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This letter presents an all-integrated reflection attenuator at 10 GHz with a high attenuation range and low off-state insertion loss using ScDDAs (Semiconductor Distributed Doped Areas) as tunable loads. The branch-line coupler topology used features a 20% bandwidth. The measured performance shows an attenuation range from 2 dB to 41 dB. With the use of integrated tunable loads into the silicon substrate, the presented device is competitive in die area, insertion loss and attenuation range while providing convenient DC biasing and straightforward frequency upscaling. The high integrability leads to perspectives of use in MMIC (Monolithic Microwave Integrated Circuit) systems at higher frequencies. Further work is presented showing improvements in ScDDA models using highly coupled semiconductor physics and electromagnetic structure co-simulation on COMSOL Multiphysics, replicating a high fidelity current-attenuation relationship by using a high resolution volumetric resistivity field instead of the previously used cuboid channel model, opening the way to high performance RF systems co designed on semiconductors.

Leucettinibs are substituted 2-aminoimidazolin-4-ones (inspired by the marine sponge natural product Leucettamine B) developed as pharmacological inhibitors of DYRK1A (dual-specificity, tyrosine phosphorylation-regulated kinase 1A), a therapeutic target for indications such as Down syndrome and Alzheimer’s disease. Leucettinib-21 was selected as a drug candidate following extensive structure/activity studies and multiparametric evaluations. We here report its physicochemical properties (X-ray powder diffraction, differential scanning calorimetry, stability, solubility, crystal structure) and drug-like profile. Leucettinib-21’s selectivity (analyzed by radiometric, fluorescence, interaction, thermal shift, residence time assays) reveals DYRK1A as the first target but also some “off-targets” which may contribute to the drug’s biological effects. Leucettinib-21 was cocrystallized with CLK1 and modeled in the DYRK1A structure. Leucettinib-21 inhibits DYRK1A in cells (demonstrated by direct catalytic activity and phosphorylation levels of Thr286-cyclin D1 or Thr212-Tau). Leucettinib-21 corrects memory disorders in the Down syndrome mouse model Ts65Dn and is now entering safety/tolerance phase 1 clinical trials.

In the context of epilepsy, understanding the interactions among different brain regions during epileptic seizures is often crucial to identify brain regions involved in the seizure onset. In this letter, we propose a dictionary-based method to detect and reconstruct the relationships between brain regions during epileptic seizures based on electroencephalographic signals. To this end, a proximal alternating linearized minimization algorithm is used to quantify the relations between each of the dictionary candidates. Then, by introducing an adaptive threshold, an estimation of the involvement of the different brain regions in the seizure onset is performed, which proves to be consistent with the clinical expertise.

This paper presents a highly compact Ku band 130nm SiGe power amplifier (PA) in a double balanced architecture. A highly compact low-loss 4 to 1 combiner is associated with a cascode topology to provide a power combination up to 1W and a high resilience to the standing wave ratio (SWR) from 2:1 to 4:1. A high thermal stability up to 120°C is ensured by an advanced configuration of transistors. A choices innovative set on the cascode stage design and layout improves the control of the impact ionization and selfheating. A driver stage allows the circuit to achieve over 20 dB of linear gain. At 30°C, 18 GHz and a supply voltage ( $\text{V}_{\mathrm {SUPPLY}}$ ) of 4.2V, this power amplifier achieves a measured saturated power ( $\text{P}_{\mathrm {sat}}$ ) of 30 dBm for an output power at the 1dB compression point (OCP $_{\mathrm {1dB}}$ ) of 28.8 dBm, a maximum power added efficiency (PAE) of 23.5% and a linear gain of 21.4 dB. The gain difference across 2:1 SWR phase variations is only 0.8 dB. The active area of the die chip is only 1.13 mm2.

Sagging cable-driven parallel robots (CDPRs) are often modeled by using the Irvine's model. We will show that their configurations may be unstable, and moreover, that assessing the stability of the robot with the Irvine's model cannot be done by checking the spectrum of a stiffness matrix associated with the platform motions. In this article, we show that the static configurations of the sagging CDPRs are local extrema of the functional describing the robot potential energy. For assessing the stability, it is then necessary to check two conditions: The Legendre–Clebsch and the Jacobi conditions, both well known in optimal control theory. We will also 1) prove that there is a link between some singularities of the CDPRs and the limits of stability and 2) show that singularities of the platform wrench system are not singularities of the geometric model of the sagging CDPRs, contrary to what happens in rigid-link parallel robotics. The stability prediction results are validated in simulation by cross-validating them by using a lumped model, for which the stability can be assessed by analyzing the spectrum of a reduced Hessian matrix of the potential energy.

Deep eutectic solvents (DES) are a category of a new class of solvents that can overcome some of the main drawbacks of typical solvents and ionic liquids (ILs). DES have been widely investigated and applied by the research community in several applications since their invention. Over the past years, the use of DES has been directed to the production of new materials and items for new products and processes. This is the case for the implementation of DES in various fields of chemical engineering directed to separations. DES have been very recently initiated to be combined into membranes for membrane processes. In this regard, this Review timely elucidates the current progress in utilizing this new generation of solvents in membrane preparation. In this work, different techniques, methods, and strategies for incorporating DES into polymer membranes for different concepts of membranes according to the final application have been reviewed. Particular emphasis has been devoted to the most relevant development works and results. After the current literature was analyzed, the main challenges and possibilities of DES in membranes were declared.

We previously demonstrated that 8 weeks of moderate-intensity endurance training is safe and improves muscle function and characteristics of sickle cell disease (SCD) patients. Here, we investigated skeletal muscle satellite cells (SCs) in SCD patients and their responses to a training program. Fifteen patients followed the training program while 18 control patients maintained a normal lifestyle. Biopsies of the vastus lateralismuscle were performed before and after training. After training, the cross-sectional area and myonuclear content in type I fibers were slightly increased in the training patients compared to non-training patients. The SC pool was unchanged in type I fibers while it was slightly decreased in type II fibers in the training patients compared to non-training patients. No necrotic fibers were detected in patients before or after training. Therefore, the slight myonuclear accretion in type I fibers in trained SCD patients may highlight the contribution of SCs to training-induced slight type I fiber hypertrophy without expansion of the SC pool. The low training intensity and the short duration of training sessions could explain the low SC response to the training program. However, the lack of necrotic fibers suggests that the training program seemed to be safe for patients’ muscle tissue.

La conciliation médicamenteuse (CM) est un processus hautement sécurisant de la prise en charge médicamenteuse des patients. Elle a été mise en place dans notre Centre Hospitalier en 2015 et a pris un essor plus significatif en 2018 avec 2 services de chirurgie (CM d’entrée) et un Centre de soins de suite et de réadaptation (CM d’entrée et de sortie). Elle était jusqu’alors réalisée par un pharmacien.

We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations [...]

Following the ideas of Zhikov and Piatnitski (Izv Math 70(1):19–67, 2006), and more precisely the stochastic two-scale convergence, this paper establishes a homogenization theorem in a stochastic setting for two nonlinear equations: the equation of harmonic maps into the sphere and the Landau–Lifschitz–Gilbert equation. These equations have strong nonlinear features, and in general their solutions are not unique.

The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis.

Sizing distribution equipment of a district heating (DH) network is a complex yet decisive process to target techno-economic optimality for these systems. This paper describes and validates a framework that uses multi-objective optimization to support decisions regarding the sizing of a DH network. A genetic algorithm (NSGA2) is employed to generate optimal pipe diameters with respect to the operational and investment cost. This framework is then validated using an elementary toy problem consisting of a straight horizontal two-tube network, with a set of identical consumers equally distributed in the network and supplied by a unique heat source. We show that the framework, on the aforementioned problem, reaches very good convergence and diversity for the optimal solutions.

