Dissertations / Theses: 'Systemic model'

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Leung, Wai-hin, and 梁瑋軒. "Neurogenesis in animal model of systemic lupus erythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/209497.

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Systemic Lupus Erythematosus (SLE) is an autoimmune disease which is characterized by high level of autoantibody detected in the body. This disease is female predominant with a male to female ratio 1: 9. SLE could cause damage to different organ systems and central nervous system is one of them. Patients diagnosed with SLE could suffer from psychiatric problems like cognitive dysfunction, depression and anxiety. Neurogenesis refers to the process by which new neurons are generated. Although it has been widely reported that neurogenesis could be enhanced under pathological conditions such as stroke, Huntington’s disease and epilepsy, study focusing on the relationship between neurogenesis and SLE remains limited. In the present study, by using NZB/W F1 mice as the animal model of SLE, we could demonstrate that there was dramatic increase of neuronal precursor cells at the corpus callosum after the onset of SLE symptoms. Meanwhile, as IBA-1 positive cells and GFAP positive cells also increased significantly there, this suggested inflammation has taken place. I hypothesized there were upregulation of immunological factors after the onset of SLE symptoms and those factors were responsible for the neurogenesis. In my in vitro study, cytokine- interferon gamma (IFN gamma) has been shown to promote neuronal progenitor cells (NPCs) to differentiate into neuronal linage but it did not obviously affect the cell proliferation and migration. For the other cytokine and chemokines, including interleukin-10 (IL-10), interleukin-8 (IL-8), macrophage-derived chemokine (MDC), stromal cell-derived factor 1 alpha (SDF-1alpha) and thymus and activation regulated chemokine (TARC), all of them had no effect on NPC proliferation and differentiation. As far as we know, this is the first study to report SLE could enhance neurogenesis. Concerning the role of inflammation and IFN gamma on the neurogenesis in our case, it should be worth for further investigation, which will benefit future development of novel treatment targeting psychiatric symptoms in SLE.
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Anatomy
Master
Master of Philosophy

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Stierand, Marc B. "Phenomenological model of culinary innovation : a systemic view." Thesis, University of Strathclyde, 2009. http://oleg.lib.strath.ac.uk:80/R/?func=dbin-jump-full&object_id=18262.

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Chen, Weiwei. "A coupled left ventricle and systemic arteries model." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/7037/.

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Mathematical modelling and computational simulation are effective tools in studying the function of the cardiovascular system and diagnosing the progress of diseases in this system, especially when clinical experiments or measurements are limited or not capable to proceed. A variety of models have been developed related to different segments in the cardiovascular system, such as the heart, the valves, the systemic arteries and the pulmonary arteries, etc. Among these studies, modelling the left ventricle (LV) and systemic arteries (SA) have drawn a great deal of attention in the last several decade due to the high pressure and high morbidity of the systemic circulation. The recent models range from lumped-parameter models, one-dimensional models to three-dimensional models,which expand our understanding of the function of the left ventricle and systemic arteries respectively, but few of them considered the interaction between two parts. Thus, the propose of this thesis is to develop a dynamic cardiac-vascular model to study the pressure and flow wave interactions in the systemic circulation. Here we employs two advanced models, a three-dimensional finite-strain structure-based LV, and a one-dimensional dynamic physiologically-based model for the systemic arteries, to complete a coupled LV-SA model. The LV model is based on Gao et al. [35]’s work. In this model, the fluid-structure interaction (FSI) is described by an Immersed Boundary (IB) approach, in which an incompressible solid is immersed in a viscous incompressible fluid, and solved by a Lagrangian Finite Element (FE) method [40]. The systemic circulation model is employed from Olufsen et al. [90]’s work, which consists of two groups of arteries, the large arteries and the small arteries or vascular beds. The large-arteries model uses a LaxWendroff scheme to compute the cross-sectional area-averaged flow and pressure based on physiological parameters of the arterial tree. The vascular beds are modelled as asymmetric structured tree, to provide outflow boundary conditions at the end of each terminal vessel in the network of large arteries. The coupling is achieved by matching the pressure and flow rate at the aortic root, i.e. the circulation model feeds back the pressure as a boundary condition to the LV model, and the flow rate from the LV is used as the inflow for the circulation model. The function of the aortic valve (AV) is modelled as follows: the AV opens when the pressure in the LV just exceeds the pressure in the proximal aorta adjacent to the valve; the AV closes when the flow rate is negative (referring to backflow) at the boundary plane in the LV proximal to the AV. The governing equations of the system is solved by a combined immersed boundary finite element (IB/FE) method, and the LaxWendroff scheme of Olufsen et al. [90]. To investigate the cardio-vascular interactions under different conditions in the LV-SA system, this thesis first simulate a standard case defined by using parameters based on measurements of healthy LV and healthy systemic arteries from two healthy subjects, and then simulating four disease-related cases based on different pathological conditions in the LV-SA model, i.e. stiffening of the large arteries, functional rarefaction, increasing heart beat rate (by shortening the systemic diastolic phase) and varied end-of-diastolic pressure. The results of pathological cases are compared with the standard case to provide a more insightful change of the pressure/flow interaction, and the change of LV contractility. To better understand the cardiac-valvular-vascular interactions, a lumped-parameter AV model is coupled in the LV-SA model to further develop it into a more detailed LV-AV-SA model. Compared to the LV-SA model (no AV), when a normal AV condition is used in the coupled LV-AV-SA model, the active tension of the LV and the peak LV pressure at early systole slightly increases, but the peak flow rate and the cardiac output barely changed. While, when a mild stenosis AV condition is applied in the LV-AV-SA model, the LV function changes dramatically, especially a dramatically increase of the peak LV pressure and the peak active tension of the LV. This indicates that the valve condition is also important in studying cardiac-vascular interactions, especially for diseased valve conditions that the effects are huge and cannot be ignored. In order to study how the valvular region affects the cross-valve pressure difference, we reconstruct the valvular region in the LV based on the mid-systolic CMR images, which shows a 93% increase of the cross-sectional area in the valvular region than early systole. The cross-valve pressure drop decreases dramatically with a expanded valvular region compared with the narrower valvular region in previous LV-SA model. This indicates that the a local stenosis in the valvular region may have significant effects on the heart function, and a better description of modelling the expanding procedure of the valvular region is needed to predict more physiological results. This thesis is a step forward for studying the cardiac-valvular-vascular interactions in the systemic circulation, and can provide dynamic pressure and flow waveforms in the LV and long the systemic arteries. Moreover, this model not only verifies the effects of pethological conditions but also quantifies change of pressure, flow rate and ventricular inotropy in the LV-SA system, which is important progress and has barely been studied before. Further approach of this work is to develop a patient-specific model in the future to diagnose the progress of disease, as well as providing practical treatment strategy.

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Elidrissi, Imane <1991&gt. "applying Markov Chain switching model to Systemic Risk measures." Master's Degree Thesis, Università Ca' Foscari Venezia, 2015. http://hdl.handle.net/10579/6943.

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Drago, Leandro. "Non-systemic metamorphosis: millipede gonopods as a model system." Doctoral thesis, Università degli studi di Padova, 2009. http://hdl.handle.net/11577/3426455.

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Arthropod post-embryonic life is characterized by periodical moult cycles. These events are essential during individual growth, given that a rigid exoskeleton wraps them. When a moult event corresponds with a relatively sudden and conspicuous change in animal’s structure, is called metamorphosis; this phenomenon is characterized by a relatively high level of processes like apoptosis and cellular proliferation. For this reason, the study of the processes involved during metamorphosis has become a very important subject in evolutionary developmental biology (evo-devo) of arthropods. The principal limit of these researches, nevertheless, is that they focus on a small number of species and to draw general conclusions based uniquely on data collected from a few model systems can be risky. Recent studies about metamorphosis underpin on species characterized in most of the cases by a systemic metamorphosis. These are mainly holometabolous insects, in which the transition to the adult is rich of changes, affecting the whole body, although often with different degrees of intensity. Most of the arthropods, exhibits minor post-embryonic changes. Less usual is a situation in which a sudden developmental change affects one or a few non terminal segments, that initially are identical to those that precede and follow them along the body. This kind of post-embryonic transformation, confined in a well defined region of the body, is defined in this thesis with the term non-systemic metamorphosis. It can be observed during the post-embryonic development of males of helminthomoph millipedes. In males helminthomorph millipedes, during post-embryonic life, a sudden changes occurs that involves only one or two pair of non terminal appendages, initially not different from the others and part of a long homonomous series. In the adults these appendages, localized in the seventh ring, are modified into gonopods, that are used as claspers or to transfer sperm during the copula. During the first stages of development the seventh ring is identical to the others and it brings two pair of conventional walking legs; in one of the following stage the legs are substituted by extremely reduced structures (called squamiform appendages), that subsequently turn into gonopods. In this thesis I investigated the metamorphosis of the eighth and ninth pair of legs, that correspond to the seventh ring of the body (a ring is a morphological unit that generally is considered as two conventional segments) in two blanulids (Nopoiulus kochii (Gervais, 1847) and Blaniulus guttulatus (Bosc, 1792)), in one nemasomatid (Nemasoma varicorne C.L. Koch, 1847) and in one polydesmid (Oxidus gracilis (C.L. Koch, 1847)) millipedes. Special attention was paid to the last stage in which males maintain the eighth (and eventually the ninth) pair of locomotory appendages, the stages in which these are substituted by squamiform appendages and the first stage with gonopods. I performed investigations on the external morphology, using optical and scanning electron microscopy. Internal anatomy was described through paraffin sections. The endoskeletal structures associated with gonopods, was studied using confocal laser scanning microscopy taking advantage of the autofluorescence of the cuticle. As documented here for the first time the external modifications caused by the non-systemic metamorphosis of diplopods are associated with a huge rearrangement of internal anatomy. The degree of intensity of internal changes is different in the four species. In the two blaniulids, the consequences that gonopods have in the general trunk architecture are bigger than in the others, in particular because of the voluminous endoskeletal structures. In N. varicorne and in O. gracilis the anatomy of the trunk is less affected. In O. gracilis it was also possible to perform some observations during the last moulting period: it is during this step that squamiform appendages become gonopods undergoing larger modifications. I also present an hypothesis on the basic mechanisms that characterize gonopod formation in millipedes, according to which the changes in the seventh ring depend from the presence of a segmental marker produced during embryonic development, that is activated only much later, at the beginnig of non-systemic metamorphosis.
Di norma gli artropodi, nella loro vita postembrionale, affrontano periodicamente cicli di muta per potersi accrescere, essendo dotati di un esoscheletro rigido che racchiude il corpo dell’animale. Quando la muta coinvolge improvvisi e vistosi cambiamenti nella struttura dell’animale si parla di metamorfosi, un fenomeno caratterizzato da numerosi eventi di apoptosi e proliferazione cellulare. Proprio per questa ragione, lo studio dei processi coinvolti nella metamorfosi è diventato un tema ricorrente ed importante per la biologia evoluzionistica dello sviluppo (evo-devo) degli artropodi. Il principale limite di queste ricerche, tuttavia, riguarda il fatto che sono limitate ad un ristretto numero di specie e trarre conclusioni generali basandosi unicamente sui dati raccolti da pochi sistemi modello può rivelarsi rischioso. Gli studi più recenti sulla metamorfosi sono stati svolti su specie caratterizzate per la maggior parte da una metamorfosi di tipo sistemico. Si tratta principalmente di insetti olometaboli, nei quali il passaggio allo stadio adulto è costellato da cambiamenti che coinvolgono tutto il corpo dell’animale, eventualmente con gradi di intensità diversi. Tuttavia nella maggior parte degli altri artropodi i cambiamenti postembrionali sono notevolmente meno estesi, come avviene, ad esempio, negli insetti emimetaboli. Una situazione sicuramente meno frequente è quella in cui ad essere investite da un brusco cambiamento nello sviluppo siano uno o pochi segmenti non terminali, inizialmente uguali ai moduli che li precedono e che li seguono lungo l’asse principale del corpo. Questo tipo di trasformazione postembrionale, confinata in un distretto del corpo ben circoscritto, è definita, in questa tesi, metamorfosi non sistemica e si può trovare nello sviluppo postembrionale dei maschi dei millepiedi elmintomorfi. Nei maschi dei millepiedi elmintomorfi, durante il processo di crescita postembrionale, avviene un brusco cambiamento che coinvolge solo uno o due paia di appendici non terminali, inizialmente non diverse da tutte quelle che le precedono e le seguono, nel mezzo di una lunga serie omonoma. Negli adulti, infatti, queste appendici, localizzate nel settimo anello del tronco, sono modificate in gonopodi, i quali sono usati come organi di presa o veicoli per il trasferimento dello sperma durante la copula. Osservando nel dettaglio lo sviluppo del settimo anello possiamo notare che: durante i primi stadi di sviluppo è identico agli altri e porta due paia di zampe convenzionali; in un qualche stadio successivo le zampe vengono sostituite da strutture estremamente ridotte (appendici squamiformi) che, successivamente, diverranno gonopodi. Lo scopo di questa tesi è quello di indagare la metamorfosi dell’ottavo e del nono paio di zampe, corrispondenti al settimo anello del tronco (unità morfologica generalmente equivalente a due segmenti convenzionali) dei seguenti diplopodi: due blaniulidi Nopoiulus kochii (Gervais, 1847) e Blaniulus guttulatus (Bosc, 1792), uno julide nemasomatide Nemasoma varicorne C.L. Koch, 1847 ed un polidesmide Oxidus gracilis (C.L. Koch, 1847). In particolare, ho analizzato l’ultimo stadio in cui i maschi presentano l’ottavo (ed eventualmente il nono) paio di appendici locomotorie, gli stadi in cui queste sono sostituite da appendici squamiformi e il primo stadio che presenta i gonopodi. Gli studi effettuati hanno previsto principalmente indagini di morfologia esterna, basate sulla microscopia ottica e sulla microscopia elettronica a scansione, mentre l’anatomia interna è stata descritta principalmente attraverso l’utilizzo di protocolli istologici. Le strutture endoscheletriche associate ai gonopodi sono state studiate attraverso l’uso del microscopio confocale a scansione laser, sfruttando l’autofluorescenza della cuticola. Dai risultati ottenuti emerge che le modificazioni esterne dovute alla metamorfosi non sistemica nei diplopodi sono associate a un notevole riarrangiamento dell’anatomia interna, documentato per la prima volta con questa tesi. Il grado di intensità dei cambiamenti interni è diverso nelle quattro specie: i due blaniulidi risentono maggiormente dell’impatto che i gonopodi hanno nell’architettura generale del tronco, in particolare a causa delle voluminose strutture endoscheletriche. Al contrario in N. varicorne, ed in particolare in O. gracilis, l’anatomia del tronco viene modificata in modo meno significativo. Nel polidesmide è stato anche possibile effettuare alcune osservazioni durante l’ultimo periodo di muta, durante il quale avvengono le maggiori modificazioni trasformando le appendici squamiformi in gonopodi. Viene inoltre presentata un’ipotesi sui meccanismi di base che caratterizzano la formazione dei gonopodi nei millepiedi, secondo la quale i cambiamenti del settimo anello dipendono dalla presenza di un marcatore segmentale prodotto durante lo sviluppo embrionale, che viene attivato solo molto più tardi, quando iniziano i cambiamenti dovuti alla metamorfosi non sistemica.

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FARINA, Gianluca. "Systemic risk measures and contagion models." Doctoral thesis, Università degli studi di Bergamo, 2014. http://hdl.handle.net/10446/30380.

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The main theme of the thesis is systemic risk measurement. This extremely young field of research has gained a lot of attention in recent times from academics and practioners alike because of global financial crises. The main contributions of the thesis can be grouped in four broad items. Firstly, we propose a novel categorization of the risk measures advanced in recent years based on the modeling assumptions they rely upon. We identified four categories: measures based on portfolio theory, econometric indicators, network analysis and measures based on multivariate default distribution. The second set of contributions regards the CIMDO framework, a methodology heavily used in systemic risk studies. We proved a new theoretical independence result that significantly extended previous ones. We also performed a comprehensive stability study where every input of the methodology was considered and whose conclusions should serve as guidance for future CIMDO users. The third contribution is a new contagion model that is both tractable and flexible enough to be used with heterogeneous portfolios. We provided several theoretical results with respect to both marginal and joint default distribution. We also detailed a recursive algorithm to calculate the portfolio loss distribution in an efficient way. An application to the problem of pricing and hedging CDO products is hence shown. Lastly, we introduced a new systemic risk measure in the context of contagion models called contagion loss ratio (CLR). It is based on attributing losses to either idiosyncratic or infection-driven events and represents the percentage of the total portfolio losses due to contagion. We showed how to calculate it in a variety of models and presented an application to the problem of banking stability.

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Yau, C. "A systemic and dynamic model for project planning and control." Thesis, Lancaster University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370308.

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Kavvouras, Georgios. "A holistic systemic model for decision support in sustainable construction." Thesis, University of Nottingham, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.523692.

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Banda, Castro Ana Lilia, and Zamorano Miguel Arturo Morales. "Psychological Empowerment: A systemic model with individual and community components." Pontificia Universidad Católica del Perú, 2014. http://repositorio.pucp.edu.pe/index/handle/123456789/101236.

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This study aimed to confirm that social participation may influence empowerment as one ofthe four components explained by the theory. The hypothesis proposes systemic interaction of two components of empowerment: intrapersonal and behavioral. 113 urban residents participated in the study. The hypotheses were tested through the use of structural modeling. An intrapersonal component of empowerment, composed of positive empowerment, negative empowerment and socio-political control was identified. This component was affected by the behavioral component that involves social organization, community action and decision making. The hypothesis is accepted and the study provides empirical support to the theory.
Se busca confirmar que la participación social puede influir en el empoderamiento comouno de sus cuatro componentes. La hipótesis propone la interacción sistémica de dos componentes del empoderamiento: intrapersonal y comportamental. Los participantes fueron 113 habitantes urbanos a quienes se les aplicó una encuesta. Los resultados evidencian que el modelamiento estructural identificó un componente intrapersonal del empoderamiento integrado por empoderamiento positivo, empoderamiento negativo y control sociopolítico. Este componente se muestra afectado por el componente de comportamiento conformado por la organización social, las acciones comunitarias y la toma de decisiones. Se acepta la hipótesis y se proporciona sustento empírico a la teoría.

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Ater, Steven L. "The interactive systemic approach an expansion of the biopsychosocial model /." Online full text .pdf document, available to Fuller patrons only, 2002. http://www.tren.com.

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Pham, Thi Hoa, and n/a. "Interrogative mood in English and Vietnamese : a systemic contrastive analysis." University of Canberra. Information Sciences, 1985. http://erl.canberra.edu.au./public/adt-AUC20060725.105609.

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The purpose of this study is to present a contrastive analysis of the different types of interrogative sentences in English and Vietnamese including their structures and meanings. It is also hoped that the result of this study will be of some use to English teachers in Vietnam in their classroom teaching and in their preparation of teaching materials. It may also be useful to Vietnamese students who are learning English, especially when learning the English interrogative mood. Hitherto, there have been different models of description of language, but the systemic model is considered to be one of the most comprehensive, since it is able to bring out the functional uses of language and can be used to describe any language. For this reason, the systemic model is adopted in this paper to describe the two systems of the English and Vietnamese interrogative mood. The varieties of the two languages, English and Vietnamese, from which examples are taken for analysis in this paper, are Southern British Standard and Standard Vietnamese ranging from colloquial to literary. Throughout each chapter, the examples are numbered in consecutive order. Examples in Vietnamese are presented with a slash mark ( / ) placed between lexical items to facilitate the matching of Vietnamese with the literal English translation which follows. The literal translation is followed by a freer English translation enclosed in quotation marks. The study consists of five chapters. In the first chapter, the author begins by summarizing different views on the nature of language and their applications in language teaching and learning, and then presents a short introduction to systemic linguistics and a brief sketch of systemic grammar. The second chapter is about the English interrogative mood. This description of the English interrogative mood is largely based on the ideas on Mood presented by D. J. Young, lecturer in English in the University of Wales Institute of Science and Technology in Britain. In the third chapter, an attempt is made to provide a detailed description of the different types of interrogative sentences in Vietnamese. Chapter four moves to a contrastive analysis which consists of a textual and then a systemic comparison and contrast of the two interrogative mood systems in English and Vietnamese. A recapitulation of what has been done in the previous chapters and some suggestions for the preparation of teaching material and the teaching of English interrogative sentences to Vietnamese students are presented in chapter five, which is the last chapter of the study.

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Reichert, Richard P. "A systemic model of leadership development for the church in Cuba." Online full text .pdf document, available to Fuller patrons only, 2003. http://www.tren.com.

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Glasscoe, Claire Anita. "Parental dysphoria following the diagnosis of cystic fibrosis : testing a systemic model." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399223.

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Stocks, M. R. "Experimental manipulation of autoimmunity in a mouse model of systemic lupus erythematosus." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47675.

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Salameh, Sacha. "A perfusable vascularized full thickness skin model for topical and systemic applications." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS466.

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De nombreux progrès ont déjà été réalisés pour développer des modèles de peau in vitro plus complexes et s’approchant de plus en plus du tissu in vivo. Cependant, la vascularisation reste l’un des défis à relever pour l’évolution des peaux reconstruites. Notre étude s'est concentrée sur le développement d'un équivalent de peau complète vascularisée et perfusée avec un réseau vasculaire plus complexe que les modèles déjà existants. Ainsi, nous avons combiné trois techniques : le moulage de la matrice, l’auto-assemblage des cellules endothéliales et la microfluidique. Ainsi, nous avons créé un équivalent de peau vascularisée constituée i) d’un épiderme différencié avec une organisation physiologique ii) de trois macrovaisseaux perfusables avec des bourgeonnements formés par angiogenèse, iii) d’un réseau microvasculaire créé par vasculogenèse et connecté aux bourgeons des macrovaisseaux. Les évaluations de l’absorption percutanée et de la diffusion systémique de composés ont démontré qu’avoir un système vasculaire perfusable et plus proche du plexus vasculaire in vivo aboutit à un modèle plus prédictif pour les évaluations d’applications topiques ou systémiques de composés. Cela inclut une large gamme d'utilisations du modèle, soit pour la connaissance, soit pour des études d'efficacité et de sécurité
There is still an unmet need of vascularized in vitro skin models mimicking human skin that could be faithfully used as an alternative to in vivo or ex vivo testing for efficacy and safety studies. Indeed, vascularization and perfusion are still two of the main remaining challenges in skin models. Our study was therefore aimed at developing a perfusable vascularized full thickness skin equivalent with a more complex blood vasculature compared to existing models. We here combined molding, auto-assembly and microfluidics techniques in order to produce a skin equivalent that recapitulates a properly differentiated epidermis and also complex vascular networks connected together in the dermal equivalent. Three perfusable vascular channels that sprouted via angiogenesis were created and eventually connected to a microvascular network, generated by endothelial cells auto-assembly, i.e. vasculogenesis. We then evaluated skin permeability of various compounds with different chemical properties and systemic delivery of a pollutant (Benzo[a]pyrene) and demonstrated that perfusion of in vivo-like vascular plexus resulted in more predictive and reliable model for topical and systemic assessments. This model could therefore further drug discovery and improve clinical translation in dermatology

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Mokbel, Rita. "Systemic risk in financial economic institutions." Thesis, Besançon, 2016. http://www.theses.fr/2016BESA2080.

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Les crises financières et les problèmes se formaient mais les indicateurs ne sont pas précis pour permettre une intervention réglementaire. La thèse propose un modèle dynamique pour le système bancaire avec une banque centrale afin de calculer un indicateur de faillite en fonction de la probabilité qu'une banque soit en faillite et les pertes rencontrées dans le réseau financier, une méthodologie qui peut améliorer la mesure, le suivi et la gestion du risque systémique.La thèse propose également des mécanismes de compensation : 1- avec un modèle considérant l'ancienneté du passif et avec un type d'actif liquide dont la vente excessive conduit à un impact sur le marché, 2 - avec un modèle considérant les participations croisées entres les banques dont les engagements interbancaires sont de différentes séniorités et avec un type d'actif liquide dont la vente excessive conduit à un impact sur le marché
Financial crisis pose important theoretical problems on creating reliable indicator of stability of financial systems on which basis the regulators could intervene. The thesis proposes a dynamic model of banking system were the central bank can calculate an indicator of potential defaults taking into consideration the probability for a bank to default and the losses encountered in the financial network, a methodology that can improve the measurement, monitoring, and the management of the systemic risk. The thesis also suggests a clearing mechanisms : 1- in a model with seniority of liabilities and one type of liquid asset whose fire sale has a market impact, 2 - in a model with crossholdings among the banks whose interbank liabilities may be senior and junior and with one liquid asset whose firing sale has a market impact

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McAndrew, Paula. "Investigating casual conversation: a systemic functional linguistic and social network model of analysing social reality." Australia : Macquarie University, 2002. http://hdl.handle.net/1959.14/44619.

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"November 2001".
Thesis (PhD)--Macquarie University, Division of Linguistics and Psychology, Dept. of Linguistics, 2002.
Bibliography: p. 285-291.
Introduction -- Language from a systemic functional perspective -- Social networks: a review of literature relevant to the Scotland Island study -- Methodology -- Analysing relational ties: a social network perspective -- A systemic functional approach to analysing social reality -- Discussion and conclusion.
This research is concerned with the study of language and the social order. Working within the systemic functional theory of language, and utilising the concept of a social network to model the social order, the primary aim is to put on display the relationship between the linguistic system and social order, between language and culture. Systemic functional grammar (Halliday, 1995; Halliday and Hasasn, 1985/9; Halliday and Matthiesen, 1997; Eggins and Slade 1997), with its emphasis on language as a social semiotic, is used to analyse the language used by a group of four women engaged in casual conversation in a small Australian island community. Here the analysis reveals how the women negotiate their social reality when speaking to each other. It shows how their social relations are shaped within a text (Hasan, 1996), and explores the notion that, despite the seemingly trivial, unconscious nature of casual interactions, power and solidarity are continually being negotiated by the participants (Halliday, 1994; Eggins and Slade, 1997). More specifically, this research examines the notion that through lexico-grammatical and semantic selections participants are able to negotiate dominant positions in interaction. Social Network analysis has been used to examine the relationship between the individual and the group. It offers a quantifiable analytical tool for describing the character of an individual's everyday social relationships (Milroy, 1987). A social network analysis is used in the present study to map the social relationships in the tight-knit network, or speech fellowship, of these women (creating a map of the context of situation in SFL terminology). Change in the social relationships and language choices is modeled by revisiting the participants 15 months later in a contextually similar environment and re-analysing the network and linguistic options. Systemic functional linguistics is then used to highlight the interdependency of language and social order. Through systematic accounts of language and the context in which it is embedded this reciprocal nature is displayed and language and social order can be seen, not as two distinct entities, but rather as one phenomena seen from two different perspectives (Halliday, 1978; Mathiessen, 1993).
Mode of access: World Wide Web.
v, 291 p. ill

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Fletcher, K. "A systemic model for a building performance and condition evaluation for primary schools." Thesis, University of Salford, 2018. http://usir.salford.ac.uk/46112/.

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Mäki-Petäjä, Kaisa Maria. "Inflammation, arterial stiffness and endothelial dysfunction : rheumatoid arthritis, a model of systemic inflammation." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612095.

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Khoshbin, Espeed. "Extracorporeal membrane oxygenation for severe systemic inflammatory response : development of a rabbit model." Thesis, University of Leicester, 2008. http://hdl.handle.net/2381/29902.

