Les cellules multiciliées jouent un rôle essentiel dans la propulsion des fluides physiologiques. Leur dysfonctionnement provoque des maladies chroniques. Contrairement à la plupart des cellules de mammifères qui possèdent un centrosome composé de deux centrioles, les cellules multiciliées possèdent une centaine de centrioles qui servent de base à la nucléation des cils motiles. Les mécanismes d'amplification de centrioles ou de régulation du nombre de centrioles dans ce type cellulaire étaient jusque-là inconnus. Les centrioles nouvellement formés étaient considérés comme apparaissant " de novo ". Une approche de vidéomicroscopie et de microscopie de super-résolution corrélative nous a d'abord permis de déterminer que tous les procentrioles sont générés à partir du centrosome préexistant. Nous démontrons que le centriole fils du centrosome est le site principal de nucléation de 95% de centrioles nouvellement formés dans les cellules multiciliées. Ces résultats réfutent par conséquent l'origine " de novo " des centrioles dans ce type cellulaire. Puis, nous montrons que la machinerie mitotique orchestre la progression spatio-temporelle de la dynamique centriolaire dans ces cellules post-mitotiques et en phase terminale de différentiation. L'amortissement de l'activité de Cdk1 empêche la rentrée en mitose tout en permettant la coordination du nombre de centrioles, leur croissance, et leur désengagement par des transitions phasiques nécessaires à la nucléation de cils motiles. Cette thèse aide à mieux comprendre la différentiation des cellules multiciliées, les ciliopathies, ainsi que l'amplification centriolaire pathologique associée avec le cancer et la microcéphalie. / Multiciliated mammalian cells play a crucial role in the propulsion of physiological fluids. Their dysfunction causes severe chronic diseases. In contrast to the strict centriole number control in cycling cells, multiciliated cell differentiation is marked by the production of up to several hundred centrioles, each nucleating a motile cilium. The mechanisms of centriole amplification or centriole number control in these cells were unknown and new centrioles were thought to appear de novo in the cytoplasm. First, videomicroscopy combined with correlative super-resolution and electron microscopy has enabled us to determine that all procentrioles are generated via runs of nucleation from the pre-existing progenitor cell centrosome. We show that the daughter centriole of the centrosome is the primary nucleation site for 95% of the new centrioles in multiciliated cells and thus refute the de novo hypothesis. Then, we provide evidence of an activation of the mitosis regulatory network during the centriole dynamic. With single cell live imaging and pharmacological modulation of mitosis regulators, we show that the mitosis machinery orchestrates the spatiotemporal progression of centriole amplification in terminally differentiating multiciliated cell progenitors. The fine-tuning of Cdk1 activity prevents mitosis while allowing the timely coordination of centriole number, growth, and disengagement through checkpoint-like phase transitions necessary for subsequent functional motile ciliation. This PhD provides a new paradigm for studying multiciliated cell differentiation, cilia-related diseases and pathological centriole amplification associated with cancer and microcephaly.

Les nanocristaux de Silicium (SiNCs) de taille inférieure à 5 nm sont des matériaux qui présentent une intense photoluminescence (PL) et capables d’amplification optique. Cette dernière propriété est un pré-requis à l’obtention d’émission stimulée sous pompage optique. Atteindre l’émission stimulé (et l’effet laser) à partir de nanostructures basées sur Si est d’un intérêt particulier dans le domaine de la photonique à base de silicium. Le but de ce travail était (i) d’étudier les propriétés optiques fondamentales de SiNCs, (ii) de concevoir et de réaliser un cristal photonique présentant une efficacité d’extraction augmentée et (iii) d’explorer la possibilité d’améliorer l’amplification optique des émetteurs de lumière à base de SiNCs en les combinant avec un cristal photonique à deux dimensions. / Silicon nanocrystals (SiNCs) of sizes below approximately 5 nm are a material with an efficient room-temperature photoluminescence (PL) and optical gain. Optical gain is a prerequisite for obtaining stimulated emission from a pumped material, and the achievement of stimulated emission (and lasing) from Si-based nanostructures is of particular interest in the field of silicon photonics. The aim of this work was (i) to investigate fundamental optical properties of SiNCs, (ii) to design and prepare a photonic crystal with enhanced light extraction efficiency and (iii) to explore a possibility of enhancing optical gain of light-emitting SiNCs by combining them with a two-dimensional photonic crystal.

L'objet de cette recherche consiste à capturer et analyser les relations entre l'architecture et les technologies récentes sous l'angle de la perception. Loin de la subjectivité supposée, l‘analyse guidée par la notion d'expérience perceptive s'appuie à la fois sur des concepts esthétiques et phénoménologiques. Cette double réflexivité porte également sur une étude de cas conceptuels et « concrets » qui opèrent la vision de la spatialité architecturale dans des tensions spéculatives entre le monde « numérique » et physique. La problématique porte sur la réception de l'architecture comme valeur culturelle et production intellectuelle, coordonnée par des moyens technologiques qui l'amplifient. S'inscrivant dans l'hypothèse qu'aujourd'hui l'architecture est loin de « servir » uniquement de réponse aux questions formelles, structurelles et fonctionnelles, la recherche démontre que l'architecture s'approche de plus en plus du champ artistique en phase d'expérimentations permanentes. Analysant les facteurs d'esthétisation de concepts variés, l'étude des cas vise à appréhender l'aspect cognitif et la valeur esthétique de la réception technologique — notion nouvelle, introduite comme un outil opératoire permettant d'aborder les aspects sensibles, hybrides et variables de la production architecturale. L'originalité de cette recherche consiste donc à analyser les connexions instables qui caractérisent les processus actuels de transitions diverses dans le domaine de l'architecture. À ce titre, cette recherche propose d'ouvrir le champ de la discussion autour du « digital » selon les principes de la singularité architecturale dans la pluralité des réceptions possibles / The purpose of this research is to capture and analyze the relationships between architecture and recent technologies in terms of perception. Far from the supposed subjectivity, this analysis guided by the notion of perceptual experience, is based on both phenomenological and aesthetic concepts. This double reflexivity also relates to the conceptual and "concrete" case studies operating the architectural vision of spatiality in speculative tensions between the "digital" and the physical word. The problematic concerns the reception of architecture as a cultural value and intellectual production, coordinated by technological means that amplify it. In keeping with the assumption that today's architecture is far away to "serve" only as a response to formal, structural and functional questions, this research shows that architecture is increasingly approaching the artistic field in phase of permanent experimentations. By analyzing the factors of aestheticization of various concepts, case study seeks to understand the cognitive and the aesthetic value of the technological reception — new notion, introduced as an operational concept to approach the sensitive, hybrid and variables issues of architectural production. The originality of this research consist of analyzing the unstable connections that characterize the current processes of various transitions in the field of architecture. As such, this research proposes to open the scope of the discussion around the "digital" according to the principles of architectural singularity in the plurality of possible receptions

Vid klinisk enbaspolymorfi (SNP) analys inkluderas DNA-kontroller med kända genotyper i varje analysomgång för att säkerställa riktigheten vad gäller analysresultatet. DNA-kontrollerna har en central roll för resultatens trovärdighet vid genotypningen. Vissa kontrollprover som används är av sällsynt genotyp och kan vara mycket svåra att få tag på. Detta arbete har utförts för att undersöka om det går att erhålla DNA-material från sällsynta genotyper med hjälp av helgenomamplifiering och på så sätt säkerställa en tillgång till dessa. I arbetet testades helgenomamplifiering med hjälp av två olika kit. De helgenomamplifierade produkternas kvantitet och kvalitet analyserades och jämfördes med det ursprungliga DNA:t, med avsikt att redogöra för det mest fördelaktiga kitet för SNP-analys i kliniskt syfte. Båda helgenomamplifierings-kiten påvisade god förmåga att amplifiera genomiskt DNA med hög kvalité. Helgenomamplifierat DNA från det bästa kitet sekvenserades och här var skillnader mellan ursprungligt och helgenomamplifierat DNA marginella. Vid sekvensanalys av ett 464 baspar långt fragment av faktor II genen och 585 baspar långt fragment av ApoE genen på fem helgenomamplifierade DNA-prover påvisades endast en eventuell diskrepans. / Clinical single nucleotide polymorphisms (SNP) analysis includes DNA controls with known genotypes in each run to ensure the accuracy of the analysis results. DNA controls have a central role for the credibility of the results in the genotyping process. Some of the used control samples are rare and can be very difficult to obtain. This work was carried out to investigate whether it is possible to obtain DNA from samples with a rare genotype using whole genome amplification and as a result ensure access to these samples. In this work the whole genome amplification method was tested by two different kits. The quantity and quality of the whole genome amplification products were analyzed and compared with the original DNA, with the intention to describe the most advantageous kit for clinical SNP analysis. Both tested kits demonstrated a good ability to amplify genomic DNA with high quality. Whole genome amplified DNA from the best kit was sequenced and the difference between the original DNA and whole genome amplified DNA was negligible. Sequence analysis of 464 base pairs of the factor II gene and 585 base pairs of the ApoE gene in five whole genome amplified DNA samples indicated only one possible discrepancy.

