substituted pyridine dicarboxamide ligands. Complexation of such cations by a novel calixarene derivative was investigated showing unexpected features, such as the position of the cation in the complex. Independent experimental studies published subsequently support these findings. Another part of the work is related to industrial liquid-liquid extraction systems using tri-n-butyl phosphate (TBP) as co-solvent, extractant, surfactant and synergist. We investigate 1) concentration effects simulating up to 60 TBP at a water/chloroform interface, 2) acidity using a neutral and ionic model of HNO 3 and 3) synergistic aspects of mixed TBP/calixarene extraction systems. These simulations provide the first microscopic insights into such issues. We finally addressed the topic of solute transfer across the water/chloroform interface. The potential of mean force for such a process has been calculated by both standard methods and novel approaches [fr

  17. Isotopic effects in mechanistic studies of biotransformations of fluorine derivatives of L-alanine catalysed by L-alanine dehydrogenase

    International Nuclear Information System (INIS)

    Szymańska-Majchrzak, Jolanta; Pałka, Katarzyna; Kańska, Marianna

    2017-01-01

    Synthesis of 3-fluoro-[2- 2 H]-L-alanine (3-F-[ 2 H]-L-Ala) in reductive amination of 3-fluoropyruvic acid catalysed by L-alanine dehydrogenase (AlaDH) was described. Fluorine derivative was used to study oxidative deamination catalysed by AlaDH applied kinetic (for 3-F-L-Ala in H 2 O - KIE’s on V max : 1.1; on V max /K M : 1.2; for 3-F-L-Ala in 2 H 2 O – on V max : 1.4; on V max /K M : 2.1) and solvent isotope effect methods (for 3-F-L-Ala - SIE’s on V max : 1.0; on V max /K M : 0.87; for 3-F-[2- 2 H]-L-Ala – on V max : 1.4; on V max /K M : 1.5). Studies explain some details of reaction mechanism. - Highlights: • Synthesis of 3-fluoro-[2- 2 H]-L-alanine was performed. • The reactions were catalysed using the enzyme L-alanine dehydrogenase. • Performed reactions involved fluorinated analogues of L-alanine. • Solvent isotope effects of deuterium were determined. • Kinetic isotope effects were determined for obtained 3-fluoro-L-alanine. • The mechanism of reaction catalysed by L-alanine dehydrogenase was proposed.

  18. Kinetic and Mechanistic Studies of Oxidation of an Antiallergic Drug with Bromamine-T in Acid and Alkaline Media

    Energy Technology Data Exchange (ETDEWEB)

    Puttaswamy; Anu Sukhdev [Bangalore Univ., Bangalore (India)

    2012-11-15

    Cetrizine dihydrochloride (CTZH) is widely used as an anti-allergic drug. Sodium N-bromo-p-toluenesulfonamide or bromamine-T (BAT) is the bromine analogue of chloramine-T (CAT) and is found to be a better oxidizing agent than CAT. In the present research, the kinetics of oxidation of CTZH with BAT in acid and alkaline media was studied at 313 K. The experimental rate laws obtained are: -d[BAT]/dt = k[BAT] [CTZH]{sup 0.80}[H{sup +}]{sup -0.48} in acid medium and -d[BAT]/dt = k[BAT][CTZH]{sup 0.48}[OH{sup -}]{sup 0.52}[PTS]{sup -0.40} in alkaline medium where PTS is p-toluenesulfonamide. Activation parameters and reaction constants were evaluated. The solvent isotope effect was studied using D{sub 2}O. The dielectric effect is positive. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as 4-chlorobenzophenone and (2-piperazin-1-yl-ethoxy)-acetic acid in both media. The rate of oxidation of CTZH is faster in acid medium. Suitable mechanisms and related rate laws have been worked out.

  19. Atmospheric chemistry of HFC-134a. Kinetic and mechanistic study of the CF3CFHO2 + NO2 reaction

    DEFF Research Database (Denmark)

    Møgelberg, T.E.; Nielsen, O.J.; Sehested, J.

    1994-01-01

    A pulse radiolysis system was used to study the kinetics of the reaction of CF3CFHO2 with NO2. By monitoring the rate of the decay of NO2 using its absorption at 400 nm the reaction rate constant was determined to be k = (5.0 +/- 0.5) x 10(-12) cm3 molecule-1 s-1. A long path length Fourier......-transform infrared technique was used to investigate the thermal decomposition of the product CF3CFHO2NO2. At 296 K in the presence of 700 Torr of air, decomposition of CF3CFHO2NO2 was rapid (greater than 90% decomposition within 3 min). The results are discussed in the context of atmospheric chemistry of CF3CFH2...

  20. Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage of Carbon-Carbon Bonds in Ketones

    DEFF Research Database (Denmark)

    Mazziotta, Andrea; Makarov, Ilya S.; Fristrup, Peter

    2017-01-01

    The hydroxide-mediated cleavage of ketones into alkanes and carboxylic acids has been reinvestigated and the substrate scope extended to benzyl carbonyl compounds. The transformation is performed with a 0.05 M ketone solution in refluxing xylene in the presence of 10 equiv of potassium hydroxide....... The reaction constitutes a straightforward protocol for the synthesis of certain phenyl-substituted carboxylic acids from 2-phenylcycloalkanones. The mechanism was investigated by kinetic experiments which indicated a first order reaction in hydroxide and a full negative charge in the rate-determining step....... The studies were complemented by a theoretical investigation where two possible pathways were characterized by DFT/M06-2X. The calculations showed that the scission takes place by nucleophilic attack of hydroxide on the ketone followed by fragmentation of the resulting oxyanion into the carboxylic acid...

  1. Synthetic Applications and Mechanistic Studies of the Hydroxide-Mediated Cleavage of Carbon-Carbon Bonds in Ketones.

    Science.gov (United States)

    Mazziotta, Andrea; Makarov, Ilya S; Fristrup, Peter; Madsen, Robert

    2017-06-02

    The hydroxide-mediated cleavage of ketones into alkanes and carboxylic acids has been reinvestigated and the substrate scope extended to benzyl carbonyl compounds. The transformation is performed with a 0.05 M ketone solution in refluxing xylene in the presence of 10 equiv of potassium hydroxide. The reaction constitutes a straightforward protocol for the synthesis of certain phenyl-substituted carboxylic acids from 2-phenylcycloalkanones. The mechanism was investigated by kinetic experiments which indicated a first order reaction in hydroxide and a full negative charge in the rate-determining step. The studies were complemented by a theoretical investigation where two possible pathways were characterized by DFT/M06-2X. The calculations showed that the scission takes place by nucleophilic attack of hydroxide on the ketone followed by fragmentation of the resulting oxyanion into the carboxylic acid and a benzyl anion.

  2. A barrier-free atomic radical-molecule reaction: N (2D) NO2 (2A1) mechanistic study

    Science.gov (United States)

    Zuo, Ming-Hui; Liu, Hui-Ling; Huang, Xu-Ri; Zhan, Jin-Hui; Sun, Chia-Chung

    The reaction of N (2D) radical with NO2 molecule has been studied theoretically using density functional theory and ab initio quantum chemistry method. Singlet electronic state [N2O2] potential energy surfaces (PES) are calculated at the CCSD(T)/aug-cc-pVDZ//B3LYP/6-311+G(d) + ZPE and G3B3 levels of theory. All the involved transition states for generation of (2NO) and (O2 + N2) lie much lower than the reactants. Thus, the novel reaction N + NO2 can proceed effectively even at low temperatures and it is expected to play a role in both combustion and interstellar processes. On the basis of the analysis of the kinetics of all pathways through which the reactions proceed, we expect that the competitive power of reaction pathways may vary with experimental conditions for the title reaction.

  3. Mechanistic studies of chemical looping desulfurization of Mn-based oxides using in situ X-ray absorption spectroscopy

    International Nuclear Information System (INIS)

    König, C.F.J.; Nachtegaal, M.; Seemann, M.; Clemens, F.; Garderen, N. van; Biollaz, S.M.A.; Schildhauer, T.J.

    2014-01-01

    2 . The presence of CO and/or CH 4 in the fuel reactor has no effect on this mechanism. Measuring the structure–performance relationship of gas cleaning materials with in situ methods will enable knowledge-based materials development for improved performance

  4. Mechanistic study on ultrasound assisted pretreatment of sugarcane bagasse using metal salt with hydrogen peroxide for bioethanol production.

    Science.gov (United States)

    Ramadoss, Govindarajan; Muthukumar, Karuppan

    2016-01-01

    This study presents the ultrasound assisted pretreatment of sugarcane bagasse (SCB) using metal salt with hydrogen peroxide for bioethanol production. Among the different metal salts used, maximum holocellulose recovery and delignification were achieved with ultrasound assisted titanium dioxide (TiO2) pretreatment (UATP) system. At optimum conditions (1% H2O2, 4 g SCB dosage, 60 min sonication time, 2:100 M ratio of metal salt and H2O2, 75°C, 50% ultrasound amplitude and 70% ultrasound duty cycle), 94.98 ± 1.11% holocellulose recovery and 78.72 ± 0.86% delignification were observed. The pretreated SCB was subjected to dilute acid hydrolysis using 0.25% H2SO4 and maximum xylose, glucose and arabinose concentration obtained were 10.94 ± 0.35 g/L, 14.86 ± 0.12 g/L and 2.52 ± 0.27 g/L, respectively. The inhibitors production was found to be very less (0.93 ± 0.11 g/L furfural and 0.76 ± 0.62 g/L acetic acid) and the maximum theoretical yield of glucose and hemicellulose conversion attained were 85.8% and 77%, respectively. The fermentation was carried out using Saccharomyces cerevisiae and at the end of 72 h, 0.468 g bioethanol/g holocellulose was achieved. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis of pretreated SCB was made and its morphology was studied using scanning electron microscopy (SEM). The compounds formed during the pretreatment were identified using gas chromatography-mass spectrometry (GC-MS) analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Cytochrome P-450-catalyzed desaturation of valproic acid in vitro. Species differences, induction effects, and mechanistic studies

    International Nuclear Information System (INIS)

    Rettie, A.E.; Boberg, M.; Rettenmeier, A.W.; Baillie, T.A.

    1988-01-01

    The cytochrome P-450-mediated desaturation of valproic acid (VPA) to its hepatotoxic metabolite, 2-n-propyl-4-pentenoic acid (4-ene-VPA), was examined in liver microsomes from rats, mice, rabbits and humans. The highest substrate turnover was found with microsomes from rabbits (44.2 +/- 2.7 pmol of product/nmol P-450/15 min), while lower activities were observed in preparations from human, mouse, and rat liver, in that order. Pretreatment of animals with phenobarbital led to enhanced rates of formation of 4-ene-VPA in vitro and yielded induction ratios for desaturation ranging from 2.5 to 8.4, depending upon the species. Comparative studies in the rat showed that phenobarbital is a more potent inducer of olefin formation than either phenytoin or carbamazepine. The mechanism of the desaturation reaction was studied by inter- and intramolecular deuterium isotope effect experiments, which demonstrated that removal of a hydrogen atom from the subterminal C-4 position of VPA is rate limiting in the formation of both 4-ene- and 4-hydroxy-VPA. Hydroxylation at the neighboring C-5 position, on the other hand, was highly sensitive to deuterium substitution at that site, but not to deuteration at C-4. Based on these findings, it is proposed that 4-ene- and 4-hydroxy-VPA are products of a common P-450-dependent metabolic pathway, in which a carbon-centered free radical at C-4 serves as the key intermediate. 5-Hydroxy-VPA, in contrast, derives from an independent hydroxylation reaction

  6. Interaction of 2-aminopyrimidine with dichloro-[1-alkyl-2-(naphthylazo imidazole]palladium(II complexes : Kinetic and mechanistic studies

    Directory of Open Access Journals (Sweden)

    Saha Sushanta

    2007-10-01

    Full Text Available Abstract Background The anticancer properties of cisplatin and palladium(II complexes stem from the ability of the cis-MCl2 fragment to bind to DNA bases. However, cisplatin also interacts with non-cancer cells, mainly through bonding molecules containing -SH groups, resulting in nephrotoxicity. This has aroused interest in the design of palladium(II complexes of improved activity and lower toxicity. The reaction of DNA bases with palladium(II complexes with chelating N,N/donors of the cis-MCl2 configuration constitutes a model system that may help explore the mechanism of cisplatin's anticancer activity. Heterocyclic compounds are found widely in nature and are essential to many biochemical processes. Amongst these naturally occurring compounds, the most thoroughly studied is that of pyrimidine. This was one of the factors that encouraged this study into the kinetics and mechanism of the interaction of 2-aminopyrimidine (2-NH2-Pym with dichloro-{1-alkyl-2-(α-naphthylazoimidazole}palladium(II [Pd(α-NaiRCl2, 1] and dichloro-{1-alkyl-2-(β-naphthylazoimidazole}palladium(II [Pd(β-NaiRCl2, 2] complexes where the alkyl R = Me (a, Et (b, or Bz (c. Results 2-NH2-Pym reacts with 1a, 1b, and 1c to yield [{1-alkyl-2-(α-naphthylazoimidazole}bis(2-aminopyrimidine]palladium(II (3a, 3b, 3c dichloride and with 2a, 2b, and 2c to yield [{1-alkyl-2-(β-naphthylazoimidazole}bis(2-aminopyrimidine]palladium(II (4a, 4b, 4c dichloride in an acetonitrile (MeCN medium. The products were characterized using spectroscopic techniques (FT-IR, UV-Vis, NMR. The ligand substitution reactions follow second order kinetics – first order dependence on the concentration of the Pd(II complex and 2-NH2-Pym. Addition of LiCl to the reaction does not influence its rate. The thermodynamic parameters (standard enthalpy of activation, Δ‡H° and standard entropy of activation, Δ‡S° were determined from variable temperature kinetic studies. The magnitude of the second order

  7. Metal, bond energy, and ancillary ligand effects on actinide-carbon σ-bond hydrogenolysis. A kinetic and mechanistic study

    International Nuclear Information System (INIS)

    Lin, Z.; Marks, T.J.

    1987-01-01

    A kineticmechanistic study of actinide hydrocarbyl ligand hydrogenolysis (An-R + H 2 → An-H + RH) is reported. For the complex Cp' 2 TH(CH 2 -t-Bu)(O-t-Bu)(Cp' = eta 5 -Me 5 C 5 ), the rate law is first-order in organoactinide and first-order in H 2 , with k/sub H2/k/sub D2/ = 2.5 (4) and k/sub THF/k/sub toluene/ = 2.9 (4). For a series of complexes, hydrogenolysis rates span a range of ca. 10 5 with Cp' 2 ThCH 2 C(CH 3 ) 2 CH 2 ≅ Cp' 2 U(CH 2 -t-Bu) (too rapid to measure accurately) > Cp' 2 Th(CH 2 -t-Bu)[OCH(t-Bu) 2 ] = Cp' 2 Th(CH 2 -t-Bu)(O-t-Bu) > Cp' 2 Th(CH 2 -t-Bu)(Cl) > Me 2 Si(Me 4 C 5 ) 2 Th(n-Bu) 2 > Cp' 2 Th(n-Bu) 2 ≅ Cp' 2 ThMe 2 > Cp' 2 Th(Me)(O 3 SCF 3 ) > Cp' 2 Th(n-Bu)[OCG(t-Bu) 2 ] ≅ Cp' 2 Th(Me)[OSiMe 2 (t-Bu)] > Cp' 2 ZrMe 2 = Cp' 2 Th(rho-C 6 H 4 NMe 2 )(O-tu-Bu) > Cp' 2 Th(Ph)(O-t-Bu) > Cp' 2 U(Me)[OCH(t-Bu) 2 ] > Cp' 2 Th(Me)[OCH(t-Bu) 2 ]. In the majority of cases, the rate law is cleanly first-order in organoactinide over 3 or more half-lives. However, for Cp' 2 ThMe 2 → (Cp' 2 ThH 2 ) 2 , an intermediate is observe by NMR that is probably [Cp' 2 Th(Me)(μ-H)] 2 . For Cp' 2 Th(Me)(O 3 SCF 3 ), a follow-up reaction, which consumes Cp' 2 TH(H)(O 3 SCF 3 ) is detected. Variable-temperature kinetic studies yield ΔH** = 3.7 (2) kcalmol and ΔS double dagger = -50.8 (7) eu for Cp' 2 Th(CH 2 -t-Bu)(O-t-Bu) and ΔH double dagger = 9 (2) kcalmol and ΔS double dagger = -45 (5) eu for Cp' 2 U(Me)[OCH(O-t-Bu) 2

  8. Shell-Dependent Photoluminescence Studies Provide Mechanistic Insights into the Off-Grey-On Transitions of Blinking Quantum Dots.

    Science.gov (United States)

    Gao, Feng; Bajwa, Pooja; Nguyen, Anh; Heyes, Colin D

    2017-03-28

    The majority of quantum dot (QD) blinking studies have used a model of switching between two distinct fluorescence intensity levels, "on" and "off". However, a distinct intermediate intensity level has been identified in some recent reports, a so-called "grey" or "dim" state, which has brought this binary model into question. While this grey state has been proposed to result from the formation of a trion, it is still unclear under which conditions it is present in a QD. By performing shell-dependent blinking studies on CdSe QDs, we report that the populations of the grey state and the on state are strongly dependent on both the shell material and its thickness. We found that adding a ZnS shell did not result in a significant population of the grey state. Using ZnSe as the shell material resulted in a slightly higher population of the grey state, although it was still poorly resolved. However, adding a CdS shell resulted in the population of a grey state, which depended strongly on its thickness up to 5 ML. Interestingly, while the frequency of transitions to and from the grey state showed a very strong dependence on CdS shell thickness, the brightness of and the dwell time in the grey state did not. Moreover, we found that the grey state acts as an on-pathway intermediate state between on and off states, with the thickness of the shell determining the transition probability between them. We also identified two types of blinking behavior in QDs, one that showed long-lived but lower intensity on states and another that showed short-lived but brighter on states that also depended on the shell thickness. Intensity-resolved single QD fluorescence lifetime analysis was used to identify the relationship between the various exciton decay pathways and the resulting intensity levels. We used this data to propose a model in which multiple on, grey, and off states exist whose equilibrium populations vary with time that give rise to the various intensity levels of single QDs

  9. Boron doped diamond sensor for sensitive determination of metronidazole: Mechanistic and analytical study by cyclic voltammetry and square wave voltammetry

    Energy Technology Data Exchange (ETDEWEB)

    Ammar, Hafedh Belhadj, E-mail: hbelhadjammar@yahoo.fr; Brahim, Mabrouk Ben; Abdelhédi, Ridha; Samet, Youssef

    2016-02-01

    The performance of boron-doped diamond (BDD) electrode for the detection of metronidazole (MTZ) as the most important drug of the group of 5-nitroimidazole was proven using cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. A comparison study between BDD, glassy carbon and silver electrodes on the electrochemical response was carried out. The process is pH-dependent. In neutral and alkaline media, one irreversible reduction peak related to the hydroxylamine derivative formation was registered, involving a total of four electrons. In acidic medium, a prepeak appears probably related to the adsorption affinity of hydroxylamine at the electrode surface. The BDD electrode showed higher sensitivity and reproducibility analytical response, compared with the other electrodes. The higher reduction peak current was registered at pH 11. Under optimal conditions, a linear analytical curve was obtained for the MTZ concentration in the range of 0.2–4.2 μmol L{sup −1}, with a detection limit of 0.065 μmol L{sup −1}. - Highlights: • SWV for the determination of MTZ • Boron-doped diamond as a new electrochemical sensor • Simple and rapid detection of MTZ • Efficiency of BDD for sensitive determination of MTZ.

  10. Boron doped diamond sensor for sensitive determination of metronidazole: Mechanistic and analytical study by cyclic voltammetry and square wave voltammetry

    International Nuclear Information System (INIS)

    Ammar, Hafedh Belhadj; Brahim, Mabrouk Ben; Abdelhédi, Ridha; Samet, Youssef

    2016-01-01

    The performance of boron-doped diamond (BDD) electrode for the detection of metronidazole (MTZ) as the most important drug of the group of 5-nitroimidazole was proven using cyclic voltammetry (CV) and square wave voltammetry (SWV) techniques. A comparison study between BDD, glassy carbon and silver electrodes on the electrochemical response was carried out. The process is pH-dependent. In neutral and alkaline media, one irreversible reduction peak related to the hydroxylamine derivative formation was registered, involving a total of four electrons. In acidic medium, a prepeak appears probably related to the adsorption affinity of hydroxylamine at the electrode surface. The BDD electrode showed higher sensitivity and reproducibility analytical response, compared with the other electrodes. The higher reduction peak current was registered at pH 11. Under optimal conditions, a linear analytical curve was obtained for the MTZ concentration in the range of 0.2–4.2 μmol L"−"1, with a detection limit of 0.065 μmol L"−"1. - Highlights: • SWV for the determination of MTZ • Boron-doped diamond as a new electrochemical sensor • Simple and rapid detection of MTZ • Efficiency of BDD for sensitive determination of MTZ

  11. Long-term habituation (LTH in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory

    Directory of Open Access Journals (Sweden)

    H. Maldonado

    1997-07-01

    Full Text Available A decade of studies on long-term habituation (LTH in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP (³15 trials, intertrial interval (ITI of 171 s invariably yielded LTH, while a weak training protocol (WTP (£10 trials, ITI = 171 s invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic administration of low doses was effective, which is likely to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an initial memory produced by spaced training and mainly expressed at an initial phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining. The initial memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide

  12. Kinetic and mechanistic studies of base-catalyzed phenylselenoetherification of (Z)- and (E)-hex-4-en-1-ols.

    Science.gov (United States)

    Divac, Vera M; Puchta, Ralph; Bugarčić, Zorica M

    2012-08-02

    The mechanism of phenylselenoetherification of (Z)- and (E)-hex-4-en-1-ols using some bases (triethylamine, pyridine, quinoline, 2,2'-bipyridine) as catalysts and some solvents [tetrahydrofuran (THF) and CCl4] as reaction media was examined through studies of kinetics of the cyclization by UV-vis spectrophotometry. It was demonstrated that the intramolecular cyclization is facilitated in the presence of bases as a result of the hydrogen bond between the base and the alkenol's OH group. The rate constants in the base-catalyzed reactions are remarkably influenced by the bulkiness and basicity of the base used and the nature of the considered nitrogen donors. The obtained values for rate constants show that the reaction with triethylamine is the fastest one. THF with higher polarity and higher basic character is better as a solvent than CCl4. Quantum-chemical calculations [MP2(fc)/6-311+G**//B3LYP/6-311+G** + ZPE(B3LYP/6-311+G**] show that the cyclization of (Z)-hex-4-en-1-ol to a tetrahydrofuranoid five-membered ring is kinetically controlled, while the cyclization of (E)-hex-4-en-1-ol to the tetrahydropyranoid six-membered ring is thermodynamically controlled. This is in accordance with previous experimental findings.

  13. Regulatory dendritic cells for promotion of liver transplant operational tolerance: Rationale for a clinical trial and accompanying mechanistic studies.

    Science.gov (United States)

    Thomson, Angus W; Humar, Abhinav; Lakkis, Fadi G; Metes, Diana M

    2018-05-01

    Dendritic cells (DC) are rare, bone marrow (BM)-derived innate immune cells that critically maintain self-tolerance in the healthy steady-state. Regulatory DC (DCreg) with capacity to suppress allograft rejection and promote transplant tolerance in pre-clinical models can readily be generated from BM precursors or circulating blood monocytes. These DCreg enhance allograft survival via various mechanisms, including promotion of regulatory T cells. In non-human primates receiving minimal immunosuppressive drug therapy (IS), infusion of DCreg of donor origin, one week before transplant, safely prolongs renal allograft survival and selectively attenuates anti-donor CD8 + memory T cell responses in the early post-transplant period. Based on these observations, and in view of the critical need to reduce patient dependence on non-specific IS agents that predispose to cardiometabolic side effects and renal insufficiency, we will conduct a first-in-human safety and preliminary efficacy study of donor-derived DCreg infusion to achieve early (18 months post-transplant) complete IS withdrawal in low-risk, living donor liver transplant recipients receiving standard-of-care IS (mycophenolate mofetil, tacrolimus and steroids). We will test the hypothesis that, although donor-derived DCreg are short-lived, they will induce robust donor-specific T cell hyporesponsiveness. We will examine immunological mechanisms by sequential analysis of blood and tissue samples, incorporating cutting-edge technologies. Copyright © 2017 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  14. Effect of Garlic, Gingko, and St. John's Wort Extracts on the Pharmacokinetics of Fexofenadine: A Mechanistic Study.

    Science.gov (United States)

    Turkanovic, Jasmina; Ward, Michael B; Gerber, Jacobus P; Milne, Robert W

    2017-05-01

    The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW; 1000 mg/kg; positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines divided into four segments (SI-SIV) and analyzed for P-gp and Oatp1a5. In vivo, SJW increased the clearance of i.v. administered fexofenadine by 28%. Garlic increased the area under the curve 0-∞ and maximum plasma concentration of orally administered fexofenadine by 47% and 85%, respectively. Ginkgo and SJW had no effect on the oral absorption of fexofenadine. In the perfused liver, garlic, ginkgo, and SJW increased the biliary clearance of fexofenadine with respect to perfusate by 71%, 121%, and 234%, respectively. SJW increased the biliary clearance relative to the liver concentration by 64%. The ratio of liver to perfusate concentrations significantly increased in all treated groups. The expression of Oatp1a5 in SI was increased by garlic (88%) and SJW (63%). There were no significant changes in the expression of P-gp. Induction of intestinal Oatp1a5 by garlic may explain the increased absorption of orally administered fexofenadine. Ginkgo had no effect on the expression of intestinal P-gp or Oatp1a5. A dual inductive effect by SJW on opposing intestinal epithelial transport by Oatp1a5 and P-gp remains a possibility. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Mechanistic studies of a cell-permeant peptide designed to enhance myosin light chain phosphorylation in polarized intestinal epithelia.

    Science.gov (United States)

    Almansour, Khaled; Taverner, Alistair; Eggleston, Ian M; Mrsny, Randall J

    2018-06-10

    Tight junction (TJ) structures restrict the movement of solutes between adjacent epithelial cells to maintain homeostatic conditions. A peptide, termed PIP 640, with the capacity to regulate the transient opening of intestinal TJ structures through an endogenous mechanism involving the induction of myosin light chain (MLC) phosphorylation at serine 19 (MLC-pS 19 ) has provided a promising new method to enhance the in vivo oral bioavailability of peptide therapeutics. PIP 640 is a decapeptide composed of all D-amino acids (rrdykvevrr-NH 2 ) that contains a central sequence designed to emulates a specific domain of C-kinase potentiated protein phosphatase-1 inhibitor-17 kDa (CPI-17) surrounded by positively-charged amino acids that provide a cell penetrating peptide (CPP)-like character. Here, we examine compositional requirements of PIP 640 with regard to its actions on MLC phosphorylation, its intracellular localization to TJ structures, and its interactions with MLC phosphatase (MLCP) elements that correlate with enhanced solute uptake. These studies showed that a glutamic acid and tyrosine within this peptide are critical for PIP 640 to retain its ability to increase MLC-pS 19 levels and enhance the permeability of macromolecular solutes of the size range of therapeutic peptides without detectable cytotoxicity. On the other hand, exchange of the aspartic acid for alanine and then arginine resulted in an increasingly greater bias toward protein phosphatase-1 (PP1) relative to MLCP inhibition, an outcome that resulted in increased paracellular permeability for solutes in the size range of therapeutic peptides, but with a significant increase in cytotoxicity. Together, these data further our understanding of the composition requirements of PIP 640 with respect to the desired goal of transiently altering the intestinal epithelial cell paracellular barrier properties through an endogenous mechanism, providing a novel approach to enhance the oral bioavailability of

  16. The effect of pregabalin or duloxetine on arthritis pain: a clinical and mechanistic study in people with hand osteoarthritis

    Directory of Open Access Journals (Sweden)

    Sofat N

    2017-10-01

    Full Text Available Nidhi Sofat,1 Abiola Harrison,1 Mark D Russell,1 Salma Ayis,2 Patrick D Kiely,3 Emma H Baker,1 Thomas Richard Barrick,4 Franklyn A Howe4 1Institute for Infection and Immunity, St George’s University of London, 2Division of Health & Social Care Research, King’s Clinical Trials Unit, King’s College London, 3Department of Rheumatology, St George’s University Hospitals NHS Foundation Trust, 4Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK Abstract: Osteoarthritis (OA is the most prevalent arthritis worldwide and is characterized by chronic pain and impaired physical function. We hypothesized that heightened pain in hand OA could be reduced with duloxetine or pregabalin. In this prospective, randomized clinical study, we recruited 65 participants, aged 40–75 years, with a Numerical Rating Scale (NRS for pain of at least 5. Participants were randomized to one of the following three groups: duloxetine, pregabalin, and placebo. The primary endpoint was the NRS pain score, and the secondary endpoints included the Australian and Canadian Hand Osteoarthritis Index (AUSCAN pain, stiffness, and function scores and quantitative sensory testing by pain pressure algometry. After 13 weeks, compared to placebo, ANOVA found significant differences between the three groups (P=0.0078. In the intention-to-treat analysis, the pregabalin group showed improvement for NRS pain (P=0.023, AUSCAN pain (P=0.008, and AUSCAN function (P=0.009, but no difference between duloxetine and placebo (P>0.05 was observed. In the per protocol analysis, NRS pain was reduced for pregabalin (P<0.0001 and duloxetine (P=0.029 compared to placebo. We conclude that centrally acting analgesics improve pain outcomes in people with hand arthritis, offering new treatment paradigms for OA pain. Keywords: pain, hand osteoarthritis, sensitization, duloxetine, pregabalin

  17. Mechanistic Studies of Cobalt-Catalyzed C(sp2)-H Borylation of Five-Membered Heteroarenes with Pinacolborane.

    Science.gov (United States)

    Obligacion, Jennifer V; Chirik, Paul J

    2017-07-07

    Studies into the mechanism of cobalt-catalyzed C(sp 2 )-H borylation of five-membered heteroarenes with pinacolborane (HBPin) as the boron source established the catalyst resting state as the trans -cobalt(III) dihydride boryl, ( iPr PNP)Co(H) 2 (BPin) ( iPr PNP = 2,6-( i Pr 2 PCH 2 ) 2 (C 5 H 3 N)), at both low and high substrate conversions. The overall first-order rate law and observation of a normal deuterium kinetic isotope effect on the borylation of benzofuran versus benzofuran-2- d 1 support H 2 reductive elimination from the cobalt(III) dihydride boryl as the turnover-limiting step. These findings stand in contrast to that established previously for the borylation of 2,6-lutidine with the same cobalt precatalyst, where borylation of the 4-position of the pincer occurred faster than the substrate turnover and arene C-H activation by a cobalt(I) boryl is turnover-limiting. Evaluation of the catalytic activity of different cobalt precursors in the C-H borylation of benzofuran with HBPin established that the ligand design principles for C- H borylation depend on the identities of both the arene and the boron reagent used: electron-donating groups improve catalytic activity of the borylation of pyridines and arenes with B 2 Pin 2 , whereas electron-withdrawing groups improve catalytic activity of the borylation of five-membered heteroarenes with HBPin. Catalyst deactivation by P-C bond cleavage from a cobalt(I) hydride was observed in the C-H borylation of arene substrates with C-H bonds that are less acidic than those of five-membered heteroarenes using HBPin and explains the requirement of B 2 Pin 2 to achieve synthetically useful yields with these arene substrates.

