La concurrence des normativités :le cas des régulations bancaires La crise financière mondiale de 2007 a conduit à un regain d’intérêt pour la question de la régulation mondiale de la finance et des banques. Cette crise a, en effet, mis en lumière les interdépendances d’un système devenu mondial au vu, d’une part, de l’internationalisation des établissements financiers (ouverture de filiales, branches à l’étranger ou joint-venture avec un établissement étranger), et d’autre part, du flux important de transactions transfrontalières. Par ces interdépendances, des prêts consentis à des personnes peu solvables aux Etats-Unis ont été à la source d’une crise mondiale. Ces interdépendances et les risques « mondiaux » qu’elles suscitent pose le problème de la régulation globale des banques et de la finance en l’absence d’un gouvernement mondial et d’un régulateur mondial. L’intuition du juriste serait sans doute de penser que cette question fut résolue par le biais de solutions de droit international public. Cependant, notre thèse démontrera que ce problème d’échelle fut dépassé au moyen d’une extension du domaine d’action des autorités de surveillance à travers laquelle celles-ci ont peu à peu investi le champ de la création, de la mise en œuvre et du respect des normes utilisées à des fins de stabilité et ont progressivement interféré avec les systèmes juridiques qui leur étaient préexistants. En d’autres termes, la question de la mondialisation du secteur bancaire et de la stabilité de celui-ci ne pose pas au droit qu’une difficulté d’échelle mais est également de nature à transformer le droit en profondeur. / Doctorat en Sciences juridiques / info:eu-repo/semantics/nonPublished

Abstract I studied the ecology of the goshawk-grouse relationship in Oulu, northern Finland, during and outside the breeding season, by radio-telemetry. This included museum samples of goshawk to obtain a better ecological as well as a better evolutionary understanding of it. The proportion of grouse in the diet of goshawks has decreased since the 1960's, in accordance with the decline of grouse populations. The main prey groups replacing the lacking grouse were corvids, squirrels and hares. The proportion of grouse was highest in spring and it decreased towards the end of the nestling phase. The most preferred grouse species were hazel grouse Bonasa bonasia and willow grouse Lagopus lagopus. Preferences for different prey types are not explained by active choices of goshawk, but by changes in the vulnerability of the prey species. The nestling phase, when food demand is highest, is not adjusted to when prey supply is highest, but before it. The size and shape of the goshawks has changed from the 1960's. Adult males became smaller but females larger. Both became relatively longer winged and tailed. Decrease of male's size may be a response to the change in the food supply. Prey types replacing grouse are generally smaller, which may cause the change in the male's morphology. Females being less active during the breeding season may not be affected. For the female to be larger is advantageous in winter when they kill 'over large' prey like mountain hares Lepus timidus and capercaillie cocks Tetrao urogallus. Wintering goshawks were mainly females in adult plumage that tended to stay in the study area. However, only one third bred locally. More than one quarter of all hawks died during the study. Although known to be inhabitants of old forests, which this study supports, goshawks are fairly well adapted to mosaic landscape resulting from modern forestry, providing that suitable sized prey is available. Females have less problems, probably because hares, the main winter prey for females, are not affected negatively by forestry, like grouse and squirrels are, the main prey for males. Goshawks have a remarkable impact on grouse populations, especially when non-territorial hawks, 'floaters' are also included. About one half of the total mortality rate of grouse may be due to goshawk predation. Goshawk predation accords to predictions of general predation theory and may be a noticeable factor contributing to cyclicity in grouse.

