Discovering Drugable Immune Targets in Gastrointestinal & Hepatic Disease

Discovering Drugable Immune Targetsin Gastrointestinal & Hepatic Diseas

Evaluation and Control of the reliability of Weld Joints in Petroleum Products Transportation Pipelines

The economic performance of petroleum products transport companies is dependent on the reliability of their equipment. Ruptures of the weld joints of petroleum products carriage pipelines have major consequences at the human, environmental and economic levels. Weld joints are potential sites of dangerous cracks. The management of reliability of weld joints in pipelines is useful to integrate the quality planning and risks throughout their life cycle and to systematically track their characteristics all along their life cycles. The use in situ of inspection results from non-destructive control techniques is an essential component of evaluation and control of reliability of pipes in their function. It requires calculation methods and tools to assist in the decision-making in support of inspection and repair campaigns. It is in this context that the present study was conducted, which is a contribution to the efforts of methodological assessment of the reliability of petroleum products transport pipelines

Opportunities for conventional and in situ cancer vaccine strategies and combination with immunotherapy for gastrointestinal cancers, a review

Survival of gastrointestinal cancer remains dismal, especially for metastasized disease. For various cancers, especially melanoma and lung cancer, immunotherapy has been proven to confer survival benefits, but results for gastrointestinal cancer have been disappointing. Hence, there is substantial interest in exploring the usefulness of adaptive immune system education with respect to anti-cancer responses though vaccination. Encouragingly, even fairly non-specific approaches to vaccination and immune system stimulation, involving for instance influenza vaccines, have shown promising results, eliciting hopes that selection of specific antigens for vaccination may prove useful for at least a subset of gastrointestinal cancers. It is widely recognized that immune recognition and initiation of responses are hampered by a lack of T cell help, or by suppressive cancer-associated factors. In this review we will discuss the hurdles that limit efficacy of conventional cancer therapeutic vaccination methods (e.g., peptide vaccines, dendritic cell vaccin

Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Introduction: Therapeutic vaccination based on synthetic long peptides (SLP®) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV). Methods: We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses ex vivo. A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility. Results: All 17 SLPs were capable of inducing interferon gamma (IFNɣ) production in samples from four or more donors that had resolved an HBV infection in the past (resolver). Further analysis of the best performing SLPs demonstrated activation of both CD8+ and CD4+ multi-functional T cells in one or more resolver and patient sample(s). When investigating which SLP could activate HBV-specific T cells, the responses could be traced back to different peptides for each patient or resolver. Discussion: This indicates that a large population of subjects with different HLA types can be covered by selecting a suitable mix of SLPs for therapeutic vaccine design. In conclusion, we designed a set of SLPs capable of inducing multifunctional CD8+ and CD4+ T cells ex vivo that create important components for a novel therapeutic vaccine to cure cHBV.</p

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Approche physico- statistique à l'étude de la fiabilité des tubes destines a la construction des gazoducs

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Analyse des propriétés et caractéristiques des aciers des tubes et leurs influences sur La fiabilité des gazoducs

118 p. : ill. ; 30 cmAméliorer la fiabilité des ouvrages de transport de gaz naturel est un objectif primordial des concepteurs des pipelines, puisqu’il intéresse la sûreté des biens et des personnes, la disponibilité et la performance des pipelines et l’économie du transport des hydrocarbures par canalisation. Un tel objectif ne peut être atteint sans l’analyse des propriétés et caractéristiques des aciers des tubes et leur influence sur la fiabilité des pipelines. Les conduites se rompent même durant la période d’essais avant la mise en exploitation. Cela s’explique par le fait que les charges et les caractéristiques physico-chimiques des matériaux et tous les autres paramètres utilisés dans le calcul de projection, sont des grandeurs aléatoires (aléas). Ainsi, les conditions de réalisation et de fonctionnement des canalisations de transport des hydrocarbures, tout au long de la durée de vie espérée, ne sont pas parfaitement connues : la conception est placée dans un univers imprécis et incertain mais modélisable par un aléa probabiliste. Dans ce contexte, ce travail se place dans le cadre de couplage entre les méthodes de la mécanique et celles des probabilités dont l’objectif est d’étudier la tenue en service des canalisations de transport des hydrocarbures. Ce qui permettra donc d’apporter une contribution au passage de la conception des codes de construction déterministe des gazoducs à celui des codes probabilistes, où à la place des facteurs de sécurité présentant des valeurs fixes, on utilisera une valeur conventionnelle de probabilité de rupture. De telles études contribuent dans la recherche des méthodes les mieux appropriées relatives à la tenue en service des canalisations qui tiennent compte des différentes sources d’incertitude