A blood group-related polymorphism of CD44 abolishes a hyaluronan-binding consensus sequence without preventing hyaluronan binding

CD44 is a widely expressed integral membrane protein that acts as a receptor for hyaluronan (HA) and is proposed to be important to cell-extracellular matrix interaction. The Indian (In) blood group antigens reside on CD44, and most individuals express the Inb antigen. Homozygosity for the Ina allele occurs as a rare event and is associated with production of alloantibody to the common Inb antigen after transfusion or pregnancy. The present study demonstrates that a single point mutation (G252 --> C) causes an Arg46 --> Pro substitution, which is responsible for the Inb/Ina polymorphism. Additional mutations were found in In(a+b-) cDNA but were not necessary to the antigenic phenotype as determined in site-directed mutagenesis studies. In studies using CD44 chimeric constructs, Arg46 has previously been shown to be crucial for maintenance of HA-binding ability to a CD44 peptide. However, the present study demonstrates that the Arg46 --> Pro substitution does not reduce HA binding to the intact CD44 protein, which contains two proposed extracellular HA-binding motifs. Down-regulation of HA binding to In(a+b-) CD44 by anti-CD44 monoclonal antibody (mAb) ligands, however, was weakened, although all mAbs tested bound In(a+b-) and In(a-b+) CD44 equally well. Competitive inhibition studies using human anti-Inb also showed that some mAbs that inhibit HA binding to CD44 may do so by interacting with a domain separate from, but affecting the structure of, the Inb epitope.     

Effects of nanomaterials on luciferase with significant protection and increased enzyme activity observed for zinc oxide nanomaterials

This principle goal of this research was to examine the effects of various nanomaterials on the activity and behavior of the firefly enzyme luciferase. Nanomaterials have been found to stabilize, and in some instances, shown to increase the activity of enzymes. In this study gold, manganese oxide (MnO), and zinc oxide (ZnO) nanomaterials were utilized in order to test their effects on enzyme activity. Luciferase was used because its activity is easy to analyze, as it typically produces a large amount of bioluminescence easily detected by a Microtiter plate reader. Following incubation with the various nanomaterials, luciferase was subjected to degradation by several protein denaturing agents, such as heat, SDS, urea, ethanol, protease, hydrogen peroxide, and pH changes. Results indicated that luciferase activity is indeed affected when combined with nanomaterials, accompanied by both increases and decreases in enzyme activity depending on the type of nanomaterial and denaturing agent used. In most of the experiments, when incubated with ZnO nanomaterials, luciferase depicted significant increases in activity and bioluminescence. Additional experiments, in which human A375 cells were treated with luciferase-nanomaterial mixtures, also depicted increased enzyme activity and bioluminescence for luciferase incubated with ZnO nanomaterials. Ultimately, our findings indicated that when luciferase was subjected to multiple types of denaturation, zinc oxide nanomaterials dramatically preserved and increased enzyme activity and bioluminescence.     

Catalytic conversion of waste biomass by hydrothermal treatment

The purpose of the work presented here is the production of liquid biofuels from wet organic waste matter in a continuous one-step catalytic process under hydrothermal conditions. The catalytic reaction of wet organic matter at near-critical water conditions (T > 300 °C, p > 22.1 MPa) is used to produce a mixture of combustible organics which can be used as liquid biofuel. In order to achieve a good product quality in a continuous one-step process, two catalysts were applied, a homogeneous potassium carbonate catalyst and a heterogeneous ZrO₂ catalyst. In addition, the reaction mixture was recirculated. The continuous flow of concentrated waste biomass feed at low flow rates and recirculation of the hot reaction mixture were the most challenging obstacles to overcome. The scale of the plant (0.1 l reactor volume) allowed for a variation of the feed, reaction temperature, and recirculation rate in order to optimise the process conditions. Still, the product quantity obtained was sufficient to perform a analytical characterisation. The experimental results confirmed the feasibility of the process. Hydrothermal treatment of waste biomass, after dewatering, resulted in a biocrude oil of high calorific value.     

Aggregating Data for Computational Toxicology Applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.     

Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors

Continued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.     

Evidence for simultaneous abiotic-biotic oxidations in a microbial-Fenton's system

The conditions that support the simultaneous activity of hydroxyl radicals (OH.) and heterotrophic aerobic bacterial metabolism were investigated using two probe compounds: (1) tetrachloroethene (PCE) for the detection of OH. generated by an iron-nitrilotriacetic acid (Fe-NTA) catalyzed Fenton-like reaction and (2) oxalate (OA) for the detection of heterotrophic metabolism of Xanthobacter flavus. In the absence of the bacterium in the quasi-steady-state Fenton's system, only PCE oxidation was observed; conversely, only OA assimilation was found in non-Fenton's systems containing X. flavus. In combined Fenton's-microbial systems, loss of both probes was observed. PCE oxidation increased and heterotrophic assimilation of OA declined as a function of an increase in the quasi-steady-state H2O2 concentration. Central composite rotatable experimental designs were used to determine the conditions that provide maximum simultaneous abiotic-biotic oxidations, which were achieved with a biomass level of 10(9) CFU/mL, 4.5 mM H2O2, and 2.5 mM Fe-NTA. These results demonstrate that heterotrophic bacterial metabolism can occur in the presence of hydroxyl radicals. Such simultaneous abiotic-biotic oxidations may exist when H2O2 is injected into the subsurface as a microbial oxygen source or as a source of chemical oxidants. In addition, hybrid abiotic-biotic systems could be used for the treatment of waters containing biorefractory organic contaminants present in recycle water, cooling water, or industrial waste streams.     

Concentrations, distribution, and persistence of fluorotelomer alcohols in sludge-applied soils near Decatur, Alabama, USA

Soil samples were collected for fluorotelomer alcohol (FTOH) analyses from six fields to which sludge had been applied and one "background" field that had not received sludge. Ten analytes in soil extracts were quantified using GC/MS. Sludge-applied fields had surface soil FTOH concentrations exceeding levels found in the background field. For 8:2nFTOH, which can degrade to perfluorooctanoic acid, impacted surface-soils ranged from 5 to 73 ng/g dry weight, clearly exceeding the background field in which 8:2nFTOH was not detected. The highest [FTOH] generally was 10:2nFTOH, which had concentrations of <5.6 to 166 ng/g. For the first time, we document the persistence of straight-chained primary FTOHs (n-FTOHs) and branch-chained secondary FTOHs (sec-FTOHs), which are transformation products of n-FTOHs, in field soils for at least five years after sludge application. Ratios of sec-FTOHs to n-FTOHs were highest for 7:2sFTOH/8:2nFTOH (～50%) and decreased with increasing chain length to a minimum for the longest-chained analytes, 13:2sFTOH/14:2nFTOH (～10%). Disappearance half-lives for FTOHs, calculated with these data, ranged from 0.85 to 1.8 years. These analytical results show that the practice of sludge application to land is a pathway for the introduction of FTOHs and, accordingly, their transformation products, perfluorocarboxylic acids, into the environment.     

Developing a Risk Assessment Model for construction safety

Problems on occupational health and safety are commonly occurred in the construction industry, including falling of materials or person from height, stepping on objects and injured by hand tools. Key of dealing with project safety and risk assessment in construction industry is important, thus, way on doing assessment and liability of assessment are necessary for all professionals. However, it is found that those professionals prone to heavily rely on their own experiences and knowledge on decision making on risk assessment, which lack of a systematic approach and lack of ways to check the reliability of the decisions. This paper investigates the need for people involved in construction to take systematic and effective risk assessments for different trades. 14 common types of trades, accidents, and accident causes are explored, in addition to suitable risk assessment methods and criteria. A Risk Assessment Model (RAM) is then developed for assessing risk levels as various project stages with various work trades. A case study is used to prove the workability and reliability of the developed RAM in the practical industry. The developed RAM is found to be benefit for predicting high-risk construction activities and thus preventing accidents occurred based on a set of historical accident data.     

Recent Results on Field Reversed Configurations from the Translation, Confinement and Sustainment Experiment

The field-reversed configuration (FRC) offers an attractive alternative approach to magnetically confined fusion because of its extremely high β, simple linear geometry, and natural divertor for helium ash removal. Multi-hundred eV and high density FRCs have been produced using the standard Field Reversed Theta Pinch (RFTP) method, with a confinement scaling that leads to fusion conditions. These FRCs are, however, limited to only tens of mWb fluxes and sub-msec lifetime. Recent progress has been made in building up the flux and sustaining the FRC current using Rotating Magnetic Fields (RMF) in the Translation, Sustainment, and Confinement (TCS) facility at the University of Washington. TCS has demonstrated formation and steadystate sustainment of standard, flux-confined, prolate FRCs. The RMF also provides stability for the n = 2 rotational mode, which is the dominant global instability observed experimentally. Simple calculations show that a strong radially inward force imposed by the RMF increases proportionally to any local outward deformation of the plasma cross section. Evidence of this has been experimentally demonstrated, and the effects of various RMF antenna geometries studied. High temperature FRCs could also be produced in TCS by translating high energy plasmoids formed in the normal theta pinch manner into the confinement chamber containing the RMF antennas. Extremely interesting results were obtained for this translation and capture process. The plasmoids can survive the violent dynamics of supersonic reflections off magnetic mirror structures, producing a stable high-β, near-FRC state with substantial flux conversion from toroidal to poloidal. This is a tribute not only to the robustness of FRCs, but also to the tendency of anFRC to assume a preferred state for a magnetized plasma. The magnetic helicity, as inferred by a simple interpretive model, is approximately preserved, possibly conforming to a high-β relaxation principle.     

Development of a more reliable version of the Matching Familiar Figures Test.

Because of the inadequate reliability of Matching Familiar Figures Test (MFFT) error scores, a longer, more reliable version was developed. As a result of item analysis of 30 MFFT-type items, 20 were selected on the basis of item—total error correlations and ability to discriminate reflective from impulsive 11-yr-old boys. Two subsequent studies with Ss of similar ages showed that split-half correlations for the new 20-item MFFT over 2 wks were .91 for latency and .89 for errors, while test–retest correlations over 5 wks were .85 and .77 for latency and errors, respectively. These results plus those of a further study with 7- and 9-yr-old boys and girls suggest that the new test (the MFF20) is suitable for use with children in the age range 7–21 yrs. (11 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)