Microstructural investigation of monoglyceride-water coagel systems by NMR and CryoSEM

Monoglyceride coagels consist of a network of plate-like crystals and are formed from a swollen gel state (alpha-gel). In order to resolve the transition mechanism, coagels were prepared with monoglycerides that differ in fatty acid composition (monomyristate and palmitate/stearate, respectively). Rheology provided information on kinetics of coagel formation and the strength of the resulting crystal network. From NMR measurements, the surface-to-volume ratio, tortuosity, and dimensionality of the network were obtained. These findings were in line with qualitative and quantitative structural information obtained from CryoSEM. As a model for the behaviour of non-monoglyceride species, the dynamics of (perdeuterated) palmitic acid was monitored in both alpha-gels and coagels. The experimental data support a two-stage mechanism. In the first stage, two-dimensional separation of D- and L-isomers in the monoglyceride bilayers of the alpha-gel occurs. This process depends primarily on lateral diffusion rate of the monoglycerides. Palmitic acid can be accommodated in the alpha-gel bilayer, but in the coagels it is separated into relative mobile and mechanically weak junction zones between the crystal plates. In the second stage of coagel formation, the crystal plates also grow in the third dimension. Both monoglyceride type and concentration determine the kinetics of this process.     

Local-global problem for Drinfeld modules

Let K be a function field with an A-algebra structure. The ring A arises in the definition of the Drinfeld module φ over K. By E(K) we denote K together with the A-module structure induced on it by φ. For any principal prime ideal (a)⊂A, we study the question whether an element x∈E(K) which is an a-fold in E(K_ν) for every place ν of K, is an a-fold in E(K). In particular, we study the group

     

Weil Pairing for Drinfeld Modules

As is well-known, there exists a Weil pairing for elliptic curves which is a perfect bilinear form from the m-torsion of the elliptic curve E to the m-th roots of unity. In this paper we will show how Andersons paper [1] gives rise to an analogue of this pairing for Drinfeld modules.The author was supported by NWO Grant 613.007.040. The author would like to thank G. Böckle and S. J. Edixhoven for their comments.     

Exhaustive search of the configurational space of heat-shock protein 90 with its inhibitor by multicanonical molecular dynamics based dynamic docking

Multicanonical molecular dynamics based dynamic docking was used to exhaustively search the configurational space of an inhibitor binding to the N-terminal domain of heat-shock protein 90 (Hsp90). The obtained structures at 300 K cover a wide structural ensemble, with the top two clusters ranked by their free energy coinciding with the native binding site. The representative structure of the most stable cluster reproduced the experimental binding configuration, but an interesting conformational change in Hsp90 could be observed. The combined effects of solvation and ligand binding shift the equilibrium from a preferred loop-in conformation in the unbound state to an α-helical one in the bound state for the flexible lid region of Hsp90. Thus, our dynamic docking method is effective at predicting the native binding site while exhaustively sampling a wide configurational space, modulating the protein structure upon binding.     

Unnatural selection: talent identification and development in sport

The early identification of talented individuals has become increasingly important across many performance domains. Current talent identification (TI) schemes in sport typically select on the basis of discrete, unidimensional measures at unstable periods in the athlete's development. In this article, the concept of talent is revised as a complex, dynamical system in which future behaviors emerge from an interaction of key performance determinants such as psychological behaviors, motor abilities, and physical characteristics. Key nonlinear dynamics concepts are related to TI approaches such as sensitivity to initial conditions, transitions, and exponential behavioral distributions. It is concluded that many TI models place an overemphasis on early identification rather than the development of potentially talented performers. A generic model of talent identification and development is proposed that addresses these issues and provides direction for future research.     

Hit-and-run algorithms for the identification of nonredundant linear inequalities

Two probabilistic hit-and-run algorithms are presented to detect nonredundant constraints in a full dimensional system of linear inequalities. The algorithms proceed by generating a random sequence of interior points whose limiting distribution is uniform, and by searching for a nonredundant constraint in the direction of a random vector from each point in the sequence. In the hypersphere directions algorithm the direction vector is drawn from a uniform distribution on a hypersphere. In the computationally superior coordinate directions algorithm a search is carried out along one of the coordinate vectors. The algorithms are terminated through the use of a Bayesian stopping rule. Computational experience with the algorithms and the stopping rule will be reported.     

A rapid assay for on-site monitoring of infliximab trough levels: a feasibility study

Monitoring levels of biologicals against tumor necrosis factor (TNF) has been suggested to improve therapeutic outcomes in inflammatory bowel diseases (IBDs). This pilot study describes a rapid lateral flow (LF)-based assay for on-site monitoring of serum trough levels of humanized monoclonal antibody infliximab (IFX). The applied chromatographic method utilizes sequential flows of diluted serum, wash buffer, and an immunoglobulin generic label on LF strips with a Test line comprised of TNF-α. The successive flows permitted enrichment of IFX at the Test line before the label was applied. The label, luminescent upconverting phosphor (UCP) particles coated with protein-A, emits a 550-nm visible light upon excitation with 980-nm infrared light. IFX concentrations were determined through measurement of UCP fluorescence at the Test line. The assay was optimized to detect IFX levels as low as 0.17 μg/mL in serum. For patients with IBD, this limit is appropriate to detect levels associated with loss of response (0.5 μg IFX/mL). The assay was evaluated with clinical samples from patients with Crohn’s disease and correlated well within the physiologically relevant range from 0.17 to 10 μg/mL with an IFX-specific ELISA. Performance of the assay was further successfully validated with samples from blood donors, IFX negative IBD patients, and rheumatoid arthritis patients that had developed anti-IFX antibodies. Because of its generic nature, the assay is suited for detecting most therapeutic anti-TNF-α monoclonal antibodies.

A stochastic method for global optimization

A stochastic method for global optimization is described and evaluated. The method involves a combination of sampling, clustering and local search, and terminates with a range of confidence intervals on the value of the global optimum. Computational results on standard test functions are included as well.