Synthesis and Biological Evaluation of Chromium Bioorganometallics Based on the Antibiotic Platensimycin Lead Structure

The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure–activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (η⁶‐pentamethylbenzene)Cr(CO)₃ ( 2 ) and (η⁶‐benzene)Cr(CO)₃ ( 3 ), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against B. subtilis 168 (Gram positive) and E. coli W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against E. coli but derivative 2 inhibits B. subtilis growth at a moderate MIC value of 0.15 mM . To test the intrinsic toxicity of chromium, several chromium salts along with {η⁶‐(3‐pentamethylphenyl propionic acid)}Cr(CO)₃ ( 5 ) and {η⁶‐(3‐phenyl propionic acid)}Cr(CO)₃ ( 6 ) were tested against both bacterial strains. No activity was observed against E. coli for any of the compounds; B. subtilis growth was not inhibited by Cr(NO₃)₃ and only very weakly by 5 , K₂Cr₂O₇ and Na₂CrO₄ at MIC values of 0.5, 0.68 and 1.24 mM , respectively. Compounds 2 , 3 , 5 and 4 (the pure organic analogue of 2 ) show similar cytotoxicity against HeLa, HepG2 and HT‐29 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds 2 , 3 and Cr(NO₃)₃ in B. subtilis were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound 2 was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in B. subtilis.     

The ABCs of Space-time-coherence Recording in Holography

Abstract

After placing prior work on time-gated holography and coherence-gated holography in a unified perspective, we broaden both with a new coherence theorem which introduces an assymetry between them and allows otherwise-impossible holograms to be formed.     

Optical particle sizing in backscatter

Several possibilities for the use of elastic light scattering in the backscatter range (scattering angle theta(s) > 140 deg) for determination of size, velocity, and refractive index of spherical particles are investigated. First the phase Doppler technique is considered. Numerical simulations of light scattering with the Lorenz-Mie theory are used to show that the phase Doppler technique is unsuitable for such backscatter configurations, except for special measurement conditions. The time-shift (or pulse-displacement) technique is then considered by use of the Fourier-Lorenz-Mie theory. Simulations show that up to four fractional signals can be obtained by use of the technique in backscatter, corresponding to the scattering order or modes: surface wave (long path), reflection, second-order refraction (inner path), and a mixture of second-order refraction (outer path) and surface wave (short path). Signal characteristics as a function of particle size, refractive index, and particle ellipticity are studied. Suggestions for a practical measurement instrument are put forward.     

Surveyance of disease frequency in a population by linkage to diagnostic laboratory databases. A system for monitoring the incidences of hyper- and hypothyroidism as part of the Danish iodine supplementation program

In Denmark an increase in iodine intake through salt iodization has been introduced in 1998. In parallel a program for surveyance of thyroid diseases in the population was developed as recommended by UNICEF and WHO. OBJECTIVE: To develop and evaluate a computer based system to identify and register new cases of hyper- and hypothyroidism in a well defined cohort, by linkage to diagnostic laboratory databases. DESIGN AND RESULTS: (1) Two sub cohorts for monitoring were defined (n=535,859), and evaluated to minimize loss of new cases. Collaboration was established with laboratories covering thyroid hormone analyses in the cohort; (2) a diagnostic algorithm was defined and evaluated against clinical practice; (3) evaluation of the laboratory methods employed by the four participating laboratories, to ensure they would reach the same diagnosis in a patient; (4) a register database was developed which used data imported from the laboratory databases to automatically identify previously unknown cases of hyper- and hypothyroidism and record diagnostic activity in the area. All parts of the registration were carefully evaluated. CONCLUSION: We describe for the first time a computer based system for prospective measuring the incidence rate of hyper- and hypothyroidism. The system is particularly useful for monitoring of iodine supplementation programmes.     

Constitutive relationships for AlZnMg, AlZnMgCr, and AlZnMgZr alloys

The effects of zinc, magnesium, chromium, and zirconium on the steady-state flow stress during hot working of both as-cast and homogenized AlZnMg(Cr/Zr) alloys were determined by means of torsion testing. The equivalent strain rates varied between 0.01/s and 10/s and the temperatures ranged from 450 °C to 560 °C. The zinc and magnesium concentration varied from 4.5 to 7.5 wt pct and from 0.8 to 1.8 wt pct, respectively. In addition, alloys containing typically 0.15 wt pct zirconium or 0.20 wt pct chromium were investigated. Magnesium, zirconium, and chromium were found to increase the flow stress, whereas zinc had practically no effect. The flow stress in the homogenized material was in most cases higher than in the as-cast material. Fitting of the coefficients in the hyperbolic sine constitutive equation to the experimental results showed that some of the coefficients could be related to concentrations of magnesium and zinc in solid solution, whereas others might be regarded as constants. The following relationship was determined between the coefficients α and n and the magnesium and zinc concentration: α=a·[Mg] ^b and n=c·[Mg] ^d +e·[Zn]+f. The coefficients a, b, c, d, e, and f were determined by fitting of these relationships to the experimental data. The steady-state flow stress calculated by means of the constitutive equations was in good agreement with the experimental steady-state flow stress.     

Neighborhood network governance, ethnic organization, and the prospects for political integration

How may ethnic organizations work as mechanisms for political integration in suburban multicultural contexts with participative and network modes of governance? The overall argument of the paper is that a shift from vertical to more horizontal modes of governance affects the prospects for ethnic associations to fulfil different democratic functions. It does so in a complex, multidimensional and somewhat contradictory way. Although network modes of governance are often argued for in terms of openness and inclusion, it should not be taken for granted that such governance structures do promote democratic functions of ethnic associations. Drawing on an in-depth case study of ethnic associations and network politics in Botkyrka, Sweden, the purpose of the article is to provide theoretically informed arguments on how the political integration potential of ethnic organization is affected when they participate in local network-like arrangements and institutions. In brief, the article outlines three arguments: (1) There are different mechanisms of ethnic organization that might contribute to a more politically integrated society. (2) More horizontal network modes of governance generate new conditions for these integrative mechanisms to emerge out of ethnic organization. (3) In such a context of network governance, the different integrative mechanisms of ethnic organizations are not always supplementary, but sometimes contradictory, causing genuine dilemmas to be dealt with by local actors.     

A large-time-stepping scheme for balance equations

A well-balanced, large-time-stepping method for conservation laws with source terms is presented. The numerical method is based on a local reformulation of the balance law as a conservation law with a discontinuous flux function, and the approximate solution of this equation by a front tracking method. This yields an unconditionally stable method which is particularly well suited to calculate stationary states. The viability of this approach is demonstrated by several numerical examples. KHK has been supported in part by an Outstanding Young Investigators Award from the Research Council of Norway.