Chemoenzymatic asymmetric synthesis of fluoxetine,atomoxetine, nisoxetine,and duloxetine

The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.     

A finite element formulation for global linear stability analysis of a nominally two‐dimensional base flow

A stabilized finite element method, to carry out the linear stability analysis of a two‐dimensional base flow to three‐dimensional perturbations that are periodic along span, is presented. The resulting equations for the time evolution of the disturbance requires a solution to the generalized eigenvalue problem. The analysis is global in nature and is also applicable to non‐parallel flows. Equal‐order‐interpolation functions for velocity and pressure are utilized. Stabilization terms are added to the Galerkin formulation to admit the use of equal‐order‐interpolation functions and to eliminate node‐to‐node oscillations that might arise in advection‐dominated flows. The proposed formulation is tested on two flow problems. First, the mode transitions in the circular Couette flow are investigated. Two scenarios are considered. In the first one, the outer cylinder is at rest, while the inner one spins. Two linearly unstable modes are identified. The primary mode is real and represents the axisymmetric Taylor vortices. The second mode is complex and consists of spiral vortices. For the counter‐rotating cylinders, the primary transition is via the appearance of spiral vortices. Excellent agreement with results from earlier studies is observed. The formulation is also utilized to investigate the parallel and oblique modes of vortex shedding past a cylinder for the Re = 100 flow. It is found that the flow is associated with a large number of unstable oblique shedding modes. The parallel mode of vortex shedding is a special case of this family of modes and is associated with the largest growth rate. Copyright © 2014 John Wiley & Sons, Ltd.     

Discrete Morse Theory for Computing Cellular Sheaf Cohomology

Sheaves and sheaf cohomology are powerful tools in computational topology, greatly generalizing persistent homology. We develop an algorithm for simplifying the computation of cellular sheaf cohomology via (discrete) Morse theoretic techniques. As a consequence, we derive efficient techniques for distributed computation of (ordinary) cohomology of a cell complex.     

Oxidation cascade with oxone: cleavage of olefins to carboxylic acids

A variety of olefins is shown to be cleaved oxidatively to the corresponding acids with oxone as the reagent. The simple methodology that works well for a range of alkenes, i.e., styrenes, nitrostyrenes, stilbenes, cinnamic acids, chalcones, etc., involves heating of the reactant with oxone in acetonitrile–water mixture (1:1, v/v) at reflux. The oxidation cascade involves initial dihydroxylation followed by oxidative cleavage and oxidation of the resultant aldehydes to acids.     

Computational design of thermostabilizing D-amino acid substitutions

Judicious incorporation of D-amino acids in engineered proteins confers many advantages such as preventing degradation by endogenous proteases and promoting novel structures and functions not accessible to homochiral polypeptides. Glycine to D-alanine substitutions at the carboxy termini can stabilize α-helices by reducing conformational entropy. Beyond alanine, we propose additional side chain effects on the degree of stabilization conferred by D-amino acid substitutions. A detailed, molecular understanding of backbone and side chain interactions is important for developing rational, broadly applicable strategies in using D-amino acids to increase protein thermostability. Insight from structural bioinformatics combined with computational protein design can successfully guide the selection of stabilizing D-amino acid mutations. Substituting a key glycine in the Trp-cage miniprotein with D-Gln dramatically stabilizes the fold without altering the protein backbone. Stabilities of individual substitutions can be understood in terms of the balance of intramolecular forces both at the α-helix C-terminus and throughout the protein.     

Pseudo-invexity and duality in nonlinear programming

The purpose of this paper is to study various duality results in nonlinear programming for pseudo-invex functions. Such results were known in the literature for invex functions.     

Use of differential scanning calorimetry to study polymer crystallization kinetics with longer half times

A method has been developed to determine polymer crystallization parameters with longer half times using differential scanning calorimetry. This method can be used irrespective of the crystallization temperature, sample weight, nature of the polymer and the sensitivity of the instrument. The results obtained from this method for polyethylene samples are compared with those obtained from dilatometry. Similar values for the kinetic parameters are obtained using both techniques. The calorimetric method has been used for other polymers such as polypropylene and poly(4-methyl-1-pentene).     

Aortoiliac imaging by projective phase sensitive MR angiography: effects of triggering and timing of data acquisition on image quality

To assess the ability of projective phase sensitive magnetic resonance (MR) angiography to visualize the aortoiliac vascular segment, and to determine the effects of triggering and timing of data acquisition om image quality, we studied 18 healthy volunteers, mean age 33.3 +/- 11 years, by color Doppler imaging and by MR angiography. MR angiography was performed at 1.5 T using a flow-adjustable gradient-echo (FLAG) sequence operated in both ECG-triggered and non-triggered acquisition modes. The images were graded in a blinded fashion by two independent observers. The data were analyzed using Pearson's chi-square analysis. Eighteen triggered time-resolved and 17 non-triggered, time-averaged MR angiograms consisting of 252 and 17 angiographic images, (AI) respectively, were analyzed. In the triggered mode 69 (27.4%) AI and in the non-triggered mode 2 (11.8%) AI were diagnostic. At least one triggered diagnostic AI was obtained in each subject. The image grades were not statistically different between observers (kappa = 0.6686). In the triggered mode diagnostic images were acquired within +/- 90 msec of the peak systolic flow velocity determined by Doppler. The proportion of diagnostic images in the triggered mode was highest (73.3%) within a 30-msec interval before the peak flow. In healthy subjects the aortoiliac segment is reliably visualized by FLAG MR angiography. The optimum results are achieved using the triggered acquisition mode and timing acquisition to the initial 180 msec of the abdominal aortic systolic flow pulse.