Dissertations / Theses on the topic 'Mechanistic model'
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Yeung, Luk Chong. "A mechanistic model of calcium-dependent synaptic plasticity /." View online version; access limited to Brown University users, 2005. http://wwwlib.umi.com/dissertations/fullcit/3174704.
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Drost, Roelof Gerrit. "MAIS, a mechanistic model of maize growth and development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ61892.pdf.
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Lenting, Christoph [Verfasser]. "Glass corrosion : Towards a Unifying Mechanistic Model / Christoph Lenting." Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1201727863/34.
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Baird, Mark E. "Towards a verified mechanistic model of plankton population dynamics." Thesis, University of Warwick, 1999. http://wrap.warwick.ac.uk/1123/.
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Plankton are a signicant component of the biogeochemical cycles that impact on the global climate. Plankton ecosystems constitute around 40 % of the annual global primary productivity, and the sinking of plankton to the deep ocean (the so-called biological pump) is the largest permanent loss of carbon from the coupled atmosphere-surface ocean-land system. The biological pump need only increase by 25 % to cancel the anthropogenically-released ux of CO2 into the atmosphere. Mechanistic models of atmosphere-ocean dynamics have proved to have superior predictive capabilities on climate phenomena, such as the El Ni~no, than empirical models. Mechanistic models are based on fundamental laws describing the underlying processes controlling a particular system. Existing plankton population models are primarily empirical, raising doubts to their ability to forecast the behaviour of the plankton system, especially in an altered global climate. This thesis works towards a mechanistic model of plankton population dynamics based primarily on physical laws, and using laboratory-determined parameters. The processes modelled include: diusion and convection to the cell surface, light capture by photosynthetic pigments, sinking and encounter rates of predators and prey. The growth of phytoplankton cells is modelled by analogy to chemical kinetics. The equations describing each process are veried by comparison to existing laboratory experiments. Process-based model verication is proposed as a superior diagnostic tool for model validation than verication based on the changing state of the system over time. To increase our ability to undertake process-based verication, a model of stable isotope fractionation during phytoplankton growth is developed and tested. The developed model has been written to complement other process-based models of biogeochemical cycles. A suite of process-based, biogeochemical models, coupled to an atmosphere-ocean circulation model, will have superior predictive capabilities compared with present global climate models.
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Nobari, Amir Hossein. "Mechanistic jet impingement model for cooling of hot steel plates." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/47099.
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Accelerated cooling on the run-out table of a hot rolling mill is a key technology to tailor microstructure and properties of advanced steels. Thus, it is crucial to develop accurate heat transfer models in order to predict the temperature history of the steel plates on run-out tables.
The present study describes a strategy to develop a mechanistic cooling model to simulate the temperature of the plate cooled by top water nozzles on a run-out table. Systematic experiments have been carried out on a pilot scale run-out table facility using two types of top nozzles: planar (curtain) and circular (axisymmetric) nozzles. Experimental results for cooling of stationary plates showed that the heat transfer rate depends strongly on the distance from the jet especially in the temperature range where the transition boiling regime occurs. Based on experimental results, a boiling curve model has been proposed that takes into account boiling heat transfer mechanisms and maps local boiling curves for cooling of stationary steel plates. The effects of water flow rate and water temperature on the heat extraction from the plate have been included in the model.
Then, systematic experimental heat transfer studies were conducted to investigate the effect of plate speed on the heat transfer rate. It was found that the plate motion influences the heat transfer rate in the film boiling and transition boiling regimes; however, it does not have an effect on the heat flux in the nucleate boiling regime. Moreover, for the circular nozzle system, it was found that the nucleate boiling heat flux does not change with lateral distance. However, heat flux in the film boiling and transition boiling regimes decreases with increasing distance from the longitudinal centerline of the plate. In the next step, a cooling model was proposed by accounting for the boiling curves of single nozzle cooling for moving plates. Transient heat conduction within the plate was analyzed and surface heat flux and temperature histories were predicted. The validity of the cooling model was examined with multiple nozzles experimental data from the literature. Very good agreement with experimental results has been obtained.Applied Science, Faculty of
Materials Engineering, Department of
Graduate
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Deen, William. "A mechanistic model of common ragweed based on photothermal time." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0019/NQ47389.pdf.
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Ma, John W. "Mechanistic model studies of living nitroxide-mediated styrene miniemulsion polymerization." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2002. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ65680.pdf.
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Hamzat, Kadri Obafemi. "A semi-mechanistic model based on oil expression from groundnuts." Thesis, Cranfield University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333986.
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Ma, Yuxin. "Empirical and Mechanistic Modelling for Process Understanding in Digital Soil Mapping." Thesis, The University of Sydney, 2019. https://hdl.handle.net/2123/21413.
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Empirical prediction of soil properties coupled with an understanding of soil processes, can uncover the complexity of the soil system. Digital soil mapping (DSM) has revolutionized the way soil information is delivered. While empirical DSM has greatly improved the quantitative prediction, we should be able to incorporate our physical and mechanistic understanding of the processes. Likewise, we should be able to use empirical knowledge to inform process-based models. This thesis delivers mechanistic and empirical models to improve the understanding of soil genesis and mapping of soil functional properties and finding the relationships between soil and environmental factors. Chapter 2 first critically reviews pedology models and DSM concepts, mapping soil classes, mapping soil profiles, mapping pedological features and processes, the relation between pedological knowledge and DSM, and the application of mechanistic pedological models in DSM. Chapter 3 investigates the use of a mechanistic pedogenesis model, State Space Soil Production and Assessment Model (SSSPAM) for modelling the spatiotemporal evolution of particle-size distribution (PSD). In Chapter 4, we used process-based understanding in a mechanistic model to help us make a better prediction of the 4D spatiotemporal distribution of SOC. Chapter 5 evaluates the proposition that soil properties can be evaluated at any depth by comparing the multi-layered 2.5D and 3D modelling with soil depth as a predictor variable. Chapter 6 investigates whether data provided from a rapid and non-destructive proximal sensor can be used to directly predict the provenance of soil samples. Overall, this thesis demonstrates that to comprehensively explain the complexity of the soils, their dynamics and relation to the soil-forming factors, it is beneficial to include knowledge of processes to model soil profile distribution and identify the unique pattern of soil distribution.
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Van, Tonder Jacob John. "Development of an in vitro mechanistic toxicity screening model using cultured hepatocytes." Thesis, University of Pretoria, 2011. http://hdl.handle.net/2263/24162.
