Cette thèse est dédiée à la compréhension de l’impact des irradiations alpha sur la stabilité mécanique et la durabilité chimique du verre nucléaire. Des irradiations externes aux ions He et aux ions Au ont été réalisées sur le verre SON68 afin de simuler l’effet des particules alpha et des noyaux de reculs. L’effet simultané des deux types de particules a été étudiée avec des irradiations à double faisceau He+Au. Pour comprendre les mécanismes fondamentaux à l'origine des modifications des propriétés physico-chimiques, les irradiations ont également été réalisées sur un verre borosilicaté à 6 oxydes appelé ISG, sur le verre à vitre Planilux et sur la silice vitreuse Spectrosil 2000. Les résultats obtenus révèlent que les deux types d’irradiation ont un impact sur la dureté, le module d’Young réduit et la densité des verres. La structure des échantillons irradiés a été analysée par RMN, Ramanet XPS. L’effet des irradiations sur la durabilité chimique a été mesuré avec des tests de lixiviations en mode statique dans une eau ultra-pure portée à 90°C. Les solutions de lixiviations ont été prélevées à intervalles de temps réguliers puis analysées par ICP-MS. L’altération chimique des échantillons a été caractérisée par la perte de masse normalisée des éléments traceurs B, Li, Si, Mo, Cs relâchés en solution. La couche d’altération a été caractérisée par imagerie MEB et par spectroscopie EDX. / Borosilicate glasses are intended to be used for the long-term confinement of high-level nuclear wastes. Alpha particles from the minor actinides induce modifications of the glass structure which could deteriorate the efficiency of the confinement. External irradiation with 1 MeV He ions and 7 MeV Au ions were performed in the SON68 glass in order to simulate effect of alpha particles and recoils nucleus. Dual beam irradiations composed by He+Au ions were also investigated in order to simulate both effects of those two kind of particles. To understand the fundamental origin in physico-chemical properties, irradiation were also carried out on a 6 oxides borosilicate glass called International Simplified Glass (ISG) and two commercially available glass Planilux and Spectrosil 2000, both from Saint-Gobain. The mechanical properties and chemical durability of each glass were studied as a function of the cumulated dose. Results show that both alpha particles and heavy ions lead to variation in hardness, reduced Young’s modulus and density. Characterization techniques such as Raman, RMN, and XPS spectroscopy were used to analyze structural modifications induced by radiations. Chemical durability of pristine and irradiated glasses was determined by monitoring the release of glass alteration elements B, Li, Si, Mo and Cs. The alteration layer was characterized by SEM imaging and EDX spectroscopy.

The induction of type I interferon (IFN) and subsequent activation of interferon stimulated genes (ISGs) represent a first line of defense against viral infection. Typically type I IFN signaling leads to the phosphorylation of the STAT1 and STAT2 transcription factors (TFs) which then form a trimetric complex with IRF-9 and translocate to the nucleus to induce ISG expression. However, the results of this study showed that IFN-mediated upregulation of the ISG Oas1b, the product of which confers resistance to flavivirus induced disease, can be induced in a STAT1-independent manner. Since numerous ISGs have antiviral functions, many viruses have evolved strategies to disrupt the type I IFN-signaling pathway. In cases when STAT1 activation is blocked by a viral infection, STAT1-independent upregulation of ISGs provides an additional strategy for the cell to mount an effective antiviral response. Infection of mouse embryofibroblasts (MEFs) with West Nile virus (WNV) induced the production of IFN beta and STAT1 and STAT2 phosphorylation but blocked nuclear translocation and binding of these TFs to the promoters of the ISGs, Oas1a, Oas1a, Irf7 and Irf1. However, each of these antiviral ISGs was efficiently upregulated in infected cells and IRF-9 was shown to be crucial for the upregulation of Oas1a, Oas1b and Irf-7. IRF-3 or IRF-7 was needed to maintain the upregulation of these genes at later times of infection. In contrast, the upregulation of Irf1 by WNV infection did not depend on the tested IRFs but was reduced by inhibition of the p38 or NF-kappa B pathways. Although Irf1 mRNA was efficiently upregulated in WNV-infected cells IRF-1 protein synthesis was blocked. The precise mechanism of the IRF-1 translational suppression is not yet known, but the suppression was shown not to be due to increased proteasomal degradation of IRF-1 nor to alternative splicing of Irf1 mRNA. Preliminary results suggest miRNAs may play an indirect role in regulating IRF-1 translation. The results of this study expand knowledge about the strategies evolved by viruses to evade host cell antiviral responses and also provide valuable insights about alternative mechanisms utilized by the host cell to counteract viral infections.

Edge Computing is considered one of the key capabilities in next generation (5G) networks, which will enable inundation of latency, throughput, and data sensitive edge-native applications. Edge application developers require infrastructure at the edge to host the application workload and network connectivity procedures to connect the application users to the nearest edge where the application workload is hosted. Distributed nature of edge infrastructure and the requirement on network connectivity makes it attractive for communication service providers (CSPs) to become Edge Service providers (ESP); similarly, hyper-scale cloud providers (HCPs) are also planning to expand as ESP building on their cloud presence targeting edge application developers. CSPs across the globe follow a standard approach for building interoperable networks and infrastructure, while HCPs do not participate in telecom standardization bodies. Standards development organizations (SDOs) such as the European Telecommunication Standardization Institute (ETSI) and 3rd Generation Partnership Project (3GPP) are working to provide a standard architecture for edge computing solution for service providers. However, the current focus of SDOs is more on architecture and not much focus on application developer experience and the Application Programming Interfaces (APIs). On the architecture itself, there are different standards and approaches available which overlap with each other. APIs proposed by different SDOs are not easily consumable by edge application developers and require simplification. On the other hand, there are not many widely known standards in the hyper-scale cloud and public cloud industry to integrate with each other except the public application programming interfaces (APIs) offered by cloud providers. To scale and succeed, edge service providers need to focus on interoperability, not only from a cloud infrastructure perspective but from a network connectivity perspective as well. This work analyzes standards defined by different standardization bodies in the 5G edge computing area and the overlaps between the standards. The work then highlights the requirements from an edge application developer perspective, investigates the deficiencies of the standards, and proposes an end-to-end edge solution architecture and a method to simplify the APIs which fulfil the need for edge-native applications. The proposed solution considers CSPs providing multi-cloud infrastructure for edge computing by integrating with HCPs infrastructure. In addition, the work investigates existing standards to integrate cloud capabilities in network platforms and elaborates the way network and cloud computing capabilities can be integrated to provide complete edge service to edge application developers or enterprises. It proposes an alternative way to integrate edge application developers with cloud service providers dynamically by offering a catalog of services. / Edge Computing anses vara en av nyckelfunktionerna i nästa generations (5G) nätverk, vilket möjliggör minskad fördröjning, ökad genomströmning och datakänsliga och kantnära applikationer. Applikationsutvecklare för Edge Computing är beroende av kantinfrastruktur som är värd för applikationen, och nätverksanslutning för att ansluta applikationsanvändarna till närmaste kant där applikationens är placerad. Även om kantapplikationer kan vara värd för vilken infrastruktur som helst, planerar leverantörer av kommunikationstjänster (CSP:er) att erbjuda distribuerad kantinfrastruktur och anslutningar. På liknande sätt planerar även molnleverantörer med hög skalbarhet (HCP) att erbjudakantinfrastruktur. CSP:er följer standardmetoden för att bygga nätverk och infrastruktur medan HCP:er inte deltar i standardiseringsorgan. Standardutvecklingsorganisationer (SDO) som europeisk telekommunikations standardiseringsinstitut (ETSI) och 3rd Generation Partnership Project (3GPP) arbetar för att tillhandahålla en standardarkitektur för Edge Computing för tjänsteleverantörer. Men nuvarande fokus är mer på arkitektur och inte mycket fokus är riktat mot applikationsutvecklares erfarenhet och API:er. I själva arkitekturen finns det olika standarder och tillvägagångssätt som överlappar varandra. API:er föreslagna av olika SDO:er är inte lättillgängliga för utvecklar av kantapplikationer och måste förenklas. Å andra sidan finns det inte många allmänt kända standarder i hyperskalära moln och offentlig molnindustri som går att integrera med varandra förutom de offentliga gränssnitten för applikationsprogrammering (API:er) som erbjuds av molnleverantörer. För att kunna betjäna omfattande applikationsutvecklare måste CSP:er erbjuda multimolnfunktioner och därmed komplettera sin egen infrastruktur med kapaciteten för HCP:er. På liknande sätt kommer HCP:er att behöva integrera anslutningstjänster utöver infrastruktur för att erbjuda kantfunktioner. Den här arbetet beskriver olika standarder definierade av olika standardiseringsorgan i Edge Computing-området för 5G, och analyzerar överlappningar mellan standarderna. Arbetet belyser sedan kraven från ett utvecklingsperspektiv av kantapplikationer, undersöker bristerna i standarderna och föreslår en lösningsarkitektur som uppfyller behovet för kantbyggda applikationer. Den föreslagna lösningen beaktar CSP:er som tillhandahåller flermolnsinfrastruktur för Edge Computing genom att integreras med HCP:s infrastruktur. Arbetet undersöker vidare befintliga standarder för att integrera molnfunktioner i nätverksplattformar och utvecklar på vilket sätt nätverks- och molntjänster kan integreras för att erbjuda kompletta tjänster till utvecklare av kantapplikationer. Arbetet föreslår ett alternativt sätt att dynamiskt integrera utvecklare av kantapplikationer med leverantörer av molntjänster genom att erbjuda en katalog av tjänster.

Human immunodeficiency virus type 1 (HIV-1) is a lentivirus that causes acquired immunodeficiency syndrome (AIDS). Since the first cases of AIDS were described in 1981, HIV-1 has become one of the most serious public health threats in the world. There are approximately 38 million people worldwide currently living with HIV-1. 28 million of these people have access to antiretroviral therapy (ART) that is highly effective in reducing viral load to undetectable levels, thereby curbing the risk of viral transmission and preventing progression to AIDS. Despite their effectiveness in suppressing HIV-1 viremia, systemic inflammation remains as a hallmark of HIV-1 infection in vivo. This persistent immune activation is often associated with non-AIDS related complications, including elevated risk of neurocognitive and cardiovascular disorders. Several different mechanisms may contribute to this chronic immune activation and inflammation in people living with HIV-1 on ART. One of the contributing factors might be HIV-1 RNA expressed from the provirus. Even though ART potently suppresses HIV-1 replication, it fails to eradicate proviruses established prior to initiation of ART. Ongoing activation of CD4+ T cells and macrophages by HIV-1 proviral transcripts might contribute to the persistent inflammation that remains even after HIV-1 suppression by ART. Previously, our laboratory has shown that induction of innate immune signaling after HIV-1 challenge of primary human dendritic cells (DCs), macrophages, or CD4+ T cells requires integration, transcription from the nascent provirus, and nuclear export of intron-containing HIV-1 RNA through the Rev-CRM1 pathway. However, these studies failed to identify the innate immune sensor of intron-containing HIV-1 RNA. Here we conducted a targeted loss-of-function screen, using shRNA-expressing lentivectors in human DCs to identify this innate immune receptor. Of the twenty-one candidate genes targeted for knockdown by shRNA, the innate immune response to HIV-1 was inhibited only by knockdown of IFIH1, MAVS, and XPO1. The effect of IFIH1 and MAVS knockdowns on HIV-1-induced immune activation was confirmed in macrophages, and rescue of the knockdown with non-targetable coding sequence showed that IFIH1 protein was required. IFIH1 mutants that are defective for interaction with MAVS blocked activation, demonstrating that MAVS acts downstream of IFIH1 in this system. Since both IFIH1 and DDX58 signal via MAVS, the specificity of HIV-1 RNA detection by IFIH1 was demonstrated by the fact that DDX58 knockdown had no effect on activation; the IFIH1-specific inhibitor Nipah virus V protein blocked the activation by HIV-1. RNA-Seq showed that IFIH1-knockdown in DCs globally disrupted the induction of IFN-1-stimulated genes. Altogether, results presented in this thesis reveal that IFIH1 is required for innate immune activation by intron-containing RNA from the HIV-1 provirus, and potentially contributes to chronic inflammation in people living with HIV-1.