Alzheimer's disease (AD) is a worldwide, incurable disease, and the most common form of dementia. Numbers of cases are rising, and since its discovery the only approved medications have treated only the symptoms, not the pathological cause. With the cost to society rising, the debilitating nature of the disease and the pressure put on the family members and support network of patients, disease modifying therapies are in dire need. Current models have proven an invaluable tool with which to study certain aspects of the disease and the genetics behind it, however the lack of clinically approved medications in the last 20 years suggests new models are needed. Based on the amyloid cascade hypothesis, this thesis initially characterises two models of β-Amyloid oligomer (Aβo) induced cognitive deficits. Both models are created by ICV injection of soluble Aβo into the brain of rat. The models differ only by the molecular weight of the Aβo 1-42, one, referred to as low molecular weight (LMW) Aβo, with stable dimers, trimers and tetramers, the other, referred to as high molecular weight (HMW) Aβo, consisting of assemblies ranging from ~50 to ~150 kDa. It was found that behavioural deficits were similar between the two, with a robust object recognition deficit, but no working memory deficit. Both models also showed a deficit in the synaptic marker PSD-95; however the LMW Aβo caused a deficit in the frontal cortex, whereas the HMW Aβo caused a hippocampal deficit. The role of the cellular prion protein (PrPC) was explored, by blocking its binding to Aβo with the antibody 6D11. Interestingly the two models showed different results. The HMW Aβo deficits were completely blocked by the 6D11 application, however the LMW Aβo deficits were only partially prevented. Finally, Fasudil, a vasodilator approved in parts of Asia, was used to inhibit Rho-kinase, showing a prevention of the cognitive deficits in the HMW Aβo model. The results of this thesis show the ICV administration of Aβo to be a useful model for investigating the effects of Aβo, provides a platform with which to study the differing effects of Aβo with different oligomeric assemblies, and a model to test therapeutic strategies with relevance to AD.

by Lee Kai Cheung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references. / Acknowledgements --- p.II / Abstract --- p.III / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Theory --- p.7 / Chapter Chapter 3 --- Application of the Connected-Moments Expansion to the S=l/2 Heisenberg Antiferromagnet Paper I --- p.16 / Chapter Chapter 4 --- Application of the Connected-Moments Expansion to the Half-filled Hubbard Model Paper II --- p.18 / Chapter Chapter 5 --- Conclusion --- p.20 / Appendix I --- p.21 / Appendix II --- p.29 / References --- p.37

This thesis investigates the origins of the political and religious movement which developed within the New Model army between March 1647 and May 1649, by examining the preceding period (1644-1647) when the army was formed and began its activity. It tries to elucidate how an army, raised with strictly military aims and subjected to a particularly rigorous discipline, could develop representative structures (General Council, agitators) and constitutional programmes. As there is relatively little direct evidence concerning the army's religion and politics before 1647, I have analysed the influences to which the soldiers would have been subjected. Two main factors have been isolated, which contributed to the process of politicisation in the New Model. One concerns the army more directly and specifically: the propaganda addressed to soldiers by Parliament (newsbooks, declarations) army commanders and especially preachers. By instilling a sense of personal commitment to a cause and justifying resistance of subjects to their King, this propaganda encouraged the soldiers to think and decide for themselves. This, in turn, tended to conflict with the unquestioning obedience required by the military code. The other factor is more long-term and tends to involve English society at large. It is a complex of processes taking place in church and state on the eve and during the civil war. In both spheres a greater participation of common people in public affairs began to develop. The spreading of "gathered churches" and the campaign of popular petitions and demonstrations in 1640-1642 are the most significant examples. Finally, some attention has been paid to the early manifestations of a political or religious radical consciousness, in the New Model and other parliamentary armies. The experience of the latter may also have had an influence on Fairfax' s army.

Governments often fund foreign nationals to live, work and study in their countries, creating specialist programmes tasked with promoting international mobility. In this thesis I establish that much of this funding is intended to serve a public diplomacy agenda, improving international relations to the benefit of the sponsor. Expectations about how offering funding to foreigners affects international relations have come to centre on what I label the ‘symmetric public diplomacy model’, which suggests that governments intend to influence other countries’ behaviour by influencing their citizens. I tested this model using a combination of panel surveys and interviews with students who took part in these programmes. Although mobility programmes do bring many educational and personal benefits to participants, my results do not support the expectation that they endow most visiting foreigners with more helpful attitudes than they would have developed had they not taken part in the programmes. While other studies have come to different conclusions on this issue, the research design employed in this thesis is better-suited to the task than most others. Mobility programmes may bring diplomatic benefits by other means. One possibility is that the act of creating, for example, scholarships for foreign nationals sends signals to foreign governments. The histories of major British scholarship programmes suggest that they were originally created to signal goodwill or distract attention from potentially-embarrassing policies. Despite this, administrators now present these programmes as tools of public diplomacy. The symmetric public diplomacy model has been applied to these programmes long after they were initially created, and I suggest that the model may have been adopted because it is useful for attracting funding to continue and expand mobility programmes.