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Hypothesis: ECMO is an acceptable supportive therapy for patients with severe SIRS despite triggering haematic response.;Objectives: To develop a reliable and reproducible animal model of SIRS to investigate strategies for reducing the haematic response.;Materials and Methods: Literature review: (I) The Systemic Thrombo-inflammatory Pathway (STIP). (II) The haematic response. Clinical studies: (I) Institutional review of ECMO for severe SIRS. (II) Comparative review of oxygenators performance. In-vivo studies: Animal experiments, (I) Development of a rabbit model of graded SIRS. (II) Dose response relationship between administered intravenous endotoxin and fatal Multi-organ Dysfunction Syndrome (MODS). (III) Inter-individual variation amongst rabbits receiving a lethal dose of endotoxin. In-vitro studies: Evaluation of the cellular and biochemical components of STIP in rabbits. (I) Development of rabbit ELISA. (II) Determination of the normal range, dose response and inter-individual variation. (III) Immunohistochemical evaluation of endotoxin induced lung injury. (IV) Dose related oxidative stress and DNA damage and (V) apoptosis in rabbit lung.;Results: There is a reciprocal relationship between graded SIRS and the outcome of ECMO. There is a linear relationship between the dose of endotoxin and the development of graded SIRS in rabbits. Significant DNA homology and cross-reactivity exists between humans and rabbits making this a useful model for immune experimentation.;Conclusions: ECMO is superior to conventional ICU management in selected groups of patients. New oxygenator technology has significantly reduced the haematic response to ECMO, however it has failed to influence survival. Cellular components such as neutrophils play a central role in SIRS activation, however thrombin appears to be the common biochemical component for feedback escalation and progression of severe SIRS to MODS.

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O’Rourke, Simon. "An intelligence model for terrorist incident prevention for Australian police: A systemic investigation." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 2010. https://ro.ecu.edu.au/theses/379.

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This study examines the role that intelligence will continue to play in the ongoing efforts to mitigate the effects of contemporary terrorism. The role of domestic policing agencies is expanding to meet the challenge of transnational organised crime and also the threat to community safety and cohesion that terrorism entails. The September 11 attacks on the twin towers in New York city showcased the darkest elements of humanity whilst the courage personified by the police, firefighters and paramedics who entered the buildings to save others illuminated al that is best, in an event that was broadcast globally into the homes of millions around the world through television via television and the Internet. Whilst shielded to some degree by distance, Australians were hit even harder by the bombings in Bali on the 12th October 2002, during which 88 Australians died and many more were injured. For many Bali was seen as a place to relax, an idyllic paradise whose peace was forever shattered with the detonation of the terrorist bombs. The traditional intelligence community needed to draw upon the existing capabilities of policing agencies to build partnerships with key community groups in an endeavour to prevent such an atrocity from happening in Australia. No longer was an advanced technical intelligence capability and the access to material obtained enough to guarantee security, material needed to be shared with the police in order to prevent an incident, thus creating the potential for national security classified material to be disclosed in subsequent court proceedings. Culture and practices underwent a paradigm shift and the police now have a role in the national intelligence community in Australia, something that continues to present significant challenges requiring new legislation to keep pace with technology and the dynamically evolving threat. Drawing upon Checkland’s (1999, p.178) Soft Systems Methodology (SSM) this research synthesised text based analytical software called Leximancer, to create a conceptual model with minimal inherent biases. It is believed that this is the first time that such an approach to SSM has been undertaken allowing the research to contribute towards the methodological field as well as the chosen study. Access to interview practitioners was granted and the results provided unique insight into the contemporary and future challenges of police counterterrorist intelligence.

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Washington, F. "Factors associated with resilience after paediatric injury : working towards a systemic model of resilience." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3026496/.

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Hillendahl, Gregory Manning. "A systemic model of the middle voice of the Greek of the New Testament." Theological Research Exchange Network (TREN), 1991. http://www.tren.com.

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Eversden, Stella. "Integrating systemic and school-based priorities into a curriculum model for secondary religious studies." Thesis, Eversden, Stella (1993) Integrating systemic and school-based priorities into a curriculum model for secondary religious studies. PhD thesis, Murdoch University, 1993. https://researchrepository.murdoch.edu.au/id/eprint/50548/.

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This study enquires about designing a curriculum model in religious education at secondary level (for ages approximately 14 upwards) which would seek to redress the problems inherent in existing models, and would aim to satisfy educational, systemic and school-based criteria in the religious education curricula of both government and non-government schools. A review of models in Britain, America, and Australia, and policies of school-based curriculum development and multiculturalism was conducted. The objective of "dialogical consciousness" was introduced, using cross-paradigm dialogue, which was considered both desirable and possible. Recommended were the adoption of a transcultural perspective by teachers, and qualified support of the home tradition rather than the less preferred alternatives of relativism or nihilism. The indoctrination issue was reviewed with a view to its avoidance in the proposed model. Also, ethical guidelines for evaluation to escape the indoctrination charge were proposed. A set of criteria was drawn up and the "cross-paradigm dialogical conscientization" (CPDC) model was identified, using a set of cross-disciplinary open-ended questions drawn from Education's parent disciplines. To test its adaptability, the CPDC model was demonstrated to be useful in both Catholic and government school systems. It was then used in principle as a basis of an ideology self-critique. It was recommended that the CPDC model be used with existing syllabuses and teaching methods to ensure that religious education might become both ethically and educationally sound, so that Religious Studies (perhaps retermed Religiology) may be included in the core curriculum, and in matriculation scores, to restore the status of religion in the curriculum and subsequently in society.

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Torvell, Megan Isabel Lily. "Acute and chronic effects of systemic inflammation on P301S tau mouse model of neurodegeneration." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/29605.

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Systemic inflammation is thought to be an important driver in chronic neurodegeneration. During systemic infection, the inflammatory status of the periphery is communicated to the brain and conserved sickness behaviours initiated. However, in the context of dementia the same inflammatory stimulus might trigger delirium. Delirium is a severe, transient neuropsychiatric condition characterised by altered levels of arousal, inattention, cognitive deficits and psychoses. Delirium and systemic inflammation exacerbate the trajectory of pre-existing dementia, and are associated with increased risk of future dementia. Accumulating experimental studies suggest microglia are “primed” by chronic neurodegeneration, such that a subsequent inflammatory insult – central or systemic – induces an increased inflammatory response which manifests as exaggerated sickness behaviours. To date there have been no studies of microglial priming in the context of pure tau pathology, without amyloid pathology, and none investigating acute sickness behaviour in such a model. The overarching aim of this thesis is to address this gap in the literature and further our understanding of the interactions between systemic inflammation, neuroinflammation and neurodegeneration in the context of tauopathy. The P301S mouse over-expresses human mutant tau protein under the Thy1.2 promoter. It develops hyperphosphorylated and insoluble tau accumulations and progressive neuronal loss. Consequently, P301S mice develop progressive hind limb paralysis. This study identified the horizontal bar task, a test of motor control and coordination, conducted at weekly intervals from 8-22 weeks of age, as a non-invasive measure of disease progression. In addition, a detailed temporal profile of pathological hallmarks at 8, 9, 10, 11, 12, 16 and 20 weeks of age was determined. Key results presented here demonstrate progressive, superficial neuronal loss in the cortex of P301S mice, with associated astrogliosis and surprisingly this occurs in the absence of apparent cortical microgliosis. In stark contrast, there is progressive microgliosis in the spinal cord of P301S mice. On this background, lipopolysaccharide (LPS), a chemical moiety found on the outer surface of gram-negative bacteria, was used to mimic a systemic bacterial infection. P301S mice and C57BL/6 control mice were injected, at 10 or 16 weeks of age, intraperitoneally with 500 μg/kg LPS or saline and were monitored in the following hours and weeks. Acutely, P301S mice showed signs of an exaggerated, longer lasting sickness response. Importantly, exaggerated acute symptoms extended beyond those typically associated with sickness behaviour; LPS induced an exaggerated acute impairment of horizontal bar performance in P301S mice and not C57BL/6 mice – a function which is known to be impaired in P301S mice later in disease. Impairments were age-dependent in terms of timing of injection. These data suggest an interaction between acute infection and existing CNS vulnerability leading to acute neurological dysfunction that is not a feature observed in sickness in a normal animal. LPS-injected P301S mice also showed, again age-dependent, increased rate of decline in motor performance compared with controls. There was no evidence of microglial priming in P301S mice. LPS caused an acute increase in AT8-positive phospho-tau however this did not persist until end stage. At 22 weeks of age there was significant disease-associated cortical neuronal loss in the vehicle-injected P301S mice, and additional superficial cortical neuronal loss in LPS-injected P301S mice and control mice. There was significant IBA1-positive microgliosis in the spinal cord of P301S mice at end stage which was further increased in LPS-injected P301S mice. Taken together these data indicate a clear and clinically relevant interaction between systemic inflammation and tau-associated neuropathology with acute and long-term functional consequences. In the absence of evidence of microglial priming, future work will explore potential mechanisms.

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ALONGI, ALESSANDRA. "Development of a prognostic model for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/1010555.