  18. Adsorption of chromium(VI) and Rhodamine B by surface modified tannery waste: Kinetic, mechanistic and thermodynamic studies

    Energy Technology Data Exchange (ETDEWEB)

    Anandkumar, J. [Centre for the Environment, Indian Institute of Technology Guwahati, Guwahati 781039, Assam (India); Mandal, B., E-mail: bpmandal@iitg.ernet.in [Department of Chemical Engineering, Indian Institute of Technology, Guwahati 781039, Assam (India)

    2011-02-28

    In this study, various activation methods have been employed to examine the potential reuse of tannery residual biomass (TRB) obtained from vegetable tanning process for the removal of Cr(VI) and Rhodamine B (RB) from aqueous solution. The maximum BET surface area (10.42 m{sup 2}/g), honey comb pore distribution and uptake of both Cr(VI) and RB were achieved when only 3-fold volume of HCl was used to activate the biomass. The pH and temperature experiment showed that they have considerable impact on the adsorption capacity of the used adsorbent. The presence of other ions (Na{sup +}, Ca{sup 2+} and NH{sub 4}{sup +}) significantly reduces the metal uptake but marginal enhancement in the dye removal was observed when Na{sup +} and NH{sub 4}{sup +} ions were present in the solution. The equilibrium data fitted satisfactorily with the Langmuir model and monolayer sorption capacity obtained as 177-217 and 213-250 mg/g for Cr(VI) and RB at 30-50 deg. C, respectively. The sorption kinetics was found to follow the pseudo-second-order kinetic model. The increase in adsorption capacity for both metal and dye with increase in temperature indicates that the uptake was endothermic in nature. The results indicate that the HCl modified TRB (A-TRB) could be employed as a low cost adsorbent for the removal of both Cr(VI) and RB from the aqueous solution including industrial wastewater.

  19. A mechanistic study on the reaction pathways leading to benzene and naphthalene in cellulose vapor phase cracking

    International Nuclear Information System (INIS)

    Norinaga, Koyo; Yang, Huamei; Tanaka, Ryota; Appari, Srinivas; Iwanaga, Keita; Takashima, Yuka; Kudo, Shinji; Shoji, Tetsuya; Hayashi, Jun-ichiro

    2014-01-01

    The reaction pathways leading to aromatic hydrocarbons such as benzene and naphthalene in gas-phase reactions of multi-component mixtures derived from cellulose fast pyrolysis were studied both experimentally and numerically. A two-stage tubular reactor was used for evaluating the reaction kinetics of secondary vapor phase cracking of the nascent pyrolysates at temperature ranging from 400 to 900 °C, residence time from 0.2 to 4.3 s, and at 241 kPa. The products of alkyne and diene were identified from the primary pyrolysis of cellulose even at low temperature range 500–600 °C. These products include acetylene, propyne, propadiene, vinylacetylene, and cyclopentadiene. Experiments were also numerically validated by a detailed chemical kinetic model consisting of more than 8000 elementary step-like reactions with over 500 chemical species. Acceptable capabilities of the kinetic model in predicting concentration profiles of the products enabled us to assess reaction pathways leading to benzene and naphthalene via the alkyne and diene from primary pyrolysates of cellulose. C 3 alkyne and diene are primary precursors of benzene at 650 °C, while combination of ethylene and vinylacetylene produces benzene dominantly at 850 °C. Cyclopentadiene is a prominent precursor of naphthalene. Combination of acetylene with propyne or allyl radical leads to the formation of cyclopentadiene. Furan and acrolein are likely important alkyne precursors in cellulose pyrolysis at low temperature, whereas dehydrogenations of olefins are major route to alkyne at high temperatures. - Highlights: • Analytical pyrolysis experiments provided data for kinetic modeling. • Detailed chemical kinetic model was used and evaluated. • Alkyne and diene were important intermediates for aromatic hydrocarbon formation. • Reaction pathways leading to aromatic hydrocarbons were proposed

  20. Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery.

    Science.gov (United States)

    Love, Kerry Routenberg; Pandya, Renuka K; Spooner, Eric; Ploegh, Hidde L

    2009-04-17

    Protein modification by ubiquitin (Ub) and ubiquitin-like modifiers (Ubl) requires the action of activating (E1), conjugating (E2), and ligating (E3) enzymes and is a key step in the specific destruction of proteins. Deubiquitinating enzymes (DUBs) deconjugate substrates modified with Ub/Ubl's and recycle Ub inside the cell. Genome mining based on sequence homology to proteins with known function has assigned many enzymes to this pathway without confirmation of either conjugating or DUB activity. Function-dependent methodologies are still the most useful for rapid identification or assessment of biological activity of expressed proteins from cells. Activity-based protein profiling uses chemical probes that are active-site-directed for the classification of protein activities in complex mixtures. Here we show that the design and use of an expanded set of Ub-based electrophilic probes allowed us to recover and identify members of each enzyme class in the ubiquitin-proteasome system, including E3 ligases and DUBs with previously unverified activity. We show that epitope-tagged Ub-electrophilic probes can be used as activity-based probes for E3 ligase identification by in vitro labeling and activity studies of purified enzymes identified from complex mixtures in cell lysate. Furthermore, the reactivity of our probe with the HECT domain of the E3 Ub ligase ARF-BP1 suggests that multiple cysteines may be in the vicinity of the E2-binding site and are capable of the transfer of Ub to self or to a substrate protein.

  1. Impaired circulating CD4+ LAP+ regulatory T cells in patients with acute coronary syndrome and its mechanistic study.

    Directory of Open Access Journals (Sweden)

    Zheng-Feng Zhu

    Full Text Available OBJECTIVE: CD4(+ latency-associated peptide (LAP(+ regulatory T cells (Tregs are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS has not been explored. We designed to investigate whether circulating frequency and function of CD4(+LAP(+ Tregs are defective in ACS. METHODS: One hundred eleven ACS patients (acute myocardial infarction and unstable angina and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA and chest pain syndrome (CPS. The frequencies of circulating CD4(+LAP(+ Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP on CD4(+ T cells were determined by flow cytometry. The function of CD4(+LAP(+ Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10 and transforming growth factor-β protein (TGF-β levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs was measured by real time-polymerase chain reaction. RESULTS: We found ACS patients had a significantly lower frequency of circulating CD4(+LAP(+ Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+ T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. CONCLUSIONS: A novel regulatory T cell subset, defined as CD4(+LAP(+ T cells is defective in ACS patients.

  2. Mechanistic studies of anticancer aptamer AS1411 reveal a novel role for nucleolin in regulating Rac1 activation.

    Science.gov (United States)

    Reyes-Reyes, E Merit; Šalipur, Francesca R; Shams, Mitra; Forsthoefel, Matthew K; Bates, Paula J

    2015-08-01

    AS1411 is a G-rich quadruplex-forming oligodeoxynucleotide that binds specifically to nucleolin, a protein found on the surface and in the cytoplasm of most malignant cells but absent from the surface/cytoplasm of most normal cells. AS1411 has shown promising clinical activity and is being widely used as a tumor-targeting agent, but its mechanism of action is not fully understood. Previously, we showed that AS1411 is taken up in cancer cells by macropinocytosis (fluid phase endocytosis) and subsequently stimulates further macropinocytosis by a nucleolin-dependent mechanism. In the current study, we have investigated the significance and molecular mechanisms of AS1411-induced macropinocytosis. Our results indicate that the antiproliferative activity of AS1411 in various cell lines correlated with its capacity to stimulate macropinocytosis. In DU145 prostate cancer cells, AS1411 induced activation of EGFR, Akt, p38, and Rac1. Activation of Akt and p38 were not critical for AS1411 activity because Akt activation was not observed in all AS1411-responsive cell lines and knockdown of p38 had no effect on AS1411's ability to inhibit proliferation. On the other hand, activation of EGFR and Rac1 appeared to play a role in AS1411 activity in all cancer cell lines examined (DU145, MDA-MB-468, A549, LNCaP) and their inhibition significantly reduced AS1411-mediated macropinocytosis and AS1411 antiproliferative activity. Interestingly, downregulation of nucleolin expression by siRNA also produced a substantial increase in activated Rac1, revealing a previously unknown role for nucleolin as a negative regulator of Rac1 activation. Our results are consistent with a model whereby AS1411 binding to nucleolin leads to sustained activation of Rac1 and causes methuosis, a novel type of nonapoptotic cell death characterized by hyperstimulation of macropinocytosis. We speculate that methuosis is a tumor/metastasis suppressor mechanism that opposes the malignant functions of Rac1 and that

  3. Reductive Elimination Leading to C-C Bond Formation in Gold(III) Complexes: A Mechanistic and Computational Study.

    Science.gov (United States)

    Rocchigiani, Luca; Fernandez-Cestau, Julio; Budzelaar, Peter H M; Bochmann, Manfred

    2018-06-21

    The factors affecting the rates of reductive C-C cross-coupling reactions in gold(III) aryls were studied by using complexes that allow easy access to a series of electronically modified aryl ligands, as well as to gold methyl and vinyl complexes, by using the pincer compounds [(C^N^C)AuR] (R=C 6 F 5 , CH=CMe 2 , Me and p-C 6 H 4 X, where X=OMe, F, H, tBu, Cl, CF 3 , or NO 2 ) as starting materials (C^N^C=2,6-(4'-tBuC 6 H 3 ) 2 pyridine dianion). Protodeauration followed by addition of one equivalent SMe 2 leads to the quantitative generation of the thioether complexes [(C^N-CH)AuR(SMe 2 )] + . Upon addition of a second SMe 2 pyridine is displaced, which triggers the reductive aryl-R elimination. The rates for these cross-couplings increase in the sequence k(vinyl)>k(aryl)≫k(C 6 F 5 )>k(Me). Vinyl-aryl coupling is particularly fast, 1.15×10 -3  L mol -1  s -1 at 221 K, whereas both C 6 F 5 and Me couplings encountered higher barriers for the C-C bond forming step. The use of P(p-tol) 3 in place of SMe 2 greatly accelerates the C-C couplings. Computational modelling shows that in the C^N-bonded compounds displacement of N by a donor L is required before the aryl ligands can adopt a conformation suitable for C-C bond formation, so that elimination takes place from a four-coordinate intermediate. The C-C bond formation is the rate-limiting step. In the non-chelating case, reductive C(sp 2 )-C(sp 2 ) elimination from three-coordinate ions [(Ar 1 )(Ar 2 )AuL] + is almost barrier-free, particularly if L=phosphine. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Overview of the South African mechanistic pavement design analysis method

    CSIR Research Space (South Africa)

    Theyse, HL

    1996-01-01

    Full Text Available A historical overview of the South African mechanistic pavement design method, from its development in the early 1970s to the present, is presented. Material characterization, structural analysis, and pavement life prediction are discussed...

  5. Acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells: application of metabolomics in mechanistic studies of antitumor agents.

    Directory of Open Access Journals (Sweden)

    Yini Wang

    Full Text Available A new acridone derivative, 2-aminoacetamido-10-(3, 5-dimethoxy-benzyl-9(10H-acridone hydrochloride (named 8a synthesized in our lab shows potent antitumor activity, but the mechanism of action remains unclear. Herein, we report the use of an UPLC/Q-TOF MS metabolomic approach to study the effects of three compounds with structures optimized step-by-step, 9(10H-acridone (A, 10-(3,5-dimethoxybenzyl-9(10H-acridone (I, and 8a, on CCRF-CEM leukemia cells and to shed new light on the probable antitumor mechanism of 8a. Acquired data were processed by principal component analysis (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA to identify potential biomarkers. Comparing 8a-treated CCRF-CEM leukemia cells with vehicle control (DMSO, 23 distinct metabolites involved in five metabolic pathways were identified. Metabolites from glutathione (GSH and glycerophospholipid metabolism were investigated in detail, and results showed that GSH level and the reduced/oxidized glutathione (GSH/GSSG ratio were significantly decreased in 8a-treated cells, while L-cysteinyl-glycine (L-Cys-Gly and glutamate were greatly increased. In glycerophospholipid metabolism, cell membrane components phosphatidylcholines (PCs were decreased in 8a-treated cells, while the oxidative products lysophosphatidylcholines (LPCs were significantly increased. We further found that in 8a-treated cells, the reactive oxygen species (ROS and lipid peroxidation product malondialdehyde (MDA were notably increased, accompanied with decrease of mitochondrial transmembrane potential, release of cytochrome C and activation of caspase-3. Taken together our results suggest that the acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells. The UPLC/Q-TOF MS based metabolomic approach provides novel insights into the mechanistic studies of antitumor drugs from a point distinct from traditional biological investigations.

  6. Intake and time dependence of blueberry flavonoid-induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity.

    Science.gov (United States)

    Rodriguez-Mateos, Ana; Rendeiro, Catarina; Bergillos-Meca, Triana; Tabatabaee, Setareh; George, Trevor W; Heiss, Christian; Spencer, Jeremy Pe

    2013-11-01

    There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.

  7. Mechanistic modelling of the drying behaviour of single pharmaceutical granules

    DEFF Research Database (Denmark)

    Thérèse F.C. Mortier, Séverine; Beer, Thomas De; Gernaey, Krist

    2012-01-01

    The trend to move towards continuous production processes in pharmaceutical applications enhances the necessity to develop mechanistic models to understand and control these processes. This work focuses on the drying behaviour of a single wet granule before tabletting, using a six...... phase (submodel 2), the water inside the granule evaporates. The second submodel contains an empirical power coefficient, b. A sensitivity analysis was performed to study the influence of parameters on the moisture content of single pharmaceutical granules, which clearly points towards the importance...

  8. Imaging pain relief in osteoarthritis (IPRO): protocol of a double-blind randomised controlled mechanistic study assessing pain relief and prediction of duloxetine treatment outcome.

    Science.gov (United States)

    Reckziegel, Diane; Bailey, Helen; Cottam, William J; Tench, Christopher R; Mahajan, Ravi P; Walsh, David A; Knaggs, Roger D; Auer, Dorothee P

    2017-06-26

    Osteoarthritis (OA) pain is a major cause of long-term disability and chronic pain in the adult population. One in five patients does not receive satisfactory pain relief, which reflects the complexity of chronic pain and the current lack of understanding of mechanisms of chronic pain. Recently, duloxetine has demonstrated clinically relevant pain relief, but only in half of treated patients with OA. Here, the aim is to investigate the neural mechanisms of pain relief and neural signatures that may predict treatment response to duloxetine in chronic knee OA pain. This is an ongoing single-centre randomised placebo-controlled mechanistic study (2:1 (placebo) allocation), using a multimodal neuroimaging approach, together with psychophysiological (quantitative sensory testing), genetics and questionnaire assessments. Eighty-one subjects with chronic knee OA pain are planned to power for between-group comparisons (placebo, duloxetine responder and duloxetine non-responder). Participants have a baseline assessment and, following 6 weeks of duloxetine (30 mg for 2 weeks, then 60 mg for 4 weeks), a follow-up evaluation. Brain imaging is performed at 3T with blood-oxygen-level dependent functional MRI at rest and during pin-prick nociceptive stimulation for main outcome assessment; arterial spin labelling and structural imaging (T1-weighted) for secondary outcome assessment. Questionnaires evaluate pain, negative affect, quality of sleep and cognition. The study has been approved by the East Midlands, Nottingham and is being carried out under the principles of the Declaration of Helsinki (64th, 2013) and Good Clinical Practice standards. Results will be disseminated in peer-reviewed journals and at scientific conferences. This trial is registered at ClinicalTrials.gov (NCT02208778).This work was supported by Arthritis Research UK (Grant 18769). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

  9. Mechanistic study of aerosol dry deposition on vegetated canopies; Etude mecaniste du depot sec d'aerosols sur les couverts vegetaux

    Energy Technology Data Exchange (ETDEWEB)

    Petroff, A

    2005-04-15

    The dry deposition of aerosols onto vegetated canopies is modelled through a mechanistic approach. The interaction between aerosols and vegetation is first formulated by using a set of parameters, which are defined at the local scale of one surface. The overall deposition is then deduced at the canopy scale through an up-scaling procedure based on the statistic distribution parameters. This model takes into account the canopy structural and morphological properties, and the main characteristics of the turbulent flow. Deposition mechanisms considered are Brownian diffusion, interception, initial and turbulent impaction, initially with coniferous branches and then with entire canopies of different roughness, such as grass, crop field and forest. (author)

  10. Mechanistic considerations used in the development of the probability of failure in transient increases in power (PROFIT) pellet-zircaloy cladding (thermo-mechanical-chemical) interactions (pci) fuel failure model

    International Nuclear Information System (INIS)

    Pankaskie, P.J.

    1980-05-01

    A fuel Pellet-Zircaloy Cladding (thermo-mechanical-chemical) interactions (PCI) failure model for estimating the Probability of Failure in Transient Increases in Power (PROFIT) was developed. PROFIT is based on (1) standard statistical methods applied to available PCI fuel failure data and (2) a mechanistic analysis of the environmental and strain-rate-dependent stress versus strain characteristics of Zircaloy cladding. The statistical analysis of fuel failures attributable to PCI suggested that parameters in addition to power, transient increase in power, and burnup are needed to define PCI fuel failures in terms of probability estimates with known confidence limits. The PROFIT model, therefore, introduces an environmental and strain-rate dependent Strain Energy Absorption to Failure (SEAF) concept to account for the stress versus strain anomalies attributable to interstitial-dislocation interaction effects in the Zircaloy cladding

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

    Science.gov (United States)

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

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

  12. New web-based applications for mechanistic case diagramming

    Directory of Open Access Journals (Sweden)

    Fred R. Dee

    2014-07-01

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

  13. Mechanistic study of competitive releases of H2O, NH3 and CO2 from deprotonated aspartic and glutamic acids: Role of conformation.

    Science.gov (United States)

    Barbier Saint Hilaire, Pierre; Warnet, Anna; Gimbert, Yves; Hohenester, Ulli Martin; Giorgi, Gianluca; Olivier, Marie-Françoise; Fenaille, François; Colsch, Benoît; Junot, Christophe; Tabet, Jean-Claude

    2017-03-15

    energy and at lower excitation conditions, respectively. The latter takes place by stabilization of the deaminated aspartate solvated with two residual molecules of water (present in the collision cell). This desolvated anion formed is an α lactone substituted by a methylene carboxylate group. The vibrational excitation acquired by [(D-H)-NH 3 ] - during its isolation is enough to allow its prompt decarboxylation with a barrier lower than 8.4kJ/mol. In addition, study of glutamic acid-like diastereomers constituted by a cyclopropane, hindering any side chain rotation, confirms the impact of the three-dimensional geometry on fragmentation pathways. A significant specific loss of water is only observed for one of these diastereomers. Other experiments, such as stable isotope labeling, need to be performed to elucidate all the observed losses from activated aspartate and glutamate anions. These first mechanistic interpretations enhance understanding of this dissociative pathway and underline the necessity of studying fragmentation of a large number of various compounds to implement properly new algorithms for de novo elucidation of unknown metabolites. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Mechanistic models for the evaluation of biocatalytic reaction conditions and biosensor design optimization

    DEFF Research Database (Denmark)

    Semenova, Daria

    . In the first case study a mechanistic model was developed to describe the enzymatic reaction of glucose oxidase and glucose in the presence of catalase inside a commercial microfluidic platform with integrated oxygen sensor spots. The simplicity of the proposed model allowed an easy calibration of the reaction...... the microfluidic device. In the second case study the flexible microfluidic platform with integrated amperometric glucose biosensors was developed for continuous monitoring of glucose consumption rates. The integration of the mixing chamber inside the platform allowed performing sample dilutions which subsequently......BRs. In the third case study the mechanistic model of the cyclic voltammetry response of the first generation glucose biosensors was developed and applied for the biosensor design optimization. Furthermore the obtained qualitative and quantitative dependencies between the model output and experimental results were...

  15. Improvement of estimation method of two-phase flow in a large diameter pipe. 2. Development of mechanistic interfacial drag force model

    International Nuclear Information System (INIS)

    Okawa, Tomio; Yoneda, Kimitoshi

    1998-01-01

    It is experimentally clarified that behavior of gas-liquid two-phase flow in large diameter pipe is different from one occurred in small diameter pipe. However, no special model for large diameter pipe is used in existing nuclear reactor safety analysis codes. In the present study, detailed investigation about the two-phase flow model used in the safety analysis was carried out to specify the physical phenomena which should be modeled more precisely. Based on the investigation, steam-water two-phase flow experiments using large diameter pipe was conducted to obtain new models. As a result, new evaluation methods for bubble size, heterogeneous distribution of void fraction, and wake formed behind bubble were developed. These new models were applied to the prediction of steam-water two-phase flow experiments using large diameter pipes to clarify their validity. It was consequently demonstrated that the accuracy of the numerical solution is remarkably improved not only for the experiment used for model development but also for the experiment where the pipe diameter, pressure, velocities, void fraction are different. (author)

  16. In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

    Science.gov (United States)

    Ndesendo, Valence M K; Choonara, Yahya E; Meyer, Leith C R; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

    2015-01-01

    The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

  17. Fuel development studies

    International Nuclear Information System (INIS)

    Michel, F.

    1986-12-01

    This paper describes the main lines of the studies carried out to develop the Fast Neutron Fuel Element, from the ''SPX1-first load'' version, to progress to high performance which will be required for the project 1500 and for the fast neutron series [fr

  18. DFT Mechanistic Study of the Selective Terminal C-H Activation of n-Pentane with a Tungsten Allyl Nitrosyl Complex

    KAUST Repository

    Lee, Richmond

    2017-01-17

    Mechanistic insights into the selective C-H terminal activation of n-pentane with tungsten allyl nitrosyl complex reported by Legzdins were gained by employing density functional theory with B3LYP hybrid functional. Using Bader’s atom in molecules (AIM) analysis on the elementary steps of the hydrogen transfer process, TS1 and TS2, it was observed that the calculated H-transfer models were closely similar to Hall’s metal-assisted σ-bond metathesis through bond critical point (BCP) comparisons. One distinguishable feature was the fact that the formal oxidation state of the W changed in the concerted H-transfer process. To better differentiate, we term these processes as ‘Formal Reductive Hydrogen Transfer’ (FRHT) for TS1 and ‘Formal Oxidative Hydrogen Transfer’ (FOHT) for TS2.

  19. DFT Mechanistic Study of the Selective Terminal C-H Activation of n-Pentane with a Tungsten Allyl Nitrosyl Complex

    KAUST Repository

    Lee, Richmond; Tan, Davin; Liu, Chaoli; Li, Huaifeng; Guo, Hao; Shyue, Jing-Jong; Huang, Kuo-Wei

    2017-01-01

    Mechanistic insights into the selective C-H terminal activation of n-pentane with tungsten allyl nitrosyl complex reported by Legzdins were gained by employing density functional theory with B3LYP hybrid functional. Using Bader’s atom in molecules (AIM) analysis on the elementary steps of the hydrogen transfer process, TS1 and TS2, it was observed that the calculated H-transfer models were closely similar to Hall’s metal-assisted σ-bond metathesis through bond critical point (BCP) comparisons. One distinguishable feature was the fact that the formal oxidation state of the W changed in the concerted H-transfer process. To better differentiate, we term these processes as ‘Formal Reductive Hydrogen Transfer’ (FRHT) for TS1 and ‘Formal Oxidative Hydrogen Transfer’ (FOHT) for TS2.

  20. From patterns to emerging processes in mechanistic urban ecology.

    Science.gov (United States)

    Shochat, Eyal; Warren, Paige S; Faeth, Stanley H; McIntyre, Nancy E; Hope, Diane

    2006-04-01

    Rapid urbanization has become an area of crucial concern in conservation owing to the radical changes in habitat structure and loss of species engendered by urban and suburban development. Here, we draw on recent mechanistic ecological studies to argue that, in addition to altered habitat structure, three major processes contribute to the patterns of reduced species diversity and elevated abundance of many species in urban environments. These activities, in turn, lead to changes in animal behavior, morphology and genetics, as well as in selection pressures on animals and plants. Thus, the key to understanding urban patterns is to balance studying processes at the individual level with an integrated examination of environmental forces at the ecosystem scale.

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

    Energy Technology Data Exchange (ETDEWEB)

    Petasis, N.A.; Staszewski, J.P.; Hu, Yong-Han; Lu, Shao-Po [Univ. of Southern California, Los Angeles, CA (United States)

    1995-12-31

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

  2. Conceptual models for waste tank mechanistic analysis. Status report, January 1991

    Energy Technology Data Exchange (ETDEWEB)

    Allemann, R. T.; Antoniak, Z. I.; Eyler, L. L.; Liljegren, L. M.; Roberts, J. S.

    1992-02-01

    Pacific Northwest Laboratory (PNL) is conducting a study for Westinghouse Hanford Company (Westinghouse Hanford), a contractor for the US Department of Energy (DOE). The purpose of the work is to study possible mechanisms and fluid dynamics contributing to the periodic release of gases from double-shell waste storage tanks at the Hanford Site in Richland, Washington. This interim report emphasizing the modeling work follows two other interim reports, Mechanistic Analysis of Double-Shell Tank Gas Release Progress Report -- November 1990 and Collection and Analysis of Existing Data for Waste Tank Mechanistic Analysis Progress Report -- December 1990, that emphasized data correlation and mechanisms. The approach in this study has been to assemble and compile data that are pertinent to the mechanisms, analyze the data, evaluate physical properties and parameters, evaluate hypothetical mechanisms, and develop mathematical models of mechanisms.

  3. Application of mechanistic models to fermentation and biocatalysis for next-generation processes

    DEFF Research Database (Denmark)

    Gernaey, Krist; Eliasson Lantz, Anna; Tufvesson, Pär

    2010-01-01

    of variables required for measurement, control and process design. In the near future, mechanistic models with a higher degree of detail will play key roles in the development of efficient next-generation fermentation and biocatalytic processes. Moreover, mechanistic models will be used increasingly......Mechanistic models are based on deterministic principles, and recently, interest in them has grown substantially. Herein we present an overview of mechanistic models and their applications in biotechnology, including future perspectives. Model utility is highlighted with respect to selection...

  4. Rational Design in Catalysis: A Mechanistic Study of β-Hydride Eliminations in Gold(I) and Gold(III) Complexes Based on Features of the Reaction Valley.

    Science.gov (United States)

    Castiñeira Reis, Marta; López, Carlos Silva; Kraka, Elfi; Cremer, Dieter; Faza, Olalla Nieto

    2016-09-06

    β-Hydride eliminations for ethylgold(III) dichloride complexes are identified as reactions with an unusually long prechemical stage corresponding to the conformational preparation of the reaction complex and spanning six phases. The prechemical process is characterized by a geared rotation of the L-Au-L group (L = Cl) driving methyl group rotation and causing a repositioning of the ligands. This requires more than 28 kcal/mol of the total barrier of 34.0 kcal/mol, according to the unified reaction valley approach, which also determines that the energy requirements of the actual chemical process leading to the β-elimination product are only about 5.5 kcal/mol. A detailed mechanistic analysis was used as a basis for a rational design of substrates (via substituents on the ethyl group) and/or ligands, which can significantly reduce the reaction barrier. This strategy takes advantage of either a higher trans activity of the ligands or a tuned electronic demand of the ethyl group. The β-hydride elimination of gold(I) was found to suffer from strong Coulomb and exchange repulsion when a positively charged hydrogen atom enforces a coordination position in a d(10)-configured gold atom, thus triggering an unassisted σ-π Au(I)-C conversion.

  5. Generative mechanistic explanation building in undergraduate molecular and cellular biology

    Science.gov (United States)

    Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

    2017-09-01

    When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among scientists, we created and applied a theoretical framework to explore the strategies students use to construct explanations for 'novel' biological phenomena. Specifically, we explored how students navigated the multi-level nature of complex biological systems using generative mechanistic reasoning. Interviews were conducted with introductory and upper-division biology students at a large public university in the United States. Results of qualitative coding revealed key features of students' explanation building. Students used modular thinking to consider the functional subdivisions of the system, which they 'filled in' to varying degrees with mechanistic elements. They also hypothesised the involvement of mechanistic entities and instantiated abstract schema to adapt their explanations to unfamiliar biological contexts. Finally, we explored the flexible thinking that students used to hypothesise the impact of mutations on multi-leveled biological systems. Results revealed a number of ways that students drew mechanistic connections between molecules, functional modules (sets of molecules with an emergent function), cells, tissues, organisms and populations.

  6. Stages in the development of a model organism as a platform for mechanistic models in developmental biology: Zebrafish, 1970-2000.

    Science.gov (United States)

    Meunier, Robert

    2012-06-01

    Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena - structures, processes or the mechanisms that explain them - through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The Role of Parathyroid Hormone-Related Protein (PTHrP in Osteoblast Response to Microgravity: Mechanistic Implications for Osteoporosis Development.

    Directory of Open Access Journals (Sweden)

    Anne Camirand

    Full Text Available Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients, but with an accelerated timeframe. This rapid effect on weight-bearing bones is also observed in astronauts who can lose up to 2% of their bone mass per month spent in Space. Despite the important implications for Spaceflight travelers and bedridden patients, the exact mechanisms involved in disuse osteoporosis have not been elucidated. Parathyroid hormone-related protein (PTHrP regulates many physiological processes including skeletal development, and has been proposed as a mechanosensor. To investigate the role of PTHrP in microgravity-induced bone loss, trabecular and calvarial osteoblasts (TOs and COs from Pthrp +/+ and -/- mice were subjected to actual Spaceflight for 6 days (Foton M3 satellite. Pthrp +/+, +/- and -/- osteoblasts were also exposed to simulated microgravity for periods varying from 6 days to 6 weeks. While COs displayed little change in viability in 0g, viability of all TOs rapidly decreased in inverse proportion to PTHrP expression levels. Furthermore, Pthrp+/+ TOs displayed a sharp viability decline after 2 weeks at 0g. Microarray analysis of Pthrp+/+ TOs after 6 days in simulated 0g revealed expression changes in genes encoding prolactins, apoptosis/survival molecules, bone metabolism and extra-cellular matrix composition proteins, chemokines, insulin-like growth factor family members and Wnt-related signalling molecules. 88% of 0g-induced expression changes in Pthrp+/+ cells overlapped those caused by Pthrp ablation in normal gravity, and pulsatile treatment with PTHrP1-36 not only reversed a large proportion of 0g-induced effects in Pthrp+/+ TOs but maintained viability over 6-week exposure to microgravity. Our results confirm PTHrP efficacy as an anabolic agent to prevent microgravity-induced cell death in TOs.

  8. Nuclear standardization development study

    International Nuclear Information System (INIS)

    Pan Jianjun

    2010-01-01

    Nuclear industry is the important part of national security and national economic development is key area of national new energy supported by government. nuclear standardization is the important force for nuclear industry development, is the fundamental guarantee of nuclear safe production, is the valuable means of China's nuclear industry technology to the world market. Now nuclear standardization faces to the new development opportunity, nuclear standardization should implement strategy in standard system building, foreign standard research, company standard building, and talented people building to meet the requirement of nuclear industry development. (author)

  9. Mechanistic considerations in benzene physiological model development.

    OpenAIRE

    Medinsky, M A; Kenyon, E M; Seaton, M J; Schlosser, P M

    1996-01-01

    Benzene, an important industrial solvent, is also present in unleaded gasoline and cigarette smoke. The hematotoxic effects of benzene in humans are well documented and include aplastic anemia, pancytopenia, and acute myelogenous leukemia. However, the risks of leukemia at low exposure concentrations have not been established. A combination of metabolites (hydroquinone and phenol, for example) may be necessary to duplicate the hematotoxic effect of benzene, perhaps due in part to the synergis...

  10. Proceedings of the international workshop on mechanistic understanding of radionuclide migration in compacted/intact systems

    International Nuclear Information System (INIS)

    Tachi, Yukio; Yui, Mikazu

    2010-03-01

    The international workshop on mechanistic understanding of radionuclide migration in compacted / intact systems was held at ENTRY, JAEA, Tokai on 21st - 23rd January, 2009. This workshop was hosted by Japan Atomic Energy Agency (JAEA) as part of the project on the mechanistic model/database development for radionuclide sorption and diffusion behavior in compacted / intact systems. The overall goal of the project is to develop the mechanistic model / database for a consistent understanding and prediction of migration parameters and its uncertainties for performance assessment of geological disposal of radioactive waste. The objective of the workshop is to integrate the state-of-the-art of mechanistic sorption and diffusion model in compacted / intact systems, especially in bentonite / clay systems, and discuss the JAEA's mechanistic approaches and future challenges, especially the following discussions points; 1) What's the status and difficulties for mechanistic model/database development? 2) What's the status and difficulties for applicability of mechanistic model to the compacted/intact system? 3) What's the status and difficulties for obtaining evidences for mechanistic model? 4) What's the status and difficulties for standardization of experimental methodology for batch sorption and diffusion? 5) What's the uncertainties of transport parameters in radionuclides migration analysis due to a lack of understanding/experimental methodologies, and how do we derive them? This report includes workshop program, overview and materials of each presentation, summary of discussions. (author)

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

    Science.gov (United States)

    LoPachin, Richard M; Gavin, Terrence

    2015-06-02

    2,5-Hexanedione (HD) and acrylamide (ACR) are considered to be prototypical among chemical toxicants that cause central-peripheral axonopathies characterized by distal axon swelling and degeneration. Because the demise of distal regions was assumed to be causally related to the onset of neurotoxicity, substantial effort was devoted to deciphering the respective mechanisms. Continued research, however, revealed that expression of the presumed hallmark morphological features was dependent upon the daily rate of toxicant exposure. Indeed, many studies reported that the corresponding axonopathic changes were late developing effects that occurred independent of behavioral and/or functional neurotoxicity. This suggested that the toxic axonopathy classification might be based on epiphenomena related to dose-rate. Therefore, the goal of this mini-review is to discuss how quantitative morphometric analyses and the establishment of dose-dependent relationships helped distinguish primary, mechanistically relevant toxicant effects from non-specific consequences. Perhaps more importantly, we will discuss how knowledge of neurotoxicant chemical nature can guide molecular-level research toward a better, more rational understanding of mechanism. Our discussion will focus on HD, the neurotoxic γ-diketone metabolite of the industrial solvents n-hexane and methyl-n-butyl ketone. Early investigations suggested that HD caused giant neurofilamentous axonal swellings and eventual degeneration in CNS and PNS. However, as our review will point out, this interpretation underwent several iterations as the understanding of γ-diketone chemistry improved and more quantitative experimental approaches were implemented. The chemical concepts and design strategies discussed in this mini-review are broadly applicable to the mechanistic studies of other chemicals (e.g., n-propyl bromine, methyl methacrylate) that cause toxic neuropathies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Mechanistic Fermentation Models for Process Design, Monitoring, and Control

    DEFF Research Database (Denmark)

    Mears, Lisa; Stocks, Stuart M.; Albæk, Mads Orla

    2017-01-01

    Mechanistic models require a significant investment of time and resources, but their application to multiple stages of fermentation process development and operation can make this investment highly valuable. This Opinion article discusses how an established fermentation model may be adapted...... for application to different stages of fermentation process development: planning, process design, monitoring, and control. Although a longer development time is required for such modeling methods in comparison to purely data-based model techniques, the wide range of applications makes them a highly valuable tool...... for fermentation research and development. In addition, in a research environment, where collaboration is important, developing mechanistic models provides a platform for knowledge sharing and consolidation of existing process understanding....

  13. Profiling the biological activity of oxide nanomaterials with mechanistic models

    NARCIS (Netherlands)

    Burello, E.

    2013-01-01

    In this study we present three mechanistic models for profiling the potential biological and toxicological effects of oxide nanomaterials. The models attempt to describe the reactivity, protein adsorption and membrane adhesion processes of a large range of oxide materials and are based on properties

  14. Generative Mechanistic Explanation Building in Undergraduate Molecular and Cellular Biology

    Science.gov (United States)

    Southard, Katelyn M.; Espindola, Melissa R.; Zaepfel, Samantha D.; Bolger, Molly S.

    2017-01-01

    When conducting scientific research, experts in molecular and cellular biology (MCB) use specific reasoning strategies to construct mechanistic explanations for the underlying causal features of molecular phenomena. We explored how undergraduate students applied this scientific practice in MCB. Drawing from studies of explanation building among…

  15. Mechanistic studies related to the metal catalyzed reduction of carbon monoxide to hydrocarbons. Final report, April 1, 1977-June 30, 1985

    International Nuclear Information System (INIS)

    Casey, C.P.

    1985-02-01

    Studies of compounds related to proposed intermediates in the hydrogenation of carbon monoxide over homogeneous and heterogeneous catalysts have been carried out. The synthesis, structure, and reactions of metal formyl compounds have been investigated. The synthesis and desproportionation reactions of hydroxymethyl metal compounds have been explored. Reactions involving interconversion of n 5 - and n'-C 5 H 5 organometallic compounds have been discovered. New synthetic routes to bimetallic compounds with bridging hydrocarbon ligands have been developed. The first bimetallic compound with a budging CH ligand has been prepared. The hydrocarbation reaction in which the CH bond of a bridging methylidyne complex adds across a carbon-carbon double bond has been discovered. New heterobimetallic compounds linked by a heterodifunctional ligand and heterobimetallic compounds with directly bonded early and late transition metals have been synthesized in a search for new CO hydrogenation catalysts. 36 refs

  16. Decontamination solution development studies

    International Nuclear Information System (INIS)

    Allen, R.P.; Fetrow, L.K.; Kjarmo, H.E.; Pool, K.H.

    1993-09-01

    This study was conducted for the Westinghouse Hanford Company (WHC) by Pacific Northwest Laboratory (PNL) as part of the Hanford Grout Technology Program (HGTP). The objective of this study was to identify decontamination solutions capable of removing radioactive contaminants and grout from the Grout Treatment Facility (GTF) process equipment and to determine the impact of these solutions on equipment components and disposal options. The reference grout used in this study was prepared with simulated double-shell slurry feed (DSSF) and a dry blend consisting of 40 wt % limestone flour, 28 wt % blast furnace slag, 28 wt % fly ash, and 4 wt % type I/II Portland cement

  17. Impact and mechanistic role of oral contraceptive pills on the number and epithelial type of ovarian cortical inclusion cysts; a clinicopathology and immunohistochemical study.

    Science.gov (United States)

    DastranjTabrizi, Ali; MostafaGharabaghi, Parvin; SheikhzadehHesari, Farzam; Sadeghi, Liela; Zamanvandi, Sharareh; Sarbakhsh, Parvin; Ghojazadeh, Morteza

    2016-03-22

    Ovarian epithelial cancers are among the most lethal women's cancers. There is no doubt about the preventive role of oral contraceptive pills (OCPs) in development of ovarian cancers. But, there are limited numbers of studies to address the effect of these agents on the number of cortical inclusion cysts (CICs), their epithelial type and suppression of the metaplastic phenomenon by these pills. The aim of this study was to clarify the role of these agents in the prevention of these cyst formation and tubal metaplasia and also examine the mesenchymal-epithelial transition theory in this context by immunohistochemical methods. The representative section(s) of ovarian cortex from a total number of 201 consecutive total abdominal hysterectomy with bilateral or unilateral salpingo-oophorectomy specimens were examined for mean number of CICs and their epithelial type between two groups of the patients. Group A included the patients who were on oral contraceptive pills for more than 5 years. All of the subjects with other contraceptive methods or a history of less than 5 years contraceptive pills usage were stratified in group B. Sections from 20 cases in which more than five inclusion cysts were found, were selected for IHC staining with calretinine and PAX8 as markers for mesothelium and mullerian epithelium respectively. The mean age of the patients was 51.67 years with no significant differences between two groups. The mean number of cysts were 1.27 and 3.23 in group A and B respectively (P =0.0001). Similarly the mean number of CICs, lined by tubal epithelium, was significantly different between two groups (0.65 vs 2.65, P =0.0001). In IHC staining 123 out of 150 CICs (82 %) were PAX+ while only 7 CICs (4.8 %) showed positive reaction for calretinin irrespective of type of epithelium. Our findings showed that the use of OCP for more than five years in women, significantly prevents development of cortical inclusion cysts in the ovaries which lined by tubal

  18. Remote connector development study

    International Nuclear Information System (INIS)

    Parazin, R.J.

    1995-05-01

    Plutonium-uranium extraction (PUREX) connectors, the most common connectors used at the Hanford site, offer a certain level of flexibility in pipe routing, process system configuration, and remote equipment/instrument replacement. However, these desirable features have inherent shortcomings like leakage, high pressure drop through the right angle bends, and a limited range of available pipe diameters that can be connect by them. Costs for construction, maintenance, and operation of PUREX connectors seem to be very high. The PUREX connector designs include a 90 degree bend in each connector. This increases the pressure drop and erosion effects. Thus, each jumper requires at least two 90 degree bends. PUREX connectors have not been practically used beyond 100 (4 in.) inner diameter. This study represents the results of a survey on the use of remote pipe-connection systems in US and foreign plants. This study also describes the interdependence between connectors, remote handling equipment, and the necessary skills of the operators

  19. Mechanistic model of mass-specific basal metabolic rate: evaluation in healthy young adults.

    Science.gov (United States)

    Wang, Z; Bosy-Westphal, A; Schautz, B; Müller, M

    2011-12-01

    Mass-specific basal metabolic rate (mass-specific BMR), defined as the resting energy expenditure per unit body mass per day, is an important parameter in energy metabolism research. However, a mechanistic explanation for magnitude of mass-specific BMR remains lacking. The objective of the present study was to validate the applicability of a proposed mass-specific BMR model in healthy adults. A mechanistic model was developed at the organ-tissue level, mass-specific BMR = Σ( K i × F i ), where Fi is the fraction of body mass as individual organs and tissues, and K i is the specific resting metabolic rate of major organs and tissues. The Fi values were measured by multiple MRI scans and the K i values were suggested by Elia in 1992. A database of healthy non-elderly non-obese adults (age 20 - 49 yrs, BMI BMR of all subjects was 21.6 ± 1.9 (mean ± SD) and 21.7 ± 1.6 kcal/kg per day, respectively. The measured mass-specific BMR was correlated with the predicted mass-specific BMR (r = 0.82, P BMR, versus the average of measured and predicted mass-specific BMR. In conclusion, the proposed mechanistic model was validated in non-elderly non-obese adults and can help to understand the inherent relationship between mass-specific BMR and body composition.

  20. Mechanistic Systems Modeling to Improve Understanding and Prediction of Cardiotoxicity Caused by Targeted Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Jaehee V. Shim

    2017-09-01

    Full Text Available Tyrosine kinase inhibitors (TKIs are highly potent cancer therapeutics that have been linked with serious cardiotoxicity, including left ventricular dysfunction, heart failure, and QT prolongation. TKI-induced cardiotoxicity is thought to result from interference with tyrosine kinase activity in cardiomyocytes, where these signaling pathways help to control critical processes such as survival signaling, energy homeostasis, and excitation–contraction coupling. However, mechanistic understanding is limited at present due to the complexities of tyrosine kinase signaling, and the wide range of targets inhibited by TKIs. Here, we review the use of TKIs in cancer and the cardiotoxicities that have been reported, discuss potential mechanisms underlying cardiotoxicity, and describe recent progress in achieving a more systematic understanding of cardiotoxicity via the use of mechanistic models. In particular, we argue that future advances are likely to be enabled by studies that combine large-scale experimental measurements with Quantitative Systems Pharmacology (QSP models describing biological mechanisms and dynamics. As such approaches have proven extremely valuable for understanding and predicting other drug toxicities, it is likely that QSP modeling can be successfully applied to cardiotoxicity induced by TKIs. We conclude by discussing a potential strategy for integrating genome-wide expression measurements with models, illustrate initial advances in applying this approach to cardiotoxicity, and describe challenges that must be overcome to truly develop a mechanistic and systematic understanding of cardiotoxicity caused by TKIs.

  1. MECHANISTIC STUDIES AND DESIGN OF HIGHLY ACTIVE CUPRATE CATALYSTS FOR THE DIRECT DECOMPOSITION AND SELECTIVE REDUCTION OF NITRIC OXIDE AND HYDROCARBONS TO NITROGEN FOR ABATEMENT OF STACK EMISSIONS

    Energy Technology Data Exchange (ETDEWEB)

    None

    1998-04-30

    A flow trough type catalytic reactor system was adequately modified for NO related catalytic and adsorption measurements, including the on-line connection of a digital chemiluminescent NO-NO{sub x} analyzer to the reactor outlet system. Moreover, we have largely completed the installation of an FTIR coupled catalytic system containing a HTEC cell for high temperature DRIFT studies. Three different barium cuprate samples, Ba{sub 2}CuO{sub 3}, BaCuO{sub 2}, and Ba{sub 2}Cu{sub 3}O{sub 5} were synthesized and characterized by powder XRD for catalytic tests. Prior to catalytic studies over these cuprates, a new, liquid indium based supported molten metal catalyst (In-SMMC) was tested in the reduction of NO by various reductants. In the presence of excess O{sub 2} and H{sub 2}O, the In-SMMC proved to be more active for the selective catalytic reduction (SCR) of NO to N{sub 2} by ethanol than most other catalysts. Using C{sub 1}-C{sub 3} alcohols as reductants, self sustained periodic oscillations observed in the NO{sub x} concentrations of reactor effluents indicated the first time that radical intermediates can be involved in the SCR of NO by alcohols. Further, In-SMMC is the only effective and water tolerant SCR catalyst reported thus far which contains SiO{sub 2} support. Thus, this novel catalyst opens up a promising new alternative for developing an effective and durable catalyst for NO{sub x} abatement in stack emission.

  2. Mechanistic Indicators of Childhood Asthma (MICA): piloting ...

    Science.gov (United States)

    Background: Modem methods in molecular biology and advanced computational tools show promise in elucidating complex interactions that occur between genes and environmental factors in diseases such as asthma; however appropriately designed studies are critical for these methods to reach their full potential. Objective: We used a case-control study to investigate whether genomic data (blood gene expression), viewed together with a spectrum of exposure effects and susceptibility markers (blood, urine and nail), can provide a mechanistic explanation for the increased susceptibility of asthmatics to ambient air pollutants. Methods: We studied 205 non-asthmatic and asthmatic children, (9-12 years of age) who participated in a clinical study in Detroit, Michigan. The study combines a traditional epidemiological design with an integrative approach to investigate the environmental exposure of children to indoor-outdoor air. The study includes measurements of internal dose (metals, allergen specific IgE, PAH and VOC metabolites) and clinical measures of health outcome (immunological, cardiovascular and respiratory). Results: Expected immunological indications of asthma have been obtained. In addition, initial results from our analyses point to the complex nature of childhood health and risk factors linked to metabolic syndrome (obesity, blood pressure and dyslipidemia). For example, 31% and 34% of the asthmatic MICA subjects were either overweight (BMI > 25) o

  3. Mechanistic insight into neurotoxicity induced by developmental insults

    International Nuclear Information System (INIS)

    Tamm, Christoffer; Ceccatelli, Sandra

    2017-01-01

    Epidemiological and/or experimental studies have shown that unfavorable prenatal environmental factors, such as stress or exposure to certain neurotoxic environmental contaminants, may have adverse consequences for neurodevelopment. Alterations in neurogenesis can have harmful effects not only for the developing nervous system, but also for the adult brain where neurogenesis is believed to play a role in learning, memory, and even in depression. Many recent advances in the understanding of the complex process of nervous system development can be integrated into the field of neurotoxicology. In the past 15 years we have been using cultured neural stem or progenitor cells to investigate the effects of neurotoxic stimuli on cell survival, proliferation and differentiation, with special focus on heritable effects. This is an overview of the work performed by our group in the attempt to elucidate the mechanisms of developmental neurotoxicity and possibly provide relevant information for the understanding of the etiopathogenesis of complex brain disorders. - Highlights: • The developing nervous system is highly sensitive to toxic insults. • Neural stem cells are relevant models for mechanistic studies as well as for identifying heritable effects due to epigenetic changes. • Depending on the dose, the outcome of exposure to neurotoxicants ranges from altered proliferation and differentiation to cell death. • The elucidation of neurotoxicity mechanisms is relevant for understanding the etiopathogenesis of developmental and adult nervous system disorders.

  4. Mechanistic Basis of Cocrystal Dissolution Advantage.

    Science.gov (United States)

    Cao, Fengjuan; Amidon, Gordon L; Rodríguez-Hornedo, Naír; Amidon, Gregory E

    2018-01-01

    Current interest in cocrystal development resides in the advantages that the cocrystal may have in solubility and dissolution compared with the parent drug. This work provides a mechanistic analysis and comparison of the dissolution behavior of carbamazepine (CBZ) and its 2 cocrystals, carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) under the influence of pH and micellar solubilization. A simple mathematical equation is derived based on the mass transport analyses to describe the dissolution advantage of cocrystals. The dissolution advantage is the ratio of the cocrystal flux to drug flux and is defined as the solubility advantage (cocrystal to drug solubility ratio) times the diffusivity advantage (cocrystal to drug diffusivity ratio). In this work, the effective diffusivity of CBZ in the presence of surfactant was determined to be different and less than those of the cocrystals. The higher effective diffusivity of drug from the dissolved cocrystals, the diffusivity advantage, can impart a dissolution advantage to cocrystals with lower solubility than the parent drug while still maintaining thermodynamic stability. Dissolution conditions where cocrystals can display both thermodynamic stability and a dissolution advantage can be obtained from the mass transport models, and this information is useful for both cocrystal selection and formulation development. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  5. Proposed key characteristics of male reproductive toxicants as a method for organizing and screening mechanistic evidence for non-cancer outcomes.

    Science.gov (United States)

    The adoption of systematic review practices for risk assessment includes integration of evidence obtained from experimental, epidemiological, and mechanistic studies. Although mechanistic evidence plays an important role in mode of action analysis, the process of sorting and anal...

  6. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available 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 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.

  7. Mechanistic Modeling of Water Replenishment Rate of Zeer Refrigerator

    Directory of Open Access Journals (Sweden)

    B. N. Nwankwojike

    2017-06-01

    Full Text Available A model for predicting the water replenishment rate of zeer pot refrigerator was developed in this study using mechanistic modeling approach and evaluated at Obowo, Imo State, Nigeria using six fruits, tomatoes, guava, okra, banana, orange and avocado pear. The developed model confirmed zeer pot water replenishment rate as a function of ambient temperature, relative humidity, wind speed, thermal conductivity of the pot materials and sand, density of air and water vapor, permeability coefficient of clay and heat transfer coefficient of water into air, circumferential length, height of pot, geometrical profile of the pot, heat load of the food preserved, heat flow into the device and gradient at which the pot is placed above ground level. Compared to the conventional approach of water replenishment, performance analysis results revealed 44% to 58% water economy when the zeer pot’s water was replenished based on the model’s prediction; while there was no significant difference in the shelf-life of the fruits preserved with both replenishment methods. Application of the developed water replenishment model facilitates optimal water usage in this system, thereby reducing operational cost of zeer pot refrigerator.

  8. Mechanistic explanation of time-dependent cross-phenomenon based on quorum sensing: A case study of the mixture of sulfonamide and quorum sensing inhibitor to bioluminescence of Aliivibrio fischeri.

    Science.gov (United States)

    Sun, Haoyu; Pan, Yongzheng; Gu, Yue; Lin, Zhifen

    2018-07-15

    Cross-phenomenon in which the concentration-response curve (CRC) for a mixture crosses the CRC for the reference model has been identified in many studies, expressed as a heterogeneous pattern of joint toxic action. However, a mechanistic explanation of the cross-phenomenon has thus far been extremely insufficient. In this study, a time-dependent cross-phenomenon was observed, in which the cross-concentration range between the CRC for the mixture of sulfamethoxypyridazine (SMP) and (Z-)-4-Bromo-5-(bromomethylene)-2(5H)-furanone (C30) to the bioluminescence of Aliivibrio fischeri (A. fischeri) and the CRC for independent action model with 95% confidence bands varied from low-concentration to higher-concentration regions in a timely manner expressed the joint toxic action of the mixture changing with an increase of both concentration and time. Through investigating the time-dependent hormetic effects of SMP and C30 (by measuring the expression of protein mRNA, simulating the bioluminescent reaction and analyzing the toxic action), the underlying mechanism was as follows: SMP and C30 acted on the quorum sensing (QS) system of A. fischeri, which induced low-concentration stimulatory effects and high-concentration inhibitory effects; in the low-concentration region, the stimulatory effects of SMP and C30 made the mixture produce a synergistic stimulation on the bioluminescence; thus, the joint toxic action exhibited antagonism. In the high-concentration region, the inhibitory effects of SMP and C30 in the mixture caused a double block in the loop circuit of the QS system; thus, the joint toxic action exhibited synergism. With the increase of time, these stimulatory and inhibitory effects of SMP and C30 were changed by the variation of the QS system at different growth phases, resulting in the time-dependent cross-phenomenon. This study proposes an induced mechanism for time-dependent cross-phenomenon based on QS, which may provide new insight into the mechanistic

  9. Newly constructed stable reporter cell lines for mechanistic studies on electrophile-responsive element-mediated gene expression reveal a role for flavonoid planarity.

    NARCIS (Netherlands)

    Boerboom, A.M.A.; Vermeulen, M.; Woude, H. van der; Bremer, B.I.; Lee-Hilz, Y.Y.; Kampman, E.; Bladeren, P.J. van; Rietjens, I.M.C.M.; Aarts, J.

    2006-01-01

    The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression modulation by certain food components. Two stably transfected luciferase reporter cell lines were developed, EpRE(hNQO1)-LUX and EpRE(mGST-Ya)-LUX, based on EpRE sequences from

  10. [Zr(NEtMe)2(guan-NEtMe)2] as a novel ALD precursor: ZrO2 film growth and mechanistic studies

    NARCIS (Netherlands)

    Blanquart, T.; Niinistö, J.; Aslam, N.; Banerjee, M.; Tomczak, Y.; Gavagnin, M.; Longo, V.; Puukilainen, E.; Wanzenboeck, H.D.; Kessels, W.M.M.; Devi, A.; Hoffmann-Eifert, S.; Ritala, M.; Leskelä, M.

    2013-01-01

    [Zr(NEtMe)2(guan-NEtMe2)2], a recently developed compound, was investigated as a novel precursor for the atomic layer deposition (ALD) of ZrO2. With water as the oxygen source, the growth rate remained constant over a wide temperature range, whereas with ozone the growth rate increased steadily with

  11. Newly constructed stable reporter cell lines for mechanistic studies on electrophile-responsive element-mediated gene expression reveal a role for flavonoid planarity

    NARCIS (Netherlands)

    Boerboom, A.M.J.F.; Vermeulen, M.; Woude, H. van der; Bremer, B.I.; Lee-Hilz, Y.Y.; Kampman, E.; Bladeren, P.J. van; Rietjens, I.M.C.M.; Aarts, J.M.M.J.G.

    2006-01-01

    The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression modulation by certain food components. Two stably transfected luciferase reporter cell lines were developed, EpRE(hNQO1)-LUX and EpRE(mGST-Ya)-LUX, based on EpRE sequences from

  12. Incorporation of lysosomal sequestration in the mechanistic model for prediction of tissue distribution of basic drugs.

    Science.gov (United States)

    Assmus, Frauke; Houston, J Brian; Galetin, Aleksandra

    2017-11-15

    The prediction of tissue-to-plasma water partition coefficients (Kpu) from in vitro and in silico data using the tissue-composition based model (Rodgers & Rowland, J Pharm Sci. 2005, 94(6):1237-48.) is well established. However, distribution of basic drugs, in particular into lysosome-rich lung tissue, tends to be under-predicted by this approach. The aim of this study was to develop an extended mechanistic model for the prediction of Kpu which accounts for lysosomal sequestration and the contribution of different cell types in the tissue of interest. The extended model is based on compound-specific physicochemical properties and tissue composition data to describe drug ionization, distribution into tissue water and drug binding to neutral lipids, neutral phospholipids and acidic phospholipids in tissues, including lysosomes. Physiological data on the types of cells contributing to lung, kidney and liver, their lysosomal content and lysosomal pH were collated from the literature. The predictive power of the extended mechanistic model was evaluated using a dataset of 28 basic drugs (pK a ≥7.8, 17 β-blockers, 11 structurally diverse drugs) for which experimentally determined Kpu data in rat tissue have been reported. Accounting for the lysosomal sequestration in the extended mechanistic model improved the accuracy of Kpu predictions in lung compared to the original Rodgers model (56% drugs within 2-fold or 88% within 3-fold of observed values). Reduction in the extent of Kpu under-prediction was also evident in liver and kidney. However, consideration of lysosomal sequestration increased the occurrence of over-predictions, yielding overall comparable model performances for kidney and liver, with 68% and 54% of Kpu values within 2-fold error, respectively. High lysosomal concentration ratios relative to cytosol (>1000-fold) were predicted for the drugs investigated; the extent differed depending on the lysosomal pH and concentration of acidic phospholipids among

  13. Specialists without spirit: limitations of the mechanistic biomedical model.

    Science.gov (United States)

    Hewa, S; Hetherington, R W

    1995-06-01

    This paper examines the origin and the development of the mechanistic model of the human body and health in terms of Max Weber's theory of rationalization. It is argued that the development of Western scientific medicine is a part of the broad process of rationalization that began in sixteenth century Europe as a result of the Reformation. The development of the mechanistic view of the human body in Western medicine is consistent with the ideas of calculability, predictability, and control-the major tenets of the process of rationalization as described by Weber. In recent years, however, the limitations of the mechanistic model have been the topic of many discussions. George Engel, a leading advocate of general systems theory, is one of the leading proponents of a new medical model which includes the general quality of life, clean environment, and psychological, or spiritual stability of life. The paper concludes with consideration of the potential of Engel's proposed new model in the context of the current state of rationalization in modern industrialized society.

  14. Application of granular activated carbon/MnFe2O4 composite immobilized on C. glutamicum MTCC 2745 to remove As(III) and As(V): Kinetic, mechanistic and thermodynamic studies

    Science.gov (United States)

    Podder, M. S.; Majumder, C. B.

    2016-01-01

    The main objective of the present study was to investigate the efficiency of Corynebacterium glutamicum MTCC 2745 immobilized on granular activated carbon/MnFe2O4 (GAC/MnFe2O4) composite to treat high concentration of arsenic bearing wastewater. Non-linear regression analysis was done for determining the best-fit kinetic model on the basis of three correlation coefficients and three error functions and also for predicting the parameters involved in kinetic models. The results showed that Fractal-like mixed 1,2 order model for As(III) and Brouser-Weron-Sototlongo as well as Fractal-like pseudo second order models for As(V) were proficient to provide realistic description of biosorption/bioaccumulation kinetic. Applicability of mechanistic models in the current study exhibited that the rate governing step in biosorption/bioaccumulation of both As(III) and As(V) was film diffusion rather than intraparticle diffusion. The evaluated thermodynamic parameters ΔG0, ΔH0 and ΔS0 revealed that biosorption/bioaccumulation of both As(III) and As(V) was feasible, spontaneous and exothermic under studied conditions.

  15. Recent STM, DFT and HAADF-STEM studies of sulfide-based hydrotreating catalysts: Insight into mechanistic, structural and particle size effects

    DEFF Research Database (Denmark)

    Besenbacher, Flemming; Brorson, M.; Clausen, B.S.

    2008-01-01

    The present article will highlight some recent experimental and theoretical studies of both unpromoted MoS2 and promoted Co-Mo-S and NiMo-S nanostructures. Particular emphasis will be given to discussion of our scanning tunnelling microscopy (STM), density functional theory (I)FT), and high...... and support effects which play an important role in practical HDS. Recent STM studies have shown that MoS2 clusters below 2-3 nm may exhibit new structural and electronic properties, and a large variety of size-dependent structures have been identified. In view of the large structure sensitivity......-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) studies which have provided insight into the detailed atomic structure. In accordance with earlier theoretical studies, the experimental studies show that the Ni-Mo-S structures may in some instances differ from the Co...

  16. In Vitro–In Vivo Correlation for Gliclazide Immediate-Release Tablets Based on Mechanistic Absorption Simulation

    OpenAIRE

    Grbic, Sandra; Parojcic, Jelena; Ibric, Svetlana; Djuric, Zorica

    2010-01-01

    The aim of this study was to develop a drug-specific absorption model for gliclazide (GLK) using mechanistic gastrointestinal simulation technology (GIST) implemented in GastroPlusTM software package. A range of experimentally determined, in silico predicted or literature data were used as input parameters. Experimentally determined pH-solubility profile was used for all simulations. The human jejunum effective permeability (Peff) value was estimated on the basis of in vitro measured Caco-2 p...

  17. A mechanistic approach to postirradiation spoilage kinetics of fish

    International Nuclear Information System (INIS)

    Tukenmez, I.

