京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21044号 / 薬科博第87号 / 新制||薬科||9(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 中山 和久, 教授 竹島 浩, 教授 井垣 達吏 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

We develop a new method for pricing options on discretely sampled arithmetic average in exponential Lévy models. The main idea is the reduction to a backward induction procedure for the difference Wn between the Asian option with averaging over n sampling periods and the price of the European option with maturity one period. This allows for an efficient truncation of the state space. At each step of backward induction, Wn is calculated accurately and fast using a piece-wise interpolation or splines, fast convolution and either flat iFT and (refined) iFFT or the parabolic iFT. Numerical results demonstrate the advantages of the method.

No description available.

My thesis work consisted in the study of cilia and flagella, organelles highly conserved in many eukaryotes, which protrude at the cell surface as a microtubular backbone, the axoneme, bounded by an extension of the plasma membrane. A major interest in the study of cilia is that they are involved in the regulation of many cell events, such as re-entry in the cell cycle, and that their dysfunction in vertebrates provokes multi-symptomatic diseases called ciliopathies. Ciliary growth is under control of IFT (intraflagellar transport) mechanism, first discovered in Chlamydomonas. The IFT complex includes at least 17 members and is is composed of two subcomplexes, IFTB linked to kinesin for anterograde transport in ciliary building, and IFTA linked to dynein for retrograde transport in recycling. In my thesis on IFT in Paramecium, I focused on IFT57/Hippi, a member of IFTB, which seems to display two different functions in human cells: biogenesis of cilia as member of the IFTB particle and gene regulation in Huntington's diseases, as part of a complex with Hip1 that binds caspase promoters involved in apoptosis. Some recent work also showed that in the cytoplasm of non-ciliate cells, IFT57, associated with IFT20 and IFT88, regulates T-cell antigen receptor (TCR) recycling in immune synapse. In Paramecium, four genes issued from two successive genome duplications encode IFT57 (IFT57A - D). The isoforms A and B on the one hand and C and D on the other hand are sufficiently close in DNA sequence to get homology dependent RNAi silencing with only one gene of each pair. I first confirmed that IFT57 Paramecium genes have a conserved IFT function in cilia formation, but apparently not in maintenance, in contrast to other IFT proteins such as IFT46. The combination of RNAi and GFP fusion localization allowed us to suggest interactions between IFT46 and IFT57 in the cytoplasm, upstream from the usual site of interaction in the basal body. I also found that IFT57A-GFP, but not IFT57C-GFP, can enter the macronucleus and that the labelling shifts from the old to the new macronucleus during sexual events (autogamy and conjugation). This result must be analysed in light of the mechanism that governs genome rearrangements during nuclear reorganization, which are dependent on transport of RNA as well as of piwi and other RNA-binding molecules from old to new macronucleus. By extension of its ciliary role, one interesting possibility is that IFT57 is a partner involved in this transport. I tried to detect the putative roles of IFT57A in sexual process and worked out a new RNAi method by hairpin RNA expression. I expressed a specific IFT57A hairpin under the control of the NOWA1 promoter (only expressed in autogamy or conjugation) and found surprisingly that this hairpin stops the autogamy process. Since another hairpin contain NSF sequence displayed a similar phenotype, I could not draw any conclusion about the role of IFT57A during autogamy. Using chimeras by exchanging parts of IFT57A and IFT57C, then by comparing this sequence to other in the Paramecium genus, I could determine the shortest region of IFT57A necessary for nuclear localization is the peptide encompassing L129 to N219, with two critical positions to functionally distinguish these two proteins.

Multilayer composite materials have a high tendency to interlaminar delamination when they are subjected to out-of-plane loading, because of their low-stiffness in the through-thickness (T-T) direction. The main aim of this research was to improve the interlaminar fracture toughness (IFT) of textile composites by using stitching as a T-T reinforcement technique. The intention was to provide greater delamination resistance and also to enhance the interlaminar fracture toughness between adjacent layers. In this research, E-glass 2x2 twill weave structure fabric layers and an epoxy resin were chosen as the base materials. Three different types of stitching; including the commonly-used modified lock-stitch and orthogonal-stitch (OS) geometries, the single-yarn orthogonal-stitch (SOS) and a newly-developed double-yarn orthogonal-stitch (DOS), as well as five different stitch densities were used to reinforce the multilayer preform lay-ups. The resin infusion moulding method was used to manufacture the E-glass/Epoxy 3D textile composites. The effect of stitched reinforcement on the Mode I-IFT mechanism was examined by performing double cantilever beam (DCB) tests and the Mode II-IFT mechanism by performing four-point bend end-notched flexure (4ENF) tests, respectively. Optical microscopy and scanning electron microscopy (SEM) imaging techniques were used to study the fracture surfaces of the stitched composite specimens, to assess the improvement in IFT mechanisms imparted by the stitched reinforcement used. The effect of stitching was analysed by comparing the various stitching geometries, stitch densities and the mechanical properties highlighted by the Mode I-IFT and Mode II-IFT results. It was found that the use of the novel double-yarn orthogonal-stitch (DOS) reinforcement allied with the use of high stitch densities gave the greatest improvement on both Mode I-IFT and Mode II-IFT tests. Moreover, in every case, the use of DOS and high stitch densities gave a significant improvement of 74.5% in Mode I-IFT and 18.3% for Mode II-IFT tests when compared with unstitched samples. It has been shown that the novel DOS stitch geometry yields significant benefits over established stitching techniques in respect of stitched reinforcement for laminated composite preforms. Besides this, the double column 5x5 mm stitch pattern reveals the highest delamination resistance performance among all the stitching formations tested for Mode I-IFT and II-IFT.

