Dissertations / Theses on the topic 'Mechanistic Approaches'
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Pidala, Joseph. "Achievement of Transplantation Tolerance: Novel Approaches and Mechanistic Insights." Scholar Commons, 2014. https://scholarcommons.usf.edu/etd/5104.
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Current immune suppressive strategies fail to induce donor-recipient immune tolerance after allogeneic hematopoietic cell transplantation. Accordingly, patients suffer morbidity and mortality from graft vs. host disease (GVHD) and prolonged immune suppressive therapy. Biologic insight into transplantation tolerance is needed, and translation of such insight to novel clinical strategies may improve clinical outcomes. We report original investigation at seminal phases of this process including initial prophylactic immune suppression, onset of acute graft vs. host disease, and ultimate immune suppression discontinuation: In a controlled randomized clinical trial, we demonstrate that sirolimus-based immune suppression reduces risk for acute GVHD, ameliorates the severity of subsequent chronic GVHD, and supports reconstitution of functional regulatory T cells. Study of tissue-infiltrating CD4+ T cell subsets in acute GVHD target organs supports a pathogenic role for Th17 cells. Finally, we demonstrate that peripheral blood transcriptional biomarkers provide mechanistic insight into human transplantation tolerance. These data signal progress, and suggest rational translational efforts to achieve transplantation tolerance.
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Delp, Johannes [Verfasser]. "Functional and mechanistic approaches to improve neurotoxicity predictions / Johannes Delp." Konstanz : KOPS Universität Konstanz, 2019. http://d-nb.info/1227841167/34.
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Watson, Susan B. "Outbreaks of taste/odour causing algal species, theoretical, mechanistic and applied approaches." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0026/NQ49547.pdf.
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Fausti, Giovanni. "Towards new approaches for the generation of phosphorus based radical : synthetic and mechanistic investigations." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMC271/document.
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Cette thèse rapporte trois modes d'activation complémentaires pour la génération de radicaux à base de phosphore, qui ont été utilisés pour la synthèse de composés organophosphorés.Tout d’abord, nous avons décrit une génération photocatalytique de radicaux phosphinoyle en utilisant le sel d'acridinium, le perchlorate de 9-mésityl-10-méthylacridinium connu sous le nom de catalyseur de Fukuzumi, en tant que photocatalyseur, et triflate de diphényliodonium comme photo-oxydant externe. Ce système purement organique nous a permis d'obtenir la première hydrophosphinylation sans métal des alcènes. Plusieurs enquêtes mécaniques, telles que la résonance paramagnétique électronique (EPR), la photolyse laser, la fluorescence et les quantum yields measurements ont été utilisées pour comprendre les facteurs qui régissent cette photoréaction.Dans le chapitre suivant, la formation de complexes Electron-Donor-Acceptor (EDA) entre les oxydes de phosphine secondaires et l'ion diphényliodonium a été utilisée pour générer un radical phosphinoyle sous irradiation bleue. Des études expérimentales et théoriques combinées ont été utilisées pour élucider la formation de complexes d'EDA. Cette stratégie a ensuite été utilisée pour décrire l'hydrophosphinylation des alcènes.Le dernier chapitre rapporte une méthode légère sans métal pour la synthèse d'oxindoles phosphorylés, qui sont des composés pharmaceutiques potentiellement actifs. La portée et les limites de cette approche ont été discutées avec des enquêtes mécanistiques préliminairesThis Thesis reports three complimentary modes of activation for the generation of phosphorus based radicals, which have been employed for the synthesis of organophosphorus compounds.We have first described a photocatalytic generation phosphinoyl radicals by using the acridinium salt, 9-mesityl-10-methylacridinium perchlorate known as Fukuzumi’ catalyst, as a photocatalyst and diphenyliodonium triflate as an external photooxidant. This purely organic system allowed us to achieve the first metal–free hydrophosphinylation of alkenes. Several mechanistic investigations, such as Electron Paramagnetic Resonance (EPR), Laser Flash Photolysis, fluorescence quenching and quantum yields measurements have been employed to understand factors governing this photoreaction.In the subsequent chapter, the formation of Electron–Donor–Acceptor complexes (EDA) between secondary phosphine oxides and the diphenyliodonium ion has been used to generate phosphinoyl radical under blue irradiation. A combined experimental and theoretical investigations have been used to elucidate the formation of EDA complexes. This strategy has then been employed to describe hydrophosphinylation of alkenes.The last chapter reports a metal–free visible light mild method for the synthesis of phosphorylated oxindoles, which are potentially active pharmaceutical compounds. Scope and limitations of this approach have been discussed along with preliminary mechanistic investigations
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Pilari, Sabine [Verfasser]. "Novel approaches to mechanistic pharmacokinetic/pharmacodynamic modeling : lumping of PBPK models and systems biology / Sabine Pilari." Berlin : Freie Universität Berlin, 2011. http://d-nb.info/1025551605/34.
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Walpole, Emily H. "Communicating Climate Adaptation: A Mechanistic and Audience-Based Investigation of Message Framing Approaches for Climate-Exacerbated Hazards." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563383189022141.
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Lischik, Colin [Verfasser], and Joachim [Akademischer Betreuer] Wittbrodt. "Combining in vivo imaging and mechanistic approaches to investigate Wnt regulation of retinal stem cells / Colin Lischik ; Betreuer: Joachim Wittbrodt." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/118744572X/34.
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Lischik, Colin Q. [Verfasser], and Joachim [Akademischer Betreuer] Wittbrodt. "Combining in vivo imaging and mechanistic approaches to investigate Wnt regulation of retinal stem cells / Colin Lischik ; Betreuer: Joachim Wittbrodt." Heidelberg : Universitätsbibliothek Heidelberg, 2019. http://d-nb.info/118744572X/34.
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Mustapha, Lateef Abimbola, and Lateef Abimbola Mustapha. "Thermo-Mechanical Characterization and Interfacial Thermal Resistance Studies of Chemically Modified Carbon Nanotube Thermal Interface Material - Experimental and Mechanistic Approaches." Diss., The University of Arizona, 2017. http://hdl.handle.net/10150/625379.
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Effective application of thermal interface materials (TIM) sandwiched between silicon and a heat spreader in a microelectronic package for improved heat dissipation is studied through thermal and mechanical characterization of high thermally conductive carbon nanotubes (CNTs) integrated into eutectic gallium indium liquid metal (LM) wetting matrix. Thermal conductivity data from Infrared microscopy tool reveals the dependence of experimental factors such as matrix types, TIM contacting interfaces, orientation of CNTs and wetting of CNTs in the matrix on the thermal behavior of TIM composite.
Observed generalized trend on LM-CNT TIM shows progressive decrease in effective thermal conductivity with increasing CNT volume fractions. Further thermal characterizations LM-CNT TIM however show over 2x increase in effective thermal conductivity over conventional polymer TIMs (i.e. TIM from silicone oil matrix) but fails to meet 10x improvement expected.
Poor wetting of CNT with LM matrix is hypothesized to hinder thermal improvement of LM-CNT TIM composite. Thus, wetting enhancement technique through electro-wetting and liquid crystal (LC) based matrix proposed to enhance CNT-CNT contact in LM-CNT TIM results in thermal conductivity improvement of 40 to 50% with introduction of voltage gradient of 2 to 24 volts on LM-CNT TIM sample with 0.1 to 1 percent CNT volume fractions over non voltage LM-CNT TIM test samples.
Key findings through this study show that voltage tests on LC- CNT TIM can cause increased CNT-CNT networks resulting in 5x increase in thermal conductivity over non voltage LC-CNT TIM and over 2x improvement over silicone-CNT TIMs. Validation of LM wetting of CNT hypothesis further shows that wetting and interface adhesion mechanisms are not the only factors required to improve thermal performance of LM-CNT TIM. Anisotropic characteristic of thermal conductivity of randomly dispersed CNTs is a major factor causing lower thermal performance of LM-CNTs TIM composite. Other factors resulting in LM-CNT TIM decreasing thermal conductivity with increasing CNT loading are (i) Lack of CNT-CNT network due to large difference in surface tension and mass density between CNTs and LM in TIM composite (ii) Structural stability of MWCNT and small MFP of phonons in ~5um MWCNTs compared to the system resulted in phonon scattering with reduced heat flow (iii) CNT percolation threshold limit not reached owing to thermal shielding due to CNT tube interfacial thermal resistance.