Li-O2batteries offer a high theoretical discharge capacity due to the formation of light discharged species such as Li2O2, which fill the porous positive electrode. However, in practice, it is challenging to reach the theoretical capacity and completely utilize the full electrode pore volume during discharge. With the formation of discharge products, the porous medium evolves, and the porosity and tortuosity factor of the positive electrode are altered through shrinkage and clogging of pores. A pore shrinks as solid discharge products accumulate, the pore clogging when it is filled (or when access is blocked). In this study, we investigate the structural evolution of the positive electrode through a combination of experimental and computational techniques. Pulsed field gradient nuclear magnetic resonance results show that the electrode tortuosity factor changes much faster than suggested by the Bruggeman relation (an equation that empirically links the tortuosity factor to the porosity) and that the electrolyte solvent affects the tortuosity factor evolution. The latter is ascribed to the different abilities of solvents to dissolve reaction intermediates, which leads to different discharge product particle sizes: on discharging using 0.5 M LiTFSI in dimethoxyethane, the tortuosity factor increases much faster than for discharging in 0.5 M LiTFSI in tetraglyme. The correlation between a discharge product size and tortuosity factor is studied using a pore network model, which shows that larger discharge products generate more pore clogging. The Knudsen diffusion effect, where collisions of diffusing molecules with pore walls reduce the effective diffusion coefficients, is investigated using a kinetic Monte Carlo model and is found to have an insignificant impact on the effective diffusion coefficient for molecules in pores with diameters above 5 nm, i.e., most of the pores present in the materials investigated here. As a consequence, pore clogging is thought to be the main origin of tortuosity factor evolution.

Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

La TEP/TDM au 18F-FDG est un examen performant pour le bilan d’extension du mélanome à haut risque de dissémination. Pour les mélanomes de Breslow≥1mm, l’échographie ganglionnaire et, en cas de négativité de celle-ci, la lymphoscintigraphie à la recherche du ganglion sentinelle restent incontournables. Pour les stades plus avancés, la TEP FDG va permettre de cartographier les lésions et de guider la stratégie thérapeutique, soit vers un traitement chirurgical, soit vers un traitement systémique, parfois une combinaison des deux. Dans le suivi des patients à haut risque, elle permet également d’identifier des récidives, y compris chez les patients asymptomatiques, avec un impact possible sur la prise en charge. Outre la détection de localisations néoplasiques secondaires fréquentes, la TEP/TDM au 18F-FDG présente l’avantage de permettre la réalisation d’une imagerie corps entier et d’identifier aisément les atteintes des tissus mous fréquentes dans les mélanomes, ainsi que d’autres atteintes plus rares, telles que celles du tube digestif. Pour la recherche des atteintes cérébrales et méningées, l’IRM reste indispensable. Les évolutions dans la prise en charge des mélanomes avancés et la recherche de biomarqueurs pour guider la stratégie thérapeutique invitent à proposer des analyses plus fines de la TEP, avec notamment l’analyse du volume métabolique et les radiomics. La combinaison des données d’imagerie métabolique avec les données biologiques et moléculaires et le développement de nouveaux traceurs TEP pourraient améliorer l’évaluation pronostique et la prédiction de la réponse aux thérapies et d’aller vers la stratégie thérapeutique « personnalisée ». De nouvelles études seront donc nécessaires pour consolider le rôle de la TEP/TDM dans cette pathologie où les innovations thérapeutiques sont multiples.

As nanofiltration applications increase in diversity, there is a need for new fabrication methods to prepare chemically and thermally stable membranes with high retention performance. In this work, thio-bromo “click” chemistry was adapted for the fabrication of a robust covalently attached and ultrathin nanofiltration membrane. The selective layer was formed on a pre-functionalized porous ceramic surface via a novel, liquid–vapor interfacial polymerization method. Compared to the most common conventional interfacial polymerization procedure, no harmful solvents and a minimal amount of reagents were used. The properties of the membrane selective layer and its free-standing equivalent were characterized by complementary physicochemical analysis. The stability of the thin selective layer was established in water, ethanol, non-polar solvents, and up to 150 °C. The potential as a nanofiltration membrane was confirmed through solvent permeability tests (water, ethanol, hexane, and toluene), PEG-in-water molecular weight cut-off measurements (≈700 g mol–1), and dye retention measurements.

Supercritical fluid extraction, using a hollow fiber membrane contactor (HFMC), is an attractive and feasible process for the food industry due to the controlled contact between the phases and the safety that the membrane processes allow. This research aimed at the extraction of vanillin from an aqueous solution with supercritical carbon dioxide (SCCO2). The highest extraction percentage and permeate flux of the system were established through the evaluation of operational parameters. The extraction was developed using an HFMC under steady-state conditions and by varying the vanillin concentration (70–500 ppm), temperature (35–50 °C) and pressure of the system (75–140 bar), aqueous solution flow rates (0.1–0.5 mL min–1), and SCCO2flowrates (50–80 mL min–1in standard conditions).Experimental results showed the feasibility of extracting vanillin in one step, obtaining extraction percentages between 24.51 and 47.97%. Simultaneously, the mass transfer analysis of the HMFC by means of numerical simulation based on the theory of a resistance-in-series model depicted the negative effect of the temperature on the extraction capacity of this system. In an overall analysis and for the changes in the pressure and temperature of the system, it was possible to demonstrate that the phase equilibrium established at the aqueous–SCCO2interface was determinant in the separation performance of this membrane contactor process.

