Le carcinome à cellules rénales claires métastatique (CCC) demeure résistant aux thérapies actuelles. Les travaux précédents ont montré des similitudes mécanistiques entre tumorigenèse et néphrogenèse. Parmi les cibles de la voie oncogénique Sonic Hedgehog-Gli, le facteur développemental Lim1 a été identifié comme un nouvel oncogène dans le CCC. Les études préliminaires suggèrent que Lim1 aurait un rôle dans l’invasion cellulaire. Aucun inhibiteur de Lim1 n’est disponible; l’ARN interférence reste l’outil le plus efficace et le plus spécifique pour l’extinction des gènes. Dans le but de développer un nouvel outil d’inhibition de Lim1 applicable en clinique, basée sur des siRNAs véhiculés par des systèmes nanométriques, une nouvelle génération de véhicules de siRNAs a été étudiée. Il s’agit de polymères diacétyléniques photo-polymérisables sous forme de nanofibres (PDA-Nf). Ces travaux démontrent le rôle invasif de Lim1 dans la dissémination métastatique et identifient les PDA-Nf comme un nouvel outil de délivrance de siRNAs très prometteur en clinique. L’avantage du ciblage de Lim1 avec cette approche, est l’absence de son expression à l’âge adulte. / Clear cell renal cell carcinoma (CCC) remains resistant to current therapies, despite the development of anti-angiogenic and the new immunotherapeutic approaches. Previous work of the laboratory has shown mechanistic similarities between tumorigenesis and nephrogenesis. Among the targets of the Sonic Hedgehog-Gli pathway which is found oncogenic in CCC, the developmental factor Lim1 has been identified as a new oncogene in CCC. Preliminary studies suggest that Lim1 would have a role in cell invasion. No Lim1 inhibitors are available; RNA interference remains the most effective and specific tool for gene silencing. In order to develop a new clinically applicable inhibition tool for Lim1, based on siRNAs carried by nanoparticles, a new generation of siRNA vehicles has been investigated. These are photo-polymerizable diacetylenic polymers in the form of nanofibers (PDA-Nf). These works demonstrate the invasive role of Lim1 in metastatic dissemination and identifies PDA-Nf as a new promising siRNA delivery tool in clinical practice. The advantage of targeting Lim1 with this nano-carrier approach is that Lim1 is not expressed in adulthood.

Field flow fractionation of particles in rotating coiled column has been investigated in recent year. In contrast to the classical mode of field flow fractionation in narrow channels, the use of rotating coiled columns offers the possibility of large sample loading. In this thesis, the potential for new cell separation methods based on the use of flow fractionation in fluctuating g-fields generated in rotating coil columns is examined. The effects of operational conditions (flow rate and rotational speed – Chapter 3 and Chapter 5); cell properties (cell flexibility – Chapter 4); and column shapes (different inner diameters and coil geometries – Chapter 6) on the flow behaviour of a model system of red blood cells (RBCs) from different species, which differ markedly in size, shape & density, flowing in a single phase of buffered saline have been characterised. Operational Conditions: For a particular rotational speed, there was a minimum flow rate which caused all the cells to be retained in the column and a maximum flow rate at which all cells were eluted. Both the minimum and maximum flow rate were increased when a higher rotational speed was applied. Differences in the behaviour of sheep & hen RBCs have been used to develop a separation method using a continuously increasing flow gradient. This separation could be speeded up by using a step flow gradient. The effects of cell load and rotational direction on the behaviour of RBCs in the column was also studied in this thesis. Cell Properties: The minimum flow rate was found to correlate with cell diameter/cell volume of the RBCs as expected for a sedimentation related process and was partially described by a theoretic equation developed for particles by Fedotov and colleagues (Fedotov et al. 2005). However cell dependent departures from this equation were found which appear to indicate that cell specific surface properties may also be involved for cells (Chapter 3). By contrast the maximum flow rate showed no correlation with cell diameter/cell volume. An effect of cell deformability on the flow separation behaviour of the cells has been demonstrated. Chemical fixation of sheep RBCs with glutaraldehyde rendered the normally deformable RBCs rigid and non-deformable and resulted in the fixed sheep RBCs eluting significantly earlier than unfixed sheep RBCs. This difference was great enough that a mixture of deformable (unfixed) and non-deformable (fixed) sheep RBCs could be separated. Fixed cells tended to show cell aggregation, which could be reduced by the addition of surfactant. Column Geometry: An effect of column shapes on the flow separation behaviour of cells has been demonstrated showing that the optimisation of column design is an important feature of this mode of cell separation. For columns with the same cross sectional area, a “horizontal” rectangular column provided better separation than a circular column and a “vertical” rectangular column gave the least efficient separation. A possible explanation for this behaviour is suggested the thinner sedimentation layer and less secondary flow. Differences in the behaviour of various species of RBCs in the “horizontal” rectangular column have been used to study the efficiency of separation of a mixture of sheep and hen RBCs, and a mixture of rabbit and hen RBCs. This work shows similarities and differences with other reports on cell/particle separations in rotating coiled columns in single phases and also in aqueous two phases systems (ATPS) and these are discussed. Fedotov P.S., Kronrod V.A. & Kasatonova O.N. (2005). Simulation of the motion of solid particles in the carries liquid flow in a rotating coiled column. J. Anal. Chem., 60, 4, 310-316.