While mixture analytical models employed are able to predict thermal behaviors consistent with CNT-CNT network and CNT- polymer matrix contact phenomenon, these models are not equipped to predict thermo-chemical attributes of CNTs in LM-CNT TIM. Extent of LM-CNT wetting and LM-solid surface interfacial contact impacts on interfacial thermal resistance are investigated through LM contact angle, XPS/AES and SEM-EDX analyses on Au/Ni and Ni coated copper surfaces. Contact angle measurements in the range of 120o at both 55oC and 125oC show non wetting of LM on CNT, Au and Ni surfaces. Interface reactive wetting elemental composition of 21 days aged LM on Au/Ni and Ni surfaces reveals Ga dissolution in Au and Ni diffusion of ~0.32um in Au which are not present for similar analysis of 1 day LM on Au/Ni surface. Formation of Au-Ni-Ga IMC and IMC-oxide iono-covalency occurrence at the interface causes reduction in surface tension and reduction in interfacial contact resistance.
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Mazloomi, Zahra. "New approaches to perfluoroalkylation of aromatic compounds, and tailor-made catalysts for C-X bond forming and water oxidation reactions. Mechanistic insights." Doctoral thesis, Universitat Rovira i Virgili, 2017. http://hdl.handle.net/10803/450517.
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Aquesta tesis esta dividida en dos parts: la primer part es va realizar a l’Institut Català d’Invstigació Química (ICIQ) desde 2012 fins a 2015, aquesta part tracta sobre la perfluoroalquilació de substrats aromatics i inclou dos projectes principals. L’objectiu del primer projecte era la producción en flux continu de CuCF3 com a reactiu trifluorometilat i la confirmació de la seva eficacia en la trifluorometilacio de diversos halurs aromatics, els quals van ser tractats amb CuCF3 i es van convertir selectivament en composotos trifluorometilats.
En el segon projecte, l’objectiu era transformar diferents halurs vinílics a anàlegs trifluorometilats i pentafluoroetilats emprant els reactius nucleòfils CuCF3 i CuC2F5, el quals ja havien estat utilitzats prèviament en el mateix grup.
La segona part s’ha dut a terme a la Universitat Rovira i Virgili (URV) a partir de 2015 fins al 2017. Aquesta part tracta sobre diferents reaccions catalítiques de formació d’enllaços C-X i estudis mecanístics sobre d’aquestes. Aquesta part conté 4 projectes d’investigació. Tres d’ells tracten sobre la síntesi i l’aplicació en varies reaccions catalítiques de gran rellevància de diversos complexes de carbens anormals amb Ir (I), Ir (III) i Ru (II). Aquests catalitzadors altament eficaços s’han aplicat amb èxit en la hidrogenació per transferència d’enllaços C = O, C = N i C = C, també en la deshidrogenació d’alcohols i l’oxidació amb aigua. L’últim projecte tracta sobre la formació catalítica asimètrica d’enllaços C-C amb una nova i versàtil lligandoteca de lligands P-N quirals. Tots els objectius d’aquesta segona part de la tesis s’han realitzat amb èxit.
En resum, en aquesta tesis s’ha realitzat diverses transformacions químiques importants, totes elles de gran interès en la formació de productes farmacèutics, agroquímics, naturals i de química fina y en ala producció d’energia neta. El treball realitzat en aquesta tesis conté aspectes fonamentals de la química i des del punt de vista química i industrial, existeix una gran demanda en el desenvolupament i millora de tots els processos mencionats.Esta tesis está dividida en dos partes: la primera parte se realizó en el Instituto Catalán de Investigación Química (ICIQ) desde 2012 hasta 2015, esta parte trata sobre la perfluoroalquilación de sustratos aromáticos e incluye dos proyectos principales. El objetivo del primer proyecto era la producción en flujo continuo de CuCF3 como reactivo trifluorometilado y la confirmación de su eficacia en la trifluorometilación de algunos haluros aromáticos, los cuales fueron tratados con CuCF3 y se convirtieron selectivamente en compuestos trifluorometilados. En el segundo proyecto, el objetivo era transformar varios haluros vinílicos a análogos trifluorometilados y pentafluoroetilados usando los reactivos nucleófilos CuCF3 y CuC2F5, los cuales habían sido utilizados previamente en el mismo grupo. La segunda parte se ha llevado a cabo en la Universidad de Rovira i Virgili (URV) a partir de 2015 hasta 2017. Esta parte trata sobre diferentes reacciones catalíticas de formación de enlaces C-X y estudios mecanísticos sobre de estas. Esta parte contiene 4 proyectos de investigación. Tres de ellos tratan sobre la síntesis y aplicación en varias reacciones catalíticas de gran relevancia de varios complejos de carbeno anormales con Ir (I), Ir (III) y Ru (II). Estos catalizadores altamente eficaces se aplicaron con éxito en la hidrogenación por transferencia de enlaces C = O, C = N y C = C, también en la deshidrogenación de alcoholes y la oxidación con agua. El último proyecto trata sobre la formación catalítica asimétrica de enlaces C-C con una nueva y versátil biblioteca de ligandos P-N quirales. Todos los objetivos de la segunda parte de la tesis se realizaron con éxito. En resumen, en esta tesis se han realizado diversas transformaciones químicas importantes, todas ellas de gran interés en la formación de productos farmacéuticos, agroquímicos, naturales, de química fina y en la producción de energía limpia. El trabajo hecho en esta tesis contiene aspectos fundamentales de la química y desde el punto de vista químico e industrial existe una gran demanda en el desarrollo y mejora de los procesos mencionados.
This dissertation divided into two main parts: the first part which had been done from 2012 until 2015 in Institute of chemical research of Catalonia (ICIQ) is about perfluoroalkylation of aromatic substrate including two main works. In the first project the goal was continuous flow production of CuCF3 as a trifluoromethylated reagent and confirming its efficiency in trifluoromethylation of some aromatic halides which were treated with batch made CuCF3 reagent and selectively converted to trifluoromethylated conterparts. In the second project the target was transforming several vinylic halides to trifluoromethylated and pentafluoroethylated analoges with nucleophilic CuCF3 and CuC2F5 reagents which were demonstrated previously in the same group. The later part has been carried out in the University of Rovira I Virgili (URV) from 2015 until 2017. Generally this part is about different catalytic C-X bond forming reactions with mechanistic insights which contains 4 research projects. Three of them are about synthesis and catalytic application of several Ir(I), Ir(III) and Ru(II) abnormal carbene complexes in several important and challenging catalytic reactions. These highly efficient catalysts successfully applied in transfer hydrogenation of C=O, C=N and C=C functionalities, alcohol dehydrogenation and water oxidation. The last project is asymmetric catalytic formation of C-C bond with a new and versatile chiral P-N ligand library. All of the objectives for the second part of thesis were performed successfully. In conclusion, various important chemical transformation were made in this thesis which all of them are vital in pharmaceuticals, agrochemicals, fine and natural products and the production of clean energy. The total works in this thesis are so important in chemistry and there is a huge demand about developing and improving the mentioned processes from the chemical and industrial point of view.
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Lieb, Dominik [Verfasser], and Ivana [Akademischer Betreuer] Ivanović-Burmazović. "Mechanistic and Synthetic Approaches for Activation of Water-and Oxygen-Species by Biomimetic Systems (Containing Manganese and Cobalt) / Dominik Lieb. Gutachter: Ivana Ivanovic-Burmazovic." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2013. http://d-nb.info/1075567556/34.
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Walubita, Lubinda F. "Comparison of fatigue analysis approaches for predicting fatigue lives of hot-mix asphalt concrete (HMAC) mixtures." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/3898.
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Hot-mix asphalt concrete (HMAC) mixture fatigue characterization constitutes a fundamental component of HMAC pavement structural design and analysis to ensure adequate field fatigue performance. HMAC is a heterogeneous complex composite material of air, binder, and aggregate that behaves in a non-linear elasto-viscoplastic manner, exhibits anisotropic behavior, ages with time, and heals during traffic loading rest periods and changing environmental conditions. Comprehensive HMAC mixture fatigue analysis approaches that take into account this complex nature of HMAC are thus needed to ensure adequate field fatigue performance. In this study, four fatigue analysis approaches; the mechanistic empirical (ME), the calibrated mechanistic with (CMSE) and without (CM) surface energy measurements, and the proposed NCHRP 1-37A 2002 Pavement Design Guide (MEPDG) were comparatively evaluated and utilized to characterize the fatigue resistance of two Texas HMAC mixtures in the laboratory, including investigating the effects of binder oxidative aging. Although the results were comparable, the CMSE/CM approaches exhibited greater flexibility and potential to discretely account for most of the fundamental material properties (including fracture, aging, healing, visco-elasticity, and anisotropy) that affect HMAC pavement fatigue performance. Compared to the other approaches, which are mechanistic-empirically based, the CMSE/CM approaches are based on the fundamental concepts of continuum micromechanics and energy theory.
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Vaidilaite-Pretorius, Agita. "Mechanistic approaches towards understanding particle formation in biopharmaceutical formations : the role of sufactant type and level on protein conformational stability, as assessed by calorimetry, and on protein size stability as assessed by dynamic light scattering, micro flow imaging and HIAC." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/13482.
