Tailoring of Surfaces with Ultrathin Layers for Controlled Binding of Biopolymers and Adhesion and Guidance of Cells

Various strategies are described for the bio-functionalization of solid substrates by design of interfacial architectures. The first approach is based on the self-assembly process of long-chain thiol molecules from solution to a (noble) metal surface. If some of these building blocks carry a binding site (ligand) for proteins (receptors, antibodies, etc.) the metal surface can be tailored for maximum specific binding while simultaneously minimizing nonspecific adsorption. The second concept is based on polymers that are covalently attached to (oxide) surfaces. The preparation of these (end-) grafted functional polymers involves either the binding of preformed macromolecules to corresponding sites at the surface of the support or the recently introduced “grafting-from” method, by which an initiator molecule is first covalently bound to the surface and then activated — either by heat or light — in the presence of suitable monomer units such that a polymer chain grows from the solid/solution interface. Finally, the functionalization of patterned surfaces by peptide chains that mimic the binding domains of cell adhesion proteins is summarized. It is demonstrated that not only the selective adhesion of neuronal cells can then be controlled, but also their development with the outgrowth of dendrites and axons.     

A Jini service to reconstruct tomographic data

Distributed computing that uses dynamic networks will change the way we work and communicate thanks to the interaction of devices and services, that are automatically added and removed from the network as needed. The Jini technology, which is built atop the Java programming language, provides a homogenous view of the network and extends the ability of code to migrate in Java. This software design model simplifies the configuration and access to hardware devices and software services in a network. Thus, it becomes possible to execute new services without pre-installing software on client machines. This new programming paradigm is especially important in medical applications, where the reliable transmission of information is essential. This paper demonstrates how single photon emission computerized tomography data can be iteratively reconstructed using a Jini service.     

Formylation products of thioamides. XIII. Reaction of N-(3-aminothioacryloyl)-formamidines with amines – Synthesis of Pyrimidine Derivatives

N-(3-Aminothioacryloyl)-formamidines 3 react with primary amines to give either 4(1H)-pyrimidinthiones 6 or transaminated N-(3-aminothioacryloyl)-formamidines 5 . Alkylation of the latter compounds gives rise to cyclised 6(1H)-pyrimidinimines 7 . The 4(1H)-pyrimidinthiones 6 can be S-alkylated to 4-alkylmercaptopyrimidinium salts 8 . Subsequent substitution of the alkylmercapto group of the 8 results in the formation of 4-aminopyrimidinium salts 9 , which can also be obtained starting from the 3 by a reversed reaction sequence that is first by S-alkylation to 3-alkylmercapto-2-azapentamethinium salts 10 and subsequent reaction with primary amines.     

Morphology and crack resistance behavior of binary block copolymer blends

Fracture behavior of binary blends comprising of styrene-butadiene block copolymers having star and triblock architectures was studied via instrumented Charpy impact test. The toughness of the ductile blends was characterized by dynamic crack resistance curves (R-curves).This study represents a systematic investigation of crack resistance behavior of nanometer structured binary block copolymer blends and the development of a new material with a combination of high toughness and transparency, usually not observed in incompatible polymer blends. While the lamellar star block copolymer shows an elastic behavior (small-scale yielding and unstable crack growth), adding of 20 wt% of the triblock copolymer leads to a stable crack growth and at 60 wt% of the triblock copolymer the strong increase of toughness values indicate a tough/high-impact transition, demonstrating the existence of novel toughening concepts for polymers based on nanometer structured materials.     

Mismatch discrimination in oligonucleotide hybridization reactions using single strand binding protein. A surface plasmon fluorescence study

We describe the use of surface plasmon- and surface plasmon fieldenhanced fluorescence spectroscopy for the detection of hybridization reactions between surface-attached probe oligonucleotides and complement strands binding from solution. These targets, exhibiting different base mismatches relative to the probe 15-mer sequences, carry a fluorophore at their 5'-end thus allowing for sensitive detection and quantification of association, k_on, and dissociation, k_off, rate constants, as well as affinity constants, K_a. We demonstrate that by the competitive binding / replacement of single strand binding proteins the mismatch discrimination can be further enhanced.     

Rational protein design of ThDP-dependent enzymes-engineering stereoselectivity

Benzoylformate decarboxylase (BFD) from Pseudomonas putida is an exceptional thiamin diphosphate-dependent enzyme, as it catalyzes the formation of (S)-2-hydroxy-1-phenylpropan-1-one from benzaldehyde and acetaldehyde. This is the only currently known S-selective reaction (92 % ee) catalyzed by this otherwise R-selective class of enzymes. Here we describe the molecular basis of the introduction of S selectivity into ThDP-dependent decarboxylases. By shaping the active site of BFD through the use of rational protein design, structural analysis, and molecular modeling, optimal steric stabilization of the acceptor aldehyde in a structural element called the S pocket was identified as the predominant interaction for adjusting stereoselectivity. Our studies revealed Leu461 as a hot spot for stereoselectivity in BFD. Exchange to alanine and glycine resulted in variants that catalyze the S-stereoselective addition of larger acceptor aldehydes, such as propanal with benzaldehyde and its derivatives-a reaction not catalyzed by the wild-type enzyme. Crystal structure analysis of the variant BFDL461A supports the modeling studies.     

DEFECT CORRECTION WITH A FULLY COUPLED INEXACT NEWTON METHOD

Abstract

We examine the characteristics of a fully coupled inexact Newton method using defect correction to obtain high-order solutions for two problems: natural convection in a square cavity and mixed-convection flow over a backward step. Newton's method produces a linearized system with a Jacobian matrix and a residual vector, each of which can be formed using different discrete operators. Solution accuracy depends on the discretization used for the residuals. Defect correction employs low-order operators for the Jacobian but high-order operators for the residuals. We employ an O(h³) convection operator in the residual vector and upwinding in the Jacobian. We find that defect correction is an efficient and effective way to achieve high-order solutions.     

Clinical experience using gabapentin adjunctively in patients with a history of mania or hypomania

Biliary, plasma, and urinary disposition of paclitaxel and paclitaxel metabolites were determined simultaneously in a patient with percutaneous biliary drain. The complete chemical structures of the major metabolites were established by mass spectrometry and NMR spectroscopy. A nonlinear elimination model was indicated by the fact that the rate of biliary excretion of paclitaxel rose as plasma concentrations fell. Dihydroxypaclitaxel was the predominant biliary metabolite, in contrast to the barely detectable levels in two previous patients. This derivative results from hydroxylation at the C6 position of the taxane ring and at the phenyl C3'-position on the C13 side chain mediated by cytochrome P450 2C8 and 3A4, respectively. In line with this mechanism, the two other main metabolites corresponded to 6alpha-hydroxypaclitaxel and to the paclitaxel derivative hydroxylated in the para-position on the phenyl ring at the C3'-position of the C13. A high CYP3A4 activity in the patient is consistent with the repeated administration of methylprednisolone for 14 days before paclitaxel treatment, a compound known to induce the CYP3A isoform, and with the increased ratio of 6beta-hydroxycortisol/cortisol in urine, an index of CYP3A activity. These findings emphasize the influence of pretreatment with corticoids on the disposition of paclitaxel.     

Goodness of fit for random rankings in Kruskal's nonmetric scaling procedure.

Analyzed random input data with J. B. Kruskal's nonmetric scaling program in order to establish null hypotheses for the goodness-of-fit measure. Various numbers of hypothetical stimuli were analyzed using the Euclidean distance metric in various dimensionalities, and the effects of tied ranks were studied. (PsycINFO Database Record (c) 2010 APA, all rights reserved)