Formation of poly(ethylene phosphates) in polycondensation of H3PO4 with ethylene glycol. Kinetic and mechanistic study

Conditions of synthesis of poly(ethylene phosphates) in reaction of H₃PO₄ with HOCH₂CH₂OH (EG), the actual path of polycondensation, and structure of the obtained polymers (mostly oligomers) and kinetics of reaction are described. Preliminary kinetic information, based on the comparison of the MALDI‐TOF‐ms and ³¹P{¹H} NMR spectra as a function of conversion is given as well. Because of the dealkylation process fragments derived from di‐ and triethylene glycols are also present in the repeating units. Structures of the end groups (? CH₂CH₂OH or ? OP(O)(OH)₂) depend on the starting ratio of [EG]₀/[H₃PO₄]₀, although even at the excess of EG the acidic end groups prevail because of the dealkylation process. In MALDI‐TOF‐ms products with P_n equal up to 21 have been observed. The average polymerization degrees (P_n) are lower and have been calculated from the proportion of the end groups. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 830–843, 2008     

Prediction of yield and long‐term failure of oriented polypropylene: Kinetics and anisotropy

The time‐dependent yield and failure behavior of off‐axis loaded uniaxially oriented polypropylene tape is investigated. The yield and failure behavior is described with an anisotropic viscoplastic model. A viscoplastic flow rule is used with an equivalent stress, based on Hill's anisotropic yield criterion, and the Eyring flow theory combined with a critical equivalent strain definition. This model is based on factorization of the rate and draw ratio dependence and is capable of quantitatively predicting the rate, angle and draw ratio dependence of the yield stress as well as time‐to‐failure in various off‐axis tensile loading conditions characterized solely from the transverse direction. © 2009 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 2026–2035, 2009     

Large-deformation properties of wheat dough in uni- and biaxial extension. Part II. Gluten dough

Glutens were isolated from flour of three European wheat cultivars which perform differently in cereal products. The rheological and fracture properties of gluten-water doughs were determined in uniaxial and biaxial extension at large deformations and small angle sinusoidal oscillation tests and compared with the mechanical properties of the parental flour doughs. At 25 °C the linear region was in the same range as that of flour dough, while at a higher temperature (45 °C) the linear region was more than an order of magnitude higher. At 45 °C the storage modulus and tan were lower than at 25 °C. Variation in moduli between cultivars was much more pronounced for gluten than for flour doughs.Similarly to flour dough in both uniaxial and biaxial extension the stress () increased more than proportionally with the strain, a phenomenon called strain hardening. The stress at a set strain and strain hardening depended much more strongly on the type of deformation for gluten than for flour dough: was higher in biaxial extension for gluten than for flour dough, but was much higher in uniaxial extension. This indicates that orientational effects in elongational flow are of even larger importance for the mechanical properties of gluten than of flour dough. It is likely that it is the glutenin fraction that, because of its large size, confers these direction dependent properties to gluten and flour doughs. Fracture stresses were much higher for gluten than for flour dough, while fracture strains were in the same range or higher. For gluten dough fracture strains increased less strongly with increasing strain rate than for flour dough. Glutens exhibiting a higher stress at a certain strain had a smaller fracture strain.Our findings confirm the conviction that the large deformation properties of flour dough are mainly governed by the gluten fraction. However, there are also differences. Compared to flour dough gluten dough exhibits (i) a stronger strain hardening, (ii) a larger difference in between uniaxial and biaxial extension and (iii) a smaller strain rate dependency of the fracture strain.     

Automated discovery of noncovalent inhibitors of SARS-CoV-2 main protease by consensus Deep Docking of 40 billion small molecules

Recent explosive growth of ‘make-on-demand’ chemical libraries brought unprecedented opportunities but also significant challenges to the field of computer-aided drug discovery. To address this expansion of the accessible chemical universe, molecular docking needs to accurately rank billions of chemical structures, calling for the development of automated hit-selecting protocols to minimize human intervention and error. Herein, we report the development of an artificial intelligence-driven virtual screening pipeline that utilizes Deep Docking with Autodock GPU, Glide SP, FRED, ICM and QuickVina2 programs to screen 40 billion molecules against SARS-CoV-2 main protease (Mpro). This campaign returned a significant number of experimentally confirmed inhibitors of Mpro enzyme, and also enabled to benchmark the performance of twenty-eight hit-selecting strategies of various degrees of stringency and automation. These findings provide new starting scaffolds for hit-to-lead optimization campaigns against Mpro and encourage the development of fully automated end-to-end drug discovery protocols integrating machine learning and human expertise.

Deep learning-accelerated docking coupled with computational hit selection strategies enable the identification of inhibitors for the SARS-CoV-2 main protease from a chemical library of 40 billion small molecules.     

The symmetric traveling salesman problem and edge exchanges in minimal 1-trees

In this article the effect of exchanging edges inside a minimal 1-tree with edges outside is analysed. In combination with an upper bound this analysis enables the elimination of variables in the symmetric traveling salesman problem. After discussion on a number of improvements for this analysis, the implementation is described in a traveling salesman algorithm based on the 1-tree relaxation. Computational results show the advantages of the edges exchanges for Euclidean problems (up to 120 cities) as well as for random table problems (up to 200 cities).