Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase

Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E = 52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E ? 300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E ? 300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E ? 300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5 times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters.     

Cross-section measurements for the 58,60,61Ni(n, α)55,57,58Fe reactions at 8.50, 9.50 and 10.50 MeV neutron energies

Cross sections of the ^58,60,61Ni(n, α)^55,57,58Fe reactions were measured at 8.50, 9.50 and 10.50 MeV neutron energies based on the HI-13 tandem accelerator of China Institute of Atomic Energy (CIAE) with enriched ⁵⁸Ni, ⁶⁰Ni, and ⁶¹Ni foil samples with backings. A twin gridded ionization chamber (GIC) was used as the charged particle detector, and an EJ-309 liquid scintillator was used to obtain the neutron energy spectra. The relative and absolute neutron fluxes were determined via three highly enriched ²³⁸U₃O₈ samples inside the GIC. The uncertainty of the present data of the ⁵⁸Ni(n, α)⁵⁵Fe reaction is smaller than most existing measurements. The present data of ⁶⁰Ni(n, α)⁵⁷Fe and ⁶¹Ni(n, α)⁵⁸Fe reactions are the first measurement results above 8 MeV. The present experimental data could be reasonably reproduced by calculations with TALYS-1.9 by adjusting several default values of theoretical model parameters.     

Problèmes diophantiens simultanés

Simultaneous Diophantine Approximations. We study a mixed simultaneous diophantine problem, with an approximation condition and a divisibility condition. We solve this problem for quadratic numbers.     

Hermite functions and weighted spaces of generalized functions

We prove that the Hermite functions are an absolute Schauder basis for many weighted spaces of (ultra)differentiable functions and ultradistributions including the space of Fourier hyperfunctions. The coefficient spaces are also determined. Dedicated to Professor H.-G. Tillmann on the occasion of his 80th birthday     

A dynamic location problem with maximum decreasing capacities

In this paper a capacitated dynamic location problem with opening, closure and reopening of facilities is formulated and a primal-dual heuristic that can solve this problem is described. The problem formulated considers the situation where a facility is open (or reopens) with a certain maximum capacity that decreases as clients are assigned to that facility during its operating periods. This problem is NP-hard. Computational results are presented and discussed. This research was partially supported by research project POCTI/ISFL-1/152 and POCTI/MAT/139/2001.     

Some inequalities for the atom-bond connectivity index of graph operations

The atom-bond connectivity index is a useful topological index in studying the stability of alkanes and the strain energy of cycloalkanes. In this paper some inequalities for the atom-bond connectivity index of a series of graph operations are presented. We also prove our bounds are tight. As an application, the ABC indices of C₄ nanotubes and nanotori are computed.     

The uncertain mortality intensity framework: Pricing and hedging unit-linked life insurance contracts

We study the valuation and hedging of unit-linked life insurance contracts in a setting where mortality intensity is governed by a stochastic process. We focus on model risk arising from different specifications for the mortality intensity. To do so we assume that the mortality intensity is almost surely bounded under the statistical measure. Further, we restrict the equivalent martingale measures and apply the same bounds to the mortality intensity under these measures. For this setting we derive upper and lower price bounds for unit-linked life insurance contracts using stochastic control techniques. We also show that the induced hedging strategies indeed produce a dynamic superhedge and subhedge under the statistical measure in the limit when the number of contracts increases. This justifies the bounds for the mortality intensity under the pricing measures. We provide numerical examples investigating fixed-term, endowment insurance contracts and their combinations including various guarantee features. The pricing partial differential equation for the upper and lower price bounds is solved by finite difference methods. For our contracts and choice of parameters the pricing and hedging is fairly robust with respect to misspecification of the mortality intensity. The model risk resulting from the uncertain mortality intensity is of minor importance.     

Optimal timing of regime switching in optimal growth models: A Sobolev space approach

This paper analyses the optimal timing of switching between alternative and consecutive regimes in optimal growth models. We derive the appropriate necessary conditions for such problems by means of standard techniques from the calculus of variations and some basic properties of Sobolev spaces.     

Complex formation of some nonionic surfactants with hydroxypropyl-β-cyclodextrin and with heptakis (2,6-di-O-methyl)-β-cyclodextrin

The interaction of six nonionic surfactants 61/xxlarge945.gif" alt="agr" align="BASELINE" BORDER="0">-[4-(1,1,3,3-tetra-methylbutyl)phenyl]-61/xxlarge969.gif" alt="ohgr" align="BASELINE" BORDER="0">-hydroxypoly(oxy-1,2-ethanediyl) with hydroxypropyl-61/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-cyclodextrin (HP61/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">CD) and dimethyl-61/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">-cyclodextrin (DIMEB) was studied by reversed-phase thin-layer chromatography in the presence and absence of sodium chloride. Each surfactant formed complexes with both cyclodextrin derivatives; however, the strength of interaction varied considerably. DIMEB formed more stable inclusion complexes with the surfactants than did HP61/xxlarge946.gif" alt="beta" align="MIDDLE" BORDER="0">CD. A longer ethyleneoxide chain decreased the strength of interaction, whereas sodium chloride exerted a negligible impact. Principal component analysis indicated that both the hydrophobicity and the specific hydrophobic surface are of the surfactant influenced the complex formation indicating the hydrophobic character of the interaction.Dedicated to Professor József Szejtli.     

Strongly indexable graphs and applications

In 1990, Acharya and Hegde introduced the concept of strongly k-indexable graphs: A (p,q)-graph G=(V,E) is said to be strongly k-indexable if its vertices can be assigned distinct numbers 0,1,2,…,p−1 so that the values of the edges, obtained as the sums of the numbers assigned to their end vertices form an arithmetic progression k,k+1,k+2,…,k+(q−1). When k=1, a strongly k-indexable graph is simply called a strongly indexable graph. In this paper, we report some results on strongly k-indexable graphs and give an application of strongly k-indexable graphs to plane geometry, viz; construction of polygons of same internal angles and sides of distinct lengths.