AK-ILS: An Active learning method based on Kriging for the Inspection of Large Surfaces

Tolerance verification permits to check the product conformity and to verify assumptions made by the designer. For conformity assessment, the uncertainty associated with the values of the measurands must be known. In fact, to evaluate form characteristics of large aircraft structure workpieces, sampling is required, so a measurement error is present: exact estimation of form characteristics would require complete knowledge of the surface. To minimise this measurement error, this paper presents a Krigingbased procedure to identify the minimum of measured points to check the conformity with a given confidence level. The proposed method is validated on a simple example of orientation tolerance and then performed to inspect the form defect on three large aircraft workpieces

AK-ILS: An Active learning method based on Kriging for the Inspection of Large Surfaces

Tolerance verification permits to check the product conformity and to verify assumptions made by the designer. For conformity assessment, the uncertainty associated with the values of the measurands must be known. In fact, to evaluate form characteristics of large aircraft structure workpieces, sampling is required, so a measurement error is present: exact estimation of form characteristics would require complete knowledge of the surface. To minimise this measurement error, this paper presents a Krigingbased procedure to identify the minimum of measured points to check the conformity with a given confidence level. The proposed method is validated on a simple example of orientation tolerance and then performed to inspect the form defect on three large aircraft workpieces

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy

Quantitative trait loci for resistance to Flavobacterium psychrophilum in rainbow trout: effect of the mode of infection and evidence of epistatic interactions.

BACKGROUND: Bacterial cold-water disease, which is caused by Flavobacterium psychrophilum, is one of the major diseases that affect rainbow trout (Oncorhynchus mykiss) and a primary concern for trout farming. Better knowledge of the genetic basis of resistance to F. psychrophilum would help to implement this trait in selection schemes and to investigate the immune mechanisms associated with resistance. Various studies have revealed that skin and mucus may contribute to response to infection. However, previous quantitative trait loci (QTL) studies were conducted by using injection as the route of infection. Immersion challenge, which is assumed to mimic natural infection by F. psychrophilum more closely, may reveal different defence mechanisms. RESULTS: Two isogenic lines of rainbow trout with contrasting susceptibilities to F. psychrophilum were crossed to produce doubled haploid F2 progeny. Fish were infected with F. psychrophilum either by intramuscular injection (115 individuals) or by immersion (195 individuals), and genotyped for 9654 markers using RAD-sequencing. Fifteen QTL associated with resistance traits were detected and only three QTL were common between the injection and immersion. Using a model that accounted for epistatic interactions between QTL, two main types of interactions were revealed. A "compensation-like" effect was detected between several pairs of QTL for the two modes of infection. An "enhancing-like" interaction effect was detected between four pairs of QTL. Integration of the QTL results with results of a previous transcriptomic analysis of response to F. psychrophilum infection resulted in a list of potential candidate immune genes that belong to four relevant functional categories (bacterial sensors, effectors of antibacterial immunity, inflammatory factors and interferon-stimulated genes). CONCLUSIONS: These results provide new insights into the genetic determinism of rainbow trout resistance to F. psychrophilum and confirm that some QTL with large effects are involved in this trait. For the first time, the role of epistatic interactions between resistance-associated QTL was evidenced. We found that the infection protocol used had an effect on the modulation of defence mechanisms and also identified relevant immune functional candidate genes

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with 5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research

The GRAVITY+ Project: Towards All-sky, Faint-Science, High-Contrast Near-Infrared Interferometry at the VLTI

The GRAVITY instrument has been revolutionary for near-infrared interferometry by pushing sensitivity and precision to previously unknown limits. With the upgrade of GRAVITY and the Very Large Telescope Interferometer (VLTI) in GRAVITY+, these limits will be pushed even further, with vastly improved sky coverage, as well as faint-science and high-contrast capabilities. This upgrade includes the implementation of wide-field off-axis fringe-tracking, new adaptive optics systems on all Unit Telescopes, and laser guide stars in an upgraded facility. GRAVITY+ will open up the sky to the measurement of black hole masses across cosmic time in hundreds of active galactic nuclei, use the faint stars in the Galactic centre to probe General Relativity, and enable the characterisation of dozens of young exoplanets to study their formation, bearing the promise of another scientific revolution to come at the VLTI.Comment: Published in the ESO Messenge

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Modélisation et résolution de problèmes de distribution et ordonnancement

A major concern of many industrial enterprises is the irnprovement of their distribution system. ln the fust part of this thesis, we show how the use of tools from applied mathematics and computer science helps to reduce distribution costs significantly. For this purpose, we propose new methods for solving the vehicle routing problem. These methods are not only efficient but also flexible (they take into account a large variety of constraints) and robust (they can be applied to very different problems, without the need to determine precisely their control parameters). Combining a simple and fast heuristic procedure with a method based on Tabu search techniques makes it possible to solve complex real life problems. Another algorithm developed in this thesis is an evolutionary method at the crossroads of the Tabu meta-heuristic and genetic algorithms. In addition to the above advantages and as opposed to most of today's heuristics, an interesting feature of this new method is the fact that it can be easily codable on parallel CPU's. The number of processors can be chosen independently from the size of the problem. The second type of problem addressed in this thesis is the optirnization of sample processing in a robotized analytical system. Recent market studies have shown a growing interest in these complex scheduling problems, which, to our knowledge, cannot be solved with currently available methods. In the second part of this work, we describe both a fast constructive heuristic and a genetic algorithm to efficiently solve scheduling problems in a robotized environment. Our methods, which have already been used in practice, are flexible and can handle a large number of constraints. More precisely, we take into account the management of a non-static resource such as a robot, of resources able to sirnultaneously process several samples, of (possibly bounded) waiting tirnes between operations on a single sample, and of flexibility in the samples processing tirnes on the resources

Lorsque la modestie s’impose : les armoiries Rochat

International audienc