60 research outputs found

    Stability investigation of polyPOSS-imide membranes for H2 puriïŹcation and their application in the steel industry

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    In the present work, the high-temperature and long-term hydrothermal stability of novel polyPOSS-imide membranes for high-temperature hydrogen separation is investigated. The polyPOSS-imide membranes are found to exhibit an appropriate stability up to 300 C. Above this temperature the membrane selectivity rapidly decreases, which is seemingly related to changes in the molecular structure coupled to silanol condensation forming siloxane groups. Surprisingly, the exposure of the membrane to temperatures of up to 300 C even increases the H2 permeance together with the selective feature of the polyPOSS-imide layer. Subsequently, the long-term hydrothermal stability of the polyPOSS-imide membranes was investigated over a period of close to 1000 h at 250 C exposing the membrane to 10 mol% steam in the feed. An increase in H2/CH4 selectivity was observed upon water addition, and even though a minor drop was noticed over time during the hydrothermal operation, the selectivity exceeds the initial selectivity obtained in the dry feed atmosphere. After the removal of steam from the feed, the performance returns to its original state prior to the exposure to any steam showing appropriate steam stability of the polyPOSS-imide membranes. A conceptual process design and assessment was performed for application of these membranes involving a combination of carbon reuse and electrification of the steel making process with co-production of hydrogen. The results indicate a CO2 avoidance of 14%. The CO2 reduction achieved using renewable electricity in the proposed scheme is a factor 2.76 higher compared to a situation where the same renewable electricity would be fed in the electricity grid.publishedVersio

    Comparing amine- and ammonium functionalized silsesquioxanes for large scale synthesis of hybrid polyimide high-temperature gas separation membranes

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    PolyPOSS-imide membranes are promising for separating H2 from larger molecules (CO2, N2, CH4) at temperatures up to 300 °C. Their fabrication involves two steps: interfacial polymerization of POSS and 6FDA, followed by thermal imidization. This work provides a systematic study of the effects of cations on membrane properties and performance. For this, two distinct POSS molecules were used: functionalized with -NH3+Cl− or, so far unexplored, -NH2. The ammonium groups are partially deprotonated by using three different bases, LiOH, NaOH, and KOH. We demonstrate that the introduced cations affect the film thickness but not the molecular composition of the polyamic acid. All polyamic acids can be imidized, but the cations reduce the imidization kinetics as well as the loss of organic crosslinkers. For flat disc membranes, at 200 °C, the absence of cations results in comparable permeability combined with higher selectivity for H2/N2. This, and the possibility to discard adding a base, motivated a scale-up study of the new POSS. For tubular membranes, much higher ideal and mixed gas selectivities are found than for membranes where NaOH was added. Results indicate that the new route allows more reproducible production of defect free membranes and has potential for larger-scale polyPOSSimide fabrication.publishedVersio

    Simultaneous assessment of mechanical and electrical function in Langendorff-perfused ex-vivo mouse hearts

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    Background: The Langendorff-perfused ex-vivo isolated heart model has been extensively used to study cardiac function for many years. However, electrical and mechanical function are often studied separately—despite growing proof of a complex electro-mechanical interaction in cardiac physiology and pathology. Therefore, we developed an isolated mouse heart perfusion system that allows simultaneous recording of electrical and mechanical function. Methods: Isolated mouse hearts were mounted on a Langendorff setup and electrical function was assessed via a pseudo-ECG and an octapolar catheter inserted in the right atrium and ventricle. Mechanical function was simultaneously assessed via a balloon inserted into the left ventricle coupled with pressure determination. Hearts were then submitted to an ischemia-reperfusion protocol. Results: At baseline, heart rate, PR and QT intervals, intra-atrial and intra-ventricular conduction times, as well as ventricular effective refractory period, could be measured as parameters of cardiac electrical function. Left ventricular developed pressure (DP), left ventricular work (DP-heart rate product) and maximal velocities of contraction and relaxation were used to assess cardiac mechanical function. Cardiac arrhythmias were observed with episodes of bigeminy during which DP was significantly increased compared to that of sinus rhythm episodes. In addition, the extrasystole-triggered contraction was only 50% of that of sinus rhythm, recapitulating the “pulse deficit” phenomenon observed in bigeminy patients. After ischemia, the mechanical function significantly decreased and slowly recovered during reperfusion while most of the electrical parameters remained unchanged. Finally, the same electro-mechanical interaction during episodes of bigeminy at baseline was observed during reperfusion. Conclusion: Our modified Langendorff setup allows simultaneous recording of electrical and mechanical function on a beat-to-beat scale and can be used to study electro-mechanical interaction in isolated mouse hearts

    Gene- and variant-specific efficacy of serum/glucocorticoid-regulated kinase 1 inhibition in long QT syndrome types 1 and 2.