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In vitro testing includes both cell-based and cell-free systems that can be used to detect toxicity induced by xenobiotics. In vitro methods are especially useful in rapidly gathering intelligence regarding the toxicity of compounds for which none is available such as new chemical entities developed in the pharmaceutical industry. In addition to this, in vitro investigations are invaluable in providing information concerning mechanisms of toxicity of xenobiotics. This type of toxicity testing has gained popularity among the research and development community because of a number of advantages such as scalability to high throughput screening, cost-effectiveness and predictive power. Hepatotoxicity is one of the major causes of drug attrition and the high cost associated with drug development poses a heavy burden on the development of new chemical entities. Early detection of hepatotoxic agents by in vitro methods will improve lead optimisation and decrease the cost of drug development and reduce drug-induced liver injury. Literature highlights the need for a cellbased in vitro model that is capable of assessing multiple toxicity parameters, which assesses a wider scope of toxicity and would be able to detect subtle types of hepatotoxicity. The present study was aimed at developing an in vitro procedure capable of mechanistically profiling the effects of known hepatotoxin dichlorodiphenyl trichloroethane (DDT) and its metabolites, dichlorodiphenyl dichloroethylene (DDE) and dichlorodiphenyl dichloroethane (DDD) on an established liver-derived cell line, HepG2, by evaluating several different aspects of cellular function using a number of simultaneous in vitro assays on a single 96 well microplate. Examined parameters have been suggested by the European Medicines Agency and include: cell viability, phase I metabolism, oxidative stress, mitochondrial toxicity and mode of cell death (apoptosis vs. necrosis). To further assess whether the developed method was capable of detecting hepatoprotection, the effect of the known hepatoprotectant, N-acetylcysteine, was determined. Viability decreased in a dose-dependent manner yielding IC50 values of 54 μM, 64 μM and 44 μM for DDT, DDE and DDD, respectively. Evaluation of phase I metabolism showed that cytochrome P4501A1 activity was dose-dependently induced. Test compounds decreasedlevels of reactive oxygen species, and significantly hyperpolarised the mitochondrialmembrane potential. Assessment of the mode of cell death revealed a significant elevation of caspase-3 activity, with DDD proving to be most potent. DDT alone induced dosedependent loss of membrane integrity. These results suggest that the tested compounds produce apoptotic death likely due to mitochondrial toxicity with subsequent caspase-3 activation and apoptotic cell death. The developed in vitro assay method reduces the time it would take to assess the tested parameters separately, produces results from multiple endpoints that broadens the scope of toxicity compared to single-endpoint methods. In addition to this the method provides results that are truly comparable as all of the assays utilise the same batch of cells and are conducted on the same plate under the exact same conditions, which eliminates a considerable amount of variability that would be unavoidable otherwise. The present study laid a solid foundation for further development of this method by highlighting the unforeseen shortcomings that can be adjusted to improve scalability and predictive power.Thesis (PhD)--University of Pretoria, 2011.
Pharmacology
unrestricted
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Zorzetto, Luiz Flavio Martins. "Bioprocess monitoring with hybrid neural network/mechanistic model based state estimators." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283350.
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Ab, Hadi H. "Mechanistic studies of the permeation behaviour of a model hydrophilic compound." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1381750/.
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Caffeine is commonly used as a model hydrophilic compound in skin research, and it also has pharmaceutical and cosmetic applications. Several topical products containing caffeine are currently being marketed, including anti-cellulite creams and gels, moisturizers, serums and shampoos. As the skin permeation of this compound is expected to be low, the aim of this work is to investigate how the topical delivery of caffeine may be optimized using chemical penetration enhancers. A range of penetration enhancers for caffeine were selected, namely ethanol (EtOH), propylene glycol (PG), isopropyl myristate (IPM), propylene glycol dipelargonate (DPPG), oleic acid (OA), dimethyl isosorbide (DMI), 1,2-pentanediol (1,2-PENT), propylene glycol monocaprylate (PGMC), propylene glycol monolaurate (PGML), Transcutol-P (TRANS), isostearylisostearate (ISIS), isopropyl isostearate (IPIS), geraniol (GER), d-limonene (LIM) and 1,8-cineole (CIN). Solubility and miscibility studies were conducted using these solvents. Based on the miscibility and solubility data, caffeine permeation using infinite dose studies in human skin was evaluated. The studies were performed for caffeine in simple single solvents namely, PG, DMI, 1,2-PENT and IPM. The effects of using more complex binary solvent systems and ternary solvent systems of these solvents were also studied. The highest flux values were observed from the ternary solvent system PG:1,2-PENT:IPM (50:45:5 v/v), which enhanced caffeine permeation up to 24 times, 43 times and 7 times compared with the single solvents PG, 1,2-PENT and IPM, respectively. Following infinite dose studies in human skin, caffeine permeation was evaluated in finite dose studies. Because of the high number of experiments required, this section of the work was conducted with porcine skin, which was easier to source compared to human skin. Porcine skin was chosen over other skin models because from the literature it has been shown that this skin model is the closest animal model to human skin. The enhancement effects on caffeine permeation by binary and ternary solvent systems were also evaluated in this study. Following the finite dose studies, mass balance studies were conducted in order to understand the distribution of the actives in the skin. After 24 hours of finite dose studies, the permeation profiles did not reach a plateau. However, the studies could not be prolonged to 48 hours with porcine skin since the solvents damaged the skin barrier, as shown by a sudden increase in permeation. Therefore, the two best ternary solvent systems were selected. It was found that the same trend of caffeine permeation was observed (PG:DMI:IPM> PG:1,2-PENT:IPM) from the finite dose studies using porcine skin and that obtained from human skin. These formulations were further evaluated in in vivo studies. The formulations were applied on human volunteers in order to investigate the effect of the formulations on the skin barrier in vivo. These studies were carried out by analysing the trans-epidermal water loss (TEWL), Attenuated Total Reflectance Fourier Transform Infrared(ATR-FTIR) scans and protein content. The TEWL measurements from the PG:1,2-PENT:IPM treated site showedsignificantly higher TEWL values up to the removal of 15 tape strips (p<0.05). It was speculated that this may be due to irritation caused by the formulation, which results in damage to the skin barrier as shown by the high TEWL values. However, no further macroscopic changes in the skin barrier were observed using the ATR-FTIR. Further evaluations of the effects of the formulations on caffeine permeation were assessed by using the tape-stripping technique. A general trend of higher protein content was observedin the stratum corneum removed from the PG:1,2-PENT:IPM treated site, compared with the PG:DMI:IPM treated site and the control site. It was noted from this study that a higher caffeine amount was detected from the PG:1,2-PENT:IPM treated site compared tothe PG:DMI:IPM treated site. In conclusion, this thesis presents evidence that caffeine permeation can be enhanced by using combinations of chemical permeation enhancers in increasingly complex combinations. The effects of the formulation on the skin barrier in vitro were successfully elucidated by modelling the permeationdata. Furthermore, in vivo data provides further insight into the effects of the formulations on caffeine permeation and on the skin barrier, which will be useful in taking forward these formulations for use in cosmetic or pharmaceutical preparations.
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Wagih, Omar. "Elucidating the mechanistic impact of single nucleotide variants in model organisms." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271713.
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Understanding how genetic variation propagate to differences in phenotypes in individuals is an ongoing challenge in genetics. Genome-wide association studies have allowed for the identification of many trait-associated genomic loci. However, they are limited in their inability to explain the altered cellular mechanism. Genetic variation can drive disease by altering a range of mechanisms, including signalling networks, TF binding, and protein folding. Understanding the impact of variants on such processes has key implications in therapeutics, drug development, and more. This thesis aims to utilise computational predictors to shed light on how cellular mechanisms are altered in the context of genetic variation and better understand how they drive both molecular and organism-level phenotypes. Many binding events in the cell are mediated by short stretches of sequence motifs. The ability to discover these underlying rules of binding could greatly aid our understanding of variant impact. Kinase–substrate phosphorylation is one of the most prominent post-translational modifications (PTMs) which is mediated by such motifs. We first describe a computational method which utilises interaction and phosphorylation data to predict sequence preferences of kinases. Our method was applied to 57% of human kinases capturing known well-characterised and novel kinase specificities. We experimentally validate four understudied kinases to show that predicted models closely resemble true specificities. We further demonstrate that this method can be applied to different organisms and can be used for other phospho-recognition domains. The described approach allows for an extended repertoire of sequence specificities to be generated, particularly in organisms for which little data is available. TF-DNA binding is another mechanism driven by sequence motifs, which is key for the tight regulation of gene expression and can be greatly altered by genetic variation. We have comprehensively benchmarked current methods used to predict non-coding variant effects on TF-DNA binding by employing over 20,000 compiled allele-specific ChIP-seq variants across 94 TFs. We show that machine learning-based approaches significantly outperform more rudimentary methods such as the position weight matrix. We further note that models for many TFs with distinct binding specificities were unable to accurately assess the impact of variants. For these TFs, we explore alternative mechanisms underlying TF-binding, such as methylation, co-operative binding, and DNA shape that drive poor performance. Our results demonstrate the complexity of predicting non-coding variant effects and the importance of incorporating alternative mechanisms into models. Finally, we describe a comprehensive effort to compile and benchmark state-of-the-art sequence and structure-based predictors of mutational consequences and predict the effect of coding and non-coding variants in the reference genomes of human, yeast, and E. coli. Predicted mechanisms include the impact on protein stability, interaction interfaces, and PTMs. These variant effects are provided through mutfunc, a fast and intuitive web tool by which users can interactively explore pre-computed mechanistic variant impact predictions. We validate computed predictions by analysing known pathogenic disease variants and provide mechanistic hypotheses for causal variants of unknown function. We further use our predictions to devise gene-level functionality scores in human and yeast individuals, which we then used to perform gene-phenotype associations and uncover novel gene-phenotype associations.
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Mense, Jelte Pierc. "New general mechanistic model for predicting civil disturbances and their characteristics." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28763.
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Since the wave of civil violence in the USA in the 1960s, many social theorists have tried to explain why riots occur. Despite at least 50 years of research since then, there is still not enough insight to anticipate large events like the 2011 Arab Spring and London riots. The main goal of this thesis is therefore to improve understanding about how underlying conditions influence and drive riot dynamics, such as the intensity, spread, and duration. I develop a new mechanistic and stochastic agent-based model for riots. Previous models have either only targeted general phenomena associated with riots, or aimed at behaviour specific to a single event. In this thesis I combine both approaches: I demonstrate how the model in which the motivation of the agents is based on general concepts, can be applied to the specific situation of the 2011 London riots. The model reproduces the majority of the behaviour observed in the London riots (r = 0.4-0.8). One of the key factors under investigation is the relationship between protests and outbursts of civil violence. Riots are often preceded by protests, such that a large pool of potential rioters is directly available. I find that the number of times a protest is repeated has greater influence on riot dynamics than the protest crowd size. The support shown during demonstrations might incite false confidence in individuals, potentially leading to quicker escalation. Another question is how contact networks and collective identity influence the spread of violence between different locations. The role of online social media (e.g. Twitter) has been a major focus in trying to explain why the violence in the 2011 Arab spring spread so quickly and so far. I investigate the role of social similarity as another factor that might have contributed to the diffusion of unrest, and demonstrate the existence of a critical transition in riot activity when increasing the density of the contact network in the model. Such increases in density beyond the critical thresholds might have been introduced by online social networks. Finally, I explore the sensitivity to cooperation of different potential riot groups. In some cases, mixed populations with different collective identities can form coalitions within neighbourhoods based on shared grievances, which could lead to increases in riot size and riot probability. I examine the influence of the social structure and spread of these populations over different neighbourhoods, as well as the overlap in grievances and different demographic structures.
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Alsirawan, M. B., X. Lai, R. Prohens, Venu R. Vangala, S. K. Pagire, S. Petroc, T. J. Bannan, D. O. Topping, and Anant R. Paradkar. "Solid-State Competitive Destabilization of Caffeine Malonic Acid cocrystal: Mechanistic and Kinetic Investigation." American Chemical Society, 2020. http://hdl.handle.net/10454/18305.
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YesThe main objective of this research is to investigate solid-state destabilization mechanism and kinetics of the model cocrystal caffeine : malonic acid (CA:MO) in presence of oxalic acid (OX) as a structural competitor. Competitive destabilization of CA:MO and subsequent formation of CA:OX takes place at temperatures significantly below its melting point. Destabilization mechanism was found to be mediated by sublimation of both CA:MO and OX. During CA:MO destabilization, free CA could not be detected and direct transformation to CA:OX cocrystal was observed. The destabilization kinetics follow Prout-Tompkins nucleation and crystal growth model with activation energy of 133.91 kJ/mol and subsequent CA:OX growth kinetic follow Ginstling – Brounshtien diffusion model with activation energy of kJ/mol.
The full-text of this article will be released for public view at the end of the publisher embargo on 28 Oct 2021.
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Al-johani, Mohammed S. "A three-dimensional mechanistic model of steam condensers using porous medium formulation." Diss., Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/19448.
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Paiement, Jean-Pierre. "Evaluation of a model system for the mechanistic study of gene targeting." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84103.
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Gene targeting is a process of recombinational exchange between a foreign molecule of DNA and its homologous chromosomal counterpart whereby the cellular machinery involved in homologous recombination accomplishes sequence exchange. The widespread use of gene targeting as a basic research and/or therapeutic tool has been precluded by its inherent inefficiency. Although many studies have reported improved gene targeting efficacy via manipulation of homologous recombination-associated proteins, reports examining the underlying molecular mechanisms of gene targeting are scant. Improvement in our understanding of these molecular mechanisms will undoubtedly lead to advancements in the study of genetic disease, and perhaps to the development of viable human gene therapy. To this end, the following is a report of the development and preliminary assessment of a model system for the study of the molecular mechanisms of gene targeting. Specifically, this system entailed the investigation of recombinational exchange between isogenic, non-functional copies of HSV-tk contained in a targeting plasmid and a stably integrated target plasmid, in Ltk-cells. Results showed an absolute random integration frequency of our targeting construct in the range of 10-4---a value ten-fold lower than classically associated with random integration. Also, linearization of our targeting plasmid outside the region of homology to our stably integrated chromosomal target appeared to be associated with an undetectable level of targeting. Similarly, non-homology---in the form of three non-silent point mutations in our target sequence---appeared to impede gene targeting. These initial results suggest that the design of this model system needs to be revised to allow proper investigation of the molecular mechanisms underlying gene targeting.
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Sostelly, Alexandre. "Mechanistic model-based drug development in the management of anticancer drugs resistance." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10203.
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La résistance aux chimiothérapies anticancéreuses constitue un problème majeur dans la prise en charge du cancer. Les transporteurs d'efflux contribuent à ce phénomène de résistance en altérant l'accumulation intracellulaire des cytotoxiques. Dans le passé, l'inhibition du transporteur d'efflux P-gp n'a pas permis de surmonter ce phénomène notamment à cause du manque de méthodes adéquates pour identifier et quantifier la pharmacologie des inhibiteurs d'efflux. Récemment de nouveaux inhibiteurs de BCRP, l'un des derniers transporteurs d'efflux découverts, ont été synthétisés permettant de retester l'intérêt de l'inhibition de ces transporteurs dans la prise en charge de la résistance aux anticancéreux. Néanmoins, afin d'éviter les mêmes écueils que lors du développement des inhibiteurs de P-gp, il est nécessaire d'utiliser d'autres approches telles que la modélisation mathématique dès le début du développement préclinique de ces inhibiteurs. Cette thèse a pour but de montrer les bénéfices de la modélisation et de la simulation dans le développement préclinique des inhibiteurs de transporteurs d'efflux et plus largement dans le développement des molécules anticancéreuses. L'exemple utilisé au travers de ce travail concerne l'étude de l'interaction entre l'irinotecan, un cytotoxique largement utilisé dans le traitement du cancer colorectal, et le MBLI87, un nouvel inhibiteur de BCRP. Deux principaux axes ont été abordés dans ce travail : - Le développement de modèles (semi-) mécanistiques à effets mixtes pour identifier et quantifier les facteurs impactant l'efficacité de la combinaison irinotecan-MBLI87 - Le développement de modèles d'inhibition de la croissance tumorale à effets mixtes pour évaluer précocement ce type d'interaction de traitements et pour optimiser la réponse tumorale. Les résultats obtenus avec l'approche de modélisation ont permis d'identifier certains des mécanismes tumoraux impactant l'efficacité des inhibiteurs de transporteur d'efflux. De plus cette approche s'est révélée supérieure aux approches classiques dans l'évaluation de ces molécules et dans l'optimisation de la réponse tumorale démontrant la puissance de la modélisation et de la simulation comme outil de développement des molécules anticancéreusesAnticancer drug resistance is a major issue in the management of cancer disease. Efflux transporters contribute to the multidrug resistance by altering the intracellular disposition of cytotoxic drugs. In the past, the inhibition of P-gp efflux transporter essentially failed because of the lack of adequate methods to identify their mechanisms of action. Recently, new inhibitors of BCRP, one of the latest efflux transporter that have been discovered, have been developed that allow re-testing the multidrug resistance inhibition through efflux inhibition. Nevertheless, to avoid the same issues of development as for P-gp inhibitors, new methods have to be used. This PhD work aims to demonstrate the benefits of mechanistic models to support the development of efflux transporter inhibitors and more generally of oncology compounds through two axes: - The development of mechanistic models of the interaction between cytotoxic and efflux transporter inhibitors - The development of quantitative tumour growth inhibition models to early evaluate oncology compounds and optimize patients’ response The results obtained with this approach allow the identification of key mechanisms of efflux transporter inhibitors and demonstrate the power of modelling and simulation to support oncology drug development
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Nowacki, Brenna M. "Verification and Calibration of State-of-the-Art CMC Mechanistic Damage Model." University of Dayton / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1461761780.
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Poon, Jonathan Ming-Hin. "A three-dimensional population balance model of granulation processes employing mechanistic kernels." Thesis, Imperial College London, 2008. http://hdl.handle.net/10044/1/8041.
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Granulation is a process for agglomeration where powder material is combined with liquid binder solution to facilitate the formation of larger, free-flowing granules. Granulation has become a mainstream process amongst the industries with applicability in numerous areas, which include the pharmaceuticals, mineral processing, fertilisers and in the production of a range of commodity products. A major driVing force for the production of granules from their ungranulated counterparts arises from the economic savings Le., increased bulk density permits savings to be made in transportation. and storage. Furthermore, granules may be tailored to possess certain desirable attributes that will suit the final application of the granules. Granulation is an example of a process that exhibits complex interactions between the underlying granulation phenomena such as nucleation, consolidation, aggregation and breakage. In addition, the granUle properties are distributed heterogeneously across the entire particle population posing as a particular challenge in generating a mathematical model that is able to accurately describe the granulation behaviour. The modelling approach used in this study is different from common practices, which tend to rely on heuristics and empiricism for the operation of the granulation process. This empirical approach signifies a disconnect from our understanding of the underlying physics of the process, which poses as a impediment towards the efficient operation of granulation processes. The work presented in this thesis attempts to address this disconnect by applying a threedimensional population balance with mechanistic representations for the underlying granulation rate processes. The population balance framework is ideally suited for this particular process, as it enables the evolution of the granules to be tracked with respect to differentiating particle traits, e.g. the granule size distribution. The selection of the desired properties is influenced by the importance of these particle properties on the end granule product, and also by their influence on key process mechanisms. A novel mechanistic nucleation kernel is developed incorporating fundamental material properties pertaining to the powder substrate and the liquid binder solution. The model form of the nucleation kernel is formulated by drawing a parallel with the collision/transition state theory. There are few literature reports on the inclusion of nucleation phenomena in the population balance models of granulation processes, let alone a mechanistic nucleation model. This study is one of the first in this regard. The recent recognition of the importance of the wetting kinetics and the nucleation thermodynamics on the nucleation phenomenon has been factored into the nucleation kernel by explicitly accounting for the effects of the liquid flow rate and the physicochemical properties of the material properties (surface tension, contact angle, and spreading coefficient). Batch granulation experiments were conducted obtaining granule measurements with respect to the size distribution, porosity and fractional binder content. Preliminary results for the validation of the population balance model with the experiment-measurements showed a good agreement, providing partial albeit valuable validation of the population balance model. This is also one of the first studies to model and validate a three-dimensional population balance model for granulation. Model based analyses were also carried out under a variety of processing conditions, which included the effects of changing formulations, droplet size effects, feed size distribution and the effects of powder and binder properties. The proposed model demonstrated the interactions for a range of feed formulations in tandem with granulating operating conditions, establishing qualitative agreement with similar findings derived from past experimental studies.
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Long, Yu. "Mechanistic insights into acid-catalysed pyrolysis of cellulose and its model compounds." Thesis, Curtin University, 2022. http://hdl.handle.net/20.500.11937/89062.
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Biomass has only been utilised as an energy source via direct combustion of bio-charcoal in the past decade, but the biomass processes also create environmental issues and low energy utilization. This study provides new insights into cellulose pyrolysis mechanisms for the benefit of advanced bio-oil and bio-product selectivity technologies and maximise the utilisation of the biomass in the future green energy market, which can effectively reduce the green house emission and its environmental issue.
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Kim, Yong Sik. "Kinetic and mechanistic studies of polyoxometalate (POM) reaction with lignin and model compounds." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31366.
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Polyoxometalates (POMs) are a rapidly growing class of metal-oxygen-cluster anions. The properties of POMs can be modified by altering the POMs chemical composition and structure. Due to low cost, commercial availability, and synthetic tractability POMs have found application in various fields of chemistry and technology. POMs are reusable and thermally stable to oxidative conditions, making them an attractive alternative to chlorine for the delignification of wood pulp. The research addressed in this dissertation deals with detailed kinetic and mechanistic studies of K₅[SiVW₁₁O₄₀]·12H₂O, a POM used in the delignification of wood pulp, oxidation of phenolic lignin model compounds and milled wood lignin (MWL). Results from lignin model studies suggest an overall second-order reaction rate; first order with respect to both POM and phenolic substrate. It was observed that electron-transfer from neutral phenols was slower than that from the corresponding phenoxide anions. Hammett studies revealed the reaction involved the formation of an electron-deficient radical intermediate where the rate-determining step is electron transfer from a neutral substrate. The structure of the substituted phenol, in terms of its electron donating/withdrawing character, along with the position of the substituent on the aromatic ring heavily influences the reaction rates. Increasing the number of ortho methoxyl groups dramatically increased the reaction rate, e.g. phenol < guaiacyl < syringyl model structures. The ortho methoxyl group(s) resonance stabilizes and delocalizes the forming phenoxyl radical intermediate. Similarly, the reaction rate of para-substituted guaiacyl and syringyl model compounds showed a dependence on the nature of the para-substituent; inductive or resonance conjugated electron withdrawing effects and inductive donating effects. The effect of POM oxidation on the chemical structure of a Lodgepole pine MWL is investigated. ¹³C nuclear magnetic resonance (NMR) spectroscopic data revealed an approximate 28% decrease in β-O-4 inter-unit linkages after POM treatment, the decrease in β-O-4 inter-unit linkages being accompanied by an increase in carbonyl content. These results suggest that POM oxidation involves side-chain (such as α-OH/β-O-4) oxidation. ¹³C NMR spectroscopy along with gel permeation chromatography revealed an increase in the degree of condensation which supports the idea that radical coupling is a major reaction pathway in this process.Forestry, Faculty of
Graduate
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Skår, Helene. "Simulation of Surfactant EOR in a Mechanistic Model with Fracture and Ekofisk Properties." Thesis, Norges teknisk-naturvitenskapelige universitet, Institutt for petroleumsteknologi og anvendt geofysikk, 2014. http://urn.kb.se/resolve?urn=urn:nbn:no:ntnu:diva-25910.