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Control and analysis of protein aggregation is an increasing challenge to biopharmaceutical research and development. Therefore it is important to understand the interactions, causes and analysis of particles in order to control protein aggregation to enable successful biopharmaceutical formulations. This work investigates the role of different non-ionic surfactants on protein conformational stability, as assessed by HSDSC, and on protein size stability as assessed by Dynamic Light Scattering (DLS), HIAC and MFI. BSA and IgG2 were used as model proteins. Thermal unfolding experiments indicated a very weak surfactant-immunoglobulin IgG2 interaction, compared to much stronger interactions for the BSA surfactant systems. The DLS results showed that BSA and IgG2 with different surfactants and concentration produced different levels of particle size growth. The heat treatment and aging of samples in the presence of Tween 20, Tween 80, Brij 35 and Pluronic F-68 surfactants led to an increase in the populations of larger particles for BSA samples, whereas IgG2 systems did not notably aggregate under storage conditions MFI was shown to be more sensitive than HIAC technique for measuring sub-visible particles in protein surfactant systems. Heat treatment and storage stress showed a significant effect on BSA and IgG2 protein sub-visible particle size stability. This work has demonstrated that both proteins with different Tween 20, Tween 80, Brij 35 and Pluronic F-68 concentrations, have different level of conformational and size stability. Also aging samples and heating stress bears the potential to generate particles, but this depends on surfactant type. Poor predictive correlations between the analytical methods were determined.
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Belger, Dennis Heinz [Verfasser], Maria Andrea [Akademischer Betreuer] Mroginski, Maria Andrea [Gutachter] Mroginski, and Silke [Gutachter] Leimkühler. "Theoretical studies for the development of a better understanding of cofactor-structure and mechanistic properties of photoreceptors and metallo-enzymes with quantum chemical and molecular dynamical approaches / Dennis Heinz Belger ; Gutachter: Maria Andrea Mroginski, Silke Leimkühler ; Betreuer: Maria Andrea Mroginski." Berlin : Technische Universität Berlin, 2020. http://d-nb.info/1205370226/34.
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Chew, Eng-Hui. "Development of antitumour quinols : a mechanistic approach." Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430303.
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Graves, Ronnie Clark II. "AN INNOVATIVE APPROACH TO MECHANISTIC EMPIRICAL PAVEMENT DESIGN." UKnowledge, 2012. http://uknowledge.uky.edu/ce_etds/4.
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The Mechanistic Empirical Pavement Design Guide (MEPDG) developed by the National Cooperative Highway Research Program (NCHRP) project 1-37A, is a very powerful tool for the design and analysis of pavements. The designer utilizes an iterative process to select design parameters and predict performance, if the performance is not acceptable they must change design parameters until an acceptable design is achieved.
The design process has more than 100 input parameters across many areas, including, climatic conditions, material properties for each layer of the pavement, and information about the truck traffic anticipated. Many of these parameters are known to have insignificant influence on the predicted performance
During the development of this procedure, input parameter sensitivity analysis varied a single input parameter while holding other parameters constant, which does not allow for the interaction between specific variables across the entire parameter space. A portion of this research identified a methodology of global sensitivity analysis of the procedure using random sampling techniques across the entire input parameter space. This analysis was used to select the most influential input parameters which could be used in a streamlined design process.
This streamlined method has been developed using Multiple Adaptive Regression Splines (MARS) to develop predictive models derived from a series of actual pavement design solutions from the design software provided by NCHRP. Two different model structures have been developed, one being a series of models which predict pavement distress (rutting, fatigue cracking, faulting and IRI), the second being a forward solution to predict a pavement thickness given a desired level of distress. These thickness prediction models could be developed for any subset of MEPDG solutions desired, such as typical designs within a given state or climatic zone. These solutions could then be modeled with the MARS process to produce am “Efficient Design Solution” of pavement thickness and performance predictions. The procedure developed has the potential to significantly improve the efficiency of pavement designers by allowing them to look at many different design scenarios prior to selecting a design for final analysis.
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Francis, Roslyn Jane. "Antibody directed enzyme prodrug therapy : a mechanistic approach." Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1445532/.
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Antibody directed enzyme prodrug therapy (ADEPT) is a two-step targeting system, which utilises pretargeting of antibody-enzyme to tumour followed by administration of a prodrug, which is converted to an active cytotoxic by the enzyme at tumour sites. This system aims to overcome cancer resistance mechanisms by the tumour specific generation of large quantities of a cytotoxic agent. ADEPT is a complex therapeutic strategy as it involves multiple components, each of which has their own unique requirements for the system as a whole to be successful. It is hypothesised that by measuring mechanism in a clinical trial setting, a greater understanding of ADEPT can be achieved. Additionally, rational modifications can be determined and implemented, thereby accelerating the development process. This thesis demonstrates how mechanistic data attained from one phase I/II ADEPT clinical trial lead to the development of a novel genetically engineered antibody-enzyme fusion protein for ADEPT, which was shown in a second clinical trial to have enhanced features for tumour targeting in ADEPT. The metabolic assessment of tumours using F-18 FDG PET was assessed during both ADEPT trials and shown to provide additional information when compared with conventional response assessment, particularly in the assessment of patients with radiological stable disease. As the data generated on ADEPT from both preclinical and clinical development is large, and the possibilities for modification to the system are numerous, an Ontology and Conceptual Model have been developed to organise the data attained on ADEPT. This thesis demonstrates that although ADEPT is a complex therapeutic strategy it can be successfully studied in a clinical setting using mechanistic clinical trial design, rational modifications can be made and data can be organised to facilitate development for the future.
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Singh, Abhyudai. "A mechanistic approach to tuning of MEMS resonators." Diss., Connect to online resource - MSU authorized users, 2006.
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Villain, Laura. "Analyse et modélisation de l'effet de l'Interleukine 7 chez les patients infectés par le VIH." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0388/document.
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Chez les patients infectés par le VIH, les traitements antirétroviraux empêchent la réplicationvirale, ce qui est suivi, dans la plupart des cas, par une restauration de la population des lymphocytesT CD4+ (CD4). Néanmoins ce n’est pas le cas pour certains patients appelés patients àfaible réponse immunitaire. Des injections d’interleukine-7 (IL7) exogène, une cytokine impliquéedans l’homéostasie des CD4, sont considérées afin de maintenir les taux de CD4 au-dessus de500 cellules par μL, taux au-dessus duquel les patients ont une espérance de vie comparable auxpersonnes non infectées par le VIH. Les essais INSPIRE ont évalué l’effet d’injections répétéesd’IL7 chez les patients à faible réponse immunologique.Nous présentons plusieurs modèles mécanistes de l’effet des injections d’IL7 sur les CD4, quiincluent des effets aléatoires afin de tenir compte de la variabilité inter-individuelle. En utilisantces modèles avec une approche Bayésienne, les paramètres individuels d’un nouveau patient sontéchantillonnés, ce qui nous permet de faire des prédictions sur sa dynamique de CD4 et donc depersonnaliser le traitement. Nous proposons quatre protocoles adaptatifs permettant de limiter letemps passé sous 500 CD4 par μL, sans pour autant augmenter le nombre d’injections. Ces protocolesont été implémentés dans une application Shiny présentant une interface facile d’utilisation,et pourront être testés lors d’essais cliniques.Le réservoir viral, principalement constitué de CD4 quiescentes infectées, est la première barrièreà l’éradication du VIH. Les injections d’IL7 entrainent une augmentation du nombre deCD4 et donc du réservoir viral ; la question est alors de savoir si les injections provoquent denouvelles infections cellulaires ou si le réservoir augmente de la même façon que les CD4. Nousconcluons que si quelques patients ont présenté des dynamiques de marqueurs compatibles avecla survenue de nouvelles infections de cellules, ce n’est pas le cas de la majorité des patients. Laconfirmation de ces phénomènes et la caractérisation de potentiels patients à risque nécessite desdonnées supplémentaires mesurables dans un essai cliniqueIn HIV infected patients, antiretroviral therapy suppresses the viral replication which is followedin most patients by a restoration of the CD4+ T cells (CD4) pool. However, it is not the case forsome patients called low immunological responders. Injections of interleukin-7 (IL7), a cytokineinvolved in the CD4 homeostasis, are considered in order to maintain the CD4 levels above 500cells per μL, the level at which life expectancy is similar to that of the non-infected. INSPIREtrials evaluated the effect of repeated injections of IL7 on low immunological responders.We present a few mechanistic models of the effect of IL7 injections on CD4, which includerandom effects to account for inter-individual variability. Using these models with a Bayesianapproach, the individual parameters of a new patient are sampled, which allows us to makepredictions about its CD4 dynamics and thus to personalize the treatment. We propose fouradaptive protocols that limit the time spent under 500 CD4 per μL, without increasing thenumber of injections. Those protocols are implemented into a Shiny app with an easy to useinterface, and they could be tested during clinical trials.The viral reservoir, mainly made up of quiescent infected CD4, is the main obstacle to HIVeradication. IL7 injections induce an increase of the level of CD4, hence of the viral reservoir ; thequestion is then to determine if the injections induce new cell infections or if the reservoir increasesin the same way as CD4. We conclude that while some patients presented marker dynamicsconsistent with the occurrence of new cell infections, this is not the case for the majority ofpatients. Confirmation of these events and characterization of potential at-risk patients requiresadditional measurable data in a clinical trial
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Berthod, Laurence Mireille Claire. "Mechanistic approach to predicting the sorption characteristics of pharmaceuticals." Thesis, University of Portsmouth, 2015. https://researchportal.port.ac.uk/portal/en/theses/mechanistic-approach-to-predicting-the-sorption-characteristics-of-pharmaceuticals(f7b45eb8-554e-4fdc-b1b1-1b0812d9c2d5).html.
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Over the past forty years concerns over the presence of pharmaceuticals in the environment have grown considerably. Some pharmaceuticals can be effectively biodegraded in wastewater treatment plants but others can be sorbed onto sludges that are often subsequently used as fertilisers or disposed of to landfill. This work aimed to understand how a given pharmaceutical will be distributed between aqueous and solid phases (characterised by the sorbed:dissolved partition coefficient, Kd) within a treatment plant, which is important to be able to make accurate risk assessments. An official guideline test to measure the partitioning of a pharmaceutical in sewage sludge is available, but it is time consuming and fastidious. As activated sewage sludge is a complex matrix, commercially available solid-phase extraction (SPE) cartridges with different chemistries were used to characterise the pharmaceutical-sludge binding processes. As part of this work a new solid-phase extraction screening method has been developed to provide rapid measurements of Kd and its performance was evaluated against partition coefficients obtained with the official guideline method with a correlation coefficient of 0.93 and a r2 of 0.94. In addition, this rapid method allowed the measurement of partition coefficients for pharmaceuticals for which values were not available in the literature and these have been used to further validate new predictive models. Predictive models based on the octanol-water partition coefficient have been developed to calculate partitioning properties of compounds in soil, and these have been extended for application to sewage sludge. These models are optimised mainly for neutral organic chemicals, and only a few consider ionic substances. The work described in this thesis compared the performance of these soil-based models for a range of pharmaceuticals, including ionisable compounds, and assessed their application for the binding of ionic and non-ionic pharmaceuticals in sewage sludge. It also explored other predictive models based on molecular descriptors obtained from chemical structure. These models provided improved predictions over previous models based solely on the octanol-water partition coefficient. In this thesis, partial least squares (PLS) and Bayesian artificial neural network (ANN) models were evaluated for their accuracy in predicting the partition coefficient for neutral, basic, acidic and zwitterionic pharmaceuticals. Literature values were used to develop the models based on a range of molecular descriptors, and their predictive ability was assessed on an external test set of compounds excluded from the model-building process. The performance of the linear PLS and non-linear ANN models were discussed, and their predictive performance and interpretability were compared. Attempts to apply the method for rapid measurement of the sorption of pharmaceuticals to soils were also made to investigate potential read-across from one environmental matrix to another but the two matrices were too dissimilar to achieve this.
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Davies, Deborah. "The ecological impact of Rhinanthus species : a mechanistic approach." Thesis, University of York, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362060.
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Liu, An. "Ferriin oxidation of benzylic 1,2-diols a mechanistic approach /." Morgantown, W. Va. : [West Virginia University Libraries], 1999. http://etd.wvu.edu/templates/showETD.cfm?recnum=861.
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Ochieng, G. M., and F. A. O. Otieno. "Data-Based Mechanistic approach to modelling of daily rainfall-flow relationship : a case of the Upper Vaal water management area." Journal for New Generation Sciences, Vol 6, Issue 1: Central University of Technology, Free State, Bloemfontein, 2008. http://hdl.handle.net/11462/497.
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Published ArticleAlthough deterministic models still dominate hydrological modelling, there is a notable paradigm shift in catchment response modelling. An approach to represent the daily rainfall-flow (R-F) relationship using Data-Based Mechanistic (DBM) modelling is presented. DBM modelling is an inductive empirical transfer function (TF) approach relating input to output. The study used secondary data from the Department of Water Affairs and Forestry for the Upper Vaal water management area at station C1H007. The R-F model identification and optimisation was implemented in the CAPTAIN Toolbox in MATLAB. The best estimated R-F model was a 2nd order TF with an input lag of one day and R 2T= 56%. In mechanistic interpretation, three parallel flow pathways were discerned; the fast flow, slow flow and the loss component each constituting 49.8%, 24% and 26.2% of the modelled flow respectively. The study demonstrates that the approach adopted herein produces reasonably satisfactory results with a minimum of the readily available catchment data.
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Wendling, Thierry. "Hierarchical mechanistic modelling of clinical pharmacokinetic data." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/hierarchical-mechanistic-modelling-of-clinical-pharmacokinetic-data(573652c9-d3fb-4233-bea7-7abd7ef48d4b).html.
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Pharmacokinetic and pharmacodynamic models can be applied to clinical study data using various modelling approaches depending on the aim of the analysis. In population pharmacokinetics for instance, simple compartmental models can be employed to describe concentration-time data, identify prognostic factors and interpolate within well-defined experimental conditions. The first objective of this thesis was to illustrate such a ‘semi-mechanistic’ pharmacokinetic modelling approach using mavoglurant as an example of a compound under clinical development. In particular, methods to accurately characterise complex oral pharmacokinetic profiles and evaluate the impact of absorption factors were investigated. When the purpose of the model-based analysis is to further extrapolate beyond the experimental conditions in order to guide the design of subsequent clinical trials, physiologically-based pharmacokinetic (PBPK) models are more valuable as they incorporate information not only on the drug but also on the system, i.e. on mammillary anatomy and physiology. The combination of such mechanistic models with statistical modelling techniques in order to analysis clinical data has been widely applied in toxicokinetics but has only recently received increasing interest in pharmacokinetics. This is probably because, due to the higher complexity of PBPK models compared to conventional pharmacokinetic models, additional efforts are required for adequate population data analysis. Hence, the second objective of this thesis was to explore methods to allow the application of PBPK models to clinical study data, such as the Bayesian approach or model order reduction techniques, and propose a general mechanistic modelling workflow for population data analysis. In pharmacodynamics, mechanistic modelling of clinical data is even less common than in pharmacokinetics. This is probably because our understanding of the interaction between therapeutic drugs and biological processes is limited and also because the types of data to analyse are often more complex than pharmacokinetic data. In oncology for instance, the most widely used clinical endpoint to evaluate the benefit of an experimental treatment is survival of patients. Survival data are typically censored due to logistic constraints associated with patient follow-up. Hence, the analysis of survival data requires specific statistical techniques. Longitudinal tumour size data have been increasingly used to assess treatment response for solid tumours. In particular, the survival prognostic value of measures derived from such data has been recently evaluated for various types of cancer although not for pancreatic cancer. The last objective of this thesis was therefore to investigate different modelling approaches to analyse survival data of pancreatic cancer patients treated with gemcitabine, and compare tumour burden measures with other patient clinical characteristics and established risk factors, in terms of predictive value for survival.
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Zhang, Wanying. "A Mechanistic Approach Towards the Discovery of Catalytic Acylation Reactions." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35646.
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The development of new, efficient methods for the formation of carbon-carbon bonds using transition metal catalysis has broad applications in the field of organic chemistry and is the key to efficient chemical synthesis. Many efforts had been made to develop efficient ways to make these linkages particularly with the aid of metals such as Rh, Pd, Ni, Ru and Cu. Our group is primarily focused on exploring how these transition metals can activate typically inert functional groups, paving way to new synthetic routes to construct more complex molecules.
Chapter 1 describes attempts that were conducted to achieve hydroacylation between an aldehyde and a non-conjugated alkene via a metal hydride intermediate. The use of RuHCl(CO)(PPh3)3 proved to be the most efficient catalyst for this transformation thus far. Mechanistic investigations were conducted to explore different possibilities to enable this transformation. This chapter also identifies a new self-aldol domino reaction, which consists of a self-aldol condensation of an aldehyde, followed by oxidation and decarbonylation giving rise to a ketone product. Finally, the use of a simple and direct method to access deuterated aldehydes using RuHCl(CO)(PPh3)3 as a catalyst and D2O as a deuterium source is outlined.
Chapter 2 describes a novel Suzuki-Miyaura system that couples esters and boronic esters to form the corresponding ketone product. It was found that an NHC-based Pd catalyst is crucial in the transformation wherein it activates the C(acyl)-O bond of the ester. It is notable that this transformation takes place with the absence of decarbonylation. Reactivity under water in the presence of surfactants was also discovered. Results in aqueous media were demonstrated to be milder than in organic conditions, while achieving similar yields. This system was also applied to coupling of esters and anilines.
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Moroni, Lorenzo. "A mechanistic approach to design smart scaffolds for tissue engineering." Enschede : University of Twente [Host], 2006. http://doc.utwente.nl/57610.
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Montuschi, Alessio. "Flexible pavement design using mechanistic-empirical methods: the Californian Approach." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2013. http://amslaurea.unibo.it/4914/.
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Alzioud, Mahmoud Ahmad. "IMPACT OF TRAFFIC MONITORING PERIOD ON ASPHALT PAVEMENT PERFORMANCE IN THE MECHANISTIC-EMPIRICAL PAVEMENT DESIGN APPROACH." University of Akron / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=akron1590252373148769.
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Addley, R. Craig. "A Mechanistic Approach to Modeling Habitat Needs of Drift-Feeding Salmonids." DigitalCommons@USU, 1993. https://digitalcommons.usu.edu/etd/5808.
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A mechanistic model is developed to determine the habitat needs of drift-feeding stream salmonids from the direct cause-and- effect relationships of environmental and physiological variables on net energy intake (NEI). The model determines NEI by subtracting energy costs (basal metabolism , swimming cost, digestion cost) and losses (egestion and excretion) from the gross energy intake obtained as a result of simulated prey capture. The prey capture portion of the model utilizes components o f the predation model of C.S. Holling and the prey capture model of N.F. Hughes and L.M. Dill to determine the rate of prey capture (gross energy intake) as a function of fish size, water velocity, water depth, water temperature, and the amount of drift. Physiological input parameters for the model are estimated from the literature.
Two separate validation tests of the model's ability to predict stream habitat use of trout, primarily cutthroat trout (Oncorhynchus clarki), in St. Charles Creek, Idaho, are presented. In both cases, the NEI model closely predicts the stream habitat that different size classes of fish utilize. The validation tests provide strong evidence that drift-feeding fish utilize stream habitats that provide high rates of NEI as determined by the model.
Sensitivity and simulation analyses of the model are used to identify the most important input parameters and to illustrate in terms of energetics why drift-feeding fish utilize various habitats. Model simulations explain why fish utilize deeper and faster habitats as they get larger and why they utilize slower habitats in the winter. In addition, it is shown that streams with high drift rates should theoretically provide more usable salmonid habitat than similar streams with lower drift rates.
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Rilatt, Ian James. "Development of amino acid-derived organozinc reagents using a mechanistic approach." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422643.
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Alsyouf, Imad. "Cost Effective Maintenance for Competitve Advantages." Doctoral thesis, Växjö universitet, Institutionen för teknik och design, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:vxu:diva-394.
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This thesis describes the role of cost effective maintenance in achieving competitive advantages. It explores by means of a survey which maintenance practices are used, and how maintenance policies are selected in Swedish industries. Also, it suggests a model for selecting the most cost effective maintenance policy, and how to improve the effectiveness of condition based maintenance decision-making. Finally it discusses how to assess the impact of maintenance practices on business strategic objectives. The main results achieved in the thesis are 1) A better understanding of maintenance organisation, management, systems and maintenance status in Swedish industry. For example, it was found that about 70% of Swedish companies still consider maintenance as a cost centre. Preventive and predictive maintenance approaches are also emphasised. 2) Most Swedish firms, i.e. about 81%, use the accumulated knowledge and experience within the company as a method for maintenance selection. Besides, about 31% use a method based on modelling the time to failure and optimisation. About 10% use failure mode effect and criticality analysis (FMECA) and decision trees and only 2% use multiple criterion decision-making (MCDM). However, the most used maintenance selection method is not the one most satisfactory to its users. Furthermore, about 30% use a combination of at least two methods. 3) A practical model for selecting and improving the most cost effective maintenance policy was developed. It is characterised by incorporating all the strengths of the four methods used in industry. 4) A mechanistic model for predicting the value of vibration level was verified both at the lab and in a case study. 5) A model for identifying, assessing, monitoring and improving the economic impact of maintenance was developed and tested in a case study. Thus it was proved that maintenance is no longer a cost centre, but could be a profit-generating function. To achieve competitive advantages, companies should do the right thing, e.g. use the most cost effective maintenance policy, and they should do it right, e.g. ensure that they have the right competence. Furthermore, they should apply the never-ending improvement cycle, i.e. Plan-Do-Check-Act, which requires identifying problem areas by assessing the savings and profits generated by maintenance and monitoring the economic impact of the applied maintenance policy. Thus, they would know where investments should be allocated to eliminate the basic reasons for losses and increase savings. The major conclusion is that proper maintenance would improve the quality, efficiency and effectiveness of production systems, and hence enhances company competitiveness, i.e. productivity and value advantages, and long-term profitability.
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Neal, Edward Alexander. "An active-template mechanistic approach to homo- and hetero-circuit [3]rotaxanes." Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/15016.
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Although known to chemists for nearly a century, interlocked structures have only been synthetically accessible since the 1980s when 'passive template' methods allowed the pre-complexation of components to increase yields. 'Active template' methods, initially developed by the Leigh group in 2006, have resulted in even higher yields of rotaxanes - "interlocked structures formed of at least one macrocycle penetrated by at least one impassably-stoppered axle" - and a phenomenal surge in interest in their properties as a result of this increased availability. This first method adapted highly efficient 'click' methodology to give the Active Template Copper-Mediated Alkyne-Azide Cycloaddition reaction (AT-CuAAC) and is still the most used rotaxane-forming method today. In this work, I provide the reader with an overview of these mechanically-interlocked architectures from synthesis to application. Later work by the Goldup group showed that a smaller macrocycle could make [2]rotaxanes (one macrocycle, one axle) with complete efficiency compared to their larger forebears, while intermediate sizes gave incomplete conversion, with unused macrocycle unrecovered. In this investigation, I then identify a series of novel doubly-interlocked [3]rotaxane products from this reaction that explain the absence of unused macrocycle. I then explore the variation of conditions and show how these novel products are favoured by high temperatures and high catalyst loading in a non-coordinating solvent, whereas their yields are suppressed in low temperatures and catalyst loading in a co-ordinating solvent with base, giving up to quantitative [2]rotaxane formation. To provide a mechanistic rationale for the formation of these products I then assess the effects of stopper length, macrocycle structure and lithiation experiments on the ratio of the [2]- to [3]rotaxane. The results of the above allow me to derive a new mechanistic hypothesis when I then test in a series of experiments to form [3]rotaxanes with two rings differing in either structure, size or both. Finally, the design, synthesis and testing of a stopper developed and used by myself for the AT-CuAAC reaction is described such that where two macrocycles differ in size, the larger can only be held in a novel heterocircuit [3]rotaxane, produced in synthetically useful yields.
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Noehren, Brian. "A mechanistic approach to the etiology and treatment of patellofemoral pain syndrome." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 112 p, 2009. http://proquest.umi.com/pqdweb?did=1885755661&sid=5&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Tredenick, Eloise Claire. "Mathematical modelling of ionic agrochemical diffusion in plant cuticles: A mechanistic approach." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/127347/1/Eloise_Tredenick_Thesis.pdf.
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Weeds cost Australian farmers four billion dollars annually. In this work theoretical models have been developed that simulate the uptake of agrochemicals in plant leaves. These models provide tools for understanding and testing the efficacy of chemicals in treating weeds, which can be used by industry to develop more effective agrochemicals.
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Rowen, Catherine Carmel, and n/a. "A New Approach Towards Bicyclo[4.2.0]octan-1-ols: Synthetic and Mechanistic Studies." Griffith University. School of Science, 2003. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20030602.131636.
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The reaction between the lithium enolate of cyclohexanone and phenyl vinyl sulfoxide resulted in the formation of the novel bicyclooctanol sulfoxides 215-217 and the monoalkylated sulfoxide 218. The effects of variation in reaction time, temperature and concentration were studied. Under optimal conditions (10 minutes, -10°C and 0.085 M) the ratio of the bicyclooctanol sulfoxides 215-217 (75% yield) to the monoalkylated sulfoxide 218 was 95:5. The bicyclooctanol sulfoxides 215-217 were characterised as the sulfone derivatives, bicyclooctanol sulfones 219 and 220. X-ray crystal structures were used to determine the relative stereochemistry of the bicyclooctanol sulfoxides 215-217 and the bicyclooctanol sulfones 219 and 220. Bicyclo[4.2.0]octano-1-ol formation was determined to occur via an ionic mechanism. Mechanistic studies were carried out using variations in reaction lighting and reaction solvent, conducting the reaction in the presence of a radical trap and quenching the reaction with a deuterium label. The role of the counterion was determined to be important in the formation of the bicyclooctanol sulfoxides 215-217. Sequestering lithium ions with HMPA and substituting lithium with potassium favoured alkylation. Substituting the lithium enolate of cyclohexanone with the dimethylaluminium enolate of cyclohexanone resulted in a different distribution of the bicyclooctanol sulfoxides 215-217 and the formation of bicyclooctanol sulfoxide 243. Transition states to account for these differences have been proposed. The stability of the bicyclooctanol sulfoxides under conditions of acid, base and heating was studied. Thermal ring opening of the bicyclooctanol sulfoxides 215 and 216 to the monoalkylated sulfoxides 218A and 218B respectively occurred with retention of the configuration at sulfur. The relative stereochemistry of the individual bicyclooctanol sulfoxides 215-217 was considered to account for the observed stability in each case. The reaction between the lithium enolate of cyclohexanone and (R)-(+)-p-tolyl vinyl sulfoxide 193 gave the bicyclooctanol tolyl sulfoxides 246, 251 and 252 and the monoalkylated tolyl sulfoxide 247. This showed that both bond rotation in the side chain of the intermediate and epimerisation at sulfur occurred in the bicyclo[4.2.0]octan-1-ol forming process. The presence of the sulfoxide functionality in phenyl vinyl sulfoxide was determined to be crucial to the formation of bicyclo[4.2.0]octan-1-ols. In the reaction with the lithium enolate of cyclohexanone, phenyl vinyl sulfide gave no reaction, phenyl vinyl sulfone gave the bicyclic disulfones 260-265, ethyl acrylate gave the diesters 266-268 and diphenylvinylphosphine oxide gave the phosphine oxide 269. The cyclobutanol 270 and the ketone 271 were the products resulting from the reaction between the reaction between the lithium enolate of acetophenone and phenyl vinyl sulfoxide. This demonstrated potential scope for the cyclisation process using both cyclic and acyclic ketones.
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Price, Laura E. "Imperfect mixing in energy and mass transport : a data-based mechanistic modelling approach." Thesis, Lancaster University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301086.
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Diart, Valerie. "The control of selectivity in free radical reactions : a mechanistic and synthetic approach." Thesis, University College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283194.
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Guiet, Jérôme. "Environmental impact on fish communities in the global ocean : a mechanistic modeling approach." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT134/document.
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La biosphère marine joue un rôle fondamental dans la dynamique du Système Terre (cycle du carbone, composition atmosphérique, etc.) et rend un certain nombre de services essentiels à l’humanité (pêcheries, séquestration du carbone notamment). Sa vulnérabilité aux changements globaux (changement climatique, exploitation croissante des ressources naturelles et pollution en particulier) rend nécessaire et urgente l’anticipation de ses évolutions possibles. Dans cette perspective, il s’agira dans cette thèse d’étudier comment les écosystèmes marins sont structurés par leur environnement et comment cette structuration peut influer sur leur fonctionnement jusqu'à l’échelle de l’océan global. Dans un premier temps un cadre de modélisation a été développé pour prendre en compte l'impact de l'environnement des individus aux populations aux communautés. Il est basé sur un modèle de spectre de biomasse représentant les communautés de poisson en utilisant seulement la taille des individus et la taille maximum des espèces comme variables. Issu d'un modèle détaillé par Maury O. & Poggiale J.C. (2013) il est implémenté pour la représentation d'une communauté de poisson générique. Des indicateurs de structure, diversité et métabolisme sont développés pour étudier les écosystèmes ainsi représentés. Une fois le cadre méthodologique définit le modèle est utilisé pour l'étude idéalisée des propriétés du spectre de biomasse contraint par des conditions environnementales variables. L'impact de la variation de production primaire ainsi que la variation de température du milieu sont plus particulièrement étudiés. Tout d'abord en statique, c'est à dire en imposant différents niveaux constants. Indépendamment du forçage les communautés ont des propriétés similaires en augmentant la production primaire, en diminuant la température du milieu. Quatre domaines se succèdent en augmentant la production primaire, diminuant la température, à l'intérieur desquels les communautés de poissons ont des caractéristiques similaires. Les différentes propriétés dans les différents domaines induisent diverses sensibilités des écosytèmes à des niveaux de production primaire et/ou température distincts. Afin de lier les résultats de ces expériences numériques à la réalité, les propriétés des écosystèmes à différentes latitudes sont simulées. Le spectre de communauté est calculé le long d'une section latitudinale de l'équateur au pôle en forçant avec des niveaux moyens de production primaire et température. Les propriétés des écosystèmes ainsi représentés éclairent sur l'observation de tailles d'espèces croissantes de l'équateur aux pôles, la règle de Bergmann. Après ces résultats pour des spectres statiques, les propriétés dynamiques des spectres de communauté sont étudiées par l'étude de la saisonnalité. En forçant les communautés à différentes latitudes par un cycle saisonnier de production primaire et température, la succession d'espèces au sein de celles-ci joue un rôle sur les propriétés des communauté. Des pôles à l'équateur cette succession est plus ou moins marquée et impact la capacité des écosystème à maintenir les espèces les plus larges tout au long de la période de basse production entre deux blooms. Une fois les propriétés du spectre de biomasse évaluées de façon idéalisée, le modèle est implémenté dans le modèle d'écosystème APECOSM afin de prendre en compte les interactions spatiales et les interactions avec l'habitat. Appliqué à l'échelle de l'océan global et forcé par les champs physiques et biogeochimiques du modèle NEMO-PISCES il permet la modélisation des caractéristiques des écosytèmes en fonction de leur environnement. Différentes caractéristiques connues des écosystèmes marins sont reproduites, notamment la règle de Bergmann. Les modèles actuels décrivant le fonctionnement des écosystèmes marins ne comportent que des représentations très simplifiées de la biodiversitéThe marine biosphere plays a fundamental role in the earth system dynamics (carbon cycle, atmosphere composition, etc.) and provides numerous essential services to humanity (fisheries, carbon sequestration). Its vulnerability to global change (climate change, growing exploitation of natural resources, pollution) makes the study of its evolutions imperative. In this framework, the aim of this thesis is the study of the structuring of the marine biodiversity by hydro-climatic variability of the global ocean, as well as how this structuring impacts on the ecosystems functioning. First, a modelling framework is developed to account for the impact of environment from individuals to populations to communities. It is based on a biomass size spectrum model which represents fish communities with individuals size and species maximum length as only variables. Detailed in Maury O. & Poggiale J. C. (2013) the model is implemented to represent a generic fish community. Indicators of structure, diversity and metabolism are developed to study so represented ecosystems. Once the methodogical framework defined the model is used for the idealized study of the biomass size spectrum properties when constrained with different environmental conditions. The impact of distinct constant primary production and temperature levels are investigated. First the static impact, forcing ecosystems with constant levels. Communities present similar properties for increasing primary production or decreasing water temperature. A succession of four domains characterized by similar fish community features are observed with increasing primary production, decreasing temperature. These distinct charateristics will induce distinct sensitivities of ecosystems function of the level of primary production or temperature. In order to link the results of these numerical experiments to reality the properties of ecosystems along latitudes are also computed. The community biomass spectrum is simulated along stations at different latitudes from pole to equator forcing with mean primary productions and temperatures. The properties of so represented communities enlight the observation of increasing species length with latitude, the so called Bergmann's rule. After the results for static spectra, the dynamic properties of fish community spectra are analyzed through the seasonality. Forcing communities at different latitudes with a seasonal primary production and temperature cycle a more or less strong species sucession is observed. The succession impacts the capacity of communities to maintain larger species during the bad season of poor conditions between two peaks of primary production. Once the properties of the biomass community spectrum investigated in an idealized manner, the model is implemented in the ecosystem model APECOSM in order to account for the spatial interactions and the link with habitat. Applied in the global ocean and forced with physical and biogeochemical NEMO-PISCES domains the model allows the modelling of ecosystems characteristics. Different known characteristics of marine ecosystems are reproduced, especially Bergmann's rule. The current models describing marine ecosystems provide a simplified representation of biodiversity (e.g. NPZD type biochemical models, Ewe or Atlantis type box models, OSMOSE and APECOSM type models). It induces a limitation of their use in the study of the impact of climate change on biodiversity and reversely; for the study of the impact of biodiversity changes on the functioning of ecosystems. The model we describe mechanistically allows the representation of the dynamic of ecosystems from individual bioenergetic and predation interactions while keeping diversity
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Arefin, Mir Shahnewaz. "EVALUATION OF THE RELIABILITY ANALYSIS APPROACH IN THE MECHANISTIC-EMPIRICAL PAVEMENT DESIGN GUIDE." University of Akron / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=akron1555623389749493.
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Tun, Zaw Lwin. "Mechanistic Approach to Multiphase Porous Media Modeling with Application of New Stress Principle." Kyoto University, 1999. http://hdl.handle.net/2433/181895.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第7886号
農博第1044号
新制||農||778(附属図書館)
学位論文||H11||N3249(農学部図書室)
UT51-99-G480
京都大学大学院農学研究科地域環境科学専攻
(主査)教授 青山 咸康, 教授 河地 利彦, 教授 三野 徹
学位規則第4条第1項該当
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Al-Tameemi, A. F. "Implementation of mechanistic-empirical approach for structural design of hydrated lime modified flexible pavement." Thesis, University of Salford, 2017. http://usir.salford.ac.uk/43369/.
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The need for improved mechanistic procedures for design, maintenance, and rehabilitation of highway and airport pavements has been recognized for many years. Mechanistic methods are based on the principles of mechanics in contrast to the particular purpose and empirical procedures that are often used. The objective of this study is the development of Mechanistic-Empirical design method by the implementation of hydrated lime effect in the proposed pavement section. Enhancing the paving material performance-related properties during design is an important step to minimize the efforts, pavement layers’ thicknesses and cost as well as develop the serviceability and design life. This can be done by modifiers, and one of the effective modification materials is the hydrated lime. Accordingly, the advantages of hydrated lime in the resistance to fatigue cracking and permanent deformation are utilized as main factors in the adopted Mechanistic-Empirical approach of this study. To achieve the objective of this study, three types of asphalt concrete mixtures that represent the pavement asphaltic courses (Wearing, Leveling and Base) of the asphalt concrete layer were produced and evaluated. As mineral filler materials, ordinary limestone dust and hydrated lime were used in this study. Five different hydrated lime percentages were selected, namely 1, 1.5, 2, 2.5 and 3 percent as partial replacement of limestone dust filler by total weight of aggregate besides a control mixture without hydrated lime. For the hydrated lime modified mix design, the introducing of lime into the mixtures was done by adding dry hydrated lime by total aggregate weight following the normal procedure for adding mineral filler. The experimental programme conducted in this study comprises of four main steps. Firstly, evaluate the effect of hydrated lime (HL) on asphalt cement physical properties. Penetration and the softening point (ring and ball) tests were conducted to study the influence of hydrated lime on asphalt cement consistency and stiffness. Secondly, the design of asphalt concrete mixtures following Marshall design procedure. The use of Marshall apparatus is to obtain the optimum asphalt content in specific values of stability, air void and density for control and hydrated lime modified mixes. This method also covers the evaluation of mixtures’ resistance to plastic flow (Marshall stability and flow). Thirdly, determine and evaluate the control and hydrated lime modified Hot Mix Asphalt (HMA) pavement mechanical responses to the two major distresses (fatigue cracking and rutting) that generally occurred in the pavement. In particular, these distresses could give an indication of failure criteria in the mechanistic-empirical design process. Finally, evaluation of pavement mixtures resistance to moisture damage regarding the effect of hydrated lime. The determined optimum asphalt contents by Marshall design procedure as related to the effect of hydrated lime were used in preparing further mixes specimens with different geometry and size for fatigue and rutting tests. The testing temperatures for permanent deformation and resilient modulus were 20oC, 40oC and 60oC, for fatigue it was 20oC and for the moisture susceptibility the temperature was 25oC. The fatigue and permanent deformation tests were done under the repeated loading using the pneumatic repeated load system (PRLS). The addition of 2.5% of hydrate lime results in a reduction in the penetration of about 28.1% of penetration at 0% of hydrated lime addition percentage to the asphalt cement. The softening point at 3% of HL is greater than softening point temperature degree at 0% by about 27%. Accordingly, the higher the addition percent of hydrated lime as a partial replacement with the mineral filler, the higher consistency and stiffness of the lime modified asphalt cement. The general trend of the tests data showed that the addition of hydrated lime up to 2.5% as a partial replacement of ordinary limestone mineral filler produced a considerable improvement in Marshall and volumetric properties, increased mixtures modulus of elasticity, enhanced the pavement resistance to rutting and fatigue cracking as well as remarkably decreased the mixtures susceptibility to moisture damage. Statistical analysis was made for prediction of fatigue life and permanent deformation of pavement as related to physical properties and hydrated lime effect; one equation is to predict the number of repetition to fatigue cracking, and the other one was about the prediction of the permanent strain in the asphaltic pavement layers. Using the permanent strain model, permanent deflection in a pavement can be calculated by multiplying the strain by the depth of the asphalt concrete layer. The models could be used as failure criteria and to give an impression of the future behavior of asphalt concrete mixtures. Mechanistic-Empirical design process was conducted for a typical three-dimensional pavement model of five layers employing Finite Element Analysis (FEA) using the general purpose software (ANSYS). The analyses were compared with another approach (Multi-layered Elastic Theory) by using the KENPAVE software after considering the influence of hydrated lime on the asphalt pavement properties and the effect of temperature on pavement layers resilient modulus values as related to the depth of flexible pavement. The performance analyses and results illustrated that the asphalt concrete layer in the pavement section reached the optimum thickness of 210 mm of asphaltic layer modified with optimum value of hydrated lime (2.5%) after iterations began with 180mm with an increment of 10mm. The profit in thickness was 30mm since the total thickness of asphalt concrete layer without hydrated lime (control mixtures) that gave approximately the same damage ratio (lower than unity) was 240 mm.
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Kern, Simon [Verfasser], and Rudi van [Akademischer Betreuer] Eldik. "Fast Reactions in Ionic Liquids – a Mechanistic Approach / Simon Kern. Betreuer: Rudi van Eldik." Erlangen : Universitätsbibliothek der Universität Erlangen-Nürnberg, 2012. http://d-nb.info/1022737244/34.
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Boutkhamouine, Brahim. "Stochastic modelling of flood phenomena based on the combination of mechanist and systemic approaches." Thesis, Toulouse, INPT, 2018. http://www.theses.fr/2018INPT0142/document.
