Relationship between prion propensity and the rates of individual molecular steps of fibril assembly.

Peptides and proteins possess an inherent propensity to self-assemble into generic fibrillar nanostructures known as amyloid fibrils, some of which are involved in medical conditions such as Alzheimer disease. In certain cases, such structures can self-propagate in living systems as prions and transmit characteristic traits to the host organism. The mechanisms that allow certain amyloid species but not others to function as prions are not fully understood. Much progress in understanding the prion phenomenon has been achieved through the study of prions in yeast as this system has proved to be experimentally highly tractable; but quantitative understanding of the biophysics and kinetics of the assembly process has remained challenging. Here, we explore the assembly of two closely related homologues of the Ure2p protein from Saccharomyces cerevisiae and Saccharomyces paradoxus, and by using a combination of kinetic theory with solution and biosensor assays, we are able to compare the rates of the individual microscopic steps of prion fibril assembly. We find that for these proteins the fragmentation rate is encoded in the structure of the seed fibrils, whereas the elongation rate is principally determined by the nature of the soluble precursor protein. Our results further reveal that fibrils that elongate faster but fracture less frequently can lose their ability to propagate as prions. These findings illuminate the connections between the in vitro aggregation of proteins and the in vivo proliferation of prions, and provide a framework for the quantitative understanding of the parameters governing the behavior of amyloid fibrils in normal and aberrant biological pathways.

On the existence of Zeno behavior in hybrid systems with non-isolated zeno equilibria

This paper presents proof-certificate based sufficient conditions for the existence of Zeno behavior in hybrid systems near non-isolated Zeno equilibria. To establish these conditions, we first prove sufficient conditions for Zeno behavior in a special class of hybrid systems termed first quadrant interval hybrid systems. The proof-certificate sufficient conditions are then obtained through a collection of functions that effectively "reduce" a general hybrid system to a first quadrant interval hybrid system. This paper concludes with an application of these ideas to Lagrangian hybrid systems, resulting in easily verifiable sufficient conditions for Zeno behavior. © 2008 IEEE.

Correlations between the performance characteristics of a liquid crystal laser and the macroscopic material properties.

In order to understand how the performance of a liquid-crystal laser depends on the physical properties of the low molar mass nematic host, we have studied the energy threshold and slope efficiency of ten optically pumped liquid-crystal lasers based on different hosts. Specifically, this leads to a variation in the birefringence, the orientational order parameter, and the order parameter of the transition dipole moment of the dye. It is found that low threshold energies and high slope efficiencies correlate with high order parameters and large birefringences. To a first approximation this can be understood by considering analytical expressions for the threshold and slope efficiency, which are derived from the space-independent rate equations for a two-level system, in terms of the macroscopic liquid crystal properties.

Embodied energy as an environmental impact indicator for basement wall construction

Attempts were made to quantify the environmental impacts of the basement walls of two commercial buildings in London. Four different retaining wall options were designed based on steel and concrete systems for each of the sites. It was considered that excavation would take place with the aid of a one or two anchors system. Evaluation of embodied energy (EE) and CO2 emissions for each of the wall designs and anchoring systems were compared. Results show that there are notable differences in EE between different wall designs. Using the averaged set of Embodied Energy Intensity (EEI) values, the use of recycled steel over virgin steel would reduce the EE of the wall significantly. The difference in anchor designs is relatively insignificant, and therefore the practicality of the design for the specific site should be the deciding factor for anchor types. Generally, the scale of environmental impacts due to constructions is large compared to other aspects in life as demonstrated with the comparisons to car emissions and household energy consumption. Copyright ASCE 2008.

The effect of a twin tunnel on the propagation of ground-borne vibration from an underground railway

Accurate predictions of ground-borne vibration levels in the vicinity of an underground railway are greatly sought after in modern urban centres. Yet the complexity involved in simulating the underground environment means that it is necessary to make simplifying assumptions about this system. One such commonly made assumption is to ignore the effects of neighbouring tunnels, despite the fact that many underground railway lines consist of twin-bored tunnels, one for the outbound direction and one for the inbound direction. This paper presents a unique model for two tunnels embedded in a homogeneous, elastic fullspace. Each of these tunnels is subject to both known, dynamic train forces and dynamic cavity forces. The net forces acting on the tunnels are written as the sum of those tractions acting on the invert of a single tunnel, and those tractions that represent the motion induced by the neighbouring tunnel. By apportioning the tractions in this way, the vibration response of a two-tunnel system is written as a linear combination of displacement fields produced by a single-tunnel system. Using Fourier decomposition, forces are partitioned into symmetric and antisymmetric modenumber components to minimise computation times. The significance of the interactions between two tunnels is quantified by calculating the insertion gains, in both the vertical and horizontal directions, that result from the existence of a second tunnel. The insertion-gain results are shown to be localised and highly dependent on frequency, tunnel orientation and tunnel thickness. At some locations, the magnitude of these insertion gains is greater than 20 dB. This demonstrates that a high degree of inaccuracy exists in any surface vibration prediction model that includes only one of the two tunnels. This novel two-tunnel solution represents a significant contribution to the existing body of research into vibration from underground railways, as it shows that the second tunnel has a significant influence on the accuracy of vibration predictions for underground railways. © 2011 Elsevier Ltd. All rights reserved.