Y-doped BaZrO3is a promising proton conductor for intermediate temperature solid oxide fuel cells. In this work, a combination of static DFT calculations and DFT based molecular dynamics (DFT-MD) was used to study proton conduction in this material. Geometry optimizations of 100 structures with a 12.5% dopant concentration allowed us to identify a clear correlation between the bending of the metal–oxygen–metal angle and the energies of the simulated cells. Depending on the type of bending, two configurations, designated as inward bending and outward bending, were defined. The results demonstrate that a larger bending decreases the energy and that the lowest energies are observed for structures combining inward bending with protons being close to the dopant atoms. These lowest energy structures are the ones with the strongest hydrogen bonds. DFT-MD simulations in cells with different yttrium distributions provide complementary microscopic information on proton diffusion as they capture the dynamic distortions of the lattice caused by thermal motion. A careful analysis of the proton jumps between different environments confirmed that the inward and outward bending states are relevant for the understanding of proton diffusion. Indeed, intra-octahedral jumps were shown to only occur starting from an outward configuration while the inward configuration seems to favor rotations around the oxygen. On average, in the DFT-MD simulations, the hydrogen bond lengths are shorter for the outward configuration which facilitates the intra-octahedral jumps. Diffusion coefficients and activation energies were also determined and compared to previous theoretical and experimental data, showing a good agreement with previous data measuring local proton motion.

We use molecular simulations of an ionic liquid in contact with a range of nanoporous carbons to investigate correlations between the ion size, pore size, pore topology, and properties of the adsorbed ions. We show that diffusion coefficients increase with the anion size and, surprisingly, with the quantity of adsorbed ions. Both findings are interpreted in terms of confinement: when the in-pore population increases, additional ions are located in less-confined sites and diffuse faster. Simulations in which the pores are enlarged while keeping the topology constant support these observations. The interpretation of properties across structures is more challenging. An interesting point is that smaller pores do not necessarily lead to a larger confinement. In this work, the highest degrees of confinement are observed for intermediate pore sizes. We also show a correlation between the quantity of adsorbed ions and the ratio between the maximum pore diameter and the pore limiting diameter.

The development of BRAF and MEK inhibitors (BRAFi/MEKi) has led to major advances in melanoma treatment. However, the emergence of resistance mechanisms limits the benefit duration and a complete response occurs in less than 20% of patients receiving BRAFi ± MEKi. In this study, we evaluated the impact of an intermittent versus continuous dosing schedule of BRAF/MEK inhibition in a melanoma model mildly sensitive to a BRAF inhibitor. The combination of a BRAFi with three different MEKi was studied with a continuous or intermittent dosing schedule in vivo,in a xenografted melanoma model and ex vivousing histoculture drug response assays (HDRAs) of patient-derived xenografts (PDX). To further understand the underlying molecular mechanisms of therapeutic efficacy, a biomarker pharmacodynamic readout was evaluated.

Molecular helices based on self-organized aromatic oligoamide foldamers have been designed and prepared in their two enantiomeric forms in order to probe their second-order nonlinear chiroptical properties in solution. The quinoline oligoamides were rationally functionalized by electron-donating and electron-withdrawing groups to afford a gradual increase of the electronic polarization of the helical architectures. Their hyper-Rayleigh scattering (HRS) responses in solution were accordingly assessed, using either linearly polarized or circularly polarized incident light. Both methods allowed us to observe nonlinear optical activity that was quantified, for the first time for molecular systems, through circular differential scattering intensity ratios. The hyper-Rayleigh optical activity study reveals important charge-transfer differences within the aromatic oligomers, depending on the helix handedness and on the extent of electronic polarization induced by the appended substituents. The origin of the enantiomeric difference is discussed considering both achiral and chiral contributions. Overall, using aromatic oligoamide foldamers as a chiral model, we demonstrate the capabilities of HRS as a complementary chiroptical method, ideally suited for the analysis of various chiral molecular and supramolecular systems in solution. The reliability and chiral discrimination sensitivity of the method can be further improved through dynamic measurements using standard polarization modulation and heterodyning techniques.

Sickle cell disease (SCD) is a genetic hemoglobinopathy leading to 2 major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known. The aim of this study was to evaluate the effects of an endurance training program on microvasculature of skeletal muscle in SCD patients. A biopsy of the vastus lateralismuscle and submaximal incremental exercise was performed before and after the training period. Of the 40 randomized SCD patients, complete data sets from 32 patients were obtained. The training group (n = 15) followed a personalized moderate-intensity endurance training program, while the nontraining (n = 17) group maintained a normal lifestyle. Training consisted of three 40-minute cycle ergometer exercise sessions per week for 8 weeks. Histological analysis highlighted microvascular benefits in the training SCD patients compared with nontraining patients, including increases in capillary density (P= .003), number of capillaries around a fiber (P= .015), and functional exchange surface (P< .0001). Conversely, no significant between-group difference was found in the morphology of capillaries. Indexes of physical ability also improved in the training patients. The moderate-intensity endurance exercise training program improved the muscle capillary network and partly reversed the microvascular defects commonly observed in skeletal muscle of SCD patients. This trial was registered at www.clinicaltrials.govas #NCT02571088.

We conduct molecular dynamics simulations of electrical double-layer capacitors (EDLCs) using a library of ordered, porous carbon electrode materials called zeolite templated carbons (ZTCs). The well-defined pore shapes of the ZTCs enable us to determine the influence of pore geometry on both charging dynamics and charge storage mechanisms in EDLCs, also referred to as supercapacitors. We show that charging dynamics are negatively correlated with the pore-limiting diameter of the electrode material and display signatures of both progressive charging and ion trapping. However, the equilibrium capacitance, unlike charging dynamics, is not strongly correlated to commonly used, purely geometric descriptors such as pore size. Instead, we find a strong correlation of capacitance to the charge compensation per carbon (CCpC), a descriptor we define in this work as the average charge of the electrode atoms within the coordination shell of a counterion. A high CCpC indicates efficient charge storage, as the strong partial charges of the electrode are able to screen counterion charge, enabling higher ion loading and thus more charge storage within the electrode at a fixed applied voltage. We determine that adsorption sites with a high CCpC tend to be found within pockets with a smaller radius of curvature, where the counterions are able to minimize their distance with multiple points on the electrode surface, and therefore induce stronger local partial charges.

In this paper we define and study a finite volume scheme for a concrete carbonation model proposed by Aiki and Muntean in [Adv. Math. Sci. Appl.19(2009) 109–129]. The model consists in a system of two weakly coupled parabolic equations in a varying domain whose length is governed by an ordinary differential equation. The numerical sheme is obtained by a Euler discretisation in time and a Scharfetter-Gummel discretisation in space. We establish the convergence of the scheme. As a by-product, we obtain existence of a solution to the model. Finally, some numerical experiments show the efficiency of the scheme.

Molecular dynamics simulations have been used extensively to determine equilibrium properties of the electrode–electrolyte interface in supercapacitors held at various potentials. While such studies are essential to understand and optimize the performance of such energy storage systems, investigation of the dynamics of adsorption during the charge of the supercapacitors is also necessary. Dynamical properties are especially important to get an insight into the power density of supercapacitors, one of their main assets. In this work, we propose a new method to coarse-grain simulations of all-atom systems and compute effective Lennard-Jones and Coulomb parameters, allowing subsequently to analyze the trajectories of adsorbing ions. We focus on pure 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide in contact with planar carbon electrodes. We characterize the evolution of the ion orientation and ion–electrode distance during adsorption and show that ions reorientate as they adsorb. We then determine the forces experienced by the adsorbing ions and demonstrate that Coulomb forces are dominant at a long range while van der Waals forces are dominant at a short range. We also show that there is an almost equal contribution from the two forces at an intermediate distance, explaining the peak of ion density close to the electrode surface.

