Microstructure dependent dynamic fracture analyses of trabecular bone based on nascent bone atomistic simulations

Trabecular bone fracture is closely related to the trabecular architecture, microdamage accumulation, and bone tissue properties. Primary constituents of trabecular tissue are hydroxyapatite (HA) mineralized type-I collagen fibers. In this research, dynamic fracture in two dimensional (2-D) micrographs of ovine (sheep) trabecular bone is modeled using the mesoscale cohesive finite element method (CFEM). The bone tissue fracture properties are obtained based on the atomistic strength analyses of a type-I collagen + HA interfacial arrangement using molecular dynamics (MD). Analyses show that the presented framework is capable of analyzing the architecture dependent fracture in 2-D micrographs of trabecular bone.     

Fouling and protein adsorption effect of low-temperature plasma treatment of membrane surfaces

Adsorption of proteins and the effect of the chemical nature of membrane surfaces on protein adsorption were investigated using¹⁴C-tagged albumin and several microporous membranes (polyvinilydene fluoride, PVDF; nylon; polypropylene, PP; and polycarbonate, PC). The membrane surfaces were modified by exposing them to low-temperature plasma of several different monomers (n-butane, oxygen, nitrogen alone or as mixtures) in a radiofrequency plasma reactor. Transients in the permeability of albumin solutions through the membranes and changes in flux of distilled water through the membranes before and after adsorption of albumin were used to investigate the role of protein adsorption on membrane fouling. The results show that the extent of adsorption of albumin on hydrophobic membranes was considerably more than that on hydrophilic membranes. The hydrophilic membranes were susceptible to electrostatic interactions and less prone to fouling. A pore-blocking model was successfully used to correlate the loss of water flux through pores of defined geometry     

Microhardness measurements of poly(methyl methacrylate) and poly(vinylidene fluoride) polyblends

The preparation of polymer blends of poly(methyl methacrylate) and poly(vinylidene fluoride) in different weight percentages is described. Vickers microhardness measurements have been made to study the effects of load and compositional ratio of the two polymers in polyblend. It is observed that poly(vinylidene fluoride) acts as a plasticizer for poly(methyl methacrylate). Evidence of increasing and decreasing strength of polyblends has been obtained for different compositional ratios of the two polymers.     

A new method for determining the local environment and orientation of individual side chains of membrane-binding peptides

We studied here the binding of the mastoparan X peptide to a zwitterionic lipid bilayer (POPC) and demonstrated that nitrile-derivatized amino acids can be used to determine the hydration state (or change in hydration state) of specific sites of membrane-interactive peptides (upon binding). We have also shown that polarized ATR-FTIR measurements can further be used to uncover information regarding the spatial orientation of individual side chains as well as their conformational preference within the lipid bilayer.     

Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics

Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.     

Tamarindus indica mucilage and its acrylamide-grafted copolymer as flocculants for removal of dyes

The application of Tamarindus indica seed mucilage (Tam), a food grade polysaccharide, and its acrylamide grafted copolymer as flocculants was assessed for the first time for removal of various types of dyes from model textile wastewater containing azo, basic, and reactive dyes. Acrylamide grafted T. indica mucilage (Tam-g-PAM) was obtained by ceric ion initiated polymerization technique. A series of contact time experiments were conducted to assess the system variables such as concentrations of mucilage and dyes and pH. These flocculants reduce the dye concentration by flocculation and settling. The grafted copolymer, Tam-g-PAM showed better results for dye removal. The optimal flocculant concentration, which was required to effect flocculation, was independent of dye concentration within the range examined. Both the flocculants performed better for removal of azo dyes than for reactive and basic dyes.     

CH···π interactions do not contribute to hydrogen transfer catalysis by glycerol dehydratase

The role of the nonbonded CH···π interaction in the hydrogen abstraction from glycerol by the coenzyme B(12)-independent glycerol dehydratase (GDH) was examined using the QM/MM (ONIOM), MP2, and CCSD(T) methods. The studied CH···π interaction included the hydrogen atom of the -C(2)H(OH)- group of the glycerol substrate and the tyrosine-339 residue of the dehydratase. A contribution of this interaction to the stabilization of the transition state for the transfer of a hydrogen atom from the adjacent terminal C(1)H(2)(OH) group to cysteine 433 was determined by ab initio HF, MP2, and CCSD(T) calculations with the aug-cc-pvDZ basis set for the corresponding methane/benzene, methanol/phenol, and glycerol radical/phenol subsystems. The calculated CH···π distance, defined as the distance between the H atom and the center of the phenol ring, shortened from 2.62 to 2.52 ? upon going from the ground- to the transition-state of the GDH-catalyzed reaction. However, this shortening was not accompanied by the expected lowering of the CH···π interaction free energy. Instead, this interaction remained weak (about -1 kcal/mol) along the entire reaction coordinate. Additionally, the mutual orientation of the CH group and the phenol ring did not change significantly during the reaction. These results suggest that the phenol group of the tyrosine-339 does not contribute to lowering the activation barrier in the enzyme, but do not exclude the possibility that tyrosine 339 facilitates proper orientation of glycerol for the electrostatic catalysis, or inhibits side-reactions of the reactive glycerol radical intermediate.     

Extraction of U(VI) by cyanex-272

Extraction of U(VI) from HNO₃, HCl and HClO₄ media using cyanex-272 (bis[2,4,4 trimethyl pentyl] phosphinic acid)/n-dodecane has been carried out. In the case of HNO₃ and HClO₄ media, the distribution ratio (D) value first decreases and then increases, whereas from HCl medium it first decreases and then remains constant with increase in H⁺ ion concentration. At lower acidities, U(VI) was extracted as UO₂(HA₂)₂ by an ion exchange mechanism, whereas at higher acidities as UO₂(NO₃)₂ ^.2(H₂A₂) following a solvation mechanism. The D for U(VI) by cyanex-272, PC-88A and DEHPA at low acidities follows the order cyanex-272 > PC-88A > DEHPA. Also, cyanex-272 was found to extract U(VI) more efficiently than TBP at 2M HNO₃. The effect of diluents on the extraction of U(VI) by cyanex-272 followed the order cyclohexane > n-dodecane > CCl₄ > benzene. The loading of U(VI) into cyanex-272/n-dodecane from 2M HNO₃ has shown that at saturation point, cyanex-272 was 78% loaded. No third phase was observed at the saturation level. The stripping of U(VI) from the loaded organic phase was not possible with water, it was poor with acetic acid and sodium acetate but quantitative with oxalic acid, ammonium carbonate and sodium carbonate.     

Permanganate-Pyruvic Acid Initiated Polymerization of Methacrylamide

A combined system of potassium permanganate and pyruvic acid was found to initiate radical polymerization of vinyl monomers, especially acrylamides. From kinetic investigations of the polymerization of methacrylamide, it was found that this initiator induced a radical polymerization which proceeded with an overall activation energy of 15.7 kcal/mol. The rate is given by

R_p=K[methacrylamide] ¹ [pyruvic acid]° [KMnO₄]¹ in aqueous and water-DMF mediums. In the presence of DMF the initial rate was found to decrease but the kinetic equation remained the same. The investigations were done at 35 ± 0.2°C in nitrogen.

Besides the clinical importance of pyruvic acid found in blood, urine, muscles, etc., it is a good initiator in conjunction with KMnO₄ for vinyl polymerization. It is therefore interesting to study the polymerization of methacrylamide using the KMnO₄-pyruvic acid redox couple in aqueous systems in order to find whether this system follows the same kinetic features of vinyl polymerization by a radical mechanism.     

Photoinduced electron transfer in a hexaphenylbenzene-based self-assembled porphyrin-fullerene triad

A hexaphenylbenzene-based zinc porphyrin dyad forms a 1:1 complex with a fullerene bearing two pyridyl groups via coordination of the pyridyl nitrogens with the zinc atoms. The fullerene is symmetrically located between the two zinc porphyrins. The binding constant for the complex is 7.3 x 10(4) M(-1) in 1,2-difluorobenzene. Photoinduced electron transfer from a porphyrin first excited singlet state to the fullerene occurs with a time constant of 3 ps, and the resulting charge-separated state has a lifetime of 230 ps. This self-assembled construct should form a basis for the construction of more elaborate model photosynthetic antenna-reaction center systems.