The effects of a second tunnel on the propagation of ground-borne vibration from an underground railway

Accurate predictions of ground-borne vibration levels in the vicinity of an underground railway are greatly sought in modern urban centers. Yet the complexity involved in simulating the underground environment means that it is necessary to make simplifying assumptions about this environment. One such commonly-made assumption is to model the railway as a single tunnel, despite many underground railway lines consisting of twin-bored tunnels. A unique model for two tunnels embedded in a homogeneous, elastic full space is developed. The vibration response of this two-tunnel system is calculated using the superposition of two displacement fields: one resulting from the forces acting on the invert of a single tunnel, and the other resulting from the interaction between the tunnels. By partitioning of the stresses into symmetric and anti-symmetric mode number components using Fourier decomposition, these two displacement fields can by calculated with minimal computational requirements. The significance of the interactions between twin-tunnels is quantified by calculating the insertion gains that result from the existence of a second tunnel. The insertion-gain results are shown to be localized and highly dependent on frequency, tunnel orientation and tunnel thickness. At some locations, the magnitude of these insertion gains is greater than 20dB. This demonstrates that a high degree of inaccuracy exists in any surface vibration-prediction model that includes only one of the two tunnels. © 2012 Springer.

The bacterial cytoskeleton modulates motility, type 3 secretion, and colonization in Salmonella.

Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its importance to virulence. In this study we have explored the contribution of the bacterial cytoskeleton to the ability of Salmonella to express and assemble virulence factors and cause disease. The bacterial actin-like protein MreB polymerises into helical filaments and interacts with other cytoskeletal elements including MreC to control cell-shape. As mreB appears to be an essential gene, we have constructed a viable ΔmreC depletion mutant in Salmonella. Using a broad range of independent biochemical, fluorescence and phenotypic screens we provide evidence that the Salmonella pathogenicity island-1 type three secretion system (SPI1-T3SS) and flagella systems are down-regulated in the absence of MreC. In contrast the SPI-2 T3SS appears to remain functional. The phenotypes have been further validated using a chemical genetic approach to disrupt the functionality of MreB. Although the fitness of ΔmreC is reduced in vivo, we observed that this defect does not completely abrogate the ability of Salmonella to cause disease systemically. By forcing on expression of flagella and SPI-1 T3SS in trans with the master regulators FlhDC and HilA, it is clear that the cytoskeleton is dispensable for the assembly of these structures but essential for their expression. As two-component systems are involved in sensing and adapting to environmental and cell surface signals, we have constructed and screened a panel of such mutants and identified the sensor kinase RcsC as a key phenotypic regulator in ΔmreC. Further genetic analysis revealed the importance of the Rcs two-component system in modulating the expression of these virulence factors. Collectively, these results suggest that expression of virulence genes might be directly coordinated with cytoskeletal integrity, and this regulation is mediated by the two-component system sensor kinase RcsC.

Influence of film cooling hole angles and geometries on aerodynamic loss and net heat flux reduction

Turbine design engineers have to ensure that film cooling can provide sufficient protection to turbine blades from the hot mainstream gas, while keeping the losses low. Film cooling hole design parameters include inclination angle (α), compound angle (β ), hole inlet geometry and hole exit geometry. The influence of these parameters on aerodynamic loss and net heat flux reduction is investigated, with loss being the primary focus. Low-speed flat plate experiments have been conducted at momentum flux ratios of IR = 0.16, 0.64 and 1.44. The film cooling aerodynamic mixing loss, generated by the mixing of mainstream and coolant, can be quantified using a three-dimensional analytical model that has been previously reported by the authors. The model suggests that for the same flow conditions, the aerodynamic mixing loss is the same for holes with different α and β but with the same angle between the mainstream and coolant flow directions (angle κ). This relationship is assessed through experiments by testing two sets of cylindrical holes with different α and β : one set with κ = 35°, another set with κ = 60°. The data confirm the stated relationship between α, β, κ and the aerodynamic mixing loss. The results show that the designer should minimise κ to obtain the lowest loss, but maximise β to achieve the best heat transfer performance. A suggestion on improving the loss model is also given. Five different hole geometries (α =35.0°, β =0°) were also tested: cylindrical hole, trenched hole, fan-shaped hole, D-Fan and SD-Fan. The D-Fan and the SD-Fan have similar hole exits to the fan-shaped hole but their hole inlets are laterally expanded. The external mixing loss and the loss generated inside the hole are compared. It was found that the D-Fan and the SD-Fan have the lowest loss. This is attributed to their laterally expanded hole inlets, which lead to significant reduction in the loss generated inside the holes. As a result, the loss of these geometries is ≈ 50 % of the loss of the fan-shaped hole at IR = 0.64 and 1.44. Copyright © 2011 by ASME.

Programmable ZnO nanowire transistors using switchable polarization of ferroelectric liquid crystal

We demonstrate modulations of electrical conductance and hysteresis behavior in ZnO nanowire transistors via electrically polarized switching of ferroelectric liquid crystal (FLC). After coating a nanowire channel in the transistors with FLCs, we observed large increases in channel conductance and hysteresis width, and a strong dependence of hysteresis loops on the polarization states associated with the orientation of electric dipole moments along the direction of the gate electric field. Furthermore, the reversible switching and retention characteristics provide the feasibility of creating a hybrid system with switch and memory functions. © 2013 American Institute of Physics.

Influence of film cooling hole angles and geometries on aerodynamic loss and net heat flux reduction

Turbine design engineers have to ensure that film cooling can provide sufficient protection to turbine blades from the hot mainstream gas, while keeping the losses low. Film cooling hole design parameters include inclination angle (a), compound angle (b), hole inlet geometry, and hole exit geometry. The influence of these parameters on aerodynamic loss and net heat flux reduction is investigated, with loss being the primary focus. Low-speed flat plate experiments have been conducted at momentum flux ratios of IR=0.16, 0.64, and 1.44. The film cooling aerodynamic mixing loss, generated by the mixing of mainstream and coolant, can be quantified using a three-dimensional analytical model that has been previously reported by the authors. The model suggests that for the same flow conditions, the aerodynamic mixing loss is the same for holes with different a and b but with the same angle between the mainstream and coolant flow directions (angle k). This relationship is assessed through experiments by testing two sets of cylindrical holes with different a and b: one set with k=35 deg, and another set with k=60 deg. The data confirm the stated relationship between α, β, k and the aerodynamic mixing loss. The results show that the designer should minimize k to obtain the lowest loss, but maximize b to achieve the best heat transfer performance. A suggestion on improving the loss model is also given. Five different hole geometries (α=35.0 deg, β=0 deg) were also tested: cylindrical hole, trenched hole, fan-shaped hole, D-Fan, and SD-Fan. The D-Fan and the SD-Fan have similar hole exits to the fan-shaped hole but their hole inlets are laterally expanded. The external mixing loss and the loss generated inside the hole are compared. It was found that the D-Fan and the SD-Fan have the lowest loss. This is attributed to their laterally expanded hole inlets, which lead to significant reduction in the loss generated inside the holes. As a result, the loss of these geometries is≈50% of the loss of the fan-shaped hole at IR=0.64 and 1.44. © 2013 by ASME.

Self-organization of reflexive behavior from spontaneous motor activity.

In mammals, the development of reflexes is often regarded as an innate process. However, recent findings show that fetuses are endowed with favorable conditions for ontogenetic development. In this article, we hypothesize that the circuitry of at least some mammalian reflexes can be self-organized from the sensory and motor interactions brought forth in a musculoskeletal system. We focus mainly on three reflexes: the myotatic reflex, the reciprocal inhibition reflex, and the reverse myotatic reflex. To test our hypothesis, we conducted a set of experiments on a simulated musculoskeletal system using pairs of agonist and antagonist muscles. The reflex connectivity is obtained by producing spontaneous motor activity in each muscle and by correlating the resulting sensor and motor signals. Our results show that, under biologically plausible conditions, the reflex circuitry thus obtained is consistent with that identified in relation to the analogous mammalian reflexes. In addition, they show that the reflex connectivity obtained depends on the morphology of the musculoskeletal system as well as on the environment that it is embedded in.