Enantiomeric Cyclic Peptides with Different Caco‐2 Permeability Suggest Carrier‐Mediated Transport

Recently, oral absorption of cyclic hexapeptides was improved by N‐methylation of their backbone amides. However, the number and position of N‐methylations or of solvent exposed NHs did not correlate to intestinal permeability, measured in a Caco‐2 model. In this study, we investigate enantiomeric pairs of three polar and two lipophilic peptides to demonstrate the participation of carrier‐mediated transporters. As expected, all the enantiomeric peptides exhibited identical lipophilicity (logD_7.4) and passive transcellular permeability determined by the parallel artificial membrane permeability assay (PAMPA). However, the enantiomeric polar peptides exhibited different Caco‐2 permeability (P_app) in both directions a–b and b–a. The same trend was observed for one of the lipophilic peptide, whereas the second lipophilic enantiomer pair showed identical Caco‐2 permeability (within the errors). These findings provide the first evidence for the involvement of carrier‐mediated transport for peptides, especially for those of polar nature.     

On the domain dependence of solutions to the compressible Navier–Stokes equations of a barotropic fluid

We prove a general compactness result for the solution set of the compressible Navier–Stokes equations with respect to the variation of the underlying spatial domain. Among various corollaries, we then prove a general existence theorem for the system in question with no restrictions on smoothness of the spatial domain. Copyright © 2002 John Wiley & Sons, Ltd.     

On the duration of the total eclipse of a satellite of a body

This paper solves the problem of the duration of the total eclipseof a satellite of a body, provided that (a) the body is sphericalin shape and the mass distribution inside the body is sphericallysymmetrical; (b) the satellite is a very small object; (c) thesatellite's orbit around a body is circular and the satellitecan pass through the centre of its shadow; (d) a source of lightis the source of the conical body's shadow (umbra) and it doesnot change its apparent position in the sky; (e) there are noperturbations on the satellite's orbit. The solution presentedrepresents the general discussion of the problem based on utilizationof some parts of the theory of contraction mappings.     

Geometro-stochastic locality in quantum spacetime and quantum diffusions

The issue of the intrinsic nonlocality of quantum mechanics raised by J. S. Bell is examined from the point of view of the recently developed method of geometro-stochastic quantization and its applications to general relativistic quantum theory. This analysis reveals that a distinction should be made between the topological concept of locality used in formulating relativistic causality and a type of geometric locality based on the concept of fiber bundle, which can be used in extending the strong equivalence principle to the quantum domain. Both play an essential role in formulating a notion of geometro-stochastic propagation based on quantum diffusions, which throws new light on the EPR paradox, on the origin of the arrow of time, and on other fundamental issues in quantum cosmology and the theory of measurement.     

Lot-sizing with fixed charges on stocks: the convex hull

In this paper, we examine a variant of the uncapacitated lot-sizing model of Wagner–Whitin that includes fixed charges on the stocks. Such a model is natural in a production environment where stocking is a complex operation, and appears as a subproblem in more general network design problems.

Linear-programming formulations, a dynamic program, the convex hull of integer solutions and a separation algorithm are presented. All these turn out to be very natural extensions of the corresponding results of Barany et al. (Math. Programming Stud. 22 (1984) 32) for the uncapacitated lot-sizing problem. The convex hull proof is based on showing that an extended facility location formulation is tight and by projecting it onto the original space of variables.     

Parallelization of population-based multi-objective meta-heuristics: An empirical study

In single-objective optimization it is possible to find a global optimum, while in the multi-objective case no optimal solution is clearly defined, but several that simultaneously optimize all the objectives. However, the majority of this kind of problems cannot be solved exactly as they have very large and highly complex search spaces. Recently, meta-heuristic approaches have become important tools for solving multi-objective problems encountered in industry as well as in the theoretical field. Most of these meta-heuristics use a population of solutions, and hence the runtime increases when the population size grows. An interesting way to overcome this problem is to apply parallel processing. This paper analyzes the performance of several parallel paradigms in the context of population-based multi-objective meta-heuristics. In particular, we evaluate four alternative parallelizations of the Pareto simulated annealing algorithm, in terms of quality of the solutions, and speedup.     

A Positive Doubly Power Bounded Operator with a Nonpositive Inverse Exists on any Infinite-dimensional AL-Space

In this paper we construct a positive doubly power bounded operator with a nonpositive inverse on an AL-space.     

A finite difference approach to the equations of age-dependent population dynamics

We establish the convergence of the finite difference scheme for the nonlinear equations of population dynamics proposed by Guertin and MacCamy. The applicability of the discrete equations to establish qualitative properties of the solution to the continuous problem is also illustrated.