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Large amounts of oil are left in reservoirs after primary and secondary recovery. To recovery as much of the remaining oil as possible, EOR techniques as chemical flooding is considered. Naturally fractured carbonates have often large amount of residual oil left in the reservoir after primary and secondary production periods. Carbonates are in general more complex reservoirs than sandstones, thus must recovery methods be tailored for the environment of the reservoir system. Chemical EOR has become more attractive after the financial crisis in 2008 because of the high oil prices. Ekofisk is naturally fractured chalk reservoir, and is the largest, oldest and longest producing reservoir on Norwegian continental shelf. To improve the recovery is surfactant injection considered as a possible EOR method. A mechanist reservoir model with Ekofisk reservoir properties and a single fracture was made with the purpose to investigate the potential of surfactant injection in Ekofisk. Several parameters that effect the performance of surfactants was investigated and the recovery results were compared with a waterflood basecase. In addition was a mechanistic model with four fractures made for further investigation of surfactant flow in a fracture network and for comparison of the performance of a surfactant flood with surfactant-polymer flood. The author’s simulation results show that surfactant injection should be considered for the field, but more research with a more advanced reservoir model with respect to possible wettability alteration, a larger fracture network and heterogeneity should be done. The model shows poor sweep efficiency in layers far from the fracture in the model, thus should an eventual chemical flood in Ekofisk be considered done with polymers. Surfactant concentration in the injection solution affects the surfactant performance the most. For the single fracture model is the recovery increased with 2,8% when surfactants are injected, and NPV was increased with 8,31E+06 $. For the 9-block model with four fractures, was the recovery improved with 3% for the surfactant-polymer flood compared with a surfactant flood. Also the NPV was increased with 3,71E+06$.
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Tabor, Joseph Edward. "A fogging scrubber to treat diesel exhaust: field testing and a mechanistic model." Thesis, Virginia Tech, 2020. http://hdl.handle.net/10919/99443.
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Diesel particulate matter (DPM) is comprised of two main fractions, organic carbon (OC) and elemental carbon (EC). DPM is the solid portion of diesel exhaust and particles are submicron in size typically ranging from 10 to 1000 nanometers. DPM is a known respirable hazard and occupational exposure can lead to negative health effects. These effects can range from irritation of the eyes, nose, and throat to more serious respirable and cardiovascular diseases. Due to the use of diesel powered equipment in confined airways, underground mine environments present an increased risk and underground mine works can be chronically overexposed. Current engineering controls used to mitigate DPM exposure include cleaner fuels, regular engine maintenance, ventilation controls, and enclosed cabs on vehicles. However even with these controls in place, workers can still be overexposed.
The author's research group has previously tested the efficacy of a novel, fog-based scrubber treatment for removing DPM from the air, in a laboratory setting. It was found that the fog treatment improved DPM removal by approximately 45% by number density compared to the control trial (fog off). The previous work stated thermal coagulation between the fog drops and the DPM, followed by gravitational settling of the drops to be the likely mechanisms responsible for the DPM removal. The current work investigated the efficacy of the fog treatment on a larger scale in an underground mine environment, by using a fogging scrubber to treat the entire exhaust stream from a diesel vehicle. A total of 11 field tests were conducted.
Based on measurements of nanoparticle number concentration at the inlet and outlet of the scrubber, the fog treatment in the current work showed an average improvement in total DPM removal of approximately 55% compared to the control (fog off) condition. It was found that the treatment more effectively removed smaller DPM sizes, removing an average of 84 to 89% of the DPM in the 11.5, 15.4, and 20.5 nanometer size bins and removing 24 to 30% of the DPM in the 88.6, 115.5, and 154 nanometer size bins. These observations are consistent with expectations since the rate of coagulation between the DPM and fog drops should be greater for smaller diameters.
Further analysis of the DPM removal was aided by the development of a mechanistic model of the fogging scrubber. The model uses the inlet data from the experimental tests as input parameters, and it outputs the outlet concentration of DPM for comparison to the experimental outlet data. Results provided support for the notion that DPM removal relies on DPM-fog drop coagulation, and subsequent removal of the DPM-laden drops as opposed to DPM removal by diffusion or inertial impaction of DPM directly to the walls. The model results suggest that inertial impaction of these drops to the scrubber walls is likely much more important than gravitational settling. Moreover, the ribbed geometry of the tubing used for the scrubber apparatus tested here appears to greatly enhance inertial impaction (via enhancement of depositional velocity) versus smooth-walled tubing. This is consistent with previous research that shows particle deposition in tubes with internally ribbed or wavy structures is enhanced compared to deposition in tubes with smooth walls.Master of Science
Diesel particulate matter (DPM) describes the solid portion of diesel exhaust. These particles are in the nanometer size range (10-1000nm) and can penetrate deep within the lungs presenting a serious health hazard. Because of the use of diesel powered equipment in confined spaces, DPM presents an occupational hazard for underground mine workers. Even with the use of cleaner fuels, regular engine maintenance, proper ventilation, and enclosed vehicle cabs, workers can still be over exposed. Previous work has shown that a water fog treatment can help to remove DPM from the air in a laboratory setting. This removal is due to the DPM particles attaching to the drops, followed by the drops settling out of the air due to gravity or impacting the walls of a tube. To explore a full scale exhaust treatment, a fogging scrubber was built using a fogger and a long tube, and was tested in an underground mine on vehicle exhaust. Experimental results showed that the fog treatment was effective at removing DPM from the exhaust. On average, the fog improved DPM removal by about 55% compared to when the treatment was not employed (fog off). To better understand the mechanisms responsible for DPM removal in the scrubber, a computer model was generated. The model uses the inlet parameters from the field tests, such as inlet DPM and fog concentration and tube geometry, and predicts the scrubber outlet DPM concentration. The model results suggest that the primary way that DPM is removed from the system is by combining with fog drops, which then hit the scrubber tube walls. This effect is probably enhanced by the ribbed structure of the scrubber tubing used here, which may be important for practical applications.
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Li, Hui. "A Mechanistic Model for CO2 Localized Corrosion of Carbon Steel." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1304558358.
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Camino, Eric M. "A Mechanistic Analysis of Gene Regulation and its Evolution in a Drosophila Model." University of Dayton / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1461242188.
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Arenas, Amado Antonio. "Development and application of a mechanistic model to predict juvenile salmon swim paths." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2813.