    2004-01-01

    Full text: In order to simulate postirradiation spoilage of fish, the mechanistic aspects of the growth of surviving microorganisms during chill storage and their product formation in irradiated fish were analyzed. Anchovy (Engraulis encrasicholus) samples those unirradiated and irradiated at 1, 2 and 3 kGy doses of gamma radiation were stored at +2 o C for 21 days. Total bacterial counts (TBC) and trimethylamine (TMA) analysis of the samples were done periodically during storage. Depending on the proposed spoilage mechanism, kinetic model equations were derived. By using experimental data of TBC and TMA in the developed model, the postirradiation spoilage parameters including growth rate constant, inital and maximum attainable TBC, lag time and TMA yield were evaluated and microbial spoilage of fish was simulated for postirradiation storage. Shelf life of irradiated fish was estimated depending on the spoilage kinetics. Dose effects on the kinetic parameters were analyzed. It is suggested that the kinetic evaluation method developed in this study may be used for quality assessment, shelf life determination and dose optimization for radiation preservation of fish

  18. Analytical techniques for mechanistic characterization of EUV photoresists

    Science.gov (United States)

    Grzeskowiak, Steven; Narasimhan, Amrit; Murphy, Michael; Ackerman, Christian; Kaminsky, Jake; Brainard, Robert L.; Denbeaux, Greg

    2017-03-01

    Extreme ultraviolet (EUV, 13.5 nm) lithography is the prospective technology for high volume manufacturing by the microelectronics industry. Significant strides towards achieving adequate EUV source power and availability have been made recently, but a limited rate of improvement in photoresist performance still delays the implementation of EUV. Many fundamental questions remain to be answered about the exposure mechanisms of even the relatively well understood chemically amplified EUV photoresists. Moreover, several groups around the world are developing revolutionary metal-based resists whose EUV exposure mechanisms are even less understood. Here, we describe several evaluation techniques to help elucidate mechanistic details of EUV exposure mechanisms of chemically amplified and metal-based resists. EUV absorption coefficients are determined experimentally by measuring the transmission through a resist coated on a silicon nitride membrane. Photochemistry can be evaluated by monitoring small outgassing reaction products to provide insight into photoacid generator or metal-based resist reactivity. Spectroscopic techniques such as thin-film Fourier transform infrared (FTIR) spectroscopy can measure the chemical state of a photoresist system pre- and post-EUV exposure. Additionally, electrolysis can be used to study the interaction between photoresist components and low energy electrons. Collectively, these techniques improve our current understanding of photomechanisms for several EUV photoresist systems, which is needed to develop new, better performing materials needed for high volume manufacturing.

  19. Mechanistic movement models to understand epidemic spread.

    Science.gov (United States)

    Fofana, Abdou Moutalab; Hurford, Amy

    2017-05-05

    An overlooked aspect of disease ecology is considering how and why animals come into contact with one and other resulting in disease transmission. Mathematical models of disease spread frequently assume mass-action transmission, justified by stating that susceptible and infectious hosts mix readily, and foregoing any detailed description of host movement. Numerous recent studies have recorded, analysed and modelled animal movement. These movement models describe how animals move with respect to resources, conspecifics and previous movement directions and have been used to understand the conditions for the occurrence and the spread of infectious diseases when hosts perform a type of movement. Here, we summarize the effect of the different types of movement on the threshold conditions for disease spread. We identify gaps in the literature and suggest several promising directions for future research. The mechanistic inclusion of movement in epidemic models may be beneficial for the following two reasons. Firstly, the estimation of the transmission coefficient in an epidemic model is possible because animal movement data can be used to estimate the rate of contacts between conspecifics. Secondly, unsuccessful transmission events, where a susceptible host contacts an infectious host but does not become infected can be quantified. Following an outbreak, this enables disease ecologists to identify 'near misses' and to explore possible alternative epidemic outcomes given shifts in ecological or immunological parameters.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Author(s).

  20. Oxidative N-Heterocyclic Carbene-Catalyzed γ-Carbon Addition of Enals to Imines: Mechanistic Studies and Access to Antimicrobial Compounds.

    Science.gov (United States)

    Zheng, Peng-Cheng; Cheng, Jiajia; Su, Shihu; Jin, Zhichao; Wang, Yu-Huang; Yang, Song; Jin, Lin-Hong; Song, Bao-An; Chi, Yonggui Robin

    2015-07-06

    The reaction mechanism of the γ-carbon addition of enal to imine under oxidative N-heterocyclic carbene catalysis is studied experimentally. The oxidation, γ-carbon deprotonation, and nucleophilic addition of γ-carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Elucidating the interplay between DNA-condensing and free polycations in gene transfection through a mechanistic study of linear and branched PEI

    DEFF Research Database (Denmark)

    Dai, Zhuojun; Gjetting, Torben; Mattebjerg, Maria Ahlm

    2011-01-01

    In the present study we compare LPEI and BPEI characteristics related to DNA condensation and their role as free polycation chains in gene transfection. Using radioactive 32P labeled DNA, we investigated the effect of free PEI chains on the cellular uptake of polyplexes. Our investigations show d...

  2. Mechanistic Studies on Chabazite-Type Methanol-to-Olefin Catalysts: Insights from Time-Resolved UV/Vis Microspectroscopy Combined with Theoretical Simulations

    NARCIS (Netherlands)

    Van Speybroeck, V.; Hemelsoet, K.L.J.; De Wispelaere, K.; Qian, Q.|info:eu-repo/dai/nl/34138609X; Van der Mynsbrugge, J.; De Sterck, B.; Weckhuysen, B.M.|info:eu-repo/dai/nl/285484397; Waroquier, M.

    2013-01-01

    The formation and nature of active sites for methanol conversion over solid acid catalyst materials are studied by using a unique combined spectroscopic and theoretical approach. A working catalyst for the methanol-to-olefin conversion has a hybrid organic–inorganic nature in which a cocatalytic

  3. Role of Re in Pt-Re/TiO2 catalyst for water gas shift reaction: A mechanistic and kinetic study.

    NARCIS (Netherlands)

    Azzam, K.G.H.; Babych, Igor V.; Seshan, Kulathuiyer; Lefferts, Leonardus

    2008-01-01

    Transient kinetic studies and in situ FTIR spectroscopy were used to follow the reaction sequences that occur during water gas shift (WGS) reaction over Pt–Re/TiO2 catalyst. Results pointed to contributions of an associative formate route with redox regeneration and two classical redox routes

  4. Enantioselective skin permeation of ibuprofen enantiomers: mechanistic insights from ATR-FTIR and CLSM studies based on synthetic enantiomers as naphthalimide fluorescent probes.

    Science.gov (United States)

    Che, Qi-en; Quan, Peng; Mu, Mao; Zhang, Xinfu; Zhao, Hanqing; Zhang, Yu; You, Song; Xiao, Yi; Fang, Liang

    2014-10-01

    The aim of this study was to investigate the mechanisms of different skin permeability of ibuprofen racemate and enantiomers. The percutaneous permeation of ibuprofen racemate and enantiomers through rabbit normal skin and damaged skin (without stratum corneum [SC]) was investigated in vitro using side-by-side diffusion cells. With the melting temperature-membrane transport model, the flux ratio of enantiomer/racemate was calculated from their thermodynamic properties obtained by differential scanning calorimetry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) study was performed to evaluate the interaction between the enantiomers and the SC. New fluorescent probes were designed and utilized in confocal laser scanning microscopy (CLSM) study for visualization of the enantioselective permeation of the enantiomers through the intact rabbit skin. The flux of (S)-ibuprofen through normal skin was significantly higher than that of (RS)-ibuprofen and (R)-ibuprofen (p skin, there was no significant difference (p > 0.05). The predicted flux ratio of (S)-ibuprofen/(RS)-ibuprofen (2.50) was in close agreement with the experimentally determined ratio (2.48). These results were supported by ATR-FTIR and CLSM studies that indicated that a chiral environment of the skin led to the enantioselective permeation of enantiomers. The chiral nature of the SC and the different physicochemical properties of the enantiomers should be taken into account in the assessment of different skin permeability of the racemate and enantiomers. The synthetic fluorescent probes used in this study could visualize the enantioselective permeation of the chiral compounds across the skin.

  5. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study

    Directory of Open Access Journals (Sweden)

    Taro Yamaguchi

    2017-08-01

    Full Text Available We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h, hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days, there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin®, a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss.

  6. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study.

    Science.gov (United States)

    Yamaguchi, Taro; Yoneyama, Masanori; Onaka, Yusuke; Imaizumi, Atsushi; Ogita, Kiyokazu

    2017-08-01

    We sought to determine the preventive effects of curcumin and its highly bioavailable preparation on noise-induced hearing loss in a novel murine model of permanent hearing loss developed by repeated exposure to noise. Upon exposure to noise (8-kHz octave band noise, 90 dB sound pressure level, 1 h), hearing ability was impaired in a temporary and reversible manner. During repeated noise exposure (1-h exposure per day, 5 days), there was a progressive increase in the auditory threshold shift at 12 and 20 kHz. The threshold shift persisted for at least 6 days after noise exposure. Oral administration of curcumin for 3 days before and each day during noise exposure significantly alleviated the hearing loss induced by repeated noise exposure. Curcumin abolished intranuclear translocation of nuclear factor-κB-p65 and generation of 4-hydroxynonenal-adducted proteins found in the cochlea after noise exposure. Theracurmin ® , a highly absorbable and bioavailable preparation of curcumin, had strong preventive effects on hearing loss induced by repeated noise exposure. Together, these data suggest that curcumin exerts a preventive effect on noise-induced hearing loss and is therefore a good therapeutic candidate for preventing sensorineural hearing loss. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  7. Atomic resolution mechanistic studies of ribocil: A highly selective unnatural ligand mimic of the E. coli FMN riboswitch

    Energy Technology Data Exchange (ETDEWEB)

    Howe, John A.; Xiao, Li; Fischmann, Thierry O.; Wang, Hao; Tang, Haifeng; Villafania, Artjohn; Zhang, Rumin; Barbieri, Christopher M.; Roemer, Terry (Merck)

    2016-08-02

    Bacterial riboswitches are non-coding RNA structural elements that direct gene expression in numerous metabolic pathways. The key regulatory roles of riboswitches, and the urgent need for new classes of antibiotics to treat multi-drug resistant bacteria, has led to efforts to develop small-molecules that mimic natural riboswitch ligands to inhibit metabolic pathways and bacterial growth. Recently, we reported the results of a phenotypic screen targeting the riboflavin biosynthesis pathway in the Gram-negative bacteria Escherichia coli that led to the identification of ribocil, a small molecule inhibitor of the flavin mononucleotide (FMN) riboswitch controlling expression of this biosynthetic pathway. Although ribocil is structurally distinct from FMN, ribocil functions as a potent and highly selective synthetic mimic of the natural ligand to repress riboswitch-mediated ribB gene expression and inhibit bacterial growth both in vitro and in vivo. Herein, we expand our analysis of ribocil; including mode of binding in the FMN binding pocket of the riboswitch, mechanisms of resistance and structure-activity relationship guided efforts to generate more potent analogs.

  8. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.

    2012-05-15

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach would be to quantitate the degree of similarity between the responses that cells show when exposed to drugs, so that consistencies in the regulation of cellular response processes that produce success or failure can be more readily identified.Results: We track drug response using fluorescent proteins as transcription activity reporters. Our basic assumption is that drugs inducing very similar alteration in transcriptional regulation will produce similar temporal trajectories on many of the reporter proteins and hence be identified as having similarities in their mechanisms of action (MOA). The main body of this work is devoted to characterizing similarity in temporal trajectories/signals. To do so, we must first identify the key points that determine mechanistic similarity between two drug responses. Directly comparing points on the two signals is unrealistic, as it cannot handle delays and speed variations on the time axis. Hence, to capture the similarities between reporter responses, we develop an alignment algorithm that is robust to noise, time delays and is able to find all the contiguous parts of signals centered about a core alignment (reflecting a core mechanism in drug response). Applying the proposed algorithm to a range of real drug experiments shows that the result agrees well with the prior drug MOA knowledge. © The Author 2012. Published by Oxford University Press. All rights reserved.

  9. A Unique (3+2) Annulation Reaction between Meldrum's Acid and Nitrones: Mechanistic Insight by ESI-IMS-MS and DFT Studies.

    Science.gov (United States)

    Lespes, Nicolas; Pair, Etienne; Maganga, Clisy; Bretier, Marie; Tognetti, Vincent; Joubert, Laurent; Levacher, Vincent; Hubert-Roux, Marie; Afonso, Carlos; Loutelier-Bourhis, Corinne; Brière, Jean-François

    2018-03-15

    The fragile intermediates of the domino process leading to an isoxazolidin-5-one, triggered by unique reactivity between Meldrum's acid and an N-benzyl nitrone in the presence of a Brønsted base, were determined thanks to the softness and accuracy of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS). The combined DFT study shed light on the overall organocatalytic sequence that starts with a stepwise (3+2) annulation reaction that is followed by a decarboxylative protonation sequence encompassing a stereoselective pathway issue. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. The use of deuterium n.m.r. spectroscopy in mechanistic studies of exchange reactions of ethers on supported metal catalysts

    International Nuclear Information System (INIS)

    Campbell, J.A.; Kemball, Charles; McDougall, G.S.

    1987-01-01

    Exchange reactions of diethyl ether (DEE) and tetrahydrofuran (THF) with deuterium have been studied over supported nickel, palladium, platinum, and rhodium catalysts. Products from most of the systems were analysed by deuterium n.m.r. spectroscopy (55.28 MHz) which gave quantitative results about the distribution of deuterium in the exchanged ethers. The results confirm earlier conclusions about the mechanism of the exchange of DEE and provide new evidence about the reactions of THF. Some hydrogenolysis occurred simultaneously with exchange of THF over both nickel and platinum. (author)

  11. In vitro solubility, dissolution and permeability studies combined with semi-mechanistic modeling to investigate the intestinal absorption of desvenlafaxine from an immediate- and extended release formulation

    DEFF Research Database (Denmark)

    Franek, F; Jarlfors, A; Larsen, F.

    2015-01-01

    Desvenlafaxine is a biopharmaceutics classification system (BCS) class 1 (high solubility, high permeability) and biopharmaceutical drug disposition classification system (BDDCS) class 3, (high solubility, poor metabolism; implying low permeability) compound. Thus the rate-limiting step...... not imply low intestinal permeability, as indicated by the BDDCS, merely low duodenal/jejunal permeability....... for desvenlafaxine absorption (i.e. intestinal dissolution or permeation) is not fully clarified. The aim of this study was to investigate whether dissolution and/or intestinal permeability rate-limit desvenlafaxine absorption from an immediate-release formulation (IRF) and Pristiq®, an extended release formulation...

  12. Mechanistic Features of Nanodiamonds in the Lapping of Magnetic Heads

    Directory of Open Access Journals (Sweden)

    Xionghua Jiang

    2014-01-01

    Full Text Available Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p0=3/2·W/πa2 and the indentation depth satisfies δ=k1P/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM, scanning electron microscopy (SEM, and Auger electron spectroscopy (AES were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm·min−1 can be obtained with 100 nm diamonds embedded in the plate.

  13. Mechanistic features of nanodiamonds in the lapping of magnetic heads.

    Science.gov (United States)

    Jiang, Xionghua; Chen, Zhenxing; Wolfram, Joy; Yang, Zhizhou

    2014-01-01

    Nanodiamonds, which are the main components of slurry in the precision lapping process of magnetic heads, play an important role in surface quality. This paper studies the mechanistic features of nanodiamond embedment into a Sn plate in the lapping process. This is the first study to develop mathematical models for nanodiamond embedment. Such models can predict the optimum parameters for particle embedment. From the modeling calculations, the embedded pressure satisfies p 0 = (3/2) · (W/πa (2)) and the indentation depth satisfies δ = k1√P/HV. Calculation results reveal that the largest embedded pressure is 731.48 GPa and the critical indentation depth δ is 7 nm. Atomic force microscopy (AFM), scanning electron microscopy (SEM), and Auger electron spectroscopy (AES) were used to carry out surface quality detection and analysis of the disk head. Both the formation of black spots on the surface and the removal rate have an important correlation with the size of nanodiamonds. The results demonstrate that an improved removal rate (21 nm · min(-1)) can be obtained with 100 nm diamonds embedded in the plate.

  14. A mechanistic study of hydrogen gas sensing by PdO nanoflake thin films at temperatures below 250 °C.

    Science.gov (United States)

    Chiang, Yu-Ju; Li, Kuang-Chung; Lin, Yi-Chieh; Pan, Fu-Ming

    2015-02-07

    We prepared PdO nanoflake thin films on the SiO2 substrate by reactive sputter deposition, and studied their sensing response to H2 at temperatures between 25 and 250 °C. In addition to the oxygen ionosorption model, which is used to describe the early H2 sensing response over the temperature range studied, the H2 sensing kinetics of the PdO thin films can be separated into three temperature regimes: temperatures below 100 °C, around 150 °C and above 200 °C. At temperatures below 100 °C, PdO reduction is the dominant reaction affecting the H2 sensing behavior. At temperatures around 150 °C, Pd reoxidation kinetically competes with PdO reduction leading to a complicated sensing characteristic. Active PdO reduction by H2 promotes the continuing growth of Pd nanoislands, facilitating dissociative oxygen adsorption and thus the subsequent Pd reoxidation in the H2-dry air gas mixture. The kinetic competition between the PdO reduction and reoxidation at 150 °C leads to the observation of an inverse of the increase in the sensor conductivity. At temperatures above 200 °C, the PdO sensor exhibits a sensor signal monotonically increasing with the H2 concentration, and the H2 sensing behavior is consistent with the Mars-van-Krevelen redox mechanism.

  15. Kinetics and Mechanistic Study of the Ruthenium(III Catalysed Oxidative Decarboxylation of L-Proline by Alkaline Heptavalent Manganese (Stopped flow technique

    Directory of Open Access Journals (Sweden)

    R. S. Shettar

    2005-01-01

    Full Text Available The kinetics of ruthenium(III catalysed oxidation of L-Proline by permanganate in alkaline medium at a constant ionic strength has been studied spectrophotometrically using a rapid kinetic accessory. The reaction between permanganate and L-Proline in alkaline medium exhibits 2:1 stoichiometry (KMnO4: L-Proline. The reaction shows first order dependence on [permanganate] and [ruthenium(III] and apparent less than unit order dependence each in L-Proline and alkali concentrations. Reaction rate increases with increase in ionic strength and decrease in solvent polarity of the medium. Initial addition of reaction products did not affect the rate significantly. A mechanism involving the formation of a complex between catalyst and substrate has been proposed. The activation parameters were computed with respect to the slow step of the mechanism and discussed

  16. Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nudeophilic catalysis by tetrazole and rate variations with the phosphorus substituents

    DEFF Research Database (Denmark)

    Dahl, Bjarne H.; Nielsen, John; Dahl, Otto

    1987-01-01

    , and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt 2 > NRr12 > N(CH 2CH 2)O > NMePh, and OMe > OCH 2CH 2CN......Tetrazole catalyzed reactions of a series of phosphoramidites, 5′ -O- DMTdT-3′-O-P(OR 1)NRNR22 (1a-h), with 3′ O-SiBu tPh 2-6-N-benzoyl-dA (2a) in acetonitrite solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a...

  17. The Oxidation of 2-(2-Methoxyethoxyethanol and 2-(2-Ethoxyethoxyethanol by Ditelluratocuprate(III: A Kinetic and Mechanistic Study

    Directory of Open Access Journals (Sweden)

    Jin-huan Shan

    2013-01-01

    Full Text Available The oxidation of 2-(2-methoxyethoxyethanol (MEE and 2-(2-ethoxyethoxyethanol (EEE by ditelluratocuprate(III (DTC had been studied spectrophotometrically in alkaline medium. The reaction between and showed first-order dependence in DTC and fractional order in MEE and EEE. The rate constant of the pseudo-first-order reaction decreased with an increase of [TeO4  2−], whereas adding [OH−] enhanced the constant. In addition, the reaction had a negative salt effect. The rate of EEE was higher than that of MEE. A suitable assumption involving preequilibriums before the rate-controlling step and a free radical mechanism was proposed, based on the kinetic data. Activation parameters and the rate constant of the rate-determining step were calculated.

  18. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells.

    Science.gov (United States)

    Rushworth, Stuart A; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J; MacEwan, David J; Bowles, Kristian M

    2015-05-01

    Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. We obtained acute myeloid leukaemia blast cells from unselected patients attending our UK hospital between Feb 19, 2010, and Jan 20, 2014. We isolated primary acute myeloid leukaemia blast cells from heparinised blood and human peripheral blood mononuclear cells to establish the activity of BTK in response to CD117 activation. Furthermore, we investigated the effects of ibrutinib on CD117-induced BTK activation, downstream signalling, adhesion to primary bone-marrow mesenchymal stromal cells, and proliferation of primary acute myeloid leukaemia blast cells. We used the Mann-Whitney U test to compare results between groups. We obtained acute myeloid leukaemia blast cells from 29 patients. Ibrutinib significantly inhibited CD117-mediated proliferation of primary acute myeloid leukaemia blast cells (p=0·028). CD117 activation increased BTK activity by inducing phosphorylated BTK in patients with CD117-positive acute myeloid leukaemia. Furthermore, ibrutinib inhibited CD117-induced activity of BTK and downstream kinases at a concentration of 100 nM or more. CD117-mediated adhesion of CD117-expressing blast cells to bone-marrow stromal cells was significantly inhibited by Ibrutinib at 500 nM (p=0·028) INTERPRETATION: As first-in-man clinical trials of ibrutinib in patients with acute myeloid leukaemia commence, the data suggest not all patients will respond. Our findings show that BTK has specific pro-tumoural biological actions downstream of surface CD117 activation, which are inhibited by ibrutinib

  19. Mechanistic study of lead desorption during the leaching process of ion-absorbed rare earths: pH effect and the column experiment.

    Science.gov (United States)

    Tang, Jie; Xue, Qiang; Chen, Honghan; Li, Wenting

    2017-05-01

    High concentrations of ammonium sulfate, often used in the in situ mining process, can result in a decrease of pH in the environment and dissolution of rare earth metals. Ammonium sulfate can also cause desorption of toxic heavy metals, leading to environmental and human health implications. In this study, the desorption behavior and fraction changes of lead in the ion-absorbed rare earth ore were studied using batch desorption experiments and column leaching tests. Results from batch desorption experiments showed that the desorption process of lead included fast and slow stages and followed an Elovich model well. The desorption rate and the proportion of lead content in the solution to the total lead in the soil were observed to increase with a decrease in the initial pH of the ammonium sulfate solution. The lead in soil included an acid-extractable fraction, reducible fraction, oxidizable fraction, and a residual fraction, with the predominant fractions being the reducible and acid-extractable fractions. Ninety-six percent of the extractable fraction in soil was desorbed into solution at pH = 3.0, and the content of the reducible fraction was observed to initially increase (when pH >4.0) and then decrease (when pH leaching tests indicated that the content of lead in the different fractions of soil followed the trend of reducible fraction > oxidizable fraction > acid-extractable fraction > residual fraction after the simulating leaching mining process. The change in pH was also found to have a larger influence on the acid-extractable and reducible fractions than the other two fractions. The proportion of the extractable fraction being leached was ca. 86%, and the reducible fraction was enriched along the migration direction of the leaching liquid. These results suggest that certain lead fractions may desorb again and contaminate the environment via acid rain, which provides significant information for environmental assessment and remediation after mining process

  20. Mechanistic study of lead desorption during the leaching process of ion-absorbed rare earths: pH effect and the column experiment

    Science.gov (United States)

    Xue, Q.; Tang, J., Sr.; Chen, H.

    2017-12-01

    High concentrations of ammonium sulfate, often used in the in-situ mining process, can result in a decrease of pH in the environment and dissolution of rare earth metals. Ammonium sulfate can also cause desorption of toxic heavy metals, leading to environmental and human health implications. In this study, the desorption behavior and fraction changes of lead in the ion-absorbed rare earth ore were studied using batch desorption experiments and column leaching tests. Results from batch desorption experiments showed that the desorption process of lead included fast and slow stages, and followed an Elovich model well. The desorption rate and the proportion of lead content in the solution to the total lead in the soil were observed to increase with a decrease in the initial pH of the ammonium sulfate solution. The lead in soil included an acid extractable fraction, reducible fraction, oxidizable fraction, and a residual fraction, with the predominant fractions being the reducible and acid extractable fractions. 96% of the extractable fraction in soil were desorbed into solution at pH=3.0, and the content of the reducible fraction was observed to initially increase (when pH>4.0) and then decrease (when pHleaching tests indicated that the content of lead in the different fractions of soil followed the trend of reducible fraction > oxidizable fraction > acid extractable fraction > residual fraction after the simulating leaching mining process. The change in pH was also found to have a larger influence on the acid extractable and reducible fractions than the other two fractions. The proportion of the extractable fraction being leached was ca. 86%, and the reducible fraction was enriched along the migration direction of the leaching liquid. These results suggest that certain lead fractions may desorb again and contaminate the environment via acid rain, which provides significant information for environmental assessment and remediation after mining process.

  1. Mechanistic study on lowering the sensitivity of positive atmospheric pressure photoionization mass spectrometric analyses: size-dependent reactivity of solvent clusters.

    Science.gov (United States)

    Ahmed, Arif; Choi, Cheol Ho; Kim, Sunghwan

    2015-11-15

    Understanding the mechanism of atmospheric pressure photoionization (APPI) is important for studies employing APPI liquid chromatography/mass spectrometry (LC/MS). In this study, the APPI mechanism for polyaromatic hydrocarbon (PAH) compounds dissolved in toluene and methanol or water mixture was investigated by use of MS analysis and quantum mechanical simulation. In particular, four different mechanisms that could contribute to the signal reduction were considered based on a combination of MS data and quantum mechanical calculations. The APPI mechanism is clarified by combining MS data and density functional theory (DFT) calculations. To obtain MS data, a positive-mode (+) APPI Q Exactive Orbitrap mass spectrometer was used to analyze each solution. DFT calculations were performed using the general atomic and molecular electronic structure system (GAMESS). The experimental results indicated that methanol significantly reduced the signal in (+) APPI, but no significative signal reduction was observed when water was used as a co-solvent with toluene. The signal reduction is more significant especially for molecular ions than for protonated ions. Therefore, important information about the mechanism of methanol-induced signal reduction in (+) APPI-MS can be gained due its negative impact on APPI efficiency. The size-dependent reactivity of methanol clusters ((CH3 OH)n , n = 1-8) is an important factor in determining the sensitivity of (+) APPI-MS analyses. Clusters can compete with toluene radical ions for electrons. The reactivity increases as the sizes of the methanol clusters increase and this effect can be caused by the size-dependent ionization energy of the solvent clusters. The resulting increase in cluster reactivity explains the flow rate and temperature-dependent signal reduction observed in the analytes. Based on the results presented here, minimizing the sizes of methanol clusters can improve the sensitivity of LC/(+)-APPI-MS. Copyright © 2015 John

  2. Mechanistic study of DNA damage and radioprotection of small molecule treatment in the irradiated proliferating and quiescent human lung fibroblast cells

    International Nuclear Information System (INIS)

    Dai, Jiawen; Baskar, Rajamanickam

    2014-01-01

    Ionizing radiation is an invaluable diagnostic and treatment tool used in various clinical applications and also in cancer control. However, assessing normal tissue injury is of a great interest. Since radiation sensitivity varies with different phases of cell cycle, understanding how these cells differ in their sensitivity will help to prevent or reduce the radiation injury. We have used both proliferating and quiescent human normal lung fibroblast cells and investigated key proteins involved in the cell cycle, DNA damage and death, further the radioprotective role of small molecule after low doses (d ≤1Gy) of radiation exposure. Among the cell cycle/death proteins investigated, p53 and phosphorylation of p53 (Ser-15) were induced in both the proliferating and quiescent phases of cells when studied at different time intervals. In the proliferating cells after irradiation along with p53, cyclin dependent kinase (CDK) inhibitors p21, p27 were induced. However, similarly in the quiescent cells along with the p53, p21 and p27 were also induced. The DNA damage assessed by phosphorylation of histone H2AX expression showed an increase even in the non-dividing quiescent cells after 1 Gy of radiation exposure. Whereas cell cycle proteins Cyclin A and E and cell death proteins Bax and cytochrome-c did not show any increase in the quiescent cells. In conclusion, human normal lung fibroblast cells that are not actively dividing are also showed similar radiation response as of proliferating cells. Furthermore, proliferating and quiescent cells treated with small molecules attenuate p53 and its downstream target protein p21 indicating radioprotection of the cells. The specific activation of p53, phosphorylation of p53 (Ser-15), p21 and phosphorylation of histone H2AX following radiation doses of d ≤ 1 Gy in the quiescent cells demonstrated in this study may give us a better understanding about the radiation response of non-dividing fibroblast cells, which is present in many

  3. Methyleneation of peptides by N,N,N,N-tetramethylethylenediamine (TEMED) under conditions used for free radical polymerization: a mechanistic study.

    Science.gov (United States)

    Shirangi, Mehrnoosh; Sastre Toraño, Javier; Sellergren, Börje; Hennink, Wim E; Somsen, Govert W; van Nostrum, Cornelus F

    2015-01-21

    Free radical polymerization is often used to prepare protein and peptide-loaded hydrogels for the design of controlled release systems and molecular imprinting materials. Peroxodisulfates (ammonium peroxodisulfates (APS) or potassium peroxodisulfates (KPS)) with N,N,N,N-tetramethylethylenediamine (TEMED) are frequently used as initiator and catalyst. However, exposure to these free radical polymerization reagents may lead to modification of the protein and peptide. In this work, we show the modification of lysine residues by ammonium peroxodisulfate (APS)/TEMED of the immunostimulant thymopentin (TP5). Parallel studies on a decapeptide and a library of 15 dipeptides were performed to reveal the mechanism of modification. LC-MS of APS/TEMED-exposed TP5 revealed a major reaction product with an increased mass (+12 Da) with respect to TP5. LC-MS(2) and LC-MS(3) were performed to obtain structural information on the modified peptide and localize the actual modification site. Interpretation of the obtained data demonstrates the formation of a methylene bridge between the lysine and arginine residue in the presence of TEMED, while replacing TEMED with a sodium bisulfite catalyst did not show this modification. Studies with the other peptides showed that the TEMED radical can induce methyleneation on peptides when lysine is next to arginine, proline, cysteine, aspargine, glutamine, histidine, tyrosine, tryptophan, and aspartic acid residues. Stability of peptides and protein needs to be considered when using APS/TEMED in in situ polymerization systems. The use of an alternative catalyst such as sodium bisulfite may preserve the chemical integrity of peptides during in situ polymerization.

  4. Mechanistic aspects of carotenoid biosynthesis

    KAUST Repository

    Moï se, Alexander R.; Al-Babili, Salim; Wurtzel, Eleanore T.

