Effects of the Protonation State of Titratable Residues and the Presence of Water Molecules on Nocodazole Binding to β‐Tubulin

Regulation of microtubule assembly by antimitotic agents is a potential therapeutic strategy for the treatment of cancer, parasite infections, and neurodegenerative diseases. One of these agents is nocodazole (NZ), which inhibits microtubule polymerization by binding to β‐tubulin. NZ was recently co‐crystallized in Gallus gallus tubulin, providing new information about the features of interaction for ligand recognition and stability. In this work, we used state‐of‐the‐art computational approaches to evaluate the protonation effects of titratable residues and the presence of water molecules in the binding of NZ. Analysis of protonation states showed that residue E198 has the largest modification in its pK_a value. The resulting E198 pK_a value, calculated with pH‐REMD methodology (pK_a=6.21), was higher than the isolated E amino acid (pK_a=4.25), thus being more likely to be found in its protonated state at the binding site. Moreover, we identified an interaction between a water molecule and C239 and G235 as essential for NZ binding. Our results suggest that the protonation state of E198 and the structural water molecules play key roles in the binding of NZ to β‐tubulin.     

Reconstructing the past: the case of the Spadina Expressway

Requirements Engineering - In order to build resilient systems that can be operational for a long time, it is important that analysts are able to model the evolution of the requirements of that...     

Analysis of a lidar voxel-derived vertical profile at the plot and individual tree scales for the estimation of forest canopy layer characteristics

The goal of the current study was to develop methods of estimating the height of vertical components within plantation coniferous forest using airborne discrete multiple return lidar. In the summer of 2008, airborne lidar and field data were acquired for Loblolly pine forest locations in North Carolina and Virginia, USA, which comprised a variety of stand conditions (e.g. stand age, nutrient regime, and stem density). The methods here implement both field plot-scale analysis and an automated approach for the delineation of individual tree crown (ITC) locations and horizontal extents through a marker-based region growing process applied to a lidar derived canopy height model. The estimation of vertical features was accomplished through aggregating lidar return height measurements into vertical height bins, of a given horizontal extent (plot or ITC), creating a vertical ‘stack’ of bins describing the frequency of returns by height. Once height bins were created the resulting vertical distributions were smoothed with a regression curve-line function and canopy layers were identified through the detection of local maxima and minima. Estimates from Lorey’s mean canopy height was estimated from plot-level curve-fitting with an overall accuracy of 5.9% coefficient of variation (CV) and the coefficient of determination (R²) value of 0.93. Estimates of height to the living canopy produced an overall R² value of 0.91 (11.0% CV). The presence of vertical features within the sub-canopy component of the fitted vertical function also corresponded to areas of known understory presence and absence. Estimates from ITC data were averaged to the plot level. Estimates of field Lorey’s mean canopy top height from average ITC data produced an R² value of 0.96 (7.9% CV). Average ITC estimates of height to the living canopy produced the closest correspondence to the field data, producing an R² value of 0.97 (6.2% CV). These results were similar to estimates produced by a statistical regression method, where R² values were 0.99 (2.4% CV) and 0.98 (4.9% CV) for plot average top canopy height and height to the living canopy, respectively. These results indicate that the characteristics of the dominant canopy can be estimated accurately using airborne lidar without the development of regression models, in a variety of intensively managed coniferous stand conditions.     

Introducing the sequential linear programming level-set method for topology optimization

This paper introduces an approach to level-set topology optimization that can handle multiple constraints and simultaneously optimize non-level-set design variables. The key features of the new method are discretized boundary integrals to estimate function changes and the formulation of an optimization sub-problem to attain the velocity function. The sub-problem is solved using sequential linear programming (SLP) and the new method is called the SLP level-set method. The new approach is developed in the context of the Hamilton-Jacobi type level-set method, where shape derivatives are employed to optimize a structure represented by an implicit level-set function. This approach is sometimes referred to as the conventional level-set method. The SLP level-set method is demonstrated via a range of problems that include volume, compliance, eigenvalue and displacement constraints and simultaneous optimization of non-level-set design variables.     

