Modelling within-host spatiotemporal dynamics of invasive bacterial disease

Mechanistic determinants of bacterial growth, death, and spread within mammalian hosts cannot be fully resolved studying a single bacterial population. They are also currently poorly understood. Here, we report on the application of sophisticated experimental approaches to map spatiotemporal population dynamics of bacteria during an infection. We analyzed heterogeneous traits of simultaneous infections with tagged Salmonella enterica populations (wild-type isogenic tagged strains [WITS]) in wild-type and gene-targeted mice. WITS are phenotypically identical but can be distinguished and enumerated by quantitative PCR, making it possible, using probabilistic models, to estimate bacterial death rate based on the disappearance of strains through time. This multidisciplinary approach allowed us to establish the timing, relative occurrence, and immune control of key infection parameters in a true host-pathogen combination. Our analyses support a model in which shortly after infection, concomitant death and rapid bacterial replication lead to the establishment of independent bacterial subpopulations in different organs, a process controlled by host antimicrobial mechanisms. Later, decreased microbial mortality leads to an exponential increase in the number of bacteria that spread locally, with subsequent mixing of bacteria between organs via bacteraemia and further stochastic selection. This approach provides us with an unprecedented outlook on the pathogenesis of S. enterica infections, illustrating the complex spatial and stochastic effects that drive an infectious disease. The application of the novel method that we present in appropriate and diverse host-pathogen combinations, together with modelling of the data that result, will facilitate a comprehensive view of the spatial and stochastic nature of within-host dynamics. © 2008 Grant et al.

Doping mechanism in tetrahedral amorphous carbon

Doping in hydrogenated amorphous silicon occurs by a process of an ionised donor atom partially compensated by a charged dangling bond. The total energies of various dopant and dopant/bonding combinations are calculated for tetrahedral amorphous carbon. It is found that charged dangling bonds are less favoured because of the stronger Coulombic repulsion in ta-C. Instead the dopants can be compensated by weak bond states in the lower gap associated with odd-membered π-rings or odd-numbered π-chains. The effect is that the doping efficiency is low but there are not charged midgap recombination centres, to reduce photoconductivity or photoluminescence with doping, as occurs in a-Si:H.

Doping mechanism in tetrahedral amorphous carbon

Doping in hydrogenated amorphous silicon occurs by a process of an ionized donor atom partially compensated by a charged dangling bond. The total energies of various dopant and dopant/bonding combinations are calculated for tetrahedral amorphous carbon. It is found that charged dangling bonds are less favored because of the stronger Coulombic repulsion in ta-C. Instead the dopants can be compensated by weak bond states in the lower gap associated with odd-membered π-rings or odd-numbered π-chains. The effect is that the doping efficiency is low but there are not charged midgap recombination centres, to reduce photoconductivity or photoluminescence with doping, as occurs in a-Si:H.

A general design method for electric machines using magnetic circuit model considering the flux saturation problem

This paper proposes an analytical approach that is generalized for the design of various types of electric machines based on a physical magnetic circuit model. Conventional approaches have been used to predict the behavior of electric machines but have limitations in accurate flux saturation analysis and hence machine dimensioning at the initial design stage. In particular, magnetic saturation is generally ignored or compensated by correction factors in simplified models since it is difficult to determine the flux in each stator tooth for machines with any slot-pole combinations. In this paper, the flux produced by stator winding currents can be calculated accurately and rapidly for each stator tooth using the developed model, taking saturation into account. This aids machine dimensioning without the need for a computationally expensive finite element analysis (FEA). A 48-slot machine operated in induction and doubly-fed modes is used to demonstrate the proposed model. FEA is employed for verification.

Sensitivity of wear rates in the micro-scale abrasion test to test conditions and material hardness

Micro-scale abrasion (ball cratering) tests were performed with different combinations of ball and bulk specimen materials, under different test conditions, such as load and abrasive slurry concentration. Wear modes were classified into two types: with rolling particle motion and with grooving particle motion. Wear rates observed with rolling particle motion were relatively insensitive to test conditions, whereas with grooving motion they varied much more. It is suggested that rolling abrasion is therefore a more appropriate mode if reproducible test results are desired. The motion of the abrasive particles can be reliably predicted from the knowledge of hardnesses and elastic properties of the ball and the specimen, and from the normal load and the abrasive slurry concentration. General trends in wear resistance measured in the micro-scale abrasion test with rolling particle motion are similar to those reported in tests with fixed abrasives with sliding particle motion, although the variation in wear resistance with hardness is significantly smaller. © 2004 Published by Elsevier B.V.

Material model of lung parenchyma based on living precision-cut lung slice testing.

We describe a novel constitutive model of lung parenchyma, which can be used for continuum mechanics based predictive simulations. To develop this model, we experimentally determined the nonlinear material behavior of rat lung parenchyma. This was achieved via uni-axial tension tests on living precision-cut rat lung slices. The resulting force-displacement curves were then used as inputs for an inverse analysis. The Levenberg-Marquardt algorithm was utilized to optimize the material parameters of combinations and recombinations of established strain-energy density functions (SEFs). Comparing the best-fits of the tested SEFs we found Wpar = 4.1 kPa(I1-3)2 + 20.7 kPa(I1 - 3)3 + 4.1 kPa(-2 ln J + J2 - 1) to be the optimal constitutive model. This SEF consists of three summands: the first can be interpreted as the contribution of the elastin fibers and the ground substance, the second as the contribution of the collagen fibers while the third controls the volumetric change. The presented approach will help to model the behavior of the pulmonary parenchyma and to quantify the strains and stresses during ventilation.

Materials selection in mechanical design

A novel materials-selection procedure has been developed and implemented in software. The procedure makes use of Materials Selection Charts: a new way of displaying material property data; and performance indices: combinations of material properties which govern performance. Optimization methods are employed for simultaneous selection of both material and shape.

Tribological properties of mems materials measured on a small-scale device

Micro-electro-mechanical systems, MEMS, is a rapidly growing interdisciplinary technology within the general field of Micro-Systems Technology which deals with the design and manufacture of miniaturised machines with major dimensions at the scale of tens, to perhaps hundreds, of microns. Because they depend on the cube of a representative dimension, component masses and inertias rapidly become small as size decreases whereas surface and tribological effects, which often depend on area, become increasingly important. Although MEMS components and their areas of contact are small, tribological conditions, measured by contact pressures or acceptable wear rates, are demanding and technical and commercial success will require careful measurement and precise control of surface topography and properties. Fabrication of small numbers of MEMS devices designed to test potential material combinations can be prohibitively expensive and thus there is a need for small scale test facilities which mimic the contact conditions within a micro-machine without themselves requiring processing within a full semiconductor foundry. The talk will illustrate some initial experimental results from a small-scale experimental device which meets these requirements, examining in particular the performance of Diamond-Like-Carbon coatings on a silicon substrate. Copyright © 2005 by ASME.

Perceptual learning, roving and the unsupervised bias

Perceptual learning improves perception through training. Perceptual learning improves with most stimulus types but fails when . certain stimulus types are mixed during training (roving). This result is surprising because classical supervised and unsupervised neural network models can cope easily with roving conditions. What makes humans so inferior compared to these models? As experimental and conceptual work has shown, human perceptual learning is neither supervised nor unsupervised but reward-based learning. Reward-based learning suffers from the so-called unsupervised bias, i.e., to prevent synaptic " drift" , the . average reward has to be exactly estimated. However, this is impossible when two or more stimulus types with different rewards are presented during training (and the reward is estimated by a running average). For this reason, we propose no learning occurs in roving conditions. However, roving hinders perceptual learning only for combinations of similar stimulus types but not for dissimilar ones. In this latter case, we propose that a critic can estimate the reward for each stimulus type separately. One implication of our analysis is that the critic cannot be located in the visual system. © 2011 Elsevier Ltd.

A novel method for rapid comparative quantitative analysis of nuclear fuel cycles

One of the greatest obstacles facing the nuclear industry is that of sustainability, both in terms of the finite reserves of uranium ore and the production of highly radiotoxic spent fuel which presents proliferation and environmental hazards. Alternative nuclear technologies have been suggested as a means of delivering enhanced sustainability with proposals including fast reactors, the use of thorium fuel and tiered fuel cycles. The debate as to which is the most appropriate technology continues, with each fuel system and reactor type delivering specific advantages and disadvantages which can be difficult to compare fairly. This paper demonstrates a framework of performance metrics which, coupled with a first-order lumped reactor model to determine nuclide population balances, can be used to quantify the aforementioned pros and cons for a range of different fuel and reactor combinations. The framework includes metrics such as fuel efficiency, spent fuel toxicity and proliferation resistance, and relative cycle performance is analysed through parallel coordinate plots, yielding a quantitative comparison of disparate cycles. © 2011 Elsevier Ltd. All rights reserved.

Magnetically actuated artificial cilia: the effect of fluid inertia.

