Co-administration of polyanions with a phosphorothioate oligodeoxynucleotide (CGP 69846A): a role for the scavenger receptor in its in vivo disposition

The effects of co-administering polyanions on the pharmacokinetics of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A), and the role of scavenger receptors in its in vivo disposition, have been investigated. Following i.v. administration, CGP 69846A was rapidly cleared from the plasma and distributed amongst high (e.g. kidney, liver, spleen), low (e.g. skeletal muscle) and negligible (e.g. brain) accumulating tissues. In addition it was shown that: 1) dextran sulphate co-administration has a dose-dependent effect on the disposition of CGP 69846A; 2) CGP 69846A undergoes renal filtration and renal accumulation largely results from tubular reabsorption; 3) cross-inhibition studies are consistent with CGP 69846A being recognized by scavenger receptors in vitro and in vivo; and 4) the scavenger receptor may be an important determinant for the in vivo disposition of CGP 69846A in mice. These studies contribute toward an increased understanding of the mechanism underlying the pharmacokinetic behaviour of phosphorothioate oligodeoxynucleotides.     

A BIST-DFT technique for DC test of analog modules

Among test techniques for analog circuits, DC test is one of the simplest method for BIST application since easy to integrate test pattern generator and response analyzer are conceivable. Precisely, this paper presents such an investigation for a CMOS operational amplifier that is latter extended to active analog filters. Since the computation of fault coverage is still a controversy question for analog cells, we develop first an evaluation technique for optimizing the tolerance band of the measurements to test. Then, using some DFT solutions we derive single DC pattern and discuss the minimal number of points to test for the detection of defects. A response analyzer is integrated with a Built-in Voltage Sensor (BIVS) and provides directly a logic pass/fail test result. Finally, the extra circuitry introduced by this BIST technique for analog modules does not exceed 5% of the total silicon area of the circuit under test and detects most of the faults.     

A hybrid approach to vehicle routing using neural networks and genetic algorithms

A competitive neural network model and a genetic algorithm are used to improve the initialization and construction phase of a parallel insertion heuristic for the vehicle routing problem with time windows. The neural network identifies seed customers that are distributed over the entire geographic area during the initialization phase, while the genetic algorithm finds good parameter settings in the route construction phase that follows. Computational results on a standard set of problems are also reported.     

Quanteninformation in Österreich

Ohne Zusammenfassung     

On the calculation of boundary stresses with the Somigliana stress identity

The computation of boundary stresses by Boundary Element Method (BEM) is usually performed either by expressing the boundary tractions in a local co-ordinate system, calculating the remaining stresses by shape function differentiation and inserting into Hooke's law or recently also by solving the hypersingular integral equation for the stresses. While direct solution of the hypersingular integral equation, the so-called Somigliana stress identity, has been shown to be more reliable, the interpretation and numerical treatment of the hypersingularity causes a number of problems. In this paper, the limiting procedure in taking the load point to the boundary is carried out by leaving the boundary smooth and the contributions of all different types of singularities to the boundary integral equation are studied in detail. The hypersingular integral in the arising boundary integral equation is then reduced to a strongly singular one by considering a traction free rigid body motion. For the numerical treatment, an algorithm for multidimensional Cauchy Principal Value (CPV) integrals is extended that is applicable for the calculation of boundary stresses. Moreover, the shape of the surrounding of the singular point is studied in detail. A numerical example of elastostatics confirms the validity of the proposed method.     

Does precontemplation represent a homogeneous stage category? A latent class analysis on German smokers.

The authors examined the subtype structure of smokers classified in the precontemplation stage of change within the transtheoretical model. From a general practice-based sample of 1,499 daily smoking patients from Germany (participation rate 80%), they used a subgroup of 929 smokers who were classified in the precontemplation stage and applied latent class analysis, using the pros and cons of nonsmoking and smoking cessation self-efficacy as the defining variables. Cross-sectional validation of the emerging classes was based on smoking behavior and processes of change variables. For longitudinal validation, generalized estimation equation analyses were used on motivational and abstinence criteria from 6-, 12-, 18-, and 24-month follow-ups. A 4-class model best represented the data. Three subtypes (labeled progressive, immotive, and disengaged pessimistic) were similar to clusters identified in U.S. studies. The 4th (disengaged optimistic), by contrast, was reminiscent of a type that had previously only emerged in a Dutch study. Cross-sectional and longitudinal validation results confirmed the distinctiveness and predictive power of the classes. The findings highlight the importance of tailoring interventions for smoking behavior change to the needs of different subgroups of precontemplating smokers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hydrogen-Bond Dynamics and Solvation of Electronically Excited States as Determined by Femtosecond Vibrational Spectroscopy

The ultrafast dynamics of site-specific hydrogen bonds between an organic chromophore serving as hydrogen acceptor and a hydrogen-donating species in solution is studied by femtosecond vibrational spectroscopy. This new method gives specific insight into microscopic structural changes of hydrogen bonds initiated by electronic excitation of the chromophore. We study H-bonded complexes of coumarin 102 with the solvent CHCl₃, and with phenol. Upon electronic excitation, the intermolecular hydrogen bond between proton donor and acceptor is cleaved within 200 fs, followed by a slower reorientation dynamics of the donor molecules extending into the picosecond regime. For CHCl₃, this slower rearrangement is interpreted in terms of polar solvation. In complexes consisting of a coumarin molecule and two phenol moieties, the slower dynamics is related to geometry changes of the phenol–phenol hydrogen bond. The consequences of those results for a microscopic picture of polar solvation are discussed.