Issues in the mapping of two diseases

Recently, there has been increased interest in the geographical modelling of two or more diseases. In this article, we consider a number of issues relating to such an endeavour including the standardization process and the comparison of univariate and bivariate disease mapping models. A principle motivation for the examination of two or more diseases is to discover similarities or dissimilarities in the geographical distribution of risk. In this article, we propose a proportional mortality approach to give clues to areas of similarity and dissimilarity. A secondary aim of bivariate modelling is to 'borrow strength' between diseases in order to provide better estimates of risk in each area. We will illustrate various modelling strategies using incidence data from 1996 to 2000 on lung and bladder cancer in Washington state.     

Electrostatic effects on the thermodynamics of protonation of reduced plastocyanin

The L12E, L12K, Q88E, and Q88K variants of spinach plastocyanin have been electrochemically investigated. The effects of insertion of net charges near the metal site on the thermodynamics of protonation and detachment from the copper(I) ion of the His87 ligand have been evaluated. The mutation-induced changes in transition enthalpy cannot be explained by electrostatic considerations. The existence of enthalpy/entropy (H/S) compensation within the protein series indicates that solvent-reorganization effects control the differences in transition thermodynamics. Once these compensating contributions are factorized out, the resulting modest differences in transition enthalpies turn out to be those that can be expected on purely electrostatic grounds. Therefore, this work shows that the acid transition in cupredoxins involves a reorganization of the H-bonding network within the hydration sphere of the molecule in the proximity of the metal center that dominates the observed transition thermodynamics and masks the differences that are due to protein-based effects.     

Measurement of the size, shape and orientation of convex bodies

Different types of solid bodies (particles) with specific shape and size are needed for industrial processes. For spherical particles, ‘sizer’ measurements are usually reported as sphere diameters. For non-spherical particles, particle shape and especially orientation must be taken into account. Particles of a specific shape will present different views when looked at from different directions.We have employed a Camsizer^® instrument to measure the distribution of projected area under different physical conditions for solid cylindrical particles:

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Under ‘ideal’ conditions, corresponding to a uniform distribution of particle orientation, measurements agreed with predictions. The celebrated theorem of Cauchy applies only to this case.

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For two other situations, measured and predicted results differed. However, from the experimental data it was possible to infer the particle orientations and hence theoretically predict the projected area distribution. Excellent agreement between theory and practice was then restored.

     

Estimation of hue discrimination thresholds using a computer interactive method

An experimental approach is described for measuring colour discrimination thresholds of human observers. Special software was developed for the accurate display of colour pairs on a high resolution CRT, using serial feedback from a spectroradiometer. Discrimination thresholds between a test and a target colour are determined by repeatedly showing an observer a circle composed of four separate quadrants, one of which has a different colour from the other three. Three quadrants are of the test colour and one of the target colour, or vice versa. Observers are asked to select the quadrant that differs from the others. An experiment is described where hue‐dependent effects affecting hue discrimination are investigated. Eighteen hue threshold values around the hue circle, at constant L = 51 and C = 25, were measured for three observers. Hue thresholds were found to vary around the hue circle, exhibiting an abrupt change in the blue to purple region (240° ≤ h_ab,10 = 300°) This change is not fully accounted for by any CIELAB‐based colour difference formula, including the most recent CIEDE2000 formula. © 2005 Wiley Periodicals, Inc. Col Res Appl, 30, 410–415, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.20153     

Why Hydroxamates May Not Be the Best Histone Deacetylase Inhibitors—What Some May Have Forgotten or Would Rather Forget?

Hydroxamate‐based histone deacetylase inhibitors (HDACIs) have been approved as therapeutic agents by the US Food and Drug Administration for use in oncology applications. While the potential utility of such HDACIs in other areas of medicinal chemistry is tremendous, there are significant concerns that “pan‐HDAC inhibitors” may be too broadly acting and/or toxic for clinical use beyond oncology. In addition to the isozyme selectivity challenge, the potential mutagenicity of hydroxamate‐containing HDAC inhibitors represents a major hindrance in their application to other therapeutic areas. Herein we report on the mutagenicity of known hydroxamates, discuss the mechanisms responsible for their genotoxicity, and review some of the current alternatives to hydroxamates. We conclude that the hydroxamate group, while providing high‐potency HDACIs, is not necessarily the best zinc‐binding group for HDACI drug discovery.     

Control of a polyphase induction generator/induction motor powerconversion system completely isolated from the utility

Two squirrel cage induction machines interconnected via a 20 kHz parallel resonant high frequency (HF) AC link and associated switching pulse density modulated (PDM) power converters are investigated, one operating as a generator and the other as a motor. No capacitors are used for the excitation of the generator or motor. Instead, the real power of the generator is controlled so as to maintain the proper link voltage and match the power between the input and output, Current regulated PDM converters operating via field oriented controllers are used to control both machines. A zero voltage switching technique is utilized with the associated PDM converters. Low harmonic distortion waveforms have been obtained both at the input and output due to the high 40 kHz switching frequency. Link voltage build-up and excitation of the generator by an initial charging circuit, power matching between input and output, and peak link voltage regulation techniques are investigated. Both computer simulations and experimental results demonstrate the feasibility of the proposed system     

Some observations relating to the stability of the BODIPY fluorophore under acidic and basic conditions

4,4-Difluoro-4-bora-1,3,5,7-tetramethyl-2,6-diethyl-8-methyl-3a,4a-diaza-s-indacene (BODIPY) fluorophore was transformed into its corresponding 4,4-dimethyl, 4,4-dimethoxy and 4,4-diphenyl analogues. The stabilities of these BODIPY fluorophores in acidic (di- and trichloroacetic acid) and basic conditions (aqueous ammonium hydroxide) were investigated using ¹¹B NMR spectroscopy.