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Prostaglandin E2 (PGE2) binds to four G-protein-coupled EP receptors, of which both EP2 and EP4 are abundantly expressed by tumor-infiltrating immune cells including DCs, NK cells, Tregs, cytotoxic T cells and TAMs. Signaling via EP2 and EP4 is immunosuppressive, preventing the mounting of effective anti-tumor immune responses leading to tumor immune escape and tumor progression. Currently, several EP4 selective antagonists and an EP2/4 dual antagonist are being developed for anti-cancer immunotherapy. Using a combination of EP2 and EP4 selective antagonists in different tumor mouse models, we could demonstrate that dual EP2/EP4 blockade is more effectively activating anti-tumor immunity compared to targeting either receptor alone. The concurrent inhibition of EP2 and EP4 resulted in tumor regression and induction of immunological memory. Together with published data showing similar findings, our results suggest that simultaneous targeting of EP2 and EP4 could be a promising new therapeutic approach to overcome cancer immune evasion. Idorsia Pharmaceuticals has identified ACT-1002-4391 as a novel, potent antagonist of EP2 and EP4 receptors with an excellent duality profile. In vitro, ACT-1002-4391 is capable of modulating immune cell proliferation and/or function and is superior to EP2 or EP4 selective inhibition in that respect. In vivo, ACT-1002-4391 displays strong and dose-dependent single agent anti-tumor efficacy in a syngeneic mouse tumor model. Based on the excellent selectivity and duality profile, ACT-1002-4391 will be advanced into clinical development by Idorsia Pharmaceuticals. Citation Format: Sébastien Jeay, Stefan Diethelm, Agnes Knopf, Marie Goxe, Marie Daugan, Julie Erupathil, Julien Pothier, Davide Pozzi, Thierry Sifferlen, Lorenza Wyder, Isabelle Lyothier, Olivier Corminboeuf, Francois Lehembre, Imke Renz, Dominique Meyer. ACT-1002-4391 - A novel potent antagonist of the prostaglandin E2 receptors EP2 and EP4 with excellent duality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1809.

Reversible solid oxide cells (rSOC) can convert excess electricity to valuable fuels in electrolysis cell mode (SOEC) and reverse the reaction in fuel cell mode (SOFC). In this work, a five - cell rSOC short stack, integrating fuel electrode (Ni-YSZ) supported solid oxide cells (Ni-YSZ parallel to YSZ vertical bar CGO parallel to LSC-CGO) with an active area of 100 cm(2), is tested for cyclic durability. The fuel electrode gases of H-2/N-2:50/50 and H-2/H2O:20/80 in SOFC and SOEC mode, respectively, are used during the 35 reversible operations. The voltage degradation of the rSOC is 1.64% kh(-1) and 0.65% kh(-1) in SOFC and SOEC mode, respectively, with fuel and steam utilisation of 52%. The post-cycle steady-state SOEC degradation of 0.74% kh(-1) suggests improved lifetime during rSOC conditions. The distribution of relaxation times (DRT) analysis suggests charge transfer through the fuel electrode is responsible for the observed degradation. (C) 2022 The Author(s). Published by Elsevier Ltd on behalf of Hydrogen Energy Publications LLC.

The characterization of solid oxide cells (SOCs) relies mainly on direct-current (DC) and alternating-current (AC) methods that provide only average surface electro-chemical responses. As such, the spatial distribution is not well captured and the complexity of the electrochemical system is not fully represented. Infrared imaging could be used to locally characterize SOCs. This method has only been performed at steady-state, but, analogous to DC and AC characterization methods, applying a thermal perturbation could improve its sensitivity. This work proposes the use of active infrared imaging to characterize an operating SOC. To demonstrate the feasibility of the proposed method, an SOC was exposed to a current pulse while monitoring the infrared response using a CMOS camera. The phase and amplitude representation of the infrared response was then computed by Fourier transform and used for rapid identification of regions of interests. Results showed that less than 10% of the SOC was useful in the electrochemical process.

While high performance of SOFC systems has already been achieved, there is still a need to increase the stack lifetime, while decreasing the system's total cost of ownership, both being linked. The increase in lifetime includes the minimization of performance degradation, but also avoidance of potentially detrimental events during operation, originating from the stack, outside the stack, or a combination of both. The present paper highlights how the detection of faulty operation as early as possible is important to implement adequate mitigation strategies, wherever applicable, according to the fault and its grade of severity. Three types of faults have been considered, fuel starvation, leakage and carbon deposition. Both hardware components and algorithms to monitor, detect, isolate, and finally correct faulty system operation have been developed and will be embedded in a real SOFC system.

Bacterial meroterpenoids constitute an important class of natural products with diverse biological properties and therapeutic potential. The biosynthetic logic for their production is unknown and defies explanation via classical biochemical paradigms. A large subgroup of naphthoquinone-based meroterpenoids exhibits a substitution pattern of the polyketide-derived aromatic core that seemingly contradicts the established reactivity pattern of polyketide phenol nucleophiles and terpene diphosphate electrophiles. We report the discovery of a hitherto unprecedented enzyme-promoted α-hydroxyketone rearrangement catalysed by vanadium-dependent haloperoxidases to account for these discrepancies in the merochlorin and napyradiomycin class of meroterpenoid antibiotics, and we demonstrate that the α-hydroxyketone rearrangement is potentially a conserved biosynthetic reaction in this molecular class. The biosynthetic α-hydroxyketone rearrangement was applied in a concise total synthesis of naphthomevalin, a prominent member of the napyradiomycin meroterpenes, and sheds further light on the mechanism of this unifying enzymatic transformation.

Nowadays, the researchers that are working on the SOFC technology, are agree that it is necessary to decrease the operating temperature at 700°C(650-750 °C) of IT-SOFC technology, which currently is around 850-900°C for electrolyte supported cell used by the three main operators –Bloom, Hexis and Sun Fire. At this temperature the reactivity and the component cost of the cell decrease. Nevertheless, some interactions between the conventional electrolyte material (YSZ) and the cathode material (lanthanum based) are still present and it is necessary to include a ceria buffer layer to avoid the possible formation of an insulating pyrochlore structure La2Zr2O7 layer at the electrolyte-cathode interface. In ceria family, the best material regarding the ionic conductivity is the samaria doped ceria. However, the gadolinia doped ceria is the most employed from the cost point of view and the availability of gadolinium in comparison with samarium. This buffer layer avoids the reactivity between electrolyte and cathode, and presents a good anionic conductivity. It must be dense, thin and adherent on electrolyte, in order to be suitable for the surface treatment process. In this paper, we present some recent results obtained on the gadolinia doped ceria coatings deposited by magnetron sputtering from metallic targets in argon-oxygen reactive gas mixtures with different substrate bias voltage. After a description of the experimental device, a first part will be dedicated to their chemical, microstructural and structural characterization (SEM, XRD,…) in relation with the magnetron sputtering deposition parameters. In a second part, the ionic transport characteristics of the half cell (Ni-YSZ/YSZ/GDC) will be investigated via impedance spectroscopy measurements performed at various temperatures up to 800°C under Ar-H2 gas mixtures. Finally, a complete cell test ((Ni-YSZ/YSZ/GDC/LSC) was performed with the Fiaxell Open Flanges test bench. This study is carried out within the framework of the European territorial cooperation program INTERREG V A France-Switzerland. It has benefited from financial support from the EU through the European Regional Development Fund (ERDF- € 139,176) and the Swiss Confederation's contribution of CHF 134,173

A solid oxide short stack composed of 6 Ni-YSZ supported cells, YSZ electrolyte and GDC-LSC oxygen electrode has been tested for 10,700 hours in steam electrolysis. Initial degradation was followed by a global stabilization of the performance after lowering the current density, with a degradation rate below 0.5% kh(-1). Post-test analysis has been conducted on two repeating units (RUs) to highlight the most significant microstructure alterations. Nickel depletion was observed in the hydrogen electrode close to the interface with the electrolyte. Formation of small pores in the electrolyte was detected along the grain boundaries. A consequent detachment related to this phenomenon was observed in proximity of the GDC compatibility layer. At the oxygen electrode side, the formation of a approximate to 1 mu m dense mixed layer of GDC and YSZ was observed. Strontium from the LSC electrode migrated through GDC pores and reacted with YSZ, forming evident SrZrO3 inclusions. Distinct accumulation of silicon at the Ni/YSZ interface and chromium on the GDC barrier layer have been observed in both RUs. Despite this range of alterations observed, the stack degradation remained limited, testified from the fact that performance decay between 4,000 and 10,000 hours of operation was virtually nil.

The objective of the current work is to support the design of a pilot hydrogen and electricity producing plant that uses natural gas (or biomethane) as raw material, as a transition option towards a 100% renewable transportation system. The plant, with a solid oxide fuel cell (SOFC) as principal technology, is intended to be the main unit of an electric vehicle station. The refueling station has to work at different operation periods characterized by the hydrogen demand and the electricity needed for supply and self-consumption. The same set of heat exchangers has to satisfy the heating and cooling needs of the different operation periods. In order to optimize the operating variables of the pilot plant and to provide the best heat exchanger network, the applied methodology follows a systematic procedure for multi-objective, i.e. maximum efficiency and minimum number of heat exchanger matches, and multi-period optimization. The solving strategy combines process flow modeling in steady state, superstructure- based mathematical programming and the use of an evolutionary-based algorithm for optimization. The results show that the plant can reach a daily weighted efficiency exceeding 60%, up to 75% when considering heat utilization.

This paper presents a model-based investigation to handle the fundamental issues for the design of co-electrolysis based power-to-methane at the levels of both the stack and system: the role of CO2 in co-electrolysis, the benefits of employing pressurized stack operation and the conditions of promoting internal methanation. Results show that the electrochemical reaction of co-electrolysis is dominated by H2O splitting while CO2 is converted via reverse water-gas shift reaction. Increasing CO2 feed fraction mainly enlarges the concentration and cathode-activation overpotentials. Internal methanation in the stack can be effectively promoted by pressurized operation under high reactant utilization with low current density and large stack cooling. For the operation of a single stack, methane fraction of dry gas at the cathode outlet can reach as high as 30 vol.% (at 30 bar and high flowrate of sweep gas), which is, unfortunately, not preferred for enhancing system efficiency due to the penalty from the pressurization of sweep gas. The number drops down to 15 vol.% (at 15 bar) to achieve the highest system efficiency (at 0.27 A/cm2). The internal methanation can serve as an effective internal heat source to maintain stack temperature (thus enhancing electrochemistry), particularly at a small current density. This enables the co-electrolysis based power-to-methane to achieve higher efficiency than the steam-electrolysis based (90% vs 86% on higher heating value, or 83% vs 79% on lower heating value without heat and converter losses).