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    AIMS Current long QT syndrome (LQTS) therapy, largely based on beta-blockade, does not prevent arrhythmias in all patients; therefore, novel therapies are warranted. Pharmacological inhibition of the serum/glucocorticoid-regulated kinase 1 (SGK1-Inh) has been shown to shorten action potential duration (APD) in LQTS type 3. We aimed to investigate whether SGK1-Inh could similarly shorten APD in LQTS types 1 and 2. METHODS AND RESULTS Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and hiPSC-cardiac cell sheets (CCS) were obtained from LQT1 and LQT2 patients; CMs were isolated from transgenic LQT1, LQT2, and wild-type (WT) rabbits. Serum/glucocorticoid-regulated kinase 1 inhibition effects (300 nM-10 ”M) on field potential durations (FPD) were investigated in hiPSC-CMs with multielectrode arrays; optical mapping was performed in LQT2 CCS. Whole-cell and perforated patch clamp recordings were performed in isolated LQT1, LQT2, and WT rabbit CMs to investigate SGK1-Inh (3 ”M) effects on APD. In all LQT2 models across different species (hiPSC-CMs, hiPSC-CCS, and rabbit CMs) and independent of the disease-causing variant (KCNH2-p.A561V/p.A614V/p.G628S/IVS9-28A/G), SGK1-Inh dose-dependently shortened FPD/APD at 0.3-10 ”M (by 20-32%/25-30%/44-45%). Importantly, in LQT2 rabbit CMs, 3 ”M SGK1-Inh normalized APD to its WT value. A significant FPD shortening was observed in KCNQ1-p.R594Q hiPSC-CMs at 1/3/10 ”M (by 19/26/35%) and in KCNQ1-p.A341V hiPSC-CMs at 10 ”M (by 29%). No SGK1-Inh-induced FPD/APD shortening effect was observed in LQT1 KCNQ1-p.A341V hiPSC-CMs or KCNQ1-p.Y315S rabbit CMs at 0.3-3 ”M. CONCLUSION A robust SGK1-Inh-induced APD shortening was observed across different LQT2 models, species, and genetic variants but less consistently in LQT1 models. This suggests a genotype- and variant-specific beneficial effect of this novel therapeutic approach in LQTS

    KCNQ1 suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome.

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    BACKGROUND AND AIMS Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy. METHODS KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes. RESULTS KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P < .0001, LQT1-SupRep vs. WT, P = ns). Under ÎČ-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour. CONCLUSIONS This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1

    A family of dual-activity glycosyltransferasesphosphorylases mediates mannogen turnover and virulence in Leishmania parasites

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    Parasitic protists belonging to the genus Leishmania synthesize the non-canonical carbohydrate reserve, mannogen, which is composed of ÎČ-1,2-mannan oligosaccharides. Here, we identify a class of dual-activity mannosyltransferase/phosphorylases (MTPs) that catalyze both the sugar nucleotide-dependent biosynthesis and phosphorolytic turnover of mannogen. Structural and phylogenic analysis shows that while the MTPs are structurally related to bacterial mannan phosphorylases, they constitute a distinct family of glycosyltransferases (GT108) that have likely been acquired by horizontal gene transfer from gram-positive bacteria. The seven MTPs catalyze the constitutive synthesis and turnover of mannogen. This metabolic rheostat protects obligate intracellular parasite stages from nutrient excess, and is essential for thermotolerance and parasite infectivity in the mammalian host. Our results suggest that the acquisition and expansion of the MTP family in Leishmania increased the metabolic flexibility of these protists and contributed to their capacity to colonize new host niches

    Thin-Wall Bulk High Temperature Superconductor as a Permanent Cryomagnet

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    International audienceThin-wall single domains with artificial patterned holes are highly interesting for stimulating superconducting and mechanical properties of bulk YBCO materials. YBCO single domains were successfully grown from multiple holes preforms by using TSIG or TSMG techniques. The thin-wall configuration enables a remarkable improvement in flux trapping and superconducting properties whatever the used growth process. Progressive oxygenation under high pressure associated to the large specific areas was shown to boost the material performances. A trapped field maximum of 0.84 T was recorded at 0.2 mm above the top surface of a 16 mm thin wall pellet at 77 K. Such complex geometry can be easily and abundantly produced by using an extrusion process. We report for the first time to our knowledge the growth of a single domain from an extruded preform. Thin-wall samples were then impregnated by resign/alloy for mechanical reinforcement
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