Characterization of Star Adhesive Sealants Based On PEG/Dextran Hydrogels

Swellable PEG amine/dextran aldehyde composite materials are emerging as a controlled, biocompatible tissue adhesive. We explain how preservation of natural tissue amines provides biocompatibility for PEG/dextran that exceeds the stringent, destructive cyanide‐based chemistry of cyanoacrylates, and adhere far better than fibrin glue. Strategic variations of material composition allow for the improvement of biocompatibility and adhesion strength. Material variations can be tailored to match the needs of specific tissue beds for an array of clinical applications. PEG/dextran cohesive properties are most responsive to variations in the PEG component (number of arms and solid content), while tissue/material adhesion strength is primarily determined by the number of aldehydes in the dextran.

     

Testing independence in nonparametric regression

We propose a new test for independence of error and covariate in a nonparametric regression model. The test statistic is based on a kernel estimator for the L₂-distance between the conditional distribution and the unconditional distribution of the covariates. In contrast to tests so far available in literature, the test can be applied in the important case of multivariate covariates. It can also be adjusted for models with heteroscedastic variance. Asymptotic normality of the test statistic is shown. Simulation results and a real data example are presented.     

Total-variation-diminishing implicit–explicit Runge–Kutta methods for the simulation of double-diffusive convection in astrophysics

We put forward the use of total-variation-diminishing (or more generally, strong stability preserving) implicit–explicit Runge–Kutta methods for the time integration of the equations of motion associated with the semiconvection problem in the simulation of stellar convection. The fully compressible Navier–Stokes equation, augmented by continuity and total energy equations, and an equation of state describing the relation between the thermodynamic quantities, is semi-discretized in space by essentially non-oscillatory schemes and dissipative finite difference methods. It is subsequently integrated in time by Runge–Kutta methods which are constructed such as to preserve the total variation diminishing (or strong stability) property satisfied by the spatial discretization coupled with the forward Euler method. We analyse the stability, accuracy and dissipativity of the time integrators and demonstrate that the most successful methods yield a substantial gain in computational efficiency as compared to classical explicit Runge–Kutta methods.     

Anodic and Cathodic Platinum Dissolution Processes Involve Different Oxide Species

The degradation of Pt-containing oxygen reduction catalysts for fuel cell applications is strongly linked to the electrochemical surface oxidation and reduction of Pt. Here, we study the surface restructuring and Pt dissolution mechanisms during oxidation/reduction for the case of Pt(100) in 0.1 M HClO₄ by combining operando high-energy surface X-ray diffraction, online mass spectrometry, and density functional theory. Our atomic-scale structural studies reveal that anodic dissolution, detected during oxidation, and cathodic dissolution, observed during the subsequent reduction, are linked to two different oxide phases. Anodic dissolution occurs predominantly during nucleation and growth of the first, stripe-like oxide. Cathodic dissolution is linked to a second, amorphous Pt oxide phase that resembles bulk PtO₂ and starts to grow when the coverage of the stripe-like oxide saturates. In addition, we find the amount of surface restructuring after an oxidation/reduction cycle to be potential-independent after the stripe-like oxide has reached its saturation coverage.     

Directed Evolution of an Iron(II)- and α-Ketoglutarate-Dependent Dioxygenase for Site-Selective Azidation of Unactivated Aliphatic C−H Bonds**

Fe^II- and α-ketoglutarate-dependent halogenases and oxygenases can catalyze site-selective functionalization of C−H bonds via a variety of C−X bond forming reactions, but achieving high chemoselectivity for functionalization using non-native functional groups remains rare. The current study shows that directed evolution can be used to engineer variants of the dioxygenase SadX that address this challenge. Site-selective azidation of succinylated amino acids and a succinylated amine was achieved as a result of mutations throughout the SadX structure. The installed azide group was reduced to a primary amine, and the succinyl group required for azidation was enzymatically cleaved to provide the corresponding amine. These results provide a promising starting point for evolving additional SadX variants with activity on structurally distinct substrates and for enabling enzymatic C−H functionalization with other non-native functional groups.     

The Alarmone Diadenosine Tetraphosphate as a Cosubstrate for Protein AMPylation

Diadenosine polyphosphates (Ap_nAs) are non-canonical nucleotides whose cellular concentrations increase during stress and are therefore termed alarmones, signaling homeostatic imbalance. Their cellular role is poorly understood. In this work, we assessed Ap_nAs for their usage as cosubstrates for protein AMPylation, a post-translational modification in which adenosine monophosphate (AMP) is transferred to proteins. In humans, AMPylation mediated by the AMPylator FICD with ATP as a cosubstrate is a response to ER stress. Herein, we demonstrate that Ap₄A is proficiently consumed for AMPylation by FICD. By chemical proteomics using a new chemical probe, we identified new potential AMPylation targets. Interestingly, we found that AMPylation targets of FICD may differ depending on the nucleotide cosubstrate. These results may suggest that signaling at elevated Ap₄A levels during cellular stress differs from when Ap₄A is present at low concentrations, allowing response to extracellular cues.     

Vinyl Halide-Modified Unsaturated Cyclitols are Mechanism-Based Glycosidase Inhibitors

Suitably configured allyl ethers of unsaturated cyclitols act as substrates of β-glycosidases, reacting via allylic cation transition states. Incorporation of halogens at the vinylic position of these carbasugars, along with an activated leaving group, generates potent inactivators of β-glycosidases. Enzymatic turnover of these halogenated cyclitols (F, Cl, Br) displayed a counter-intuitive trend wherein the most electronegative substituents yielded the most labile pseudo-glycosidic linkages. Structures of complexes with the Sulfolobus β-glucosidase revealed similar enzyme-ligand interactions to those seen in complexes with a 2-fluorosugar inhibitor, the lone exception being displacement of tyrosine 322 from the active site by the halogen. Mutation of Y322 to Y322F largely abolished glycosidase activity, consistent with lost interactions at O5, but minimally affected (7-fold) rates of carbasugar hydrolysis, yielding a more selective enzyme for unsaturated cyclitol ether hydrolysis.