Halogenated pyrroles (halopyrroles) are common chemical moieties found in bioactive bacterial natural products. The halopyrrole moieties of mono- and dihalopyrrole-containing compounds arise from a conserved mechanism in which a proline-derived pyrrolyl group bound to a carrier protein is first halogenated and then elaborated by peptidic or polyketide extensions. This paradigm is broken during the marine pseudoalteromonad bacterial biosynthesis of the coral larval settlement cue tetrabromopyrrole (1), which arises from the substitution of the proline-derived carboxylate by a bromine atom. To understand the molecular basis for decarboxylative bromination in the biosynthesis of 1, we sequenced two Pseudoalteromonas genomes and identified a conserved four-gene locus encoding the enzymes involved in its complete biosynthesis. Through total in vitro reconstitution of the biosynthesis of 1 using purified enzymes and biochemical interrogation of individual biochemical steps, we show that all four bromine atoms in 1 are installed by the action of a single flavin-dependent halogenase: Bmp2. Tetrabromination of the pyrrole induces a thioesterase-mediated offloading reaction from the carrier protein and activates the biosynthetic intermediate for decarboxylation. Insights into the tetrabrominating activity of Bmp2 were obtained from the high-resolution crystal structure of the halogenase contrasted against structurally homologous halogenase Mpy16 that forms only a dihalogenated pyrrole in marinopyrrole biosynthesis. Structure-guided mutagenesis of the proposed substrate-binding pocket of Bmp2 led to a reduction in the degree of halogenation catalyzed. Our study provides a biogenetic basis for the biosynthesis of 1 and sets a firm foundation for querying the biosynthetic potential for the production of 1 in marine (meta)genomes.

In this work, the effect of sulphur poisoning of the Ni-YSZ electrode of an SOEC operated in co-electrolysis mode was investigated. Short-term tests with exposure up to 5 ppmv of SO2 were performed at OCV and under polarization ( 0.25 A c m − 2 ). The two-stages degradation pattern observed consisted of an initial fast voltage increase followed by a slower voltage increase similar to that of an SOFC exposed to H2S. Electrochemical impedance spectroscopy and the analysis of the distribution of relaxation times showed that both the catalytic and electrochemical reactions were affected by SO2. After extended periods in SO2-free reactant, only a partial recovery of the performances was observed even when exposure amounted to only 0.5 ppmv of SO2 independently on the current density. A durability test at a constant polarization of 0.5 A c m − 2 showed a voltage ‘runaway’ behavior during successive exposures to 1 ppmv and 2 ppmv of SO2. This behavior originated from a drastic increase of the serial resistance, which almost completely recovered when the SO2 supply was cut. This behavior was not observed during exposure to 0.5 ppmv of SO2, suggesting that, in these test conditions, the voltage ‘runaway’ behavior could be avoided at a sub-ppmv level. Successive exposure-recovery cycles were found to weaken the SOEC tolerance to SO2 and a low frequency pseudo-inductive arc was observed in the impedance response during and after the second exposure to SO2.

While the global fuel utilization of solid oxide fuel cells (SOFCs) is limited by the stack aging rate, the fuel excess is typically used in a burner, and thus limiting the system electrical efficiency. Further, natural-gas-fueled SOFCs require treated water for the steam reforming process, which increases operational cost. Here, we introduce a novel micro anode off-gas recirculation fan that is driven by a partial-admission (21%) and low-reaction (15%) steam turbine with a tip diameter of 15 mm. The 30 W turbine is propelled by pressurized steam, which is generated from the excess stack heat. The shaft runs on dynamic steam-lubricated bearings and rotates up to 175 krpm. For a global fuel utilization of 75% and a constant fuel mass flow rate, the electrical gross DC efficiency based on the lower heating value was improved from 52 % to 57 % with the anode off-gas recirculation, while the local fuel utilization decreased from 75% to 61%, which is expected to significantly increase stack lifetime. For a global fuel utilization of 85%, gross efficiencies of 66% in part load (4.5 kWe) and 61% in full load (6.3 kWe) were achieved with the anode off-gas recirculation. The results suggest that the steam-driven anode off-gas recirculation can achieve a neutral water consumption.

This work presents the poisoning effect of organic oxo-silicon compounds (siloxanes) which are generally found in sewage biogas. Lifetime and durability associated with solid oxide fuel cell (SOFC) technology is strongly related to the amount of contaminants that reach the stack. Several experiments on Ni anode-supported (AS) single cells are performed in order to clarify the mechanism of degradation and also the possibility of cell performance recovery. Three experiments focus on the degradation and recovery of AS Ni-YSZ fed with H-2, co-feeding 5 ppm D4-siloxane (octamethylcyclotetrasiloxane, C8H24O4Si4) as representative compound for the organic silicon species, at 800 degrees C. A fourth experiment focuses on the durability of the AS Ni-YSZ cell with variable concentrations of the impurity (0-5ppm), during steady state polarization (0.25Acm(-2)) for 250 h, using simulated biogas-reformate fuel H-2/CO/CO2/H2O: irreversible degradation was observed with the D4-impurity feed in the anode gas. Post-test scanning electron microscopy (SEM) results indicate formation of SiO2(s) deposits, which block pores and reduce the TPB length.

A chemoenzymatic approach to generate fully functional acyl coenzyme A molecules that are then used as substrates to drive in situ acyl transfer reactions is described. Mass spectrometry-based assays to verify the identity of acyl coenzyme A enzymatic products are also illustrated. The approach is responsive to a diverse array of carboxylic acids that can be elaborated to their corresponding coenzyme A thioesters, with potential applications in wide-ranging chemical biology studies that utilize acyl coenzyme A substrates.

