Дисертації з теми "Systems biology model"
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Coskun, Sarp Arda. "PATHCASE-SB MODEL SIMULATION AND MODEL COMPOSITION TOOLS FOR SYSTEMS BIOLOGY MODELS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1328556115.
Повний текст джерелаVeliz-Cuba, Alan A. "The Algebra of Systems Biology." Diss., Virginia Tech, 2010. http://hdl.handle.net/10919/28240.
Повний текст джерелаPh. D.
Karlstädt, Anja [Verfasser]. "A systems biology approach to model cardiomyocyte metabolism / Anja Karlstädt." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/1043197656/34.
Повний текст джерелаKonieczka, Jay, Kevin Drew, Alex Pine, Kevin Belasco, Sean Davey, Tatiana Yatskievych, Richard Bonneau, and Parker Antin. "BioNetBuilder2.0: bringing systems biology to chicken and other model organisms." BioMed Central, 2009. http://hdl.handle.net/10150/610006.
Повний текст джерелаthis engine translates between alternate gene names as well as between orthologs in multiple species. Additionally, BioNetBuilder is now implemented to be part of the Gaggle, thereby allowing seamless communication of interaction data to any software implementing the widely used Gaggle software. Using BioNetBuilder, we constructed a chicken interactome possessing 72,000 interactions among 8,140 genes directly in the Cytoscape environment. In this paper, we present a tutorial on how to do so and analysis of a specific use case.CONCLUSION:BioNetBuilder 2.0 provides numerous user-friendly systems biology tools that were otherwise inaccessible to researchers in chicken genomics, as well as other model systems. We provide a detailed tutorial spanning all required steps in the analysis. BioNetBuilder 2.0, the tools for maintaining its data bases, standard operating procedures for creating local copies of its back-end data bases, as well as all of the Gaggle and Cytoscape codes required, are open-source and freely available at http://err.bio.nyu.edu/cytoscape/bionetbuilder/ webcite.
Avva, Jayant. "Complex Systems Biology of Mammalian Cell Cycle Signaling in Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1295625781.
Повний текст джерелаGay, Steven. "Subgraph Epimorphisms : Theory and Application to Model Reductions in Systems Biology." Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC265.
Повний текст джерелаThis thesis develops a framework of graph morphisms and applies it to model reduction in systems biology. We are interested in the following problem: the collection of systems biology models is growing, but there is no formai relation between models in this collection. Thus, the task of organizing the existing models, essential for model refinement and coupling, is left to the modeler. In mathematical biology, model reduction techniques have been studied for a long time, however these techniques are far too restrictive to be applied on the scales required by systems biology. We propose a model reduction framework based solely on graphs, allowing to organize models in a partial order. Systems biology models will be represented by their reaction graphs. To capture the process of reduction itself, we study a particular kind of graph morphisms: subgraph epimorphisms, which allow both vertex merging and deletion. We first analyze the partial order emerging from the merge/delete graph operations, then develop tools to solve computational problems raised by this framework, and finally show both the computational feasibility of the approach and the accuracy of the reaction graphs/subgraph epimorphisms framework on a large repository of systems biology models
Prescott, Thomas Paul. "Large-scale layered systems and synthetic biology : model reduction and decomposition." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:205a18fb-b21f-4148-ba7d-3238f4b1f25b.
Повний текст джерелаFeist, Adam Michael. "Model-driven metabolic engineering of Escherichia coli a systems biology approach /." Diss., [La Jolla] : University of California, San Diego, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3354731.
Повний текст джерелаTitle from first page of PDF file (viewed June 2, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
Vesty, Eleanor Fay. "Understanding developmental processes in early-diverging plant model systems." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7498/.
Повний текст джерелаGhosh, Krishnendu. "Formal Analysis of Automated Model Abstractions under Uncertainty: Applications in Systems Biology." University of Cincinnati / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1330024977.
Повний текст джерелаToni, Tina. "Approximate Bayesian computation for parameter inference and model selection in systems biology." Thesis, Imperial College London, 2010. http://hdl.handle.net/10044/1/11481.