The effect of meditation on brain activity has been the topic of many studies in healthy subjects and in patients suffering from chronic diseases. These effects are either explored during meditation practice (state effects) or as a longer-term result of meditation training during the resting-state (trait). The topic of this article is to first review these findings by focusing on electroencephalography (EEG) changes in healthy subjects with or without experience in meditation. Modifications in EEG baseline rhythms, functional connectivity and advanced nonlinear parameters are discussed in regard to feasibility in clinical applications. Secondly, we provide a state-of-the-art of studies that proposed meditative practices as a complementary therapy in patients with epilepsy, in whom anxiety and depressive symptoms are prevalent. In these studies, the effects of standardized meditation programs including elements of traditional meditation practices such as mindfulness, loving-kindness and compassion are explored both at the level of psychological functioning and on the occurrence of seizures. Lastly, preliminary results are given regarding our ongoing study, the aim of which is to quantify the effects of a mindfulness self-compassion (MSC) practice on interictal and ictal epileptic activity. Feasibility, difficulties, and prospects of this study are discussed.

As a longtime RVer I have learned that diesel fuel foams (or blows back if there is no auto stop). To help with the resulting mess, I take a full-size [...]

Exercise could be a triggering factor for vaso-occlusive crises in patients with sickle-cell disease. We aimed to investigate whether a patient-adapted training programme of moderate endurance exercise could be safe and beneficial for patients with sickle-cell disease.

Abstract Objective--To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy. Design--Prospective cohort study. Setting--Tertiary referral centre. Patients--40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) [...]

In Vivo and in Vitro Studies Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of [...]

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La loi du 2 février 2016 a créé de nouveaux droits pour les patients en fin de vie, dont celui d’une sédation profonde et continue maintenue jusqu’au décès à la demande du patient. Elle suscite des débats sur ses enjeux éthiques, notamment au sein des professionnels expérimentés de soins palliatifs.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1532-5415.2009.02645.x Byline: Odile Debouverie (*), Remi Coudroy (*), Isabelle Merlet-Chicoine (*), Francois Salmon ([dagger]), Roger Gil ([double dagger]), Marc Paccalin (s.,[parallel]) Author Affiliation: (*)Pole de Geriatrie, CHU La Miletrie, Poitiers, France ([dagger])Service de Medecine Nucleaire CHU La Miletrie, Poitiers, France ([double dagger])Centre Memoire de Ressources et de Recherche, EA 3808 Universite de Poitiers, CHU La Miletrie, Poitiers, France (s.)Pole de Geriatrie, Centre Memoire de Ressources et de Recherche, EA3808 Universite de Poitiers, CHU La Miletrie, Poitiers, France ([parallel])CIC INSERM U802, Poitiers, France

An heteropolyanion compound consisting of saturated Dawson anions and trivalent iron cations, a2H3FeP2W17MoO62has been synthesized and characterized by various spectroscopic methods, IR, UV-Vis, 31P NMR and ESI-MS. The catalytic performances of heteropolyanion were tested for degradation of aqueous Malachite Green dye under Fenton process. The degradation reaction was monitored by UV-visible and IR spectroscopy. The effects of different reaction parameters such as the initial pH of the medium, the initial hydrogen peroxide concentration, the catalyst mass, the initial MG concentration and the reaction temperature on the oxidative degradation of malachite green has been investigated. The optimal reacting conditions were found to be pH = 3, initial hydrogen peroxide was 0.31 M, and the catalyst mass was 0.03 g, for initial MG concentration of 20 mg.L–1at 30°C. After optimizing operating parameters, the dye was demineralized after 7 h of reaction.

Polymorphisms in the adenylate cyclase 9 (ADCY9) gene influence the benefits of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on cardiovascular events after acute coronary syndrome. We hypothesized that Adcy9inactivation could improve cardiac function and remodeling following myocardial infarction (MI) in absence of CETP activity.

Glioblastoma stem-like cells (GSCs) compose a tumor-initiating and -propagating population, remarkably vulnerable to variation in the stability and integrity of the lysosomal compartment. Previous work showed that the expression and activity of the paracaspase MALT1 control GSC viability via lysosome abundance. However, the underlying mechanisms remain elusive. By combining RNAseq with proteome-wide label-free quantification, we now report that MALT1 repression in patient-derived GSCs alters the homeostasis of cholesterol, which accumulates in late endosomes (LE)-lysosomes. This failure in cholesterol supply culminates in cell death and autophagy defects, which can be partially reverted by providing exogenous membrane-permeable cholesterol to GSCs. From a molecular standpoint, a targeted lysosome proteome analysis unraveled that Niemann-Pick type C (NPC) lysosomal cholesterol transporters are diluted when MALT1 is impaired. Accordingly, we found that NPC1/2 inhibition and silencing partially mirror MALT1 loss-of-function phenotypes. This supports the notion that GSC fitness relies on lysosomal cholesterol homeostasis.