    2014-01-01

    precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A recently developed concept that could explain the role of the poly-cis pathway in carotenoid synthesis is that the intermediates of this pathway have additional physiological

  5. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    International Nuclear Information System (INIS)

    Li, Jason Z.; Ke, Yuebin; Misra, Hara P.; Trush, Michael A.; Li, Y. Robert; Zhu, Hong; Jia, Zhenquan

    2014-01-01

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  6. Mechanistic studies of cancer cell mitochondria- and NQO1-mediated redox activation of beta-lapachone, a potentially novel anticancer agent

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jason Z. [Virginia Tech CRC, Blacksburg, VA (United States); Ke, Yuebin [Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Misra, Hara P. [Virginia Tech CRC, Blacksburg, VA (United States); Trush, Michael A. [Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD (United States); Li, Y. Robert [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Virginia Tech-Wake Forest University SBES, Blacksburg, VA (United States); Department of Biology, University of North Carolina at Greensboro, NC (United States); Zhu, Hong, E-mail: zhu@campbell.edu [Campbell University School of Osteopathic Medicine, Buies Creek, NC (United States); Jia, Zhenquan, E-mail: z_jia@uncg.edu [Department of Biology, University of North Carolina at Greensboro, NC (United States)

    2014-12-15

    Beta-lapachone (beta-Lp) derived from the Lapacho tree is a potentially novel anticancer agent currently under clinical trials. Previous studies suggested that redox activation of beta-Lp catalyzed by NAD(P)H:quinone oxidoreductase 1 (NQO1) accounted for its killing of cancer cells. However, the exact mechanisms of this effect remain largely unknown. Using chemiluminescence and electron paramagnetic resonance (EPR) spin-trapping techniques, this study for the first time demonstrated the real-time formation of ROS in the redox activation of beta-lapachone from cancer cells mediated by mitochondria and NQO1 in melanoma B16–F10 and hepatocellular carcinoma HepG2 cancer cells. ES936, a highly selective NQO1 inhibitor, and rotenone, a selective inhibitor of mitochondrial electron transport chain (METC) complex I were found to significantly block beta-Lp meditated redox activation in B16–F10 cells. In HepG2 cells ES936 inhibited beta-Lp-mediated oxygen radical formation by ∼ 80% while rotenone exerted no significant effect. These results revealed the differential contribution of METC and NQO1 to beta-lapachone-induced ROS formation and cancer cell killing. In melanoma B16–F10 cells that do not express high NQO1 activity, both NOQ1 and METC play a critical role in beta-Lp redox activation. In contrast, in hepatocellular carcinoma HepG2 cells expressing extremely high NQO1 activity, redox activation of beta-Lp is primarily mediated by NQO1 (METC plays a minor role). These findings will contribute to our understanding of how cancer cells are selectively killed by beta-lapachone and increase our ability to devise strategies to enhance the anticancer efficacy of this potentially novel drug while minimizing its possible adverse effects on normal cells. - Highlights: • Both isolated mitochondria and purified NQO1 are able to generate ROS by beta-Lp. • The differential roles of mitochondria and NQO1 in mediating redox activation of beta-Lp • In cancer cells with

  7. Kinetic and Mechanistic Studies for the Gas-phase Reaction of Ozone with 2, 3-Dimethyl-2-Butene and 1, 3-Butadiene

    Directory of Open Access Journals (Sweden)

    Ismael Abdulsatar AL Mulla

    2017-09-01

    Full Text Available The reactions of ozone with 2,3-Dimethyl-2-Butene (CH32C=C(CH32 and 1,3-Butadiene CH2=CHCH=CH2 have been investigated under atmospheric conditions at 298±3K in air using both relative and absolute rate techniques, and the measured rate coefficients are found to be in good agreement in both techniques used. The obtained results show the addition of ozone to the double bond in these compounds and how it acts as function of the methyl group substituent situated on the double bond. The yields of all the main products have been determined using FTIR and GC-FID and the product studies of these reactions establish a very good idea for the decomposition pathways for the primary formed compounds (ozonides and give a good information for the effect of the methyl group on the degradation pathways. The results have been discussed from the view point of their importance in the atmospheric oxidation of these pollutants.

  8. Structural and mechanistic studies on β-hydroxydecanoly thioester dehydrase and its inhibition by the suicide substrate, 3-decynoic acid, n-acetylcysteamine thioester

    International Nuclear Information System (INIS)

    Li, W.B.

    1987-01-01

    β-Hydroxydecanoyl thioester dehydrase catalyzes the interconversion of thioesters of (R)-3-hydroxydecanoic acid, (E)-2-decenoic acid, and (Z)-3-decenoic acid. Dehydrase is irreversibly inactivated by the N-acetylcysteamine thioester of 3-decynoic acid (3-decynoyl-NAC). This is the classic example of suicide enzyme inactivation. The structure of the dehydrase-inactivator adduct is still unclear. The purpose of this thesis is to determine the structure of the inactivator moiety and the stoichiometry of the inactivation of this dimeric enzyme, as well as to conduct structural studies on dehydrase itself. 3-[2- 13 C]Decynoyl-NAC was synthesized and incubated with homogeneous dehydrase. The spectra showed that dehydrase adds to the inactivator so as to quickly produce an (E)-3-(N/sup im/-histidinyl)-3-decenoyl thioester adduct at the active site. This species is slowly converted to the 2-decenoyl thioester congener. Titration of dehydrase with 3-[2 13 C]decynoyl-NAC under these conditions clearly indicated that 2 moles of inactivator are bound to each mole of dehydrase dimer. These experiments provide a self-consistent picture of dehydrase inactivation by 3-decynoyl-NAC and normal dehydrase-catalyzed reactions. Dehydrase was cleaved by chemical fragmentation, and the resulting mixture of peptides were separated by reversed-phase HPLC. Partial N-terminal sequences of purified peptides were obtained by automated Edman technology

  9. Synthetic and mechanistic study of oxycarbene-like coupling reaction patterns of actinide eta2-acyl complexes with carbon monoxide and isocyanides

    International Nuclear Information System (INIS)

    Moloy, K.G.; Fagan, P.J.; Manriquez, J.M.; Marks, T.J.

    1986-01-01

    This contribution reports the synthesis and characterization of the ylide complexes Cp' 2 Th[OC(CH 2 -t-Bu)C-(PR 3 )O[(Cl) (Cp' = eta 5 -C 5 Me 5 ; R = Me, Ph) formed by the carbonylation of Cp' 2 Th(Cl)(eta 2 -COCH 2 -t-Bu) (1) in the presence of phosphines. Isotopic tracer studies with 13 CO indicate that the labeled carbon atom is incorporated regiospecifically at the ylide α-carbon atom position. The carbonylation of 1 to yield the enedionediolate (Cp' 2 Th[OC(CH 2 -t-Bu)CO](Cl)] 2 (2) or the ylide complexes was found to obey a second-order rate law where rate = kP/sub CO/[1]; k = 1.50 (5) x 10 -5 min -1 torr -1 for both carbonylations at 30.8 0 C. The rate of formation of the ylide complexes was also found to be independent of solvent, phosphine concentration, and type of phosphine used. The carbonylation of 1 is therefore inferred to involve a rate-determining coupling of CO with the acyl to yield an intermediate ketene or ketene-like complex. 51 references, 4 figures, 3 tables

  10. Unravelling Mechanistic Aspects of the Gas-Phase Ethanol Conversion: An Experimental and Computational Study on the Thermal Reactions of MO2 (+) (M=Mo, W) with Ethanol.

    Science.gov (United States)

    González-Navarrete, Patricio; Schlangen, Maria; Wu, Xiao-Nan; Schwarz, Helmut

    2016-02-24

    The ion/molecule reactions of molybdenum and tungsten dioxide cations with ethanol have been studied by Fourier transform ion-cyclotron resonance mass spectrometry (FT-ICR MS) and density functional theory (DFT) calculations. Dehydration of ethanol has been found as the dominant reaction channel, while generation of the ethyl cation corresponds to a minor product. Cleary, the reactions are mainly governed by the Lewis acidity of the metal center. Computational results, together with isotopic labeling experiments, show that the dehydration of ethanol can proceed either through a conventional concerted [1,2]-elimination mechanism or a step-wise process; the latter occurs via a hydroxyethoxy intermediate. Formation of C2 H5 (+) takes place by transfer of OH(-) from ethanol to the metal center of MO2 (+) . The molybdenum and tungsten dioxide cations exhibit comparable reactivities toward ethanol, and this is reflected in similar reaction rate constants and branching ratios. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Mechanistic study on the nuclear modifier gene MSS1 mutation suppressing neomycin sensitivity of the mitochondrial 15S rRNA C1477G mutation in Saccharomyces cerevisiae.

    Science.gov (United States)

    Zhou, Qiyin; Wang, Wei; He, Xiangyu; Zhu, Xiaoyu; Shen, Yaoyao; Yu, Zhe; Wang, Xuexiang; Qi, Xuchen; Zhang, Xuan; Fan, Mingjie; Dai, Yu; Yang, Shuxu; Yan, Qingfeng

    2014-01-01

    The phenotypic manifestation of mitochondrial DNA (mtDNA) mutations can be modulated by nuclear genes and environmental factors. However, neither the interaction among these factors nor their underlying mechanisms are well understood. The yeast Saccharomyces cerevisiae mtDNA 15S rRNA C1477G mutation (PR) corresponds to the human 12S rRNA A1555G mutation. Here we report that a nuclear modifier gene mss1 mutation suppresses the neomycin-sensitivity phenotype of a yeast C1477G mutant in fermentable YPD medium. Functional assays show that the mitochondrial function of the yeast C1477G mutant was impaired severely in YPD medium with neomycin. Moreover, the mss1 mutation led to a significant increase in the steady-state level of HAP5 (heme activated protein), which greatly up-regulated the expression of glycolytic transcription factors RAP1, GCR1, and GCR2 and thus stimulated glycolysis. Furthermore, the high expression of the key glycolytic enzyme genes HXK2, PFK1 and PYK1 indicated that enhanced glycolysis not only compensated for the ATP reduction from oxidative phosphorylation (OXPHOS) in mitochondria, but also ensured the growth of the mss1(PR) mutant in YPD medium with neomycin. This study advances our understanding of the phenotypic manifestation of mtDNA mutations.

  12. Anti-dermatophytic activity of bakuchiol: in vitro mechanistic studies and in vivo tinea pedis-inhibiting activity in a guinea pig model.

    Science.gov (United States)

    Lau, Kit-Man; Wong, Jack Ho; Wu, Yu-On; Cheng, Ling; Wong, Chun-Wai; To, Ming-Ho; Lau, Ching-Po; Yew, David Tai-Wai; Leung, Ping-Chung; Fung, Kwok-Pui; Hui, Mamie; Ng, Tzi-Bun; Lau, Clara Bik-San

    2014-06-15

    Bakuchiol was an active antifungal compound isolated from Psoraleae Fructus by means of bioassay-guided fractionation in our previous study. The present work aimed to investigate the underlying mechanisms and the therapeutic effect of bakuchiol in Trichophyton mentagrophytes-induced tinea pedis. After exposure to bakuchiol at 0.25-fold, 0.5-fold and 1-fold of minimum inhibitory concentration (MIC) (3.91 μg/ml) for 24h, the fungal conidia of T. mentagrophytes demonstrated a significant dose-dependent increase in membrane permeability. Moreover, bakuchiol at 1-fold MIC elicited a 187% elevation in reactive oxygen species (ROS) level in fungal cells after a 3-h incubation. However, bakuchiol did not induce DNA fragmentation. In a guinea pig model of tinea pedis, bakuchiol at 1%, 5% or 10% (w/w) concentration in aqueous cream could significantly reduce the fungal burden of infected feet (p<0.01-0.05). In conclusion, this is the first report to demonstrate that bakuchiol is effective in relieving tinea pedis and in inhibiting the growth of the dermatophyte T. mentagrophytes by increasing fungal membrane permeability and ROS generation, but not via induction of DNA fragmentation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Mechanistic and Structural Studies of Protein-Only RNase P Compared to Ribonucleoproteins Reveal the Two Faces of the Same Enzymatic Activity

    Directory of Open Access Journals (Sweden)

    Cédric Schelcher

    2016-06-01

    Full Text Available RNase P, the essential activity that performs the 5′ maturation of tRNA precursors, can be achieved either by ribonucleoproteins containing a ribozyme present in the three domains of life or by protein-only enzymes called protein-only RNase P (PRORP that occur in eukaryote nuclei and organelles. A fast growing list of studies has investigated three-dimensional structures and mode of action of PRORP proteins. Results suggest that similar to ribozymes, PRORP proteins have two main domains. A clear functional analogy can be drawn between the specificity domain of the RNase P ribozyme and PRORP pentatricopeptide repeat domain, and between the ribozyme catalytic domain and PRORP N4BP1, YacP-like Nuclease domain. Moreover, both types of enzymes appear to dock with the acceptor arm of tRNA precursors and make specific contacts with the corner of pre-tRNAs. While some clear differences can still be delineated between PRORP and ribonucleoprotein (RNP RNase P, the two types of enzymes seem to use, fundamentally, the same catalytic mechanism involving two metal ions. The occurrence of PRORP and RNP RNase P represents a remarkable example of convergent evolution. It might be the unique witness of an ongoing replacement of catalytic RNAs by proteins for enzymatic activities.

  14. Oxidation of 3,4,5-trimethoxybenzaldehyde by pyridinium fluorochromate in N,N-dimethyl formamide medium: A kinetic and mechanistic study

    Directory of Open Access Journals (Sweden)

    Basanti Lal Hiran

    2016-09-01

    Full Text Available Kinetics of oxidation of 3,4,5-trimethoxybenzaldehyde (TMBA by pyridinium fluorochromate (PFC in N,N-dimethyl formamide (DMF medium in the presence of toluene para-sulfonic acid (TsOH has been studied. The reaction is first order each in [PFC], [TMBA] and [TsOH]. The rate of oxidation remains unaltered by the variation of NaClO4 but addition of MnSO4 decreases the rate. The effects of the dielectric constant of the medium and the ionic strength indicate the reaction to be of ion–dipole type. The stoichiometry of the reaction is 1:1 and the product of oxidation is the corresponding 3,4,5-trimethoxybenzoic acid and Cr(III. The reaction rates have been determined at different temperatures and the activation parameters were calculated. The reaction failed to induce the polymerization of acrylonitrile, i.e., absence of free radicals. A suitable mechanism involving the slow formation of an unstable chromate ester and a rate law has been proposed.

  15. Mechanistic studies of the oxidation of soluble species of ruthenium in nitric acid solutions. Application to the removal of ruthenium from nuclear fuel dissolution solutions

    International Nuclear Information System (INIS)

    Carron, V.

    2001-01-01

    Ruthenium is one of the most troublesome fission products during nuclear fuel reprocessing. His removal from nitric acid fuel dissolution solutions, above the PUREX process, is under consideration. Electro-volatilization could be a possible way to eliminate this element. It consists in the oxidation of soluble ruthenium species coupled with the volatilization of formed RuO 4 . Soluble species are nitrate and nitro complexes of nitrosyl ruthenium RuNO 3+ . The first part of this work deals with the direct oxidation of RuNO 3+ at a golden or a platinum anode. It has been investigated by cyclic voltammetry and infrared and UV-visible reflectance spectroscopy. The oxidation of RuNO 3+ begins with an adsorption step, which precedes the formation of RuO 4 . Then a reaction between RuO 4 and RuNO 3+ occurs to produce a Ru IV compound, which is also electro-oxidized to RuO 4 . The second part concerns potentiostatic electro-volatilization experiences. The rate of electro-volatilization decreases with increasing HNO 3 concentration. At low concentrations, kinetic is controlled by the volatilization of RuO 4 . The rate-determining step is the oxidation of RuNO 3+ at concentrations higher than 1 M. In HNO 3 4 M, the addition of AgNO 3 is required to accelerate the oxidation of RuNO 3+ . The last part is devoted to the study of the indirect oxidation of RuNO 3+ . The electrocatalytic power of electro-generated Ag II is illustrated by voltammetric techniques and potentiostatic electrolysis. The existence of a limit concentration of AgNO 3 is shown (which value depends on experimental conditions) beyond which kinetic is controlled by the RuO 4 volatilization step. These results indicate that the electro-volatilization kinetic could be increased by optimizing the volatilization conditions. (author)

  16. Gigantol from Dendrobium chrysotoxum Lindl. binds and inhibits aldose reductase gene to exert its anti-cataract activity: An in vitro mechanistic study.

    Science.gov (United States)

    Wu, Jie; Li, Xue; Wan, Wencheng; Yang, Qiaohong; Ma, Weifeng; Chen, Dan; Hu, Jiangmiao; Chen, C-Y Oliver; Wei, Xiaoyong

    2017-02-23

    Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as "Shihu" or "Huangcao". D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties. To characterize the interaction between gigantol extracted from D. chrysotoxum Lindl and the AR gene, and determine gigantol's efficacy against cataractogenesis. Human lens epithelial cells (HLECs) were induced by glucose as the model group. Reverse transcription polymerase chain reaction (RT-PCR) was used to assess AR gene expression. Then, the mode of interaction of gigantol with the AR gene was evaluated by UV-visible spectroscopy, atomic force microscope (AFM) and surface-enhanced Raman spectroscopy (SERS). The binding constant was determined by UV-visible. Gigantol depressed AR gene expression in HLECs. UV-visible spectra preliminarily indicated that interaction between the AR gene and gigantol may follow the groove mode, with a binding constant of 1.85×10 3 L/mol. Atomic force microscope (AFM) data indicated that gigantol possibly bound to insert AR gene base pairs of the double helix. Surface-enhanced Raman spectroscopy (SERS) studies further supported these observations. Gigantol extracted from D. chrysotoxum Lindl not only has inhibitory effects on aldose reductase, but also inhibits AR gene expression. These findings provide a more comprehensive theoretical basis for the use of Dendrobium for the treatment of diabetic cataract. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  17. Mechanistic studies of mercury adsorption and oxidation by oxygen over spinel-type MnFe{sub 2}O{sub 4}

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yingju [State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Liu, Jing, E-mail: liujing27@mail.hust.edu.cn [State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China); Shenzhen Institute of Huazhong University of Science and Technology, Shenzhen 518000 (China); Zhang, Bingkai; Liu, Feng [State Key Laboratory of Coal Combustion, School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2017-01-05

    Highlights: • Hg adsorption and oxidation mechanisms on MnFe{sub 2}O{sub 4} were studied using DFT method. • Hg{sup 0} adsorption on Mn-terminated MnFe{sub 2}O{sub 4} (100) surface is a chemisorption process. • HgO shows high chemical reactivity for its adsorption on MnFe{sub 2}O{sub 4} surface. • The reaction between adsorbed Hg and surface oxygen is the rate-determining step. - Abstract: MnFe{sub 2}O{sub 4} has been regarded as a very promising sorbent for mercury emission control in coal-fired power plants because of its high adsorption capacity, magnetic, recyclable and regenerable properties. First-principle calculations based on density functional theory (DFT) were used to elucidate the mercury adsorption and oxidation mechanisms on MnFe{sub 2}O{sub 4} surface. DFT calculations show that Mn-terminated MnFe{sub 2}O{sub 4} (1 0 0) surface is much more stable than Fe-terminated surface. Hg{sup 0} is physically adsorbed on Fe-terminated MnFe{sub 2}O{sub 4} (1 0 0) surface. Hg{sup 0} adsorption on Mn-terminated MnFe{sub 2}O{sub 4} (1 0 0) surface is a chemisorption process. The partial density of states (PDOS) analysis indicates that Hg atom interacts strongly with surface Mn atoms through the orbital hybridization. HgO is adsorbed on the MnFe{sub 2}O{sub 4} surface in a chemical adsorption manner. The small HOMO–LUMO energy gap implies that HgO molecular shows high chemical reactivity for HgO adsorption on MnFe{sub 2}O{sub 4} surface. The energy barriers of Hg{sup 0} oxidation by oxygen on Fe- and Mn-terminated MnFe{sub 2}O{sub 4} surfaces are 206.37 and 76.07 kJ/mol, respectively. Mn-terminated surface is much more favorable for Hg{sup 0} oxidation than Fe-terminated surface. In the whole Hg{sup 0} oxidation process, the reaction between adsorbed mercury and surface oxygen is the rate-determining step.

  18. Existing pavement input information for the mechanistic-empirical pavement design guide.

    Science.gov (United States)

    2009-02-01

    The objective of this study is to systematically evaluate the Iowa Department of Transportations (DOTs) existing Pavement Management Information System (PMIS) with respect to the input information required for Mechanistic-Empirical Pavement Des...

  19. Rapid Discrimination Among Putative Mechanistic Models of Biochemical Systems.

    Science.gov (United States)

    Lomnitz, Jason G; Savageau, Michael A

    2016-08-31

    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.

  20. Testing mechanistic models of growth in insects.

    Science.gov (United States)

    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. © 2015 The Author(s).

  1. Mechanistic model for microbial growth on hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Mallee, F M; Blanch, H W

    1977-12-01

    Based on available information describing the transport and consumption of insoluble alkanes, a mechanistic model is proposed for microbial growth on hydrocarbons. The model describes the atypical growth kinetics observed, and has implications in the design of large scale equipment for single cell protein (SCP) manufacture from hydrocarbons. The model presents a framework for comparison of the previously published experimental kinetic data.

  2. Mechanistic studies of plasma polymerization of allylamine

    Czech Academy of Sciences Publication Activity Database

    Chourkov, A.; Biederman, H.; Slavinská, D.; Hanley, L.; Macková, Anna; Grinevich, A.; Boldryeva, H.

    2005-01-01

    Roč. 109, č. 48 (2005), s. 23086-23095 ISSN 1520-6106 Institutional research plan: CEZ:AV0Z10480505 Keywords : quartz-crystal microbalance * atomic-force microscopy * guide mode spectroscopy Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 4.033, year: 2005

  3. Electrocatalytic carbon dioxide reduction - a mechanistic study

    NARCIS (Netherlands)

    Schouten, Klaas Jan Schouten

    2013-01-01

    This thesis presents new insights into the reduction of carbon dioxide to methane and ethylene on copper electrodes. This electrochemical process has great potential for the storage of surplus renewable electrical energy in the form of hydrocarbons. The research described in this thesis focuses on

  4. Mechanistic Study of Monodisperse Iron Oxide Nanocrystals ...

    African Journals Online (AJOL)

    To gain better insight into the formation of iron oxide nanocrystals from the solution phase thermal decomposition of iron (III) oleate complex, different reaction conditions including time, heating ramp, as well as concentrations of iron oleate precursor and oleic acid ligand were systematically varied and the resulting ...

  5. Mechanistic modeling analysis of micro-evolutive responses from a Caenorhabditis elegans population exposed to a radioactive metallic stress

    International Nuclear Information System (INIS)

    Goussen, Benoit

    2013-01-01

    The evolution of toxic effects at a relevant scale is an important challenge for the ecosystem protection. Indeed, pollutants may impact populations over long-term and represent a new evolutionary force which can be adding itself to the natural selection forces. Thereby, it is necessary to acquire knowledge on the phenotypics and genetics changes that may appear in populations submitted to stress over several generations. Usually statistical analyses are performed to analyse such multi-generational studies. The use of a mechanistic mathematical model may provide a way to fully understand the impact of pollutants on the populations' dynamics. Such kind of model allows the integration of biological and toxic processes into the analysis of eco-toxicological data and the assessment of interactions between these processes. The aim of this Ph.D. project was to assess the contributions of the mechanistic modelling to the analysis of evolutionary experiment assessing long-term exposure. To do so, a three step strategy has been developed. Foremost, a multi-generational study was performed to assess the evolution of two populations of the ubiquitous nematode Caenorhabditis elegans in control conditions or exposed to 1.1 mM of uranium. Several generations were selected to assess growth, reproduction, and dose-responses relationships, through exposure to a range of concentrations (from 0 to 1.2 mM U) with all endpoints measured daily. A first statistical analysis was then performed. In a second step, a bio-energetic model adapted to the assessment of eco-toxicological data (DEBtox) was developed on C. elegans. Its numerical behaviour was analysed. Finally, this model was applied to all the selected generations in order to infer parameters values for the two populations and to assess their evolutions. Results highlighted an impact of the uranium starting from 0.4 mM U on both C. elegans' growth and reproduction. Results from the mechanistic analysis indicate this effect is due

  6. Evaluation of mechanistic DNB models using HCLWR CHF data

    International Nuclear Information System (INIS)

    Iwamura, Takamichi; Watanabe, Hironori; Okubo, Tsutomu; Araya, Fumimasa; Murao, Yoshio.

    1992-03-01

    An onset of departure from nucleate boiling (DNB) in light water reactor (LWR) has been generally predicted with empirical correlations. Since these correlations have less physical bases and contain adjustable empirical constants determined by best fitting of test data, applicable geometries and flow conditions are limited within the original experiment ranges. In order to obtain more universal prediction method, several mechanistic DNB models based on physical approaches have been proposed in recent years. However, the predictive capabilities of mechanistic DNB models have not been verified successfully especially for advanced LWR design purposes. In this report, typical DNB mechanistic models are reviewed and compared with critical heat flux (CHF) data for high conversion light water reactor (HCLWR). The experiments were performed using triangular 7-rods array with non-uniform axial heat flux distribution. Test pressure was 16 MPa, mass velocities ranged from 800 t0 3100 kg/s·m 2 and exit qualities from -0.07 to 0.19. The evaluated models are: 1) Wisman-Pei, 2) Chang-Lee, 3) Lee-Mudawwar, 4) Lin-Lee-Pei, and 5) Katto. The first two models are based on near-wall bubble crowding model and the other three models on sublayer dryout model. The comparison with experimental data indicated that the Weisman-Pei model agreed relatively well with the CHF data. Effects of empirical constants in each model on CHF calculation were clarified by sensitivity studies. It was also found that the magnitudes of physical quantities obtained in the course of calculation were significantly different for each model. Therefore, microscopic observation of the onset of DNB on heated surface is essential to clarify the DNB mechanism and establish a general DNB mechanistic model based on physical phenomenon. (author)

  7. Mechanistic CHF modeling for natural circulation applications in SMR

    Energy Technology Data Exchange (ETDEWEB)

    Luitjens, Jeffrey [Department of Nuclear Engineering and Radiation Health Physics, Oregon State University, 3451 SW Jefferson Way, Corvallis, OR 97331 (United States); Wu, Qiao, E-mail: qiao.wu@oregonstate.edu [Department of Nuclear Engineering and Radiation Health Physics, Oregon State University, 3451 SW Jefferson Way, Corvallis, OR 97331 (United States); Greenwood, Scott; Corradini, Michael [Department of Engineering Physics, University of Wisconsin, 1415 Engineering Drive, Madison, WI 53706 (United States)

    2016-12-15

    A mechanistic critical heat flux correlation has been developed for a wide range of operating conditions which include low mass fluxes of 540–890 kg/m{sup 2}-s, high pressures of 12–13 MPa, and critical heat fluxes of 835–1100 kW/m{sup 2}. Eleven experimental data points have been collected over these conditions to inform the development of the model using bundle geometry. Errors of within 15% have been obtained with the proposed model for predicting the critical heat flux value, location, and critical pin power for a non-uniform heat flux applied to a 2 × 2 bundle configuration.

  8. A metabonomic approach for mechanistic exploration of pre-clinical toxicology.

    Science.gov (United States)

    Coen, Muireann

    2010-12-30

    Metabonomics involves the application of advanced analytical tools to profile the diverse metabolic complement of a given biofluid or tissue. Subsequent statistical modelling of the complex multivariate spectral profiles enables discrimination between phenotypes of interest and identifies panels of discriminatory metabolites that represent candidate biomarkers. This review article presents an overview of recent developments in the field of metabonomics with a focus on application to pre-clinical toxicology studies. Recent research investigations carried out as part of the international COMET 2 consortium project on the hepatotoxic action of the aminosugar, galactosamine (galN) are presented. The application of advanced, high-field NMR spectroscopy is demonstrated, together with complementary application of a targeted mass spectrometry platform coupled with ultra-performance liquid chromatography. Much novel mechanistic information has been gleaned on both the mechanism of galN hepatotoxicity in multiple biofluids and tissues, and on the protection afforded by co-administration of glycine and uridine. The simultaneous identification of both the metabolic fate of galN and its associated endogenous consequences in spectral profiles is demonstrated. Furthermore, metabonomic assessment of inter-animal variability in response to galN presents enhanced mechanistic insight on variable response phentoypes and is relevant to understanding wider aspects of individual variability in drug response. This exemplar highlights the analytical and statistical tools commonly applied in metabonomic studies and notably, the approach is applicable to the study of any toxin/drug or intervention of interest. The metabonomic approach holds considerable promise and potential to significantly advance our understanding of the mechanistic bases for adverse drug reactions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  9. Mechanistic modeling for mammography screening risks

    International Nuclear Information System (INIS)

    Bijwaard, Harmen

    2008-01-01

    Full text: Western populations show a very high incidence of breast cancer and in many countries mammography screening programs have been set up for the early detection of these cancers. Through these programs large numbers of women (in the Netherlands, 700.000 per year) are exposed to low but not insignificant X-ray doses. ICRP based risk estimates indicate that the number of breast cancer casualties due to mammography screening can be as high as 50 in the Netherlands per year. The number of lives saved is estimated to be much higher, but for an accurate calculation of the benefits of screening a better estimate of these risks is indispensable. Here it is attempted to better quantify the radiological risks of mammography screening through the application of a biologically based model for breast tumor induction by X-rays. The model is applied to data obtained from the National Institutes of Health in the U.S. These concern epidemiological data of female TB patients who received high X-ray breast doses in the period 1930-1950 through frequent fluoroscopy of their lungs. The mechanistic model that is used to describe the increased breast cancer incidence is based on an earlier study by Moolgavkar et al. (1980), in which the natural background incidence of breast cancer was modeled. The model allows for a more sophisticated extrapolation of risks to the low dose X-ray exposures that are common in mammography screening and to the higher ages that are usually involved. Furthermore, it allows for risk transfer to other (non-western) populations. The results have implications for decisions on the frequency of screening, the number of mammograms taken at each screening, minimum and maximum ages for screening and the transfer to digital equipment. (author)

  10. Adsorption of Cd(II) by Mg–Al–CO{sub 3}- and magnetic Fe{sub 3}O{sub 4}/Mg–Al–CO{sub 3}-layered double hydroxides: Kinetic, isothermal, thermodynamic and mechanistic studies

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Ran-ran; Yan, Liang-guo, E-mail: yanyu-33@163.com; Yang, Kun; Hao, Yuan-feng; Du, Bin

    2015-12-15

    Highlights: • The Mg–Al–CO{sub 3}- and magnetic Fe{sub 3}O{sub 4}/Mg–Al–CO{sub 3}–LDH can efficiently remove Cd(II) from aqueous solutions. • The adsorption mechanisms of Cd(II) were discussed in detail. • The adsorption kinetic, isothermal and thermodynamic properties of Cd(II) were studied. • Magnetic Fe{sub 3}O{sub 4}/Mg–Al–CO{sub 3}–LDH can be quickly and easily separated using a magnet. - Abstract: Understanding the adsorption mechanisms of metal cations on the surfaces of solids is important for determining the fate of these metals in water and wastewater treatment. The adsorption kinetic, isothermal, thermodynamic and mechanistic properties of cadmium (Cd(II)) in an aqueous solution containing Mg–Al–CO{sub 3}- and magnetic Fe{sub 3}O{sub 4}/Mg–Al–CO{sub 3}-layered double hydroxide (LDH) were studied. The results demonstrated that the adsorption kinetic and isotherm data followed the pseudo-second-order model and the Langmuir equation, respectively. The adsorption process of Cd(II) was feasible, spontaneous and endothermic in nature. X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy were used to explain the adsorption mechanisms. The characteristic XRD peaks and FTIR bands of CdCO{sub 3} emerged in the LDH spectra after Cd(II) adsorption, which indicated that the adsorption of Cd(II) by LDHs occurred mainly via CdCO{sub 3} precipitation, surface adsorption and surface complexation. Furthermore, the magnetic Fe{sub 3}O{sub 4}/Mg–Al–CO{sub 3}-LDH can be quickly and easily separated using a magnet before and after the adsorption process.

  11. Mechanistic aspects of carotenoid biosynthesis

    KAUST Repository

    Moïse, Alexander R.