All-optical signal processing techniques for phase-shift keyed (PSK) systems were developed theoretically and demonstrated experimentally. Nonlinear optical effects in fibers, in particular four-wave mixing (FWM) that occurs via the ultra-fast Kerr nonlinearity, offer a flexible framework within which numerous signal processing functions can be accomplished. This research has focused on the regenerative capabilities of various FWM configurations in the context of processing PSK signals. Phase-preserving amplitude regeneration, phase regeneration, and phase-regenerative wavelength conversion are analyzed and demonstrated experimentally. The single-pump phase-conjugation process was used to regenerate RZ-DPSK pulse amplitudes with different input noise distributions, and the impact on output phase characteristics was studied. Experiments revealed a limited range over which amplitude noise could effectively be suppressed without introduction of phase noise, particularly for signals with intensity pattern effects. Phase regeneration requires use of phase-sensitive amplification (PSA), which occurs in nonlinear interferometers when the pump and signal frequencies are degenerate (NI-PSA), or in fiber directly through single-stage (degenerate) or cascaded (non-degenerate) FWM processes. A PSA based on a Sagnac interferometer provided the first experimental demonstration of DPSK phase and amplitude regeneration. The phase-regenerative capabilities of the NI-PSA are limited in practice by intrinsic noise conversion (amplitude to phase noise) and to a lesser extent by the requirement to modulate the pump wave to suppress stimulated Brillouin scattering (SBS). These limitations are relaxed in novel materials with higher SBS thresholds and nonlinearities. Degenerate FWM provides PSA in a traveling-wave configuration that intrinsically suppresses the noise conversion affecting the NI-PSA, while providing stronger phase-matched gain. Experiments confirmed superior phase-regenerative behavior to the NI-PSA with simultaneous reduction of amplitude noise for NRZ-DPSK signals. Phase-regenerative wavelength conversion (PR-WC) provides the regenerative properties of PSA at a new wavelength, and was proposed and demonstrated for the first time in this research. The parallel implementation of two FWM processes, phase-conjugation and frequency conversion, provides two idlers which exhibit interesting and useful regenerative properties. These were investigated theoretically and experimentally. Ideal phase-regenerative behavior is predicted when the contributing FWM processes are equally phase-matched, which can be maintained over any interaction length or wavelength shift provided the pump powers are properly adjusted. Depleted-pump regime PR-WC provides simultaneous phase and amplitude regeneration. Experiments confirmed regenerative behavior for wavelength shifts of the idlers up to 5 nm. Two techniques for phase regeneration of 4-level PSK signals were developed and evaluated. The first is based on parallel operation of PSAs suitable for processing 2-level PSK signals, where phase projection and regeneration are combined to recover the input data. Analysis of this scheme outlined the conditions required for effective phase regeneration and for practical implementation using known PSAs. A novel process based on FWM (parallel phase-conjugation followed by PSA) was developed and analyzed, and demonstrated using numerical simulations. These studies provide a basis for further work in this area.