Les inhibiteurs de checkpointimmunitaires (ICI) constituent désormais la première ligne de traitement pour le mélanome avancé. Cependant, il y a peu de facteurs prédictifs et pronostiques permettant d’identifier les patients qui en bénéficieront. Quelques études ont montré que le volume métabolique tumoral total (TMTV), déterminé sur une TEP/TDM FDG pouvait avoir une valeur pronostique. En outre, un nouveau paramètre TEP, le Dmax, correspondant à la plus grande distance entre deux lésions sur une TEP, a été proposé dans le lymphome agressif et pourrait affiner la stratification du risque. Dans une analyse rétrospective, nous avons étudié la valeur pronostique du TMTV et du Dmax pré-thérapeutiques. Nous avons également comparé leur valeur pronostique avec celle d’éléments clinicobiologiques reconnus tels que les LDH et le nombre de sites métastatiques.

La croissance de biofilms sur les parois des réseaux et des circuits d'eaux est un problème récurrent en terme de santé publique. Les légionelles qui se développent dans les réseaux d'eaux chaudes et les tours aéroréfrigérantes ont été à l'origine de plus de 1000 cas annuels de légionellose en France au cours des 3 dernières années, la létalité étant d'environ 14 %. Pour maîtriser ce développement bactérien, il est nécessaire de posséder une meilleure compréhension des biofilms, de leur croissance et de leur composition. Dans ce but, trois années de travail de collaboration entre la société Henkel Concorde et 2 équipes CNRS (UMR 6008 et UPR 15) ont permis de développer un outil de détermination de l'épaisseur moyenne du biofilm. Sur des unités pilote en laboratoire et sur site industriel, cette mesure de l'épaisseur du biofilm s'est révélée suffisamment précise et sensible pour suivre l'évolution de la formation d'un biofilm dans un circuit d'eau et pour déterminer l'efficacité des traitements appliqués. L'utilisation de cet outil de surveillance a permis d'optimiser les traitements appliqués (nature, dose, fréquence d'injection) et conduit à une réduction significative des biomasses fixées, au maintien de la propreté des circuits et donc à une maîtrise accrue du risque légionelle.

L’exploration du nodule pulmonaire solitaire (NPS) et celle du cancer bronchopulmonaire non à petites cellules se sont rapidement imposées comme des indications clés de la TEP (désormais TEP-TDM) au 18F-fluorodésoxyglucose (FDG). Dans cette mise au point, nous évaluerons dans un premier temps la place de cet examen, en complément de l’imagerie TDM, pour l’exploration du NPS. Nous mettrons en avant les perspectives de la recherche actuelle visant à mieux caractériser le nodule pulmonaire. Nous définirons ensuite la place actuelle de l’imagerie TEP-TDM dans la prise en charge globale du cancer bronchopulmonaire. Nous ferons le point sur les indications consensuelles, comme le bilan d’extension initial, et nous évaluerons les indications émergentes comme l’optimisation des champs de radiothérapie ou l’évaluation pronostique.

Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor‐2 (FGF‐2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF‐2 limited hypoxia‐induced downregulation of HGF release. Using three‐dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF‐2 treatment increased the fraction of Stro‐1+/CD146+ progenitor cells. We then applied in vitro FGF‐2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF‐2 priming is more efficient than hypoxia at increasing SHED‐induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF‐2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. The results from the present study show that fibroblast growth factor‐2 (FGF‐2) priming is more efficient than hypoxia at increasing dental pulp stem cells derived from deciduous teeth (SHED)‐induced vascularization compared with nonprimed controls. Together, these data demonstrate that FGF‐2 priming enhances the angiogenic potential of SHED through the secretion of both hepatocyte growth factor and vascular endothelial growth factor. Tissue engineering strategies using implantation of cellularized biomaterials are promising approaches for large tissue defect reconstruction. Additional key factors regulating the angiogenic capacity of dental pulp stem cells derived from deciduous teeth (SHED) were characterized. The presented data demonstrate that fibroblast growth factor‐2 priming enhances the angiogenic potential of SHED through the secretion of hepatocyte growth factor and vascular endothelial growth factor.