The present paper investigates the variation in performances in co-electrolysis of steam/CO2 on SOEC single cells caused by the progressive increase of CO2 inlet concentration and current density. Steam electrolysis and co-electrolysis were investigated on circular Ni-YSZ supported cells produced by SOLIDpower (“ASC-700” type cells). The thin film electrolyte is constituted by YSZ and the oxygen electrode by LSCF-GDC. The active area corresponds to 12.56 cm2 (2 cm of radius). The cells were fed with different H2O/CO2 mixtures, while keeping 10% H2 of the inlet molar flow in order to avoid re-oxidation of the Ni-YSZ support. A sensitivity analysis was performed looking in particular at the effects of inlet gas composition, gas flows and temperature on the performances. I-V characterization and EIS measurements at different current densities were carried out for each sequence. In steam electrolysis mode, the reference inlet molar flow was equal to 150 Nml/min (90% H20, 10% H2), at 750°C. The I-V curve showed a voltage of 0.861V at OCV, 1.049V at 0.5 A/cm2 and 1.253V at 1 A/cm2. A sensitivity analysis was performed varying the temperature (700°C, 750°C and 800°C), the inlet air flow (100 Nml/min, 300 Nml/min and 500 Nml/min) and the total inlet fuel flow (from 8 to 16 Nml/min/cm2). In this case, the steam conversion factor was kept constant equal to 50% (adjusting the current imposed). EIS analysis exhibits that ohmic and polarization resistances decrease with current densities lower than 0.4 A/cm2 and then rise with higher values. As expected, the increase of temperature has a positive impact on the performances, while the change of air and fuel flow slightly affects them. In co-electrolysis mode the CO2 and H2O content was varied, keeping constant the total molar flow and the hydrogen fraction as explained before. As shown in the enclosed image, the area specific resistance (ASR) increases with the CO2 concentration in the mixture and gas transport limitation occurs at lower current densities. Also in this case a sensitivity analysis was conducted changing the temperature (from 700°C to 800°C) and the resulting EIS plots demonstrate different ongoing processes favored at high current densities. In particular, the reverse water-gas-shift reaction plays an important role on the overall balance of the gas species, and it directly depends on temperature and inlet fuel composition. Figure 1

A Triode Solid Oxide Fuel Cell is a novel cell architecture that aims to control the electrocatalytic activity under low steam reforming conditions, or poisoning conditions. This fuel cell design introduces a third electrode (auxiliary electrode) of the same nature of the cathode while the anode is common between the two circuits (Figure 1). The auxiliary circuit, which electrically connects the anode with the auxiliary electrode, is operated in electrolysis mode while the fuel cell circuit runs in its conventional way. During the triode operation, performance enhancement is recorded especially when a significant electrode overpotential is presented; this can be the case for SOFC anode feeds with natural gas and gasoline fuels, or when it is being poisoned from impurities. A two-dimensional stationary isothermal model is developed and implemented in commercial software, COMSOL Multiphysics (version 4.3b). The model is based on composite electrodes, where the equations for mass, momentum and charge transport, along with electrochemical global kinetics (Butler-Volmer equation) and charge conservation are solved simultaneously. Exchange current densities are fitted from experimental data to reproduce the observed behavior of the cell. The model, able to predict conventional and triode operation, gives guidelines for the electrodes geometry design that needs to be adopted in order to favor the expected improvements. In particular, it is noted that the aspect ratio between the electrodes distance cathode-auxiliary and the electrolyte thickness is a key parameter. The interaction between the main and auxiliary circuits is then discussed in terms of equipotential and current lines in a cross section of the cell for two different geometries: anode and electrolyte supported cells. The improvements achievable in triode operation are also calculated in terms of electric current surplus that is possible to obtain in the fuel cell circuit while imposing an electrolysis voltage of 1.7 V in the auxiliary circuit. Figure 1

This paper presents an experimental study of the impact of toluene on the performance of anode-supported (AS) Ni-YSZ SOFC operating at ~800 °C, 0.25 A/cm2 fed with H2 and reformed biosyngas. Toluene was added to the fuel stream and its concentration increased stepwise from tens to thousands of ppm. Each poisoning test was followed by a recovery step (no toluene in the fuel stream) for the duration of 25 hours. The main goal of this work is to define a concentration threshold of toluene as a model tar compound in the fuel stream and later to identify the degradation mechanism caused by this tar compound. Polarization behavior, current-voltage and electrochemical impedance spectroscopy (EIS) were analyzed to evaluate the cell performance. A linear degradation is observed at concentrations above 1000 ppmv for the cell which was fed with pure H2 (cf Figure) The degradation was due to local C(s) deposition. In contrast, toluene even up to 3500 ppm did not cause a severe degradation when the cell was fed with reformed biosyngas. Figure 1

The prevalent anode supported thin electrolyte solid oxide fuel cells (ASC) used today are highly susceptible to failure under redox conditions. The expansion caused during the oxidation of Ni to NiO can destroy the support, leading to irreversible cell damage. To counter this problem, Fiaxell SOFC Technologies (Switzerland) has engineered the microstructure of their cells, to confer added redox stability to their anode supported cell (2R-cell™). This commercial cell was investigated within the Eurostars-Roxsolidcell project against thermal and redox cycling. A 2R-cell with a 10cm2 active area LSCF cathode on a CGO buffer layer, was placed between alumina felts, mounted inside a seal-less open flange setup kept in an oven, and operated at a temperature of 780°C. A nickel foam and a gold grid were used for the current collection at the anode and cathode respectively. Dry hydrogen (180 Nml/min) was fed to the anode and air (500 Nml/min) to the cathode. 20 thermal cycles were performed between 780 and 100°C, using 200°C/h heating ramps and natural cooling, followed by 20 redox cycles, during which air was fed to the anode for 1 hour at 780°C, causing the cell potential to drop to zero. V-i polarisation curves and electrochemical impedance spectroscopy (EIS) measurements were performed before and after each consecutive cycle in order to monitor the performance losses. The OCV remained stable during the whole test whereas the area specific resistance (ASR) measured at 0.5 A/cm2 increased by +1.3 mΩcm2 per thermal cycle and by +1.8 mΩcm2per redox cycle. The EIS measurements showed that the degradation during the thermal cycling was mainly due to an increase of the ohmic losses. In the case of the redox-cycling, the cell degradation after stabilisation principally came from high frequency polarisation losses (cf. Figure), which were attributed to changes in the anode functional layer microstructure. The cell was examined after the test by scanning electron microscopy (SEM). No delamination of the cathode was observed, however, fragmentation of the anode active layer was apparent. Figure 1

Lifetime and durability issues connected with Solid Oxide Fuel Cell (SOFC) technology are strongly related to the amount of contaminants that reach the stack. In this study the focus is on organic silicon compounds (siloxanes) and their highly detrimental effects on the performance of SOFC Ni-YSZ anodes. The involved mechanism of degradation is clarified and quantified through several test runs and subsequent post-mortem analysis on tested samples. In particular, experiments on both Ni anode-supported single cells and 11-cell-stacks are performed, co-feeding D4-siloxane (octamethylcyclotetrasiloxane, C8H24O4Si4) as model compound for the organic silicon species which are generally found in sewage biogas. High degradation rates are observed already at ppb(v) level of contaminant in the fuel stream. Post-test analysis revealed that Si (as silica) is mostly deposited at the inlet of the fuel channel on both the interconnect and the anode side of the cell suggesting a relatively fast condensation-type process. Deposition of the Si was found on the interconnect and on the anode contact layer, throughout the anode support and the three phase boundary in the anode, correlating with the observed increase of polarization losses from the EIS analysis of tested cells. (C) 2015 Elsevier B.V. All rights reserved.

To improve the industry benchmark of solid oxide fuel cell (SOFC) systems, we consider anode off-gas recirculation (AOR) using a small-scale fan. Evolutionary algorithms compare different system design alternatives with hot or cold recirculation. The system performance is evaluated through multi-objective optimization (MOO) criteria, i.e., maximization of electrical efficiency and cogeneration efficiency. The aerodynamic efficiency and rotordynamic stability of the high-speed recirculation fan is investigated in detail. The results obtained suggest that improvements to the best SOFC systems, in terms of net electrical efficiency, are achievable, including for small power scale (10 kWe).

The vanadium-dependent chloroperoxidase Mcl24 was discovered to mediate a complex series of unprecedented transformations in the biosynthesis of the merochlorin meroterpenoid antibiotics. In particular, a site-selective naphthol chlorination is followed by a sequence of oxidative dearomatization/terpene cyclization reactions to build up the stereochemically complex carbon framework of the merochlorins in one step. Inspired by the enzyme reactivity, we developed a chemical chlorination protocol paralleling the biocatalytic process. These chemical studies led to the identification of previously overlooked merochlorin natural products.

A mechanistic study of the ring contraction of spirocyclopropane isoxazolidines to form β-lactams is reported. Based on experimental and computational investigations, we propose a concerted mechanism that proceeds with retention of configuration during cyclopropane cleavage.

The polycycles merochlorin A and B are complex halogenated meroterpenoid natural products with significant antibacterial activities and are produced by the marine bacterium Streptomyces sp. strain CNH-189. Heterologously produced enzymes and chemical synthesis are employed herein to fully reconstitute the merochlorin biosynthesis in vitro. The interplay of a dedicated type III polyketide synthase, a prenyl diphosphate synthase, and an aromatic prenyltransferase allow formation of a highly unusual aromatic polyketide-terpene hybrid intermediate which features an unprecedented branched sesquiterpene moiety from isosesquilavandulyl diphosphate. As supported by in vivo experiments, this precursor is furthermore chlorinated and cyclized to merochlorin A and isomeric merochlorin B by a single vanadium-dependent haloperoxidase, thus completing the remarkably efficient pathway.

A novel bioconjugation strategy is presented that relies on the coupling of diazonium terephthalates with amines in proteins. The diazonium captures the amine while the vicinal ester locks it through cyclization, ensuring no reversibility. The reaction is highly efficient and proceeds under mild conditions and short reaction times. Densely functionalized, complex natural products were directly coupled to proteins using low concentrations of coupling partners.

This paper presents the processing steps for producing thin planar and tubular oxygen separation membranes by thermoplastic forming of Ba0.5Sr0.5Co0.8Fe0.2O3-delta (BSCF) with polystyrene (PS) and stearic acid (SA) as binder. The influence of powder content on the shape stability of thin membranes (tubular and planar structures) during the thermoplastic processing route was investigated. The effect of powder content on mixing torque and the rheological behavior were investigated. The effect of the powder content could be analytically described using the model proposed by Frankel and Acrivos. The deformation of free standing green bodies was investigated using disks. The result showed that increasing the powder content is remarkably effective to minimize the deformation of the membrane during the thermal debinding step. By using a high powder content (60 vol%) and a multicomponent binder system composed of PS, SA and paraffin wax (PW), it was possible to achieve disks and thin wall tubular structures without deformation after sintering. Using capillary rheometer an unexpected decrease in the total extrusion pressure was measured for the feedstock containing PW. The change in apparent activation energy between 800-1000 degrees C was not related to the membrane properties. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.

In this study, two short SOE stacks (6-cells) were characterized in steam-electrolysis mode. The first was based on Ni-YSZ supported cells with LSCF-based air electrodes. The second included LSC-based air electrodes specifically developed within the SOFC600 project. The stacks were fed with a 90% steam, 10% hydrogen mixture, and characterized between 600 and 700 degrees C. For the LSCF-based stack, an average cell voltage of 1.6V was reached at -1Acm(-2) and 700 degrees C, corresponding to 60% steam conversion. The LSC-based stack showed better performances, with 1.25V at -0.8Acm(-2) and 700 degrees C. Durability tests were performed around the thermoneutral voltage (1.35V) for resp. 2,400 (LSCF) and 1,500h (LSC). The average stack degradation rates were resp. +2.8% (kh)(-1) (LSCF) and +1.9% (kh)(-1) (LSC). Twelve load-cycles were also performed on the LSC-stack with no apparent degradation. In addition, co-electrolysis was performed between 750 and 850 degrees C by feeding the stack with a 60% H2O, 30% CO2, and 10% H-2 mixture. Ninety-five percent conversion was reached and the measured outlet syngas composition was close to that predicted by thermodynamics. Steam electrolysis tests were carried out in the same conditions for comparison. The stack performance in the co-electrolysis mode was slightly lower than in the electrolysis mode.

