Float-polishing process and analysis of float-polished quartz

A fluid-mechanical model is developed for the float-polishing process. In this model laminar flow between the sample and the lap results in pressure gradients at the grooves that support the sample on a fluid layer. The laminar fluid motion also produces supersmooth, damage-free surfaces. Quartz substrates for applications in high-stress environments were float polished, and their surfaces were analyzed by optical scatterometry, photoacoustic spectroscopy, and atomic force microscopy. The removal of 100 µm of material by a lapping-polishing process, with final float polishing, left low levels of subsurface damage, with a surface roughness of approximately 0.2-nm rms

PEArL: a systems approach to demonstrating authenticity in information systems design

The process of information systems (IS) design has been dominated by the demands inherent in providing a technical solution to a perceived problem or need. Engineering IS design methods applied in order to satisfy the problem situation tend to have a preoccupation with verifying specifications as being mathematically correct. Diffculties arise when the ideas underpinning verification are extended in an attempt to ‘prove’ the validity of a proposed design for an IS. A pure engineering approach does not facilitate a response to the subjective elements within social situations, which experience has shown to be essential in demonstrating the pertinence of new designs to those concerned. We suggest that, by applying interpretivist systems ideas, it is possible to support concerned individuals in reflecting upon crucial aspects of the inquiry, enabling those individuals to judge the relevance or ‘authenticity’ of the learning, according to their own values and beliefs. The elements of participants, engagement, authority, relationships and learning are suggested as being crucial. These make up the mnemonic PEArL, which is offered as an aide-mémoire for those concerned with IS design

Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition ofmeasles virus replication

A series of coumarin and pyranocoumarin analogues were evaluated in vitro for antiviral efficacy against measles virus (MV), strain Chicago. Of the 22 compounds tested for inhibition, six were found to have selectivity indices greater than 10. These were compounds 5-hydroxy-7-propionyloxy- 4-propylcoumarin (2a), 5,7-bis(tosyloxy)-4- propylcoumarin (7); 5-hydroxy-4-propyl-7-tosyloxy- coumarin (8); 6,6-dimethyl-9-propionyloxy-4- propyl-2H,6H-benzo[1,2-b:3,4-b′]dipyran-2-one (9); 6,6-dimethyl-9-pivaloyloxy-4-propyl-2H,6Hbenzo[ 1,2-b:3,4-b′]dipyran-2-one (10); and 7,8-cis- 10,11,12-trans-4-propyl-6,6,10,11-tetramethyl- 7,8,9-trihydroxy-2H,6H,12H-benzo[1,2-b:3,4-b′:5,6- b′′]tripyran-2-one (18). Three of the active drugs were propyl coumarin analogues (2a, 7 and 8), two were dipyranone or chromeno-coumarins (9 and 10), and one was a benzotripyranone with a coumarin nucleus (18). Some appeared to be rather specific and potent inhibitors of MV with EC50 values ranging from 0.2 to 50 μg/ml and the majority of the EC50 values being less than 5 μg/ml. The compounds inhibited an additional nine strains of MV, and in virucidal tests the drugs did not physically disrupt the virion to inhibit virus replication. The inhibitory activity for one of the compounds tested (7) was somewhat dependent on virus concentration and it was still active when added to cells up to 24 h after virus exposure. When used in combination with ribavirin, compound 7 appeared not to profoundly affect the antiviral efficacy of ribavirin or its cell-associated toxicity. However, a slightly antagonistic MVinhibitory effect was observed at the highest concentration of ribavirin used in combination with most concentrations of compound 7 tested. This and related compounds may be valuable leads in the development of a potent and selective class of MV inhibitors that could be used in future in the clinic

Inhibition of measles virus replication by 5\u27-Norcarbocyclic nucleoside analogs

Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world, sometimes as the result of severe, chronic, lethal disease. In an effort to develop therapies to supplement immunization strategies, a number of 5′-nor carbocyclic adenosine analogues were evaluated for anti-MV activity in CV-1 monkey kidney cells. Of those compounds tested, those either unsubstituted at C4 or possessing a hydroxyl, azido or amino substituent at that position were the most active, with particularly significant inhibition of MV, strain Chicago-1. The EC50 values against this strain ranged from100 mg/ml in actively growing and stationary-phase cells. Results suggest that these compounds may be clinically useful anti-MV virus agents

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure

Loitering with intent: dealing with human-intensive systems

This paper discusses the professional roles of information systems analysts and users, focusing on a perspective of human intensive, rather than software intensive information systems. The concept of ‘meaningful use’ is discussed in re-lation to measures of success/failure in IS development. The authors consider how a number of different aspects of reductionism may distort analyses, so that processes of inquiry cannot support organizational actors to explore and shape their requirements in relation to meaningful use. Approaches which attempt to simplify complex problem spaces, to render them more susceptible to ‘solution’ are problematized. Alternative perspectives which attempt a systematic, holistic complexification, by supporting contextual dependencies to emerge, are advocated as a way forward

Slow Dissociation of a Charged Ligand: Analysis of the Primary Quinone QA Site of Photosynthetic Bacterial Reaction Centers

Reaction centers (RCs) are integral membrane proteins that undergo a series of electron transfer reactions during the process of photosynthesis. In the QA site of RCs from Rhodobacter sphaeroides, ubiquinone-10 is reduced, by a single electron transfer, to its semiquinone. The neutral quinone and anionic semiquinone have similar affinities, which is required for correct in situ reaction thermodynamics. A previous study showed that despite similar affinities, anionic quinones associate and dissociate from the QA site at rates ≈104 times slower than neutral quinones indicating that anionic quinones encounter larger binding barriers (Madeo, J.; Gunner, M. R. Modeling binding kinetics at the QA site in bacterial reaction centers. Biochemistry2005, 44, 10994–11004). The present study investigates these barriers computationally, using steered molecular dynamics (SMD) to model the unbinding of neutral ground state ubiquinone (UQ) and its reduced anionic semiquinone (SQ–) from the QA site. In agreement with experiment, the SMD unbinding barrier for SQ– is larger than for UQ. Multi Conformational Continuum Electrostatics (MCCE), used here to calculate the binding energy, shows that SQ– and UQ have comparable affinities. In the QA site, there are stronger binding interactions for SQ– compared to UQ, especially electrostatic attraction to a bound non-heme Fe2+. These interactions compensate for the higher SQ– desolvation penalty, allowing both redox states to have similar affinities. These additional interactions also increase the dissociation barrier for SQ– relative to UQ. Thus, the slower SQ– dissociation rate is a direct physical consequence of the additional binding interactions required to achieve a QA site affinity similar to that of UQ. By a similar mechanism, the slower association rate is caused by stronger interactions between SQ– and the polar solvent. Thus, stronger interactions for both the unbound and bound states of charged and highly polar ligands can slow their binding kinetics without a conformational gate. Implications of this for other systems are discussed

Caenorhabditis elegans N-glycan Core β-galactoside Confers Sensitivity towards Nematotoxic Fungal Galectin CGL2

The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a Galβ1,4Fucα1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the Galβ1,4Fucα1,6GlcNAc trisaccharide at 1.5 Å resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms