Development of a Position Sensitive Neutron Detector with High Efficiency and Energy Resolution for Use at High-Flux Beam Sources

We are developing a high-efficiency neutron detector with 1 cm position resolution and coarse energy resolution for use at high-flux neutron source facilities currently proposed or under construction. The detector concept integrates a segmented ³He ionization chamber with the position sensitive, charged particle collection methods of a MicroMegas detector. Neutron absorption on the helium produces protons and tritons that ionize the fill gas. The charge is amplified in the field region around a wire mesh and subsequently detected in current mode by wire strips mounted on a substrate. One module consisting of a high-voltage plate, a field-shaping high-voltage plate, a grid and wire strips defines a detection region. For 100 % efficiency, detector modules are consecutively placed along the beam axis. Analysis over several regions with alternating wire strip orientation provides a two-dimensional beam profile. By using ³He, a 1/v absorption gas, each axial region captures neutrons of a different energy range, providing an energy-sensitive detection scheme especially useful at continuous beam sources.     

Quantitative Analysis of Tau-Microtubule Interaction Using FRET

The interaction between the microtubule associated protein, tau and the microtubules is investigated. A fluorescence resonance energy transfer (FRET) assay was used to determine the distance separating tau to the microtubule wall, as well as the binding parameters of the interaction. By using microtubules stabilized with Flutax-2 as donor and tau labeled with rhodamine as acceptor, a donor-to-acceptor distance of 54 ± 1 Å was found. A molecular model is proposed in which Flutax-2 is directly accessible to tau-rhodamine molecules for energy transfer. By titration, we calculated the stoichiometric dissociation constant to be equal to 1.0 ± 0.5 µM. The influence of the C-terminal tails of αβ-tubulin on the tau-microtubule interaction is presented once a procedure to form homogeneous solution of cleaved tubulin has been determined. The results indicate that the C-terminal tails of α- and β-tubulin by electrostatic effects and of recruitment seem to be involved in the binding mechanism of tau.     

Pre-Analytical Considerations for Successful Next-Generation Sequencing (NGS): Challenges and Opportunities for Formalin-Fixed and Paraffin-Embedded Tumor Tissue (FFPE) Samples

In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research.     

Engineering cell attachments to scaffolds in cartilage tissue engineering

One of the challenges of tissue engineering, a promising cell-based treatment for damaged or diseased cartilage, is designing the scaffold that provides structure while the tissue regenerates. In addition to the scaffold material’s biocompatibility, mechanical properties, and ease of manufacturing, scaffold interactions with the cells must also be considered. In cartilage tissue engineering, a range of scaffolds with various degrees of cell attachment have been proposed, but the attachment density and type have yet to be optimized. Several techniques have been developed to modulate cell adhesion to the scaffold. These studies suggest that the need for cell attachment in cartilage tissue engineering may vary with cell type, stage of differentiation, culture condition, and scaffold material. Further studies will elucidate the role of cell attachment in cartilage regeneration and enhance efforts to engineer cell-based cartilage therapies.     

Planning a City through ‘Dialogue’: Deliberative Policy-making in Action in Western Australia

Deliberative policy-making is an alternative method of generating new planning strategies based on the public deliberation of citizens and stakeholders. Four ideals of deliberative policy-making espoused by deliberative democracy theorists are identified. Using this framework the ‘Dialogue with the City’ process undertaken by the Western Australian Government to develop the Network City spatial planning strategy for the Perth metropolitan region is examined. While this process went further than most towards realising the ideals of deliberative policy-making, the Government was not able to fully achieve the ideals of inclusive decision-making, equitable decision-making, deliberation toward the common good and consensus decision-making. It is most likely that the deliberative approach to policy-making does not represent a new model for governing; rather, these participation techniques constitute a more sophisticated model for involving citizens and stakeholders in planning.