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Utility companies and regulatory agencies are interested in understanding juvenile salmon swimming patterns as they approach hydropower dams because it can allow them to assess fish bypass efficiency and conduct fish survival studies. A model capable of predicting juvenile salmon swim paths can assist in the design of fish bypasses and diversion structures. This thesis presents a mechanistic model tailored to simulate swimming patterns of juvenile salmon swimming in forebays, tailraces, and free-flowing rivers. The model integrates information on juvenile salmon behavior at both field and laboratory scale and literature on juvenile salmon swimming capabilities.
Simulated fish swim paths are determined by solving Newton's Second Law. Most of the model parameters are represented by probability distributions. Behavioral responses are triggered for the most part by the flow acceleration and pressure. The model uses conditional probability distributions of thrust magnitude and direction, given flow acceleration. Simulated fish select a swimming direction referenced to the flow velocity vector. To consider juvenile salmon's tendency to coast with the flow, the model intersperses periods of active swimming and gliding. Chinook salmon measured swim paths were analyzed. The flow variables at the fish locations were obtained from CFD simulations. Juvenile salmon mean thrust was determined from solving Newton's Second Law at every measured location. Results show that as flow acceleration increases, the juvenile salmon average thrust increases and the probability of gliding decreases. Chinook salmon tend to migrate tail-first as flow acceleration increases. For the flow accelerations of 5x10-4 m/s2 and 1x10-2 m/s2, approximately 85% and 95% of the analyzed fish migrated tail-first, respectively. The model capacity to predict fish migration route selection, fish-like trajectories, and residence times was tested at two hydropower dams. On average, migration routes were predicted with 17 percent of relative error. Model predictions for fish average residence times were within 10 percent of measured values.
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Rantow, Felix Suryaman Soroush Masoud Grady Charles. "Mechanistic modeling and model-based studies in spontaneous solution polymerization of alkyl acrylate monomers /." Philadelphia, Pa. : Drexel University, 2006. http://hdl.handle.net/1860/1306.
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Roy, Shouvik. "Mechanistic studies of physico-chemical stability of model therapeutic proteins using pharmaceutically relevant factors /." Connect to full text via ProQuest. IP filtered, 2006.
Find full textAbstract:
Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 161-173). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
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Groenewegen, Hendrik Cornelis. "Therapeutic and mechanistic explorations of in-stent restenosis in the rat aortic stenting model." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/.
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Smith, Robert A. W. "The role of monoethanolamine in hair bleaching and dyeing : mechanistic insights from model formulations." Thesis, University of York, 2014. http://etheses.whiterose.ac.uk/8316/.
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Primarily, the focus of this project was to investigate hair bleaching and dyeing mechanisms, in the presence of ammonia or ethanolamine (MEA), at room temperature. Firstly, the mechanism of hair bleaching by alkaline hydrogen peroxide was explored, using homogeneous solutions of Sepia melanin free acid (MFA) as a model for hair melanin. UV-vis spectroscopy was applied to study the rate of melanin bleaching under various conditions. It was established that both hydroxyl radicals and perhydroxyl anions are involved in the bleaching of melanin. Hydrogen peroxide decomposition and Sepia melanin oxidation were then monitored using homogenous model bleaching solutions, to see if differences in hair bleaching when MEA is used instead of ammonia could be explained by a change in chemistry. Dissimilarities were found in ligand-free and etidronic acid (HEDP) systems when the base was altered, due to the presence of differing metal complexes. However, when strong chelating ligands such as ethylenediaminetetraacetic acid (EDTA) are used, no differences were apparent in homogenous model bleaching systems. The mechanism of dye formation inside hair fibres was then investigated, due to the observation that catalase accelerates the oxidation of dye primaries in aqueous solutions. Dye formation was studied by UV-vis spectroscopy. It was shown that metal ion centres are predominantly responsible for the formation of dyes in the hair cortex. Fe(III) proved to be a more effective catalyst for dye production than Cu(II). Finally, the effect of MEA on the rate of hair dye formation in aqueous systems was studied, using HPLC and UV-vis spectroscopy. The rate of colour formation in MEA based formulations was found to be greater than in ammonia systems, possibly due to slower degradation of the dyes in MEA systems. It was also found that nucleophilic attack of MEA on preformed dye molecules leads to the formation of different dyes, which incorporate the base into their structure. The formation of these dyes greatly changes the colour of model aqueous dye solutions.
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Kim, Jaeyeon. "Model Analysis of Adipose Tissue and Whole Body Metabolism In Vivo." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1216436630.
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Siriwardena, Dylan. "Determination of Immunomodulatory Bioactivity Biomarkers and Mechanistic Insights in Umbilical Cord Mesenchymal Stromal Cells." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/38497.
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Detrimental immune and inflammatory responses contribute to the pathogenesis of various conditions, including Crohn’s disease, Lupus, and sepsis.1,2,3 Unfortunately, novel treatments for detrimental immune and inflammatory responses have been met with little success. Mesenchymal stromal cells (MSCs) represent a promising cellular therapy to treat immune and inflammatory disorders due to their ability to suppress the immune system. However, despite their promise, clinical trials that have employed MSC cellular therapies have produced varying and sometimes conflicting results. These discrepancies have been partially attributed to the cellular heterogeneity within MSC populations. To address these discrepancies, I performed transcriptomic and proteomic analysis of MSCs with varying immunomodulatory capacity to identify robust immunomodulatory biomarkers and gain better mechanistic insights into MSC immunomodulatory function. In this study, MSCs with differing immunomodulatory function were identified and the effect of in vitro passaging and proinflammatory induction on immunomodulatory ability was characterized. To characterize MSC immunomodulatory control mechanisms, RNA sequencing and proteomic analyses were performed on MSCs with different immunomodulatory capabilities. These analyses enabled the identification of potential immunomodulatory biomarkers and regulatory mechanisms. Finally, to test the therapeutic efficacy of immunomodulatory MSC subpopulations, I developed a humanize mouse model for sepsis. Overall, this work contributes to our understanding of MSC immunomodulation and to the development of a robust MSC cellular therapeutics.
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Czamanski-Cohen, J., and K. L. Weihs. "The Bodymind Model: A platform for studying the mechanisms of change induced by art therapy." Elsevier, 2016. http://hdl.handle.net/10150/621993.
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This paper introduces the Bodymind model of Art Therapy and delineates the processes through which it has salutary effects on individuals coping with a variety of health related challenges. The goal of this model is to articulate how activation, reorganization, growth and reintegration of the self can emerge from bodymind processes activated by art therapy. It provides a framework for the conduct of research that will test the key theoretical mechanisms through which art therapy benefits clients. We expect this model to be a spring board for discussion, debate and development of the profession of art therapy. Furthermore, we hope readers can use this model to conduct sound mechanistic studies. This paper can inform social scientists and medical professionals on the manner in which art making can contribute to health.
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Dominguez, Olivo Juan M. "Electrochemical Model of Carbon Dioxide Corrosion in the Presence of Organic Corrosion Inhibitors." Ohio University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1577092234789695.
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Guo, Juen. "A study of glucose metabolism and ketosis development in periparturient cows using a mechanistic model." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/2383.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2005.Thesis research directed by: Animal Sciences. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Luo, Zairen. "Flexible Pavement Condition Model Using Clusterwise Regression and Mechanistic-Empirical Procedure for Fatigue Cracking Modeling." See Full Text at OhioLINK ETD Center (Requires Adobe Acrobat Reader for viewing), 2005. http://www.ohiolink.edu/etd/view.cgi?toledo1133560069.
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Dissertation (Ph.D.)--University of Toledo, 2005.Typescript. "A dissertation [submitted] as partial fulfillment of the requirements of the Doctor of Philosophy degree in Engineering." Bibliography: leaves 90-99.
