Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

Macroscopic and Microscopic Structures of Cesium Lead Iodide Perovskite from Atomistic Simulations

A first‐principles‐based effective Hamiltonian is developed and employed to investigate finite‐temperature structural properties of a prototype of perovskite halides, that is CsPbI₃. Such simulations, when using first‐principles‐extracted coefficients, successfully reproduce the existence of an orthorhombic Pnma state and its iodine octahedral tilting angles around room temperature. However, they also yield a direct transformation from Pnma to cubic $Pm\overline{3}m$ upon heating, unlike measurements that reported the occurrence of an intermediate long‐range‐tilted tetragonal P4/mbm phase in‐between the orthorhombic and cubic phases. Such disagreement, which may cast some doubts about the extent to which first‐principle methods can be trusted to mimic hybrid perovskites, can be resolved by “only” changing one short‐range tilting parameter in the whole set of effective Hamiltonian coefficients. In such a case, some reasonable values of this specific parameter result in the predictions that i) the intermediate P4/mbm state originates from fluctuations over many different tilted states; and ii) the cubic $Pm\overline{3}m$ phase is highly locally distorted and develops strong transverse antiphase correlation between first‐nearest neighbor iodine octahedral tiltings, before undergoing a phase transition to P4/mbm under cooling.     

Perceptually-weighted evaluation criteria for segmentation masks in video sequences

In order to complement subjective evaluation of the quality of segmentation masks, this paper introduces a procedure for automatically assessing this quality. Algorithmically computed figures of merit are proposed. Assuming the existence of a perfect reference mask (ground truth), generated manually or with a reliable procedure over a test set, these figures of merit take into account visually desirable properties of a segmentation mask in order to provide the user with metrics that best quantify the spatial and temporal accuracy of the segmentation masks. For the sake of easy interpretation, results are presented on a peaked signal-to-noise ratio-like logarithmic scale.     

Retaining maximum antioxidative potency of wheat germ oil refined by molecular distillation

A process of physical refining wheat germ oil using the technique of molecular distillation (MD) is presented in this work. Wheat germ oil was obtained from the germ by solvent extraction using hexane and also by cold pressing. The oil extracted with hexane was degummed and bleached before deacidification in order to modify the parameters of phosphorus and color. The goal in carrying out the stage of physical refining by MD was to preserve the maximum amount of original antioxidative potential obtained from extraction of the crude oil. The effect of evaporation temperature of one‐stage MD on the efficiency of free fatty acid elimination was studied. The antioxidant portion was followed by means of analytic determination of tocopherols by high‐performance liquid chromatography. Tocopherol retention up to 98% was achieved in the oil extracted by pressing, and yields of up to 96% were achieved in the oil extracted with hexane. Copyright © 2007 Society of Chemical Industry     

High density polyethylene-wood flour composite lumber: efficacy of two proprietary biocides in the control of fungal colonization and discoloration

Two proprietary biocides were compounded and extruded at three concentrations, respectively, into high density polyethylene-maple wood flour lumber (HDPE-MWL) and evaluated for their efficacy to control fungal colonization and discoloration using the ASTM Standard G 21-96. Although the silver biocide used in this study did not control fungal colonization and discoloration of HDPE-MWL, statistically significant difference was observed between the highest silver biocide concentration and those of the two lower silver biocide concentrations. The latter exhibited no significant difference with the controls. In contrast, the three levels of zinc biocides showed significant difference from each other with respect to their efficacy against fungal colonization and discoloration of HDPE-MWL. Overall, only the zinc biocide was efficacious against fungal colonization and discoloration. The biocide containing zinc as an active biocidal agent was most efficacious at 1% (by weight) concentration.     

Mechanism of the skeletal isomerisation of linear butenes over ferrierite: analysis of side reactions

An investigation of the effect of reaction conditions on product distribution in the skeletal isomerisation reaction of linear butenes has been carried out. The main reaction routes over ferrierite have been identified. Beside the main product isobutene, major by-product formation occurs. The unwanted reactions include dimerisation of butene to form octenes, hydrogen transfer yielding small amounts of saturated C₃ and C₄ hydrocarbons and disproportionation producing propene and pentenes. The most abundant by-products were pentene and propene, though these were not formed in equimolar amounts as could be expected. Oligomerisation experiments of propene over ferrierite produced large amounts of butene and pentene, revealing the presence of adsorbed nonene. The cracking of this surface species to hexene and propene is the most likely reaction route for the excess propene formation. This additional path to propene formation operates mainly at temperatures above 623 K.     

Global complete observability and output-to-state stability imply the existence of a globally convergent observer

We consider systems which are globally completely observable and output-to-state stable. The former property guarantees the existence of coordinates such that the dynamics can be expressed in observability form. The latter property guarantees the existence of a state norm observer and therefore the possibility of bounding any continuous state functions. Both properties allow to conceptually build an observer from an approximation of an exponentially attractive invariant manifold in the space of the system state and an output driven dynamic extension. The proposed observer provides convergence to zero of the estimation error within the domain of definition of the solutions. The work of A. Astolfi is partly supported by the Leverhulme Trust.     

Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A-chain immunotoxins in human leukemic T cells

Recent studies have shown that cyclosporin A (CsA) may affect ricin A-chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively). Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101 F(ab')2 RTA-IT (ninefold and eightfold, respectively). The effect of human plasma, originating from four patients enrolled in a phase I high-dose CsA regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case, with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding, internalization, intracellular trafficking, or degradation. Analysis of internalized T101 RTA-IT molecules showed that these were essentially intact, which suggests that these enhancers may act only on a small population of RTA-ITs that escapes present investigational techniques. In conclusion, because the concentrations used are clinically achievable, Cs appear to be promising agents for in vivo enhancement of RTA-ITs.     

Microwave-Assisted Reaction Sintering of Bismuth Titanate-Based Ceramics

Bismuth titanate-based ceramics, pure and doped with 5 mol% WO₃, were prepared by reaction-sintering using a microwave oven. High densities, ≥96% of theoretical density were achieved with very short thermal treatments, with soaking time ranging from 5 to 15 min. Relatively small platelet-like grains were formed, and microstructure seemed not to be strongly affected by doping nor soaking time. Electrical measurements were performed and, as expected, a decrease of electrical conductivity was observed in WO₃-doped materials. The results of reaction-sintered samples, both conventional as well as microwave sintered, are compared with those of samples prepared with previously calcined powders and sintered using microwaves as well as a conventional electric furnace.