"This dissertation documents a study on parameter estimation methods for comprehensive pyrolysis modeling. There are four parts to this work, which are (1) evaluating effects of applying different kinetic models to pyrolysis modeling of fiberglass reinforced polymer composites; (2); evaluation of pyrolysis parameters for fiberglass reinforced polymer composites based on multi-objective optimization; (3) parameter estimation for comprehensive pyrolysis modeling: guidance and critical observations; and (4) engineering guide for estimating material pyrolysis properties for fire modeling. In the first section (Section 1), evaluation work is conducted to determine the effects of applying different kinetic models (KMs), developed based on thermal analysis using TGA data, when used in typical 1D pyrolysis models of fiberglass reinforced polymer (FRP) composites. The study shows that that increasing complexity of KMs to be used in pyrolysis modeling is unnecessary for the FRP samples investigated. Additionally, the findings from this research indicates that the basic assumption of considering thermal decomposition of each computational cell in comprehensive pyrolysis modeling as equivalent to that in a TGA experiment becomes inapplicable at depth and higher heating rates. The second part of this dissertation (Section 2) reports the results from a study conducted to investigate the ability of global, multi-objective and multi-variable optimization methods to estimate material parameters for comprehensive pyrolysis models. The research materials are two fiberglass reinforced polymer (FRP) composites that share the same fiberglass mats but with two different resin systems. One resin system is composed of a single component and the other system is composed of two components (resin and fire retardant additive). The results show that for a well-configured parameter estimation exercise using the optimization method described above, (1) estimated results are within ± 100% of the measurements in general; (2) increasing complexity of the kinetic modeling for a single component system has insignificant effect on estimated values; (3) increasing complexity of the kinetic modeling for a multiple component system with each element having different thermal characteristics has positive effect on estimated values; and (4) parameter estimation using an optimization method with appropriate level of complexity in kinetic model and optimization targets can find estimations that can be considered as effective material property values. The third part of this dissertation (Section 3) proposes a process for conducting parameter estimation for comprehensive pyrolysis models. The work describes the underlying concepts considered in the proposed process and gives discussions of its limitations. Additionally, example cases of parameter estimation exercise are shown to illustrate the application of the parameter estimation process. There are four materials considered in the example cases – thermoplastics (PMMA), corrugated cardboard, fiberglass reinforced polymer composites and plywood. In the last part (Section 4), the actual Guide, a standardized procedure for obtaining material parameters for input into a wide range of pyrolysis models is presented. This is a step-by-step process that provides a brief description of modeling approaches and assumptions; a typical mathematical formulation to identify model parameters in the equations; and methods of estimating the model parameters either by independent measurements or optimization in pair with the model. In the Guide, example cases are given to show how the process can be applied to different types of real-world materials. "

Epidemics have caused major human and monetary losses through the course of human civilization. It is very important that epidemiologists and public health personnel are prepared to handle an impending infectious disease outbreak. the ever-changing demographics, evolving infrastructural resources of geographic regions, emerging and re-emerging diseases, compel the use of simulation to predict disease dynamics. By the means of simulation, public health personnel and epidemiologists can predict the disease dynamics, population groups at risk and their geographic locations beforehand, so that they are prepared to respond in case of an epidemic outbreak. As a consequence of the large numbers of individuals and inter-personal interactions involved in simulating infectious disease spread in a region such as a county, sizeable amounts of data may be produced that have to be analyzed. Methods to visualize this data would be effective in facilitating people from diverse disciplines understand and analyze the simulation. This thesis proposes a framework to simulate and visualize the spread of an infectious disease in a population of a region such as a county. As real-world populations have a non-homogeneous demographic and spatial distribution, this framework models the spread of an infectious disease based on population of and geographic distance between census blocks; social behavioral parameters for demographic groups. the population is stratified into demographic groups in individual census blocks using census data. Infection spread is modeled by means of local and global contacts generated between groups of population in census blocks. the strength and likelihood of the contacts are based on population, geographic distance and social behavioral parameters of the groups involved. the disease dynamics are represented on a geographic map of the region using a heat map representation, where the intensity of infection is mapped to a color scale. This framework provides a tool for public health personnel and epidemiologists to run what-if analyses on disease spread in specific populations and plan for epidemic response. By the means of demographic stratification of population and incorporation of geographic distance and social behavioral parameters into the modeling of the outbreak, this framework takes into account non-homogeneity in demographic mix and spatial distribution of the population. Generation of contacts per population group instead of individuals contributes to lowering computational overhead. Heat map representation of the intensity of infection provides an intuitive way to visualize the disease dynamics.