An alternative way to process data from polarization measurements for fuel cell model validation is proposed. The method is based on re- and subsampling of IV data, with which repetitive estimations are obtained for the model parameters. This way statistics such as standard deviations and correlations between the parameters may be experimentally derived. Histograms may also be produced, approximating the probability distributions that they follow. Two experimental case studies are discussed. In the first case, observations are made on the behavior of the parameter values for two mathematical models. As the number of data points (measurement points) employed in the estimation of the parameters increases, parameters with high variances converge to specific values. On the contrary, parameters with small variances diverge linearly. The parameters' histograms do not usually follow normal distributions rather they show a connection between the number of peaks in the graphs and correlations of the parameters. The second case study is an application on a fast degraded SOFC button cell, where the values and the histograms of the parameters are compared before and after degradation.

One of the major limitations of the nickel (Ni) - yttria-stabilized zirconia (YSZ) anode support for solid oxide fuel cells (SOFC) is its low capability to withstand transients between reducing and oxidizing atmospheres ("RedOx" cycle), owing to the Ni-to-NiO volume expansion. This work presents results on different anode supports fabricated by tape casting. Three compositions are prepared, as the outcome of a preceding design of experiment approach. The NiO proportion is 40, 50 and 60 wt% of the anode composite.

Oxygen permeability measurements of Ba0.5Sr0.5Co0.8Fe0.2O3−δ (BSCF) disk shaped membranes fabricated by thermoplastic processing and sintered at different temperatures (1000–1100 °C), showed no influence of the grain size on the oxygen permeation fluxes. To further investigations, Electron Backscattered Diffraction (EBSD) and Conductive mode (CM) microscopy methods were used for texture analysis and observation of the local electrical behavior in the BSCF membranes, respectively. EBSD results revealed that the grain size of the membranes increased with increasing the sintering temperature from an average of 3.32 μm at 1000 °C to 18.25 μm at 1100 °C. Also, it was seen that there was no textural difference between the different samples. CM analysis demonstrated that the electronic conductivity of the grains and grain boundaries was similar in the membrane sintered at 1000 °C. Finally, the stability of the membrane under the operation conditions was tested, and it was found that the permeation flux was nearly constant at 900 °C after an operation time of more than 50 h, whereas oxygen permeation flux declined after a relative short time at 825 °C.

The total synthesis of Microcin SF608 is reported. Access to the octahydroindole core structure of Microcin SF608 relies on the TMSOTf/NEt(3)-mediated opening of an oxabicyclic ring system. Additional highlights of the synthetic strategy that is reported include a highly regioselective epoxide reduction and photolytic excision of a 3 degrees alcohol.

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The locally-resolved degradation behavior was studied during 1900 hours in a SOFC repeat-element. In-situ measurements of local electrochemical performance were made on 18 locations over a segmented anode-supported cell. The evolution of local current densities, overpotentials and area-specific resistances was studied, showing a reorganization of the electrochemical reaction with time. The extent and the spatial distribution of degradation were established for different electrochemical reactions steps using impedance spectroscopy. The low-frequency cathode contribution was the mostly altered process, followed by the charge transfer reaction on anode side. Post-experiment analyses allowed to identify three major pollutants on the cathode side (chromium, silicon and sulfur), whose spatial distributions corresponded to the observed local degradation. Chromium was present only near the air inlet, while silica was found to affect a larger area, with decreasing amounts along the flow. Sources of pollutants were identified in system components as well as within the stack repeat-element.

An axially chiral reactive precursor—a trans-configured Pd(II) chelate complex—toward the planar chiral bis-palladacycle FBIP-Cl, which was recently shown to be an excellent enantioselective catalyst for both aza-Claisen rearrangements and direct Michael additions, has been identified and allows us to explain the stereochemical outcome of the first reported direct diastereoselective bis-cyclopalladation. In contrast to the trans-configured chelate complex, its cis-configured counterpart turned out to be a dead end under the initial cyclopalladation conditions and required harsher conditions for C−H activation.

Mixed ionic–electronic conducting $$La_{0.5} Sr_{0.5} Fe_{1 - x} B_x O_{3 - \delta } $$ (B: Al, Cr, Zr, Ga, Ti, Sn, Ta, V, Mg, and In with x = 0, 0.1, 0.2) perovskite materials were produced via solid-state synthesis. In order to study the effect of B-site substitution on the expansion behavior of these materials, their thermal expansion in air up to 900°C and isothermal expansion at the same temperature from air to Ar were measured by dilatometry. Ti and Ta were found to be the most effective substitutions in suppressing the isothermal expansion. The isothermal expansion at 900°C from air to Ar was reduced by 50% by substitution of 20% Ti or 10% Ta. Therefore, these compositions were further characterized by 4-probe total DC conductivity and permeation measurements under air/Ar gradient. The total conductivity of $$La_{0.5} Sr_{0.5} FeO_{3 - \delta } $$ was decreased by more than one order of magnitude at low temperatures and from 430 S/cm, which is the maximum, to around 100 S/cm at 500°C with the addition of Ti and Ta. The normalized oxygen permeation of LSF at 900°C decreased from 0.18 to 0.05 μmol/cm2s and 0.07 μmol/cm2s with the substitution of 20% Ti and 10% Ta, respectively.

