The total quasi-steady-state approximation for complex enzyme reactions

Biochemistry in general and enzyme kinetics in particular have been heavily influenced by the model of biochemical reactions known as Michaelis–Menten kinetics. Assuming that the complex concentration is approximately constant after a short transient phase leads to the usual Michaelis–Menten (MM) approximation (or standard quasi-steady-state approximation (sQSSA)), which is valid when the enzyme concentration is sufficiently small. This condition is usually fulfilled for in vitro experiments, but often breaks down in vivo. The total QSSA (tQSSA), which is valid for a broader range of parameters covering both high and low enzyme concentrations, has been introduced in the last two decades. We extend the tQSSA to more complex reaction schemes, like fully competitive reactions, double phosphorylation, Goldbeter–Koshland switch and we show that for a very large range of parameters our tQSSA provides excellent fitting to the solutions of the full system, better than the sQSSA and the single reaction tQSSA. Finally, we discuss the need for a correct model formulation when doing “reverse engineering”, which aims at finding unknown parameters by fitting the model to experimentally obtained data. We show that the estimated parameters are much closer to the real values when using the tQSSA rather than the sQSSA, which overestimates the parameter values greatly.     

Leon J. Yarrow (1921–1982).

Presents an obituary for Leon J. Yarrow. Yarrow was born on September 30, 1921, in Shenandoah, Pennsylvania. His father died when Leon was very young, and he experienced some of the transitions in attachments and care that may well have influenced his life-long research interest in the importance of early experience for the developing child. At age 15 Leon entered the University of Pennsylvania, where he majored in psychology. In 1951 Leon accepted the first research position that was made available in the old U.S. Children's Bureau. He initiated a longitudinal investigation of adopted children that focused on the consequences of the infant's transition from foster care to the adoptive parents. As his findings became known, social work practice was modified to favor adoption at the earliest ages. Leon spent a major part of his career at the National Institutes of Health (NIH). His associates there were uniformly touched by his personal warmth, his unrelentingly high standards for developmental studies, and the conceptual elegance with which he grasped problems. Leon died July 28, 1982, of a heart attack, the day before he planned to embark on a summer vacation with his family. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.

This study examined pain sensitivity and pain modularity mechanisms (e.g., beta-endorphin levels, blood pressure) in women with premenstrual dysphoric disorder (PMDD; n=27) and healthy controls (n=27) during the follicular and luteal phases of the menstrual cycle. Physiological measures were taken during rest and ischemic pain testing. In both cycle phases, PMDD women (a) displayed lower resting cortisol and beta-endorphin levels and (b) exhibited shorter pain threshold and tolerance times and greater pain unpleasantness ratings during pain. PMDD women also reported greater pain unpleasantness and intensity and had lower beta-endorphin levels in their luteal phase and tended to display higher blood pressure levels at rest and during pain testing. Results suggest that endogenous opioids may be pathophysiologically relevant to PMDD and that the hypothalamic-pituitary-gonadal axis may modulate pain sensitivity in PMDD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A GC–MS-based metabonomic investigation of blood serum from irritable bowel syndrome patients undergoing intervention with acidified milk products

In the present study, the use of gas chromatography mass spectrometry (GC–MS)-based metabonomics to characterize blood serum in an intervention study of patients suffering from the common gastrointestinal disorder irritable bowel syndrome (IBS) was investigated. The patients included in the study consumed an acidified milk product with (n = 30) or without probiotics (n = 31) (Lactobacillus paracasei F19, Lactobacillus acidophilus LA-5 and Bifidobacterium lactis BB-12) for an 8-week period, and blood serum samples were collected before and after the intervention. Acidified milk is commonly used as a delivering vector for probiotics in commercial consumer settings. The serum samples were extracted and derivatized using N-Methyl-N-(trimethylsilyl) trifluoroacetamide (MSTFA), and GC–MS analysis was carried out. Multivariate data analysis including principal component analysis (PCA), orthogonal partial least squares-discriminant analysis (OPLS-DA), and S-plot was applied on the obtained GC–MS data, which revealed higher serum lactate, glutamine, proline creatinine/creatine, and aspartic acid levels and lower serum glucose levels after the intervention period for both treatment groups. Consequently, the present study indicated an effect of acidified milk consumption on the plasma metabolite profile, which was independent of a concomitant intake of probiotics. In addition, the present study demonstrates that GC–MS is a useful analytical technique for metabonomics studies of blood serum.     

Optimisation of dispersion compensating fibres for cabled long-haulapplications

Dispersion compensating fibres for dispersion-flattened hybrid transmission lines based on non-dispersion shifted fibres have been experimentally investigated. Average values obtained from the production of thousands of kilometres of fibres with different dispersions and thereby different compensation length ratios are given. Optimisation of hybrid lines for minimisation of span attenuation and fibre nonlinearity is described     

From oxygen adsorption to the growth of thin oxides on silicon surfaces

Oxidation of silicon surfaces at relatively low temperatures is shown to go through several activated steps, in the form of configurations inert to further uptake of oxygen. Starting from room temperature adsorption, different configurations of oxygen atoms adsorbed on and in the Si(1 1 1) and Si(0 0 1) surfaces are found, with history and/or coverage dependent energy barriers connecting them. From well below to slightly above an effective oxide coverage of a monolayer, clustering of up to three oxygen atoms around one single silicon atom has been predicted for the Si(0 0 1) surface to represent one such energy minimum; this model is confirmed here experimentally. These and other clusters are shown to agglomerate into silicon dioxide islands before coalescing into a contiguous, inert layer upon higher oxygen supplies. Another problem addressed here is the presence of molecular adsorbates in the oxidation reaction path, an issue which is still debated in the literature. For the Si(1 1 1) surface a molecular, charged oxygen species has earlier been found at temperatures up to room temperature, but not for the Si(0 0 1) surface. This is confirmed in the present experiments, and new data for this state shows that it is highly mobile until quenched at a critical oxygen coverage. It is not the initial state of oxygen on silicon, and therefore not the precursor for atomic insertion of oxygen; rather, it is found to co-exists with atomic oxygen inserted in back-bonds, at a certain, low coverage regime in which parts of the Si(1 1 1) surface are still ordered.     

Individual variation for cognitive decline: Quantitative methods for describing patterns of change.

What are the best quantitative methods for studying cognitive decline? This question was investigated in a sample of 638 individuals aged 50 years and older from the Swedish Adoption/Twin Study of Aging. A battery of cognitive tests tapping multiple domains was administered to each individual from 2 to 7 times over a span of 10 years. Four methods of operationalizing cognitive decline were compared: change scores, a criterion-based method, least squares, and random effects regression (RER). The RER results were most consistent with a significant decline across measures and differences between demented and nondemented individuals. Predicted slopes from the RER model also showed the strongest interrelationships within and across cognitive domains as indicated by factor analysis results and stronger associations with demographic, health, and psychosocial predictors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)