Large-scale level set topology optimization for elasticity and heat conduction

Structural and Multidisciplinary Optimization - This paper addresses the issue of minimizing support material in additive manufacturing (AM) during topology optimization (TO) in order to reduce...     

Level set topology optimization of cooling channels using the Darcy flow model

Structural and Multidisciplinary Optimization - The level set topology optimization method for 2D and 3D cooling channels, considering convective heat transfer for high Reynolds number flows, is...     

Two weighted eight-order classes of iterative root-finding methods

In this paper we design, by using the weight function technique, two families of iterative schemes with order of convergence eight. These weight functions depend on one, two and three variables and they are used in the second and third step of the iterative expression. Dynamics on polynomial and non-polynomial functions is analysed and they are applied on the problem of preliminary orbit determination by using a modified Gauss method. Finally, some standard test functions are to check the reliability of the proposed schemes and allow us to compare them with other known methods.     

Raman spectroscopy of urea–formaldehyde resins and model compounds

Laser Raman spectroscopy was used to analyze the structures of urea–formaldehyde resins. Band assignments were made on the basis of Raman studies of model compounds. Methylol and certain methylene functionalities could be differentiated in both the model compounds and the resins. Spectra of the resins at various stages of cure were also examined. Trends noted agreed with earlier studies on the kinetics and the proposed mechanism of the cure process. Laser Raman spectroscopy offers promise for elucidating the structures of urea–formaldehyde resins and for providing insight into the molecular phenomena of the cure and degradation of these resins.     

Quaternary System Al2O3–CaO–MgO–SiO2: II Study of the Crystallization Volume of MgAl2O4

Solid-state compatibility and melting relations of MgAl₂O₄ in the quaternary system Al₂O₃–CaO–MgO–SiO₂ were studied by firing and quenching selected samples located in the 65 wt% MgAl₂O₄, plane followed by microstructural and energy dispersive X-ray analysis. A projection of the liquidus surface of the primary crystallization volume of MgAl₂O₄ was constructed from CaO, SiO₂ and exceeding Al₂O₃, not involved in stoichiometric MgAl₂O₄ formation; those three amounts were recalculated to 100 wt%. The temperature and character of six invariant points, where four solids co-exist with a liquid phase, were defined. One maximum point was localized and the positions of the isotherms were tentatively established. The effect of CaO, SiO₂, and Al₂O₃ impurities on the high temperature behavior of spinel materials was also discussed.     

Ascorbic acid consumption and serum levels in smokers and non-smokers adult men in Hermosillo,Sonora, México

Ascorbic acid is one of the important antioxidant nutrients that can aid in the prevention of oxidative cellular damage. Adequate dietary intake is essential as humans can not synthesize this vitamin. It has been reported that smokers require higher dietary intakes to maintain their serum levels. The objective of this study was to determine serum levels of ascorbic acid in young male smokers and non smokers in the city of Hermosillo, Sonora, Mexico. In addition, their dietary intake of ascorbic acid was determined by a 24 h dietary recall. The dietary intake of ascorbic acid in 12 smokers was 64 +/- 11 mg/d and in 13 non smokers it was 70 +/- 12 mg/d. The smokers in this study did not meet the dietary recommendation of 100 mg/d. Serum ascorbic acid values in smokers and non smokers were 24.2 +/- 6.9 mumol/L and 30.9 +/- 3.7 mumol/L respectively. No significant difference was found among the 2 groups. Although the average serum ascorbic acid values fell within the range considered normal, 50% of the smokers had individual values that were below 23 mumol/L, indicating that these subjects have hipovitaminosis. A positive correlation between intake and serum levels was obtained for smokers (r = 0.71; p = 0.03). The results of this study suggest smokers may be at increased risk for chronic diseases due to their low intake and low serum levels of ascorbic acid.