Design of amino acid aldehydes as transition-state analogue inhibitors of arginase

Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. Chiral L-amino acids bearing aldehyde side chains have been synthesized in which the electrophilic aldehyde C=O bond is isosteric with the C=N bond of L-arginine. This substitution is intended to facilitate nucleophilic attack by the metal-bridging hydroxide ion upon binding to the arginase active site. Syntheses of the amino acid aldehydes have been accomplished by reduction, oxidation, and Wittig-type reaction with a commercially available derivative of L-glutamic acid. Amino acid aldehydes exhibit inhibition in the micromolar range, and the X-ray crystal structure of arginase I complexed with one of these inhibitors, (S)-2-amino-7-oxoheptanoic acid, has been determined at 2.2 A resolution. In the enzyme-inhibitor complex, the inhibitor aldehyde moiety is hydrated to form the gem-diol: one hydroxyl group bridges the Mn(2+)(2) cluster and donates a hydrogen bond to D128, and the second hydroxyl group donates a hydrogen bond to E277. The binding mode of the neutral gem-diol may mimic the binding of the neutral tetrahedral intermediate and its flanking transition states in arginase catalysis.     

Impact of flow-through regime on the cultivation of epithelial cells on quartz crystal resonators in micro fluidic channels

In this contribution the impact of culture medium flow on the cultivation of Madin-Darby canine kidney cells on quartz crystal resonators (QCRs) was studied. Cells were cultivated at different medium flow rates in a bioreactor chip containing 4 QCRs. Confluency and motility of cells were analyzed based on light microscopical pictures and impedance spectra of the resonators. Results were compared with cells cultivated in culture flasks mounted on a shaker and CFD simulation results of the bioreactor chip. Based on our studies the flow-regime in the micro fluidic channel geometry has major impact e.g. on the cell division rate.     

Divergence-free finite elements for the numerical solution of a hydroelastic vibration problem

In this paper, we analyze a divergence-free finite element method to solve a fluid–structure interaction spectral problem in the three-dimensional case. The unknowns of the resulting formulation are the fluid and solid displacements and the fluid pressure on the interface separating both media. The resulting mixed eigenvalue problem is approximated by using appropriate basis of the divergence-free lowest order Raviart–Thomas elements for the fluid, piecewise linear elements for the solid and piecewise constant elements for the interface pressure. It is proved that eigenvalues and eigenfunctions are correctly approximated and some numerical results are reported in order to assess the performance of the method.     

An augmented stress‐based mixed finite element method for the steady state Navier‐Stokes equations with nonlinear viscosity

A new stress‐based mixed variational formulation for the stationary Navier‐Stokes equations with constant density and variable viscosity depending on the magnitude of the strain tensor, is proposed and analyzed in this work. Our approach is a natural extension of a technique applied in a recent paper by some of the authors to the same boundary value problem but with a viscosity that depends nonlinearly on the gradient of velocity instead of the strain tensor. In this case, and besides remarking that the strain‐dependence for the viscosity yields a more physically relevant model, we notice that to handle this nonlinearity we now need to incorporate not only the strain itself but also the vorticity as auxiliary unknowns. Furthermore, similarly as in that previous work, and aiming to deal with a suitable space for the velocity, the variational formulation is augmented with Galerkin‐type terms arising from the constitutive and equilibrium equations, the relations defining the two additional unknowns, and the Dirichlet boundary condition. In this way, and as the resulting augmented scheme can be rewritten as a fixed‐point operator equation, the classical Schauder and Banach theorems together with monotone operators theory are applied to derive the well‐posedness of the continuous and associated discrete schemes. In particular, we show that arbitrary finite element subspaces can be utilized for the latter, and then we derive optimal a priori error estimates along with the corresponding rates of convergence. Next, a reliable and efficient residual‐based a posteriori error estimator on arbitrary polygonal and polyhedral regions is proposed. The main tools used include Raviart‐Thomas and Clément interpolation operators, inverse and discrete inequalities, and the localization technique based on triangle‐bubble and edge‐bubble functions. Finally, several numerical essays illustrating the good performance of the method, confirming the reliability and efficiency of the a posteriori error estimator, and showing the desired behavior of the adaptive algorithm, are reported. © 2017 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 33: 1692–1725, 2017     

Spectrophotometric determination of mercury(II) and silver(I) with copper(II) and diethyldithiocarbamate in the presence of triton X-100

Procedures for the determination of mercury and silver by displacement of diethyldithiocarbamate (DDTC) from its copper complex in the presence of 1% Triton X-100, and measurement of the decrease in the Cu(DDTC)(2) absorbance, are described. The use of the surfactant avoids the need for an extraction step. Reproducibility within 1% and detection limits of 0.25 ppm Hg(II) and 0.45 ppm Ag(I) have been obtained, and linear calibration ranges up to 13 ppm Hg(II) and 15 ppm Ag(I). In the presence of 0.1M EDTA very good selectivity is achieved.     

Synthetic carbapenem antibiotics II. Stereoisomers of 7-hydroxyethyl-2,2,5-trimethyl-3-oxa-1-azabicyclo[4.2.O]octan-8-one

The titled compounds are key synthetic intermediates in the structure-activity relationship studies of novel 1-methyl carbapenem antibiotics. Preparation and structural determination of these stereoisomers by x-ray crystallography and proton NMR spectroscopy are reported.