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Gene knockout experiments have shown that many genes are dispensable for a given biological function. In this review, we make an assessment of male and female germ cell-specific genes dispensable for the function of reproduction in mice, the inactivation of which does not affect fertility. In particular, we describe the deletion of a 1 Mb block containing nineteen paralogous genes of the oogenesin/Pramel family specifically expressed in female and/or male germ cells, which has no consequences in both sexes. We discuss this notion of dispensability and the experiments that need to be carried out to definitively conclude that a gene is dispensable for a function.

Ce travail étudie l’impact de l’épidémie de SARS-CoV2 et des recommandations qui ont été diffusées depuis le 16 mars sur l’activité des réunions de concertations pluridisciplinaires (RCP). L’activité des RCP d’Occitanie a été mesurée à partir des fiches RCP extraites du dossier communicant de cancérologie qui regroupe toutes les RCP. L’activité précédant le confinement a été comparée à celles des périodes de confinement (jusqu’au 24 avril) et des périodes équivalentes en 2019. Les critères de jugement étaient le nombre de réunions tenues, le nombre moyen de dossiers examinés par réunion, dont les premières présentations, et le nombre moyen de médecins présents. Les 191 RCP ont organisé 3943 réunions et étudié 72 070 dossiers (dont 30 127 premières soumissions). Nous avons observé une baisse de 8 % du nombre de réunions après le confinement. Le nombre de dossiers examinés a diminué de 23 % dans le mois suivant et jusqu’à 33 % dans la troisième quinzaine. Le nombre de médecins participant aux réunions a diminué initialement de 25 %. L’impact a été plus important dans la partie méditerranéenne de la région. Cette première étude à l’échelle d’une région montre que si l’impact de l’épidémie sur le nombre de RCP qui se sont réunies a été modeste, et que les RCP ont suivi les recommandations d’optimisation du quorum, la diminution du nombre de premières présentations laisse présager un retard au diagnostic et à la prise en charge des patients. Elle devra être complétée par des travaux qualitatifs et quantitatifs afin d’estimer l’impact réel de l’épidémie sur la prise en charge globale oncologique.

The RECONFIGURE Functional Engineering Simulator (FES) is a simulation software tool based on the MATLAB°/Simulink° modeling & simulation environment, specifically designed to support the industrial verification and benchmarking of the Fault Detection and Diagnosis (FDD) and Fault Tolerant Control (FTC) algorithm prototypes designed by the partners of the RECONFIGURE project. The FES includes the benchmark scenarios defined by Airbus for the evaluation of the FDD/FTC designs, namely sensor faults, actuator faults and icing conditions. Although based on a reusable generic-purpose simulation infrastructure layer, the FES has been customized for the verification campaign to be executed with the Airbus benchmark model. Although the development of the FES has not concluded at the time of writing this article, we can describe the software architecture, design and simulation capabilities of this tool within the context of an industrial verification & validation process.

This paper details the industrial challenges, goals and objectives of the European Framework 7th project termed “REconfiguration of CONtrol in Flight for Integral Global Upset REcovery” (RECONFIGURE). This project aims at investigating and developing advanced aircraft Guidance, Navigation and Control (GNC) technologies that facilitate the automated handling of off-nominal events and optimize the aircraft status and flight. These technologies will extend the operation of the current GNC functionalities that assist the pilot and optimize the aircraft performance. Thus, the aim is to provoke a change in aircraft transport towards: “Full-time, all-event availability of performance-enhancement electrical fly-by-wire”. Three key enablers have been identified for moving towards this new paradigm: Flight Parameter Estimation, Fault Detection and Diagnosis, and Fault Tolerant Control.

Primordial follicles embedded in the ovarian cortex are the source of developing follicles. Follicle growth activation and development up to the small antral follicle stage are controlled by cell interactions. The sheep ovary offers an appropriate non-rodent model to study these interactions, thanks to the development of in vitro and in vivo experimental approaches, ex vivo molecular analyses and in silico mathematical modeling. Each primordial follicle, composed of an oocyte surrounded by a single layer of quiescent granulosa cells, relies on nutrients and growth factors supplied by the surrounding stroma of connective tissue. In vitro cultures of ovarian cortex have shown that primordial follicles are activated by the lifting of mechanisms maintaining quiescence, some of them involving AMH secreted by already growing follicles. Afterwards, follicle development is supported by a finely tuned molecular dialog between the growing oocyte and proliferating granulosa cells. The isolation of preantral follicles and their development in vitro as individual follicles perturb this dialog, leading to an acceleration of follicular maturation. In vivo, mutations in the oocyte factors BMP15, GDF9 or their receptor BMPR1B also impair this dialog, leading to an imbalance between oocyte growth and cell proliferation, which can be reproduced by models for cell dynamics. During the growth of preantral follicles, the recruitment and differentiation of theca cells from the ovarian stroma provide them with a structural and vascularized support. In vivo exposure of sheep fetal ovaries to testosterone imprints the stroma cells so that the expression of genes involved in extracellular matrix organization and cell-cell adhesion is affected in theca at adulthood; this leads to a lower ovarian tissue rigidity that can account for the accelerated follicle growth observed in androgenized ewes. A better knowledge of cell interactions during early follicular development will help to improve the biotechnology methods of fertility preservation.

