An improved synthesis of (2E,4Z)-6-(benzyloxy)-4-bromohexa-2,4-dien-1-ol

An improved synthesis of (2E,4Z)-6-(benzyloxy)-4-bromohexa-2,4-dien-1-ol has been devised. This new route increases the throughput and yield of the diene product by circumventing a low yielding preparation of boronic acid intermediate as well as removing the need to use multi-gram quantities of highly toxic thallium salts. In the process of developing this new route, a higher yielding preparation of ( E)-3-hydroxyprop-1-enylboronic acid was also achieved. (c) 2007 Elsevier Ltd. All rights reserved

A method for mapping and quantifying whole organ diffusion-weighted image distortion in MR imaging of the prostate.

A computational algorithm was designed to produce a measure of DW image distortion across the prostate. This algorithm was tested and validated on virtual phantoms incorporating known degrees and distributions of distortion. A study was then carried out on DW image volumes from three sets of 10 patients who had been imaged previously. These volumes had been radiologically assessed to have, respectively, 'no distortion' or 'significant distortion' or the potential for 'significant distortion' due to susceptibility effects from hip prostheses. Prostate outlines were drawn on a T2-weighted (T2W) image 'gold-standard' volume and on an ADC image volume derived from DW images acquired over the same region. The algorithm was then applied to these outlines to quantify and map image distortion. The proposed method correctly reproduced known distortion values and distributions in virtual phantoms. It also successfully distinguished between the three groups of patients: mean distortion in 'non-distorted' image volumes, 1.942 ± 0.582 mm; 'distorted', 4.402 ± 1.098 mm; and 'hip patients' 8.083 ± 4.653 mm; P < 0.001. This work has demonstrated and validated a means of quantifying and mapping image distortion in clinical prostate MRI cases

A generalized Poisson equation and short-range self-interaction energies

We generalize the Poisson equation to attenuated Newtonian potentials. If the attenuation is at least exponential, the equation provides a local mapping between the density and its potential. We use this to derive several density functionals for the short-range self-interaction energy

Self-consistent-field calculations of core excited states

The accuracy of core excitation energies and core electron binding energies computed within a Δself-consistent-field framework is assessed. The variational collapse of the core excited state is prevented by maintaining a singly occupied core orbital using an overlap criterion called the maximum overlap method. When applied to a wide range of small organic molecules, the resulting core excitation energies are not systematically underestimated as observed in time-dependent density functional theory and agree well with experiment. The accuracy of this approach for core excited states is illustrated by the calculation of the pre-edge features in x-ray absorption spectra of plastocyanin, which shows that accurate results can be achieved with Δself-consistent-field calculations when used in conjunction with uncontracted basis functions.N.A.B. is grateful to the ANU for a 2007 Visiting Fellowship

Online Bayesian phylodynamic inference in BEAST with application to epidemic reconstruction

Reconstructing pathogen dynamics from genetic data as they become available during an outbreak or epidemic represents an important statistical scenario in which observations arrive sequentially in time and one is interested in performing inference in an 'online' fashion. Widely-used Bayesian phylogenetic inference packages are not set up for this purpose, generally requiring one to recompute trees and evolutionary model parameters de novo when new data arrive. To accommodate increasing data flow in a Bayesian phylogenetic framework, we introduce a methodology to efficiently update the posterior distribution with newly available genetic data. Our procedure is implemented in the BEAST 1.10 software package, and relies on a distance-based measure to insert new taxa into the current estimate of the phylogeny and imputes plausible values for new model parameters to accommodate growing dimensionality. This augmentation creates informed starting values and re-uses optimally tuned transition kernels for posterior exploration of growing data sets, reducing the time necessary to converge to target posterior distributions. We apply our framework to data from the recent West African Ebola virus epidemic and demonstrate a considerable reduction in time required to obtain posterior estimates at different time points of the outbreak. Beyond epidemic monitoring, this framework easily finds other applications within the phylogenetics community, where changes in the data -- in terms of alignment changes, sequence addition or removal -- present common scenarios that can benefit from online inference.Comment: 20 pages, 3 figure

Resolutions of the Coulomb operator

We discuss a generalization of the resolution of the identity by considering one-body resolutions of two-body operators, with particular emphasis on the Coulomb operator. We introduce a set of functions that are orthonormal with respect to 1∕r₁₂ and propose that the resulting “resolution of the Coulomb operator,” r₁₂⁻¹=∣ϕi><ϕi∣, may be useful for the treatment of large systems due to the separation of two-body interactions. We validate our approach by using it to compute the Coulomb energy of large systems of point charges

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease

Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy

Trichostatin A Blocks Aldosterone-Induced Na+ Transport And Control Of Serum- And Glucocorticoid-Inducible Kinase 1 In Cortical Collecting Duct Cells

Background and Purpose: Aldosterone stimulates epithelial Na+ channel (ENaC)-dependent Na+ retention in the cortical collecting duct (CCD) of the kidney by activating mineralocorticoid receptors that promote expression of serum and glucocorticoid-inducible kinase 1 (SGK1). This response is critical to BP homeostasis. It has previously been suggested that inhibiting lysine deacetylases (KDACs) can post-transcriptionally disrupt this response by promoting acetylation of the mineralocorticoid receptor. The present study critically evaluates this hypothesis. Experimental Approach: Electrometric and molecular methods were used to define the effects of a pan-KDAC inhibitor, trichostatin A, on the responses to a physiologically relevant concentration of aldosterone (3 nM) in murine mCCDcl1 cells. Key Results: Aldosterone augmented ENaC-induced Na+ absorption and increased SGK1 activity and abundance, as expected. In the presence of trichostatin A, these responses were suppressed. Trichostatin A-induced inhibition of KDAC was confirmed by increased acetylation of histone H3, H4, and α-tubulin. Trichostatin A did not block the electrometric response to insulin, a hormone that activates SGK1 independently of increased transcription, indicating that trichostatin A has no direct effect upon the SGK1/ENaC pathway. Conclusions and Implications: Inhibition of lysine de-acetylation suppresses aldosterone-dependent control over the SGK1–ENaC pathway but does not perturb post-transcriptional signalling, providing a physiological basis for the anti-hypertensive action of KDAC inhibition seen in vivo