published_or_final_version / Chinese Medicine / Master / Master of Philosophy

This thesis established the cubature method developed by Gyurkó & Lyons (2010) and Lyons & Victor (2004) for the Heath–Jarrow–Morton (HJM) model. The HJM model was first proposed by Heath, Jarrow, and Morton (1992) to model the evolution of interest rates through the dynamics of the forward rate curve. These dynamics are described by an infinite-dimensional stochastic equation with the whole forward rate curve as a state variable. To construct the cubature method, we first discretize the infinite dimensional HJM equation and thereafter apply stochastic Taylor expansion to obtain cubature formulae. We further used their results to construct cubature formulae to degree 3, 5, 7 and 9 in 1-dimensional space. We give, a considerable step by step calculation regarding construction of cubature formulae on Wiener space.

Dans une première partie théorique, nous nous penchons sur une analyse rigoureuse des performances de l'algorithme Sequential Monte Carlo (SMC) conduisant à des résultats de type bornes L^p et inégalités de concentration. Nous abordons notamment le cas particulier des SMC associés à des schémas de température, et analysons sur ce sujet un processus à schéma adaptatif.Dans une seconde partie appliquée, nous illustrons son utilisation par la résolution de problèmes inverses concrets en électromagnétisme. Le plus important d'entre eux consiste à estimer les propriétés radioélectriques de matériaux recouvrant un objet de géométrie connue, et cela à partir de mesures de champs rétrodiffusés. Nous montrons comment l'algorithme SMC, couplé à des calculs analytiques, permet une inversion bayésienne, et fournit des estimées robustes enrichies d'estimations des incertitudes. / Sequential and Quantum Monte Carlo methods, as well as genetic type search algorithms, can be interpreted as a mean field and interacting particle approximation of Feynman-Kac models in distribution spaces. The performance of these population Monte Carlo algorithms is strongly related to the stability properties of nonlinear Feynman-Kac semigroups. In a first theoretical part, we analyze these models in terms of Dobrushin ergodic coefficients of the reference Markov transitions and the oscillations of the potential functions. Sufficient conditions for uniform concentration inequalities w.r.t. time are expressed explicitly in terms of these two quantities. We provide an original perturbation analysis that applies to annealed and adaptive FK models, yielding what seems to be the first results of this kind for these type of models. Special attention is devoted to the particular case of Boltzmann-Gibbs measures' sampling. In this context, we design an explicit way of tuning the number of Markov Chain Monte Carlo iterations with temperature schedule. We also propose and analyze an alternative interacting particle method based on an adaptive strategy to define the temperature increments. In a second, applied part, we illustrate the use of these SMC algorithms in the field of inverse problems. Mainly, the following electromagnetism (EM) inverse problem is addressed. It consists in estimating local radioelectric properties of materials recovering an object from global EM scattering measurements, at various incidences and wave frequencies. This large scale ill-posed inverse problem is explored by an intensive exploitation of an efficient 2D Maxwell solver, distributed on high performance computing machines. Applied to a large training data set, a statistical analysis reduces the problem to a simpler probabilistic metamodel, on which Bayesian inference can be performed. Considering the radioelectric properties as a hidden dynamic stochastic process, that evolves in function of the frequency, it is shown how the Sequential Monte Carlo methods can take benefit of the structure and provide local EM property estimates.

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Chan, Chun Kit. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 147-161). / Abstracts in English and Chinese. / Chapter Chaper 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction to cerebral stroke --- p.1 / Chapter 1.2 --- Different types of cerebral stroke --- p.2 / Chapter 1.3 --- Statistics --- p.3 / Chapter 1.4 --- Symptoms of cerebral stroke --- p.4 / Chapter 1.5 --- Complications of cerebral stroke --- p.5 / Chapter 1.6 --- Risks and preventions of cerebral stroke --- p.6 / Chapter 1.7 --- Cerebral stroke treatment --- p.8 / Chapter 1.8 --- Post stroke rehabilitation --- p.11 / Chapter 1.9 --- Mechanisms of stroke --- p.15 / Chapter 1.9.1 --- Energy production failure and loss of ionic homeostasis --- p.15 / Chapter 1.9.2 --- Excitotoxicity --- p.16 / Chapter 1.9.3 --- Calcium ions mediated toxicity --- p.17 / Chapter 1.9.4 --- Passive neuronal cell death --- p.18 / Chapter 1.9.5 --- Oxidative stress --- p.19 / Chapter 1.9.6 --- Inflammation --- p.22 / Chapter 1.9.7 --- Apoptosis --- p.25 / Chapter 1.10 --- Potential therapeutic agents for cerebral stroke --- p.24 / Chapter 1.10.1 --- Anti-oxidative enzyme and free radical scavengers --- p.24 / Chapter 1.10.2 --- Ions channel blockers and glutamate antagonists --- p.26 / Chapter 1.10.3 --- Anti-inflammatory agent --- p.28 / Chapter 1.10.4 --- Anti-apoptotic agent --- p.28 / Chapter 1.11 --- Experimental model of cerebral ischemia-reperfusion --- p.29 / Chapter 1.11.1 --- In vitro model (oxygen and glucose deprivation model) --- p.29 / Chapter 1.11.2 --- In vivo model (Middle cerebral artery occlusion) --- p.31 / Chapter 1.12 --- Traditional Chinese Medicine (TCM) --- p.32 / Chapter 1.12.1 --- General Introduction to Traditional Chinese Medicine --- p.32 / Chapter 1.12.2 --- TCM and cerebral stroke --- p.33 / Chapter 1.12.3 --- Chinese compound formula --- p.34 / Chapter 1.12.4 --- Introduction to individual herb --- p.34 / Chapter 1.12.4.1 --- Astragali Radix (Pinyin name: Huangqi) --- p.34 / Chapter 1.12.4.2 --- Rhizoma Chuanxiong (Pinyin name: Chuanxiong) --- p.35 / Chapter 1.12.4.3 --- Radix Salviae Miltorrhizae (Pinyin name: Danshen) --- p.35 / Chapter 1.12.4.4 --- Cassia Obtusifolia Linne (Pinyin name: Jue Ming Zi) --- p.36 / Chapter 1.12.4.5 --- Radix Glycyrrhizae (Pinyin name: Gancao) --- p.37 / Chapter 1.12.4.6 --- Radix Angelicae Sinensis (Pinyin name: Dongquai) --- p.37 / Chapter 1.12.4.7 --- Paeoniae Veitchii Radix (Pinyin name: Chi Shao) --- p.38 / Chapter 1.12.5 --- Salvianolic acid B --- p.39 / Chapter 1.13 --- Aim of study --- p.40 / Chapter Chapter 2 --- Materials and Methods --- p.41 / Chapter 2.1 --- Materials --- p.41 / Chapter 2.1.1 --- Drug --- p.41 / Chapter 2.1.1.1 --- Herbal Medicine --- p.41 / Chapter 2.1.1.2 --- Herbal extraction of PSR --- p.42 / Chapter 2.1.1.3 --- Herbal extraction of individual herb --- p.43 / Chapter 2.1.1.4 --- Salvianolic acid B --- p.43 / Chapter 2.1.2 --- Chemical --- p.44 / Chapter 2.1.3 --- Animal --- p.48 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- (AAPH)- induced erythrocyte hemolysis --- p.49 / Chapter 2.2.2 --- Cell Culture study --- p.51 / Chapter 2.2.2.1 --- Cell Line --- p.51 / Chapter 2.2.2.2 --- Cell differentiation --- p.52 / Chapter 2.2.2.3 --- In vitro model of ischemia - Oxygen glucose deprivation (OGD) experiment --- p.53 / Chapter 2.2.2.4 --- Cell viability assay --- p.54 / Chapter 2.2.3 --- In vivo Study --- p.54 / Chapter 2.2.3.1 --- Cerebral blood flow (CBF) measurement --- p.54 / Chapter 2.2.3.2 --- In vivo transient focal cerebral ischemia model - Middle cerebral artery occlusion (MCAo) --- p.55 / Chapter 2.2.3.3 --- Administration of PSR --- p.57 / Chapter 2.2.3.4 --- Administration of salvianolic acid B (SAB) --- p.59 / Chapter 2.2.3.5 --- Measurement of brain infarct volume --- p.60 / Chapter 2.2.3.6 --- In vivo anti-oxidative enzyme activity determination in the brain --- p.61 / Chapter 2.2.3.6.1 --- Brain tissue preparation --- p.61 / Chapter 2.2.3.6.2 --- Tissue homogenization and protein extraction --- p.61 / Chapter 2.2.3.6.3 --- Protein concentration determination --- p.63 / Chapter 2.2.3.6.4 --- Catalase activity determination in the brain --- p.63 / Chapter 2.2.3.6.5 --- Glutathione Peroxidase (GPx) activity determination in the brain --- p.64 / Chapter 2.2.3.6.6 --- The Superoxide Dismutase (SOD) activity determination in the brain --- p.65 / Chapter 2.2.3.7 --- Behavioral Evaluation --- p.66 / Chapter 2.2.3.7.1 --- Neurological behavioural test --- p.66 / Chapter 2.2.3.7.2 --- Shuttle box escape experiment --- p.67 / Chapter 2.3 --- Statistical analyses --- p.71 / Chapter Chapter 3 --- Results --- p.72 / Chapter 3.1 --- In vitro model of ischemia - Oxygen glucose and deprivation (OGD) experiment --- p.72 / Chapter 3.2 --- AAPH assay of PSR --- p.75 / Chapter 3.3 --- AAPH assay of individual herb --- p.77 / Chapter 3.4 --- Brain slices after middle cerebral artery occlusion (MCAo) experiment --- p.81 / Chapter 3.5 --- Brain infarct volume of single dose protocol --- p.83 / Chapter 3.6 --- Neurological behavioural test of single dose protocol --- p.85 / Chapter 3.7 --- Brain infarct volume of double doses protocol --- p.87 / Chapter 3.8 --- Neurological behavioural test of double doses protocol --- p.89 / Chapter 3.9 --- Determination of superoxide dismutase (SOD) activity in the brain --- p.91 / Chapter 3.10 --- Determination of glutathione peroxidase (GPx) activity in the brain --- p.93 / Chapter 3.11 --- Determination of catalase activity in the brain --- p.95 / Chapter 3.12 --- Brain infarction volume of Salvianolic acid B (SAB) treatment --- p.98 / Chapter 3.13 --- Neurological behavioural test of SAB treatment --- p.100 / Chapter 3.14 --- Shuttle box performance in training and testing series --- p.102 / Chapter 3.15 --- Change in shuttle box performance (% avoidance c.f. last day of training) in testing series --- p.104 / Chapter 3.16 --- Escape latency in testing and training series --- p.107 / Chapter 3.17 --- Change in escape latency (c.f. last day of training) in testing series --- p.109 / Chapter 3.18 --- Brain infarct volume of shuttle box escape experiment --- p.112 / Chapter 3.19 --- Neurological score in shuttle box escape experiment --- p.114 / Chapter Chapter 4 --- Discussion --- p.117 / Chapter 4.1 --- The protective effect of PSR in in vitro oxygen and glucose deprivation (OGD) on human neuroblastoma SH-SY5Y cell line --- p.117 / Chapter 4.1.1 --- OGD model and cell line --- p.117 / Chapter 4.1.2 --- Protective effect of PSR in OGD experiment --- p.118 / Chapter 4.1.3 --- Free radical scavenging property of PSR --- p.120 / Chapter 4.2 --- The protective effects of PSR in in vivo middle cerebral artery (MCAo) model --- p.121 / Chapter 4.2.1 --- The shortcomings of in vitro OGD model --- p.121 / Chapter 4.2.2 --- Development of in vivo MCAo model and TTC staining --- p.122 / Chapter 4.2.3 --- Protective effect of PSR in MCAo experiment (single dose protocol) --- p.124 / Chapter 4.2.4 --- Protective effect of PSR in MCAo experiment (double doses protocol) --- p.125 / Chapter 4.2.5 --- The effect of PSR toward neurological deficits --- p.127 / Chapter 4.2.6 --- Anti-oxidative effects of PSR in MCAo model --- p.128 / Chapter 4.3 --- The protective effects of SAB in in vivo middle cerebral artery (MCAo) model --- p.130 / Chapter 4.3.1 --- Free radical scavenging property of different herbs --- p.130 / Chapter 4.3.2 --- Selection of pure compound that used to treat stroke --- p.131 / Chapter 4.3.3 --- Protective effect of Salvianolic B in MCAo experiment --- p.132 / Chapter 4.3.4 --- The effect of SAB toward neurological deficits --- p.133 / Chapter 4.4 --- The effects of PSR and SAB on stroked rats' performance in shuttle box escape experiment --- p.134 / Chapter 4.4.1 --- Establishment of shuttle box escape experiment --- p.134 / Chapter 4.4.2 --- Effects of PSR and SAB on avoidance performance --- p.135 / Chapter 4.4.3 --- Effects of PSR and SAB on escape latency --- p.138 / Chapter 4.5 --- Assessment on the contribution of SAB to the protective effect of PSR --- p.140 / Chapter 4.6 --- Comparison of acute and chronic testing --- p.140 / Chapter 4.6.1 --- The protective effect of the drugs (Histopathological examination) --- p.140 / Chapter 4.6.2 --- The severity of motor deficit (Neurological score) --- p.141 / Chapter Chapter 5 --- Conclusion and Future prospect --- p.143 / Chapter 5.1 --- Conclusion --- p.143 / Chapter 5.2 --- Future prospect --- p.144 / References --- p.147

 As the aging in reproductive system proceeds, females will eventually enter the period of menopause, during which a series of physiological changes occurs. The decline of estrogen level during menopausal transition is thought to associate with various menopausal symptoms. Although hormone replacement therapy can be adopted to deal with the estrogen-deficient state, side effects such as cancer risk cannot be overlooked. Alternatively, Erxian Decoction (EXD), a Chinese medicine formula for treating menopausal symptoms has been used clinically for more than 60 years without adverse effects reported. Some pharmacological properties of EXD have been reported in previous research, which are thought to be contributed by its multiple bioactive components. Thus in the present study, the pharmacological properties of EXD have been further evaluated. The drug compatibility of Traditional Chinese Medicine (TCM) formula, EXD, was also demonstrated. At last, a novel approach for identification of bioactive components from Chinese medicine formula was introduced using EXD as study model. To evaluate the multiple pharmacological properties of EXD, proteins involved in steroidogenesis in ovaries of aged female rats were measured by immunoblotting analysis. On top of that, serum lipid profiles and the related proteins were determined by colorimetric assay and immunoblotting analysis respectively. Also, anti-osteoporotic properties and drug compatibility of EXD were evaluated by in vitro methods such as proliferation assay, osteoclast differentiation assay, ELISA assay or immunoblotting analysis. Lastly, a novel approach for identification of bioactive components in relation to the subsequent bioactivity from traditional Chinese medicinal formula was introduced using HPLC profiles. From the results, it was demonstrated that EXD can modulate steroidogenesis in aged female rat model at least through up-regulation of ovarian aromatase, protein kinase B and estrogen receptor beta at protein level. Besides, EXD also exerts antihyperlipidemic effects in aged female rats as reflected from the decreased serum total cholesterol and LDL-cholesterol levels via regulation of HMG CoA reductase and LDL-receptor, the key proteins for cholesterol synthesis and LDL-cholesterol clearance. In vitro study has also demonstrated the anti-osteoporotic properties of EXD through stimulation of osteoblast proliferation and inhibition of proliferation and differentiation of osteoclast precursor cells. The later was proved to be mediated by down-regulation of NFATc1 proteins, a key protein for osteoclastogenesis. The roles of the drugs categories according to the drug compatibility of traditional Chinese medicine contributing to the optimal anti-osteoporotic properties of EXD were also elucidated. Since the diverse pharmacological properties of a Chinese medicinal formula are often the results of the effects of complex bioactive constituents in the extract, yet identification of the bioactive components has been a tedious task. Thus in the last part of the study, a novel approach for identification of bioactive component from Chinese medicinal formula has been developed. By comparing the HPLC profiles of EXD extracted by different decoction method in relation to their pharmacological properties, six bioactive chemicals were successfully identified which may contribute to the stimulatory effect of EXD on ovarian aromatase and hepatic catalase expression. / published_or_final_version / Chinese Medicine / Master / Master of Philosophy

abstract / Chinese Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Orthopaedic Surgery / Master / Master of Philosophy