Introduction Intensive treatments like autologous stem cells transplantations are final standard treatment in lymphoma and myeloma for young people (1,2). In the context of population's ageing, those treatments should be eligible for older patients. One of the major causes which did not allowed these procedures in elderly patients is the reports of the impact of the age on the process of mobilisation of peripheral stem cell (3). We proceed a retrospective study to explore the feasibility of stem cells collection in patients older than 65 years, compared to younger people. Material and patients During the period of 1999–2006, we identified all the patients older than 65 years, with myeloma and lymphoma, who performed peripheral stem cells collection in Brest's blood collection centre. We excluded patients for bone marrow collection. Patients were eligible if they achieved more than 2.106CD34/kg. Then we compared the results obtained in older patients with the results obtained in younger people. Results We identified 100 patients older than 65 years between the 359 patients who underwent peripheral stem cell harvest in Brest's harvest centre. We excluded 37 others patients for non-conformity. The elderly patients were significantly older (age 68.9 vs. 49.3 y, p<10−6). No differences were seen for the number of collection between the older and the younger patients (1.59 vs. 1.50, p>0.05). The number of CD34/kg per patient was sufficient to realise more than one autologous transplantation in both groups of patients (5.3 vs. 6.67, p=0.004). Samples were sufficiently rich for CD34/kg (4.36 vs. 5.54, p=0.02). Patients were harvested in one (60), two (25) or more than 2 collections (15). Among the older patients, 71% achieved a sufficient collection of more than 2.106CD34/kg in one sample only. Conclusion We identified one hundred patients older than 65 years, during a period of 8 years, who performed peripheral stem cells collection, with sufficient wealth (>2.106CD34/kg). The majority of patients, 60%, need only one stem cells harvesting. The study confirmed that old patients could be harvested like young people, and eligible for stem cells autologous transplantation.

Background: AZA is an approved drug for MDS by FDA, currently being investigated in AML. ATUs are patient named programs launched by French health authorities for yet unapproved but promising drugs, and one is ongoing for AZA in MDS and AML. Patients: 108 AML pts from 29 centres included from Sept 2004 to June 2007 in this program, and who had completed at least one course of AZA, are analyzed. They received AZA 75 mg/m2/d (d 1–7) (SC) every 4 weeks, planned for a minimum of 4 courses. Results: Median age was 75 y [range 43–91], M/F was 66/42. 51 pts had AML without and 57 pts with preceding MDS, p-AML and s-AML, respectively (resp). Pts had M0, 1, 2, 3, 4, 5, 6, and 7, in 8, 16, 30, 0, 21, 15, 6 and 4% of cases, resp. 42, 17 and 12 pts were resistant, in first or second relapse, resp, to previous cytotoxic chemotherapy (CT), including intensive anthr-AraC CT in 64 pts and LD AraC in 7, while 37 pts (all with s-AML) were untreated. Karyotype was normal, fav (t(8;21), inv 16), unfav (−7/7q- or complex), int (all others) and NA in 38, 0, 45, 18 pts and 7 pts, resp. Pts received a median of 4 cycles [range 2–16]. Response was assessed only after 4 cycles, unless pts progressed before. Thus, 15 pts were not yet evaluable. Of the remaining 93 pts, 12 (13%) achieved CR, 34 (36%) PR, (OR=49%) and 43 (46%) were considered failure. 4 pts died before end of cycle 2, without evidence of progression. 35 of the 46 responders received maintenance therapy after response was achieved. Allogeneic SCT was performed in 5 responders (2 CR+3 PR). Myelosuppression lead to dose reduction in 16% pts and hospitalization in 17% pts but no toxic death was seen. Other side effects included local reactions (reversible with local NSAID) (19%), grade I-II GI disorders (52%). OR was 34% (11% CR+23% PR) in p-AML and 60% in s-AML pts (12% CR+48% PR) (p<0.05). In p-AML, OR was 75%, 17%, 11% for normal, int and unfav karyotype (p<0.001), while in s-AML, OR was 73%, 57%, 48% for normal, int and unfav karyotype (p=NS). Considering previous treatments, OR in p-AML was 63% and 24% for pts in 1st relapse and > 1 relapse/refractory, resp (p<0.05). In s-AML, OR was 61% and 46%, in previously treated or not pts, resp (p=NS). Median actuarial response duration was 6 months (m) (range 1–22+) in s-AML, and 3 m (1–28+) in p-AML. Median actuarial survival was 9 m [3–30] and 5 m [2–31+[in s- and p-AML, resp. Conclusion: In this very high risk population (in relapse, refractory or post MDS), AZA gave 49% CR and PR, which were higher in s-AML. A prognostic value of cytogenetics and of prior treatment for response was seen in p-AML, but was only marginal in s-AML. An update will be presented.