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Introduction: Macrophage activation syndrome (MAS) is a potentially life-threatening complication of systemic juvenile idiopathic arthritis (SJIA) characterized by heterogeneous organ involvement and severity. Early identification of patients at high risk of complicated clinical course may improve outcome by helping initiate prompt, appropriate immunosuppressive and supportive treatments. Yet, despite recent progress in clarifying the underlying immunological mechanisms, factors driving organ damage and severe outcome are not entirely understood, nor has the prognostic value of routinely gathered clinical and laboratory factors been fully explored. Objectives: To develop a prognostic model for SJIA-MAS based on routinely available parameters at disease onset, accounting for patient heterogeneity, possible latent factors, non-linear relationships and confounders. Methods: We examined a retrospective multinational cohort of 362 patients diagnosed with SJIA-MAS. The relationships between demographic, laboratory features at MAS onset (such as hemoglobin, whole blood cells, platelets, ERS, CRP, AST, ALT, bilirubin, fibrinogen, d-dimer, ferritin and creatinine), therapeutic interventions and outcomes were analyzed. Outcomes of interest included a “severe course” (defined as ICU admission or death), occurring of organs failure and CSN dysfunction. To identify potential phenotypes related to clinical features and outcome, we explored laboratory parameter patterns at MAS onset through Latent class modeling, which detects multiple unobserved clusters in heterogeneous populations. A structural causal approach was then used for investigating causal pathways leading to severe outcomes. Directed acyclic graphs (DAGs) were employed to depict possible causal relationships between the candidate biomarkers, potential confounding variables, and the outcomes, and inform the choice of adjustment sets in multivariate regression models. We assessed the possible relationships between variables and outcomes by penalized likelihood logistic regression and identified optimal cut off points for prognostic factors using Multiple Adaptive Regression Splines (MARS) and Classification and Regression Trees (CART). To account for possible treatment confounders, the effect of cyclosporine and etoposide use on outcomes was estimated using augmented inverse probability weighting (IPW) with double robust methods. Finally, results from previous analyses were incorporated in a probabilistic framework through a Bayesian network (BN) model, which provides risk estimates for specific clinical scenarios and quantifies the amount of information contributed from the identified prognostic variables. Results: The latent class model revealed six clusters based on biomarkers at MAS onset, characterized by the following features: mild alterations of white blood cells, platelets, fibrinogen, d-dimer and ferritin values, considered the baseline type (cluster 1, n =115); hyperferritinemia with low organs involvement (cluster 2, n = 101); elevation of inflammatory markers (cluster 3, n =51); hepatobiliary involvement (cluster 4, n = 41); severe pancytopenia, liver and kidney failure with higher elevation of LDH, d-dimer, ferritin (cluster 5, n = 30); biliary and renal dysfunction (cluster 6, n = 24). Cluster 2 and 3 presented lower age and SJIA duration at MAS onset compared to other subgroups. Cluster membership was predictive of severe course (p<0.001), CSN involvement (p<0.001), Hemorrhagic complications (p <0.001) and Heart failure (p<0.001), with patients in cluster 5 showing the highest risk of severe course and heart failure, and increased occurrence of CNS and Hemorrhagic manifestations in both cluster 5 and 6. In multivariate regression models, parameters at onset associated with risk of severe course were creatinine (OR 1,6 [95% CI 1.13–2.3]; p = 0.008) and albumin levels (OR 0,65 [95% CI 0.44–0.98]; p = 0.044) Higher risk of CNS involvement was found for patients younger at MAS onset (OR 0,62 [95% CI 0.42–0.92]; p = 0.018). Na (OR 0.0,89 [95% CI 0.82–0.96]; p = 0.006) and creatinine values (OR 1.69 [95% CI 1.14–2.5]; p = 0.009) were identified as independent predictors of mortality. There was no evidence for an effect of etoposide (OR 1.03 [95% CI 0.91–1.12]) and cyclosporine (OR 1.04 [95% CI 0.92–1.19]) on severe course. BNs defined distinct groups with different probability of severe outcomes, achieving a c-index of 0.76 for mortality, 0.81 for severe course and 0.81 for CNS involvement. Adding the obtained latent clusters to the BN model increased the prediction accuracy for severe course up to a c-index of 0.83. Based on information theory metrics (mutual information) from the BN model, decision algorithms for each outcome and a web-based decision support tool for external users were implemented. Conclusions: We developed a probabilistic prognostic model of SJIA-MAS based on routinely available data. This stratification tool may facilitate informed decision-making about the clinical management of these patients. The probabilistic and information-theoretic approach offers a framework for further validation, expansion and integration of the model with emerging molecular biomarkers.

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Schrader, Lauran N. "Does ANA-positive SLE human serum promote development of Libman-Sacks endocarditis in the NP-SLE Lewis rat model?" Muncie, IN : Ball State University, 2009. http://cardinalscholar.bsu.edu/675.

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Byler, Stefanie Lynn. "Systemic bacterial endotoxin plus MPTP as a model of Parkinson's disease in C57BL/J6 mice." Fort Worth, Tex. : Texas Christian University, 2007. http://etd.tcu.edu/etdfiles/available/etd-08302007-162100/unrestricted/byler.pdf.

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Lewis, Myles J. D. r. "The Effects of Autoimmunity on Atherosclerosis in a Novel Mouse Model of Systemic Lupus Erythematosus." Thesis, Imperial College London, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516784.

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Imani, Markid Maghsoud. "Balancism : a new legal and economic model for just distribution wealth and systemic financial stability." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/balancism-a-new-legal-and-economic-model-for-just-distribution-wealth-and-systemic-financial-stability(a07c75dd-a15d-42b4-9e9c-6626ded2376c).html.

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The modern economic and financial systems have not so far secured a just and fair system of distribution of wealth and have frequently been exposed as containing systemic instabilities. In response, some think that there is no choice but to follow the laws and claims of Capitalism. Others have argued that it is time to revive and implement Socialism. Still others have voiced their support that the Islamic model would be the best solution. This thesis, which is an interdisciplinary and a comparative work, aims to suggest a new solution. The alternative system introduced in this research project is a comprehensive paradigm and three-tier model. The first tier covers the ultimate objective (social justice), the new foundational theory (rights-and-duties balance/benefits-and-burdens balance “Balancism”) as well as fundamental principles and policies of the model (e.g., distribution of the proceeds of natural wealth resources according to the reasonable and legitimate needs of human beings, distribution of subordinate wealth on the basis of contribution, application of an unlimited proportionate liability standard instead of the current limited liability norm, implementation of sharing-in-income arrangement instead of modern labour employment structure, securing basic essential needs of humanity, preventing concentration of wealth, and minimizing risk rather than taking advantage of it). In the second tier, major tools, products, and facilities are suggested for distribution of the proceeds of primary wealth resources and also for for-profit, profit-free, philanthropic, microfinance, intermediary, and risk hedging activities. The third tier deals with the superstructure and political regime of the alternative system. It consists of a “House of Wealth” and a “House of Market Control”. The Houses have to follow and apply the rules of balance, the first in the system of distribution of primary wealth and the second in the circulation of subordinate wealth, in order to ensure that justice prevails.

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Young, Anne Michelle. "A Systemic Model for Family Functioning: Mutual Influences of Spousal Attachment, Marital Adjustment, and Coparenting." Thesis, University of North Texas, 2017. https://digital.library.unt.edu/ark:/67531/metadc1011822/.

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The current study examined direct and indirect influences of romantic attachment processes, marital adjustment, and the coparenting relationship on family functioning. Data was collected from a community sample of 86 heterosexual couples with a child aged eight to eleven living in the home. Both spouses completed a demographic questionnaire, the Experiences in Close Relationships Scale, the Dyadic Adjustment Scale, the Coparenting Scale, and the Self-Report Family Inventory as part of a larger study on family processes in middle childhood. Data analysis included multilevel modeling, utilizing the actor-partner interdependence model. Results indicated that marital adjustment mediated the association between attachment processes and family functioning, suggesting that a healthy marital relationship is an important variable that helps explain links between attachment security and the family functioning. Findings also highlighted the benefit of conceptualizing adult romantic attachment, marital, and coparental subsystems within a systemic framework.

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Clement, Priscillia. "High school dropout : systemic implications and the GED as a model of redress for dropouts /." View abstract, 2001. http://library.ccsu.edu/ccsu%5Ftheses/showit.php3?id=1639.

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Thesis (M.S.)--Central Connecticut State University, 2001.
Thesis advisor: Jane Fried. " ... in partial fulfillment of the requirements for the degree of Master of Science in School Counseling." Includes bibliographical references (leaves 75-80). Also available via the World Wide Web.

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Huang, Yu-Hsing. "Having a New Pair of Glassess : Applying Systemic Accident Models on Road Safety." Doctoral thesis, Linköpings universitet, CSELAB - Cognitive Systems Engineering Laboratory, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8189.

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The main purpose of the thesis is to discuss the accident models which underlie accident prevention in general and road safety in particular, and the consequences of relying on a particular model have for actual preventive work. The discussion centres on two main topics. The first topic is whether the underlying accident model, or paradigm, of traditional road safety should be exchanged for a more complex accident model, and if so, which model(s) are appropriate. From a discussion of current developments in modern road traffic, it is concluded that the traditional accident model of road safety needs replacing. An analysis of three general accident model types shows that the work of traditional road safety is based on a sequential accident model. Since research in industrial safety has shown that such model are unsuitable for complex systems, it needs to be replaced by a systemic model, which better handles the complex interactions and dependencies of modern road traffic. The second topic of the thesis is whether the focus of road safety should shift from accident investigation to accident prediction. Since the goal of accident prevention is to prevent accidents in the future, its focus should theoretically be on how accidents will happen rather than on how they did happen. Despite this, road safety traditionally puts much more emphasis on accident investigation than prediction, compared to areas such as nuclear power plant safety and chemical industry safety. It is shown that this bias towards the past is driven by the underlying sequential accident model. It is also shown that switching to a systemic accident model would create a more balanced perspective including both investigations of the past and predictions of the future, which is seen as necessary to deal with the road safety problems of the future. In the last chapter, more detailed effects of adopting a systemic perspective is discussed for four important areas of road safety, i.e. road system modelling, driver modelling, accident/incident investigations and road safety strategies. These descriptions contain condensed versions of work which has been done in the FICA and the AIDE projects, and which can be found in the attached papers.

