Oral Dosage Development of a Human Rhinovirus and Non-Polio Enterovirus Inhibitor

WIN 63843, a Picornavirus replication inhibitor, is physically and chemically stable in the solid state, to light, elevated temperature, and humidity. This 3-ary15-trifluoromethyl disubstituted 1,2,4-oxadiazole compound has very low water solubility but is highly soluble in ethanol and in safflower seed and corn oils. Solubility in the vegetable oils is doubled by the synergistic effect of ethanol at the 16% alcohol concentration. Vegetuble oil solutions of WIN 63843 are thermally stable but react slowly in the presence of light resulting in an amidoxime compound (WIN 65489) formed by opening of the 1,2,4-oxadiazole ring. This reaction does not occur in oil solutions containing small concentrations of ethanol. Of biophannaceutical interest, the addition of ethanol or PEG-400 solutions of WIN 63843 to human gastric fluid resulted in oily droplet formation whereas crystals form upon addition of these solutions to water. Also, the compound is greater than 8,000 times more soluble in human gastric fluid.     

Heterostructure complementary technology

A complementary inverter configuration based on two new heterostructure field-effect devices is proposed. The FETs are fabricated in a common substrate grown by molecular-beam epitaxy. The devices rely on the formation of inversion layers at heterojunction interfaces.     

Oxygen enhanced crack growth in nickel-based superalloys and materials damage prognosis

This paper summarizes the results from a comprehensive multidisciplinary study to better understand the role of niobium and other strengthening elements in enhancing crack growth by oxygen in nickel-based superalloys at high temperatures, and considers its importance for materials damage prognosis and life cycle engineering in high temperature service. Three γ′ strengthened powder metallurgy (P/M) alloys, with 0, 2.5 and 5 wt pct Nb and comparable volume fractions (about 53 vol pct) of γ′′ precipitates, were specially designed for this study. Coordinated crack growth, microstructural and surface chemistry studies were conducted on the alloys. They were complemented by oxidation studies of Nb, Ni₃Nb, NbC, Ni₃Al and Ni₃Ti, and analyses of fracture surfaces of interrupted crack growth specimens by X-ray photoelectron spectroscopy (XPS). The findings taken in toto show that oxygen enhancement of crack growth is the result of the formation of a brittle film of surface oxides along grain boundaries and interfaces ahead of the crack tip by the preferential oxidation of Nb, Ti and Al in the Nb-rich carbides and Ni₃Al, Ni₃Ti and Ni₃Nb (in Inconel 718) precipitates. The results also showed that the oxidation of Nb-rich carbides alone can significantly enhance crack growth in oxygen. The findings are discussed in relation to the previously proposed crack growth mechanisms, and their applications.     

Contamination of potable roof-collected rainwater in Auckland, New Zealand

One-hundred and twenty-five domestic roof-collected rainwater supplies in four rural Auckland districts were investigated in a cross-sectional survey to determine water quality. Samples of cold faucet water were analysed for physico-chemical and microbiological determinands, including metals (zinc, copper and lead), bacterial indicator organisms--heterotrophic plate count (HPC), total coilforms (TC), faecal coliforms (FC), enterococci (ENT), bacterial pathogens including Salmonella spp., Legionella spp., Campylobacter spp., Aeromonas spp. and the protozoa, Cryptosporidium and Giardia. Twenty-two supplies (17.6%) exceeded one or more of the maximum acceptable values (MAV) or maximum guideline values for chemical determinands of the New Zealand Drinking Water Standards (NZDWS) and 70 (56.0%) supplies exceeded the microbiological criteria of < 1 FC/100 mL. Eighteen supplies (14.4%) exceeded the NZDWS MAV for lead of 0.01 mg/L and three (2.4%) exceeded that for copper, of 2 mg/L. Those supplies with lead or galvanised iron comprising part of the roof or collecting system were more likely to show lead contamination (p = 0.019) as were those supplies with a pH less than 7 (p = 0.013). The presence of the indicator organisms HPC, TC, FC and ENT were all significantly correlated with one another. Aeromonas spp. were identified in 20 (16.0%) supplies. There was a positive association between the presence of Aeromonas and the bacterial indicator organisms. Households reporting at least one member with gastrointestinal symptoms in the month prior to sampling, were more likely to have Aeromonas spp. identified in their water supply than those households without symptoms (odds ratio 3.22, 95% CI 1.15-9.01, p = 0.021). Salmonella typhimurium was detected in one of 115 (0.9%) supplies. Legionella spp. and Campylobacter spp. were not detected. There were 50 supplies sampled for protozoa (sampling criteria: > or = 30 FC or > or = 60 ENT). Cryptosporidium oocysts were detected in 2 (4%) of these. Giardia was not detected. This study demonstrates that roof-collected rainwater systems provide potable supplies of relatively poor physiochemical and microbiological quality in the Auckland area. Further research is required on Aeromonas spp. as potential indicators of both microbiological quality and health risk along with design and maintenance strategies to minimise contamination of potable roof-collected rainwater supplies.     

Electrical and optical properties of the four-terminaldouble-heterostructure opto-electronic switch

The authors extend the theory of the three-terminal double-heterostructure opto-electronic switch (DOES) device, in which the third terminal (the injector) makes contact to the bulk section of the active region, to the four-terminal DOES, in which the fourth terminal (the source) accesses the inversion channel at the n-n heterojunction. The source is shown to be capable of initiating switching at lower current densities than the injector. The effects of incident light on the device are also examined, yielding results similar to the injection of carriers at the source and injector. Incomplete ionization of the charge sheet and two-dimensional quantum effects in the channel, which have been neglected in previous DOES models, have been included. These effects are shown to affect significantly the characteristics of the device and to reduce the discrepancy between simulated and experimental results     

Electrical switching in the three terminal double heterostructure opto-electronic switching device—Active layer contact

Electrical switching times in the three terminal double heterostructure opto-electronic switch are measured and analyzed. For a discrete device with a large parasitic input-output capacitance a switch-on time of 4 ns and a switch-off time of 26 ns were obtained. It is shown that the speed was limited by the time constant determined by the relatively large device capacitance of the discrete device and the 50 Ω measurement impedance of a matched system. Both of these parameters would be considerably reduced by device integration.     

The conserved arginine in rho-GTPase-activating protein is essential for efficient catalysis but not for complex formation with Rho.GDP and aluminum fluoride

The Rho family of small GTP-binding proteins are downregulated by an intrinsic GTPase, which is enhanced by GTPase-activating proteins (GAPs). RhoGAPs contain a single conserved arginine residue that has been proposed to be involved in catalysis. Here, the role of this arginine has been elucidated by mutagenesis followed by determination of catalytic and equilibrium binding constants using single-turnover kinetics, isothermal titration calorimetry, and scintillation proximity assays. The turnover numbers for wild-type, R282A, and R282K RhoGAPs were 5.4, 0.023, and 0.010 s-1, respectively. Thus, the function of this arginine could not be replaced by lysine or alanine. Nevertheless, the R282A mutation had a minimal effect on the binding affinity of RhoGAP for either Rho. GTP or Rho.GMPPNP, which confirms the importance of the arginine residue for catalysis as opposed to formation of the protein-protein complex. The R282A mutant RhoGAP still increased the hydrolysis rate of Rho.GTP by 160-fold, whereas the wild-type enzyme increased it by 38000-fold. We conclude that this arginine contributes half of the total reduction of activation energy of catalysis. In the presence of aluminum fluoride, the R282A mutant RhoGAP binds almost as well as the wild type to Rho.GDP, demonstrating that the conserved arginine is not required for this interaction. The affinity of wild-type RhoGAP for the triphosphate form of Rho is similar to that for Rho.GDP with aluminum fluoride. These last two observations show that this complex is not associated with the free energy changes expected for the transition state, although the Rho.GDP.AlF4-.RhoGAP complex might well be a close structural approximation.     

Effects of Microbial Transglutaminase on the Wheat Proteins of Bread and Croissant Dough

ABSTRACT: Transglutaminase is a crosslinking enzyme that is finding increasing use in foods, yet the molecular changes responsible for its effects are not fully understood. Proteins were extracted from bread and croissant doughs that had been treated with transglutaminase and compared to those from control doughs by size exclusion high performance liquid chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. Transglutaminase increased the amount of protein extracted in the gliadin fraction in both bread and croissant doughs. In croissant doughs, a corresponding decrease in the protein extracted in the albumin to globulin fraction was seen. In each case, crosslinking of the high molecular weight glutenins was observed. The possible role of each of these changes on the functional properties of baked products is discussed.