Tubular membranes of La0.6Ca0.4Fe0.75Co0.25O3−δ and La0.5Sr0.5Fe1−yTiyO3−δ (y = 0, 0.2) for the application of partial oxidation of methane to syngas were produced by thermoplastic extrusion and investigated by oxygen permeation measurements. The optimum ceramic content in the feedstock for extrusion was found to be 51 vol% as a result of rheology measurements. Tubes with an outer diameter of 4.8–5.5mmand thickness of 0.25–0.47mm were produced with densities higher than 95% of the theoretical density. The oxygen permeation flux of the tubular membranes wasmeasured with air on one side and Ar or Ar +CH4 mixture on the other side. The oxygen permeation rate decreased with Ti-substitution while it was considerably increased by introduction of 5% methane into the system. The normalized oxygen fluxes in air/Ar gradient at 900 ◦C were measured to be 0.06, 0.051, and 0.012 mol cm−2 s−1 for LCFC, LSF, and LSFT2, respectively, and 0.18 mol cm−2 s−1 for LSFT2 with 5% methane.

Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full account of our studies directed toward the total synthesis of gelsemoxonine that relies on a conceptually new approach for the construction of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction was employed to access a key β-lactam intermediate, which could be further elaborated to the azetidine of the natural product. In the course of our studies, we have gained detailed insight into this intriguing transformation. Furthermore, we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We also document an enantioselective synthesis of a key precursor en route to gelsemoxonine.

These are the first examples of total enzymatic syntheses of meroterpenoid natural products.

The influence of partial substitution of Fe with Ti on the oxygen transport properties of La1−x Sr x FeO3 membranes was investigated in view of their application for oxygen separation. Samples of composition % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX % garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz % aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeGaca % ackaa0lGqaaiaa-XeacaWFHbWaaSbaaSqaaiaaicdacaGGUaGaaGyn % aaqabaGccaWFtbGaa8NCamaaBaaaleaacaaIWaGaaiOlaiaaiwdaae % qaaOGaaeOraiaabwgadaWgaaWcbaGaaGymaiabgkHiTiaadMhaaeqa % aOGaaeivaiaabMgadaWgaaWcbaGaamyEaaqabaGccaqGpbWaaSbaaS % qaaiaaiodacqGHsislcqaH0oazaeqaaaaa!4C93! $$ La_{{0.5}} Sr_{{0.5}} {\text{Fe}}_{{1 - y}} {\text{Ti}}_{y} {\text{O}}_{{3 - \delta }} $$ (y=0, 0.2) were prepared and their oxygen transport properties characterised by potential step relaxation and by oxygen permeation measurement in an air/argon gradient. With the first technique, chemical diffusion % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX!% MathType!MTEF!2!1!+-% feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX% garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz% aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq% Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq% Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaada% qadaqaamaaGaaabaGaamiraaGaay5adaaacaGLOaGaayzkaaaaaa!3AA4! $${( {\widetilde{D}} )}$$ and surface exchange (k S) coefficients were obtained by fitting of the current relaxation data to a single expression valid over the complete time range. The Ti-substituted composition gave slightly larger values of % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX!% MathType!MTEF!2!1!+-% feaaeaart1ev0aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbbjxAHX% garmWu51MyVXgatuuDJXwAK1uy0HwmaeHbfv3ySLgzG0uy0Hgip5wz% aebbnrfifHhDYfgasaacH8qrps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq% Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq% Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeWaeaaakeaada% aiaaqaaiaadseaaiaawoWaaaaa!391B! $${\widetilde{D}}$$ and k S. The trend was opposite for the measured oxygen permeation flux. In the latter experience, ordering of oxygen vacancies was observed at lower temperature, reducing significantly the performance of the material.

Microcin SF608 (I), closely related to marine aeruginosins, is synthesized in 21 steps from a common oxabicyclic building block.

The effect of the bulk microstructure (grain size distribution, grain boundary composition on the oxygen transport properties of La0.5Sr0.5FeO3membranes was investigated. For this purpose, samples with different microstructures were prepared by modifying the sintering duration and/or temperature. The average grain sizes, ranging from 0.20 to 1.43μ m, were determined from SEM analysis. The oxygen transport properties of the samples were characterised by permeation measurement. The fluxes presented a change in the activation energy which was attributed to a change in the rate limiting step, from bulk diffusion at lower temperature ( 900°). Only the transport through the bulk was influenced by the microstructure, with the highest flux for the smallest grains. This would imply that oxygen transport occurs more rapidly along the grain boundaries that through the bulk. Grain and grain boundary compositions were analysed by TEM.

Electrochemical techniques were applied to a coulometric titration cell to study oxygen nonstoichiometry and transport in the perovskite-type oxide La0.4Ba0.6Fe0.8Co0.2O3-delta. Slow scan voltammetry (3mV/s) was used to obtain oxygen nonstoichiometry vs. the oxygen partial pressure (p(O2)) data. The voltammograms were further analysed using a simple defect model to yield the absolute value of the oxygen nonstoichiometry. Relaxation measurements were performed to obtain chemical diffusion and surface exchange coefficients. In particular, the suitability of converting the relaxation data to the frequency domain for analysis purpose was examined. Impedance spectroscopy measurements were also performed on the same cell to allow direct comparison. A satisfactory agreement was obtained for the chemical diffusion coefficients but the surface exchange coefficient values were systematically different by a factor 2 to 3. This discrepancy was attributed to the short-time extrapolation used in the numerical conversion procedure. Finally, other transport coefficients (ionic conductivity, DV and DO) were calculated from the chemical diffusion and nonstoichiometry data.

