Highly enantioselective fluoromalonate addition to α,β-unsaturated aldehydes

A highly enantioselective organocatalytic fluoromalonate addition to α,β-unsaturated aldehydes is reported. The reaction is catalyzed by simple and commercially available secondary amines, affording the corresponding 1,4-adducts with high yields and enantioselectivities.     

Analysis of a pressure-stabilized finite element approximation of the stationary Navier-Stokes equations

Summary. The purpose of this paper is to analyze a finite element approximation of the stationary Navier-Stokes equations that allows the use of equal velocity-pressure interpolation. The idea is to introduce as unknown of the discrete problem the projection of the pressure gradient (multiplied by suitable algorithmic parameters) onto the space of continuous vector fields. The difference between these two vectors (pressure gradient and projection) is introduced in the continuity equation. The resulting formulation is shown to be stable and optimally convergent, both in a norm associated to the problem and in the norm for both velocities and pressure. This is proved first for the Stokes problem, and then it is extended to the nonlinear case. All the analysis relies on an inf-sup condition that is much weaker than for the standard Galerkin approximation, in spite of the fact that the present method is only a minor modification of this. Received May 25, 1998 / Revised version received August 31, 1999 / Published online July 12, 2000     

Enantioselective Organocatalytic Addition of Oxazolones to 1,1‐Bis(phenylsulfonyl)ethylene: A Convenient Asymmetric Synthesis of Quaternary α‐Amino Acids

A new, easy, and highly enantioselective method for the synthesis of quaternary α‐alkyl‐α‐amino acids based on organocatalysis is reported. The addition of oxazolones to 1,1‐bis(phenylsulfonyl)ethylene is efficiently catalyzed by simple chiral bases or thioureas. The reaction affords α,α‐disubstituted α‐amino acid derivatives with complete C4 regioselectivity and with excellent yields and enantioselectivities. This methodology is complementary to previously reported enantioselective approaches to quaternary α‐amino acids and allows the synthesis of α‐phenyl‐α‐alkyl‐α‐amino acids and α‐tert‐butyl‐α‐alkyl‐α‐amino acids. It has distinct advantages in terms of operational simplicity, enviromentally friendly conditions, and suitability for large‐scale reactions.     

Stochastic theory of large-scale enzyme-reaction networks: finite copy number corrections to rate equation models

Chemical reactions inside cells occur in compartment volumes in the range of atto- to femtoliters. Physiological concentrations realized in such small volumes imply low copy numbers of interacting molecules with the consequence of considerable fluctuations in the concentrations. In contrast, rate equation models are based on the implicit assumption of infinitely large numbers of interacting molecules, or equivalently, that reactions occur in infinite volumes at constant macroscopic concentrations. In this article we compute the finite-volume corrections (or equivalently the finite copy number corrections) to the solutions of the rate equations for chemical reaction networks composed of arbitrarily large numbers of enzyme-catalyzed reactions which are confined inside a small subcellular compartment. This is achieved by applying a mesoscopic version of the quasisteady-state assumption to the exact Fokker-Planck equation associated with the Poisson representation of the chemical master equation. The procedure yields impressively simple and compact expressions for the finite-volume corrections. We prove that the predictions of the rate equations will always underestimate the actual steady-state substrate concentrations for an enzyme-reaction network confined in a small volume. In particular we show that the finite-volume corrections increase with decreasing subcellular volume, decreasing Michaelis-Menten constants, and increasing enzyme saturation. The magnitude of the corrections depends sensitively on the topology of the network. The predictions of the theory are shown to be in excellent agreement with stochastic simulations for two types of networks typically associated with protein methylation and metabolism.     

Quality assurance in research: incorporating ISO9001:2000 into a GMP quality management system in a pharmaceutical R+D+I center

There is currently no universal or standardized quality system for the recognition of excellence of a research center. Knowledge and competence may not be enough in the current rapidly changing world in which high productivity and continuous improvement are essential. The purpose of this study was to assess the impacts of implementing the ISO9001:2000:2000 standard in an academic research center dedicated to R+D+I (research, development and innovation) in the pharmaceutical industry. The article describes the stages we followed to implement the ISO9001:2000 system, which was achieved by integrating it into the previous regulatory system of GMP (Good Manufacturing Practices). As a result of implementing ISO9001:2000, the center has seen distinct improvements, such as fewer errors in project documentation, improved assessment of customer satisfaction, and the effective implementation of periodic plans, e.g., in calibration, preventive maintenance, and investments. Overall, ISO9001:2000 implementation has been beneficial for the organization and could be applied to other research centers.     

Definition of norm coherent generalized scalar products and quantum similarity

Complete matrix sums and inward products are employed within vector spaces to define a generalized scalar product, searching at the same time for coherent definitions with the related general order norms. The theoretical background developed in this way permits to connect such mathematical constructs with quantum similarity and QSPR.     

Approximation of the inductionless MHD problem using a stabilized finite element method

In this work, we present a stabilized formulation to solve the inductionless magnetohydrodynamic (MHD) problem using the finite element (FE) method. The MHD problem couples the Navier–Stokes equations and a Darcy-type system for the electric potential via Lorentz’s force in the momentum equation of the Navier–Stokes equations and the currents generated by the moving fluid in Ohm’s law. The key feature of the FE formulation resides in the design of the stabilization terms, which serve several purposes. First, the formulation is suitable for convection dominated flows. Second, there is no need to use interpolation spaces constrained to a compatibility condition in both sub-problems and therefore, equal-order interpolation spaces can be used for all the unknowns. Finally, this formulation leads to a coupled linear system; this monolithic approach is effective, since the coupling can be dealt by effective preconditioning and iterative solvers that allows to deal with high Hartmann numbers.