Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues

Physical forces generated by cells drive morphologic changes during development and can feedback to regulate cellular phenotypes. Because these phenomena typically occur within a 3-dimensional (3D) matrix in vivo, we used microelectromechanical systems (MEMS) technology to generate arrays of microtissues consisting of cells encapsulated within 3D micropatterned matrices. Microcantilevers were used to simultaneously constrain the remodeling of a collagen gel and to report forces generated during this process. By concurrently measuring forces and observing matrix remodeling at cellular length scales, we report an initial correlation and later decoupling between cellular contractile forces and changes in tissue morphology. Independently varying the mechanical stiffness of the cantilevers and collagen matrix revealed that cellular forces increased with boundary or matrix rigidity whereas levels of cytoskeletal and extracellular matrix (ECM) proteins correlated with levels of mechanical stress. By mapping these relationships between cellular and matrix mechanics, cellular forces, and protein expression onto a bio-chemo-mechanical model of microtissue contractility, we demonstrate how intratissue gradients of mechanical stress can emerge from collective cellular contractility and finally, how such gradients can be used to engineer protein composition and organization within a 3D tissue. Together, these findings highlight a complex and dynamic relationship between cellular forces, ECM remodeling, and cellular phenotype and describe a system to study and apply this relationship within engineered 3D microtissues.

Streaming covariance selection with applications to adaptive querying in sensor networks

Sensor networks can be naturally represented as graphical models, where the edge set encodes the presence of sparsity in the correlation structure between sensors. Such graphical representations can be valuable for information mining purposes as well as for optimizing bandwidth and battery usage with minimal loss of estimation accuracy. We use a computationally efficient technique for estimating sparse graphical models which fits a sparse linear regression locally at each node of the graph via the Lasso estimator. Using a recently suggested online, temporally adaptive implementation of the Lasso, we propose an algorithm for streaming graphical model selection over sensor networks. With battery consumption minimization applications in mind, we use this algorithm as the basis of an adaptive querying scheme. We discuss implementation issues in the context of environmental monitoring using sensor networks, where the objective is short-term forecasting of local wind direction. The algorithm is tested against real UK weather data and conclusions are drawn about certain tradeoffs inherent in decentralized sensor networks data analysis. © 2010 The Author. Published by Oxford University Press on behalf of The British Computer Society. All rights reserved.

Exploiting Chinese character models to improve speech recognition performance

The Chinese language is based on characters which are syllabic in nature. Since languages have syllabotactic rules which govern the construction of syllables and their allowed sequences, Chinese character sequence models can be used as a first level approximation of allowed syllable sequences. N-gram character sequence models were trained on 4.3 billion characters. Characters are used as a first level recognition unit with multiple pronunciations per character. For comparison the CU-HTK Mandarin word based system was used to recognize words which were then converted to character sequences. The character only system error rates for one best recognition were slightly worse than word based character recognition. However combining the two systems using log-linear combination gives better results than either system separately. An equally weighted combination gave consistent CER gains of 0.1-0.2% absolute over the word based standard system. Copyright © 2009 ISCA.

On the transition from displacement to mixing ventilation with a localized heat source

We investigate the steady state natural ventilation of a room heated at the base and consisting of two vents at different levels. We explore how the air flow rate and internal temperature relative to the exterior vary as a function of the vent areas, position of the vents and heat load in order to establish appropriate ventilation strategies for a room. When the room is heated by a distributed source, the room becomes well mixed and the steady state ventilation rate depends on the heating rate, the area of the vents and the distance between the lower and upper level vents. However, when the room is heated by a localised source the room becomes stratified. If the effective ventilation area is sufficiently large, then the interface separating the two layers lies above the inlet vent and the lower layer is comprised of ambient fluid. In this case the upper layer is warmer than in the well mixed case and the ventilation rate is smaller. However, if the effective area for ventilation is sufficiently small, then the interface separating the two layers lies below the inlet vent and the lower layer is comprised of warm fluid which originates as the cold incoming fluid mixes during descent from the vent through the upper layer. In this case both the ventilation rate and the upper layer temperature are the same as in the case of a distributed heat load. As the vertical separation between lower and upper level vents decreases, then the temperature difference between the layers falls to zero and the room becomes approximately well mixed. These findings suggest how the appropriate ventilation strategy for a room can be varied depending on the exterior temperature, with mixing ventilation more suitable for winter conditions and displacement ventilation for warmer external temperatures.