In this thesis we study the regional and global linkages as evidence of markets integration of the stock markets in Frankfurt, Amsterdam, Prague the U.S. and the dynamics of volatility transmission of related foreign exchange rates using multivariate GARCH approach. For each of the model classes, a theoretical review, basic properties and estimation procedure are provided. We illustrate approach by applying the models to daily market data. Our two main aims are discussing and report the existence of regional and global stock markets linkages and provide comparison of such multivariate GARCH models on the data sample. We find out that the estimated time-varying conditional correlations indicate limited integration among the markets which implies that investors can benefit from the risk reduction by investigating in the different stock markets especially during the crisis.

In this paper, the development and control of a switched reluctance motor (SRM) applied to the intelligent electric vehicle are presented. In the SRM control policy, speed control and constant torque/constant power control are implemented with modified PI(RISC) control and a chopped current control(CCC). The control policy can restrain torque ripple effectively, and the vibration and acoustic noise are reduced involuntarily. Simultaneously, The speed response to sudden load change becomes less dramatic. Simulate results suggest that modified PI is more powerful than fuzzy control and PI. In the experiment, this paper compares the advantages and disadvantages of PI, fuzzy control and modified PI under no load, fixed load and unfixed load condition. Finally, a Digital Signal Processor(DSP)is adopted to verify the accuracy of simulation, which contributes to the planning of the program composition flow.

This thesis consists of three studies that cover topics in inflation and output growth, and their uncertainties in G7 and developing countries. We utilise the Consumer Price Index (CPI) and Industrial Price Index (IPI) as proxies for the inflation rate (price level) and the growth rate (output), respectively. Chapter 2 considers the case of three developing countries Turkey, Egypt and Syria. We analyse the inflation and growth using asymmetric PGARCH model. In accordance with this, we estimate all the models using two alternative distributions the normal and Student’s t. Moreover, dummy variables are chosen in the inflation data according to some economic events in Turkey, Egypt and Syria. Even more, the mean equation is adjusted to include these dummy variables on the intercept. To summarize, the results show an evidence of the Cukierman–Meltzer (1986) hypothesis, which is labelled as the ‘opportunistic Fed’ by Grier and Perry (1998), in Egypt and Syria. On the other hand, an evidence of the Holland (1995) hypothesis is obtained in Turkey, this result suggests that the ‘stabilizing Fed’ notion is plausible. Moreover, an evidence for the first leg of Friedman (1977) hypothesis is obtained in Egypt and Turkey. Chapter 3 examines the causal relationship between inflation and output growth, and their variabilities for G7 countries by applying the bivariate constant conditional correlation CCC – GARCH (1,1)-ML models. Moreover, we employ the models including dummy variables in the mean equations to investigate the impact of economic events on inflation and output. Briefly, there are evidences of the second leg of Friedman (1977) hypothesis in the US, UK, Germany, Italy, France and Canada while there is an evidence of Dotsey and Sarte (2000) in Japan. In addition, there are evidences for positive effect of inflation uncertainty on inflation in the US, Germany, Japan and France in line of Cukierman and Meltzer (1986) hypothesis. Moreover, the results of estimation CCC-GARCH (1,1) in mean models including dummy variables highlight a strong support for the two legs of Friedman (1977) hypothesis and Cukierman and Meltzer (1986). Lastly, Chapter 4 is based on examining the inflation rates for three developing countries Turkey, Syria and Egypt by applying the Bai and Perron (2003) breakpoint specification technique in the monthly inflation data of our sample. As a result, three possible break points for each of the inflation rates in the conditional variance have been determined. In addition, we employ GARCH model to control the breaks in the conditional mean and variance equations. To conclude, the autoregressive coefficients seem to cause a statistically significant impact on the breaks only in the case of Turkey, also, the parameters of the mean equation show time varying characteristics across three breaks. As far as the conditional variance is concerned the ARCH parameter (?) shows no time varying behaviour while for the GARCH parameter only one significant break seems to impact the inflation rate in Syria.

