Competition of Secondary versus Tertiary Carbenium Routes for the Type B Isomerization of Alkenes over Acid Zeolites Quantified by Ab Initio Molecular Dynamics Simulations

International audienceThe skeletal isomerization of alkenes catalyzed by zeolites involves secondary and tertiary carbenium ions for which respective reactivity cannot be easily assessed by standard theoretical approaches. Thanks to ab initio molecular dynamics, starting from 4-methyl-hex-1-ene (a monobranched C7 alkene), we identify and compare two mechanistic routes for skeletal isomerization: (i) a type B isomerization transforming a secondary carbenium into a tertiary carbenium (conventional route), and (ii) a two-step route involving an intramolecular 1,3 hydride-shift producing a tertiary carbenium, followed by a type B isomerization between two tertiary carbenium ions. We find that, in the case of the secondary cation, the relevant species from a kinetic point of view is the corresponding π-complex. The transition states found for type B isomerization reactions are edge-protonated cyclopropanes (edge-PCP) that exhibit similar stabilities and structures. The transition state for the 1,3-hydride shift is an edge-type PCP with one elongated C–C bond that is more stable than the one found for type B isomerization. From this analysis, we deduce relevant kinetic constants and quantify the respective contribution of both pathways to the global reaction rate. Although the secondary carbenium ions are poorly stable species, we show that they can hold a significant part of the reaction flux. Finally, we discuss, in detail, our kinetic and mechanistic insights with previous kinetic modeling data reported in the literature

On the origin of the difference between type A and type B skeletal isomerization of alkenes catalyzed by zeolites : the crucial input of ab initio molecular dynamics

International audienceAlkene skeletal isomerization elementary steps catalyzed by acid zeolites are key reactions in refining, petrochemistry and biomass conversion. We unravel the atomic-scale origin of the higher rate constant of type A isomerization (involving a direct alkyl transfer, without any change in the branching degree) than the one of type B isomerization (involving non-classical carbonium ions such as protonated cyclopropane (PCP), inducing a change in the branching degree) of C7 carbenium ions in chabazite. Accurate free energy barriers are calculated at 300 and 500 K for both reactions by means of molecular dynamics in combination with blue moon ensemble approach, whereas the static approach is shown to fail to describe these reactions. The slow transformation between individual rotational isomers, causing non-ergodic sampling of reactant state, largely overlooked in literature, is carefully addressed in the present work. At 500 K (representative of experimental conditions), free energy barriers of 83.4 kJ/mol and 15.0 kJ/mol are determined for type B and type A isomerization respectively. The much lower barrier for type A is thus recovered, and assigned to a loose transition state, with free rotation of the migrating alkyl group, while the transition state of type B isomerization is tighter, with such a rotation blocked, due to the simultaneous hydride shift taking place on the edge of the PCP

Location of the Active Sites for Ethylcyclohexane Hydroisomerization by Ring Contraction and Expansion in the EUO Zeolitic Framework

International audienceIdentifying the location of the active sites in a zeolite is a current challenge, impeding the design of optimal catalysts. In this work, we identify the location of the most active sites of 1-ethylcyclohexene isomerization in the EUO framework (10 MR channels, 12 MR side pockets) thanks to DFT calculations corroborated by experiments. Skeletal isomerization of cycloalkenes is a crucial industrial reaction for the bifunctional isomerization of ethylbenzene. Ethylcyclohexene is protonated by framework protons into cyclic carbenium ions, which undergo ring contraction–expansion reactions through protonated cyclopropane (PCP) like transition states. Ab initio calculations clearly show that the acid sites located at the intersection between the channel and the pocket stabilize much less the cyclic carbenium ions involved in the reaction than 12 MR pockets and 10 MR channel sites due to stronger dispersion stabilizing interactions. This computational finding is fully confirmed experimentally by the comparison of the catalytic performances of the H-EU-1 and H-ZSM-50 zeolites in ethylcyclohexane hydroisomerization. Both zeolites possess the EUO structure but with different location of the acid sites. The ratio in turnover frequencies is quantitatively rendered by the DFT-calculated free energy profiles. Diffusion measurements reveal similar ethylcyclohexane diffusion times for the two zeolites, supporting that the difference in activity is primarily driven by the location of the active sites

Field study of cross-reef dynamics above the Ouano coral barrier, New Caledonia, France