Повний текст джерелаChen, Daphne Wei-chen. "Integrative modelling of glucocorticoid induced apoptosis with a systems biology approach." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/integrative-modelling-of-glucocorticoid-induced-apoptosis-with-a-systems-biology-approach(a05039a1-f3e3-44d2-959e-0fade52a28a1).html.
Повний текст джерелаArat, Seda. "A Mathematical Model of a Denitrification Metabolic Network in Pseudomonas aeruginosa." Thesis, Virginia Tech, 2012. http://hdl.handle.net/10919/46208.
Повний текст джерелаMaster of Science
Eydgahi, Hoda. "A quantitative framework For large-scale model estimation and discrimination In systems biology." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/82347.
Повний текст джерелаCataloged from PDF version of thesis.
Includes bibliographical references (p. 103-111).
Using models to simulate and analyze biological networks requires principled approaches to parameter estimation and model discrimination. We use Bayesian and Monte Carlo methods to recover the full probability distributions of free parameters (initial protein concentrations and rate constants) for mass action models of receptor-mediated cell death. The width of the individual parameter distributions is largely determined by non-identifiability but co-variation among parameters, even those that are poorly determined, encodes essential information. Knowledge of joint parameter distributions makes it possible to compute the uncertainty of model-based predictions whereas ignoring it (e.g. by treating parameters as a simple list of values and variances) yields nonsensical predictions. Computing the Bayes factor from joint distributions yields the odds ratio (~20-fold) for competing "direct" and "indirect" apoptosis models having different numbers of parameters. The methods presented in this thesis were then extended to make predictions in eight apoptosis mini-models. Despite topological uncertainty, the simulated predictions can be used to drive experimental design. Our results illustrate how Bayesian approaches to model calibration and discrimination combined with single-cell data represent a generally useful and rigorous approach to discriminating between competing hypotheses in the face of parametric and topological uncertainty.
by Hoda Eydgahi.
Ph.D.
Gómez, Uribe Carlos Alberto. "Systems of chemical reactions in biology : dynamics, stochasticity, spatial effects and model reduction." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/43803.
Повний текст джерелаThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references (p. 221-232).
Cells are continuously sensing and processing information from their environments and responding to it in sensible ways. The communication networks on which such information is handled often consist of systems of chemical reactions, such as signaling pathways or metabolic networks. This thesis studies the dynamics of systems of chemical reactions in the context of biological cells. The first part of this thesis analyzes the osmo-regulation network in yeast, responsible for the regulation of internal osmolarity. We measure the system's step response in single cells, and find that the steady state is independent of the input, a property termed perfect adaptation that relies on integral feedback control. We then consider the signaling cycle, a pattern of chemical reactions that is often present in signaling pathways, in which a protein can be either active (e.g., phosphorylated) or inactive (e.g., unphosphorylated). We identify new regimes of static and dynamic operation, and find that these cycles can be tuned to transmit or digitize time-varying signals, while filtering input noise. The second part of this thesis considers systems of chemical reactions where stochastic effects are relevant, and simplifies the standard models. We develop an approximate model for the time-evolution of the average concentrations and their variances and covariances in systems with and without spatial gradients. We also describe a framework to identify and derive approximate models for variables that evolve at different time scales in systems without spatial gradients. These tools can help study the impact of stochastic and spatial effects on system behavior.
by Carlos Alberto Gómez Uribe.
Ph.D.
Urquiza, García José María Uriel. "Mathematical model in absolute units for the Arabidopsis circadian oscillator." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31132.
Повний текст джерелаBatenchuk, Cory. "Development of a Mathematical Model to Understand, Design & Improve Oncolytic Virus Therapies." Thesis, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31182.
Повний текст джерелаOvidiu, Parvu. "Computational model validation using a novel multiscale multidimensional spatio-temporal meta model checking approach." Thesis, Brunel University, 2016. http://bura.brunel.ac.uk/handle/2438/11863.
Повний текст джерелаAisenberg, Jeremy Charles. "A Critical Review of Telomerase Biology and Model Systems for the Study of Telomerase." VCU Scholars Compass, 2006. http://hdl.handle.net/10156/2120.
Повний текст джерелаJones, Thomas Carroll Jr. "JigCell Model Connector: Building Large Molecular Network Models from Components." Thesis, Virginia Tech, 2017. http://hdl.handle.net/10919/78277.
