Machine learning applied to enzyme turnover numbers reveals protein structural correlates and improves metabolic models.

Knowing the catalytic turnover numbers of enzymes is essential for understanding the growth rate, proteome composition, and physiology of organisms, but experimental data on enzyme turnover numbers is sparse and noisy. Here, we demonstrate that machine learning can successfully predict catalytic turnover numbers in Escherichia coli based on integrated data on enzyme biochemistry, protein structure, and network context. We identify a diverse set of features that are consistently predictive for both in vivo and in vitro enzyme turnover rates, revealing novel protein structural correlates of catalytic turnover. We use our predictions to parameterize two mechanistic genome-scale modelling frameworks for proteome-limited metabolism, leading to significantly higher accuracy in the prediction of quantitative proteome data than previous approaches. The presented machine learning models thus provide a valuable tool for understanding metabolism and the proteome at the genome scale, and elucidate structural, biochemical, and network properties that underlie enzyme kinetics

Plant Size, Turnover and Productivity in Malaysian Manufacturing

Malaysian manufacturing has an asymmetrical structure: small and medium-sized enterprises dominate in numbers, but contribute relatively little to total output, employment, and exports as compared to their larger counterparts. In light of an increasingly competitive environment arising from globalization, a sound knowledge of turnover patterns within the sector by plant size and its potential impact on aggregate productivity growth is imperative. We find that turnover, particularly of large plants, makes a substantial contribution to overall productivity growth in manufacturing. Hence, from a policy perspective, facilitating turnover might be as important as supporting existing plants in promoting aggregate productivity growthPlant turnover; plant size; productivity; manufacturing; Malaysia

Social marketing: Immunizing against unethical practice

A simple approach for the catalytic conversion of primary alcohols into their corresponding esters and amides, with evolution of H2 gas using in situ formed ruthenium PNP- and PNN-pincer catalysts, is presented. The evaluation showed conversions for the esterification with turnover numbers as high as 4300, and 4400 for the amidation

Three-Dimensional Phthalocyanine Metal-Catecholates for High Electrochemical Carbon Dioxide Reduction.

The synthesis of a new anionic 3D metal-catecholate framework, termed MOF-1992, is achieved by linking tetratopic cobalt phthalocyanin-2,3,9,10,16,17,23,24-octaol linkers with Fe3(-C2O2-)6(OH2)2 trimers into an extended framework of roc topology. MOF-1992 exhibits sterically accessible Co active sites together with charge transfer properties. Cathodes based on MOF-1992 and carbon black (CB) display a high coverage of electroactive sites (270 nmol cm-2) and a high current density (-16.5 mA cm-2; overpotential, -0.52 V) for the CO2 to CO reduction reaction in water (faradaic efficiency, 80%). Over the 6 h experiment, MOF-1992/CB cathodes reach turnover numbers of 5800 with turnover frequencies of 0.20 s-1 per active site

Turbulent mixing at a stable density interface : the variation of the buoyancy flux–gradient relation

Experiments conducted on mixing across a stable density interface in a turbulent Taylor–Couette flow show, for the first time, experimental evidence of an increase in mixing efficiency at large Richardson numbers. With increasing buoyancy gradient the buoyancy flux first passes a maximum, then decreases and at large values of the buoyancy gradient the flux increases again. Thus, the curve of buoyancy flux versus buoyancy gradient tends to be N-shaped (rather than simply bell shaped), a behaviour suggested by the model of Balmforth et al. (J. Fluid Mech. vol. 428, 1998, p. 349). The increase in mixing efficiency at large Richardson numbers is attributed to a scale separation of the eddies active in mixing at the interface; when the buoyancy gradient is large mean kinetic energy is injected at scales much smaller than the eddy size fixed by the gap width, thus decreasing the eddy turnover time. Observations show that there is no noticeable change in interface thickness when the mixing efficiency increases; it is the mixing mechanism that changes. The curves of buoyancy flux versus buoyancy gradient also show a large variability for identical experimental conditions. These variations occur at time scales one to two orders of magnitude larger than the eddy turnover time scale

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Theoretical values of convective turnover times and Rossby numbers for solar-like, pre-main sequence stars

Magnetic fields are at the heart of the observed stellar activity in late-type stars, and they are presumably generated by a dynamo mechanism at the interface layer between the radiative and the convective stellar regions. Since dynamo models are based on the interaction between differential rotation and convective motions, the introduction of rotation in the ATON 2.3 stellar code allows for explorations regarding a physically consistent treatment of magnetic effects in stellar structure and evolution, even though there are formidable mathematical and numerical challenges involved. As examples, we present theoretical estimates for both the local (tau_c) and global (tau_g) convective turnover times for rotating pre-main sequence solar-type stars, based on up-to-date input physics for stellar models. Our theoretical predictions are compared with the previous ones available in the literature. In addition, we investigate the dependence of the convective turnover time on convection regimes, the presence of rotation and atmospheric treatment. Those estimates, this quantities can be used to calculate the Rossby number, Ro, which is related to the magnetic activity strength in dynamo theories and, at least for main-sequence stars, shows an observational correlation with stellar activity. More important, they can also contribute for testing stellar models against observations. Our theoretical values of tau_c, tau_g and Ro qualitatively agree with those published by Kim & Demarque (1996). By increasing the convection efficiency, tau_g decreases for a given mass. FST models show still lower values. The presence of rotation shifts tau_g towards slightly higher values when compared with non-rotating models. The use of non-gray boundary conditions in the models yields values of tau_g smaller than in the gray approximation.Comment: 10 pages, 14 figures, accepted for publication in A&