La mutation F508del dans la protéine CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) est considérée comme un facteur de risque indépendant de maladie osseuse liée à la mucoviscidose. Nous avons évalué la densité minérale osseuse et les paramètres histomorphométriques de la formation osseuse et la masse osseuse chez des souris homozygotes F508del-CFTR (F508del) et contrôle(WT), de la même portée, âgées de 6 semaines (pré-pubères), 10 semaines (pubères) et 14 semaines (jeunes adultes), dans deux sexes. L'architecture osseuse des souris F508del et WT a été évaluée par densitométrie osseuse, micro-CT et l'analyse des paramètres dynamiques de la formation osseuse a été réalisée par double marquage, in vivo. Les niveaux de sérum de l'insuline-like growth factor 1 (IGF-1) et l'ostéocalcine ont également été déterminés. Une diminution de la densité minérale osseuse, de la masse osseuse et une altération de l'architecture osseuse trabéculaire fémorale ont été observées chez les souris F508del par rapport aux témoins à 6, 10 et 14 semaines. Une diminution du taux de formation osseuse dans F508del été mise en évidence, par rapport aux souris témoins, indépendamment de l'âge et du sexe. En outre, nous avons observé un taux sérique d'IGF-1 plus faibles chez la souris F508del par rapport aux souris WT tandis que le taux sérique d'ostéocalcine est normal. Nos résultats démontrent que la mutation F508del-CFTR affecte la masse osseuse trabéculaire en réduisant la formation osseuse.Le N-butyldeoxynojyrimicin (NB-DNJ, le miglustat [Zavesca], les Laboratoires Actelion, Suisse) est un médicament approuvé pour le traitement de la pathologie osseuse de la maladie de Gaucher de type I. Il a été montré que le miglustat normalise le transport des ions sodiques et chlorures dépendant de la protéine CFTR au niveau de la muqueuse nasale des souris F508del. La microarchitecture osseuse de la souris F508del par rapport à son contrôle a été évaluée après l'administration du miglustat à une dose de 120 mg / kg / jour par gavage pendant 28 jours. Les niveaux de sérum IGF-1 et 17β-estradiol (E2) ont également été déterminés. Le traitement, de 4 semaines, avec le miglustat, normalise le volume osseux trabéculaire des vertèbres lombaires de la souris F508del. Cette augmentation du volume osseux est associée à une augmentation du taux de formation osseuse et une augmentation sérique de E2, mais pas au taux sérique d'IGF-1 chez la souris F508del traitées par rapport aux souris non traitées F508del.Nos données montrent clairement que l'administration orale de miglustat normalise la masse osseuse par une augmentation de la formation osseuse chez des souris F508del. Ces résultats appuient fortement le potentiel thérapeutique du miglustat chez les patients atteints de la maladie osseuse associée à la mucoviscidose. / The F508del mutation in the cystic fibrosis transmembrane conductance regulator (Cftr) gene is believed to be an independent risk factor for cystic fibrosis-related bone disease.We evaluated the bone mineral density and histomorphometric parameters of bone formation and bone mass in F508del-CFTR homozygous mice (F508del) and littermate (WT) controls at 6 (prepubertal), 10 (pubertal) and 14 (young adult) weeks of age in two genders. The bone architecture of F508del and WT mice was evaluated by bone densitometry, micro-CT and analysis of dynamic parameters of bone formation. Levels of serum insulin-like growth factor 1 (IGF-1) and osteocalcin were also determined. Reduced bone mineral density, lower femoral bone mass and altered trabecular bone architecture were observed in F508del compared to controls at 6, 10, and 14 weeks of age. A decrease in bone formation rate in F508del was evidenced compared to control mice, independently of age and sex. Additionally, we found lower IGF-1 levels in F508del mice compared to WT mice whereas osteocalcin level was normal. Our findings demonstrate that the F508del mutation in CFTR impacts trabecular bone mass by reducing bone formation.N-butyldeoxynojyrimicin (NB-DNJ, miglustat [Zavesca], Laboratoires Actelion, Suisse) an approved drug for treating bone pathology in type I Gaucher disease, was reported to normalizes sodium and Cftr-dependent chloride transport in nasal mucosa of F508del cystic fibrosis mice. The bone microarchitecture of F508del mice relative to WT littermates was evaluated after an administration of 120 mg/kg/day miglustat by oral gavage for 28 days. Levels of serum IGF-1 and 17β-estradiol (E2) were also determined. Once-day treatments with miglustat, over 4 weeks, normalized trabecular bone volume of the lumbar spine in F508del mice. This increase of bone volume was related to both an increased rate of bone formation and increased serum E2 level but not IGF-1 level in miglustat-treated F508del mice compared to untreated F508del mice.Our data provides clear evidence that oral administration of miglustat normalizes bone mass by increasing bone formation in F508del mice; these findings strongly support the therapeutic potential of miglustat in patients with cystic fibrosis related bone disease.Key words : cystic fibrosis, bone disease, miglustat

In the railway industry, and premium luxury and super sports sectors of the automotive industry, traditional cast iron brake discs are gradually being replaced with advanced composites such as carbon fibre reinforced carbon silicon carbide (Cf/C-SiC). These materials offer the ability to operate at higher temperatures, whilst displaying improved friction performance, and vastly reduced wear rates. Their primary benefit comes from being approximately one third of the density of the incumbent material used in the industry, grey cast iron (GCI), a cast iron with a high proportion of graphite flakes formed during solidification. This reduced density means that brake discs manufactured from Cf/C-SiC materials are a highly suitable proposition for a future automotive market, where weight saving in an attempt to meet ever restrictive CO2 emissions is a must. The understanding surrounding the friction mechanisms involved with these new materials has been lacking, until recently, with the majority of the international research focused on the manufacturing methods. Research has shown that friction performance, particularly bedding friction, is highly dependent on the successful formation of a friction transfer film (FTF) at the surface of any disc, comprised from wear debris from both the disc and pad. Prior research carried out at Loughborough University has identified that Cf/C-SiC materials do not readily form such a layer, as might be seen on a GCI equivalent, due to the intrinsically heterogeneous nature of the composite material.

With the dramatic growth of the Internet, it is much easier for us to acquire information than before. It is, however, relatively difficult to extract desired information through the huge information pool. One method is to rely on the search engines by analyzing the queried keywords to locate the relevant information. The other one is to recommend users what they may be interested in via recommender systems that analyze the users¡¦ past preferences or other users with similar interests to lessen our information processing loadings. Typical recommendation techniques are classified into content-based filtering technique and collaborative filtering (CF) technique. Several research works in literature have indicated that the performance of collaborative filtering is superior to that of content-based filtering in that it is subject to neither the content format nor users¡¦ past experiences. The collaborative filtering technique, however, has its own limitation of the sparsity problem. To relieve such a problem, researchers proposed several CF-typed variants, including item-based CF and trust-based CF. Few works in literature, however, focus on their performance comparison. The objective of this research is thus to evaluate both approaches under different settings such as the sparsity degrees, data scales, and number of neighbors to make recommendations. We conducted two experiments to examine their performance. The results show that trust-based CF is generally better than item-based CF in sparsity problem. Their difference, however, becomes insignificant with the sparsity decreasing. In addition, the computational time for trust-based CF increases more quickly than that for item-based CF, even though both exhibit exponential growths. Finally, the optimal number of nearest neighbors in both approaches does not heavily depend on the data scale but displays steady robustness.

With the rapid growth of Internet, more and more information is disseminated in the World Wide Web. It is therefore not an easy task to acquire desired information from the Web environment due to the information overload problem. To overcome this difficulty, two major methods, information retrieval and information filtering, arise. Recommender systems that employ information filtering techniques also emerge when the users¡¦ requirements are too vague in mind to express explicitly as keywords. Collaborative filtering (CF) refers to compare novel information with common interests shared by a group of people for recommendation purpose. But CF has major problem: sparsity. This problem refers to the situation that the coverage of ratings appears very sparse. With few data available, the user similarity employed in CF becomes unstable and thus unreliable in the recommendation process. Recently, several collaborative filtering variations arise to tackle the sparsity problem. One of them refers to the item-based CF as opposed to the traditional user-based CF. This approach focuses on the correlations of items based on users¡¦ co-rating. Another popular variation is the trust-based CF. In such an approach, a second component, trust, is taken into account and employed in the recommendation process. The objective of this research is thus to propose a hybrid approach that takes both advantages into account for better performance. We propose the item-level trust-based collaborative filtering (ITBCF) approach to alleviate the sparsity problem. We observe that ITBCF outperforms TBCF in every situation we consider. It therefore confirms our conjecture that the item-level trusts that consider neighbors can stabilize derived trust values, and thus improve the performance.

Durant ce processus central qu’est la biogenèse des ARNm, la formation de la queue polyA est une étape clé impliquant de nombreuses activités enzymatiques et complexe protéiques. CF IA (Facteur de Clivage 1A) est un complexe macromoléculaire essentiel pour les deux étapes de clivage et de polyadénylation durant la formation de la queue poly(A) à l’extrémité 3’ de l’ARNm de levure. Constitué par les protéines RNA14, RNA15, Pcf11 et CLP1 dans une stœchiométrie supposée 2:2:1:1. Cependant, contrairement au complexe CPF (Facteur de Clivage et de Polyadénylation) qui porte les activités de clivage et de polyadénylation, aucune activité enzymatique n’a pu être associé au CF IA, suggérant un rôle d’architecture via d’une part la liaison à l’ARN et à d’autres complexes d’autre part. Dans ce travail, j’ai pu combiner les données obtenues par différentes approches biophysiques pour apporter des précisions sur l’organisation structurale au sein du CF IA mais également étudier l’importance biologique de certains motifs spécifiques. / During this major process which is mRNA biogenesis, the formation of the polyA tail is a key step involving numerous enzymatic activities and protein complex. CF IA (Cleavage Factor IA) is a macromolecular complex essential for both cleavage and polyadenylation steps during the formation of the 3'-end poly(A) tail of the yeast mRNA. Composed by RNA14, RNA15, Pcf11 and CLP1 yeast proteins in an assumed stochiometry of 2:2:1:1. However, unlike CPF (Cleavage and Polyadenylation Factor) complex hosting the both cleavage and polyadenylation activities, no enzymatic activity has been associated to CF IA, suggesting a scaffolding and/or positioning activity through the binding on the one hand to the RNA and on the other hand to other complexes. In this work, I was able to cross-use different biophysical technics to get insights on the structural organization within the CF IA as well as studying the biological importance of some specifics sequences.