Повний текст джерелаMaster of Science
Gowen, Christopher. "Model-Guided Systems Metabolic Engineering of Clostridium thermocellum." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2529.
Повний текст джерелаPerron, Amélie. "NTS2 neurotensin receptors : distribution, interactions, and cellular dynamics in model systems and rat brain." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=102692.
Повний текст джерелаHarland, Christopher William 1983. "Desiccation resistance and viscoelasticity in model membrane systems." Thesis, University of Oregon, 2010. http://hdl.handle.net/1794/10993.
Повний текст джерелаLipid membranes are a basic structural element of all cells. They provide a framework for the physical organization of the cell, act as a scaffold for numerous proteins, and serve as the host site for countless chemical reactions integral to cell function. Several key problems in membrane biophysics hinge on reliable methods for measuring membrane material properties. Properties such as rigidity, fluidity, charge density, etc., are important factors that govern membrane structure and function. As such, we need controllable, reliable, and quantitative methods of probing membrane material properties. In pursuit of such methods, we completed two related projects that, while distinct, aimed to create and apply quantitative measures of membrane material properties to current problems in biophysics. The first of these two lines of inquiry centered on the pervasive, pathogenic family of mycobacteria that is known to not only cause several diseases but also to survive prolonged periods of dehydration. We developed an experimental model system that mimics the structure of the mycobacterial envelope consisting of an immobile hydrophobic layer supporting a two-dimensionally fluid, glycolipid-rich outer monolayer. With this system, we show that glycolipid containing monolayers, in great contrast to phospholipid monolayers, survive desiccation with no loss of integrity, as assessed by both fluidity and protein binding, revealing a possible cause of mycobacterial persistence. In the second line of inquiry, we developed another general platform for probing membrane material properties that has produced the first reported observations of viscoelasticity in lipid membranes. We utilized recently developed microrheological techniques on freestanding lipid bilayer systems using high speed video particle tracking. The complex shear modulus of the bilayers was extracted at a variety of temperatures that span the liquid-ordered to disordered phase transition of the membranes. At many temperatures measured, the membranes displayed viscoelastic behavior reminiscent of a Maxwell material, namely elastic at high frequencies and viscous at low frequencies. Moreover, the viscoelastic behavior was suppressed at the critical phase transition temperature where the membranes behave as a purely viscous fluid. Surprisingly, the viscoelastic behavior was found in all of several distinct membrane compositions that were examined.
Committee in charge: Dr. Daniel Steck, Chair; Dr. Raghuveer Parthasarathy, Research Advisor; Dr. Darren Johnson; Dr. Heiner Linke; Dr. John Toner
Wilcock, Paul. "A systems biology approach for investigating oral squamous cell carcinoma (OSCC)." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/a-systems-biology-approach-for-investigating-oral-squamous-cell-carcinoma-oscc(8ec3728b-1928-450f-b467-76996fa970fb).html.
Повний текст джерелаQuo, Chang Feng. "Reverse engineering homeostasis in molecular biological systems." Thesis, Georgia Institute of Technology, 2013. http://hdl.handle.net/1853/49144.
Повний текст джерелаSmith, Aaron. "Vertex model approaches to epithelial tissues in developmental systems." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:4d19f232-764c-4e27-bca9-d2ede0ec2db9.
Повний текст джерелаDaruwalla, Anahita. "Understanding Carotenoid and Retinoid Biochemical Diversity using Novel Archaeal and Eukaryotic Model Systems." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1626709424672807.
Повний текст джерелаMarín, de Mas Igor Bartolomé. "Development and application of novel model-driven and data-driven approaches to study metabolism in the framework of systems medicine." Doctoral thesis, Universitat de Barcelona, 2015. http://hdl.handle.net/10803/296313.
