Reactivity of V/Nb mixed oxides in the oxidehydrogenation of propane under co-feed and under redox-decoupling conditions

V/Nb mixed oxides were prepared, characterized and tested as catalysts for the oxidehydrogenation of propane to propylene. The reactivity tests were carried out under co-feed and under redox-decoupling conditions, with alternate-feeds of propane and air (cyclic operation). The comparison between co-feed and alternate-feed operations evidenced that in the latter case a higher selectivity to propylene is achieved at low propane conversion. This was attributed to a reaction mechanism mainly involving propane dehydrogenation rather than oxidehydrogenation, occurring on the reduced catalysts. The selectivity to propylene, however, under both operating conditions decreased with increasing propane conversion. During reaction under redox-decoupling conditions VNbO₅ decomposed yielding vanadium oxide and V/Nb mixed oxides having V/Nb ratio lower than 1. The former compound played the major role in the reaction cycle.     

Two Subtle Amino Acid Changes in a Transaminase Substantially Enhance or Invert Enantiopreference in Cascade Syntheses

Amine transaminases (ATAs) are powerful enzymes for the stereospecific production of chiral amines. However, the synthesis of amines incorporating more than one stereocenter is still a challenge. We developed a cascade synthesis to access optically active 3‐alkyl‐substituted chiral amines by combining two asymmetric synthesis steps catalyzed by an enoate reductase and ATAs. The ATA wild type from Vibrio fluvialis showed only modest enantioselectivity (14 % de) in the amination of (S)‐3‐methylcyclohexanone, the product of the enoate‐reductase‐catalyzed reaction step. However, by protein engineering we created two variants with substantially improved diastereoselectivities: variant Leu56Val exhibited a higher R selectivity (66 % de) whereas the Leu56Ile substitution caused a switch in enantiopreference to furnish the S‐configured diastereomer (70 % de). Addition of 30 % DMSO further improved the selectivity and facilitated the synthesis of (1R,3S)‐1‐amino‐3‐methylcyclohexane with 89 % de at 87 % conversion.     

Anhydrobiosis in yeasts: Psychrotolerant yeasts are highly resistant to dehydration

Yeast cells are able to transition into a state of anhydrobiosis (temporary reversible suspension of metabolism) under conditions of desiccation. One of the most efficient approaches for understanding the mechanisms underlying resistance to dehydration–rehydration is to identify yeasts, which are stable under such treatments, and compare them with moderately resistant species and strains. In the current study, we investigated the resistance to dehydration–rehydration of six psychrotolerant yeast strains belonging to two species. All studied strains of Solicoccozyma terricola and Naganishia albida were found to be highly resistant to dehydration–rehydration. The viability of S. terricola strains was close to 100%. Such results have not been previously reported in studies of anhydrobiosis in yeasts. The plasma membrane changes, revealed by determining its permeability under various rehydration conditions, were also surprisingly minimal. Thus, the high level of resistance of psychrotolerant yeast strains might be related to the chemical composition and molecular organisation of their plasma membranes. Aside from plasma membrane characteristics, other important factors may also influence the maintenance of yeast cell viability under conditions of dehydration–rehydration.     

Floating modular drug delivery systems with buoyancy independent of release mechanisms to sustain amoxicillin and clarithromycin intra-gastric concentrations

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5?h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8?h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly’s permanence in the stomach for at least 4?h.     

Light-Controllable Binary Switch Activation of CAR T Cells

Major challenges to chimeric antigen receptor (CAR) T cell therapies include uncontrolled immune activity, off-tumor toxicities and tumor heterogeneity. To overcome these challenges, we engineered CARs directed against small molecules. By conjugating the same small molecule to distinct tumor-targeting antibodies, we show that small molecule specific-CAR T cells can be redirected to different tumor antigens. Such binary switches allow control over the degree of CAR T cell activity and enables simultaneous targeting of multiple tumor-associated antigens. We also demonstrate that ultraviolet light-sensitive caging of small molecules blocks CAR T cell activation. Exposure to ultraviolet light, uncaged small molecules and restored CAR T cell-mediated killing. Together, our data demonstrate that a light-sensitive caging system enables an additional level of control over tumor cell killing, which could improve the therapeutic index of CAR T cell therapies.     

Gas-Carburizing Kinetics of a Low-Alloy Steel

Gas-carburizing kinetics of a low-alloy steel (Pyrowear 53) was investigated by thermogravimetric experiments. Kinetic curves were modeled by adapting the approximate integral method, and the diffusion coefficient of carbon as well as the rate constant of the surface reaction were estimated. These parameters were evaluated after several carburizing procedures, which differ from each other in the surface treatments performed before the carburizing step. It is known that the carbon enrichment is low when this steel is carburized without any pretreatment, and this behavior was found to be related to a low value of carbon diffusivity. The interaction between the selective oxidation of alloying elements by the carburizing atmosphere and carbon diffusion is discussed. The pretreatment procedures investigated in this work consist of different combinations of oxidation, reduction, and grit-blasting processes. The most effective procedures involve oxidation in dry air or oxidation in wet air followed by grit blasting.     

Electrosynthesis of valuable conducting polymers from the anodic coupling of β-substituted oligothiophenes

Electrochemical polymerization of thiophene oligomers (n = 4) bearing an hexamethylenic ω-methoxy functionalized side chain at the 3-3″′ position of the thiophene rings, was performed in different solvents and electrode surfaces. The degree of polymerization and the electrochemical behaviour of the different electrosynthetized polymers were compared with a polymer obtained by a chemical method. The polymeric films were characterized using cyclic voltammetry, FT-IR, AFM and SEM microscopy.     

Investigation of HNCO adsorption and hydrolysis on Fe-ZSM5

The adsorption of HNCO on Fe-ZSM5 was investigated in detail by DRIFT spectroscopy and compared to the adsorption on H-ZSM5, Al₂O₃, SiO₂, Fe₂O₃/Al₂O₃ and Fe₂O₃/SiO₂. At 150 °C, HNCO adsorbs dissociatively on Fe-ZSM5 producing principally isocyanate species (–NCO) adsorbed on Al and Fe sites. In the presence of water the hydrolysis of the –NCO groups to NH₃ was observed. Comparison of the DRIFT results with measurements of the catalytic activity of coated cordierite monoliths suggests that –NCO groups are likely intermediate species in the hydrolysis of HNCO over Fe-ZSM5.     

Unilateral Contact Problem for Aging Viscoelastic Beams

The frictionless unilateral contact problem of a viscoelastic Bernoulli–Euler beam resting on a viscoelastic soil is studied. The mathematical formulation involves equilibrium equations, compatibility equations, and constitutive laws, with an aging integral-type form. The unilateral nature of the contact is imposed through a compatibility inequality, which allows the determination of the contact imprint at each time. Further, the governing integro-differential equation for the unknown contact pressure is derived. As special cases, the elastic Winkler-type soil and the rigid soil conditions are discussed. A numerical approach is presented, which employs the finite difference method along space and an adaptive step-by-step algorithm along time. The procedure allows for time discontinuities of both external loads and contact pressure. Several selected numerical examples are presented and the influence of the most important material and geometrical parameters are shown. For the simplest situations, it was possible to compare the results obtained with known analytical solutions.     

Design and Synthesis of Fluorescent Methylphenidate Analogues for a FRET-Based Assay of Synapsin III Binding

We previously described synapsin III (Syn III) as a synaptic phosphoprotein that controls dopamine release in cooperation with α-synuclein (aSyn). Moreover, we found that in Parkinson's disease (PD), Syn III also participates in aSyn aggregation and toxicity. Our recent observations point to threo-methylphenidate (MPH), a monoamine re-uptake inhibitor that efficiently counteracts the freezing-gait characteristic of advanced PD, as a ligand for Syn III. We have designed and synthesised two different fluorescently labelled MPH derivatives, one with Rhodamine Red (RHOD) and one with 5-carboxytetramethylrhodamine (TAMRA), to be used for assessing MPH binding to Syn III by FRET. TAMRA-MPH exhibited the ideal characteristics to be used as a FRET acceptor, as it was able to enter into the SK-N-SH cells and could interact specifically with human green fluorescent protein (GFP)-tagged Syn III but not with GFP alone. Moreover, the uptake of TAMRA-MPH and co-localization with Syn III was also observed in primary mesencephalic neurons. These findings support that MPH is a Syn III ligand and that TAMRA-conjugated drug molecules might be valuable tools to study drug-ligand interactions by FRET or to detect Syn III in cytological and histological samples.