    2014-01-08

    Carotenoid synthesis is based on the analysis of the phenotype of several mutant strains of tomato lacking carotenoid synthetic genes. Carotenoids are tetraterpenes derived through the condensation of the five-carbon (C5) universal isoprenoid precursors isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A recently developed concept that could explain the role of the poly-cis pathway in carotenoid synthesis is that the intermediates of this pathway have additional physiological roles that extend beyond serving as precursors of lycopene. This concept is based on the analysis of the phenotype of several mutant strains of tomato lacking carotenoid synthetic genes. The feedback regulation of early carotenoid synthetic genes in response to a block in upstream metabolism represents a paradigm shift in our understanding of the mechanism and regulation of carotenoid synthesis and of metabolic regulation in general. The molecular details of a signaling pathway that regulates carotenogenesis in response to the levels of carotenoid precursors are still unclear.

  12. Numerical simulation in steam injection wellbores by mechanistic approach; Simulacao numerica do escoamento de vapor em pocos por uma abordagem mecanicista

    Energy Technology Data Exchange (ETDEWEB)

    Souza Junior, J.C. de; Campos, W.; Lopes, D.; Moura, L.S.S. [PETROBRAS, Rio de Janeiro, RJ (Brazil); Thomas, A. Clecio F. [Universidade Estadual do Ceara (UECE), CE (Brazil)

    2008-07-01

    This work addresses to the development of a hydrodynamic and heat transfer mechanistic model for steam flow in injection wellbores. The problem of two-phase steam flow in wellbores has been solved recently by using available empirical correlations from petroleum industry (Lopes, 1986) and nuclear industry (Moura, 1991).The good performance achieved by mechanistic models developed by Ansari (1994), Hasan (1995), Gomez (2000) and Kaya (2001) supports the importance of the mechanistic approach for the steam flow problem in injection wellbores. In this study, the methodology to solve the problem consists in the application of a numerical method to the governing equations of steam flow and a marching algorithm to determine the distribution of the pressure and temperature along the wellbore. So, a computer code has been formulated to get numerical results, which provides a comparative study to the main models found in the literature. Finally, when compared to available field data, the mechanistic model for downward vertical steam flow in wellbores gave better results than the empirical correlations. (author)

  13. Mechanistic species distribution modeling reveals a niche shift during invasion.

    Science.gov (United States)

    Chapman, Daniel S; Scalone, Romain; Štefanić, Edita; Bullock, James M

    2017-06-01

    Niche shifts of nonnative plants can occur when they colonize novel climatic conditions. However, the mechanistic basis for niche shifts during invasion is poorly understood and has rarely been captured within species distribution models. We quantified the consequence of between-population variation in phenology for invasion of common ragweed (Ambrosia artemisiifolia L.) across Europe. Ragweed is of serious concern because of its harmful effects as a crop weed and because of its impact on public health as a major aeroallergen. We developed a forward mechanistic species distribution model based on responses of ragweed development rates to temperature and photoperiod. The model was parameterized and validated from the literature and by reanalyzing data from a reciprocal common garden experiment in which native and invasive populations were grown within and beyond the current invaded range. It could therefore accommodate between-population variation in the physiological requirements for flowering, and predict the potentially invaded ranges of individual populations. Northern-origin populations that were established outside the generally accepted climate envelope of the species had lower thermal requirements for bud development, suggesting local adaptation of phenology had occurred during the invasion. The model predicts that this will extend the potentially invaded range northward and increase the average suitability across Europe by 90% in the current climate and 20% in the future climate. Therefore, trait variation observed at the population scale can trigger a climatic niche shift at the biogeographic scale. For ragweed, earlier flowering phenology in established northern populations could allow the species to spread beyond its current invasive range, substantially increasing its risk to agriculture and public health. Mechanistic species distribution models offer the possibility to represent niche shifts by varying the traits and niche responses of individual

  14. Mechanistic Insight into the Dehydro-Diels-Alder Reaction of Styrene-Ynes.

    Science.gov (United States)

    Kocsis, Laura S; Kagalwala, Husain N; Mutto, Sharlene; Godugu, Bhaskar; Bernhard, Stefan; Tantillo, Dean J; Brummond, Kay M

    2015-12-04

    The Diels-Alder reaction represents one of the most thoroughly studied and well-understood synthetic transformations for the assembly of six-membered rings. Although intramolecular dehydro-Diels-Alder (IMDDA) reactions have previously been employed for the preparation of naphthalene and dihydronaphthalene substrates, low yields and product mixtures have reduced the impact and scope of this reaction. Through the mechanistic studies described within, we have confirmed that the thermal IMDDA reaction of styrene-ynes produces a naphthalene product via loss of hydrogen gas from the initially formed cycloadduct, a tetraenyl intermediate. Alternatively, the dihydronaphthalene product is afforded from the same tetraenyl intermediate via a radical isomerization process. Moreover, we have identified conditions that can be used to achieve efficient, high-yielding, and selective IMDDA reactions of styrene-ynes to form either naphthalene or dihydronaphthalene products. The operational simplicity and retrosynthetic orthogonality of this method for the preparation of naphthalenes and dihydronaphthalenes makes this transformation appealing for the synthesis of medicinal and material targets. The mechanistic studies within may impact the development of other thermal transformations.

  15. Application of mechanistic empirical approach to predict rutting of superpave mixtures in Iraq

    Directory of Open Access Journals (Sweden)

    Qasim Zaynab

    2018-01-01

    Full Text Available In Iraq rutting is considered as a real distress in flexible pavements as a result of high summer temperature, and increased axle loads. This distress majorly affects asphalt pavement performance, lessens the pavement useful service life and makes serious hazards for highway users. Performance of HMA mixtures against rutting using Mechanistic- Empirical approach is predicted by considering Wheel-Tracking test and employing the Superpave mix design requirements. Roller Wheel Compactor has been locally manufactured to prepare slab specimens. In view of study laboratory outcomes that are judged to be simulative of field loading conditions, models are developed for predicting permanent strain of compacted samples of local asphalt concrete mixtures after considering the stress level, properties of local material and environmental impacts variables. All in all, laboratory results were produced utilizing statistical analysis with the aid of SPSS software. Permanent strain models for asphalt concrete mixtures were developed as a function of: number of passes, temperature, asphalt content, viscosity, air voids and additive content. Mechanistic Empirical design approach through the MnPAVE software was applied to characterize rutting in HMA and to predict allowable number of loading repetitions of mixtures as a function of expected traffic loads, material properties, and environmental temperature.

  16. Simulating the Risk of Liver Fluke Infection using a Mechanistic Hydro-epidemiological Model

    Science.gov (United States)

    Beltrame, Ludovica; Dunne, Toby; Rose, Hannah; Walker, Josephine; Morgan, Eric; Vickerman, Peter; Wagener, Thorsten

    2016-04-01

    Liver Fluke (Fasciola hepatica) is a common parasite found in livestock and responsible for considerable economic losses throughout the world. Risk of infection is strongly influenced by climatic and hydrological conditions, which characterise the host environment for parasite development and transmission. Despite on-going control efforts, increases in fluke outbreaks have been reported in recent years in the UK, and have been often attributed to climate change. Currently used fluke risk models are based on empirical relationships derived between historical climate and incidence data. However, hydro-climate conditions are becoming increasingly non-stationary due to climate change and direct anthropogenic impacts such as land use change, making empirical models unsuitable for simulating future risk. In this study we introduce a mechanistic hydro-epidemiological model for Liver Fluke, which explicitly simulates habitat suitability for disease development in space and time, representing the parasite life cycle in connection with key environmental conditions. The model is used to assess patterns of Liver Fluke risk for two catchments in the UK under current and potential future climate conditions. Comparisons are made with a widely used empirical model employing different datasets, including data from regional veterinary laboratories. Results suggest that mechanistic models can achieve adequate predictive ability and support adaptive fluke control strategies under climate change scenarios.

  17. Ghana Journal of Development Studies

    African Journals Online (AJOL)

    Ghana Journal of Development Studies (GJDS) is a multi-, trans- and an ... The Political Economy of Decentralisation and the Challenge of Improved Service Delivery ... Tax Collection in Northern Ghana during British Colonail Rule (1898 – 1950) ... District of South Africa · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

  18. A mechanistic nitrogen limitation model for CLM(ED)

    Science.gov (United States)

    Ali, A. A.; Xu, C.; McDowell, N. G.; Rogers, A.; Wullschleger, S. D.; Fisher, R.; Vrugt, J. A.

    2014-12-01

    Photosynthetic capacity is a key plant trait that determines the rate of photosynthesis; however, in Earth System Models it is either a fixed value or derived from a linear function of leaf nitrogen content. A mechanistic leaf nitrogen allocation model have been developed for a DOE-sponsored Community Land Model coupled to the Ecosystem Demography model (CLM-ED) to predict the photosynthetic capacity [Vc,max25 (μmol CO2 m-2 s-1)] under different environmental conditions at the global scale. We collected more than 800 data points of photosynthetic capacity (Vc,max25) for 124 species from 57 studies with the corresponding leaf nitrogen content and environmental conditions (temperature, radiation, humidity and day length) from literature and the NGEE arctic site (Barrow). Based on the data, we found that environmental control of Vc,max25 is about 4 times stronger than the leaf nitrogen content. Using the Markov-Chain Monte Carlo simulation approach, we fitted the collected data to our newly developed nitrogen allocation model, which predict the leaf nitrogen investment in different components including structure, storage, respiration, light capture, carboxylation and electron transport at different environmental conditions. Our results showed that our nitrogen allocation model explained 52% of variance in observed Vc,max25 and 65% variance in observed Jmax25 using a single set of fitted model parameters for all species. Across the growing season, we found that the modeled Vc,max25 explained 49% of the variability in measured Vc,max25. In the context of future global warming, our model predicts that a temperature increase by 5oC and the doubling of atmospheric carbon dioxide reduced the Vc,max25 by 5%, 11%, respectively.

  19. Comparison of Two-Phase Pipe Flow in OpenFOAM with a Mechanistic Model

    International Nuclear Information System (INIS)

    Shuard, Adrian M; Mahmud, Hisham B; King, Andrew J

    2016-01-01

    Two-phase pipe flow is a common occurrence in many industrial applications such as power generation and oil and gas transportation. Accurate prediction of liquid holdup and pressure drop is of vast importance to ensure effective design and operation of fluid transport systems. In this paper, a Computational Fluid Dynamics (CFD) study of a two-phase flow of air and water is performed using OpenFOAM. The two-phase solver, interFoam is used to identify flow patterns and generate values of liquid holdup and pressure drop, which are compared to results obtained from a two-phase mechanistic model developed by Petalas and Aziz (2002). A total of 60 simulations have been performed at three separate pipe inclinations of 0°, +10° and -10° respectively. A three dimensional, 0.052m diameter pipe of 4m length is used with the Shear Stress Transport (SST) k - ω turbulence model to solve the turbulent mixtures of air and water. Results show that the flow pattern behaviour and numerical values of liquid holdup and pressure drop compare reasonably well to the mechanistic model. (paper)

  20. Comparison of Two-Phase Pipe Flow in OpenFOAM with a Mechanistic Model

    Science.gov (United States)

    Shuard, Adrian M.; Mahmud, Hisham B.; King, Andrew J.

    2016-03-01

    Two-phase pipe flow is a common occurrence in many industrial applications such as power generation and oil and gas transportation. Accurate prediction of liquid holdup and pressure drop is of vast importance to ensure effective design and operation of fluid transport systems. In this paper, a Computational Fluid Dynamics (CFD) study of a two-phase flow of air and water is performed using OpenFOAM. The two-phase solver, interFoam is used to identify flow patterns and generate values of liquid holdup and pressure drop, which are compared to results obtained from a two-phase mechanistic model developed by Petalas and Aziz (2002). A total of 60 simulations have been performed at three separate pipe inclinations of 0°, +10° and -10° respectively. A three dimensional, 0.052m diameter pipe of 4m length is used with the Shear Stress Transport (SST) k - ɷ turbulence model to solve the turbulent mixtures of air and water. Results show that the flow pattern behaviour and numerical values of liquid holdup and pressure drop compare reasonably well to the mechanistic model.

  1. Mechanistic facility safety and source term analysis

    International Nuclear Information System (INIS)

    PLYS, M.G.

    1999-01-01

    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

  2. Melanie Klein's metapsychology: phenomenological and mechanistic perspective.

    Science.gov (United States)

    Mackay, N

    1981-01-01

    Freud's metapsychology is the subject of an important debate. This is over whether psychoanalysis is best construed as a science of the natural science type or as a special human science. The same debate applies to Melanie Klein's work. In Klein's metapsychology are two different and incompatible models of explanation. One is taken over from Freud's structural theory and appears to be similarly mechanistic. The other is clinically based and phenomenological. These two are discussed with special reference to the concepts of "phantasy" and "internal object".

  3. Fuel swelling importance in PCI mechanistic modelling

    International Nuclear Information System (INIS)

    Arimescu, V.I.

    2005-01-01

    Under certain conditions, fuel pellet swelling is the most important factor in determining the intensity of the pellet-to-cladding mechanical interaction (PCMI). This is especially true during power ramps, which lead to a temperature increase to a higher terminal plateau that is maintained for hours. The time-dependent gaseous swelling is proportional to temperature and is also enhanced by the increased gas atom migration to the grain boundary during the power ramp. On the other hand, gaseous swelling is inhibited by a compressive hydrostatic stress in the pellet. Therefore, PCMI is the net result of combining gaseous swelling and pellet thermal expansion with the opposing feedback from the cladding mechanical reaction. The coupling of the thermal and mechanical processes, mentioned above, with various feedback loops is best simulated by a mechanistic fuel code. This paper discusses a mechanistic swelling model that is coupled with a fission gas release model as well as a mechanical model of the fuel pellet. The role of fuel swelling is demonstrated for typical power ramps at different burn-ups. Also, fuel swelling plays a significant role in avoiding the thermal instability for larger gap fuel rods, by limiting the potentially exponentially increasing gap due to the positive feedback loop effect of increasing fission gas release and the associated over-pressure inside the cladding. (author)

  4. The coefficient of restitution of pressurized balls: a mechanistic model

    Science.gov (United States)

    Georgallas, Alex; Landry, Gaëtan

    2016-01-01

    Pressurized, inflated balls used in professional sports are regulated so that their behaviour upon impact can be anticipated and allow the game to have its distinctive character. However, the dynamics governing the impacts of such balls, even on stationary hard surfaces, can be extremely complex. The energy transformations, which arise from the compression of the gas within the ball and from the shear forces associated with the deformation of the wall, are examined in this paper. We develop a simple mechanistic model of the dependence of the coefficient of restitution, e, upon both the gauge pressure, P_G, of the gas and the shear modulus, G, of the wall. The model is validated using the results from a simple series of experiments using three different sports balls. The fits to the data are extremely good for P_G > 25 kPa and consistent values are obtained for the value of G for the wall material. As far as the authors can tell, this simple, mechanistic model of the pressure dependence of the coefficient of restitution is the first in the literature. *%K Coefficient of Restitution, Dynamics, Inflated Balls, Pressure, Impact Model

  5. STS Case Study Development Support

    Science.gov (United States)

    Rosa de Jesus, Dan A.; Johnson, Grace K.

    2013-01-01

    The Shuttle Case Study Collection (SCSC) has been developed using lessons learned documented by NASA engineers, analysts, and contractors. The SCSC provides educators with a new tool to teach real-world engineering processes with the goal of providing unique educational materials that enhance critical thinking, decision-making and problem-solving skills. During this third phase of the project, responsibilities included: the revision of the Hyper Text Markup Language (HTML) source code to ensure all pages follow World Wide Web Consortium (W3C) standards, and the addition and edition of website content, including text, documents, and images. Basic HTML knowledge was required, as was basic knowledge of photo editing software, and training to learn how to use NASA's Content Management System for website design. The outcome of this project was its release to the public.

  6. Mechanistic insights on the cycloisomerization of polyunsaturated precursors catalyzed by platinum and gold complexes.

    Science.gov (United States)

    Soriano, Elena; Marco-Contelles, José

    2009-08-18

    Organometallic chemistry provides powerful tools for the stereocontrolled synthesis of heterocycles and carbocycles. The electrophilic transition metals Pt(II) and Au(I, III) are efficient catalysts in these transitions and promote a variety of organic transformations of unsaturated precursors. These reactions produce functionalized cyclic and acyclic scaffolds for the synthesis of natural and non-natural products efficiently, under mild conditions, and with excellent chemoselectivity. Because these transformations are strongly substrate-dependent, they are versatile and may yield diverse molecular scaffolds. Therefore, synthetic chemists need a mechanistic interpretation to optimize this reaction process and design a new generation of catalysts. However, so far, no intermediate species has been isolated or characterized, so the formulated mechanistic hypotheses have been primarily based on labeling studies or trapping reactions. Recently, theoretical DFT studies have become a useful tool in our research, giving us insights into the key intermediates and into a variety of plausible reaction pathways. In this Account, we present a comprehensive mechanistic overview of transformations promoted by Pt and Au in a non-nucleophilic medium based on quantum-mechanical studies. The calculations are consistent with the experimental observations and provide fundamental insights into the versatility of these reaction processes. The reactivity of these metals results from their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the pi-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. 1,n-Enynes (n = 3-8) are particularly important precursors, and their transformation may yield a variety of cycloadducts depending on the molecular structure. However, the calculations suggest that these different cyclizations would have closely related reaction mechanisms, and we propose a unified mechanistic

  7. Causation at Different Levels: Tracking the Commitments of Mechanistic Explanations

    DEFF Research Database (Denmark)

    Fazekas, Peter; Kertész, Gergely

    2011-01-01

    connections transparent. These general commitments get confronted with two claims made by certain proponents of the mechanistic approach: William Bechtel often argues that within the mechanistic framework it is possible to balance between reducing higher levels and maintaining their autonomy at the same time...... their autonomy at the same time than standard reductive accounts are, and that what mechanistic explanations are able to do at best is showing that downward causation does not exist....

  8. Mechanistic and Economical Characteristics of Asphalt Rubber Mixtures

    Directory of Open Access Journals (Sweden)

    Mena I. Souliman

    2016-01-01

    Full Text Available Load associated fatigue cracking is one of the major distress types occurring in flexible pavement systems. Flexural bending beam fatigue laboratory test has been used for several decades and is considered to be an integral part of the new superpave advanced characterization procedure. One of the most significant solutions to prolong the fatigue life for an asphaltic mixture is to utilize flexible materials as rubber. A laboratory testing program was performed on a conventional and Asphalt Rubber- (AR- gap-graded mixtures to investigate the impact of added rubber on the mechanical, mechanistic, and economical attributes of asphaltic mixtures. Strain controlled fatigue tests were conducted according to American Association of State Highway and Transportation Officials (AASHTO procedures. The results from the beam fatigue tests indicated that the AR-gap-graded mixtures would have much longer fatigue life compared with the reference (conventional mixtures. In addition, a mechanistic analysis using 3D-Move software coupled with a cost analysis study based on the fatigue performance on the two mixtures was performed. Overall, analysis showed that AR modified asphalt mixtures exhibited significantly lower cost of pavement per 1000 cycles of fatigue life per mile compared to conventional HMA mixture.

  9. Requirements on mechanistic NPP models used in CSS for diagnostics and predictions

    International Nuclear Information System (INIS)

    Juslin, K.

    1996-01-01

    Mechanistic models have for several years with good experience been used for operators' support in electric power dispatching centres. Some models of limited scope have already been in use at nuclear power plants. It is considered that also advanced mechanistic models in combination with present computer technology with preference could be used in Computerized Support Systems (CSS) for the assistance of Nuclear Power Plant (NPP) operators. Requirements with respect to accuracy, validity range, speed flexibility and level of detail on the models used for such purposes are discussed. Quality Assurance, Verification and Validation efforts are considered. A long term commitment in the field of mechanistic modelling and real time simulation is considered as the key to successful implementations. The Advanced PROcess Simulation (APROS) code system and simulation environment developed at the Technical Research Centre of Finland (VTT) is intended also for CSS applications in NPP control rooms. (author). 4 refs

  10. Fetal programming of CVD and renal disease: animal models and mechanistic considerations.

    Science.gov (United States)

    Langley-Evans, Simon C

    2013-08-01

    The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under- or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena.

  11. Student Development and Developmental Studies.

    Science.gov (United States)

    Champaigne, John

    1982-01-01

    Reviews the nine-stage Perry Scheme of Intellectual and Ethical Development, detailing three major student orientations--dualism, multiplicity, and commitments in relativism. Suggests techniques developmental educators can use to communicate with, support, and challenge students to promote intellectual development. Underscores the importance of…

  12. Mechanistic-Empirical (M-E) Design Implementation & Monitoring for Flexible Pavements : 2018 PROJECT SUMMARY

    Science.gov (United States)

    2018-06-01

    This document is a summary of the tasks performed for Project ICT-R27-149-1. Mechanistic-empirical (M-E)based flexible pavement design concepts and procedures were previously developed in Illinois Cooperative Highway Research Program projects IHR-...

  13. Permanent deformation testing for a new South African mechanistic pavement design method

    CSIR Research Space (South Africa)

    Anochie-Boateng, Joseph

    2012-01-01

    Full Text Available The South Africa National Road Agency Limited together with the CSIR are undertaking a research and development project to support the revision of the South African mechanistic-empirical pavement design method. An important part of this project...

  14. Students' Interpretations of Mechanistic Language in Organic Chemistry before Learning Reactions

    Science.gov (United States)

    Galloway, Kelli R.; Stoyanovich, Carlee; Flynn, Alison B.

    2017-01-01

    Research on mechanistic thinking in organic chemistry has shown that students attribute little meaning to the electron-pushing (i.e., curved arrow) formalism. At the University of Ottawa, a new curriculum has been developed in which students are taught the electron-pushing formalism prior to instruction on specific reactions--this formalism is…

  15. In Silico Augmentation of the Drug Development Pipeline: Examples from the study of Acute Inflammation.

    Science.gov (United States)

    An, Gary; Bartels, John; Vodovotz, Yoram

    2011-03-01

    The clinical translation of promising basic biomedical findings, whether derived from reductionist studies in academic laboratories or as the product of extensive high-throughput and -content screens in the biotechnology and pharmaceutical industries, has reached a period of stagnation in which ever higher research and development costs are yielding ever fewer new drugs. Systems biology and computational modeling have been touted as potential avenues by which to break through this logjam. However, few mechanistic computational approaches are utilized in a manner that is fully cognizant of the inherent clinical realities in which the drugs developed through this ostensibly rational process will be ultimately used. In this article, we present a Translational Systems Biology approach to inflammation. This approach is based on the use of mechanistic computational modeling centered on inherent clinical applicability, namely that a unified suite of models can be applied to generate in silico clinical trials, individualized computational models as tools for personalized medicine, and rational drug and device design based on disease mechanism.

  16. The use of mechanistic descriptions of algal growth and zooplankton grazing in an estuarine eutrophication model

    Science.gov (United States)

    Baird, M. E.; Walker, S. J.; Wallace, B. B.; Webster, I. T.; Parslow, J. S.

    2003-03-01

    A simple model of estuarine eutrophication is built on biomechanical (or mechanistic) descriptions of a number of the key ecological processes in estuaries. Mechanistically described processes include the nutrient uptake and light capture of planktonic and benthic autotrophs, and the encounter rates of planktonic predators and prey. Other more complex processes, such as sediment biogeochemistry, detrital processes and phosphate dynamics, are modelled using empirical descriptions from the Port Phillip Bay Environmental Study (PPBES) ecological model. A comparison is made between the mechanistically determined rates of ecological processes and the analogous empirically determined rates in the PPBES ecological model. The rates generally agree, with a few significant exceptions. Model simulations were run at a range of estuarine depths and nutrient loads, with outputs presented as the annually averaged biomass of autotrophs. The simulations followed a simple conceptual model of eutrophication, suggesting a simple biomechanical understanding of estuarine processes can provide a predictive tool for ecological processes in a wide range of estuarine ecosystems.

  17. Mechanistic curiosity will not kill the Bayesian cat

    NARCIS (Netherlands)

    Borsboom, D.; Wagenmakers, E.-J.; Romeijn, J.-W.

    2011-01-01

    Jones & Love (J&L) suggest that Bayesian approaches to the explanation of human behavior should be constrained by mechanistic theories. We argue that their proposal misconstrues the relation between process models, such as the Bayesian model, and mechanisms. While mechanistic theories can answer

  18. Mechanistic curiosity will not kill the Bayesian cat

    NARCIS (Netherlands)

    Borsboom, Denny; Wagenmakers, Eric-Jan; Romeijn, Jan-Willem

    Jones & Love (J&L) suggest that Bayesian approaches to the explanation of human behavior should be constrained by mechanistic theories. We argue that their proposal misconstrues the relation between process models, such as the Bayesian model, and mechanisms. While mechanistic theories can answer

  19. "Ratio via Machina": Three Standards of Mechanistic Explanation in Sociology

    Science.gov (United States)

    Aviles, Natalie B.; Reed, Isaac Ariail

    2017-01-01

    Recently, sociologists have expended much effort in attempts to define social mechanisms. We intervene in these debates by proposing that sociologists in fact have a choice to make between three standards of what constitutes a good mechanistic explanation: substantial, formal, and metaphorical mechanistic explanation. All three standards are…

  20. Ghana Journal of Development Studies: Submissions

    African Journals Online (AJOL)

    University for Development Studies P. O. Box 520 ... A Book by a Corporate Author University for Development Studies (2003). Strategic plan (2003-2008). Tamale, Ghana: ... Accra, Ghana: National Development Planning Commission.

  1. Theories in Social Policy and Development Studies

    DEFF Research Database (Denmark)

    Schmidt, Johannes Dragsbæk

    Theories in Social Policy and Development Studies Presentation for the PhD Seminar - Theories, Concepts and Methods in Development Studies and Sociology......Theories in Social Policy and Development Studies Presentation for the PhD Seminar - Theories, Concepts and Methods in Development Studies and Sociology...

  2. Toward a mechanistic modeling of nitrogen limitation for photosynthesis

    Science.gov (United States)

    Xu, C.; Fisher, R. A.; Travis, B. J.; Wilson, C. J.; McDowell, N. G.

    2011-12-01

    The nitrogen limitation is an important regulator for vegetation growth and global carbon cycle. Most current ecosystem process models simulate nitrogen effects on photosynthesis based on a prescribed relationship between leaf nitrogen and photosynthesis; however, there is a large amount of variability in this relationship with different light, temperature, nitrogen availability and CO2 conditions, which can affect the reliability of photosynthesis prediction under future climate conditions. To account for the variability in nitrogen-photosynthesis relationship under different environmental conditions, in this study, we developed a mechanistic model of nitrogen limitation for photosynthesis based on nitrogen trade-offs among light absorption, electron transport, carboxylization and carbon sink. Our model shows that strategies of nitrogen storage allocation as determined by tradeoff among growth and persistence is a key factor contributing to the variability in relationship between leaf nitrogen and photosynthesis. Nitrogen fertilization substantially increases the proportion of nitrogen in storage for coniferous trees but much less for deciduous trees, suggesting that coniferous trees allocate more nitrogen toward persistence compared to deciduous trees. The CO2 fertilization will cause lower nitrogen allocation for carboxylization but higher nitrogen allocation for storage, which leads to a weaker relationship between leaf nitrogen and maximum photosynthesis rate. Lower radiation will cause higher nitrogen allocation for light absorption and electron transport but less nitrogen allocation for carboxylyzation and storage, which also leads to weaker relationship between leaf nitrogen and maximum photosynthesis rate. At the same time, lower growing temperature will cause higher nitrogen allocation for carboxylyzation but lower allocation for light absorption, electron transport and storage, which leads to a stronger relationship between leaf nitrogen and maximum

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

    Science.gov (United States)

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

    2016-07-08

    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. © 2016 American Institute of Chemical Engineers.

  4. Mechanistic applicability domain classification of a local lymph node assay dataset for skin sensitization.

    Science.gov (United States)

    Roberts, David W; Patlewicz, Grace; Kern, Petra S; Gerberick, Frank; Kimber, Ian; Dearman, Rebecca J; Ryan, Cindy A; Basketter, David A; Aptula, Aynur O

    2007-07-01

    The goal of eliminating animal testing in the predictive identification of chemicals with the intrinsic ability to cause skin sensitization is an important target, the attainment of which has recently been brought into even sharper relief by the EU Cosmetics Directive and the requirements of the REACH legislation. Development of alternative methods requires that the chemicals used to evaluate and validate novel approaches comprise not only confirmed skin sensitizers and non-sensitizers but also substances that span the full chemical mechanistic spectrum associated with skin sensitization. To this end, a recently published database of more than 200 chemicals tested in the mouse local lymph node assay (LLNA) has been examined in relation to various chemical reaction mechanistic domains known to be associated with sensitization. It is demonstrated here that the dataset does cover the main reaction mechanistic domains. In addition, it is shown that assignment to a reaction mechanistic domain is a critical first step in a strategic approach to understanding, ultimately on a quantitative basis, how chemical properties influence the potency of skin sensitizing chemicals. This understanding is necessary if reliable non-animal approaches, including (quantitative) structure-activity relationships (Q)SARs, read-across, and experimental chemistry based models, are to be developed.

  5. Ruthenium-Catalyzed Formal Dehydrative [4 + 2] Cycloaddition of Enamides and Alkynes for the Synthesis of Highly Substituted Pyridines: Reaction Development and Mechanistic Study.

    Science.gov (United States)

    Wu, Jicheng; Xu, Wenbo; Yu, Zhi-Xiang; Wang, Jian

    2015-07-29

    Reported herein is a ruthenium-catalyzed formal dehydrative [4 + 2] cycloaddition of enamides and alkynes, representing a mild and economic protocol for the construction of highly substituted pyridines. Notably, the features of broad substrate scope, high efficiency, good functional group tolerance, and excellent regioselectivities were observed for this reaction. Density functional theory (DFT) calculations and experiments have been carried out to understand the mechanism and regiochemistry. DFT calculations suggested that this formal dehydrative [4 + 2] reaction starts with a concerted metalation deprotonation of the enamide by the acetate group in the Ru catalyst, which generates a six-membered ruthenacycle intermediate. Then alkyne inserts into the Ru-C bond of the six-membered ruthenacycle, giving rise to an eight-membered ruthenacycle intermediate. The carbonyl group (which comes originally from the enamide substrate and is coordinated to the Ru center in the eight-membered ruthenacycle intermediate) then inserts into the Ru-C bond to give an intermediate, which produces the final pyridine product through further dehydration. Alkyne insertion step is a regio-determining step and prefers to have the aryl groups of the used alkynes stay away from the catalyst in order to avoid repulsion of aryl group with the enamide moiety in the six-membered ruthenacycle and to keep the conjugation between the aryl group and the triple C-C bond of the alkynes. Consequently, the aryl groups of the used alkynes are in the β-position of the final pyridines, and the present reaction has high regioselectivity.

  6. Toward a mechanistic understanding of human-induced rapid environmental change: A case study linking energy development, avian nest predation, and predators

    Science.gov (United States)

    Hethcoat, Matthew G.; Chalfoun, Anna D.