National audienceMostly present in tropical regions, coral reefs both provide a unique habitat for a wide variety of living organisms and very efficient protection against ocean action on nearshore and lagoon areas. Recent tsunamis and cyclones events demonstrated that the weakening of coral barriers can have tremendous consequences on nearshore areas, including submersion, erosion and overwash deposit. The present field work aims to study the hydrodynamic processes over a reef barrier, focusing in particular of the offshore wave energy transmission toward the lagoon. The selected field site is the Ouano lagoon, New Caledonia, France. A three-months survey has been performed from september to november 2013 including wave measurements by pressure sensors at the outside reef, above the reef flat and inside the lagoon and velocity profiles measurements at selected places inside the lagoon. During the studied season, the reef is permanently exposed to long swell waves with significant wave height ranging from 0.4 to 2.7m. The wave energy over the reef flat is mostly controlled by the tidal elevation rather than by the incoming swell energy : the higher the mean level, the stronger the wave energy. Significant energy transfers toward low frequencies occur modulated by the tidal elevation. From mid to high tide, the energy transfer during wave breaking is dominant and the wave dynamics over the reef is focused in the infragravity band. From mid to low tide, the contribution of friction processes increases as the mean level decreases. Cross-reef current measurements show that the fluxes are overwhelmingly directed toward the lagoon. Few and short events of outflow are observed during the smallest swell periods either at high tide or at the beginning of rising tide. For small swells, the cross-reef current is modulated by the tidal elevation, while for large incoming waves the fluxes are much stronger (up to 40cm/s) and nearly constant

Kinetics of Cytotoxic Lymphocytes Reconstitution after Induction Chemotherapy in Elderly AML Patients Reveals Progressive Recovery of Normal Phenotypic and Functional Features in NK Cells

International audienceNK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n = 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated. Interestingly, the development of NK cells appeared altered as the most immature CD56 bright NK cells were seriously underrepresented. Finally, we showed that NK cell functions were only partially restored 6 weeks after CT as degranulation capabilities of NK cells recovered, whereas cytokine production remained low. Our data point out NK cells as antitumor effectors peculiarly hampered by leukemic cells. This study may indicate a timeline when NK-mediated therapies or other immunotherapies could be performed, particularly for patients excluded of hematopoietic stem cell transplantation

Impact of gene mutations on treatment response and prognosis of acute myeloid leukemia secondary to myeloproliferative neoplasms

International audienceAcute myeloid leukemias secondary (sAML) to myeloproliferative neoplasms (MPN) have variable clinical courses and outcomes, but remain almost always fatal. Large cohorts of sAML to MPN are difficult to obtain and there is very little scientific literature or prospective trials for determining robust prog-nostic markers and efficient treatments. We analyzed event-free survival (EFS) and overall survival (OS) of 73 patients with MPN who progressed to sAML, based on their epidemiological characteristics , the preexisting MPN, the different treatments received, the different prognostic groups and the responses achieved according to the ELN, and their mutational status determined by next-generation DNA sequencing (NGS). For 24 patients, we were able to do a comparative NGS analysis at both MPN and sAML phase. After acute transformation EFS and OS were respectively of 2.9 months (range: 0-48.1) and 4.7 months (range: 0.1-58.8). No difference in EFS or OS regarding the previous MPN, the ELN2017 prognostic classification, the first-line therapy or the response was found. After univariate analysis, three genes, TP53, SRSF2 and TET2, impacted pejoratively sAML prognosis at sAML time. In multivariate analysis, TP53 (P 5 .0001), TET2 (P 5 .011) and SRSF2 (P 5 .018) remained independent prognostic factors. Time to sAML transformation was shorter in SRSF2-mutated patients (51.2 months, range: 14.7-98) than in SRSF2-unmutated patients (133.8 months, range: 12.6-411.2) (P < .001). Conventional clinical factors (age, karyotype, ELN2017 prognostic classification, treatments received, treatments response, Allo-SCT.. .) failed to predict the patients' outcome. Only the mutational status appeared relevant to predict patients' prognosis at sAML phase

Wave transformation over a barrier reef

This paper reports a combined observational and numerical study of wave transformation over barrier reefs. The field instrumentation, which consists in a cross-shore network of pressure sensors and one high resolution velocity profiler, has been deployed for more than two months over the Ouano reef barrier, New Caledonia. The combined analysis of observations and numerical simulations shows that the reef barrier acts as an efficient, but depth-dependent, filter for incoming wave energy. The data analysis reveals the presence of very low frequency standing wave patterns due to reflection either at the reef barrier inner boundary or at the lagoon shore. Another striking feature is the development of undular bore trains over the reef flat.Environmental Fluid Mechanic

Genomic analysis of myeloproliferative neoplasms in chronic and acute phases

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NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML

International audienceNKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT).NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46high phenotype (p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression (p = 0.303).In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness

Correction: NKp30 expression is a prognostic immune biomarker for stratification of patients with intermediate-risk acute myeloid leukemia

International audience[This corrects the article DOI: 10.18632/oncotarget.17747.]