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Kristensen, Erik Kaergaard. "Systemic barriers to a future transformation of the building industry from a buyer controlled to a seller driven industry : an analysis of key systemic variables in the building industry, such as 'procurement model', 'buyer perception', 'production mode' and 'leadership and management', principally in a Danish development context and seen from the perspective of the architect." Thesis, Robert Gordon University, 2011. http://hdl.handle.net/10059/699.

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It has always been a ‘mystery’, why the Danish building industry stagnated after the industrial breakthrough, and never was able to adapt the industrial production, business culture, buyer perception, and leadership and management, used in nearly all other Danish industries. This study offers a new approach to understanding the problem - by analysing systemic barriers to the industry’s transformation to a seller driven industry, in the context of a widespread neglect of the need for industrialisation (a problem addressed by relatively little literature) with the building remaining a manual, craft based industry, based on the old building process and its associated business model. Industrialisation has instead taken place in the building materials industry, which in a Danish context is a separate and highly industrialised industry. To analyse the barriers for transformation in the building industry a multidimensional approach is applied: First the building industry and modern industries are compared. Two archetype models are created using the above mentioned variables; one model for the building industry and its “Buyer Controlled Procurement Model” and one for modern industries and their “Seller Driven Marketing Model” with interrelated production and sale, enabling them to sell to unknown customers. Next the statistical productivity trends and other secondary data are examined to analyse, if the Seller Driven Marketing Model is performing better. Finally a Delphi Panel Consultation is conducted to discuss future development scenarios. Michel Foucault’s principles of historical analysis and his ‘episteme’ concept are used to analyse the outcome of the Delphi Panel Consultation.

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Wu, Haijing, and 吴海竞. "The generation of tolerogenic dendritic cells in SLE and study of their mechanisms of action and therapeutic application in a lupus mouse model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/206689.

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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is characterized by auto-reactive T and B lymphocytes and abundant auto-antibodies against nuclear components that form immune-complexes and lead to inflammation, organ dysfunction and failure. The current treatment for SLE includes corticosteroid and immunosuppressant agents which are associated with side effects. Immunotherapy such as tolerogenic dendritic cells (DCs) and regulatory T cells have potential therapeutic implications in autoimmune diseases. DCs are professional antigen presenting cells with important role in promoting immune response and maintaining peripheral tolerance. Alternatively activated DC (aaDC) derived from treating monocyte-derived DCs with vitamin D3 and dexamethasone has demonstrated tolerogenicity and suppressed activation and proliferation of allogeneic T cells in in vitro human studies. As circulating DCs in SLE patients were reported to be hyperactive with increased expression of co-stimulatory molecules and hyper-responsiveness to immunostimulatory stimuli. Therefore, this study aims to examine if aaDCs derived from SLE patients possess tolerogenic properties, to delineate the underlying mechanisms and to examine for therapeutic effect by adoptive transfer of tolerogenic DCs in lupus mouse model. We found that lupus aaDCs derived in vitro displayed semi-mature phenotype with lower expression of co-stimulatory molecules compared with mature DCs. The tolerogenic phenotype remained stable despite challenge by CD40L, CpG-DNA and SLE serum. Lupus aaDCs showed comparable tolerogenic properties as aaDCs from healthy subjects with suppressive effect on allogeneic T cell activation and proliferation. In addition, lupus and normal aaDCs were shown to polarize normal and lupus naïve T cells into IL-10+ suppressive T cells that showed antigen-nonspecific suppressive effect on allogeneic third-party T cells. On the other hand, lupus and normal aaDCs skewed memory T cells to less inflammatory phenotype with reduced expression of IFN-ɤ and IL-17. Although aaDCs displayed a cytokine profile of IL-12loIL-10hi, addition of neutralizing anti-IL-10 and exogenous IL-12 did not reverse the suppressive effect of aaDCs on allogeneic T cells, suggesting their tolerogenicity was not related to cytokine imbalance between IL-12 and IL-10. Furthermore, aaDCs were found to express reduced level of RelB, a transcription factor regulating DC differentiation and maturation. As RelB can be a potential target to induce stable tolerogenic DCs, we constructed RelB shRNA to silence RelB in bone marrow derived DCs (BMDCs) from MRL/MPJ mice. The RelB shRNA transduced BMDCs showed lower level of RelB compared with scramble control shRNA, and displayed tolerogenic phenotype with decreased co-stimulatory molecules, but had no effect on the expression of chemokine receptors. When co-cultured with allogenic CD4+ T cells, RelB shRNA modified BMDCs showed suppressive function on T cell activation and proliferation and increased the production of IL-10 by T cells. However, in vivo study based on 5 mice per treatment group did not show significant effect of RelB shRNA modified BMDCs on disease progress of lupus mice compared to control mice. In conclusion, lupus aaDCs demonstrated tolerogenic properties with induction of IL-10 producing T cells with regulatory functions. RelB shRNA modified BMDCs showed tolerogenic properties in vitro but their in vivo effect on alleviation of murine lupus disease needs further study.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy

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Patchev, Stephanie Anna. "The architecture and limbic activity patterns of rapid eye movement sleep as symptomatic and prognostic factors in an animal model of post-traumatic stress disorder." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-177784.

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Christoforidis, John Byron, Karen Briley, Katherine Binzel, Prayna Bhatia, Lai Wei, Krishan Kumar, and Michael Vinzenz Knopp. "Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model." ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2017. http://hdl.handle.net/10150/627123.

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PURPOSE. To determine the intravitreal pharmacokinetic properties and to study the systemic biodistribution characteristics of 1-124-labeled bevacizumab, ranibizumab, and aflibercept with positron emission tomography-computed tomography (PET/CT) imaging in a nonhuman primate model. METHODS. Three groups with four owl monkeys per group underwent intravitreal injection with 1.25 mg/0.05 mL 1-124 bevacizumab, 0.5 mg/0.05 mL 1-124 ranibizumab, or 2.0 mg/0.05 mL 1-124 aflibercept in the right eye of each subject. All subjects were imaged using PET/CT on days 0, 1, 2, 4, 8, 14, 21, 28, and 35. Serum blood draws were performed at hours 1, 2, 4, 8, 12 and days 1, 2, 4, 8, 14, 21, 28, and 35. Radioactivity emission measurements were used to determine the intravitreal half-lives of each agent and to study the differences of radioactivity uptake in nonocular organs. RESULTS. The intravitreal half-lives were 3.60 days for 1-124 bevacizumab, 2.73 days for 1-124 ranibizumab, and 2.44 days for 1-124 aflibercept. Serum levels were highest and most prolonged for bevacizumab as compared to both ranibizumab and aflibercept. All agents were primarily excreted through the renal and mononuclear phagocyte systems. However, bevacizumab was also found in significantly higher levels in the liver, heart, and distal femur bones. CONCLUSIONS. Among the three anti-VEGF agents used in clinical practice, bevacizumab demonstrated the longest intravitreal retention time and aflibercept the shortest. Significantly higher and prolonged levels of bevacizumab were found in the serum as well as in the heart, liver, and distal bones. These differences may be considered by clinicians when formulating treatment algorithms for intravitreal therapies with these agents.

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Stikeleather, James A. "Toward a Systemic Model for Governance and Strategic Management: Evaluating Stakeholder Theory Versus Shareholder Theory Approaches." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7092.

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The research’s intent is improvement in governance and strategic management initially by comparing Shareholder Theory and Stakeholder Theory and making results useful for both Practitioner and Academic audiences. A conceptual model for how a society establishes and evolves the roles it legitimizes for a business to support reasoning about those roles and the process originating the expectations, responsibilities, obligations, contributions and freedom to act in the roles is proposed. Understanding this process would enable better governance and strategic management of a firm while avoiding unintended consequences when fulfilling the role and consequences for failing the role. The model becomes a basis for comparing Shareholder and Stakeholder Theories. Context for the model comes from practitioner narratives around changes occurring in business and their themes around the relationship of a business with its ecosystem. To incorporate both the societal and business relationship components, the model building process was based upon concepts and ideas from General Systems, Economics, Sociology, Neuroscience, Philosophy, Evolution, Complexity and Complex Adaptive Systems, Semiotics, as well as Business. This was an iterative abductive, inductive, deductive process with each iteration compared to relevant theory, integrated across the subject domains, then tested against other academic research on the issue, evidence of the model in practice, and a culturomics study across social and industry literature. These results are exploratory, descriptive, directional, and suggestive for future research opportunities. Problems with Stakeholder Theory are identified but potentially addressed with the conceptual model, in turn suggesting a systemic approach to governance and strategic management. It was determined that Shareholder Theory results in many unintended consequences detrimental to society and the firm. The conceptual model provides points of intervention in the process and suggests potential tooling for governance and strategic management. A side effect of the research was a perspective on the practitioner / academic divide as the research grappled with the “wicked problem” nature and transdisciplinary nature of process being described. By introducing systems and complexity paradigms in the model, potential ways to address the divide are suggested, such as 3 level analysis (micro, meso, macro).

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Little, Mark Alan Pasha Matthew. "The role of anti-neutrophil cytoplasm antibodies in an experimental model of systemic small vessel vasculitis." Thesis, Imperial College London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430867.

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Altaleb, Naderah. "Assessing the potential of rAAV9 systemic gene therapy for GM2 gangliosidoses using a Sandhoff mouse model." Nature Publishing Group, 2014. http://hdl.handle.net/1993/30287.

