In vitro biotransformation of (R)- and (S)-thalidomide: application of circular dichroism spectroscopy to the stereochemical characterization of the hydroxylated metabolites

Circular dichroism (CD) spectroscopy was successfully used for the stereochemical characterization of the hydroxylated metabolites formed during the in vitro biotransformation of (R)- and (S)-thalidomide. Incubation extracts of the individual enantiomers were analyzed by HPLC on an achiral stationary phase combined with CD detection. The CD data of the almost enantiopure eluates of the metabolites were compared with the CD spectra quantum chemically calculated for the respective structures. The results allowed us a reliable determination of the absolute stereostructure for all of the metabolites. The chiral center of thalidomide is unaffected by the stereoselective biotransformation process. (3'R,5'R)-trans-5'-hydroxythalidomide is the main metabolite of (R)-thalidomide, which epimerizes spontaneously to give the more stable (3'S,5'R)-cis isomer. On the contrary, (S)-thalidomide is preferentially metabolized by hydroxylation in the phthalimide moiety, resulting in the formation of (S)-5-hydroxythalidomide.     

Variation of composition of an enteric formulation based on Kollicoat MAE 30 D

Using a formulation described previously with Kollicoat MAE 30 D as the film-forming agent, the effect of variations in plasticizer type and quantity and talc concentration on the preparation and processing of spray-coating suspensions and the properties of isolated films and film-coated caffeine tablets prepared using them was investigated. In the preparation and processing of spray-coating suspensions, the plasticizers polyethylene glycol (PEG) 400, PEG1500, and TEC (triethyl citrate) tended to coagulate at all concentrations investigated, while Cremophor RH 40 coagulated above 10% (expressed as a percentage of the mass of the film-forming agent used). Analogous preparations using propylene glycol (PG), PEG6000, and Lutrol F 68, on the other hand, were found to be stable at all concentrations. The instability was not caused by the Kollicoat MAE 30 D polymer dispersion as such, but by interactions between the finely dispersed pigments and other formulation ingredients. Equivalent nonpigmented preparations are stable and do not coagulate. With all the plasticizers investigated, the minimum film-forming temperature (MFT) fell, albeit to differing degrees, as the amount of plasticizer increased. Similarly, the tensile strength of isolated films declined as plasticizer concentration increased, while the reverse was true as regards their elongation at break. Whereas neither the subsequent disintegration time nor the rate of release of active ingredient at pH 6.8 was significantly affected by the various plasticizer additives, the different film-coated tablet formulations with a core containing a powerful disintegrant exhibited varying degrees of permeability to simulated gastric fluid. With PEG6000, permeability increased as the plasticizer concentration increased, while Lutrol F 68 provided an optimum barrier at 20%, and PG provided a good barrier between 10% and 30%. No gastroresistance was obtained with TEC at 10%. Only the best plasticizer formulations were used in the trials with different talc concentrations, namely, those formulations with 20% PEG6000, 20% Lutrol F 68, 20% PG, and 10% PG. When talc was added, the MFT rose, reaching its maximum at 13% talc (as a proportion of the film-forming agent). In the test for gastroresistance, film-coated caffeine tablets without talc absorbed distinctly more acid than those containing talc. Above 27% talc, the acid resistance improved only insignificantly. On the other hand, during this test, only a maximum of 3% of the active ingredient was released into the gastric juice. Of the variants investigated, the formulation with 20% PG and 27% talc performed best.     

A survey of database design transformations based on the Entity-Relationship model

At present, the Entity-Relationship (ER) model is the most important paradigm for conceptual database design. Since the model was introduced in the mid-seventies, a large body of literature has been published on transforming conceptual ER schemas or diagrams into logical data models. The purpose of this paper is to survey this literature. A first focus is on transformation approaches from the ER model to traditional data models, i.e. to the relational, the network, or the hierarchical model; this is then complemented by a discussion of more recent transformations to object-oriented models. A second focus is on considering the process of reverse engineering, i.e. transformations from a logical model back into the ER model; finally, an overview of direct transformations between various logical data models is presented.     

Einfluß von Wasserdampf im Sintergas auf das Verhalten von Metallpulvern mit unter Sinterbedingungen reduzierbaren Oxydschichten

An aus Elektrolyteisen-, Karbonylnickel- und Kupferpulver hergestellten Preßkörpern Untersuchung ihres Sinterverhaltens unter Wasserstoffgas mit Zusätzen von 0,1 und 10 Vol.-% Wasserdampf bei Sintertemperaturen von 870 bis 1200 °C und Sinterdauern von 0 bis 8 h. Messung von Dichte, 0,2-Orenze, Zugfestigkeit und Bruchdehnung der Proben in Abhängigkeit vom Wasserdampfgehalt im Sintergas und dementsprechende thermochemische Deutung der Versuchsergebnisse.     

Energy Globe Award 2002

Mitteilungen

Energy Globe Award 2002     

Academic intrinsic motivation in young elementary school children.

Two studies, 1 longitudinal and 1 cross-sectional, demonstrate that for young elementary school children, academic intrinsic motivation is a reliable, valid, and significant construct. It was positively related to achievement, IQ, and perception of competence, and inversely related to anxiety. Academic intrinsic motivation at age 9 was significantly predicted by motivation measured 1 and 2 years earlier, above and beyond the contribution of IQ and achievement. Children with higher academic intrinsic motivation at ages 7 and 8 were more likely to show higher motivation at age 9. Whereas young children could reliably distinguish between subject areas of academic intrinsic motivation, only math motivation showed consistently specific relations to other math criteria. Findings are discussed with regard to developmental theories of intrinsic motivation and the significance of academic intrinsic motivation for children's education. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Utilizing Instructional Consultations to Enhance the Teaching Performance of Engineering Faculty

Although many kinds of data can be used to guide instructional consultations, research comparing the efficacy of such data is scant, especially in engineering. In this study, multiple modes of assessment were used to evaluate the impact of consultations informed by different kinds of data. This study illuminates two key aspects of instructional consultations: (1) their efficacy varies depending on the kind of data used to guide them, with student feedback from a Small Group Instructional Diagnosis (SGID) having the largest positive impact, and (2) the instructional consultant plays a key role in helping both interpret the available data and identify strategies for improvement. These findings suggest three implications for practice: (1) whenever possible, SGID‐based consultations should be offered systematically and proactively for engineering faculty, (2) data for other kinds of consultations should be tailored to the needs of the individual instructor, and (3) instructional consultants should be available to collaborate with faculty to enhance their teaching, thereby building an engineering culture that actively supports teaching and learning.     

Classification of spatial textures in benign and cancerous glandular tissues by stereology and stochastic geometry using artificial neural networks

Stereology and stochastic geometry can be used as auxiliary tools for diagnostic purposes in tumour pathology. Whether first-order parameters or stochastic-geometric functions are more important for the classification of the texture of biological tissues is not known. In the present study, volume and surface area per unit reference volume, the pair correlation function and the centred quadratic contact density function of epithelium were estimated in three case series of benign and malignant lesions of glandular tissues. The information provided by the latter functions was summarized by the total absolute areas between the estimated curves and their horizontal reference lines. These areas are considered as indicators of deviation of the tissue texture from a completely uncorrelated volume process and from the Boolean model with convex grains, respectively. We used both areas and the first-order parameters for the classification of cases using artificial neural networks (ANNs). Learning vector quantization and multilayer feedforward networks with backpropagation were applied as neural paradigms. Applications included distinction between mastopathy and mammary cancer (40 cases), between benign prostatic hyperplasia and prostatic cancer (70 cases) and between chronic pancreatitis and pancreatic cancer (60 cases). The same data sets were also classified with linear discriminant analysis. The stereological estimates in combination with ANNs or discriminant analysis provided high accuracy in the classification of individual cases. The question of which category of estimator is the most informative cannot be answered globally, but must be explored empirically for each specific data set. Using learning vector quantization, better results could often be obtained than by multilayer feedforward networks with backpropagation.     

Organocatalytic Enantioselective Strecker Synthesis of α‐Quaternary α‐Trifluoromethyl Amino Acids

The first organocatalytic enantioselective Strecker synthesis of α‐quaternary α‐trifluoromethylated amino acids has been developed. Employing Takemoto’s thiourea catalyst the nucleophilic addition of trimethylsilyl cyanide to trifluoromethyl ketimines affords α‐amino nitriles in good to excellent yields (50–99%) and very good enantioselectivities (ee=83–95%). The enantiopure amino nitriles can be obtained by recrystallization. Deprotection and hydrolysis leads to the title amino acids.