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Les systèmes de prévision des crues décrivent les transformations pluie-débit en se basant sur des représentations simplifiées. Ces représentations modélisent les processus physiques impliqués avec des descriptions empiriques, ou basées sur des équations de la mécanique classique. Les performances des modèles actuels de prévision des crues sont affectées par différentes incertitudes liées aux approximations et aux paramètres du modèle, aux données d’entrée et aux conditions initiales du bassin versant. La connaissance de ces incertitudes permet aux décideurs de mieux interpréter les prévisions et constitue une aide à la décision lors de la gestion de crue. L’analyse d’incertitudes dans les modèles hydrologiques existants repose le plus souvent sur des simulations de Monte-Carlo (MC). La mise en œuvre de ce type de techniques requiert un grand nombre de simulations et donc un temps de calcul potentiellement important. L'estimation des incertitudes liées à la modélisation hydrologique en temps réel reste donc une gageure. Dans ce projet de thèse, nous développons une méthodologie de prévision des crues basée sur les réseaux Bayésiens (RB). Les RBs sont des graphes acycliques dans lesquels les nœuds correspondent aux variables caractéristiques du système modélisé et les arcs représentent les dépendances probabilistes entre ces variables. La méthodologie présentée propose de construire les RBs à partir des principaux facteurs hydrologiques contrôlant la génération des crues, en utilisant à la fois les observations disponibles de la réponse du système et les équations déterministes décrivant les processus concernés. Elle est conçue pour prendre en compte la variabilité temporelle des différentes variables impliquées. Les dépendances probabilistes entre les variables (paramètres) peuvent être spécifiées en utilisant des données observées, des modèles déterministes existants ou des avis d’experts. Grâce à leurs algorithmes d’inférence, les RBs sont capables de propager rapidement, à travers le graphe, différentes sources d'incertitudes pour estimer leurs effets sur la sortie du modèle (ex. débit d'une rivière). Plusieurs cas d’études sont testés. Le premier cas d’étude concerne le bassin versant du Salat au sud-ouest de la France : un RB est utilisé pour simuler le débit de la rivière à une station donnée à partir des observations de 3 stations hydrométriques localisées en amont. Le modèle présente de bonnes performances pour l'estimation du débit à l’exutoire. Utilisé comme méthode inverse, le modèle affiche également de bons résultats quant à la caractérisation de débits d’une station en amont par propagation d’observations de débit sur des stations en aval. Le deuxième cas d’étude concerne le bassin versant de la Sagelva situé en Norvège, pour lequel un RB est utilisé afin de modéliser l'évolution du contenu en eau de la neige en fonction des données météorologiques disponibles. Les performances du modèle sont conditionnées par les données d’apprentissage utilisées pour spécifier les paramètres du modèle. En l'absence de données d'observation pertinentes pour l’apprentissage, une méthodologie est proposée et testée pour estimer les paramètres du RB à partir d’un modèle déterministe. Le RB résultant peut être utilisé pour effectuer des analyses d’incertitudes sans recours aux simulations de Monte-Carlo. Au regard des résultats enregistrés sur les différents cas d’études, les RBs se révèlent utiles et performants pour une utilisation en support d’un processus d'aide à la décision dans le cadre de la gestion du risque de crueFlood forecasting describes the rainfall-runoff transformation using simplified representations. These representations are based on either empirical descriptions, or on equations of classical mechanics of the involved physical processes. The performances of the existing flood predictions are affected by several sources of uncertainties coming not only from the approximations involved but also from imperfect knowledge of input data, initial conditions of the river basin, and model parameters. Quantifying these uncertainties enables the decision maker to better interpret the predictions and constitute a valuable decision-making tool for flood risk management. Uncertainty analysis on existing rainfall-runoff models are often performed using Monte Carlo (MC)- simulations. The implementation of this type of techniques requires a large number of simulations and consequently a potentially important calculation time. Therefore, quantifying uncertainties of real-time hydrological models is challenging. In this project, we develop a methodology for flood prediction based on Bayesian networks (BNs). BNs are directed acyclic graphs where the nodes correspond to the variables characterizing the modelled system and the arcs represent the probabilistic dependencies between these variables. The presented methodology suggests to build the RBs from the main hydrological factors controlling the flood generation, using both the available observations of the system response and the deterministic equations describing the processes involved. It is, thus, designed to take into account the time variability of different involved variables. The conditional probability tables (parameters), can be specified using observed data, existing hydrological models or expert opinion. Thanks to their inference algorithms, BN are able to rapidly propagate, through the graph, different sources of uncertainty in order to estimate their effect on the model output (e.g. riverflow). Several case studies are tested. The first case study is the Salat river basin, located in the south-west of France, where a BN is used to simulate the discharge at a given station from the streamflow observations at 3 hydrometric stations located upstream. The model showed good performances estimating the discharge at the outlet. Used in a reverse way, the model showed also satisfactory results when characterising the discharges at an upstream station by propagating back discharge observations of some downstream stations. The second case study is the Sagelva basin, located in Norway, where a BN is used to simulate the accumulation of snow water equivalent (SWE) given available weather data observations. The performances of the model are affected by the learning dataset used to train the BN parameters. In the absence of relevant observation data for learning, a methodology for learning the BN-parameters from deterministic models is proposed and tested. The resulted BN can be used to perform uncertainty analysis without any MC-simulations to be performed in real-time. From these case studies, it appears that BNs are a relevant decisionsupport tool for flood risk management
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McElroy, Jennifer A. "Adsorption of substituted aromatic compounds by activated carbon a mechanistic approach to quantitative structure activity relationships /." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0009140.
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Behl, Stephan [Verfasser], and Herwig [Akademischer Betreuer] Stibor. "Diversity effects on ecosystem processes : a mechanistic approach using plankton communities / Stephan Behl. Betreuer: Herwig Stibor." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2012. http://d-nb.info/1025821971/34.
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Fugit, Kyle Daniel. "QUANTIFICATION OF FACTORS GOVERNING DRUG RELEASE KINETICS FROM NANOPARTICLES: A COMBINED EXPERIMENTAL AND MECHANISTIC MODELING APPROACH." UKnowledge, 2014. http://uknowledge.uky.edu/pharmacy_etds/37.
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Advancements in nanoparticle drug delivery of anticancer agents require mathematical models capable of predicting in vivo formulation performance from in vitro characterization studies. Such models must identify and incorporate the physicochemical properties of the therapeutic agent and nanoparticle driving in vivo drug release. This work identifies these factors for two nanoparticle formulations of anticancer agents using an approach which develops mechanistic mathematical models in conjunction with experimental studies.
A non-sink ultrafiltration method was developed to monitor liposomal release kinetics of the anticancer agent topotecan. Mathematical modeling allowed simultaneous determination of drug permeability and interfacial binding to the bilayer from release data. This method also quantified the effects of topotecan dimerization and surface potential on total amount of drug released from these liposomal formulations. The pH-sensitive release of topotecan from unilamellar vesicles was subsequently evaluated with this method. A mechanistic model identified three permeable species in which the zwitterionic lactone form of topotecan was the most permeable. Ring-closing kinetics of topotecan from its carboxylate to lactone form were found to be rate-limiting for topotecan drug release in the neutral pH region.
Models were also developed to non-invasively analyze release kinetics of actively-loaded liposomal formulations of topotecan in vivo. The fluorescence excitation spectra of released topotecan were used to observe release kinetics in aqueous solution and human plasma. Simulations of the intravesicular pH in the various release media indicated accelerated release in plasma was a consequence of increased intravesicular pH due to ammonia levels in the plasma instead of alterations in bilayer integrity. Further studies were performed to understand the roles of dimerization, ion-pairing, and precipitation on loading and release kinetics obtained from actively-loaded topotecan.
Extension of this type of modeling for other types of nanoparticles was illustrated with doxorubicin-conjugated polymeric micelles. Mathematical modeling of experimental studies monitoring doxorubicin release identified conjugation stability during storage, hydrazone hydrolysis kinetics, and unconjugated doxorubicin partitioning affected micellar doxorubicin release. This work identifies several of the key parameters governing drug release from these liposomal and micellar nanoparticles and lays the framework for future development of in vivo release models for these formulations.
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Kelly, David P. "Pentlandite exsolution in the Fe-Ni-S system : a mechanistic approach to pentlandite/pyrrhotite ore textures." Thesis, Aston University, 1985. http://publications.aston.ac.uk/14368/.
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Murphy, Michael Ray. "A mechanistic-empirical approach to characterizing subgrade support and pavement structural condition for network-level applications /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Flagmeier, Patrick. "An interdisciplinary approach to studying mechanistic, structural and toxic features of protein aggregates associated with neurodegenerative disorders." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274344.
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The misfolding and aggregation of proteins is closely associated with more than fifty human disorders, including Alzheimer's and Parkinson's diseases, all of which are currently incurable and many represent a major threat to human life. The mechanism of protein aggregation is subject to extensive studies. The damaging effects associated with protein aggregation have been attributed to amyloidogenic species that are present during the misfolding process. In particular, oligomeric species are, however, intrinsically difficult to study as a consequence of their low abundance and highly heterogeneous nature. The first chapter of my thesis gives an introduction into the field of protein folding and misfolding with a focus on the study of protein aggregation, and toxic effects relevant to human disorders. The second chapter of my thesis describes the development of a methodology that enables the study of aggregate induced lipid bilayer permeability, possibly the most general mechanism of protein aggregate toxicity. Surface-tethered lipid vesicles functioning as optochemical probes sensitive to membrane integrity are imaged using total internal reflection microscopy. It is shown that oligomeric species of the 42-residue form of the Aβ peptide (Aβ42) are responsible for the membrane disruption. The methodology can be applied to the study of other proteins such as α-synuclein and tau, and the ability of antibodies and chaperones to counteract the aggregate induced lipid bilayer permeability can be assessed. Furthermore, lipid bilayer permeability induced by aggregates formed in human induced pluripotent stem cells can be studied. The third chapter presents a new approach for the measurement of protein aggregation kinetics by following the development of the lipid bilayer permeability over the course of the aggregation process of Aβ42. The aggregation kinetics can be modulated with molecular chaperones and pre-formed seed fibrils, which allows secondary nucleation to be identified as the process that drives the formation of species responsible for the lipid bilayer permeability. The fourth chapter describes the development of a three-pronged strategy to study the mechanism of α-synuclein amyloid formation. The aggregation is studied in the presence of lipid vesicles or pre-formed fibrils at neutral or acidic pH of the solution. The influence of single-point mutations on the aggregation of α-synuclein is described. Furthermore, the strategy is applied to the characterisation of the ability of antibodies and small molecules to inhibit the aggregation, and thus has the potential for the development of therapeutical agents. The work presented in the fifth chapter characterises the amyloid fibril populations formed by α-synuclein and mutational variants associated with familial Parkinson's disease. X-ray crystallography, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy and atomic force microscopy have all been applied to the analysis of these amyloid fibrils. Finally, the sixth chapter summarises the results described in this thesis and points out future opportunities in the context of fundamental and translational studies related to the research area of protein misfolding disorders.
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Ludsin, Stuart A. "Exploration of spatiotemporal patterns in recruitment and community organization of Lake Erie fishes : a multiscale, mechanistic approach /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488203552780048.
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