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The infantile GM2 gangliosidoses are severe neurodegenerative disorders, caused by a defect in the β-hexosaminidase system. They are characterized by lysosomal accumulation of the substrate, GM2 ganglioside, which results in severe neuronal damage and death in the early years of life. Sandhoff mice deficient in both major hexosaminidase isozymes, Hex A and Hex B, mimic the disease severity in the human condition including the motor deterioration, histopathological findings, and premature death. To investigate the utility of systemic adeno-associated virus 9 (AAV9)-based gene delivery in treating GM2 gangliosidoses, we evaluated the therapeutic outcome of a single intravenous injection of recombinant AAV9 encoding the complementing Hexb gene in a Sandhoff mouse model. We showed prolonged survival, preserved motor function, and reduced GM2 ganglioside accumulation as well as inflammation when systemic AAV9 therapy was administered to 1-2 days old mice. However, the formation of liver or lung tumours accompanied the positive therapeutic effect.

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Mandelli, Andrea Paola. "Unfolding the immune response against Staphylococcus aureus-mediated systemic sequelae of skin recurrences." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1203731.

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Staphylococcal protein A (SpA) is a surface-associated virulence factor of Staphylococcus aureus (S. aureus) which binds human immunoglobulins via both Fc and Fab fragment masking the pathogen to the host immune system. This activity interacts with the normal maturation of the host immune system during an infection and allows S. aureus to cause recurrent infections as, for example, skin recurrences. Skin recurrences are not only bothersome superficial infections that require continuous treatments, but may also evolve in more complicated and systemic complications. Immunization with SpA protects animals against S. aureus systemic infections unmasking the pathogen to the host immune system, which turns out to recognize bacterial antigens otherwise hidden by SpA activity. The aim of this project was to assess the protective effect of SpAmut against skin recurrences and systemic complications in a mouse model of Skin and Soft Tissues Infections (SSTIs) set up in C57BL/6 mice, which are naturally susceptible to re-infections with S. aureus. Vaccination with SpAmut adjuvanted with AS01 (SpAmut/AS01) was able to limit bacterial spreading from the skin through the blood, abrogating S. aureus infiltration to the kidneys (target for systemic disease). S. aureus-specific protein microarrays were used to compare sera of mice vaccinated with SpAmut/AS01 and then infected with those of mice only infected for their ability to recognize a selection of S. aureus antigens. Vaccination with SpAmut/AS01 was able to unmask several S. aureus antigens to the immune system during SSTIs in mice. Interestingly, mice infected with S. aureus did not develop measurable antibodies against the mutated version of SpA, whereas infection in vaccinated mice significantly increased the avidity of antibodies against SpAmut induced by previous immunization. Furthermore, only sera from vaccinated and infected mice allowed internalization of S. aureus by human phagocytes in vitro, suggesting a functional role in mediating the in vivo observed protection. Overall, these data support the essential role of vaccination with SpA, an immunomodulator antigen of S. aureus, in the induction of a functional specific antibody response during recurrences, contributing to the control of systemic bacterial dissemination, one of the main complications developed during S. aureus-mediated SSTIs.

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Daniels, Katherine Jean. "Couples' construction of meaning of an Alzheimer's disease diagnosis : a systemic approach." Diss., Manhattan, Kan. : Kansas State University, 2008. http://hdl.handle.net/2097/1057.

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Galliano, Karin. "Children"s perceptions of marital conflict, parent-child relations and anxiety in children: a proposed systemic model." FIU Digital Commons, 1999. http://digitalcommons.fiu.edu/etd/3439.

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Few studies have examined the effects of a divorce on internalizing symptomatology in children, and none have done so in a clinic sample. The present study examined this issue in a clinic sample of children with anxiety disorders (aged 6-16). Because past research has found that it is not divorce but the child’s perspective of marital conflict that is the crucial factor in examining negative outcomes, it was hypothesized that children who reported worry about marital conflict would show greater internalizing symptomatology than those who reported no worries, regardless of whether they came from intact or divorced homes. Internalized symptomatology was operationalized by children’s scores on anxiety and depression scales, as well as the number and severity of clinical diagnoses. Results revealed that worriers had significantly higher levels of anxiety than non-worriers. They were also elevated in depression. The results did not support the hypothesis that worriers from divorced homes would show the most severe internalizing symptomatology. Results are discussed in terms of the marital conflict and the childhood anxiety literature.

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Oliveira, Perla Novais de. "Transformação genética de tomate \'Micro-Tom\' com o gene enhanced disease susceptibility 5 (EDS5) isolado de Citrus sinensis." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/11/11144/tde-02022016-155536/.

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Nos anos recentes, a atividade agrícola da citricultura vem enfrentando grandes problemas fitossanitários, principalmente, com relação à viabilidade econômica decorrente do controle das doenças. A bactéria Candidatus Liberibacter spp. está associada ao HLB, a principal doença que limita a produção das plantas cítricas. Assim, muitos pesquisadores têm voltado suas atenções para estudarem e encontrarem genes-alvo na resposta do hospedeiro a este patógeno para utilização no melhoramento genético. Nesse sentido, métodos de transformação genética das plantas cítricas são essenciais, porém características inerentes à espécie limitam seu cultivo in vitro e requerem um maior tempo para crescimento e propagação. Com isso, torna-se importante o estudo em plantas modelo, principalmente, para seguir protocolos de validação de genes. De acordo com o exposto, o gene EDS5 isolado de Citrus sinensis, associado ao mecanismo de Resistência Sistêmica Adquirida (SAR) foi superexpresso por meio da transformação genética em tomateiro (Solanum lycopersicum L. Micro-Tom). Após o crescimento dos brotos regenerados, foram identificadas as plantas positivas por meio de análise de GUS e PCR. Linhagens transgênicas homozigotas foram obtidas com avaliação da resistência ao antibiótico canamicina.
In the recent years, the agricultural activity of the citrus industry has been facing big phytosanitary problems, mainly with regard to economic viability arising from disease control. The bacterium Candidatus Liberibacter spp. is associated with HLB, the main disease that limits the production of citrus trees. Thus, many researchers have been returning their attentions to study and find target genes in the host response to this pathogen for use in the genetic improvement. In this way, methods of genetic transformation of citrus plants are essential, but the inherent characteristics of the species border your in vitro cultivation and require a longer time for growth and propagation. Therefore, it is important to study of model plants, mainly for genetic validation protocols. Thus, the EDS5 gene isolated from Citrus sinensis, associated with Systemic Acquired Resistance mechanism (SAR) was overexpressed by genetic transformation in tomato (Solanum lycopersicum L. Micro-Tom). After the growth of regenerated shoots, positive plants were identified by PCR and GUS analysis. Homozygous transgenic lines were obtained with evaluation of resistance to kanamycin.

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Yasar, Muhammet Murat. "A Complex Systems Model for Understanding the Causes of Corruption: Case Study - Turkey." Thesis, University of North Texas, 2005. https://digital.library.unt.edu/ark:/67531/metadc4827/.

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It is attempted with this dissertation to draw an explanatory interdisciplinary framework to clarify the causes of systemic corruption. Following an intense review of political sciences, economics, and sociology literatures on the issue, a complex systems theoretical model is constructed. A political system consists of five main components: Society, interest aggregators, legislative, executive and private sector, and the human actors in these domains. It is hypothesized that when the legitimacy level of the system is low and morality of the systemic actors is flawed, selected political, social and economic incentives and opportunities that may exist within the structure of the systemic components might -individually or as a group- trigger corrupt transactions between the actors of the system. If left untouched, corruption might spread through the system by repetition and social learning eventually becoming the source of corruption itself. By eroding the already weak legitimacy and morality, it may increase the risk of corruption even further. This theoretical explanation is used to study causes of systemic corruption in the Turkish political system. Under the guidance of the complex systems theory, initial systemic conditions, -legacy of the predecessor of Turkey Ottoman Empire-, is evaluated first, and then political, social and economic factors that are presumed to be breeding corruption in contemporary Turkey is investigated. In this section, special focus is given on the formation and operation of amoral social networks and their contribution to the entrenchment of corruption within the system. Based upon the findings of the case study, the theoretical model that is informed by the literature is reformed: Thirty five system and actor level variables are identified to be related with systemic corruption and nature of the causality between them and corruption is explained. Although results of this study can not be academically generalized for obvious reasons; the analytical framework proposed here can be referenced by policy makers who are willing to trace the roots of systemic corruption in developing countries.

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LEMOS, OLIVEIRA MENDONCA ROSANGELA MIRIAM. "Systemic Network Innovation and Its Application in the Brazilian Context of the "Estrada Real"." Doctoral thesis, Politecnico di Torino, 2014. http://hdl.handle.net/11583/2534088.