Le changement de business model est présenté aujourd’hui comme un enjeu majeur pour les entreprises. Il apparaît en effet comme un levier d’innovation et peut contribuer au développement d’un avantage concurrentiel. Si les travaux s’accordent sur ce point, ils montrent également que la cohérence globale du business model est un facteur de performance. Les dirigeants sont alors confrontés à un dilemme : faut-il changer le business model pour innover ou privilégier le statu quo pour assurer la profitabilité de l’entreprise ?Le business model est défini comme une configuration de choix déterminant la façon dont une entreprise crée de la valeur et du profit. Pour éclairer le thème du changement, nous avons formulé la question de recherche comme suit : « Quelles sont les variations de la configuration du BM d’une entreprise dans un contexte de changement ? ». Nous avons mené une étude longitudinale pour observer le comportement des cinq principaux labels phonographiques, les « majors », qui sont confrontés à une baisse importante des ventes de disques. Une analyse des 356 décisions identifiées entre 1998 et 2008 permet de retracer l’ensemble des variations de leur business model. D’abord, cette recherche aboutit à l’identification de quatre logiques de changement qui sont de multiples façons de transformer la configuration du BM. Ensuite, cette étude met en valeur la dynamique du changement en étudiant les interactions et les interdépendances entre les composantes du business model. Enfin nous mettons en évidence une série de facteurs internes et externes qui ont une incidence sur les trajectoires des entreprises. Cette recherche intègre ainsi plusieurs éléments de l’environnement comme facteurs influençant les décisions de changement. / Business model change emerges as a major issue for organizations today. It represents a key driver for innovation and a potential path to competitive advantage. However, research emphasizes the need for consistency which leads to greater performance for organizations. Therefore, managers are facing a dilemma: should the business model be changed for the sake of innovation or should the status quo be maintained to protect the firms’ profitability? Business models are defined as the configuration of choices that determine the way organizations create value and profits. The purpose of this research is to study the evolution of the business model configuration in the context of change. Insights are drawn from in-depth longitudinal case studies on the five main record labels, the « majors » who are facing a significant decline in CD sales. The analysis of 356 strategic decisions from 1998 to 2008 enables us to describe precisely the transformation of their business model. First, we identify four logics of change which represent multiple ways to transform the business model configuration. Second, our research emphasizes the dynamic of change by studying interactions and interdependencies between the components of business models. Lastly, we identify a series of internal and external factors that impact the trajectories of organizations. Furthermore, this research demonstrates the influence of the environment on change process.

Given an o-minimal structure on the real field, we consider an elementary extension to a non-archimedean field R, and interpret the algebraically closed field K=R[sqrt(-1)] on this extension. We construct two pregeometries on K: one by considering images under C-definable holomorphic functions, and the other by considering images under proper restrictions of C-definable holomorphic functions together with algebraic functions (i.e. zeros of polynomials).We show that these two pregeometries are the same, generalising a result of A. Wilkie for complex holomorphic functions. We also do some work towards generalising another result of his on local definability of complex holomorphic functions to our non-archimedean setting.

Many novel materials, such as the vanadates MgV 2O5, the cuprates SrCu 2O3, conducting polymers and organic salts which involve longer-range Coulomb interactions, can be modeled by the extended Hubbard model. In this thesis, we applied the strong-coupling perturbation theory to study a generalized extended Hubbard model characterized by the inter-chain electron hopping t' and the inter-chain nearest-neighbor interaction V' as well as the on-site interaction U, the intra-chain nearest-neighbor interaction V and the intra-chain electron hopping t at strong coupling limit for quarter and half band fillings. / The early strong coupling perturbation expansion was only up to the fourth order in t/U and t/V expansion, which is good for the large values of interaction, U/t > 10. However, for real physical systems, the reasonable range of U/t should be from 4 to 10. In order to investigate the physical systems more accurately, we worked out a perturbation expansion up to the sixth order, hence obtained an effective Hamiltonian in t/U, t/V, t/V', t'/U, t'/V and t'/V' expansion for the extended Hubbard model in half and quarter band filings. The effective Hamiltonian obtained only contains the spin-spin correlation terms. For the half-filled band, we calculated the four spin-spin correlation terms and applied the first and second nearest-neighbor correlation of the linear Heisenberg model obtained by Hulthen and Takahashi and the third nearest-neighbor correlation obtained by Kazumitsu Sakai's group to calculate the ground state energy for the 1-D extended Hubbard chain with the realistic Coulomb interactions, U/t ranges from 4 to 14 and V/t ranges from 0 to 2 respectively. For the quarter-filled case, we worked out the effective Hamiltonian for the 1-D and the 2-D cases and calculated the spin-spin correlation functions by the spin-wave theory. We calculated the ground state energy with the same ranges of the on-site interaction input in the half-filled case and the V/t ranges from 1.5 to 4.0 for the 1-D, the quasi 2-D (t > t', t'/V ∼ t/V) and the isotropic 2-D (t = t', V = V') case respectively. In order to check the validity of the perturbation expansion, we proceeded numerical calculations of the ground state energy by exact diagonalization for the same values of U, V, t, V' and t' for both the half-filled and the quarter-filled cases. / Lee Wing Fai = 強耦合擴展 Hubbard模型之微擾計算 / 李榮輝. / "August 2005." / Adviser: Lin Hai Qing. / Source: Dissertation Abstracts International, Volume: 67-01, Section: B, page: 0323. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 157-160). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307. / Lee Wing Fai = Qiang ou he kuo zhan Hubbard mo xing zhi wei rao ji suan / Li Ronghui.

Osteoarthritis (OA) is a chronic, degenerative condition of articular joints. The prevalence of OA is high in many mammalian populations, though our understanding of the disease is limited, with the initiating factors and the early phenotype of the disease being poorly characterised. Clinically, the early-stage of OA is rarely identified, precluding the identification and treatment of affected individuals. Consequently, in vitro models of OA typically reflect the later stages of the disease, and are rarely validated against the naturally-occurring disease. This project utilised tissue from a naturally-occurring canine disease (medial coronoid process disease) to characterise the transcriptome of early-stage OA, and inform different in vitro models, to try and refine the model conditions. Medial coronoid processes from affected dogs were removed and graded histologically, both manually and through the development of a semi-automated assessment. Early-stage OA was characterised by a decrease in the chondrocyte density, an increase in the thickness of the articular cartilage and a loss of proteoglycan. No histological changes in bone morphology were noted in early-stage OA. A transcriptomic approach was adopted, in which the transcriptome of earlystage canine OA was assessed in the coronoid process samples. The canine data generated were meta-analysed alongside published datasets from in vivo models of early-stage OA. These data were from rodent models of the disease. A panel of genes were identified as being associated with the early stage of the disease across multiple datasets. By immunoassay, synovial fluid was screened for pro-inflammatory cytokines and in affected canine joints, interleukin 8 was found to be increased. Three in vitro models (cytokine stimulation of monolayer cell cultures, cyclic compression of agarose embedded cells and impact loading of osteochondral cores) were refined through modification of their stimuli. An identified panel of differentially expressed genes were used to screen each model under different parameters. Hierarchical clustering analysis was used to cluster the panel of conditions so that those which most closely reflected the naturally occurring disease were selected for more detailed transcriptomic analysis by microarray. Chondrocytes and osteoblasts were stimulated with a range of cytokine conditions, using IL-1β and IL-8 based on use in the literature and immunoassay findings. Monolayers were stimulated for a range of times and conentrations with either a single stimulus or multiple cytokines in the medium. The cells responded differently to the cytokine stimulus, requiring different stimuli to most closely replicate the transcriptomic profile of the natural disease. Microarray profiling revealed that cytokine stimulation enriched genes associated with the extracellular matrix and the extracellular region in both cells types. For the cyclic compression model, cells were embedded in an agarose gel matrix and cyclically compressed for various time periods followed by various incubation periods after compression. Both chondrocytes and osteoblasts responded in a similar manner to the cyclic compression stimulus when a post loading incubation step was included to replicate the transcriptomic profile of the natural disease. Cyclic compression enriched gene clusters associated with response to oxidative stress and the extracellular matrix When osteochondral cores were harvested from joints and impacted to represent a traumatic injury, the model could not replicate the transcriptomic model of the natural disease, although increased sGAG release nitric oxide (NO) production was observed. Degradation of mRNA in both tissues was a feature of this model regardless of the loading condition, which precluded further analysis by microarray, but highlighted the significant limitations that were associated with this model. None of the three models tested could accurately reflect the transcriptomic changes of the early-stage OA phenotype in cartilage or bone. A unified model, combining cytokine stimulation with cyclic compression drove cells towards the diseased phenotype in bone. Inflammatory pathways were activated as well as the proteases MMP3 and MMP13. However, chondrocytes were seemingly unresponsive to the multifactorial model, and this will require further analysis. The chronic nature of OA makes it difficult to match in vitro models to the transcriptomic phenotype identified in naturally occurring OA, particularly with respect to the differential expression of structural genes which were identified in the naturally occurring disease but not the models. This work highlights the limitations of existing models, but proposes a validation process which can be used to direct invitro models towards the naturally occurring phenotype.