Using internal fibre geometry to improve the performance of pin-loaded holes in composite materials

The anisotropic nature of fibre reinforced composites leads to large stress concentrations around pin-loaded holes through standard weave cloths. Proper understanding of how this anisotropic nature affects the load distribution around holes can be utilised to reduce these con-centrations if sufficient thought is given to the internal fibre geometry near to the hole. Such local reinforcements need not be highly complex and can be readily produced without excessive effort, producing significant improvements in performance. © 1996 Kluwer Academic Publishers.

High impulsivity predicting vulnerability to cocaine addiction in rats: some relationship with novelty preference but not novelty reactivity, anxiety or stress.

RATIONALE: Impulsivity is a vulnerability marker for drug addiction in which other behavioural traits such as anxiety and novelty seeking ('sensation seeking') are also widely present. However, inter-relationships between impulsivity, novelty seeking and anxiety traits are poorly understood. OBJECTIVE: The objective of this paper was to investigate the contribution of novelty seeking and anxiety traits to the expression of behavioural impulsivity in rats. METHODS: Rats were screened on the five-choice serial reaction time task (5-CSRTT) for spontaneously high impulsivity (SHI) and low impulsivity (SLI) and subsequently tested for novelty reactivity and preference, assessed by open-field locomotor activity (OF), novelty place preference (NPP), and novel object recognition (OR). Anxiety was assessed on the elevated plus maze (EPM) both prior to and following the administration of the anxiolytic drug diazepam, and by blood corticosterone levels following forced novelty exposure. Finally, the effects of diazepam on impulsivity and visual attention were assessed in SHI and SLI rats. RESULTS: SHI rats were significantly faster to enter an open arm on the EPM and exhibited preference for novelty in the OR and NPP tests, unlike SLI rats. However, there was no dimensional relationship between impulsivity and either novelty-seeking behaviour, anxiety levels, OF activity or novelty-induced changes in blood corticosterone levels. By contrast, diazepam (0.3-3 mg/kg), whilst not significantly increasing or decreasing impulsivity in SHI and SLI rats, did reduce the contrast in impulsivity between these two groups of animals. CONCLUSIONS: This investigation indicates that behavioural impulsivity in rats on the 5-CSRTT, which predicts vulnerability for cocaine addiction, is distinct from anxiety, novelty reactivity and novelty-induced stress responses, and thus has relevance for the aetiology of drug addiction.

Characterisation of cell adhesion to substrate materials and the resistance to enzymatic and mechanical cell-removal

Cell-implant adhesive strength is important for prostheses. In this paper, an investigation is described into the adhesion of bovine chondrocytes to Ti6Al4V-based substrates with different surface roughnesses and compositions. Cells were cultured for 2 or 5 days, to promote adhesion. The ease of cell removal was characterised, using both biochemical (trypsin) and mechanical (accelerated buoyancy and liquid flow) methods. Computational fluid dynamics (CFD) modelling has been used to estimate the shear forces applied to the cells by the liquid flow. A comparison is presented between the ease of cell detachment indicated using these methods, for the three surfaces investigated. © 2008 Materials Research Society.