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ABSTRACT: The question that this work proposes to answer is already part of its title: “How to make ideas become a resource for social-economic improvement”. In order to approach an answer, a new strategy must be found, since this is a long lasting question, especially in contexts of developing countries with large social differences, such as Brazil. We have then started from the Systemic Design methodology which proposes the valorisation of the territory, people, relations and the optimization of resources. The application was set to be the Brazilian territory of the “Estrada Real”, on the state of Minas Gerais. The subject “ideas”, took us to investigate aspects of innovation, also because many institutional strategies in public and private spheres, are based on its potential as a development driver. Then, besides the institutional strategies themselves, we have studied some cases of actions that had as goals the promotion of a region, cases of incentive for entrepreneurship. Analysing these cases from the point of view of the Systemic Design has allowed to identify their positive aspects, elements of attention or that should be changed, and propose approaches for its improvement. This previous work has raised other elements to be investigated. What would be the ideal size of a company? What, in fact, can be called technology? Who would be responsible for the changes we need? Here the economic bias has emerged very strong. It had then to be conciliated with other values of the Systemic Design. This has culminated in the development of the Systemic Network of Integral Endeavors, a concept yet broader than that of clusters. This includes the evolution of the elaboration of Business Models, which nowadays’ is largely adopted to plan innovative businesses. Then some real businesses were studied to exemplify some of the values and concepts previously treated. Finally, the historical legacies of the “Estrada Real” and nowadays’ features were researched. That has allowed the identification of nuances of resources and of a project that would have the potential of involving, as desired, many social classes, in a subject that is part of the territory history. As another product of this research, besides the identification of the “best practices” themselves, an instrument for the collection of data and elaboration of guidelines was created. Considering the importance of the participation of all stakeholders in the definition of actual actions to be taken, this instrument will assist on the debate to the distilling of “best practices” to be adopted for the initiatives in the “Estrada Real”. This experience will be able to assist in its evolution for the planning of the Olympics and Paralympics events in Brazil in 2016. SOMMARIO: Il problema che questo lavoro si propone di rispondere è già parte del suo titolo: come fare diventare le idee una risorsa per il miglioramento economico e sociale. Per avvicinarsi a una risposta si deve trovare una nuova strategia, poiché questo è un problema di lunga data, specialmente nei contesti dei paesi in via di sviluppo con grandi contrasti sociali, come il Brasile. Abbiamo allora iniziato dalla metodologia del Design Sistemico, che propone la valorizzazione del territorio, delle persone, delle relazioni e l'ottimizzazione delle risorse. La ricerca applicata è stata impostata per essere il territorio brasiliano della “Estrada Real”, nello stato del Minas Gerais. L'argomento “idee”, ci ha portato a investigare sugli aspetti dell'innovazione, anche perché molte strategie istituzionali nelle sfere private e pubbliche, sono basate sulle potenzialità di apportatori di sviluppo. Allora, accanto alle stesse strategie istituzionali, abbiamo studiato alcuni casi studi, da quelle che avevano come obiettivo la promozione di una regione, a quelle per l'incentivazione dell'imprenditorialità. L'analisi di questi casi dal punto di vista del Design Sistemico ha consentito di identificare gli aspetti positivi, gli elementi sui quali bisogna porre attenzione o che devono essere cambiati, e di proporre approcci per un ulteriore miglioramento. Questo lavoro precedente ha sollevato ulteriori elementi di studio. Quali sarebbero le dimensioni ideali di un'azienda? Che cosa possiamo chiamare con il termine “tecnologia”? Chi sarebbe il responsabile per i cambiamenti di cui abbiamo bisogno? Qui, l'influenza economica è emersa molto forte. E doveva allora essere conciliata con gli altri valori del Design Sistemico. Ciò è culminato con la Rete Sistemica delle Imprese Integrali (“Systemic Network of Integral Endeavors”), un concetto ancora più ampio di quello dei “cluster” e include l'evoluzione dell'elaborazione del modello di Business, che al giorno d'oggi è ampiamente adottato per pianificare i business innovativi. Si sono allora studiati dei business reali per semplificare alcuni dei valori e dei concetti precedentemente trattati. Infine, si è fatta una ricerca sulle eredità storiche e sulle caratteristiche odierne della “Estrada Real”. Questo ha consentito l'identificazione delle sfumature delle risorse e di un progetto che vorrebbe avere il potenziale di coinvolgere molte classi sociali, in una materia che è parte del territorio storico. Come altro prodotto di questa ricerca, accanto all'identificazione delle stesse migliori pratiche, si è creato uno strumento per la raccolta dei dati e l'elaborazione delle linee guida. Considerata l'importanza della partecipazione di tutti gli stakeholder nella definizione delle azioni attuali da intraprendere, questo strumento assisterà nel dibattito sul “distillare” quali possano essere le “migliori pratiche” da adottare per le iniziative nella “Estrada Real”. Quest'esperienza consentirà di assistere nella evoluzione della pianificazione degli eventi Olimpici e Paraolimpici del Brasile 2016.

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47

Hauff, Thomas R. "An assessment and application of the systemic linguistic model of verbal aspect in the New Testament proposed by Stanley E. Porter." Theological Research Exchange Network (TREN), 1996. http://www.tren.com.

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Griffin, Marley A. "A model for examining antinuclear antibody circulation and binding capabilities of human serum from systemic lupus erythematosus patients." Virtual Press, 2007. http://liblink.bsu.edu/uhtbin/catkey/1371840.

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Antinuclear antibodies (ANA) are used in screening and diagnosis of autoimmune connective tissue disorders including systemic lupus erythematosus (SLE). CNS related disorders are prevalent in SLE patients (–80%) and ANA binds specific sites within the brain. To investigate ANA infiltration across the blood-brain barrier (BBB), an ANA injectable Lewis rat model was created using 3 rat groups (saline, ANA, and ANA with histamine; since histamine promotes BBB permeability). ANA serum levels were tested for all three rat groups and rats injected with histamine demonstrated signs of histadelia. Brain slices were obtained and examined for the presence of ANA using immunofluorescence. ANA infiltration across the BBB was observed in ANA injected groups. Though the ANA and ANA histamine groups were significantly different from controls (p<0.034, p<0.030, respectively), no significance between ANA and ANA histamine groups was observed. This model could further be used to examine BBB permeability and potential drug therapy.
Department of Physiology and Health Science

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Whibley, Natasha. "The role of effector and regulatory helper T cells in a murine model of systemic Candida albicans infection." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=192231.

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Diseases caused by fungi are increasing worldwide and are often associated with high mortality rates. In particular, the normally harmless commensal Candida albicans can cause serious disease if immunological and physiological barriers are perturbed, leading to systemic infection, which is fatal in up to 45% of cases. The adaptive immune response is believed to be important in protection against systemic candidiasis, however, the roles of different helper T (Th) cell subsets, particularly Foxp3+ regulatory T (Treg) cells, remain largely unexplored. The aims of this study were to adapt a mouse model of systemic C. albicans infection to test whether the numbers of Th1, Th2, Th17 and Foxp3+ Treg cells increase in mice with systemic C. albicans infection, and determine their contribution to disease. C. albicans drove the expansion of Th1, Th2 and Th17 cells, as well as multiple Foxp3+ populations that displayed characteristics of natural Treg, induced Treg, Th17 and Th1 cells in vitro and in vivo. The expanded Foxp3+ T cells inhibited Th1 and Th2, but promoted Th17, responses to C. albicans antigens in vitro and exacerbated disease, since their depletion in vivo reduced kidney fungal burden and inflammatory lesions. Furthermore, systemic infection with a weakly virulent C. albicans strain was associated with reduced Treg responses compared to those induced during lethal systemic infection. These data lead to a model for systemic candidiasis whereby Treg expansion promotes Th17 responses that drive pathology, and have implications for future immunotherapy.

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Shirreff, Lisa M. "Characterization of an M. marinum Vaccine| Examination of Both Mucosal Immunity and Systemic Immunity in a Fish Model." Thesis, University of Louisiana at Lafayette, 2016. http://pqdtopen.proquest.com/#viewpdf?dispub=10163372.

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Mycobacterium marinum (Mm) shares at least 80% amino acid sequence identity with over 3,000 orthologous genes of Mycobacterium tuberculosis (Mtb) and is thus used as a surrogate pathogen for Mtb research. Our laboratory investigates mycobacteriosis using Japanese medaka ( Oryzias latipes) as an aquatic animal model. Mm disease presentation in medaka is similar to Mtb disease presentation in humans, including growth in macrophages, granulomatous lesions, and lifelong chronic disease. We have previously shown that a major route of infection in fish is through an oral route and have thus developed methods to infect medaka with Mm utilizing mosquito larvae as vectors. Recently, our lab was able to show that Mm is able to cross the gut epithelia of medaka in a relatively short-time frame and travel to the underlying submucosa. Therefore, Mm must have the ability to attach to the gut mucosal layer and evade killing by GALT immune cells. Mm is apparently able to exploit macrophages of the mucosal immune system to transport the bacteria to target organs like the head kidney, liver, and spleen for a systemic infection. Utilizing an Mm strain engineered to carry a deletion in the RD-1 region, known to include a number of virulence genes, our lab has shown that mucosal immunity against Mm can be induced in medaka. We have shown that exposure to the mutant RD-1 strain offers some protection against a chronic wild-type oral challenge. Since we know that mutant RD-1 can elicit a mucosal immune response, I tested to see if sensitizing mucosal immunity would also induce systemic immunity by first priming fish with mutant RD-1 and then subsequently challenging them with wild type Mm via an IP route. This thesis demonstrates that mucosal immunity is limited to the gut and thus does not appear to provide broad systemic immunity. Additionally, I tested to see if systemic vaccination would protect against a systemic virulent wild-type challenge by vaccinating and challenging fish via an IP route of infection. Results showed that systemic vaccination does not induce systemic immunity and thus does not protect against an IP injected virulent challenge. Collectively, results from this thesis have shown mutant RD-1 to only be effective as a vaccine against mycobacteriosis if given orally since it was shown to only induce a mucosal immune response and only be protective against an oral virulent wild type challenge.

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Dissertations / Theses on the topic 'Systemic model'

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