    2015-01-01

    Demographic consequences of human-induced rapid environmental change (HIREC) have been widely documented for many populations. The mechanisms underlying such patterns, however, are rarely investigated and yet are critical to understand for effective conservation and management.

  7. An Emphasis on Perception: Teaching Image Formation Using a Mechanistic Model of Vision.

    Science.gov (United States)

    Allen, Sue; And Others

    An effective way to teach the concept of image is to give students a model of human vision which incorporates a simple mechanism of depth perception. In this study two almost identical versions of a curriculum in geometrical optics were created. One used a mechanistic, interpretive eye model, and in the other the eye was modeled as a passive,…

  8. In silico, experimental, mechanistic model for extended-release felodipine disposition exhibiting complex absorption and a highly variable food interaction.

    Directory of Open Access Journals (Sweden)

    Sean H J Kim

    Full Text Available The objective of this study was to develop and explore new, in silico experimental methods for deciphering complex, highly variable absorption and food interaction pharmacokinetics observed for a modified-release drug product. Toward that aim, we constructed an executable software analog of study participants to whom product was administered orally. The analog is an object- and agent-oriented, discrete event system, which consists of grid spaces and event mechanisms that map abstractly to different physiological features and processes. Analog mechanisms were made sufficiently complicated to achieve prespecified similarity criteria. An equation-based gastrointestinal transit model with nonlinear mixed effects analysis provided a standard for comparison. Subject-specific parameterizations enabled each executed analog's plasma profile to mimic features of the corresponding six individual pairs of subject plasma profiles. All achieved prespecified, quantitative similarity criteria, and outperformed the gastrointestinal transit model estimations. We observed important subject-specific interactions within the simulation and mechanistic differences between the two models. We hypothesize that mechanisms, events, and their causes occurring during simulations had counterparts within the food interaction study: they are working, evolvable, concrete theories of dynamic interactions occurring within individual subjects. The approach presented provides new, experimental strategies for unraveling the mechanistic basis of complex pharmacological interactions and observed variability.

  9. Anodic Cyclization Reactions and the Mechanistic Strategies That Enable Optimization.

    Science.gov (United States)

    Feng, Ruozhu; Smith, Jake A; Moeller, Kevin D

    2017-09-19

    Oxidation reactions are powerful tools for synthesis because they allow us to reverse the polarity of electron-rich functional groups, generate highly reactive intermediates, and increase the functionality of molecules. For this reason, oxidation reactions have been and continue to be the subject of intense study. Central to these efforts is the development of mechanism-based strategies that allow us to think about the reactive intermediates that are frequently central to the success of the reactions and the mechanistic pathways that those intermediates trigger. For example, consider oxidative cyclization reactions that are triggered by the removal of an electron from an electron-rich olefin and lead to cyclic products that are functionalized for further elaboration. For these reactions to be successful, the radical cation intermediate must first be generated using conditions that limit its polymerization and then channeled down a productive desired pathway. Following the cyclization, a second oxidation step is necessary for product formation, after which the resulting cation must be quenched in a controlled fashion to avoid undesired elimination reactions. Problems can arise at any one or all of these steps, a fact that frequently complicates reaction optimization and can discourage the development of new transformations. Fortunately, anodic electrochemistry offers an outstanding opportunity to systematically probe the mechanism of oxidative cyclization reactions. The use of electrochemical methods allows for the generation of radical cations under neutral conditions in an environment that helps prevent polymerization of the intermediate. Once the intermediates have been generated, a series of "telltale indicators" can be used to diagnose which step in an oxidative cyclization is problematic for less successful transformation. A set of potential solutions to address each type of problem encountered has been developed. For example, problems with the initial

  10. Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

    Science.gov (United States)

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

  11. Mechanistic Prediction of the Effect of Microstructural Coarsening on Creep Response of SnAgCu Solder Joints

    Science.gov (United States)

    Mukherjee, S.; Chauhan, P.; Osterman, M.; Dasgupta, A.; Pecht, M.

    2016-07-01

    Mechanistic microstructural models have been developed to capture the effect of isothermal aging on time dependent viscoplastic response of Sn3.0Ag0.5Cu (SAC305) solders. SnAgCu (SAC) solders undergo continuous microstructural coarsening during both storage and service because of their high homologous temperature. The microstructures of these low melting point alloys continuously evolve during service. This results in evolution of creep properties of the joint over time, thereby influencing the long term reliability of microelectronic packages. It is well documented that isothermal aging degrades the creep resistance of SAC solder. SAC305 alloy is aged for (24-1000) h at (25-100)°C (~0.6-0.8 × T melt). Cross-sectioning and image processing techniques were used to periodically quantify the effect of isothermal aging on phase coarsening and evolution. The parameters monitored during isothermal aging include size, area fraction, and inter-particle spacing of nanoscale Ag3Sn intermetallic compounds (IMCs) and the volume fraction of micronscale Cu6Sn5 IMCs, as well as the area fraction of pure tin dendrites. Effects of microstructural evolution on secondary creep constitutive response of SAC305 solder joints were then modeled using a mechanistic multiscale creep model. The mechanistic phenomena modeled include: (1) dispersion strengthening by coarsened nanoscale Ag3Sn IMCs in the eutectic phase; and (2) load sharing between pro-eutectic Sn dendrites and the surrounding coarsened eutectic Sn-Ag phase and microscale Cu6Sn5 IMCs. The coarse-grained polycrystalline Sn microstructure in SAC305 solder was not captured in the above model because isothermal aging does not cause any significant change in the initial grain size and orientation of SAC305 solder joints. The above mechanistic model can successfully capture the drop in creep resistance due to the influence of isothermal aging on SAC305 single crystals. Contribution of grain boundary sliding to the creep strain of

  12. Annals of Humanities and Development Studies

    African Journals Online (AJOL)

    The Annals of Humanities and Development Studies publishes papers in all aspects of humanities and rural, social and cultural development, including peace and international cooperation activities related to societal transformation in developing countries. Papers arising from original research and case studies or forming ...

  13. Emerging Donors Study | IDRC - International Development ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2010-10-20

    Oct 20, 2010 ... The four countries that were studied are Brazil, India, China and South Africa. The specific objectives of the studies were to: understand each country's approach to international development assistance and cooperation in developing countries; understand their approach to research for development in ...

  14. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

    Directory of Open Access Journals (Sweden)

    Wei Hsum Yap

    2015-01-01

    Full Text Available Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS. The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

  15. Mechanistic approach to the sodium leakage and fire analysis

    International Nuclear Information System (INIS)

    Yamaguchi, Akira; Muramatsu, Toshiharu; Ohira, Hiroaki; Ida, Masao

    1997-04-01

    In December 1995, a thermocouple well was broken and liquid sodium leaked out of the intermediate heat transport system of the prototype fast breeder reactor Monju. In the initiating process of the incident, liquid sodium flowed out through the hollow thermocouple well, nipple and connector. As a result, liquid sodium, following ignition and combustion, was dropping from the connector to colide with the duct and grating placed below. The collision may cause fragmentation and scattering of the sodium droplet that finally was piled up on the floor. This report deals with the development of computer programs for the phenomena based on mechanistics approach. Numerical analyses are also made for fundamental sodium leakage and combustion phenomenon, sodium combustion experiment, and Monju incident condition. The contents of this report is listed below: (1) Analysis of chemical reaction process based on molecular orbital method, (2) Thermalhy draulic analysis of the sodium combustion experiment II performed in 1996 at O-arai Engineering Center, PNC, (3) Thermalhy draulic analysis of room A-446 of Monju reactor when the sodium leakage took place, (4) Direct numerical simulation of sodium droplet, (5) Sodium leakage and scattering analysis using three dimensional particle method, (6) Multi-dimensional combustion analysis and multi-point approximation combustion analysis code. Subsequent to the development work of the programs, they are to be applied to the safety analysis of the Fast Breeder Reactor. (author)

  16. A mechanistic approach to the generation of sorption databases

    International Nuclear Information System (INIS)

    Bradbury, M.H.; Baeyens, B.

    1992-01-01

    Sorption of radionuclides in the near and far fields of an underground nuclear waste repository is one of the most important processes retarding their release to the environment. In the vast majority of cases sorption data have been presented in terms of empirical parameters such as distribution coefficients and isotherm equations. A consequence of this empirical methodology is that the sorption data are only strictly valid under the experimental conditions at which they were measured. Implicit in this approach is the need to generate large amounts of data and fitting parameters necessary for an empirical description of sorption under all realistically conceivable conditions which may arise in space and time along the migration pathway to Man. An alternative approach to the problem is to try to understand, and develop model descriptions of, underlying retention mechanisms and to identify those systems parameters which essentially determine the extent of sorption. The aim of this work is to see to what extent currently existing mechanistic models, together with their associated data, can be applied to predict sorption data from laboratory experiments on natural systems. This paper describes the current status of this work which is very much in an early stage of development. An example is given whereby model predictions are compared with laboratory results for the sorption of Np at trace concentrations under oxidizing conditions on a series of minerals relevant to granite formations. 31 refs., 11 figs., 5 tabs

  17. The central extended amygdala in fear and anxiety: Closing the gap between mechanistic and neuroimaging research.

    Science.gov (United States)

    Fox, Andrew S; Shackman, Alexander J

    2017-11-30

    Anxiety disorders impose a staggering burden on public health, underscoring the need to develop a deeper understanding of the distributed neural circuits underlying extreme fear and anxiety. Recent work highlights the importance of the central extended amygdala, including the central nucleus of the amygdala (Ce) and neighboring bed nucleus of the stria terminalis (BST). Anatomical data indicate that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated to assemble states of fear and anxiety. Neuroimaging studies show that the Ce and BST are engaged by a broad spectrum of potentially threat-relevant cues. Mechanistic work demonstrates that the Ce and BST are critically involved in organizing defensive responses to a wide range of threats. Studies in rodents have begun to reveal the specific molecules, cells, and microcircuits within the central extended amygdala that underlie signs of fear and anxiety, but the relevance of these tantalizing discoveries to human experience and disease remains unclear. Using a combination of focal perturbations and whole-brain imaging, a new generation of nonhuman primate studies is beginning to close this gap. This work opens the door to discovering the mechanisms underlying neuroimaging measures linked to pathological fear and anxiety, to understanding how the Ce and BST interact with one another and with distal brain regions to govern defensive responses to threat, and to developing improved intervention strategies. Copyright © 2017. Published by Elsevier B.V.

  18. Modeling of the pyruvate production with Escherichia coli: comparison of mechanistic and neural networks-based models.

    Science.gov (United States)

    Zelić, B; Bolf, N; Vasić-Racki, D

    2006-06-01

    Three different models: the unstructured mechanistic black-box model, the input-output neural network-based model and the externally recurrent neural network model were used to describe the pyruvate production process from glucose and acetate using the genetically modified Escherichia coli YYC202 ldhA::Kan strain. The experimental data were used from the recently described batch and fed-batch experiments [ Zelić B, Study of the process development for Escherichia coli-based pyruvate production. PhD Thesis, University of Zagreb, Faculty of Chemical Engineering and Technology, Zagreb, Croatia, July 2003. (In English); Zelić et al. Bioproc Biosyst Eng 26:249-258 (2004); Zelić et al. Eng Life Sci 3:299-305 (2003); Zelić et al Biotechnol Bioeng 85:638-646 (2004)]. The neural networks were built out of the experimental data obtained in the fed-batch pyruvate production experiments with the constant glucose feed rate. The model validation was performed using the experimental results obtained from the batch and fed-batch pyruvate production experiments with the constant acetate feed rate. Dynamics of the substrate and product concentration changes was estimated using two neural network-based models for biomass and pyruvate. It was shown that neural networks could be used for the modeling of complex microbial fermentation processes, even in conditions in which mechanistic unstructured models cannot be applied.

  19. Ghana Journal of Development Studies: Editorial Policies

    African Journals Online (AJOL)

    Dr. Nkegbe is Editorial Secretary and Head of Department, Department of Economics and Entrepreneurial Studies, Faculty of Integrated Development Studies, University for Development Studies. He holds a Ph.D in Agricultural and Food Economics from the University of Reading, United Kingdom. He is a Senior Lecturer in ...

  20. The Combined Use of Correlative and Mechanistic Species Distribution Models Benefits Low Conservation Status Species.

    Directory of Open Access Journals (Sweden)

    Thibaud Rougier

    Full Text Available Species can respond to climate change by tracking appropriate environmental conditions in space, resulting in a range shift. Species Distribution Models (SDMs can help forecast such range shift responses. For few species, both correlative and mechanistic SDMs were built, but allis shad (Alosa alosa, an endangered anadromous fish species, is one of them. The main purpose of this study was to provide a framework for joint analyses of correlative and mechanistic SDMs projections in order to strengthen conservation measures for species of conservation concern. Guidelines for joint representation and subsequent interpretation of models outputs were defined and applied. The present joint analysis was based on the novel mechanistic model GR3D (Global Repositioning Dynamics of Diadromous fish Distribution which was parameterized on allis shad and then used to predict its future distribution along the European Atlantic coast under different climate change scenarios (RCP 4.5 and RCP 8.5. We then used a correlative SDM for this species to forecast its distribution across the same geographic area and under the same climate change scenarios. First, projections from correlative and mechanistic models provided congruent trends in probability of habitat suitability and population dynamics. This agreement was preferentially interpreted as referring to the species vulnerability to climate change. Climate change could not be accordingly listed as a major threat for allis shad. The congruence in predicted range limits between SDMs projections was the next point of interest. The difference, when noticed, required to deepen our understanding of the niche modelled by each approach. In this respect, the relative position of the northern range limit between the two methods strongly suggested here that a key biological process related to intraspecific variability was potentially lacking in the mechanistic SDM. Based on our knowledge, we hypothesized that local

  1. On the antibacterial effects of manuka honey: mechanistic insights

    Directory of Open Access Journals (Sweden)

    Roberts AEL

    2015-10-01

    Full Text Available Aled Edward Lloyd Roberts,* Helen Louise Brown,* Rowena Eleri Jenkins Department of Biomedical Sciences, Cardiff Metropolitan University, Cardiff, Wales, UK *These authors contributed equally to this work Abstract: Antimicrobial resistance (AMR is an increasing clinical problem precipitated by the inappropriate use of antibiotics in the later parts of the 20th Century. This problem, coupled with the lack of novel therapeutics in the development pipeline, means AMR is reaching crisis point, with an expected annual death rate of ten million people worldwide by 2050. To reduce, and to potentially remedy this problem, many researchers are looking into natural compounds with antimicrobial and/or antivirulence activity. Manuka honey is an ancient antimicrobial remedy with a good track record against a wide range of nosocomial pathogens that have increased AMR. Its inhibitory effects are the result of its constituent components, which add varying degrees of antimicrobial efficacy to the overall activity of manuka honey. The antimicrobial efficacy of manuka honey and some of its constituent components (such as methylglyoxal and leptosperin are known to bestow some degree of antimicrobial efficacy to manuka honey. Despite growing in vitro evidence of its antimicrobial efficacy, the in vivo use of manuka honey (especially in a clinical environment has been unexpectedly slow, partly due to the lack of mechanistic data. The mechanism by which manuka honey achieves its inhibitory efficacy has recently been identified against Staphylococcus aureus and Pseudomonas aeruginosa, with both of these contrasting organisms being inhibited through different mechanisms. Manuka honey inhibits S. aureus by interfering with the cell division process, whereas P. aeruginosa cells lyse in its presence due to the reduction of a key structural protein. In addition to these inhibitory effects, manuka honey is known to reduce virulence, motility, and biofilm formation. With this

  2. Stress and food allergy: mechanistic considerations.

    Science.gov (United States)

    Schreier, Hannah M C; Wright, Rosalind J

    2014-04-01

    Recent years have seen a marked increase in food allergy prevalence among children, particularly in Western countries, that cannot be explained by genetic factors alone. This has resulted in an increased effort to identify environmental risk factors underlying food allergies and to understand how these factors may be modified through interventions. Food allergy is an immune-mediated adverse reaction to food. Consequently, considerations of candidate risk factors have begun to focus on environmental influences that perturb the healthy development of the emerging immune system during critical periods of development (eg, prenatally and during early childhood), particularly in the gut. Given that psychosocial stress is known to play an important role in other allergic and inflammatory diseases, such as asthma, its potential role in food allergy is a growing area of research. However, research to date has largely focused on animal studies. This review synthesizes relevant animal research and epidemiological data, providing proof of concept for moderating influences of psychological stress on food allergy outcomes in humans. Pathways that may underlie associations between psychosocial stress and the expression of food allergy are discussed. Copyright © 2014 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Smith, James A.

    2009-01-01

    How will migrating birds respond to changes in the environment under climate change? What are the implications for migratory success under the various accelerated climate change scenarios as forecast by the Intergovernmental Panel on Climate Change? How will reductions or increased variability in the number or quality of wetland stop-over sites affect migratory bird species? The answers to these questions have important ramifications for conservation biology and wildlife management. Here, we describe the use of continental scale simulation modeling to explore how spatio-temporal changes along migratory flyways affect en-route migration success. We use an individually based, biophysical, mechanistic, bird migration model to simulate the movement of shorebirds in North America as a tool to study how such factors as drought and wetland loss may impact migratory success and modify migration patterns. Our model is driven by remote sensing and climate data and incorporates important landscape variables. The energy budget components of the model include resting, foraging, and flight, but presently predation is ignored. Results/Conclusions We illustrate our model by studying the spring migration of sandpipers through the Great Plains to their Arctic breeding grounds. Why many species of shorebirds have shown significant declines remains a puzzle. Shorebirds are sensitive to stop-over quality and spacing because of their need for frequent refueling stops and their opportunistic feeding patterns. We predict bird "hydrographs that is, stop-over frequency with latitude, that are in agreement with the literature. Mean stop-over durations predicted from our model for nominal cases also are consistent with the limited, but available data. For the shorebird species simulated, our model predicts that shorebirds exhibit significant plasticity and are able to shift their migration patterns in response to changing drought conditions. However, the question remains as to whether this

  4. A mechanistic compartmental model for total antibody uptake in tumors.

    Science.gov (United States)

    Thurber, Greg M; Dane Wittrup, K

    2012-12-07

    Antibodies are under development to treat a variety of cancers, such as lymphomas, colon, and breast cancer. A major limitation to greater efficacy for this class of drugs is poor distribution in vivo. Localization of antibodies occurs slowly, often in insufficient therapeutic amounts, and distributes heterogeneously throughout the tumor. While the microdistribution around individual vessels is important for many therapies, the total amount of antibody localized in the tumor is paramount for many applications such as imaging, determining the therapeutic index with antibody drug conjugates, and dosing in radioimmunotherapy. With imaging and pretargeted therapeutic strategies, the time course of uptake is critical in determining when to take an image or deliver a secondary reagent. We present here a simple mechanistic model of antibody uptake and retention that captures the major rates that determine the time course of antibody concentration within a tumor including dose, affinity, plasma clearance, target expression, internalization, permeability, and vascularization. Since many of the parameters are known or can be estimated in vitro, this model can approximate the time course of antibody concentration in tumors to aid in experimental design, data interpretation, and strategies to improve localization. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Polymerization kinetics of wheat gluten upon thermosetting. A mechanistic model.

    Science.gov (United States)

    Domenek, Sandra; Morel, Marie-Hélène; Bonicel, Joëlle; Guilbert, Stéphane

    2002-10-09

    Size exclusion high-performance liquid chromatography analysis was carried out on wheat gluten-glycerol blends subjected to different heat treatments. The elution profiles were analyzed in order to follow the solubility loss of protein fractions with specific molecular size. Owing to the known biochemical changes involved during the heat denaturation of gluten, a mechanistic mathematical model was developed, which divided the protein denaturation into two distinct reaction steps: (i) reversible change in protein conformation and (ii) protein precipitation through disulfide bonding between initially SDS-soluble and SDS-insoluble reaction partners. Activation energies of gluten unfolding, refolding, and precipitation were calculated with the Arrhenius law to 53.9 kJ x mol(-1), 29.5 kJ x mol(-1), and 172 kJ x mol(-1), respectively. The rate of protein solubility loss decreased as the cross-linking reaction proceeded, which may be attributed to the formation of a three-dimensional network progressively hindering the reaction. The enhanced susceptibility to aggregation of large molecules was assigned to a risen reaction probability due to their higher number of cysteine residues and to the increased percentage of unfolded and thereby activated proteins as complete protein refolding seemed to be an anticooperative process.

  6. Mechanistic interpretation of glass reaction: Input to kinetic model development

    International Nuclear Information System (INIS)

    Bates, J.K.; Ebert, W.L.; Bradley, J.P.; Bourcier, W.L.

    1991-05-01

    Actinide-doped SRL 165 type glass was reacted in J-13 groundwater at 90 degree C for times up to 278 days. The reaction was characterized by both solution and solid analyses. The glass was seen to react nonstoichiometrically with preferred leaching of alkali metals and boron. High resolution electron microscopy revealed the formation of a complex layer structure which became separated from the underlying glass as the reaction progressed. The formation of the layer and its effect on continued glass reaction are discussed with respect to the current model for glass reaction used in the EQ3/6 computer simulation. It is concluded that the layer formed after 278 days is not protective and may eventually become fractured and generate particulates that may be transported by liquid water. 5 refs., 5 figs. , 3 tabs

  7. Journal of Development and Communication Studies

    African Journals Online (AJOL)

    The Journal of Development and Communications Studies (JDCS), published online and in print by Development Media Consulting, is a biannual academic, peer ... civil society, politicians and the public, research recommendations for the benefit of social development in Malawi and Africa, foremost, and the world, second.

  8. Mechanistic positron emission tomography studies: demonstration of a deuterium isotope effect in the monoamine oxidase-catalyzed binding of (/sup 11/C)L-deprenyl in living baboon brain

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.; Wolf, A.P.; MacGregor, R.R.; Dewey, S.L.; Logan, J.; Schlyer, D.J.; Langstrom, B.

    1988-11-01

    The application of positron emission tomography (PET) to the study of biochemical transformations in the living human and animal body requires the development of highly selective radiotracers whose concentrations in tissue provide a record of a discrete metabolic process. L-N-(11C-methyl)Deprenyl ((11C)L-deprenyl), a suicide inactivator of monoamine oxidase (MAO) type B, has been developed as a radiotracer for mapping MAO B in the living human and animal brain. In this investigation, (11C)L-deprenyl (1) and (11C)L-deprenyl-alpha, alpha-2H2 (2) have been compared in three different baboons by PET measurement of carbon-11 uptake and retention in the brain and the measurement of the amount of unchanged tracer in the arterial plasma over a 90-min time interval. For one baboon, N-(11C-methyl-2H3)L-deprenyl (3) was also studied. Kinetic parameters calculated using a three-compartment model revealed a deuterium isotope effect of 3.8 +/- 1.1. Comparison of the two tracers (1 and 2) in mouse brain demonstrated that deuterium substitution significantly reduced the amount of radioactivity bound to protein. HPLC and GLC analysis of the soluble radioactivity in mouse brain after injection of (11C)L-deprenyl showed the presence of (11C)methamphetamine as a major product along with unidentified labeled products. Sodium dodecyl sulfate-polyacrylamide electrophoresis with carbon-14-labeled L-deprenyl showed that a protein of molecular weight 58,000 was labeled. These results establish that MAO-catalyzed cleavage of the alpha carbon-hydrogen bond on the propargyl group is the rate limiting (or a major rate contributing) step in the retention of carbon-11 in brain and that the in vivo detection of labeled products in brain after the injection of (11C)L-deprenyl provides a record of MAO activity.

  9. Predicting interactions from mechanistic information: Can omic data validate theories?

    International Nuclear Information System (INIS)

    Borgert, Christopher J.

    2007-01-01

    To address the most pressing and relevant issues for improving mixture risk assessment, researchers must first recognize that risk assessment is driven by both regulatory requirements and scientific research, and that regulatory concerns may expand beyond the purely scientific interests of researchers. Concepts of 'mode of action' and 'mechanism of action' are used in particular ways within the regulatory arena, depending on the specific assessment goals. The data requirements for delineating a mode of action and predicting interactive toxicity in mixtures are not well defined from a scientific standpoint due largely to inherent difficulties in testing certain underlying assumptions. Understanding the regulatory perspective on mechanistic concepts will be important for designing experiments that can be interpreted clearly and applied in risk assessments without undue reliance on extrapolation and assumption. In like fashion, regulators and risk assessors can be better equipped to apply mechanistic data if the concepts underlying mechanistic research and the limitations that must be placed on interpretation of mechanistic data are understood. This will be critically important for applying new technologies to risk assessment, such as functional genomics, proteomics, and metabolomics. It will be essential not only for risk assessors to become conversant with the language and concepts of mechanistic research, including new omic technologies, but also, for researchers to become more intimately familiar with the challenges and needs of risk assessment

  10. Explanation and inference: Mechanistic and functional explanations guide property generalization

    Directory of Open Access Journals (Sweden)

    Tania eLombrozo

    2014-09-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  12. The Microsociological Approach on Local Development Studies

    Directory of Open Access Journals (Sweden)

    Lic. Domingos António-Lópes

    2015-10-01

    Full Text Available In the past two decades, societies, economies and cultures of the countries developed and developing have lived deep structural changes of marked breadth and impact processes in everyday lives.  Today we are witnessing a new era of technological and organizational restructuring that affects the ways to produce and manage local development. Sociology as a social science has begun to rethink development from the voices of a variety of actors, to strike with them rhythms and intensities of the social and cultural dynamics. This article is a sociological study on local development from the perspective of culture, placing the concepts of social space and socialization practices. An analysis of documentary sources which favoured the systematization of the concepts of development and local development.Keywords:  development, local development, socialization, cultural practices, social space, social capital.

  13. RELATIONSHIPS BETWEEN SOIL MICROBIAL BIOMASS, AGGREGATE STABILITY AND AGGREGATE ASSOCIATED-C: A MECHANISTIC APPROACH

    Directory of Open Access Journals (Sweden)

    Patrizia Guidi

    2014-01-01

    Full Text Available For the identification of C pools involved in soil aggregation, a physically-based aggregate fractionation was proposed, and  additional pretreatments were used in the measurement of the 1-2 mm aggregate stability in order to elucidate the relevance of the role of soil microorganisms with respect to the different aggregate breakdown mechanisms. The study was carried out on three clay loam Regosols, developed on calcareous shales, known history of organic cultivation.Our results showed that the soil C pool controlling the process of stabilisation of aggregates was related to the microbial community. We identified the resistance to fast wetting as the major mechanism of aggregate stability driven by microorganims. The plausible hypothesis is that organic farming promotes fungi growth, improving water repellency of soil aggregates by fungal hydrophobic substances. By contrast, we failed in the identification of C pools controlling the formation of aggregates, probably because of the disturbance of mechanical tillage which contributes to the breakdown of soil aggregates.The physically-based aggregate fractionation proposed in this study resulted useful in the  mechanistically understanding of the role of microorganisms in soil aggregation and it might be suggested for studying the impact of management on C pools, aggregates properties and their relationships in agricultural soils.

  14. Mechanistic Insights of Vitamin D Anticancer Effects.

    Science.gov (United States)

    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. © 2016 Elsevier Inc. All rights reserved.

  15. An improved mechanistic critical heat flux model for subcooled flow boiling

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young Min [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1997-12-31

    Based on the bubble coalescence adjacent to the heated wall as a flow structure for CHF condition, Chang and Lee developed a mechanistic critical heat flux (CHF) model for subcooled flow boiling. In this paper, improvements of Chang-Lee model are implemented with more solid theoretical bases for subcooled and low-quality flow boiling in tubes. Nedderman-Shearer`s equations for the skin friction factor and universal velocity profile models are employed. Slip effect of movable bubbly layer is implemented to improve the predictability of low mass flow. Also, mechanistic subcooled flow boiling model is used to predict the flow quality and void fraction. The performance of the present model is verified using the KAIST CHF database of water in uniformly heated tubes. It is found that the present model can give a satisfactory agreement with experimental data within less than 9% RMS error. 9 refs., 5 figs. (Author)

  16. An improved mechanistic critical heat flux model for subcooled flow boiling

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Young Min [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Chang, Soon Heung [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1998-12-31

    Based on the bubble coalescence adjacent to the heated wall as a flow structure for CHF condition, Chang and Lee developed a mechanistic critical heat flux (CHF) model for subcooled flow boiling. In this paper, improvements of Chang-Lee model are implemented with more solid theoretical bases for subcooled and low-quality flow boiling in tubes. Nedderman-Shearer`s equations for the skin friction factor and universal velocity profile models are employed. Slip effect of movable bubbly layer is implemented to improve the predictability of low mass flow. Also, mechanistic subcooled flow boiling model is used to predict the flow quality and void fraction. The performance of the present model is verified using the KAIST CHF database of water in uniformly heated tubes. It is found that the present model can give a satisfactory agreement with experimental data within less than 9% RMS error. 9 refs., 5 figs. (Author)

  17. Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

    International Nuclear Information System (INIS)

    Stites, Edward C

    2013-01-01

    Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients. (paper)

  18. Drug-disease modeling in the pharmaceutical industry - where mechanistic systems pharmacology and statistical pharmacometrics meet.