Abstract Healthy subjects show wide interindividual variation in their heart rate behavior, but the factors affecting heart rate dynamics are not well known. This research was undertaken to evaluate heart rate variability (HRV) and baroreflex sensitivity (BRS) in a large random sample of subjects without evidence of heart disease, and to estimate the relation of heart rate behavior to age, sex and cardiovascular risk factors. Short-term HRV was analyzed from 15-minute periods of standardized recording in supine and upright positions using time and frequency domain measures, and BRS was calculated using the Valsalva maneuver in an original randomly selected population of 600 hypertensive and 600 control middle-aged subjects. In addition, HRV was analyzed from the same segments using new measures based on fractals and complexity (chaos theory) of R - R interval dynamics in the same random population, and from 24-hour period in 114 healthy subjects aged from 1 to 82 years. Large interindividual variation was observed in the measures of HRV and BRS in middle-aged subjects; coefficient of variation (CV) of the standard deviation of R - R intervals (SDNN) 39% (54 ± 21 ms) and CV of BRS 49% (9.9 ± 4.9 ms/mmHg). In healthy middle-aged men, SDNN was weakly related to age (r = -0.19, p < 0.01), HDL cholesterol (0.19, p < 0.01), serum insulin (-0.23, p < 0.001) and triglyceride (-0.25, p < 0.001) levels. In women, SDNN was only related to insulin levels (r = -0.23, p < 0.001). BRS was related to systolic blood pressure (r = -0.31 and -0.30, in men and women respectively, p < 0.001 for both) and blood glucose (r = -0.25, p < 0.01) and serum insulin levels (r = -0.34, p < 0.001) in women. Lesser intersubject variation was observed in the non-linear measures of HRV; CV 14% of short-term scaling exponent (a1), a measure of fractal-like correlation properties of HRV, (1.21 ± 0.17) and CV 12% of approximate entropy, a measure of complexity, (1.13 ± 0.14). Neither a1 or ApEn was related to any risk factors. Women had lower overall short-term HRV (p < 0.01) and BRS (p < 0.001), but a higher spectral high-frequency component of HRV, higher ApEn and lower a1 (p < 0.001 for all) compared to men. The impairment in overall HRV was confined to the hypertensive subjects with metabolic features of the insulin resistance syndrome (IRS, n = 69), but the BRS and spectral high-frequency component were also impaired in hypertensive subjects without IRS compared to normotensive subjects. The 24-hour cardiac interbeat interval dynamics changed markedly from childhood to old age. Children showed similar complexity and fractal correlation properties of R - R intervals as young adults. Healthy aging resulted in R - R interval dynamics with higher regularity and predictability and altered fractal scaling. The traditional measures of HRV and BRS are weakly related to many cardiovascular risk factors in subjects without heart disease, but the interindividual variation of HRV and BRS is only partly explained by these factors, suggesting a genetic background of the intersubject variation in cardiovascular autonomic regulation. The new dynamical measures of HRV show less interindividual variation than the conventional measures of HRV in healthy subjects and are not related to cardiovascular risk variables, suggesting that these dynamical measures quantify the "intrinsic" capacity of a healthy cardiovascular control system without the significant influence of life-style, metabolic or demographic variables. However, there are sex and age-related differences also in the fractal and complexity measures of heart rate behavior.

No description available.

No description available.

The low affinity IgE receptor, CD23, is expressed by a wide variety of cells and cleaved from its original 45 kDa size to several smaller soluble CD23 proteins. Soluble CD23 function depends on the form of the protein and its interaction with various ligands. CD23 is believed to play an important role in regulating allergic responses and in inflammation, amongst others. β2 integrins are important in a variety of cell-adhesion reactions during immune-inflammatory mechanisms and the binding of their natural ligands generates outside-in cellular signalling, leading to cell activation. Although the binding of CD23 to β2 integrins contributes to this signalling in monocytes, the interaction site for CD23 is unknown. This study focused on the interaction of three soluble CD23 proteins with the β2 integrins CD11b/CD18 and CD11c/CD18. Differentiated HL60, THP1 and U937 monocytic cells were used to demonstrate the binding of three recombinant CD23 constructs (corresponding to 16, 25 and 33 kDa human soluble CD23) to upregulated CD11b/CD18 and CD11c/CD18. This binding was partially blocked by an antibody specific for the CD11b/CD18 αI domain, demonstrating that αI domains are involved in binding to CD23. Recombinant αI domain proteins of CD11b and CD11c were demonstrated to bind CD23 using ELISA and in surface plasmon resonance spectroscopy. The dissociation constants for CD23-CD11b/CD18 and CD23-CD11c/CD18 are comparable to other integrin ligands. This study has shown that CD23 interacts directly with the αI domains of β2 integrins and that the interaction surface likely spans the lectin domain as well as either the stalk and/or C-terminal tail of CD23. This study also looked at the effect that soluble CD23 proteins had on monocyte biology. It appears that iv sCD23 proteins have little effect on the phagocytic or chemotactic ability of monocytes, while an increase in oxidative burst was shown with the 16 kDa and 25 kDa CD23 proteins. Signalling pathways for the production of reactive oxygen species were investigated and it appears that the CD23 proteins signal mainly through the phosphoinositide-3 kinase pathway, although the mitogen activated protein kinase and Src kinase pathways may also play a role. These data suggest that sCD23 proteins induce outside-in signalling of β2 integrins and are able to change the activation state of CD11b/CD11c by stimulating oxidative burst. This needs to be further investigated by determining how the three sCD23 proteins are binding the CD11 proteins and investigating further leukocyte function and inflammatory responses by the cells.

Both CD23 and the β2 integrins (also known as CD11/CD18) have very important immunological functions, especially during the allergic response where the binding of CD23 to β2 integrins contributes to various types of signalling in monocytes which can result in drastic sensitivities experienced by some allergic individuals. CD23, also known as the low affinity receptor for immunoglobulin E or (FcεRII), is a type II transmembrane glycoprotein which is synthesized by haematopoietic cells and has biological activity in both membrane-bound and freely soluble forms. It acts via a number of receptors, including the β2 integrins. β2 integrins are specifically found on leukocytes and they play important roles in cell–cell or cell–matrix adhesion via their ability to bind multiple ligands. These molecules occur as heterodimers consisting of an alpha (α) and beta (β) subunit. The α-subunits of β2 integrins contain an approximately 200-amino-acid inserted domain or I-domain which is implicated in ligand binding function. There are four different types of β2 integrins, namely CD11a, CD11b, CD11c and CD11d, all dimers with the common beta subunit, CD18. CD23 and CD11/18 are natural ligands of each other; however the interaction site for CD23 is unknown. It is postulated that the integrin recognizes a tripeptide motif in a small disulfide-bonded loop at the N-terminus of the lectin head region of CD23, which is focussed around Arg172, Lys173 and Cys174 (RKC). This study thus focused on the interaction between the I-domain of CD11 (b and c) and a recombinant 25kDa construct of sCD23. In order to understand the characteristics of ligand binding between the relevant proteins of interest, alanine substitutions on the RKC motif of CD23 were made via site-directed mutagenesis. Consequently, a recombinant form of the I-domain of CD11 (b and c) as well as a wild type (containing the RKC motif) and mutant form (containing an AAC motif) of sCD23 were expressed and purified. The CD11 recombinant proteins were purified via affinity chromatography and the CD23 recombinant proteins via gel filtration chromatography. In addition, synthetic (CD23 derived) peptides, one containing the RKC sequence and the other the AAC sequence, were designed and custom synthesized. The synthetic peptides as well as the recombinant CD23 proteins were then analyzed for their interaction with the CD11 I-domain via ELISA. Subsequent ELISA analyses showed that the native sCD23 and the RKC peptide were able to bind to the integrin α I-domain whereas the mutant sCD23 and the corresponding synthetic AAC peptide failed to bind. This interaction was also analysed via flow cytometry using differentiated U937 cells, yielding similar results. ELISA analyses for the sCD23-CD11b I-domain interaction showed a Kd of 0.36 ± 0.14 μM whereas the RKC-CD11b I-domain interaction yielded a Kd of 1.75 ± 0.58 μM. Similarly, the sCD23-CD11c I-domain interaction yielded a Kd of 0.39 ± 0.09 μM and 1.53 ± 0.72 μM for the RKC-CD11c I-domain interaction. Peptide inhibitory analysis, analysed via ELISA and flow cytometry, reinforced the fact that the RKC motif on sCD23 is a prerequisite for ligand binding of the CD11b/c I-domain.

Despite our understanding of the role of the survival motor neuron protein (SMN) in cytoplasmic small ribonucleoproteins (snRNP) assembly, it is unclear how loss of this protein causes motor neuron degeneration in Spinal Muscular Atrophy (SMA). It could be explained by defects in functions that are specific to tissues most affected in SMA. In neurons, SMN localizes to neuronal RNA granules, RNA-containing foci in axons. They regulate many aspects of mRNA fate which include transport along neurites, mRNA stability, and mRNA translation. Most recently, our work provided evidence for SMN’s role in mRNA translation. Specifically, we demonstrated that SMN associates with polyribosomes and may repress translation of specific mRNA targets. Our group demonstrated that SMA-causing mutations within the Tudor domain of SMN completely abolished this activity. This indicates the potential significance of this novel SMN function in the SMA pathology. To further investigate SMN’s function in regulating translation, our group performed a proteomic screen on polysome-containing sucrose gradient fractions. We identified and validated novel interacting partners for SMN that may act as co-factors to regulate translation. DDX5 (an RNA helicase) is an unexpected novel interacting partner as it is known for its role in micro-RNA processing. Moreover, we observe that FMRP, a recognized protein in translational complexes, is required for the presence of SMN and DDX5 in polysomal fractions. With these latest findings, we updated our model of the molecular mechanism by which SMN regulates translation. This work provides more insights on how SMN regulates translation, a newly uncovered role for SMN in motor neurons. Identification of the molecular targets that are misregulated due to loss of this function may reveal new information on the pathogenesis of SMA.

The thesis presents an analysis of the influence of the international tin agreements (ITA) on the world tin industry between 1956 to 1985. The ITAs, the first of which came into effect in 1956, were jointly operated by tin producing and consuming countries. The International Tin Council (ITC) used a buffer stock and export controls to maintain the price of tin within a band. This experiment in stabilizing tin prices ended in October 1985, when the ITC was unable to continue its operations because it ran out of financial resources. The study first analyzes the market structure of the world tin industry in some detail. Then an econometric model which attempts to capture the behaviour of supply, demand and price of tin over the 30 year period is constructed. Particular attention was paid to the estimation of the tin production functions for major tin producing countries. In many of these countries, the output of the tin depended not only on the price of tin but also on the policies of the ITC as well as the internal political environment of the country. The model is then used to simulate a scenario in which the ITC does not intervene in the tin market. The differences in the price and revenue levels between the actual and simulated scenario are computed. The simulation results show that the tin agreements succeeded in their objective of reducing the variability of price and producers' revenue. In addition, the average level of price and revenues under the ITC regime was higher than under the non-intervention scenario. In evaluating policy options, it was shown that the establishment of a cartel is not viable in the long term for both economic and political reasons. The recommended policy options include improving access to futures markets, providing better transparency of tin market operations, the establishment of government policies which provide better incentives for tin mining and tin using industries in the major tin producing countries and continued efforts in research and development with the aim of lowering costs of production and increasing the uses for tin. / Business, Sauder School of / Graduate

The focus of this dissertation is upon the role of economic relations in the international legal system, with special emphasis on the newly established World Trade Organisation (Hereinafter, WTO) and its implications for developing countries. This organisation has replaced the General Agreement on Tariffs and Trade (Hereinafter, GATT) as the overall mechanism for regulating international trade. The trade policies of the WTO will be assessed in the light of how they affect developing countries in global trade. Issues of importance to be reviewed include the aims and principles of the WTO, factors leading to its institutionalisation and the improvements it makes upon the GATT, with due regard to the manner in which its laws affect the relationship between developed countries and developing ones in multilateral trade.