Повний текст джерелаLa presente tesis doctoral se centra en el desarrollo de herramientas computacionales que permitan el estudio de los mecanismos moleculares que ocurren dentro de la célula. Mas específicamente estudia el metabolismo celular desde diferentes puntos de vista usando y desarrollando métodos computacionales basados en diversas metodologías. Así pues en un primer capitulo se desarrolla un método basado en el analista de los flujos metabólicos en estado no estacional isotópico utilizando modelos cinéticos para estudiar el fenómeno de la canalización metabólica en hepatocitos. Este fenómeno modifica la topología metabólica alterando el fenotipo. Nuestro método nos permitió discriminar varios modelos con distintas topología prediciendo la existencia de canalización metabólica en la glucólisis. En el segundo capitulo se desarrolló un método para analizar el metabolismo tumoral teniendo en cuenta la heterogeneidad de poblaciones. En concreto estudiamos dos subpoblaciones extraídas de una linea celular de cáncer de próstata. Para ello utilizamos un modelo a gran escala de todo el metabolismo celular humano. El análisis reflejó la existencia de diferencias notables a nivel de vías metabólicas concretas, confiriendo a cada subpoblacion sensibilidades distintas a diferentes fármacos. En esta linea se demostró que mientras las células PC-3M eran sensibles al etomoxir e insensibles al calcitriol, las PC-3S presentaban una sensibilidad opuesta. En el tercero y ultimo capitulo de la tesis desarrollamos un nuevo método computacional que integra aproximaciones probabilísticas y mecanicistas para integrar diferentes tipos de datos en un análisis basado en modelos discretos. Para ello utilizamos como caso de concepto el estudio de la adaptación anómala al entrenamiento de pacientes con EPOC. El análisis reveló diferencias importantes a nivel de metabolismo energético en comparación con el grupo control.
Johansson, Rikard. "Model-Based Hypothesis Testing in Biomedicine : How Systems Biology Can Drive the Growth of Scientific Knowledge." Doctoral thesis, Linköpings universitet, Avdelningen för medicinsk teknik, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-141614.
Повний текст джерелаAnvändandet av matematiska verktyg har inom biologi och medicin traditionellt sett varit mindre utbredd jämfört med andra ämnen inom naturvetenskapen, såsom fysik och kemi. Ett ökat behov av verktyg som databehandling, bioinformatik, statistik och matematisk modellering har trätt fram tack vare framsteg under de senaste decennierna. Dessa framsteg är delvis ett resultat av utvecklingen av storskaliga datainsamlingstekniker. Inom alla områden av biologi och medicin så har dessa data avslöjat en hög nivå av interkonnektivitet mellan komponenter, verksamma på många kontrollnivåer och med flera återkopplingar både mellan och inom varje nivå av kontroll. Tillgång till storskaliga data är emellertid inte synonymt med en detaljerad mekanistisk förståelse för det underliggande systemet. Snarare uppnås en mekanisk förståelse först när vi bygger en hypotes vars prediktioner vi kan testa experimentellt. Att identifiera intressanta prediktioner som är av kvantitativ natur, kräver generellt sett matematisk modellering. Detta kräver i sin tur att det studerade systemet kan formuleras till en matematisk modell, såsom en serie ordinära differentialekvationer, där olika hypoteser kan uttryckas som precisa matematiska uttryck som påverkar modellens output. Inom vissa delområden av biologin har utnyttjandet av matematiska modeller haft en lång tradition, såsom den modellering gjord inom elektrofysiologi av Hodgkin och Huxley på 1950‑talet. Det är emellertid just på senare år, med ankomsten av fältet systembiologi, som matematisk modellering har blivit ett vanligt inslag. Den något långsamma adapteringen av matematisk modellering inom biologi är bl.a. grundad i historiska skillnader i träning och terminologi, samt brist på medvetenhet om exempel som illustrerar hur modellering kan göra skillnad och faktiskt ofta är ett krav för en korrekt analys av experimentella data. I detta arbete tillhandahåller jag sådana exempel och demonstrerar den matematiska modelleringens och hypotestestningens allmängiltighet och tillämpbarhet i tre olika biologiska system. I Arbete II visar vi hur matematisk modellering är nödvändig för en korrekt tolkning och analys av dominant-negativ-inhiberingsdata vid insulinsignalering i primära humana adipocyter. I Arbete III använder vi modellering för att bestämma transporthastigheter över cellkärnmembranet i jästceller, och vi visar hur denna teknik är överlägsen traditionella kurvpassningsmetoder. Vi demonstrerar också frågan om populationsheterogenitet och behovet av att ta hänsyn till individuella skillnader mellan celler och befolkningen som helhet. I Arbete IV använder vi matematisk modellering för att förkasta tre hypoteser om hur fenomenet facilitering uppstår i pyramidala nervceller hos råttor och möss. Vi visar också hur en överlevande hypotes kan beskriva all data, inklusive oberoende valideringsdata. Slutligen utvecklar vi i Arbete I en metod för modellselektion och modelldiskriminering med hjälp av parametrisk ”bootstrapping” samt kombinationen av olika empiriska fördelningar av traditionella statistiska tester. Vi visar hur det empiriska ”log-likelihood-ratio-testet” är den bästa kombinationen av två tester och hur testet är applicerbart, inte bara för modellselektion, utan också för modelldiskriminering. Sammanfattningsvis är matematisk modellering ett värdefullt verktyg för att analysera data och testa biologiska hypoteser, oavsett underliggande biologiskt system. Vidare utveckling av modelleringsmetoder och tillämpningar är därför viktigt eftersom dessa sannolikt kommer att spela en avgörande roll i framtiden för biologi och medicin, särskilt när det gäller att hantera belastningen från ökande datamängder som blir tillgänglig med nya experimentella tekniker.