    Science.gov (United States)

    Helmlinger, Gabriel; Al-Huniti, Nidal; Aksenov, Sergey; Peskov, Kirill; Hallow, Karen M; Chu, Lulu; Boulton, David; Eriksson, Ulf; Hamrén, Bengt; Lambert, Craig; Masson, Eric; Tomkinson, Helen; Stanski, Donald

    2017-11-15

    Modeling & simulation (M&S) methodologies are established quantitative tools, which have proven to be useful in supporting the research, development (R&D), regulatory approval, and marketing of novel therapeutics. Applications of M&S help design efficient studies and interpret their results in context of all available data and knowledge to enable effective decision-making during the R&D process. In this mini-review, we focus on two sets of modeling approaches: population-based models, which are well-established within the pharmaceutical industry today, and fall under the discipline of clinical pharmacometrics (PMX); and systems dynamics models, which encompass a range of models of (patho-)physiology amenable to pharmacological intervention, of signaling pathways in biology, and of substance distribution in the body (today known as physiologically-based pharmacokinetic models) - which today may be collectively referred to as quantitative systems pharmacology models (QSP). We next describe the convergence - or rather selected integration - of PMX and QSP approaches into 'middle-out' drug-disease models, which retain selected mechanistic aspects, while remaining parsimonious, fit-for-purpose, and able to address variability and the testing of covariates. We further propose development opportunities for drug-disease systems models, to increase their utility and applicability throughout the preclinical and clinical spectrum of pharmaceutical R&D. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Mechanistic study and modeling of radionuclides retention by the hydrated calcium silicates (HCS) of cements; Etude mecanistique et modelisation de la retention de radionucleides par les silicates de calcium hydrates (CSH) des ciments

    Energy Technology Data Exchange (ETDEWEB)

    Pointeau, I

    2000-09-01

    This work attempts to investigate the modelling of radioisotopes (Cs{sup +}, Pb{sup 2+}, Eu{sup 3+}) immobilization in cement matrix, in the frame of the design of engineered barrier of a deep radwaste repository. The model development concept consists of three major steps: - surface chemistry modelling of the calcium silicate hydrate CSH, used to simulate hydrated cement behaviour; - solid analysis of the batch sorption experiments: identification of the uptake mechanism; - both previous steps are used, with isotherm data, in the modelling of the radioisotopes immobilization in the CSH matrix. Final results: (all modelling are available for all the range of studied Ca/Si ratios and have been validated with predictive calculations). - A thermodynamic modelling of the CSH surface chemistry has been developed. The labile calcium and proton sorption constants on silanol sites (>SiOH) have been extracted. - Cs{sup +} is sorbed on two sites. The silanol site (weak site) has a high site density (10 sites.nm{sup -2}), which accounts for the CSH unsaturation in high [CS{sup +}]. A strong site is also identified. - Pb{sup 2+} immobilization in CSH matrix is modelled with surface equilibria and solubility equilibrium. - Eu{sup 3+} fixation has been investigated with solid analysis: Site-Selective anti Time-Resolved Luminescence Spectroscopy, XPS and SEM-EDS. Eu{sup 3+} thus does not precipitate in CSH water but is sorbed on the CSH surface (high hydroxylated environment). Europium is also (minority site) inserted in the CSH framework. (author)

  20. Mechanistic understanding of monosaccharide-air flow battery electrochemistry

    Science.gov (United States)

    Scott, Daniel M.; Tsang, Tsz Ho; Chetty, Leticia; Aloi, Sekotilani; Liaw, Bor Yann

    Recently, an inexpensive monosaccharide-air flow battery configuration has been demonstrated to utilize a strong base and a mediator redox dye to harness electrical power from the partial oxidation of glucose. Here the mechanistic understanding of glucose oxidation in this unique glucose-air power source is further explored by acid-base titration experiments, 13C NMR, and comparison of results from chemically different redox mediators (indigo carmine vs. methyl viologen) and sugars (fructose vs. glucose) via studies using electrochemical techniques. Titration results indicate that gluconic acid is the main product of the cell reaction, as supported by evidence in the 13C NMR spectra. Using indigo carmine as the mediator dye and fructose as the energy source, an abiotic cell configuration generates a power density of 1.66 mW cm -2, which is greater than that produced from glucose under similar conditions (ca. 1.28 mW cm -2). A faster transition from fructose into the ene-diol intermediate than from glucose likely contributed to this difference in power density.

  1. Mechanistic modeling of insecticide risks to breeding birds in ...

    Science.gov (United States)

    Insecticide usage in the United States is ubiquitous in urban, suburban, and rural environments. In evaluating data for an insecticide registration application and for registration review, scientists at the United States Environmental Protection Agency (USEPA) assess the fate of the insecticide and the risk the insecticide poses to the environment and non-target wildlife. At the present time, current USEPA risk assessments do not include population-level endpoints. In this paper, we present a new mechanistic model, which allows risk assessors to estimate the effects of insecticide exposure on the survival and seasonal productivity of birds known to use agricultural fields during their breeding season. The new model was created from two existing USEPA avian risk assessment models, the Terrestrial Investigation Model (TIM v.3.0) and the Markov Chain Nest Productivity model (MCnest). The integrated TIM/MCnest model has been applied to assess the relative risk of 12 insecticides used to control corn pests on a suite of 31 avian species known to use cornfields in midwestern agroecosystems. The 12 insecticides that were assessed in this study are all used to treat major pests of corn (corn root worm borer, cutworm, and armyworm). After running the integrated TIM/MCnest model, we found extensive differences in risk to birds among insecticides, with chlorpyrifos and malathion (organophosphates) generally posing the greatest risk, and bifenthrin and ë-cyhalothrin (

  2. Selected studies in HTGR reprocessing development

    International Nuclear Information System (INIS)

    Notz, K.J.

    1976-03-01

    Recent work at ORNL on hot cell studies, off-gas cleanup, and waste handling is reviewed. The work includes small-scale burning tests with irradiated fuels to study fission product release, development of the KALC process for the removal of 85 Kr from a CO 2 stream, preliminary work on a nonfluidized bed burner, solvent extraction studies including computer modeling, characterization of reprocessing wastes, and initiation of a development program for the fixation of 14 C as CaCO 3

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

    Science.gov (United States)

    Olden, Peter C

    2012-01-01

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

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

    Science.gov (United States)

    Chater, Nick

    2014-04-01

    Cognitive science views thought as computation; and computation, by its very nature, can be understood in both rational and mechanistic terms. In rational terms, a computation solves some information processing problem (e.g., mapping sensory information into a description of the external world; parsing a sentence; selecting among a set of possible actions). In mechanistic terms, a computation corresponds to causal chain of events in a physical device (in engineering context, a silicon chip; in biological context, the nervous system). The discipline is thus at the interface between two very different styles of explanation--as the papers in the current special issue well illustrate, it explores the interplay of rational and mechanistic forces. Copyright © 2014 Cognitive Science Society, Inc.

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

    International Nuclear Information System (INIS)

    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.

    2013-01-01

    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

  6. FOAM3D: A numerical simulator for mechanistic prediciton of foam displacement in multidimensions

    Energy Technology Data Exchange (ETDEWEB)

    Kovscek, A.R.; Patzek, T.W. [Lawrence Berkeley Laboratory, Berkeley, CA (United States); Radke, C.J. [Univ. of California, Berkeley, CA (United States)

    1995-03-01

    Field application of foam is a technically viable enhanced oil recovery process (EOR) as demonstrated by recent steam-foam field studies. Traditional gas-displacement processes, such as steam drive, are improved substantially by controlling gas mobility and thereby improving volumetric displacement efficiency. For instance, Patzek and Koinis showed major oil-recovery response after about two years of foam injection in two different pilot studies at the Kern River field. They report increased production of 5.5 to 14% of the original oil in place over a five year period. Because reservoir-scale simulation is a vital component of the engineering and economic evaluation of any EOR project, efficient application of foam as a displacement fluid requires a predictive numerical model of foam displacement. A mechanistic model would also expedite scale-up of the process from the laboratory to the field scale. No general, mechanistic, field-scale model for foam displacement is currently in use.

  7. Mechanistic study on the fluorination of K[B(CN)4] with ClF enabling the high yield and large scale synthesis of K[B(CF3)4] and K[(CF3)3BCN].

    Science.gov (United States)

    Bernhardt, Eduard; Finze, Maik; Willner, Helge

    2011-10-17

    The fluorination of K[B(CN)(4)] with ClF is studied by millimolar test reactions in aHF and CH(2)Cl(2) solution and by subsequent identification of intermediates such as B-CF═NCl, B-CF(2)-NCl(2), and B-CF(3) species as well as NCl(3) by (19)F, (11)B NMR, and Raman spectroscopy, respectively. At first one cyano group of K[B(CN)(4)] is converted fast into a CF(3) group, and with increasing fluorination the reaction becomes slower and several intermediates could be observed. On the basis of these results, a synthesis was developed for K[B(CF(3))(4)] on a 0.2 molar scale by treatment of K[B(CN)(4)] diluted in aHF with ClF. The course of the reactions was followed by (i) monitoring the vapor pressure inside the reactor, (ii) observing the heat dissipation during ClF uptake, and (iii) measuring the volume of the released nitrogen gas. Since the fluorination of the last cyano group proceeds very slowly, the selective synthesis of K[(CF(3))(3)BCN] on a 0.2 molar scale is possible, as well. The analysis of the mechanisms, thermodynamics, and kinetics of the fluorination reactions is supported by density functional theory (DFT) calculations.

  8. Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics.

    Directory of Open Access Journals (Sweden)

    Chonggang Xu

    Full Text Available Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO(2 concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO(2 concentration, temperature, and radiation when evaluated against published data of V(c,max (maximum carboxylation rate and J(max (maximum electron transport rate. A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO(2 concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions and the

  9. Toward a mechanistic modeling of nitrogen limitation on vegetation dynamics.

    Science.gov (United States)

    Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D; Wilson, Cathy J; Cai, Michael; McDowell, Nate G

    2012-01-01

    Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO(2) concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO(2) concentration, temperature, and radiation when evaluated against published data of V(c,max) (maximum carboxylation rate) and J(max) (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO(2) concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions and the vegetation

  10. Toward a Mechanistic Modeling of Nitrogen Limitation on Vegetation Dynamics

    Science.gov (United States)

    Xu, Chonggang; Fisher, Rosie; Wullschleger, Stan D.; Wilson, Cathy J.; Cai, Michael; McDowell, Nate G.

    2012-01-01

    Nitrogen is a dominant regulator of vegetation dynamics, net primary production, and terrestrial carbon cycles; however, most ecosystem models use a rather simplistic relationship between leaf nitrogen content and photosynthetic capacity. Such an approach does not consider how patterns of nitrogen allocation may change with differences in light intensity, growing-season temperature and CO2 concentration. To account for this known variability in nitrogen-photosynthesis relationships, we develop a mechanistic nitrogen allocation model based on a trade-off of nitrogen allocated between growth and storage, and an optimization of nitrogen allocated among light capture, electron transport, carboxylation, and respiration. The developed model is able to predict the acclimation of photosynthetic capacity to changes in CO2 concentration, temperature, and radiation when evaluated against published data of Vc,max (maximum carboxylation rate) and Jmax (maximum electron transport rate). A sensitivity analysis of the model for herbaceous plants, deciduous and evergreen trees implies that elevated CO2 concentrations lead to lower allocation of nitrogen to carboxylation but higher allocation to storage. Higher growing-season temperatures cause lower allocation of nitrogen to carboxylation, due to higher nitrogen requirements for light capture pigments and for storage. Lower levels of radiation have a much stronger effect on allocation of nitrogen to carboxylation for herbaceous plants than for trees, resulting from higher nitrogen requirements for light capture for herbaceous plants. As far as we know, this is the first model of complete nitrogen allocation that simultaneously considers nitrogen allocation to light capture, electron transport, carboxylation, respiration and storage, and the responses of each to altered environmental conditions. We expect this model could potentially improve our confidence in simulations of carbon-nitrogen interactions and the vegetation feedbacks

  11. Mechanistic insight into oxide-promoted palladium catalysts for the electro-oxidation of ethanol.

    Science.gov (United States)

    Martinez, Ulises; Serov, Alexey; Padilla, Monica; Atanassov, Plamen

    2014-08-01

    Recent advancements in the development of alternatives to proton exchange membrane fuel cells utilizing less-expensive catalysts and renewable liquid fuels, such as alcohols, has been observed for alkaline fuel cell systems. Alcohol fuels present the advantage of not facing the challenge of storage and transportation encountered with hydrogen fuel. Oxidation of alcohols has been improved by the promotion of alloyed or secondary phases. Nevertheless, currently, there is no experimental understanding of the difference between an intrinsic and a synergistic promotion effect in high-pH environments. This report shows evidence of different types of promotion effects on palladium electrocatalysts obtained from the presence of an oxide phase for the oxidation of ethanol. The correlation of mechanistic in situ IR spectroscopic studies with electrochemical voltammetry studies on two similar electrocatalytic systems allow the role of either an alloyed or a secondary phase on the mechanism of oxidation of ethanol to be elucidated. Evidence is presented for the difference between an intrinsic effect obtained from an alloyed system and a synergistic effect produced by the presence of an oxide phase. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Mechanistic insights of intestinal absorption and renal conservation of folate in chronic alcoholism.

    Science.gov (United States)

    Wani, Nissar Ahmad; Thakur, Shilpa; Najar, Rauf Ahmad; Nada, Ritambhara; Khanduja, Krishan Lal; Kaur, Jyotdeep

    2013-03-01

    Folate mediated one-carbon metabolism is of fundamental importance for various cellular processes, including DNA synthesis and methylation of biological molecules. Due to the exogenous requirement of folate in mammals, there exists a well developed epithelial folate transport system for regulation of normal folate homeostasis. The intestinal and renal folate uptake is tightly and diversely regulated and disturbances in folate homeostasis like in alcoholism have pathological consequences. The study was sought to delineate the regulatory mechanism of folate uptake in intestine and reabsorption in renal tubular cells that could evaluate insights of malabsorption during alcoholism. The folate transporters PCFT and RFC were found to be associated with lipid rafts of membrane surfaces in intestine and kidney. Importantly, the observed lower intestinal and renal folate uptake was associated with decreased levels of folate transporter viz. PCFT and RFC in lipid rafts of intestinal and renal membrane surfaces. The decreased association of folate transporters in lipid rafts was associated with decreased protein and mRNA levels. In addition, immunohistochemical studies showed that alcoholic conditions deranged that localization of PCFT and RFC. These findings could explain the possible mechanistic insights that may result in folate malabsorption during alcoholism. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Mechanistic rationalization of unusual sigmoidal kinetic profiles in the Machetti-De Sarlo cycloaddition reaction.

    Science.gov (United States)

    Mower, Matthew P; Blackmond, Donna G

    2015-02-18

    Unusual sigmoidal kinetic profiles in the Machetti-De Sarlo base-catalyzed 1,3-dipolar cycloaddition of acrylamide to N-methylnitroacetamide are rationalized by detailed in situ kinetic analysis. A dual role is uncovered in which a substrate acts as a precursor to catalyze its own reaction. Such kinetic studies provide a general protocol for distinguishing among different mechanistic origins of induction periods in complex organic reactions.

  14. Employability of Graduates from International Development Studies ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Knowledge to shape learning This study will collect and analyze longitudinal data ... Canadian Consortium of University Programs in International Development ... Call for new OWSD Fellowships for Early Career Women Scientists now open ... an opportunity for the awardees to develop their skills and network with some of ...

  15. Study and development of amplitude coder

    International Nuclear Information System (INIS)

    Tripon, M.

    1987-06-01

    The lengthening door aimed to the memorization of the analog impulse peak delivered by the detectors has been developed in two versions. A converter with successive approximation was chosen whose very bad differential linearity has been corrected by the gliding scale method: a computer simulation allowed to characterize the correction efficiency. Two versions with eight impulse channel have been studied and developed [fr

  16. Identifying mechanistic similarities in drug responses

    KAUST Repository

    Zhao, C.; Hua, J.; Bittner, M. L.; Ivanov, I.; Dougherty, a. E. R.

    2012-01-01

    Motivation: In early drug development, it would be beneficial to be able to identify those dynamic patterns of gene response that indicate that drugs targeting a particular gene will be likely or not to elicit the desired response. One approach

  17. CASID and Canadian Journal of Development Studies ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    CASID and Canadian Journal of Development Studies : Organizational Strengthening 2007- ... with its Executive Council, as well as an external organizational assessment. ... Sharing opportunities for innovation in climate change adaptation.

  18. Mechanistic aspects of failure of mineralized tissue

    Science.gov (United States)

    Nalla, Ravi Kiran

    Over the past few decades, there has been increased interest in the structure and properties of mineralized biological tissues like bone and dentin (a structurally simpler analogue of bone that makes up the bulk of the human tooth). In particular, there has been considerable research into the mechanical properties of such tissues and into how they fracture. An understanding of these properties is of great importance from the perspective of developing a realistic framework for life prediction, particularly in light of the effect of microstructural modifications from aging, disease, remodeling, etc. Central to these issues is the resistance to fracture of these materials, and the microstructural mechanisms that are the source of such resistance. Understanding such properties in the context of the inherent hierarchical complexity of the microstructure of these tissues is of obvious importance. However, surprisingly, such questions have largely remained unanswered and to a large extent, even uninvestigated. The present study initially seeks to focus on the fracture and fatigue behavior of dentin and to extend the observations to cortical bone. Accordingly, fracture mechanics based experiments were conducted to evaluate the fracture toughness of dentin in the context of the anisotropy with respect to the underlying microstructure, and discussed in terms of the salient toughening mechanisms active in this material. In light of the presence of such mechanisms, the fracture toughness properties were then evaluated in terms of resistance-curve (R-curve) behavior, i.e., fracture resistance increasing with crack extension. Furthermore, dentin is known to be susceptible to failure under cyclic loading. The "stress-life" and fatigue-crack propagation data obtained through a systematic investigation of the effects of prolonged cyclical loading are discussed. It is concluded that the presence of small incipient flaws in human teeth of the order of 250 mum in size will not

  19. Universities' Role in Regional Development: A Case Study of University for Development Studies, Ghana

    Science.gov (United States)

    Abonyi, Usman Kojo

    2016-01-01

    This study, employing an interpretive research paradigm, sought to investigate into how University for Development Studies (UDS) is responding to its regional development mandate with a specific focus on how it is responding to human capital development, innovation capabilities, and social and environmental development in northern Ghana. A study…

  20. Mechanistic effect modeling for ecological risk assessment: where to go from here?

    Science.gov (United States)

    Grimm, Volker; Martin, Benjamin T

    2013-07-01

    Mechanistic effect models (MEMs) consider the mechanisms of how chemicals affect individuals and ecological systems such as populations and communities. There is an increasing awareness that MEMs have high potential to make risk assessment of chemicals more ecologically relevant than current standard practice. Here we discuss what kinds of MEMs are needed to improve scientific and regulatory aspects of risk assessment. To make valid predictions for a wide range of environmental conditions, MEMs need to include a sufficient amount of emergence, for example, population dynamics emerging from what individual organisms do. We present 1 example where the life cycle of individuals is described using Dynamic Energy Budget theory. The resulting individual-based population model is thus parameterized at the individual level but correctly predicts multiple patterns at the population level. This is the case for both control and treated populations. We conclude that the state-of-the-art in mechanistic effect modeling has reached a level where MEMs are robust and predictive enough to be used in regulatory risk assessment. Mechanistic effect models will thus be used to advance the scientific basis of current standard practice and will, if their development follows Good Modeling Practice, be included in a standardized way in future regulatory risk assessments. Copyright © 2013 SETAC.

  1. Comparative analysis of perturbed molecular pathways identified in in vitro and in vivo toxicology studies

    NARCIS (Netherlands)

    Wiesinger, Martin; Mayer, Bernd; Jennings, Paul; Lukas, Arno

    The development of in vitro toxicological testing strategies are hampered by the difficulty in extrapolation to the intact organism. Academic toxicological literature contains a wealth of mechanistically rich information, especially arising from omic studies, which could potentially be utilized to

  2. Phenomenological and mechanistic modeling of melt-structure-water interactions in a light water reactor severe accident

    International Nuclear Information System (INIS)

    Bui, V.A.

    1998-01-01

    The objective of this work is to address the modeling of the thermal hydrodynamic phenomena and interactions occurring during the progression of reactor severe accidents. Integrated phenomenological models are developed to describe the accident scenarios, which consist of many processes, while mechanistic modeling, including direct numerical simulation, is carried out to describe separate effects and selected physical phenomena of particular importance

  3. Mechanistic dissection of plant embryo initiation

    NARCIS (Netherlands)

    Radoeva, T.M.

    2016-01-01

    Land plants can reproduce sexually by developing an embryo from a fertilized egg cell, the zygote. After fertilization, the zygote undergoes several rounds of controlled cell divisions to generate a mature embryo. However, embryo formation can also be induced in a variety of other cell types in

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

    Science.gov (United States)

    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. © 2013 The Authors. Biological Reviews © 2013 Cambridge Philosophical Society.

  5. A mechanistic modeling and data assimilation framework for Mojave Desert ecohydrology

    Science.gov (United States)

    Ng, Gene-Hua Crystal.; Bedford, David; Miller, David

    2014-01-01

    This study demonstrates and addresses challenges in coupled ecohydrological modeling in deserts, which arise due to unique plant adaptations, marginal growing conditions, slow net primary production rates, and highly variable rainfall. We consider model uncertainty from both structural and parameter errors and present a mechanistic model for the shrub Larrea tridentata (creosote bush) under conditions found in the Mojave National Preserve in southeastern California (USA). Desert-specific plant and soil features are incorporated into the CLM-CN model by Oleson et al. (2010). We then develop a data assimilation framework using the ensemble Kalman filter (EnKF) to estimate model parameters based on soil moisture and leaf-area index observations. A new implementation procedure, the “multisite loop EnKF,” tackles parameter estimation difficulties found to affect desert ecohydrological applications. Specifically, the procedure iterates through data from various observation sites to alleviate adverse filter impacts from non-Gaussianity in small desert vegetation state values. It also readjusts inconsistent parameters and states through a model spin-up step that accounts for longer dynamical time scales due to infrequent rainfall in deserts. Observation error variance inflation may also be needed to help prevent divergence of estimates from true values. Synthetic test results highlight the importance of adequate observations for reducing model uncertainty, which can be achieved through data quality or quantity.

  6. A mechanistic modeling and data assimilation framework for Mojave Desert ecohydrology

    Science.gov (United States)

    Ng, Gene-Hua Crystal; Bedford, David R.; Miller, David M.

    2014-06-01

    This study demonstrates and addresses challenges in coupled ecohydrological modeling in deserts, which arise due to unique plant adaptations, marginal growing conditions, slow net primary production rates, and highly variable rainfall. We consider model uncertainty from both structural and parameter errors and present a mechanistic model for the shrub Larrea tridentata (creosote bush) under conditions found in the Mojave National Preserve in southeastern California (USA). Desert-specific plant and soil features are incorporated into the CLM-CN model by Oleson et al. (2010). We then develop a data assimilation framework using the ensemble Kalman filter (EnKF) to estimate model parameters based on soil moisture and leaf-area index observations. A new implementation procedure, the "multisite loop EnKF," tackles parameter estimation difficulties found to affect desert ecohydrological applications. Specifically, the procedure iterates through data from various observation sites to alleviate adverse filter impacts from non-Gaussianity in small desert vegetation state values. It also readjusts inconsistent parameters and states through a model spin-up step that accounts for longer dynamical time scales due to infrequent rainfall in deserts. Observation error variance inflation may also be needed to help prevent divergence of estimates from true values. Synthetic test results highlight the importance of adequate observations for reducing model uncertainty, which can be achieved through data quality or quantity.

  7. Inhibition of amyloid oligomerization into different supramolecular architectures by small molecules: mechanistic insights and design rules.

    Science.gov (United States)

    Brahmachari, Sayanti; Paul, Ashim; Segal, Daniel; Gazit, Ehud

    2017-05-01

    Protein misfolding and aggregation have been associated with several human disorders, including Alzheimer's, Parkinson's and Huntington's diseases, as well as senile systemic amyloidosis and Type II diabetes. However, there is no current disease-modifying therapy available for the treatment of these disorders. In spite of extensive academic, pharmaceutical, medicinal and clinical research, a complete mechanistic model for this family of diseases is still lacking. In this review, we primarily discuss the different types of small molecular entities which have been used for the inhibition of the aggregation process of different amyloidogenic proteins under diseased conditions. These include small peptides, polyphenols, inositols, quinones and their derivatives, and metal chelator molecules. In recent years, these groups of molecules have been extensively studied using in vitro, in vivo and computational models to understand their mechanism of action and common structural features underlying the process of inhibition. A salient feature found to be instrumental in the process of inhibition is the balance between the aromatic unit that functions as the amyloid recognition unit and the hydrophilic amyloid breaker unit. The establishment of structure-function relationship for amyloid-modifying therapies by the various functional entities should serve as an important step toward the development of efficient therapeutics.

  8. Disruption of steroidogenesis: Cell models for mechanistic investigations and as screening tools.

    Science.gov (United States)

    Odermatt, Alex; Strajhar, Petra; Engeli, Roger T

    2016-04-01

    In the modern world, humans are exposed during their whole life to a large number of synthetic chemicals. Some of these chemicals have the potential to disrupt endocrine functions and contribute to the development and/or progression of major diseases. Every year approximately 1000 novel chemicals, used in industrial production, agriculture, consumer products or as pharmaceuticals, are reaching the market, often with limited safety assessment regarding potential endocrine activities. Steroids are essential endocrine hormones, and the importance of the steroidogenesis pathway as a target for endocrine disrupting chemicals (EDCs) has been recognized by leading scientists and authorities. Cell lines have a prominent role in the initial stages of toxicity assessment, i.e. for mechanistic investigations and for the medium to high throughput analysis of chemicals for potential steroidogenesis disrupting activities. Nevertheless, the users have to be aware of the limitations of the existing cell models in order to apply them properly, and there is a great demand for improved cell-based testing systems and protocols. This review intends to provide an overview of the available cell lines for studying effects of chemicals on gonadal and adrenal steroidogenesis, their use and limitations, as well as the need for future improvements of cell-based testing systems and protocols. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. A mechanistic determination of horizontal flow regime bound using void wave celerity

    Energy Technology Data Exchange (ETDEWEB)

    Park, J.W. [Ajou Univ., Suwon (Korea, Republic of)

    1995-09-01

    The two-phase flow regime boundaries in a horizontal channel has been investigated by using the behavior of the second order void wave celerities. The average two-fluid model has been constituted with closure relations for horizontally stratified and bubbly flows. A vapor phase turbulent stress model for a smooth interface geometry has been included. It is found that the second order waves (i.e., eigenvalues) propagate in opposite direction with almost the same speed when the liquid phase is stationary. Using the well-posedness limit of the two-phase system, the dispersed-stratified flow regime boundary has been modeled. Two-phase Froude number has been theoretically found to be a convenient parameter in quantifying the flow regime boundary as a function of the void fraction. It is found that interaction between void wave celerities become stronger as the two-phase Froude number is reduced. This result should be interpreted as that gravity and the relative velocity are key parameters in determining flow regime boundaries in a horizontal flow. The influence of the vapor phase turbulent stress found to stabilize the flow stratification. This study clearly shows that the average two-fluid model is very effective for a mechanistic determination of horizontal flow regimes if appropriate closure relations are developed.

  10. Mechanistic Analysis of Cocrystal Dissolution as a Function of pH and Micellar Solubilization.

    Science.gov (United States)

    Cao, Fengjuan; Amidon, Gordon L; Rodriguez-Hornedo, Nair; Amidon, Gregory E

    2016-03-07

    The purpose of this work is to provide a mechanistic understanding of the dissolution behavior of cocrystals under the influence of ionization and micellar solubilization. Mass transport models were developed by applying Fick's law of diffusion to dissolution with simultaneous chemical reactions in the hydrodynamic boundary layer adjacent to the dissolving cocrystal surface to predict the pH at the dissolving solid-liquid interface (i.e., interfacial pH) and the flux of cocrystals. To evaluate the predictive power of these models, dissolution studies of carbamazepine-saccharin (CBZ-SAC) and carbamazepine-salicylic acid (CBZ-SLC) cocrystals were performed at varied pH and surfactant concentrations above the critical stabilization concentration (CSC), where the cocrystals were thermodynamically stable. The findings in this work demonstrate that the pH dependent dissolution behavior of cocrystals with ionizable components is dependent on interfacial pH. This mass transport analysis demonstrates the importance of pH, cocrystal solubility, diffusivity, and micellar solubilization on the dissolution rates of cocrystals.

  11. A mechanistic determination of horizontal flow regime bound using void wave celerity

    International Nuclear Information System (INIS)

    Park, J.W.

    1995-01-01

    The two-phase flow regime boundaries in a horizontal channel has been investigated by using the behavior of the second order void wave celerities. The average two-fluid model has been constituted with closure relations for horizontally stratified and bubbly flows. A vapor phase turbulent stress model for a smooth interface geometry has been included. It is found that the second order waves (i.e., eigenvalues) propagate in opposite direction with almost the same speed when the liquid phase is stationary. Using the well-posedness limit of the two-phase system, the dispersed-stratified flow regime boundary has been modeled. Two-phase Froude number has been theoretically found to be a convenient parameter in quantifying the flow regime boundary as a function of the void fraction. It is found that interaction between void wave celerities become stronger as the two-phase Froude number is reduced. This result should be interpreted as that gravity and the relative velocity are key parameters in determining flow regime boundaries in a horizontal flow. The influence of the vapor phase turbulent stress found to stabilize the flow stratification. This study clearly shows that the average two-fluid model is very effective for a mechanistic determination of horizontal flow regimes if appropriate closure relations are developed

  12. The quest for a mechanistic understanding of biodiversity-ecosystem services relationships.

    Science.gov (United States)

    Duncan, Clare; Thompson, Julian R; Pettorelli, Nathalie

    2015-10-22

    Ecosystem services (ES) approaches to biodiversity conservation are currently high on the ecological research and policy agendas. However, despite a wealth of studies into biodiversity's role in maintaining ES (B-ES relationships) across landscapes, we still lack generalities in the nature and strengths of these linkages. Reasons for this are manifold, but can largely be attributed to (i) a lack of adherence to definitions and thus a confusion between final ES and the ecosystem functions (EFs) underpinning them, (ii) a focus on uninformative biodiversity indices and singular hypotheses and (iii) top-down analyses across large spatial scales and overlooking of context-dependency. The biodiversity-ecosystem functioning (B-EF) field provides an alternate context for examining biodiversity's mechanistic role in shaping ES, focusing on species' characteristics that may drive EFs via multiple mechanisms across contexts. Despite acknowledgements of a need for B-ES research to look towards underlying B-EF linkages, the connections between these areas of research remains weak. With this review, we pull together recent B-EF findings to identify key areas for future developments in B-ES research. We highlight a means by which B-ES research may begin to identify how and when multiple underlying B-EF relationships may scale to final ES delivery and trade-offs. © 2015 The Author(s).

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

    Science.gov (United States)

    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.

  14. Descriptive and mechanistic models of crop–weed competition

    NARCIS (Netherlands)

    Bastiaans, L.; Storkey, J.

    2017-01-01

    Crop-weed competitive relations are an important element of agroecosystems. Quantifying and understanding them helps to design appropriate weed management at operational, tactical and strategic level. This chapter presents and discusses simple descriptive and more mechanistic models for crop-weed

  15. A mechanistic model on methane oxidation in the rice rhizosphere

    NARCIS (Netherlands)

    Bodegom, van P.M.; Leffelaar, P.A.; Goudriaan, J.

    2001-01-01

    A mechanistic model is presented on the processes leading to methane oxidation in rice rhizosphere. The model is driven by oxygen release from a rice root into anaerobic rice soil. Oxygen is consumed by heterotrophic and methanotrophic respiration, described by double Monod kinetics, and by iron

  16. Precision and accuracy of mechanistic-empirical pavement design

    CSIR Research Space (South Africa)

    Theyse, HL

    2006-09-01

    Full Text Available are discussed in general. The effects of variability and error on the design accuracy and design risk are lastly illustrated at the hand of a simple mechanistic-empirical design problem, showing that the engineering models alone determine the accuracy...

  17. The mechanistic bases of the power-time relationship

    DEFF Research Database (Denmark)

    Vanhatalo, Anni; Black, Matthew I; DiMenna, Fred J

    2016-01-01

    .025) and inversely correlated with muscle type IIx fibre proportion (r = -0.76, P = 0.01). There was no relationship between W' (19.4 ± 6.3 kJ) and muscle fibre type. These data indicate a mechanistic link between the bioenergetic characteristics of different muscle fibre types and the power-duration relationship...

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

    Science.gov (United States)

    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…

  19. Journal of Development and Communication Studies: Advanced ...

    African Journals Online (AJOL)

    PROMOTING ACCESS TO AFRICAN RESEARCH ... Journal of Development and Communication Studies: Advanced Search ... of characters; e.g., soci* morality would match documents containing "sociological" or "societal" .... Journal of Business and Administrative Studies, Journal of Business Research, Journal of Child ...

  20. Mec