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Bargh, Mary Katharine. "A mechanistic model to predict nutritional effects on milk fatty acid profile in dairy cows." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ56303.pdf.
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Singh, Sunil. "Engineered Organotypic Breast Tumor Model for Mechanistic Studies of Tumor-Stromal Interactions and Drug Discovery." University of Akron / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=akron1616940345310981.
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Read, Jonathan M. "The effect of plant traits and resource supply characteristics on plant competition : a mechanistic model." Thesis, University of Stirling, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244695.
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McCormack, John Patrick. "A three-dimensional mechanistic ozone transport model: Applications to midlatitude trends and 11-year variability." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290698.
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Thirteen years of satellite-based total ozone measurements, extending from January 1979 through December 1991, are analyzed with a multiple regression statistical model to isolate the components of interannual variability associated with (1) linear trends and (2) the 11-year variation in solar ultraviolet irradiance. Lower stratospheric temperature and geopotential height data obtained from satellite- and ground-based sources are analyzed in similarly, providing a comprehensive assessment of the interannual variability in the lower stratosphere over the 1979-1991 period. The results of the statistical analyses indicate coherent variations in ozone, temperature, and geopotential height at extratropical latitudes in NH winter which are related to both the trend and solar-cycle components; the amplitudes of these variations exhibit pronounced spatial dependences. A three-dimensional mechanistic ozone transport model is used to describe the spatial distribution of total ozone in NH winter using observed lower stratospheric temperature and geopotential height fields. Application of this model on a year-to-year basis demonstrates that a large percentage of the observed interannual variability in the spatial distribution of total ozone is directly associated with changes in the dynamical structure of the lower stratosphere. The influence of dynamical variability on zonal mean total ozone is also investigated using an empirical approach. From the results of the observational and modeling studies, it is concluded that changes in the dynamics of the lower stratosphere over the 1979-1991 period have contributed significantly to the observed total ozone trends in the Northern Hemisphere. In contrast, the observed variability in total ozone associated with the 11-year solar cycle could not be explained in terms of a systematic variation in the dynamical forcing of the lower stratosphere in-phase with the 11-year cycle.
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Britton, Peter C., Jessica M. McKinney, Todd M. Bishop, Wilfred R. Pigeon, and Jameson K. Hirsch. "Insomnia and Risk for Suicidal Behavior: A Test of a Mechanistic Transdiagnostic Model in Veterans." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/etsu-works/5545.
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Background: Insomnia has been shown to have direct and indirect associations with suicidal ideation, attempts, and death in U.S. military and veteran populations. However, transdiagnostic models of insomnia and psychopathology have not been used to examine the contribution of psychopathology.
Method: The present study is a secondary analysis examining the associations among insomnia symptoms, posttraumatic stress disorder (PTSD) and depressive symptoms, interpersonal theory of suicide variables, and risk for suicidal behavior in community veterans (n = 392). Serial mediation was used to test sequential associations, allowing for examination of direct and indirect associations.
Results: The model with insomnia, PTSD, and depressive symptoms, and thwarted belongingness, accounted for 29% of the variance in risk. Insomnia symptoms had an indirect association through PTSD and depressive symptoms, and thwarted belongingness. The model with insomnia, PTSD, and depressive symptoms, and perceived burdensomeness accounted for 35% of the variance in risk. Insomnia symptoms had an indirect association through PTSD and depressive symptoms, and perceived burdensomeness.
Limitations: Data are cross-sectional, precluding the testing of causal associations.
Conclusions: In veterans, insomnia symptoms may be associated with increased PTSD and depressive symptoms, which may be associated with increased risk for suicidal behavior directly and indirectly through relationship disruptions.
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Lin, Yangchen. "Macroscopic insights from mechanistic ecological network models in a data void." Thesis, University of Cambridge, 2015. https://www.repository.cam.ac.uk/handle/1810/254976.
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Complexity science has come into the limelight in recent years as the scientific community begins to grapple with higher-order natural phenomena that cannot be fully explained via the behaviour of components at lower levels of organization. Network modeling and analysis, being a powerful tool that can capture the interconnections that embody complex behaviour, has therefore been at the forefront of complexity science. In ecology, the network paradigm is relatively young and there remain limitations in many ecological network studies, such as modeling only one type of species interaction at a time, lack of realistic network structure, or non-inclusion of community dynamics and environmental stochasticity. I introduce bioenergetic network models that bring together for the first time many of the fundamental structures and mechanisms of species interactions present in real ecological communities. I then use these models to address some outstanding questions that are relevant to understanding ecological networks at the systems level rather than at the level of subsets of interactions. Firstly, I find that realistic red-shifted environmental noise, and synchrony of species responses to noise, are associated with increased variability in ecosystem properties, with implications for predictive ecological modeling which usually assumes white noise. Next, I look at simultaneous species extinction and invasion, finding that as their individual impacts increase, their combined impact becomes decreasingly additive. In addition, the greater the impact of extinction or invasion, the lesser their reversibility via reintroduction or eradication of the species in question. For modifications of pairwise species interactions by third-party species, a phenomenon that has so far been studied one interaction at a time, I find that the many interaction modifications that occur concurrently in a community can collectively have systematic effects on total biomass and species evenness. Finally, examining a higher level of organization in the form of compartmentalized networks, I find that the relationship between intercompartment connectivity and the impacts of species decline depends considerably on network topology and whether the consumer-resource functional response is prey- or ratio-dependent. Overall, the results vary considerably across model communities with different parameterizations, underscoring the contingency and context dependence of nature that scientists and policy makers alike should no longer ignore. This work hopes to contribute to a growing multidisciplinary understanding, appreciation and management of complex systems that is fundamentally transforming the modern world and giving us insights on how to live more harmoniously within our environment.
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Rezsöhazy, Jeanne. "Data-model fusion approach using tree-ring width series, a mechanistic growth model and an Earth system model to reconstruct the large-scale climate variability." Thesis, Aix-Marseille, 2021. http://www.theses.fr/2021AIXM0618.
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Les largeurs des cernes d’arbres représentent les proxys les plus couramment utilisés pour reconstruire le climat du dernier millénaire à haute résolution temporelle. L’approche repose souvent sur une relation entre les séries de largeurs de cernes et le climat estimé par une régression linéaire. Les hypothèses de linéarité et stationnarité sous-jacentes peuvent être parfois inadéquates. Les modèles mécanistes de croissance d’arbre peuvent dépasser certaines des limitations de l’approche statistique. Dans cette thèse, nous proposons d’inclure pour la première fois un tel modèle mécaniste, MAIDEN, au sein d’une procédure d’assimilation de données afin de potentiellement améliorer les reconstructions du climat à large échelle. Nous avons tout d’abord développé un protocole de calibration du modèle MAIDEN applicable à n’importe quel site de latitude extra-tropicale. Nous avons ainsi montré que MAIDEN est performant à l’échelle globale et que d’importants bénéfices associés à son niveau de complexité font de lui un candidat attractif pour les reconstructions climatiques. Le modèle MAIDEN a ensuite été inclus avec succès au sein d’une procédure d’assimilation de données en tant que proxy system model pour permettre une comparaison robuste des sorties d’un modèle climatique aux observations de largeurs de cernes. La procédure a été testée pour reconstruire la variabilité climatique des quatre derniers siècles dans l’hémisphère sud. Même si les résultats sont encourageants, des analyses supplémentaires sont nécessaires pour démontrer une amélioration significative des reconstructions à large échelle comparativement à un modèle de régression avec l’assimilation de donnéesTree-ring width represent the most commonly used proxy to reconstruct the climate of the last millennium at high resolution, thanks to their large-scale availability. The approach often relies on a relationship between tree-ring width series and climate estimated on the basis of a linear regression. The underlying linearity and stationarity assumptions may be inadequate. Dendroclimatic process-based models may be able to overcome some of the limitations of the statistical approach. In this thesis, we propose to include for the first time a dendroclimatic process-based model, MAIDEN, into a data assimilation procedure in order to potentially improve large-scale climate reconstructions. We have first developed a protocol to calibrate and apply MAIDEN to potentially any sites with tree-ring width data in the extratropical region. We have shown that MAIDEN can be applied at global scale with a good performance and that clear benefits associated with its level of complexity make it an appealing candidate for paleoclimate reconstructions. Subsequently, the MAIDEN model has been successfully incorporated into a data assimilation procedure as a proxy system model to robustly compare climate model outputs with tree-ring width observations. The procedure has been tested to reconstruct the climate variability in the Southern Hemisphere over the last four centuries. Even if the results are encouraging, additional analysis are needed in order to establish that it may significantly improve large-scale climate reconstructions compared to a regression model in the data assimilation framework
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Larsson, Dhana E. "Analyses of Dose-Response and Mechanistic Action of Different Anti-Cancer Drugs for Neuroendocrine Tumor Cell Lines." Doctoral thesis, Uppsala universitet, Institutionen för medicinska vetenskaper, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-158833.
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Cancer is a disease with poor response rates on available treatments. Problems with resistance and intolerance against cancer drugs are major reasons for failure of the drugs. The need to discover new cancer drugs is important. In this thesis screening of new cancer drugs and evaluation of their mechanism of action are discussed. The aim of the thesis was to find new compounds active against neuroendocrine tumors (NETs). In paper I, we screened 1280 substances on two bronchial carcinoid cell lines and one pancreatic carcinoid cell line. Eleven of these compounds were found to have antitumor activity at low concentrations. The most active agents were brefeldin A, emetine, bortezomib and idarubicin, having IC50 values (the concentration of the drug where > 50% of the cells die) < 1μM. In addition, sanguinarine, Bay11-7085, mitoxantrone, doxorubicin, β-lapachone, NSC 95397 and CGP- 74514A were active with IC50 values < 10 μM. In paper II, additional studies have been undertaken to investigate the combination effect of the most active drugs with conventional cytotoxic drugs used in clinical practice. If synergistic or additive effects are found, drugs with different mechanism of action and toxicity profiles may be combined, making it possible to reduce the toxic effects yet maintaining the antitumor activity. In paper III, studies were undertaken to find the mechanistic action, apoptosis or necrosis, of the drugs NSC 95397, brefeldin A, bortezomib and sanguinarine in NETs. All four drugs were shown to induce caspase-3 activity and nuclear fragmentation/condensation in the neuroendocrine tumor cell lines, indicating that their antitumor activity was induction of apoptosis. In paper IV, the mechanism of action was studied for CGP-74514A and emetine. Both drugs worked by induction of apoptosis. In addition, their cytotoxic activity was studied in a three-dimensional model, the in vitro hollow fiber model. The Hollow Fiber model permits more realistic simulation of in vivo drug effects in a controlled system providing data that more accurately reflects biological responses. Our results showed that the hollow fiber model may be suitable for studies of new drugs in the neuroendocrine tumor cell lines.Title corrected from: Analyses of Dos-Response and Mechanistic Action of Different Anti-Cancer Drugs for Neuroendocrine Tumor Cell Lines
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Sjödin, Martin. "Regulation of Proton Coupled Electron Transfer from Amino Acids in Artificial Model Systems: A Mechanistic Study." Doctoral thesis, Uppsala University, Department of Physical Chemistry, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4132.
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Amino acid radicals are key redox intermediates in several natural enzymes including Cytochrome c peroxidase, DNA photolyase, ribonucletide reductase, cytochrome c oxidase and photosystem II. Electron transfer from amino acids is often coupled to deprotonation and this thesis concerns the coupling of electron transfer from tyrosine and tryptophan to trisbipyridineruthenium(III) with deprotonation in model complexes. Specifically the mechanisms for these proton coupled electron transfer reactions have been studied and the controlling parameters have been identified, the possible mechanisms being stepwise electron transfer followed by deprotonation and deprotonation followed by electron transfer or concerted electron transfer/deprotonation.
Proton coupled electron transfer reactions have been studied using nano-second flash photolysis in water solution and the effect of pH, temperature, reaction driving force, deuteration and nature of the amino acid has been determined. I have shown that the rate constant for the concerted reaction depends intrinsically on the mixing entropy of the released proton and that the pH-dependence can be used as an experimental tool for mechanistic discrimination. Moreover I have shown that the concerted reaction inherently has a high reorganisation energy due to the coupling of the electron motion with deprotonation. Hydrogen bonding to the transferring proton however significantly reduces this reorganisation energy. The concerted reaction also has a relatively high driving force counteracting the high reorganisation energy in the competition between the concerted reaction and the stepwise electron transfer first reaction. The relative importance of the high reorganisation energy and the high driving force for the concerted reaction determines the mechanistic outcome of the reaction, the stepwise reaction being favoured by high over-all driving forces and the concerted reaction by high pH.
By comparing my results from model complexes with tyrosineZ oxidation in photosystem II, I give strong evidence for a concerted electron transfer/deprotonation mechanism.
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Sjödin, Martin. "Regulation of proton coupled electron transfer from amino acids in artificial model systems : a mechanistic study /." Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4132.
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Angenendt, Alexandra. "Ecophysiological studies of field beans : a simple yet mechanistic crop growth model for Vicia faba L." Thesis, University of Reading, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250720.
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Gaber, Noha. "Development of a mechanistic model to assess the distribution of heavy metals in municipal wastewater treatment." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342771.
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Hicks, Mark. "Reactivity and mechanistic studies of small molecules at model metal oxide surfaces : underpinning PuO2 safe storage." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/69894/.
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The nuclear fuel cycle represents the nuclear power generation process, from mining the uranium ore to the treatment of waste. The fuel cycle is divided into two parts, the front end of the process and the back end of the process, with the nuclear power station being in the middle1. The processes before reaching the nuclear power station consist of uranium exploration, mining, refining, isotope enriching and fuel element fabrication1. Uranium is mined in twenty countries, but 52% of the world supply of uranium comes from just 6 countries. These countries are Canada, Australia, Russia, Kazakhstan, Namibia and Niger. Uranium is mined in several different types of mine. These include an open pit mine, an underground mine or in-situ leaching mine. In an open pit mine the ore lies close to the surface and the overlying layer of rock is removed creating a large pit where the ore is easily extractable. An underground mine is used when the ore lies deeper under the surface and the construction of access shafts and tunnels under the ground are needed to gain access to the uranium ore. The uranium ore is sometimes contained in ground water or a porous material, such as sand. In this case, a process called in-situ leaching is used to extract the uranium ore. Either acid or alkali (depending on the nature of the groundwater) is added to the ground water to dissolve the ore, and the resulting solution is pumped out. The ore then undergoes a milling process to extract the uranium oxides needed for fuel fabrication. Milling is normally carried out close to the mine where the ore has been extracted. The ore is crushed and then leached with sulphuric acid in order to dissolve the uranium oxides.