Intrafraction motion during frameless radiosurgery using Varian HyperArc and BrainLab Elements immobilization systems.

Commercial systems such as Varian HyperArcTM and BrainLab Elements MultiMetTM have been developed that allow radiosurgery treatment of multiple brain metastases using a single isocenter. Each software package places increased demands on frameless immobilization and requires the use of a specific immobilization system: the QFix-Encompass system for Varian and the BrainLab frameless-mask system for BrainLab. At our institution, patients receiving traditional radiosurgery (one isocenter per target lesion) were treated using both immobilization systems.

Using chiral peptide substitutions to probe the structure function relationship of a key residue of Aβ42.

Amyloid beta-protein 42 plays an important role in the onset and progression of Alzheimer's disease. Familial mutations have identified the glutamate residue 22 as a hotspot with regard to peptide neurotoxicity. We introduce an approach to study the influence of systematic sidechain modification at this residue, employing chirality as a structural probe.

Introduction of d-Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity.

The amyloid beta peptide 42 (Aβ42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the β-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide to form fibrils, which was correlated with changes at the level of the fibrillary architecture.

Biofilm Formation and Detachment in Gram-Negative Pathogens Is Modulated by Select Bile Acids.

Biofilms are a ubiquitous feature of microbial community structure in both natural and host environments; they enhance transmission and infectivity of pathogens and provide protection from human defense mechanisms and antibiotics. However, few natural products are known that impact biofilm formation or persistence for either environmental or pathogenic bacteria. Using the combination of a novel natural products library from the fish microbiome and an image-based screen for biofilm inhibition, we describe the identification of taurine-conjugated bile acids as inhibitors of biofilm formation against both Vibrio cholerae and Pseudomonas aeruginosa.

Living in the matrix: assembly and control of Vibrio cholerae biofilms.

Nearly all bacteria form biofilms as a strategy for survival and persistence. Biofilms are associated with biotic and abiotic surfaces and are composed of aggregates of cells that are encased by a self-produced or acquired extracellular matrix. Vibrio cholerae has been studied as a model organism for understanding biofilm formation in environmental pathogens, as it spends much of its life cycle outside of the human host in the aquatic environment.

Development of benzo[1,4]oxazines as biofilm inhibitors and dispersal agents against Vibrio cholerae.

Bacterial biofilms are estimated to be associated with over 65 percent of all nosocomial infections. However, no therapeutics have been approved by the FDA which directly mediate biofilm formation or persistence. Herein we report oxazine as a highly potent inhibitor, disperser and in the presence of the appropriate antibiotic eradicator of V.

Trichlorosilane mediated asymmetric reductions of the C=N bond.

Chiral amines are key components in numerous bioactive molecules. The development of efficient and economical ways to access molecules containing this functional group still remains a challenge at the forefront of synthetic chemistry. Of the methods that do exist, the trichlorosilane mediated organocatalytic reduction of ketimines offers significant potential as an alternative strategy.

Enantioselective preparation of P-chiral phosphine oxides.

A highly efficient chiral auxiliary-based strategy for the asymmetric synthesis of P-chiral phosphine oxides in >98:2 er has been developed. The methodology involves the highly stereoselective formation of P-chiral oxazolidinones that then undergo displacement with a variety of Grignard reagents to prepare the desired phosphine oxides.