A Bayesian Approach to the Restoration of Degraded Audio Signals

In this paper we derive the a posteriori probability for the location of bursts of noise additively superimposed on a Gaussian AR process. The theory is developed to give a sequentially based restoration algorithm suitable for real-time applications. The algorithm is particularly appropriate for digital audio restoration, where clicks and scratches may be modelled as additive bursts of noise. Experiments are carried out on both real audio data and synthetic AR processes and Significant improvements are demonstrated over existing restoration techniques. © 1995 IEEE

Monte Carlo filtering and smoothing with application to time-varying spectral estimation

We develop methods for performing filtering and smoothing in non-linear non-Gaussian dynamical models. The methods rely on a particle cloud representation of the filtering distribution which evolves through time using importance sampling and resampling ideas. In particular, novel techniques are presented for generation of random realisations from the joint smoothing distribution and for MAP estimation of the state sequence. Realisations of the smoothing distribution are generated in a forward-backward procedure, while the MAP estimation procedure can be performed in a single forward pass of the Viterbi algorithm applied to a discretised version of the state space. An application to spectral estimation for time-varying autoregressions is described.

Innovation processes within the healthcare industry: Determining critical success factors aligned to product strategies

The impact of differing product strategies on product innovation processes pursued by healthcare firms is discussed. The critical success factors aligned to product strategies are presented. A definite split between pioneering product strategies and late entrant product strategies is also recognised.

Addition of ferromagnetic CoFe2O4 to YBCO thin films for enhanced flux pinning

An attempt has been made to prepare a YBa2Cu3O 7-δ (YBCO) thin film doped with ferromagnetic CoFe 2O4. Transmission electron microscopy of the resultant samples shows, however, that Y(Fe, Co)O3 forms as a nanoparticulate dispersion throughout the film in preference to CoFe2O4, leaving the YBCO yttrium deficient. As a consequence, the superconducting properties of the sample are poor, with a self-field critical current density of just 0.25 MA cm-2. Magnetic measurements indicate however that the Y(Fe, Co)O3 content, together with any other residual phases, is also ferromagnetic, and some interesting features are present in the in-field critical current behaviour, including a reduced dependence on applied field and a strong c-axis peak in the angular dependence. The work points the way towards future attempts utilising YFeO3 as an effective ferromagnetic pinning additive for YBCO. © 2009 Elsevier B.V. All rights reserved.

Analytically-based approach to rotor-stator interaction noise in mean swirling flow

A method for modelling and predicting the noise generated by the interaction between the unsteady wake shed from the rotor and a downstream row of stators in a modern ultra-high bypass ducted turbofan engine is described. An analytically-based model is developed to account for three main features of the problem. First, the way in which a typical unsteady wake disturbance from the rotor interacts and is distorted by the mean swirling flow as it propagates downstream. The analysis allows for the inclusion of mean entropy gradients and entropy perturbations. Second, the effects of real stator-blade geometry and proper representation of the genuinely three-dimensional nature of the problem. Third, to model the propagation of the resulting noise back upstream in mean swirling flow. The analytical nature of the problem allows for the inclusion of all wake harmonics and enables the response at all blade passing frequencies to be determined. Example results are presented for an initial wake distribution corresponding to a genuine rotor configuration. Comparisons between numerical data and the asymptotic model for the wake evolution are made. Copyright © 2004 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.

The ensemble statistics of the energy of a random system subjected to harmonic excitation

This paper is concerned with the ensemble statistics of the response to harmonic excitation of a single dynamic system such as a plate or an acoustic volume. Random point process theory is employed, and various statistical assumptions regarding the system natural frequencies are compared, namely: (i) Poisson natural frequency spacings, (ii) statistically independent Rayleigh natural frequency spacings, and (iii) natural frequency spacings conforming to the Gaussian orthogonal ensemble (GOE). The GOE is found to be the most realistic assumption, and simple formulae are derived for the variance of the energy of the system under either point loading or rain-on-the-roof excitation. The theoretical results are compared favourably with numerical simulations and experimental data for the case of a mass loaded plate. © 2003 Elsevier Ltd. All rights reserved.