Gauges, Ralph [Verfasser], and Ursula [Akademischer Betreuer] Kummer. "Standards and Tools for Model Exchange and Analysis in Systems Biology / Ralph Gauges ; Betreuer: Ursula Kummer." Heidelberg : Universitätsbibliothek Heidelberg, 2011. http://d-nb.info/1179229126/34.
Повний текст джерелаNarayan, Mahesh. "Functional characterization of (beta)-lactoglobulin; studies of free radical and reactive oxygen species in model and biological systems /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487943341529796.
Повний текст джерелаHengenius, James B. "Quantitative modeling of spatiotemporal systems| Simulation of biological systems and analysis of error metric effects on model fitting." Thesis, Purdue University, 2015. http://pqdtopen.proquest.com/#viewpdf?dispub=3687049.
Повний текст джерелаUnderstanding the biophysical processes underlying biological and biotechnological processes is a prerequisite for therapeutic treatments and technological innovation. With the exponential growth of computational processing speed, experimental findings in these fields have been complemented by dynamic simulations of developmental signaling and genetic interactions. Models provide means to evaluate "emergent" properties of systems sometimes inaccessible by reductionist approaches, making them test beds for biological inference and technological refinement.
The complexity and interconnectedness of biological processes pose special challenges to modelers; biological models typically possess a large number of unknown parameters relative to their counterparts in other physical sciences. Estimating these parameter values requires iterative testing of parameter values to find values that produce low error between model and data. This is a task whose length grows exponentially with the number of unknown parameters. Many biological systems require spatial representation (i.e., they are not well-mixed systems and change over space and time). Adding spatial dimensions complicates parameter estimation by increasing computational time for each model evaluation. Defining error for model-data comparison is also complicated on spatial domains. Different metrics compare different features of data and simulation, and the desired features are dependent on the underlying research question.
This dissertation documents the modeling, parameter estimation, and simulation of two spatiotemporal modeling studies. Each study addresses an unanswered research question in the respective experimental system. The former is a 3D model of a nanoscale amperometric glucose biosensor; the model was used to optimize the sensor's design for improved sensitivity to glucose. The latter is a 3D model of the developmental gap gene system that helps establish the bodyplan of Drosophila melanogaster; I wished to determine if the embryo's geometry alone was capable of accounting for observed spatial distributions of gap gene products and to infer feasible genetic regulatory networks (GRNs) via parameter estimation of the GRN interaction terms. Simulation of the biosensor successfully predicted an optimal electrode density on the biosensor surface, allowing us to fabricate improved biosensors. Simulation of the gap gene system on 1D and 3D embryonic demonstrated that geometric effects were insufficient to produce observed distributions when simulated with previously reported GRNs. Noting the effects of the error definition on the outcome of parameter estimation, I conclude with a characterization of assorted error definitions (objective functions), describe data characteristics to which they are sensitive, and end with a suggested procedure for objective function selection. Choice of objective function is important in parameter estimation of spatiotemporal system models in varied biological and biotechnological disciplines.
Keane, Harriet. "Network pharmacology of the MPP+ cellular model of Parkinson's disease." Thesis, University of Oxford, 2015. http://ora.ox.ac.uk/objects/uuid:1e18e521-c1a3-4f1b-9572-9c68e0f16c2f.
Повний текст джерелаSundqvist, Nicolas. "Can you trust your model? A showcase study of validation in 13C metabolic flux analysis." Thesis, Linköpings universitet, Institutionen för medicinsk teknik, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-156328.
Повний текст джерелаWu, Zujian. "A generic approach to behaviour-driven biochemical model construction." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/7413.
Повний текст джерелаAlborgeba, Zainab. "Development and evaluation of a cost-effectiveness analysis model for sepsis diagnosis." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19155.
Повний текст джерелаParsons, Sven David Charles. "Natural animal model systems to study tuberculosis." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/4505.
Повний текст джерелаENGLISH ABSTRACT: The growing global epidemic of human tuberculosis (TB) results in 8 million new cases of this disease and 2 million deaths annually. Control thereof will require greater insight into the biology of the causative organism, Mycobacterium tuberculosis, and into the pathogenesis of the disease. This will benefit the design of new vaccines and diagnostic assays which may reduce the degree of both disease transmission and progression. Animal models have played a vital role in the understanding of the aetiology, pathogenesis, and treatment of TB. Much of such insight has been obtained from experimental infection models, and the development of new vaccines, for example, is dependant on these. Nonetheless, studies utilising naturally occurring TB in animals, such as those which have investigated the use of interferon-gamma release assays (IGRA) for its diagnosis, have contributed substantially to the body of knowledge in this field. However, there are few such examples, and this study sought to identify and investigate naturally occuring animal TB in South Africa as an opportunity to gain further insight into this disease. During the course of this study, the dassie bacillus, a distinctly less virulent variant of M. tuberculosis, was isolated from a rock hyrax from the Western Cape Province of South Africa. This has provided new insight into the widespread occurrence of this organism in rock hyrax populations, and has given impetus to further exploring the nature of the difference in virulence between these pathogens. Also investigated was M. tuberculosis infection in dogs in contact with human TB patients. In so doing, the first reported case of canine TB in South Africa was described, v a novel canine IGRA was developed, and a high level of M. tuberculosis infection in these animals was identified. This supports human data reflecting high levels of transmission of this pathogen during the course of human disease. Additionally, the fact that infected companion animals may progress to disease and potentially act as a source of human infection was highlighted. However, an attempt to adapt a flow cytometric assay to study cell-mediated immune responses during canine TB revealed the limitations of such studies in species in which the immune system remains poorly characterised. The use of IGRAs to diagnose TB was further explored by adapting a human assay, the QuantiFERON-TB Gold (In-Tube Method), for use in non-human primates. These studies have shown that such an adaption allows for the sensitive detection of TB in baboons (Papio ursinus) and rhesus macaques (Macaca mulatta) and may be suitable for adaption for use in other species. However, they have also evidenced the limitation of this assay to specifically detect infection by M. tuberculosis. Finally, to contextualise the occurrence of the mycobacterial infections described above, and other similar examples, these have been reviewed as an opinion piece. Together, these investigations confirm that animal models will continue to make important contributions to the study of TB. More specifically, they highlight the opportunities that naturally occuring animal TB provides for the discovery of novel insights into this disease.
AFRIKAANSE OPSOMMING: Wêreldwye tuberkulose (TB) epidemie veroorsaak agt miljoen nuwe gevalle en twee miljoen sterftes jaarliks. Ingryping by die beheer hiervan vereis begrip van die biologie van die mikroörganisme Mycobacterium tuberculosis, die oorsaak van TB, asook van die patogenese van die siekte self. Hierdie kennis kan lei tot ontwerp van nuwe entstowwe en diagnostiese toetse wat gevolglik beide die oordrag- en vordering van die siekte mag bekamp. Dieremodelle speel lankal 'n rol in ons begrip van die etiologie-, patogenese- en behandeling van TB. Insig is grotendeels verkry vanaf eksperimentele infeksiemodelle, en ontwikkeling van entstowwe, onder andere, is afhanklik van soortgelyke modelle. Desnieteenstaande, studies wat natuurlike TB voorkoms in diere ondersoek, byvoorbeeld dié wat op die ontwikkeling van interferon-gamma vrystellingstoetse (IGVT) fokus, het merkwaardige bydrae gemaak tot kennis en begrip in hierdie studieveld. Daar is slegs enkele soortgelyke voorbeelde. Om hierdie rede is die huidige studie uitgevoer waarbinne natuulike diere-TB geïdentifiseer en ondersoek is in Suid-Afrika om verdere kennis en insig te win aangaande TB. Die "dassie bacillus", bekend om beduidend minder virulent te wees as M. tuberculosis, is tydens hierdie studie geïsoleer vanuit 'n klipdassie (Procavia capensis) in die Wes-Kaapse provinsie, Suid-Afrika. Insig in die wydverspreide voorkoms van hierdie organisme in klipdassie bevolkings is gevolglik verkry en verskaf momentum om die aard van verskil in virulensie tussen dié patogene te bestudeer. vii Voorts is M. tuberculosis infeksie bestudeer in honde wat in kontak is met menslike TB pasiënte en word die eerste geval van honde TB dus in Suid-Afrika beskryf. In hierdie groep diere, is 'n hoë vlak van M. tuberculosis infeksie geïdentifiseer deur gebruik te maak van 'n nuut ontwikkelde IGVT vir die diagnose van honde TB. Gevolglik ondersteun dié studie bevindinge van menslike studies wat toon dat besondere hoë vlakke van M. tuberculosis oordrag voorkom gedurende die verloop van die siekte. Verder toon die studie dat geïnfekteerde troeteldiere 'n bron van menslike infeksie kan wees. 'n Poging om 'n vloeisitometriese toets te ontwikkel om die aard van selgefundeerde immuunreaksies te bestudeer in honde met TB toon die beperkings van dergelike studies in spesies waarin die immuunsisteem gebrekkig gekarakteriseer is. Die gebruik van IGVT'e in die diagnose van TB is verder ondersoek deur 'n menslike toets (QuantiFERON-TB Gold, In-Tube Method) aan te pas vir die gebruik van nie-menslike primaat gevalle. Hierdie studies toon gevolglik dat so 'n aanpassing toepaslik is vir hoogs sensitiewe deteksie van TB in chacma bobbejane (Papio ursinus) en rhesus ape (Macaca mulatta), en mag ook aangepas word vir gebruik in ander spesies. Tog word die beperkings van hierdie toets om infeksie wat spesifiek deur M. tuberculosis veroorsaak uitgelig. Ter afsluiting word hierdie studie in konteks geplaas deur 'n oorsig te gee van bogenoemde- en soortgelyke gevalle van dierlike infeksie deur mikobakterieë in Suid-Afrika. Hierdie studies bevestig dat dieremodelle steeds belangrike toevoegings maak tydens die bestudering van TB en lig veral die moontlikhede uit dat bestudering van natuulike TB in diere kan lei tot die ontdekking van nuwe insigte ten opsigte van die siekte self.
Jha, Sumit Kumar. "Model Validation and Discovery for Complex Stochastic Systems." Research Showcase @ CMU, 2010. http://repository.cmu.edu/dissertations/10.
Повний текст джерелаMitchell, Simon. "A computational model of human iron metabolism." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/a-computational-model-of-human-iron-metabolism(c3afe167-4a40-42aa-8fd8-a65e47dfe7eb).html.
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Повний текст джерелаKarkutla, Raja K. "Agent Based and Stochastic Simulations for Non-homogeneous Systems." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1271708137.
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Повний текст джерелаBakhtiyari, Elnaz. "Analysis of differentially expressed genes (DEGs) in neuronal cells from the cerebral cortex of Alzheimer’s disease mouse model." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19218.
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Повний текст джерелаMaster of Science
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Повний текст джерелаLuise, Fabiana. "A systems biology approach to model the development of the mouse second branchial arch in mouse embryonic stem cells." Thesis, University of Manchester, 2018. https://www.research.manchester.ac.uk/portal/en/theses/a-systems-biology-approach-to-model-the-development-of-the-mouse-second-branchial-arch-in-mouse-embryonic-stem-cells(95f1e66d-4260-413c-bc9a-2eb106df4c84).html.
Повний текст джерела