How environment affects drug activity: Localization,compartmentalization and reactions of a vanadium insulin-enhancing compound,dipicolinatooxovanadium(V)

The chemical and biological properties of a simple and traditional V(5+) coordination complex, dipicolinatooxovanadium(V) (abbreviated [VO₂dipic]^?), are described in order to present a hypothesis for a novel mode of action wherein a hydrophobic membrane environment plays a key role. Specifically, we propose that the compartmentalization and both chemical and biological transformations of vanadium-complexes direct whether beneficial or toxic effects will be observed with this class of compounds. This concept is based on the formation of high levels of uncontrollable reactive oxygen species (ROS) from one-electron reactions or alternative events possibly initiated by a two-electron reaction which may be directly or indirectly beneficial by reducing the high levels of ROS. The properties of dipicolinatooxovanadium(V) compounds in aqueous solution (D.C. Crans, et al., Inorg. Chem. 39 (2000) 4409–4416) are very different from those in organic solvents (S.K. Hanson, et al., J. Am. Chem. Soc. 131 (2009) 428–429) and these differences may be key for their mode of action. Since other vanadium complexes are known to hydrolyze upon administration, the low stability of the aqueous complex requires entrapment in hydrophobic environments for such a complex to exist sufficiently long to have an effect. The suggestion that the environment changes the reactivity of the compounds is consistent with the very different modes of action by which one complex act. In short, a novel hypothesis is presented for a mode of action of vanadium compounds based on differences in properties resulting from environmental conditions. These considerations are supported by recent evidence supporting a role for membranes and signal transduction events (D.A. Roess, et al. Chem. Biodivers. 5 (2008) 1558–1570) of the insulin-enhancing properties of these compounds.     

Modification of the thermoresistance to spray-drying of a cold-adapted subtilisin by genetic engineering

The thermoresistance of a cold-adapted subtilisin dried by spray-drying was studied. Proteolytic activity of this enzyme was measured before and after spray-drying. Without chemical additives, spray-drying yields ranged from 2–13%. The use of arabic gum and lactose in the composition of the enzyme solutions allowed the strengthening of the enzyme structures and increased water mobility in the product. Increase of water mobility led to a shorter residence time of the product in the spray-drier and a net yield increase was obtained (yield higher than 50%). The effect of two selective mutations on the thermoresistance to spray-drying of the cold-adapted subtilisin was also investigated. Mutation T85D (introduction of an additional link with an ion Ca²⁺ necessary for enzyme activity, by substitution of Asp for Thr 85) had no effect on the thermoresistance of the subtilisin to spray-drying. Mutation H121W (introduction of an additional aromatic link by substitution of Trp for His 121) reduced the drying yield from 66% (not modified subtilisin) to 52%. This higher thermosensitivity could be explained by an increase of the hygroscopic character of the modified subtilisin (mutation H121W).     

Electrode Kinetics and Sensitivity of Nanostructured Electrodes from Different Carbon Fiber Precursor Materials

Correlation of properties of common carbon fiber precursor materials, polyacrylonitrile (PAN) and pitch, with kinetics and sensitivity of microdisk electrodes, PAN T650, PAN HCB and Pitch P25, nanostructured by an electrochemical etching method was tested. Sensitivity of PAN electrodes is higher but kinetics are slower than at pitch electrodes due to more defects in PAN. Because of more surface oxides at PAN T650 adsorption of dopamine is greater than at PAN HCB electrodes but for uric acid adsorption is greater at PAN HCB. Uric acid sensitivity is related to high conductivity of PAN fibers, with an inverse relationship observed for dopamine.     

A Unique Architecture Based on 1 D Semiconductor,Reduced Graphene Oxide,and Chalcogenide with Multifunctional Properties

A unique heterostructured optoelectronic material (HOM), consisting of a reduced graphene oxide (RGO) layer with spatially distributed CdS, suspended by zinc oxide (ZnO) nanorods, is presented. The key features of this HOM are the assembly of the components in a manner so as to realize an effective integration between the constituents and the ability to modify the electronic properties of the RGO. For the first time, the location of RGO (as a suspended layer) along with the tuning of its charge‐transport properties (n‐/p‐type) and its influence on the photo(electro)chemical processes has been examined systematically by using this ZnO/RGO/CdS HOM as a case study. The n‐type RGO interlayer facilitates >100 % increase in the photocurrent density and 25 % increase in the photodegradation of a dye, compared to ZnO/CdS, thus demonstrating its multifunctionality. At 3.2 mA cm^?2, this HOM architecture helps to achieve the highest photocurrent density utilizing ZnO, RGO, and CdS as building blocks in any form. The work is significant for the following reasons: i) other one dimensional (1D) oxides/chalcogenides or 1D oxides/dyes may be designed with similar architectures; ii) HOMs with tunable optical absorbance and charge‐transport properties could be realized; iii) related application areas (e.g., sensing or solar fuel generation) should be greatly benefited.     

Analysis of nucleotide variation within the triose‐phosphate isomerase gene of Giardia duodenalis from sheep and its zoonotic implications

This study explored the genetic composition of Giardia in fecal samples from 284 individual lambs on pasture‐based sheep farms in three regions of Victoria, Australia. An approach, combining targeted sequencing, phylogenetic analysis and PCR‐coupled restriction endonuclease fingerprinting, was used to identify and genetically categorize Giardia present in 43 (15.1%) of the 284 samples and to infer their zoonotic potential. The specific identity and genetic classification were based on the phylogenetic analysis of sequence data for a portion of the triose‐phosphate isomerase gene. Fourteen different sequence variants (including seven sequences that contained between one and five polymorphic sites) representing two distinct assemblages of Giardia (recognized in the current literature) were defined, of which 13 were new records. One dominant sequence type (with accession no. GQ444447, representing a genotype within assemblage A) has been detected previously in humans and is thus considered to be of zoonotic potential. (Nucleotide sequences reported in this article are available in the GenBank database under accession nos. GQ444447–GQ444451 and GQ444454–GQ444462).     

Electric biasing of the divertor tiles in compass-D

It has been suggested that by electrically biasing the divertor tiles in a tokamak, one could create a toroidally-asymmetric potential structure in the scrape-off layer (SOL) plasma. The resultingE×B convective motion should increase the plasma transport in the SOL and thereby reduce the heat load on the divertor plates. This paper describes plans for such experiments on COMPASS-D and preliminary theoretical modelling. The COMPASS-D divertor target consists of 24 graphite tiled toroidal segments. The inner and outer strike point tiles on all these segments will be insulated from each other, and cabling will be installed to allow for biasing of individual tiles in any combination. Theoretical analysis suggests that the electrostatic potential perturbations caused by the biasing will be confined to the divertor region below the X-point, and that substantial SOL broadening can be achieved by applying modest voltages. Aside from active control of SOL transport, it is hoped that the biasing will be useful to probe other divertor and SOL physics issues. Presented at the Workshop on the Role of Electric Fields in Plasma Confinement and Exhaust, Budapest, 18–19 June, 2000. This work was jointly funded by the UK Department of Trade and Industry and Euratom, and was supported by US DoE under contract W-7405-ENG-48 at LLNL.     

Fiber orientation kinetics of a concentrated short glass fiber suspension in startup of simple shear flow

The common approach for simulating the evolution of fiber orientation during flow in concentrated suspensions is to use an empirically modified form of Jeffery's equation referred to as the Folgar–Tucker (F-T) model. Direct measurements of fiber orientation were performed in the startup of shear flow for a 30 wt% short glass fiber-filled polybutylene terephthalate (PBT-30); a matrix that behaves similar to a Newtonian fluid. Comparison between predictions based on the F-T model and the experimental fiber orientation show that the model over predicts the rate of fiber reorientation. Rheological measurements of the stress growth functions show that the stress overshoot phenomenon approaches a steady state at a similar strain as the fiber microstructure, at roughly 50 units. However, fiber orientation measurements suggest that a steady state is not reached as the fiber orientation continues to slowly evolve, even up to 200 strain units. The addition of a “slip” parameter to the F-T model improved the model predictions of the fiber orientation and rheological stress growth functions.