Quantitative approaches for characterising fibrillar protein nanostructures

Polypeptide sequences have an inherent tendency to self-assemble into filamentous nanostructures commonly known as amyloid fibrils. Such self-assembly is used in nature to generate a variety of functional materials ranging from protective coatings in bacteria to catalytic scaffolds in mammals. The aberrant self-assembly of misfolded peptides and proteins is also, however, implicated in a range of disease states including neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. It is increasingly evident that the intrinsic material properties of these structures are crucial for understanding the thermodynamics and kinetics of the pathological deposition of proteins, particularly as the mechanical fragmentation of aggregates enhances the rate of protein deposition by exposing new fibril ends which can promote further growth. We discuss here recent advances in physical techniques that are able to characterise the hierarchical self-assembly of misfolded protein molecnles and define their properties. © 2010 Materials Research Society.

Quantitative RNA-seq analysis of the campylobacter jejuni transcriptome

Campylobacter jejuni is the most common bacterial cause of foodborne disease in the developed world. Its general physiology and biochemistry, as well as the mechanisms enabling it to colonize and cause disease in various hosts, are not well understood, and new approaches are required to understand its basic biology. High-throughput sequencing technologies provide unprecedented opportunities for functional genomic research. Recent studies have shown that direct Illumina sequencing of cDNA (RNA-seq) is a useful technique for the quantitative and qualitative examination of transcriptomes. In this study we report RNA-seq analyses of the transcriptomes of C. jejuni (NCTC11168) and its rpoN mutant. This has allowed the identification of hitherto unknown transcriptional units, and further defines the regulon that is dependent on rpoN for expression. The analysis of the NCTC11168 transcriptome was supplemented by additional proteomic analysis using liquid chromatography-MS. The transcriptomic and proteomic datasets represent an important resource for the Campylobacter research community. © 2011 SGM.

Methodological implications of critical realism for mixed-methods research

Building on recent developments in mixed methods, we discuss the methodological implications of critical realism and explore how these can guide dynamic mixed-methods research design in information systems. Specifically, we examine the core ontological assumptions of CR in order to gain some perspective on key epistemological issues such as causation and validity, and illustrate how these shape our logic of inference in the research process through what is known as retroduction. We demonstrate the value of a CR-led mixed-methods research approach by drawing on a study that examines the impact of ICT adoption in the financial services sector. In doing so, we provide insight into the interplay between qualitative and quantitative methods and the particular value of applying mixed methods guided by CR methodological principles. Our positioning of demi-regularities within the process of retroduction contributes a distinctive development in this regard. We argue that such a research design enables us to better address issues of validity and the development of more robust meta-inferences.

Joint experimental and numerical approach to three-dimensional shock control bump research

Previous studies of transonic shock control bumps have often been either numerical or experimental. Comparisons between the two have been hampered by the limitations of either approach. The present work aims to bridge the gap between computational fluid dynamics and experiment by planning a joint approach from the outset. This enables high-quality validation data to be produced and ensures that the conclusions of either aspect of the study are directly relevant to the application. Experiments conducted with bumps mounted on the floor of a blowdown tunnel were modified to include an additional postshock adverse pressure gradient through the use of a diffuser as well as introducing boundary-layer suction ahead of the test section to enable the in-flow boundary layer to be manipulated. This has the advantage of being an inexpensive and highly repeatable method. Computations were performed on a standard airfoil model, with the flight conditions as free parameters. The experimental and computational setups were then tuned to produce baseline conditions that agree well, enabling confidence that the experimental conclusions are relevant. The methods are then applied to two different shock control bumps: a smoothly contoured bump, representative of previous studies, and a novel extended geometry featuring a continuously widening tail, which spans the wind-tunnel width at the rear of the bump. Comparison between the computational and experimental results for the contour bump showed good agreement both with respect to the flow structures and quantitative analysis of the boundary-layer parameters. It was seen that combining the experimental and numerical data could provide valuable insight into the flow physics, which would not generally be possible for a one-sided approach. The experiments and computational fluid dynamics were also seen to agree well for the extended bump geometry, providing evidence that, even though thebumpinteracts directly with the wind-tunnel walls, it was still possible to observe the key flow physics. The joint approach is thus suitable even for wider bump geometries. Copyright © 2013 by S. P. Colliss, H. Babinsky, K. Nubler, and T. Lutz. Published by the American Institute of Aeronautics and Astronautics, Inc.