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In advanced oestrogen receptor-positive, HER2-negative breast cancer, acquired resistance to aromatase inhibitors frequently stems from ESR1-mutated subclones, which might be sensitive to fulvestrant. The PADA-1 trial aimed to show the efficacy of an early change in therapy on the basis of a rising ESR1 mutation in blood (bESR1We did a randomised, open-label, phase 3 trial in 83 hospitals in France. Women aged at least 18 years with oestrogen receptor-positive, HER2-negative advanced breast cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited and monitored for rising bESR1From March 22, 2017, to Jan 31, 2019, 1017 patients were included, of whom 279 (27%) developed a rising bESR1PADA-1 is the first prospective randomised trial showing that the early therapeutic targeting of bESR1Pfizer.

In the present work, L-glutamic acid production by Corynebacterium glutamicum fermentation on date juice extracts applying two fed-batch feeding modes, pulsed and continuous, were investigated. According to the obtained results, the continuous feeding fed-batch mode was found to be the most efficient process. Moreover the continuous feeding rate mode with a feeding medium containing date juice sugars enriched with ammonium sulfate was found even more favorable as it enhances the L-glutamic acid production by approximately 2.35 fold more than the batch culture and by about 1.17 fold more than the pulsed feeding. In this respect, comparing the traditional batch culture to the continuously fed culture with a medium containing date juice sugars with ammonium sulfate showed increases of 135.47% in L-glutamic acid production, 104% in productivity, 39.09% in biomass, and 47.69% in the yield respectively allowing us to reach a final L-glutamic acid concentration of about 138 g/L, the highest ever published.

Opuntia ficus indica (OFI) waste was evaluated as a fermentation feedstock for lactic acid production using Lactobacillus plantarum. Dilute acid pretreatment of the OFI cladodes (OFIC) was performed for extracting maximum fermentable sugars by optimizing process parameters using statistical optimization method. The best results were obtained with HCl 1% (v/v), temperature 120 ◦C, residence time 40 min, granulation 350 μm and substrate loading 5% (w/v), the sugar concentration reached 24 g/L with low concentration of hydroxymethylfurfural. The feasibility of producing lactic acid from OFI fruit peel (OFIFP) as a source of carbon was also investigated. Lactobacillus plantarum was shown to have a capacity for lactic acid production from OFIC350 (granulation 350 μm) hydrolysate and OFIFP extract without detoxification. The highest lactic acid yields of 0.46 and 0.78 g/g were obtained from enzymatic hydrolysate of pretreated OFIC350 and OFIFP extract, respectively. info:eu-repo/semantics/publishedVersion

International audience; The hollow fiber membrane bioreactor (HFMB) has been investigated for the cultivation of mammalian Chinese hamster ovary cell expansion. The experiments were carried out in Petri’s dishes and in the hollow fiber membrane bioreactor having 20 fibers (S2025 from FiberCell Systems). The approach to HFMB modelling which combines the model of cell growth kinetics and hydrodynamics has been proposed. The hydrodynamic model is made using ANSYS Fluent software. The mathematical model of HFMB was developed, allowing the study of the hydrodynamics into the lumen and the extracapillary spaces, the filtration through the membrane fiber with the cell expansion on outer membrane surface. The direct nutrient medium flow variant into the extracapillary space was suggested. Based on the numerical simulations, the optimal parameters were selected for daily changes in the medium flow-rate into the lumen space. The HFMB scaling up was performed for the larger size HFMB (60 fibers).

International audience

International audience; Biocatalytic processes continue to find increasing application in industry. Therefore enzyme immobilization has also become of increasing importance as a means of allowing enzyme containment within reactors operating in continuous mode or else separation of enzyme after use in (fed-)batch reactors, as well as potential recycle. Whilst much has been reported in the scientific literature about enzyme immobilization methods, in many cases the protocol leads to losses in enzyme activity. In this review we outline the reasons for loss of activity during immobilization and highlight suitable diagnostic tests to elucidate the precise cause and thereby methods to restore activity. The need for standardized reporting of immobilization methods is also emphasized as a means of benchmarking alternative approaches.

The feasibility of baker's yeast production using fruits and peels of Opuntia ficus indica (OFI) as carbohydrate feedstock was investigated. Two response surface methodologies involving central composite face centered design (CCFD) were successfully applied. The effects of four independent variables on baker's yeast production from OFI fruit juice was evaluated using the first CCFD. The best results were obtained with 24 H of inoculum age, 30 degrees C temperature, 200 rpm of agitation, and 10% inoculum size. At the maximum point, the biomass concentration reached 9.29 g/L. A second CCFD was performed to optimize the sugar extraction from OFI fruit peels. The potential of these latter as a fermentation substrate was determined. From the experimental results, the OFI fruit peel is an appropriate carbon source for the production of baker's yeast. The maximum biomass concentration was 12.51 g/L. Different nitrogen supplements were added to promote the yields of baker's yeast. Corn steep liquor was found to be the best alternative nutrient source of casein hydrolysate and yeast extract for baker's yeast production. info:eu-repo/semantics/publishedVersion

National audience; Les aidants familiaux jouent un rôle central auprès des patients présentant un cancer de stade avancé. Parmi les proches susceptibles d’apporter une aide aux personnes malades, les conjoints, en raison des liens qui les unissent et parce qu’ils partagent leur vie quotidienne, sont sans doute les plus confrontés à la maladie. Ils sont également majoritairement désignés comme étant l’aidant principal. L’irruption de la maladie et le besoin d’accompagnement qu’elle nécessite, viennent bouleverser en profondeur les différents équilibres structurant leur quotidien et leur organisation. Ils viennent aussi questionner la nature des relations qu’ils entretiennent, dans une diversité d’espace-temps soumise à une régulation précise et rigoureuse permettant la stabilité des activités sociales de ses membres. L’aide à apporter n’étant jamais entièrement prévisible ni planifiable, les conjoints doivent constamment adapter leurs comportements, modifier leur(s) rôle(s) et leur aide en fonction des évolutions de la maladie, de l’état de santé et du vécu du proche malade. Ils doivent donc apprendre à devenir « compétents » et tenter de tirer parti de combinaisons appropriées de ressources, qu’elles soient internes ou externe au couple. S’interroger, à partir d’une enquête qualitative, sur ces aspects organisationnels et structurels de l’aide apportée par les conjoints nous a semblé important dans cette étude car la nature de ces choix et leurs conséquences peuvent considérablement venir renforcer, ou au contraire affaiblir, le degré d’implication des aidants, leur potentielle reconnaissance vis-à-vis de leur rôle d’accompagnement ainsi que leur propre état de santé et leur qualité de vie. L’objectif de notre analyse était donc d'identifier les compétences mobilisées, développées ou réactualisés par les conjoints de patients présentant un cancer du côlon, ainsi que les ressources associées dans lesquelles ils choisissent ou non de puiser.

The production of lactic acid from date juice by Lactobacillus caseisubsp. rhamnosus in batch and fed-batch cultures has been investigated. The fed-batch culture system gave better results for lactic acid production and volumetric productivity. The aim of this work is to determine the effects of the feeding rate and the concentration of the feeding medium containing date juice glucose on the cell growth, the consumption of glucose and the lactic acid production by Lactobacillus casei subsp. rhamnosus in fed-batch cultures. For this study, two concentrations of the feeding medium (62 and 100 g/L of date juice glucose) were tested at different feeding rates (18, 22, 33, 75 and 150 mL/h). The highest volumetric productivity (1.3 g/L.h) and lactic acid yield (1.7 g/g) were obtained at a feeding rate of 33 mL/h and a date juice glucose concentration of 62 g/L in the feeding medium. As a result, most of the date juice glucose was completely utilised (residual glucose 1 g/L), and a maximum lactic acid production level (89.2 g/L) was obtained.

Sawdust wood (SW) is a promising lignocellulosic biomass for lactic acid production due to its abundant availability, low cost and high carbohydrates content that can be converted to fermentable sugars. The dilute acid hydrolysis of SW was investigated in this study and Lactococcus lactis was used to determine the feasibility of utilizing WS as feedstock for the production of lactic acid. Central composite design (CCD) was employed to optimize sulfuric acid, substrate loading and hydrolysis time for maximum sugar recovery. The results obtained were interpreted by analysis of variance and response surface methodology. The optimal acid hydrolysis conditions were as follows: sulfuric acid concentration of 8% (v/v) with substrate loading of 16% (w/v) and hydrolysis time of 2h. Under the optimal conditions, a glucose concentration of 8.78g/L was achieved. A regression model was generated according to the experimental data. Upon statistical analysis, coefficient of determination (R2 ) obtained was 0.96. Lactococcus lactis was found to be a potent lactic acid bacteria (LAB) strain for the production of lactic acid utilizing acid hydrolysate of WS and yeast extract as carbon and nitrogen sources, respectively. The maximum lactic acid concentration of 9.87g/L was obtained with a yield of 1.1g/g.