Physical, chemical and corrosion properties of a hexavalent chromium conversion coating (CCC) and that of a commercial third generation trivalent chromium system; Tripass LT1500, on zinc electrodeposited steel has been studied. Moreover, the role of additives has been studied to elucidate film formation and corrosion resistance mechanisms. Micro-cracking and self-repair corrosion protection behaviour commonly associated with hexavalent CCCs has also been investigated. Scanning Electron Microscopy (SEM) studies showed that for both hexavalent and trivalent CCCs were in general, flat with a spherical-like structure and in the case of the former microcracked beyond 122 nm conversion coating thickness. In general, the micro-crack pattern observed e.g. a dense crack network, depended upon the underlying zinc substrate morphology. The study has also demonstrated the effect of SEM imaging and prior specimen preparation conditions on hexavalent CCC micro-cracking and blistering. X-ray Photoelectron Spectroscopy (XPS), Auger Electron Spectroscopy (AES) and Infrared (IR) data has indicated that the hexavalent CCC film formation appears to be a electrochemical/sol-gel mechanism given the lack of zinc content at surface and subsurface regions within the conversion coating, presence of H2O and in particular the contribution of Cr(OH)3 as opposed to Cr2O3. An alternative film formation mechanism may exist for trivalent CCC given a higher proportion of zinc at surface and sub-surface regions, IR data analysis indicating that chromium is possibly deposited from a chromium (III) complex ion such as [CrC2O4(H2O)4] + , moreover as Cr(OH)3 and Cr2O3 compounds as indicated by XPS data analysis. The role of cobalt nitrate during film formation is unclear given that cobalt was not detected within the trivalent CCC from XPS and AES data. Electrochemical LPR measurements, polarisation curves and XPS data has shown in general, self-repair corrosion protection properties for hexavalent CCC to be lacking. Instead, it is proposed that the corrosion protection behaviour for hexavalent and trivalent CCC to be barrier. Polarisation curves and LPR data showed that the corrosion resistance performance for trivalent CCC was higher than hexavalent CCC, in general. LPR data showed that the omission of cobalt nitrate and increased addition of sodium molybdate content within the Tripass LT1500 treatment solution formulation was found to overall decrease corrosion resistance within the trivalent CCC. In addition, silica based topcoat and black trivalent CCCs was also investigated and characterised using AES, SEM and LPR. Zinc whiskers was also observed from zinc electrodeposits following exposure to thermal treatment (150°C for 1 h). Elemental analysis and grain pattern investigations failed to help determine the cause of zinc whisker initiation. Zinc whiskers was seen to protrude out of hexavalent and trivalent CCCs, with the latter requiring a longer thermal exposure time.

Countercurrent chromatography (CCC) is an advanced liquid-liquid extraction technique that purifies chemical components from complex mixtures. The Brunel CCC' is a J-type centrifuge based upon this technique. This machine can process 5g quantities of sample every 5 hours [Sutherland 1998]. To process 1 tonne of sample per year would require 200 Brunel CCCs, which is not practical as an industrial process. A practical alternative is to use one machine with 200 times the processing capability. To construct such a machine requires a greater understanding of the stationary phase retention inside a coil (column) and the column efficiency (mass transfer between the mobile and stationary phases). This thesis contains research into stationary phase retention. A hypothesis that all J-type centrifuges act as constant pressure drop pumps is proposed. This hypothesis combined with the Hagan-Poiseuille equation for laminar flow produces a theoretical basis for plotting the stationary phase retention against the square root of the mobile phase flow rate as proposed by Du et al [1999]. Supporting experimental evidence is presented showing that the mobile phase flows in a laminar manner and that the pressure drop across a coil is constant for a given set of operating conditions. It is shown that the pressure drop is the same in both normal and reverse phase modes if specific conditions are met. The pressure drop is shown to be independent of tubing bore for helical coils provided that the same helical pitch is used. The experimental results also show how the pressure drop varies with the phase system and rotational speed. Hopefully this is a significant advance in predicting the stationary phase retention of industrial scale J-type centrifuges.