Quantification of pathogen load, although challenging, is of paramount importance for accurate diagnosis and clinical management of a range of infectious diseases in a point-of-need testing (PONT) scenario such as in resource-limited settings. We formulated a quantification approach to test the standard-curve based absolute quantification ability of isothermal recombinase polymerase amplification (RPA) assay. As a test of principle, a 10-fold dilution series of Leishmania donovani (LD) genomic DNA prepared in nuclease-free-water (NFW), and from culture-spiked-blood (CSB) were tested, and a 15 min assay was performed. A modified algorithm was formulated to derive the detection outcome. The threshold-record times (Tr) in seconds thus obtained were plotted against the initial load of parasite genomes for log-linear regression analysis. The quantitative RPA (Q-RPA) assay was further evaluated against a LD quantitative (q)-PCR assay with DNA extracted from visceral and post-Kala-azar dermal leishmaniasis case specimens and stratified into different ranges of threshold cycle (Ct). The best-fitted regression models were found linear with mean r2/root mean square error (RMSE) values of residual points (in seconds) estimated as 0.996/8.063 and 0.992/7.46 for replicated series of NFW and CSB, respectively. In both series, the lower limit of detection reached less than 0.1 parasite genome equivalent DNA. Absolute agreement between Q-RPA and LD-qPCR was found for test positivity, and strong positive correlations were observed between the Tr and Ct values (r = 0.89; p < 0.0001) as well as between the absolute parasite loads (r = 0.87; p < 0.0001) quantified by respective assays. The findings in this very first Q-RPA assay for leishmaniasis are suggestive of its potential in monitoring LD load in clinical specimens, and the development of rapid Q-RPA assays for other infectious diseases.

京都大学 / 新制・課程博士 / 博士(工学) / 甲第24603号 / 工博第5109号 / 新制||工||1977(附属図書館) / 京都大学大学院工学研究科建築学専攻 / (主査)教授 松島 信一, 教授 竹脇 出, 教授 池田 芳樹 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

No description available.

京都大学 / 新制・課程博士 / 博士(農学) / 甲第25357号 / 農博第2623号 / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 保川 清, 教授 井上 和生, 教授 谷 史人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

Dans cet ouvrage, nous cherchons à comprendre l‘impact des perceptions sur la production et la gestion de la sécurité dans le réseau du transport en commun de Montréal. Quinze entrevues de recherche ont été effectuées avec des policiers de l‘Unité-Métro pour dégager les principaux éléments qui entrent dans la conception du risque. Les policiers sont appelés à travailler dans un environnement où, d‘une part, il n‘y a jamais eu d‘attaques terroristes, mais d‘autre part qui demeure une cible potentielle à la fois pour les experts, les gouvernements et dans la culture populaire. Nos résultats montrent que les policiers se développent une perception du risque qui leur est propre. En général, ils ont une attitude pragmatique qui leur permet de relativiser les situations et de décider lesquelles nécessitent une intervention de leur part. De plus, les policiers adoptent des stratégies de justification et de protection qui minimisent la perception du risque. Nos participants soulignent que ces stratégies sont nécessaires pour leur permettre d‘effectuer leurs tâches quotidiennes. Ainsi, afin d‘échapper à la paranoïa, les policiers évitent de penser à la menace terroriste et focus plutôt leur attention sur la criminalité sur laquelle ils ont l‘impression d‘avoir un pouvoir réel. Toutefois, la vigilance reste de mise. Malgré que les policiers ne conçoivent pas le risque de la même manière que les gestionnaires, la présence de l‘Unité-Métro demeure un élément important de production de la sécurité sur le terrain. / The research presented in this thesis aims to understand the impact of perceptions on the production and management of security in the Montreal transit system. Fifteen research interviews were conducted with police officers from the Metro Unit to identify the key elements involved in the perception of risk. The police officers are called to work in an environment where, on the one hand, there has never been any terrorist attacks, but on the other, remains a potential target according to experts, governments and popular culture. Our results show that the police officers develop a perception of risk specific to their tasks. In general, they have a pragmatic attitude which allows them to quickly sort situations and decide which ones need their attention. In addition, the police officers adopt justification and protection strategies that allow them to minimize their perception of risk. Participants insist that these strategies are necessary to enable them to perform their daily tasks. Thus, in order to escape falling into a paranoid state, the police officers avoid thinking about the terrorist threat, preferring to focus their attention on the crimes on which they believe to have an actual power. However, vigilance is still required. Although the police officers did not perceive the risk in the same way as administrators, the presence of the Metro Unit remains an important part of the production of security in the Montreal transit system.