Phenothiazinium photosensitisers IX. Tetra- and pentacyclic derivatives as photoantimicrobial agents

Methylene blue derivatives, synthesised as novel photosensitising agents are usually simple auxochromic variations on the lead compound. The current paper represents the initial report on the synthesis and biological testing of a new class of phenothiazinium derivatives, having either one or two tetrahydropyridine rings fused to the phenothiazinium chromophore. The derivatives exhibited extended absorption wavelengths, increased amphiphilic character and much greater photoantimicrobial efficacies compared to methylene blue, some examples being more effective even than dimethyl methylene blue. The high activities of this class of photosensitiser recommend its use in infection control, both locally and in blood product decontamination.     

Domain organization of the extracellular region of CD45

CD45 is a large, heavily glycosylated, transmembrane proteinphosphotyrosine phosphatase found on all nucleated cells ofhaematopoietic origin. In lymphocytes, the cytoplasmic phosphataseis necessary for efficient signalling through the antigen receptorbut in contrast little is known about the interactions of theextracellular region of the molecule. This consists of a mucin-likeregion, a novel cysteine-containing region and a region containingthree putative fibronectin type III domains. To confirm thisorganization and to identify parts potentially important forfunction, we have expressed fragments of the extracellular domainof rat CD45 as recombinant soluble proteins. Proteins correspondingto two, three and four domains of CD45 were expressed in secretedforms. Single domains and constructs for proteins with truncationsof the predicted domains were not expressed. This is consistentwith the proposed structural organization. Determination ofthe positions of the disulphide bonds in the N-terminal cysteine-containingregion and the first fibronectin type III domain identifiednovel disulphide bonds within the fibronectin type III domainand an unusual inter-domain disulphide linkage. Circular dichroismspectroscopy indicated that this region of rat CD45 has mainlyß-strand secondary structure and no -helical content.These studies support the proposed domain organization of CD45.     

Electrochemical waste water treatment: Electrooxidation of acetaminophen

Oxidation of acetaminophen at boron-doped diamond (BDD) and at Ti/SnO₂ anodes in a plug-flow divided electrochemical reactor led to electrochemical combustion, whereas at Ti/IrO₂ benzoquinone was the exclusive product except at very long electrolysis times. The difference is explicable in terms of the different mechanisms of oxidation: direct oxidation at the anode for Ti/IrO₂ vs. indirect oxidation involving electrogenerated hydroxyl radicals at BDD and Ti/SnO₂. At BDD, at which the efficiency of degradation of acetaminophen was greatest, the rate of electrolysis at constant concentration was linearly dependent on the current, and at constant current linearly dependent on the concentration. Current efficiencies for mineralization up to 26% were achieved without optimization of the cell design.     

Examination of the kinetics of herpes simplex virus glycoprotein D binding to the herpesvirus entry mediator, using surface plasmon resonance

Previously, we showed that truncated soluble forms of herpes simplex virus (HSV) glycoprotein D (gDt) bound directly to a truncated soluble form of the herpesvirus entry mediator (HveAt, formerly HVEMt), a cellular receptor for HSV. The purpose of the present study was to determine the affinity of gDt for HveAt by surface plasmon resonance and to compare and contrast the kinetics of an expanded panel of gDt variants in binding to HveAt in an effort to better understand the mechanism of receptor binding and virus entry. Both HveAt and gDt are dimers in solution and interact with a 2:1 stoichiometry. With HveAt, gD1(306t) (from the KOS strain of HSV-1) had a dissociation constant (KD) of 3.2 x 10(-6) M and gD2(306t) had a KD of 1.5 x 10(-6) M. The interaction between gDt and HveAt fits a 1:1 Langmuir binding model, i.e., two dimers of HveAt may act as one binding unit to interact with one dimer of gDt as the second binding unit. A gD variant lacking all signals for N-linked oligosaccharides had an affinity for HveAt similar to that of gD1(306t). A variant lacking the bond from cysteine 1 to cysteine 5 had an affinity for HveAt that did not differ from that of the wild type. However, variants with double cysteine mutations that eliminated either of the other two disulfide bonds showed decreased affinity for HveAt. This result suggests that two of the three disulfide bonds of gD are important for receptor binding. Four nonfunctional gDt variants, each representing one functional domain of gD, were also studied. Mutations in functional regions I and II drastically decreased the affinity of gDt for HveAt. Surprisingly, a variant with an insertion in functional region III had a wild-type level of affinity for HveAt, suggesting that this domain may function in virus entry at a step other than receptor binding. A variant with a deletion in functional region IV [gD1(Delta290-299t)] exhibited a 100-fold enhancement in affinity for HveAt (KD = 3.3 x 10(-8) M) due mainly to a 40-fold increase in its kinetic on rate. This agrees with the results of other studies showing the enhanced ability of gD1(Delta290-299t) to block infection. Interestingly, all the variants with decreased affinities for HveAt exhibited decreased kinetic on rates but only minor changes in their kinetic off rates. The results suggest that once the complex between gDt and HveAt forms, its stability is unaffected by a variety of changes in gD.     

Formation of TiN/TiC-Fe composites from ilmenite (FeTiO3) concentrate

The production of a ceramic hard material-metal composite directly from a mineral concentrate has great potential application. An homogenizing pretreatment of a mixture of ilmenite (FeTiO₃) and graphite, followed by annealing under an argon ambient, showed the formation of titanium carbide and elemental iron. Annealing of the same powder in nitrogen resulted in the formation of a composite of elemental iron and titanium nitride. The nitride was formed at a lower temperature than the carbide with almost complete conversion after 1 hour at 1000 °C. The rate of carbide formation was controlled by carbon diffusion, whereas the nitridation reaction was controlled by either oxygen or nitrogen diffusion. The TiC was found to form via TiC_0.5, which slowly increased its carbon content until near stoichiometric TiC was formed; stoichiometric TiN formed directly with no intermediate phases. Titanium carbide showed the presence of a second phase with a slightly smaller unit cell size; this was due to interdiffusion between the iron and TiC. The titanium carbide composite was found to be composed of 3 to 4 μm anhedral iron grains dispersed in the titanium-rich matrix. There was no segregation in the iron/titanium nitride composite with apparently submicron distribution.     

Measurement of the absorption spectrum of polytetrafluoroethylene in the near millimetre region by an untuned cavity

The absorption spectrum of polytetrafluoroethylene has been measured between 3 and 15 cm^?1, a region which until now has been virtually unexplored. Absorption was found to arise almost entirely from amorphous regions of the sample and absorption in crystalline regions is small. A novel feature of the investigation is that measurements are made in an untuned cavity which has the advantage for low loss materials, that losses from reflection, scatter, and diffraction become unimportant. Loss measurements can be made on samples even when they are in the form of fine powder.     

Solar thermal electric power systems: Comparison of line-focus collectors

Three types of line-focusing collectors: parabolic though, fixed slats with movable absorber and movable slats with fixed absorber, are evaluated to find those systems that are capable of producing the lowest costs of electrical energy. Minimum costs per kW-hr are found using sequential optimization techniques that consider variations in rim angle, reflectance, aperture width, length, orientation, tracking, contour error, slat width, slat curvature, tangent slat angle, slope, installation methods, materials, fabrication methods, absorptance, emittance, cover transmittance, field shape, layout, pipe sizes, insulation thicknesses and turbine-generator-cooling lower efficiencies and designs. This approach provides a uniform treatment of both cost and performance for a solar thermal electric power system. This uniform treatment of solar thermal electric power systems for all collector types insures that valid comparisons are made.