Atomic X-ray Spectroscopy of Accreting Black Holes

Current astrophysical research suggests that the most persistently luminous objects in the Universe are powered by the flow of matter through accretion disks onto black holes. Accretion disk systems are observed to emit copious radiation across the electromagnetic spectrum, each energy band providing access to rather distinct regimes of physical conditions and geometric scale. X-ray emission probes the innermost regions of the accretion disk, where relativistic effects prevail. While this has been known for decades, it also has been acknowledged that inferring physical conditions in the relativistic regime from the behavior of the X-ray continuum is problematic and not satisfactorily constraining. With the discovery in the 1990s of iron X-ray lines bearing signatures of relativistic distortion came the hope that such emission would more firmly constrain models of disk accretion near black holes, as well as provide observational criteria by which to test general relativity in the strong field limit. Here we provide an introduction to this phenomenon. While the presentation is intended to be primarily tutorial in nature, we aim also to acquaint the reader with trends in current research. To achieve these ends, we present the basic applications of general relativity that pertain to X-ray spectroscopic observations of black hole accretion disk systems, focusing on the Schwarzschild and Kerr solutions to the Einstein field equations. To this we add treatments of the fundamental concepts associated with the theoretical and modeling aspects of accretion disks, as well as relevant topics from observational and theoretical X-ray spectroscopy.Comment: 63 pages, 21 figures, Einstein Centennial Review Article, Canadian Journal of Physics, in pres

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction

Identification et caractérisation fonctionnelle de gènes impliqués dans l'induction et la régulation de la réaction hypersensible et la résistance locale acquise chez la tabac

La réaction d hypersensibilité (HR) est l un des mécanismes de défense les plus efficaces dont dispose la plante pour lutter contre l attaque par des agents pathogènes. Phénotypiquement, la HR correspond à la mort programmée des cellules percevant l infection. Dans les cellules adjacentes, on observe une forte induction de réponses de défense. Cette zone correspond à la part vivante de la HR, que nous appelons résistance locale acquise ou LAR en références aux travaux de Ross au début des années 1960. HR et LAR participent ensembles au confinement de l infection au site d attaque. Alors que la HR est induite par des signaux exogènes issus de l agent pathogène, la LAR est induite par des signaux endogènes libérés par les cellules en état de HR. Ainsi, les gènes inducteurs du phénomène LAR, dont aucun n était connu, présentent un patron d expression spécifique de la HR. Le premier objectif de ma thèse a été de mettre en œuvre une stratégie permettant de selectionner des gènes potentiellement impliqués dans l induction du phénomène LAR. Un criblage par Differential Display Reverse Transcript Polymerase Chain Reaction a permis de sélectionner 24 ESTs (expressed sequence tag), parmi 5000 à 10000 transcripts analysés, présentant une expression spécifique au cours de la HR induite par infiltration d élicitine dans les feuilles de tabac. Le deuxième objectif de ma thèse a été de mettre en œuvre une analyse fonctionnelle de gain et de perte de fonction pour tester le rôle potentiel dans la mise en place du phénomène LAR de trois gènes parmi les vingt quatre issus du crible. J ai pu montrer que, parmi les 3 gènes, l extinction par Virus-Induced Gene Silencing du gène NtRING1, codant une E3 ligase putative à domaine RING, retarde la mise en place de la HR et l induction de gènes de défense. Parmi les cinq gènes issus du crible et analysés fonctionnellement jusqu à présent, NtRING1 et NtLRP1 semblent impliqués dans l exécution de la HR.The hypersensitive response (HR) is one of the most efficient plant defense mechanisms against pathogens. Phenotypically, the HR corresponds to the lesions developing at the infection sites. In the narrow zone surrounding the cells undergoing the HR cell death, a strong activation of defense responses occurs contributing to a local, highly inhospitable environment for the invading pathogen. This latter phenomenon was called localized acquired resistance (LAR). It corresponds to the living component of the HR. Whereas the HR is induced by exogenous signals issuing from the pathogen, LAR is triggerred by endogenous signals issuing from the plant cells undergoing the HR. Consequently, the genes inducing LAR, whose none are known yet, should be characterized by a HR-specific expression profile. The first part of this work consisted in the set-up of a strategy aimed to isolated such latter genes. A screening by Differential Display Reverse Transcript Polymerase Chain Reaction allowed to isolate 24 ESTs (expressed sequence tag) with such an expression profile. A second part of the work consisted in the functional characterization, by loss- and gain-of-function experiements, of 3 genes issuing from that screen. Among the three genes, silencing by Virus-Induced Gene Silencing of NtRING1, encoding a putative E3 ligase with a RING-finger motive delays the HR in tobacco induced by ß-megaspemin, a well as the expression of different defense-related genes. Among the 5 genes issuing from the screen and so far analyzed at the fonctional level, NtRING1 and NtLRP1 appeared involved in the execution of the HR.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF