Etude système de diodes lasers à verrouillage de modes pour la radio-sur-fibre en bande millimétrique

Ce travail de thèse s inscrit dans la recherche des solutions économiquementviables pour des réseaux personnels à hauts débits (plusieurs Gbps à plusieursdizaines de Gbps) opérationnels en bande millimétrique autour de 60 GHz. Aucas où ces réseaux servent un nombre élevé d utilisateurs, ils comprendront unemultitude d antennes afin d assurer l accès sans fil rapide. Afin de réduire aumaximum le coût d un module d antenne, les réseaux doivent fournir un signalanalogue à des porteuses millimetriques. Une solution prometteuse pour les systèmesde distribution qui correspond à ces besoins sont des structures à fibreoptique, laquelle permet une transmission à faibles pertes et à haute bande passante.On parle de l approche "radio-sur-fibre" (en anglais, radio-over-fiber). Laproblématique est de pouvoir générer et moduler un signal aux fréquences millimétriqueslors de la transmission optique - et ce avec des composant bas coûts.La technique utilisée dans le cadre de cette thèse est l emploi des diodes laser àverrouillage de modes. Ces derniers vont pouvoir générer des hautes fréquencestout en ne nécessitant qu une alimentation continue, et ils peuvent être modulésde manière directe ou externe. Les lasers à semi-conducteurs employés ici sontd une génération encore à l état d étude puisqu il s agit des lasers à boites (ouîlots) quantiques. Ces lasers ont montrés de très bonnes capacités à générer dessignaux électriques aux fréquences autour de 60 GHz, bien qu ayant encore, pourl instant, à une stabilité de fréquence (ou de phase) limitée. Dans le cadre des systèmesde communication opto/micro-ondes, peu de travaux approfondis ont étémenés sur ces structures.Au cours de cette thèse, plusieurs études ont été effectuées. La première portesur les propriétés générales d un système construit à partir de ce type de laser(puissances disponibles, figure de bruit, linéarité etc.). Une deuxième étude aété consacrée aux effets de la propagation des signaux dans les systèmes baséssur les lasers à verrouillage de modes, notamment de la dispersion chromatiquelaquelle a un effet considérable sur les distances de transmission. Les deux étudesmettent en avant l importance d une limitation du nombre de modes générés parla diode laser afin d optimiser non seulement le gain du lien et la puissance RFrécupérée, mais aussi la figure de bruit du système. Lors d une troisième étude, lastabilité en fréquence/phase s est révélée critique, car le bruit de fréquence/phaselimite la qualité de la transmission en introduisant un plancher d erreur mêmepour des rapports signal-a-bruit très élevés. Des différentes générations de lasersà boites (îlots) quantiques et à verrouillage de modes ont été testées. Le problèmedu bruit de fréquence et de phase persiste et ne peut pas être résolu en utilisantles techniques classiques comme les boucles à verrouillage de phase conventionnelles.Une solution pour ce problème a été développée pour les systèmes detransmission; elle permet simultanément un ajustement de fréquence supérieure(précision de quelques Hz à quelques kHz) à celle donnée par le processus de fabricationdes diodes lasers (précision de quelques GHz), ainsi qu une stabilisationde fréquence et de phase.This dissertation is related to the search for an economically sustainable solutionfor high data rate (several Gbps to several tens of Gbps) personal area networksoperating in the millimeter-wave region around 60 GHz. If such networks supplya large number of users, they need to encompass a multitude of antenna pointsin order to assure wireless access to the network. With the aim of reducing thecost of an antenna module, the networks should at best provide quasi "readyto-radiate" signals to the modules, i.e. at millimeter-wave carrier frequencies.Thanks to their low transmission loss and their high bandwidth, optical fiber distributionarchitectures represent a promising solution. The technique is referredto as the so-called "radio-over-fiber" approach whereby the analog radio signalwill be transported to the access point by an optical wave. The challenge herebyis the generation and modulation of an optical signal by a millimeter-wave radiosignal using preferably cost-efficient system components. The technique proposedherein is based on the use of mode-locked laser diodes which can generatesignals at very high frequencies under the condition of continuous current supply.Mode-locked laser diodes can be modulated both directly and externally. Thediodes employed in this work are based on so-called quantum dots (or quantumdashes); these are material structures which are themselves still subject to intensivephysical research. Signals at millimeter-wave frequencies (around 60 GHz)can easily be generated by such lasers. However, their frequency and phase stabilityis as yet limited. In the context of radio-over-fiber communication systems,these structures have not yet been studied in detail.In the course of this dissertation, several aspects are considered. A first systemstudy treats the basic properties of a system built from this type of laser source(available signal power, system noise figure, linearity etc.). A second study isdevoted to an investigation of propagation effects like dispersion, which considerablyinfluence the attainable transmission distances. An essential result of bothstudies is the importance of limiting the laser spectrum to a small number of lasermodes for an optimization of link gain, generated RF power, and system noisefigure. A third study deals with the limited frequency and phase stability whichturn out to be critical factors for transmission quality. The study of several generationsof quantum dot/dash lasers has revealed that the problems of frequencyand phase noise persist and cannot be solved using classical techniques involvinge.g. conventional phase-locked loops. In this dissertation, a solution is presentedwhich not only allows a more precise adjustment of the laser frequency (precisionin the order of Hz to kHz) than that given by the manufacturing process of thelaser (precision in the order of GHz), but also enables a stabilization of frequencyand phase.SAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Sequence Heterogeneity in NS5A of Hepatitis C Virus Genotypes 2a and 2b and Clinical Outcome of Pegylated-Interferon/Ribavirin Therapy

Pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy is a current standard treatment for chronic hepatitis C. We previously reported that the viral sequence heterogeneity of part of NS5A, referred to as the IFN/RBV resistance-determining region (IRRDR), and a mutation at position 70 of the core protein of hepatitis C virus genotype 1b (HCV-1b) are significantly correlated with the outcome of PEG-IFN/RBV treatment. Here, we aimed to investigate the impact of viral genetic variations within the NS5A and core regions of other genotypes, HCV-2a and HCV-2b, on PEG-IFN/RBV treatment outcome. Pretreatment sequences of NS5A and core regions were analyzed in 112 patients infected with HCV-2a or HCV-2b, who were treated with PEG-IFN/RBV for 24 weeks and followed up for another 24 weeks. The results demonstrated that HCV-2a isolates with 4 or more mutations in IRRDR (IRRDR[2a]≥4) was significantly associated with rapid virological response at week 4 (RVR) and sustained virological response (SVR). Also, another region of NS5A that corresponds to part of the IFN sensitivity-determining region (ISDR) plus its carboxy-flanking region, which we referred to as ISDR/+C[2a], was significantly associated with SVR in patients infected with HCV-2a. Multivariate analysis revealed that IRRDR[2a]≥4 was the only independent predictive factor for SVR. As for HCV-2b infection, an N-terminal half of IRRDR having two or more mutations (IRRDR[2b]/N≥2) was significantly associated with RVR, but not with SVR. No significant correlation was observed between core protein polymorphism and PEG-IFN/RBV treatment outcome in HCV-2a or HCV-2b infection. Conclusion: The present results suggest that sequence heterogeneity of NS5A of HCV-2a (IRRDR[2a]≥4 and ISDR/+C[2a]), and that of HCV-2b (IRRDR[2b]/N≥2) to a lesser extent, is involved in determining the viral sensitivity to PEG-IFN/RBV therapy

Signatures of mutational processes in human cancer.

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis', is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Guanine-rich sequences are a dominant feature of exosomal microRNAs across the mammalian species and cell types

Exosome is an extracellular vesicle released from multivesicular endosomes and contains micro (mi) RNAs and functional proteins derived from the donor cells. Exosomal miRNAs act as an effector during communication with appropriate recipient cells, this can aid in the utilization of the exosomes in a drug delivery system for various disorders including malignancies. Differences in the miRNA distribution pattern between exosomes and donor cells indicate the active translocation of miRNAs into the exosome cargos in a miRNA sequencedependent manner, although the molecular mechanism is little known. In this study, we statistically analyzed the miRNA microarray data and revealed that the guanine (G)-rich sequence is a dominant feature of exosome-dominant miRNAs, across the mammalian species-specificity and the cell types. Our results provide important information regarding the potential use of exosome cargos to develop miRNA-based drugs for the treatment of human diseases