Cilia are small microtubule based protrusions found on most cells of the vertebrate body. In humans, defects in the structure or function of cilia results in a large class of developmental and homeostatic diseases known collectively as the ciliopathies. Ciliogenesis is accomplished by the concerted action of a number of molecular pathways including the intraflagellar transport (IFT) system. IFT is a group of ~20 highly conserved proteins that assemble into large macromolecular complexes known as trains. These trains act to carry cargo bi-directionally between the cell body and ciliary tip, via interaction with the microtubule motors kinesin and dynein. IFT train dynamics are required for both cilia structure and function, however the controls on these dynamics are still incompletely understood. Here, I present the first platform for study of IFT dynamics within vertebrate multiciliated cells, an understudied population with critical functions in development and homeostasis. Using this platform, I demonstrate that the planar cell polarity effector protein Fuz is required for IFT dynamics via its control of the cytoplasmic localization of a subset of IFT proteins. Subsequently, I find that a Fuz binding partner, the putative small GTPase Rsg1, is also required for IFT protein localization and dynamics. Additionally, I describe a role for Rsg1 in basal body docking, one of the earliest events of ciliogenesis. Finally, I show that the poorly studied protein TTC29 is required for a specific subset of IFT dynamic behaviors. These data reveal novel regulatory motifs for ciliogenesis and demonstrate, specifically, the complexities of IFT regulation in the cytoplasm and within the cilium itself. Finally, they suggest that multiciliated cells provide a tractable platform for generating robust datasets for the investigation ciliary dynamics. Such studies are critical for informing our understanding of the molecular etiology of human ciliopathic diseases. / text

Highly fractured and vuggy oil reservoirs represent a challenge for enhanced oil recovery (EOR) methods. The fractured networks provide flow paths several orders of magnitude greater than the rock matrix. Common enhanced oil recovery methods, including gases or low viscosity liquids, are used to channel through the high permeability fracture networks causing poor sweep efficiency and early breakthrough. The purpose of this research is to determine the feasibility of using foam in highly fractured reservoirs to produce oil-rich zones. Multiple surfactant formulations specifically tailored for a distinct oil type were analyzed by aqueous stability and foam stability tests. Several core floods were performed and targeted effects such as foam quality, injection rate, injection type, permeability, gas saturation, wettability, capillary pressure, diffusion, foam squeezing, oil flow, microemulsion flow and gravity segregation. Ultimately, foam was successfully propagated under various core geometries, initial conditions and injections methods. Consequently, fluids were able to divert to unswept matrix and improve the ultimate oil recovery. / text

This thesis describes the work that I have carried out in the Laboratory of Neurophysiolgy at the Université Libre de Bruxelles, under the supervision of Prof. Serge Schiffmann, in collaboration with Prof. Stéphane Schurmans of Université of Liège.The work is divided in two distinct but related projects and the results section is thus divided into two main chapters. The results described are presented in the form of two manuscripts, the first chapter is named “Ciliary phosphoinositides regulation by INPP5E controls Shh signaling by allowing trafficking of Gpr161 in neural stem cells primary cilium”.The second is named “Regulation of phosphoinositides ciliary levels controls trafficking and ciliogenesis in ependymal cells”.Since both manuscripts are comprehensive regarding the results, and methods, these are inserted as such into the thesis.An expanded introduction to the field, placing the results into context, precedes these two chapters. An extended discussion section follows each chapter; it presents some elements of discussion not included in the manuscripts, the implications of the results and the scope for further research. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

<p>Bone loss diseases, including osteoporosis affect millions of people worldwide. Understanding the underlying mechanisms behind bone homeostasis and adaptation is essential to uncovering new therapeutic targets for the prevention and treatment of bone loss diseases. Primary cilia have been implicated in the development and mechanosensation of various tissue types, including bone. The goal of the studies outlined in this thesis is to determine the mechanosensory role of primary cilia in bone cell function, bone growth, and adaptation. This goal was achieved by exploring two specific scenarios. In the first study, mice models with conditional knockouts of MKS5, a ciliary protein, in osteocytes were utilized to demonstrate that dysfunctional primary cilia in those cells result in impaired loading-induced bone formation. The hypothesis tested is that the existence of functioning primary cilia on osteocytes is crucial for proper bone adaptation following stress. The results of this study support the hypothesis, with the conditional knockout mice showing significantly lower loading-induced bone formation compared to controls. The second study highlighted the importance of the osteoblast primary cilia in bone growth by using mice models with osteoblast-specific deletion of the cilia. The hypothesis tested is that the presence of the primary cilia is crucial for proper bone growth. The results show that conditional knockout mice have lower body weights, decreased femur length, and a significantly lower rate of bone formation, confirming that the primary cilia play a great role in bone growth and development. This study has highlighted the role of primary cilia in bone health and this topic merits further investigation. </p>

京都大学 / 新制・課程博士 / 博士(薬科学) / 甲第24205号 / 薬科博第158号 / 新制||薬科||17(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 中山 和久, 教授 井垣 達吏, 教授 土居 雅夫 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM