Silicon carbide equipments for process intensification of silicon reactions.

Bluestar Silicones, one of the worldwide leaders in silicones chemistry, proposes a R&D project, aiming to design new equipment for the transposition of batch to continuous processes. The safety and environmental issues linked to this type of chemicals, and the productivity targets as well require innovative technologies characterized by a fair corrosion resistance and high heat and mass transfer performances. A preliminary prototype of heat exchanger reactor made of silicon carbide plates has been developed by the LGC in collaboration with a SME specialist of SiC, Boostec. It has allowed the pilot feasibility with some reactions of industrial interest for a Bluestar Silicones to be highlighted. Now, it is necessary to pursue this effort and beyond the feasibility step to go on up to the design of an industrial reactor. This project corresponds to a programme of innovative process development in order to design cleaner, safer and less consuming devices

Effects of potassium fertilization and throughfall exclusion on the hydraulic redistribution of soil water in Eucalyptus grandis plantations

The transport of water from moist soil layers to dry through the roots of some species is an important process for plant survival during long dry periods. The objective of the present study was to evaluate if Eucalyptus grandis roots growing in a tropical region characterized by long dry periods passively move water from deep to shallow soil layers, which is known as “hydraulic redistribution”. The experiment was carried out at the Itatinga experimental station (SP, Brazil) that included four contrasting experimental plots resulting from the combination of two set of treatments: with/without potassium fertilization (+K/-K, respectively) and with/without throughfall exclusion (+W/-W, respectively). Sap flow was measured in superficial Eucalyptus coarse roots from the end of the 2014 dry season to the end of the 2015 rainy. We detected reverse sap flow (water in superficial roots going to the soil surface far from the trunks) all of the months, even during the rainy season, and in all the treatments, except in -K-W, where reverse flow started two months after the beginning of the rains (January). The lowest flow densities in superficial roots were observed in -K and/or -W, but reverse flow occurred in more roots or during more days per month than in treatments +K and +W

Planification adaptative des essais de phase I en cancérologie

AIX-MARSEILLE2-BU Pharmacie (130552105) / SudocSudocFranceF

Translational Modeling of Anticancer Efficacy to Predict Clinical Outcomes in a First-in-Human Phase 1 Study of MDM2 Inhibitor HDM201

We report on a retrospective model-based assessment of the predictive value of translating antitumor drug activity from in vivo experiments to a phase I clinical study in cancer patients treated with the MDM2 inhibitor, HDM201. Tumor growth inhibition models were developed describing the longitudinal tumor size data in human-derived osteosarcoma xenograft rats and in 96 solid tumor patients under different HDM201 treatment schedules. The model structure describing both datasets captures the delayed drug effect on tumor growth via a series of signal transduction compartments, including a resistance component. The models assumed a drug-killing effect on both sensitive and resistant cells and parameterized to estimate two tumor static plasma drug concentrations for sensitive (TSCS) and resistant cells (TSCR). No change of TSCS and TSCR with schedule was observed, implying that antitumor activity for HDM201 is independent of treatment schedule. Preclinical and clinical model-derived TSCR were comparable (48 ng/mL vs. 74 ng/mL) and demonstrating TSCR as a translatable metric for antitumor activity in clinic. Schedule independency was further substantiated from modeling of clinical serum growth differentiation factor-15 (GDF-15) as a downstream marker of p53 pathway activation. Equivalent cumulative induction of GDF-15 was achieved across schedules when normalized to an equivalent total dose. These findings allow for evaluation of optimal dosing schedules by maximizing the total dose per treatment cycle while mitigating safety risk with periods of drug holiday. This approach helped guide a phase I dose escalation study in the selection of an optimal dose and schedule for HDM201

Towards high temperature electronic modules in which all components would be attached using silver sintering

International audienceThis article points out the fact that conventional low temperature silver sintering processes do not seem to satisfy the needs for reliability when they are used to assemble passive components (such as multilayers ceramic capacitors) in electronic modules undergoing wide amplitude thermal cycles (−65°C / +200°C). These processes indeed lead to very porous microstructures of silver which favors rapid fatigue cracks propagation [1], [2], [3]. Even if these types of porous microstructures may be suitable for die attach, tests presented in this paper show they cannot resist to the levels of thermomechanical stress reached in attachment joints of multilayers ceramic capacitors (MLCCs). To find process parameters minimizing porosity in attachment joints of capacitors, measurements of the shrinkage of silver during sintering have been carried out by dilatometry. Then the impact of densification of attachment joints on the ageing behavior and on the mechanical behavior of assemblies has been assessed in this study

Contribution of machine learning to tumor growth inhibition modeling for hepatocellular carcinoma patients under Roblitinib (FGF401) drug treatment.

Machine learning (ML) opens new perspectives in identifying predictive factors of efficacy among a large number of patients' characteristics in oncology studies. The objective of this work was to combine ML with population pharmacokinetic/pharmacodynamic (PK/PD) modeling of tumor growth inhibition to understand the sources of variability between patients and therefore improve model predictions to support drug development decisions. Data from 127 patients with hepatocellular carcinoma enrolled in a phase I/II study evaluating once-daily oral doses of the fibroblast growth factor receptor FGFR4 kinase inhibitor, Roblitinib (FGF401), were used. Roblitinib  PKs was best described by a two-compartment model with a delayed zero-order absorption and linear elimination. Clinical efficacy using the longitudinal sum of the longest lesion diameter data was described with a population PK/PD model of tumor growth inhibition including resistance to treatment. ML, applying elastic net modeling of time to progression data, was associated with cross-validation, and allowed to derive a composite predictive risk score from a set of 75 patients' baseline characteristics. The two approaches were combined by testing the inclusion of the continuous risk score as a covariate on PD model parameters. The score was found as a significant covariate on the resistance parameter and resulted in 19% reduction of its variability, and 32% variability reduction on the average dose for stasis. The final PK/PD model was used to simulate effect of patients' characteristics on tumor growth inhibition profiles. The proposed methodology can be used to support drug development decisions, especially when large interpatient variability is observed