Use of a sonogashira-acetylide coupling strategy for the synthesis of the aromatic spiroketal skeleton of gamma-rubromycin

[reaction: see text] The synthesis of the fused aromatic spiroketal core of gamma-rubromycin is described via addition of an aryl acetylide fragment to an aryl acetaldehyde fragment. In turn, the aryl acetylene precursor was readily prepared with use of a Sonogashira reaction.     

Karhunen-Loeve local characterization of spatiotemporal chaos in a reaction-diffusion system

By computing the Karhunen-Loeve decomposition (KLD) correlation length xi(KLD) of a reaction-diffusion system in the extensive chaos regime, we show that it is a sensitive measure of spatial dynamical inhomogeneities. It reveals substantial spatial nonuniformity of the dynamics at the boundaries and can also detect slow spatial variations in system parameters. The intensive length xi(KLD) can be easily computed from small local subsystems and is found to have a similar parametric dependence as the two-point correlation length computed over the full system size.     

Invariant manifolds and the stability of traveling waves in scalar viscous conservation laws

The stability of traveling wave solutions of scalar viscous conservation laws is investigated by decomposing perturbations into three components: two far-field components and one near-field component. The linear operators associated to the far-field components are the constant coefficient operators determined by the asymptotic spatial limits of the original operator. Scaling variables can be applied to study the evolution of these components, allowing for the construction of invariant manifolds and the determination of their temporal decay rate. The large time evolution of the near-field component is shown to be governed by that of the far-field components, thus giving it the same temporal decay rate. We also give a discussion of the relationship between this geometric approach and previous results, which demonstrate that the decay rate of perturbations can be increased by requiring that initial data lie in appropriate algebraically weighted spaces.     

Microstrain in hydroxyapatite carbon nanotube composites

Synchrotron radiation diffraction data were collected from hydroxyapatite–carbon nanotube bioceramic composites to determine the crystallite size and to measure changes in non‐uniform strain. Estimates of crystallite size and strain were determined by line‐profile fitting of discrete peaks and these were compared with a Rietveld whole‐pattern analysis. Overall the two analysis methods produced very similar numbers. In the commercial hydroxyapatite material, one reflection in particular, (0 2 3), has higher crystallite size and lower strain values in comparison with laboratory‐synthesized material. This could indicate preferential crystal growth in the [0 2 3] direction in the commercial material. From the measured strains in the pure material and the composite, there was a degree of bonding between the matrix and strengthening fibres. However, increasing the amount of carbon nanotubes in the composite has increased the strain in the material, which is undesirable for biomedical implant applications.     

Polyether antibiotic CP44,161

The crystal structure of antibiotic CP44,161, 6-(7-{2-ethyl-2-[5-(1-hydroxy­methyl)-5-methyl-2,3,4,5-tetra­hydro-2-furyl]-4,10,-­12-tri­methyl-1,6,8-trioxadi­spiro­[4.1.5.3]­pentadec-13-en-9-yl}-4-hydroxy-3,5-di­methyl-6-oxononyl)-2-hydroxy-3-methyl­benzoic acid monohydrate, C₄₃H₆₆O₁₀·H₂O, has been determined by X-ray crystallography. The mol­ecule adopts a cyclic conformation, with a centrally located water mol­ecule contributing to the stability of the conformation through hydrogen-bonding interactions.     

Photoelectron imaging of tetrahydrofuran cluster anions (THF)(n) (-) (1≤n≤100)

Anionic tetrahydrofuran clusters (THF)(n) (-) (1≤n≤100) are studied with photoelectron imaging as gas-phase precursors for electrons solvated in THF. Photoelectron spectra of clusters up to n=5 show two peaks, one of which is attributed to a solvated open chain radical anion and the other to the closed THF ring. At n=6, the spectra change shape abruptly, which become more characteristic of (THF)(n) (-) clusters containing solvated electrons. From n=6-100, the vertical detachment energies (VDEs) of these solvated electron clusters increase from 1.96 to 2.71 eV, scaling linearly with n(-1/3). For fully deuterated (THF-d8)(n) (-) clusters, the apparent transition to a solvated electron cluster is delayed to n=11. Extrapolation of the VDEs to infinite cluster size yields a value of 3.10 eV for the bulk photoelectric threshold. The relatively large VDEs at onset and small stabilization with increasing cluster size compared to other solvated electron clusters may reflect the tendency of the bulk solvent to form preexisting voids that can readily solvate a free electron.     

Development,validation, and implementation of capillary gel electrophoresis as a replacement for SDS‐PAGE for purity analysis of IgG2 mAbs

Capillary gel electrophoresis (CGE) methods with UV detection were developed for reduced and non‐reduced mAb analysis. These methods can be used to evaluate mAb purity, offering more reproducible quantitation compared with that of traditional SDS‐PAGE methods. These CGE methods have been utilized as platform technology for bioprocess development, formulation development, mAb characterization, drug substance/drug product release testing as well as a required methodology for stability testing. We have found these CGE methods to be applicable across a platform of mAbs in preclinical and clinical development, with the majority of mAbs requiring no modification to the method conditions. This methodology has been ICH validated and transferred to several supporting organizations. The data presented herein describes the development of CGE methodology, platform application to mAb purity analysis, ICH validation, reliability metrics, and considerations on technology enhancement for improved performance and throughput.     

A general dual-bolus approach for quantitative DCE-MRI

Purpose

To present a dual-bolus technique for quantitative dynamic contrast-enhanced MRI (DCE-MRI) and show that it can give an arterial input function (AIF) measurement equivalent to that from a single-bolus protocol.

Methods

Five rabbits were imaged using a dual-bolus technique applicable for high-resolution DCE-MRI, incorporating a time resolved imaging of contrast kinetics (TRICKS) sequence for rapid temporal sampling. AIFs were measured from both the low-dose prebolus and the high-dose main bolus in the abdominal aorta. In one animal, TRICKS and fast spoiled gradient echo (FSPGR) acquisitions were compared.

Results

The scaled prebolus AIF was shown to match the main bolus AIF, with 95% confidence intervals overlapping for fits of gamma-variate functions to the first pass and linear fits to the washout phase, with the exception of one case. The AIFs measured using TRICKS and FSPGR were shown to be equivalent in one animal.

Conclusion

The proposed technique can capture even the rapid circulation kinetics in the rabbit aorta, and the scaled prebolus AIF is equivalent to the AIF from a high-dose injection. This allows separate measurements of the AIF and tissue uptake curves, meaning that each curve can then be acquired using a protocol tailored to its specific requirements.