Computer-aided design of a factor Xa inhibitor by using MCSS functionality maps and a CAVEAT linker search

We have investigated a new approach to efficiently find a novel inhibitor against a serine protease (i.e. an activated coagulation factor X, FXa) by using de novo design programs and the X-ray crystal structure of the target enzyme. FXa is a coagulant enzyme that generates thrombin (a serine protease) and participates in both intrinsic and extrinsic coagulation pathways. We adopted multiple copy simultaneous search (MCSS) and CAVEAT linker search techniques, which disclosed a novel FXa inhibitor (T01312) consisting of two binding moieties (the benzamidinyl and adamantyl groups) and a linker unit (the carboxybenzylamine group). The inhibitory activity of T01312 against FXa was determined to be a small K(i)-value of 48nM, which is two orders of magnitude smaller than that against thrombin. An X-ray crystal analysis of T01312 complexed with trypsin (an analogue of FXa) and docking studies of T01312 with trypsin and FXa showed that: (i) the benzamidinyl group is a predominant binding moiety in the anionic pocket (S1 site) with an asparatic acid residue; (ii) a hydrophobic pocket (S4 site) is the binding site of the adamantyl group; (iii) the carboxylate group of the linker contributes to the selectivity for FXa against thrombin. Thus, the combination of the knowledge of the X-ray crystal structure of the target molecule with MCSS and CAVEAT linker search techniques proved to be an effective hit-finding method that does not require the screening of huge compound libraries.     

Prospective predictors of posttraumatic stress disorder symptoms: Direct and mediated relations.

This study assessed the relations between pretrauma risk (neuroticism, negative affect, prior distress) and protective (self-esteem, optimism) factors and posttraumatic stress disorder (PTSD) symptoms and potential mediators (subjective event-related distress, unsupportive social interactions, perceived control) of those relations. Students (N = 1,528) at four U.S. universities completed online surveys assessing pretrauma risk and protective factors at Time 1 (T1); 84% (N = 1,281) completed a survey 2 months later (T2). PTSD symptoms and the three potential mediators were assessed among those who experienced potentially traumatic events between T1 and T2 (n = 264). PTSD symptoms related to prior traumas were controlled in all analyses. In structural equation modeling (SEM) analyses, the relation between risk factors and PTSD symptoms was mediated by unsupportive social interactions. Protective factors did not independently predict PTSD symptoms when risk factors also were included in the SEM models. Implications for research and practice are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Arsenic behavior in paddy fields during the cycle of flooded and non-flooded periods

The behavior of As in paddy fields is of great interest considering high As contents of groundwater in several Asian countries where rice is the main staple. We determined the concentrations of Fe, Mn, and As in soil, soil water, and groundwater samples collected at different depths down to 2 m in an experimental paddy field in Japan during the cycle of flooded and non-flooded periods. In addition, we measured the oxidation states of Fe, Mn, and As in situ in soil samples using X-ray absorption near-edge structure (XANES) and conducted sequential extraction of the soil samples. The results show that Fe (hydr)oxide hosts As in soil. Arsenic in irrigation waters is incorporated in Fe (hydr)oxide in soil during the non-flooded period, and the As is quickly released from soil to water during the flooded period because of reductive dissolution of the Fe (hydr)oxide phase and reduction of As from As(V) to As(III). The enhancement of As dissolution by the reduction of As is supported by high As/Fe ratios of soil water during the flooded period and our laboratory experiments where As(III) concentrations and As(III)/As(V) ratios in submerged soil were monitored. Our work, primarily based on data from an actual paddy field, suggests that rice plants are enriched in As because the rice grows in flooded paddy fields when mobile As(III) is released to soil water.     

Antibacterial activity of Bacillus amyloliquefaciens phage endolysin without holin conjugation

To characterize the enzymatic activity and antibacterial activity of endolysin encoded by a Bacillus amyloliquefaciens phage, the open reading frame encoding endolysin was amplified by PCR and cloned into the expression plasmid pET21d(+). The resultant plasmid was used to transform Escherichia coli JM109(DE3). Production of endolysin in the cytosol facilitated cell lysis without coproduction of holin, which is considered to degrade or alter the cytoplasmic membrane. The phage endolysin was overexpressed and purified. Although the specific activity of the purified phage endolysin towards lyophilized Micrococcus luteus cells was 1/11 of the activity of chicken egg white lysozymes, the endolysin showed stronger antibacterial activity towards E. coli W3110, E. coli JM109(DE3) and Pseudomonas aeruginosa PAO1 than chicken egg white lysozymes. The antibacterial activity of the endolysin towards these three bacterial strains was marked when EDTA was added to the endolysin solution.     

Simulation of migration from a multi-layer laminated film intended for retort foods

Migration from multi-layer laminated film pouches intended for retort foods was investigated through HPLC analysis with a fluorescence detector, and measurements of residue on evaporation, consumption of potassium permanganate and total organic carbon. HPLC analysis revealed that the levels of migrants in oil and the water which were heated in the pouches (121 degrees C, 30 min) were ten times of those in the corresponding official simulants under the official conditions; n-heptane (25 degrees C, 60 min), and water (95 degrees C, 30 min). Bisphenol A diglycidyl ether and related compounds were found in the oil and the water heated in the pouches, as well as in the simulants. These compounds were thought to have been present in the adhesive between the laminated films, and migrated through the food-contact film of the package. Consumption of potassium permanganate and residue on evaporation of the heated water were ten times of those of the water simulant, while the total organic carbon level of the heated water was several-hold greater than that of the water simulant. In addition, migrant levels per surface area of the pouch were one-fourth of the concentrations per content volume of the pouch. Since compliance with the legal limits is evaluated based on the concentration per surface area, real migration into foods would be underestimated by a factor of another four.     

Core-Shell Type Polymer Microspheres Prepared from Diblock Copolymer Films

In the first part of this article, the preparation method for core-shell type polymer microspheres from diblock copolymer films is reviewed. The core-shell type polymer microspheres were obtained from the crosslinking reaction in spherical microdomains formed by diblock copolymer film. In the second section, the solution and solid properties of core-shell type microspheres are reviewed. The micelle of core-shell type microsphere moved like pseudolatex. Its solubility depended strongly on that of shell segments. Finally, the miscibility behaviors of binary core-shell type microsphere blends are reported briefly.     

The effect of cyber-friends on loneliness and social anxiety: Differences between high and low self-evaluated physical attractiveness groups

This study examined the causal relationships between the number of cyber-friends participants had and their social anxiety or loneliness. We predicted that participants who gave low self-evaluations of physical attractiveness would be able to lower their social anxiety or reduce their loneliness through Internet-based interpersonal relationships. Also, such effects would be more prominent if the cyber-friends were of the opposite sex. A two-wave panel study was conducted with 178 Japanese undergraduate students (63 men and 115 women; mean age was 20.29). Results showed that for those who gave a low evaluation of their physical attractiveness, having a large number of cyber-friends lowered their social anxiety and reduced the loneliness felt in friendships. These effects differed by gender of the cyber-friends. In particular, for those who gave a low evaluation of their physical attractiveness, having a large number of cyber-friends of the same sex had a positive effect on social anxiety. In contrast, cyber-friends of the opposite sex had no effect on social anxiety, but had a complex effect upon loneliness. Namely, while a large number of cyber-friends of the opposite sex reduced the loneliness felt in friendships, it also heightened the loneliness felt in family relationships. Implications of these results for further research and practice are provided.     

Synthesis of non-equilibrium phases in immiscible metals mechanically mixed by high pressure torsion

The structural changes in mechanically mixed metals of immiscible combinations of elements caused by bulk mechanical alloying (MA) through the use of high pressure torsion (HPT) were investigated in Ag–Ni and Nb–Zr systems. There was no alloying between Ag and Ni on atomic scale even after 100 rotations of HPT. On the other hand, the β-Zr phase started to appear after HPT 2 rotations in the Nb–Zr system, even though β-Zr is a high temperature phase. Further, Nb and Zr were completely mixed to form a bcc structured single phase after HPT 100 rotations. The sequence of alloying in the Nb–Zr system during HPT was discussed. These results clearly suggest that non-equilibrium phases can form in the Nb–Zr system by bulk MA by the use of HPT.     

Compositional SOS and beyond: a coalgebraic view of open systems

In this paper we address the issue of providing a structured coalgebra presentation of transition systems with algebraic structure on states determined by an equational specification Γ. More precisely, we aim at representing such systems as coalgebras for an endofunctor on the category of Γ-algebras. The systems we consider are specified by using arbitrary SOS rules, which in general do not guarantee that bisimilarity is a congruence. We first show that the structured coalgebra representation works only for systems where transitions out of complex states can˜be derived from transitions out of corresponding component states. This decomposition property of transitions indeed ensures that bisimilarity is a congruence. For a system not satisfying this requirement, next we propose a closure construction which adds context transitions, i.e., transitions that spontaneously embed a state into a bigger context or vice versa. The notion of bisimulation for the enriched system coincides with the notion of dynamic bisimilarity for the original one, i.e., with the coarsest bisimulation which is a congruence. This is sufficient to ensure that the structured coalgebra representation works for the systems obtained as result of the closure construction.