The effect of the bulk microstructure (grain size distribution, grain boundary length) on the oxygen transport properties of permeation membranes is investigated in this work. For this purpose, La0.5Sr0.5FeO3-? samples with different microstructures have been prepared by modifying the sintering duration and/or temperature. The average grain sizes, ranging from 0.20 to 1.43 micron, were determined from SEM analysis. The oxygen transport properties of these samples were characterised by permeation measurement as a function of temperature in an air/argon oxygen partial pressure gradient. The fluxes presented a change in the activation energy which was attributed to a change in the rate limiting step, from bulk diffusion at lower temperature (900°C). Only the transport through the bulk was influenced by the microstructure, with the highest flux for the smallest grains. At 800°C, the fluxes were respectively 0.06, 0.03 and 0.01 micromol/cm2s through 1 mm thick samples of average grain sizes of 0.20, 0.63 and 1.43 micron, respectively. This would imply that oxygen transport occurs more rapidly along the grain boundaries than through the bulk. Grain boundary structure and composition were analysed by TEM.

Three perovskite-type compounds of composition La0.4Ca0.6Fe1-xCoxO3-d (x=o, o.25 and 0.5) were investigated for use as oxygen separation membranes for the partial oxidation (POX) of methane to syngas. Special attention was given to the question of their stability in real operating conditions. A permeation set-up was specially designed to measure oxygen fluxes through these materials when placed in a strong pO2 gradient. It also facilitated testing the long-term stability of the specimen. Permeation measurements performed in an air/argon gradient between 800 and 1000 °C showed that the highest fluxes were obtained with the highest content of cobalt (La0.4Ca0.6Fe0.5Co0.5 O3-d =La0.4Ca0.6Fe0.75Co0.25 O3-d >La0.4Ca0.6FeO3-d ). In addition, comparison between the fluxes of samples of different thickness gave clear evidence of surface limitations in the oxygen transport. The long-term stability test showed opposite trends: only the two lowest Co containing compounds (x = 0 and 0.25) sustained and air/(Ar + H2) gradient over more than 600 h. The other (x = 0.5) broke shortly after the introduction of H2. In the presence of H2, the oxygen flux was increased by a factor 10 compared to Ar and reached 0.83 mmol/cm2s for La0.4Ca0.6Fe0.75Co0.25O3-d at 900°C. Post-operation SEM examination of the cross-section and both surfaces revealed that the surface exposed to H2 had started to decompose resulting in the formation of a thin porous layer but the bulk of the material remained unchanged.

Serine proteases play key roles in many biological processes and are associated with several human diseases such as thrombosis or cancer. During the search for selective inhibitors of serine proteases, a family of linear peptides named the aeruginosins was discovered in marine cyanobacteria. We herein report an entry route into the synthetically challenging core fragment of these natural products. Starting from the common oxabicyclic building block 11, we accessed the octahydroindole core of the aeruginosins, exemplified by the total synthesis of microcin SF608 (2). Key to the synthetic strategy is a highly efficient nucleophilic opening of an oxabicyclo[2.2.1]heptane producing the hydroindole motif of microcin SF608. Moreover, during the synthetic efforts we have observed an unusual regioselective epoxide reduction. Detailed experimental studies of this reaction led us to propose a mechanistic rationale involving intramolecular hydrogen atom delivery by a carbamate NH group to control the regioselectivity of the homolytic epoxide cleavage.

Chemical diffusion (D) and surface exchange (k) coefficients for SrFeO3-delta were measured using an electrochemical cell combined with electrochemical impedance spectroscopy (EIS) and potential step technique (PS) in the temperature range of 850-915°C. A value of 4x10-5 cm2/s and a k value of 8x10-5 cm/s were obtained at 900°C. Slow scan (0.5-3 microV/s) cyclic voltametry (CV) was performed in the same temperature range, using the same electrochemical cell to obtain oxygen nonstoichiometry data. The oxygen nonstoichiometry (delta) at 900°C in air was determined as 0.4. A plateau corresponding to delta = 0.5 was observed below an oxygen partial pressure (pO2) of 10-6 atm. These results were shown to be consistent with the literature data. Nonstoichiometry data were further analysed using the existing defect models, and the limits of the independent point defect approximation and the necessity of considering interactions between point defects and clusters were established. Keywords: Strontium Ferrate/Ferrite; Oxygen transport; Oxygen nonstoichiometry.

Oxygen diffusion is treated in a dense electronically conducting cobaltate pellet blocked ionically on one surface, electronically on the other, and sealed on its cylindrical periphery. A procedure is developed for extracting the chemical diffusion and surface exchange coefficients for oxygen by use of the asymptotic equations derived for the current response to a potential step at short and long times. It is shown that, while the formation of interfacial phases by reaction between the sample and the electrolyte may affect the surface exchange coefficient, the chemical diffusion coefficient data determined by the present approach are independent of such interfacial phenomena. The consistency of data obtained from several specimens with varying thickness and manner of interfacing with the electrolyte validates the diffusion model and the method used for data analysis. An oxygen permeation cell is also developed in this work as a modification of the diffusion cell. The new cell allows monitoring of the permeation rate by electrochemical means. The steady-state permeation data obtained by the permeation cell are consistent with the chemical-diffusion and surface- exchange coefficients measured by the blocked diffusion cell as long as the assumptions of the related theoretical models are satisfied. This is a further validation of the diffusion model and the related methodology developed here for obtaining the necessary data for characterizing oxygen exchange and transport in such materials.

Gelsemoxonine (1) is a Gelsemium alkaloid incorporating an unusual azetidine. Its total synthesis was achieved employing a novel ring contraction of a spirocyclopropane isoxazolidine to furnish a β-lactam intermediate. This β-lactam ring was further elaborated into the azetidine of Gelsemoxonine. In addition, the synthesis includes a highly diastereoselective reductive Heck cyclization for the installation of the oxindole ring system as well as a directed hydrosilylation of an alkyne to access the ethyl ketone of the natural product.