This thesis deals with the application using digitally controlled current amplifiers DACA (Digitally Adjustable Current Amplifer), which was developed at the Department of Telecommunications FEEC in cooperation with ON Semiconductor in 2010. In introduction is decribed the topic of active filters and oscillators. Farther active current components, besides DACA are described current conveyor UCC (Universal Current Conveyor), current amplifier DO-CF (Dual-Output Current Follower), MO-CF (Multiple-Output Current Follower) and FD-CF (Fully Diferential Current Follower) and operational transconductant amplifier BOTA (Balanced-Output Operational Transconductance Amplifer) and MOTA (Multiple-Output Operational Transconductance Amplifier). The following is a compilation of theories circuits using signal flow graphs, which are designed using a simulated filter circuits to control the cutoff frequency or the quality factor. Then design and simulation with auxiliary oscillator circuit AGC for controlling the oscillation frequency. Simulations are conducted with ideal models and with models that include some real properties. The conclusion of this work is devoted to the printed circuit board design for a selected filter circuit realization and measurement.

No description available.

In this thesis, a new scheme based on the concept of compress-and-forward (CF) technique has been proposed. And expectation maximization (EM) algorithm is utilized to attain the aim of converging to a local optimum solution. According to the characteristic of EM algorithm, destination node would feed back a better decision to the relay node to be the next initial value. After the iteration, relay node would obtain a better detection result which would converge to a local optimum performance. At last the destination node would receive the optimum detection result from each relay and make a final decision. In the new structure, channel estimation can also be made at the relay node by EM algorithm, which is the reason why it is called joint distributed detection and estimation. Simulation shows that the proposed scheme would acquire an iteration gain at both the relay and destination node.

An improved understanding of the mucus biophysical alteration in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients is a milestone towards a more accurate and effective treatment of these common and highly debilitating conditions. Little is known about the variations in mucus structure between ill and healthy individuals. An established fact, however, is the role of the mucus obstruction in the exacerbation of the two conditions which impairs the physiological cleaning mechanism of the airways (mucociliary clearance) and is assessed as the strongest predictor of mortality. Therefore, it appears relevant to investigate which properties and structural changes are responsible of the impaired clearance of airway mucus. This thesis presents investigations of mucus on the basis of mucin structure observed in healthy, COPD and cystic fibrosis bronchial mucus samples. AFM (atomic force microscopy) and synchrotron SAXS (small angle X-ray scattering) techniques were used to characterise the structural features of the mucin molecules and allowed to identify the dumbbell structure of airways mucin monomers. The analysis of structural and dimensional features of mucins, highlighted a greater similarity of COPD with the healthy sample rather than with cystic fibrosis. The water sorption analysis using QCM-D (quartz crystal microbalance with dissipation monitoring), established a divergent behaviour between COPD and cystic fibrosis. Compared to healthy specimen, the mucus from COPD donors, showed a greater tendency to absorb water while cystic fibrosis mucus, in contrast, displayed the lowest water absorption.

In 1999, a new species of minnow, Chrosomus sp. cf. saylori (Clinch dace), was discovered in the Tennessee drainage of Virginia. Chrosomus sp. cf. saylori are listed as a Federal Species of Concern and on Virginia\'s Wildlife Action Plan as Tier II- Very High Conservation Need because of potential threats from habitat degradation, high population fragmentation, and a largely unknown distribution. Consequently, a management plan for C. sp. cf. saylori is of utmost importance, but more information regarding its distribution and life history is required before such a plan can be implemented. In 2011 and 2012 I sampled 60 headwater streams in the upper Clinch River watershed, Virginia.  From this and historical data, I conclude that C. sp. cf. saylori are restricted to eight small tributaries to the Clinch River.  Multivariate analysis of habitat correlates indicated that C. sp. cf. saylori populations are found in small, high elevation streams with gravel substrate and forested watersheds.  Three species distribution models were unable to predict C. sp. cf. saylori distribution.  Morphological traits were significantly different between C. sp. cf. saylori and other Chrosomus, thereby providing an initial indication of speciation and differing niche roles. I observed a nest association with Campostoma anomalum.  Gonad weight was lower for C. sp. cf. saylori than closely-related congeners. Together, this information indicates that C. sp. cf. saylori are narrowly distributed and populations are small, fragmented, and of questionable viability.  In the future, long-term monitoring efforts and genetics analyses should be completed and additional protection measures pursued. / Master of Science