This thesis analyses, derives and evaluates specification tests of Generalized Auto-Regressive Conditional Heteroskedasticity (GARCH) regression models, both univariate and multivariate. Of particular interest, in the first half of the thesis, is the derivation of robust test procedures designed to assess the Constant Conditional Correlation (CCC) assumption often employed in multivariate GARCH (MGARCH) models. New asymptotically valid conditional moment tests are proposed which are simple to construct, easily implementable following the full or partial Quasi Maximum Likelihood (QML) estimation and which are robust to non-normality. In doing so, a non-normality robust version of the Tse's (2000) LM test is provided. In addition, a new and easily programmable expressions of the expected Hessian matrix associated with the QMLE is obtained. The finite sample performances of these tests are investigated in an extensive Monte Carlo study, programmed in GAUSS.In the second half of the thesis, attention is devoted to nonparametric testing of GARCH regression models. First simultaneous consistent nonparametric tests of the conditional mean and conditional variance structure of univariate GARCH models are considered. The approach is developed from the Integrated Generalized Spectral (IGS) and Projected Integrated Conditional Moment (PICM) procedures proposed recently by Escanciano (2008 and 2009, respectively) for time series models. Extending Escanciano (2008), a new and simple wild bootstrap procedure is proposed to implement these tests. A Monte Carlo study compares the performance of these nonparametric tests and four parametric tests of nonlinearity and/or asymmetry under a wide range of alternatives. Although the proposed bootstrap scheme does not strictly satisfy the asymptotic requirements, the simulation results demonstrate its ability to control the size extremely well and therefore the power comparison seems justified. Furthermore, this suggests there may exist weaker conditions under which the tests are implementable. The simulation exercise also presents the new evidence of the effect of conditional mean misspecification on various parametric tests of conditional variance. The testing procedures are also illustrated with the help of the S&P 500 data. Finally the PICM and IGS approaches are extended to the MGARCH case. The procedure is illustrated with the help of a bivariate CCC-GARCH model, but can be generalized to other MGARCH specifications. Simulation exercise shows that these tests have satisfactory size and are robust to non-normality. The marginal mean and variance tests have excellent power; however the covariance marginal tests lack power for some alternatives.

The goal of this thesis is three-fold: to examine complementation in Balinese from typological, syntactic, and cognitive perspectives. This thesis contributes to typological studies of complementation by providing a descriptive account of the distinguishing syntactic properties of four types of Balinese clausal complements: sentence-like (s-like), Subject Control (SC), Object Control (OC), and Raising complements. The data presented in this thesis demonstrate the clausal complement in Balinese can be differentiated through the kinds of elements that can be admitted within the complements: the type of complementizer, aspectual auxiliaries, modals, temporal specifications, and overt subjects. The theoretical aspect of this thesis is the application of Minimalist theory to account for the syntactic structure of Balinese monoclausal and biclausal constructions. This thesis also addresses a theoretical problem related to the syntactic structure of complementation within Generative syntax: finiteness. The presence of modals, aspectual auxiliaries, and the temporal specification of the complement do not signify finiteness in Balinese. Instead, finiteness in Balinese is marked by the licensing of overt subjects in the clausal complement, following the argument made by Kurniawan & Davies (2015), based on the evidence provided through the comparison of control complements and their subjunctive sentence-like complement counterparts. The cognitive processing of Balinese complementation is investigated through two sentence processing experiments with the goals of understanding how ambiguous Crossed Control Construction (CCC) sentences are processed in comparison to the processing of unambiguous Subject Control (SC) sentences and Raising sentences. The self-paced reading experiment focuses on the comparison of reading times for the verbs in these three types of sentences when the animacy of the subject is manipulated (i.e. animate or inanimate clause-initial DP). The results suggest that CCC sentences are processed differently than the SC and Raising sentences. The second experiment aims at investigating the effect of discourse context on the interpretation of the ambiguous CCC sentences. The results show the influence of context that primes subject control interpretation on the processing of Balinese SC and CC sentences.

During the New Deal, the Civilian Conservation Corps (CCC) put young men to work in state and national parks across the United States. One of such parks, Big Bend National Park, is the focus of this study. The CCC had two camps within the park, one from 1934 to 1937 and another from 1940 to 1942. During their time in Big Bend, the CCC constructed many projects including a road, trails, cabins, and other various structures. The purpose of this study is to delineate the role of the CCC in creating Big Bend National Park and the experience of the CCC during their time in the Big Bend camp. This study determines the role of the CCC through a discussion of the planning done by the CCC for Big Bend National Park and the work completed by the CCC in the park. In doing so, it argues that the CCC played a substantial and significant role in the development and character of the park. This study works to understand the experience of the CCC in Big Bend through a discussion of education, safety, and an investigation of a commanding officer. Through this discussion, the role of the federal government and national organization in the local camps can be seen, as can the value they placed in the enrollees.