Natural cilia are hairlike microtubule-based structures that are able to move fluid on the micrometer scale using asymmetric motion. In this article, we follow a biomimetic approach to design artificial cilia lining the inner surfaces of microfluidic channels with the goal of propelling fluid. The artificial cilia consist of polymer films filled with superparamagnetic nanoparticles, which can mimic the motion of natural cilia when subjected to a rotating magnetic field. To obtain the magnetic field and associated magnetization local to the cilia, we solve the Maxwell equations, from which the magnetic body moments and forces can be deduced. To obtain the ciliary motion, we solve the dynamic equations of motion, which are then fully coupled to the Navier-Stokes equations that describe the fluid flow around the cilia, thus taking full account of fluid inertial forces. The dimensionless parameters that govern the deformation behavior of the cilia and the associated fluid flow are arrived at using the principle of virtual work. The physical response of the cilia and the fluid flow for different combinations of elastic, fluid viscous, and inertia forces are identified.

Branching toughens fibrous networks.

Fibrous collagenous networks are not only stiff but also tough, due to their complex microstructures. This stiff yet tough behavior is desirable for both medical and military applications but it is difficult to reproduce in engineering materials. While the nonlinear hyperelastic behavior of fibrous networks has been extensively studied, the understanding of toughness is still incomplete. Here, we identify a microstructure mimicking the branched bundles of a natural type I collagen network, in which partially cross-linked long fibers give rise to novel combinations of stiffness and toughness. Finite element analysis shows that the stiffness of fully cross-linked fibrous networks is amplified by increasing the fibril length and cross-link density. However, a trade-off of such stiff networks is reduced toughness. By having partially cross-linked networks with long fibrils, the networks have comparable stiffness and improved toughness as compared to the fully cross-linked networks. Further, the partially cross-linked networks avoid the formation of kinks, which cause fibril rupture during deformation. As a result, the branching allows the networks to have stiff yet tough behavior.

Composite hydrogels for nucleus pulposus tissue engineering

Tissue engineering offers a paradigm shift in the treatment of back pain. Engineered intervertebral discs could replace degenerated tissue and overcome the limitations of current treatments, which substantially alter the biomechanical properties of the spine. The centre of the disc, the nucleus pulposus, is an amorphous gel with a large bound water content and it can resist substantial compressive loads. Due to similarities in their compositions, hydrogels have frequently been considered as substitutes for the nucleus pulposus. However, there has been limited work characterising the time-dependent mechanical behaviour of hydrogel scaffolds for nucleus pulposus tissue engineering. Poroelastic behaviour, which plays a key role in nutrient transport, is of particular importance. Here, we investigate the time-dependent mechanical properties of gelatin and agar hydrogels and of gelatin-agar composites. The time-dependent properties of these hydrogels are explored using viscoelastic and poroelastic frameworks. Several gel formulations demonstrate comparable equilibrium elastic behaviour to the nucleus pulposus under unconfined compression, but permeability values that are much greater than those of the native tissue. A range of time-dependent responses are observed in the composite gels examined, presenting the opportunity for targeted design of custom hydrogels with combinations of mechanical properties optimized for tissue engineering applications. © 2011 Elsevier Ltd.

Nonsmooth geometry and collapse of flexible structures under smooth loads

While static equilibria of flexible strings subject to various load types (gravity, hydrostatic pressure, Newtonian wind) is well understood textbook material, the combinations of the very same loads can give rise to complex spatial behaviour at the core of which is the unilateral material constraint prohibiting compressive loads. While the effects of such constraints have been explored in optimisation problems involving straight cables, the geometric complexity of physical configurations has not yet been addressed. Here we show that flexible strings subject to combined smooth loads may not have smooth solutions in certain ranges of the load ratios. This non-smooth phenomenon is closely related to the collapse geometry of inflated tents. After proving the nonexistence of smooth solutions for a broad family of loadings we identify two alternative, critical geometries immediately preceding the collapse. We verify these analytical results by dynamical simulation of flexible chains as well as with simple table-top experiments with an inflated membrane.

Sensor graphs for guaranteed cooperative localization performance

A group of mobile robots can localize cooperatively, using relative position and absolute orientation measurements, fused through an extended Kalman filter (ekf). The topology of the graph of relative measurements is known to affect the steady-state value of the position error covariance matrix. Classes of sensor graphs are identified, for which tight bounds for the trace of the covariance matrix can be obtained based on the algebraic properties of the underlying relative measurement graph. The string and the star graph topologies are considered, and the explicit form of the eigenvalues of error covariance matrix is given. More general sensor graph topologies are considered as combinations of the string and star topologies, when additional edges are added. It is demonstrated how the addition of edges increases the trace of the steady-state value of the position error covariance matrix, and the theoretical predictions are verified through simulation analysis.