Convergence of regenerative medicine and synthetic biology to develop standardized and validated models of human diseases with clinical relevance

In order to progress beyond currently available medical devices and implants, the concept of tissue engineering has moved into the centre of biomedical research worldwide. The aim of this approach is not to replace damaged tissue with an implant or device but rather to prompt the patient's own tissue to enact a regenerative response by using a tissue-engineered construct to assemble new functional and healthy tissue. More recently, it has been suggested that the combination of Synthetic Biology and translational tissue-engineering techniques could enhance the field of personalized medicine, not only from a regenerative medicine perspective, but also to provide frontier technologies for building and transforming the research landscape in the field of in vitro and in vivo disease models.

Estimating the parameters of stochastic volatility models using option price data

This article describes a maximum likelihood method for estimating the parameters of the standard square-root stochastic volatility model and a variant of the model that includes jumps in equity prices. The model is fitted to data on the S&P 500 Index and the prices of vanilla options written on the index, for the period 1990 to 2011. The method is able to estimate both the parameters of the physical measure (associated with the index) and the parameters of the risk-neutral measure (associated with the options), including the volatility and jump risk premia. The estimation is implemented using a particle filter whose efficacy is demonstrated under simulation. The computational load of this estimation method, which previously has been prohibitive, is managed by the effective use of parallel computing using graphics processing units (GPUs). The empirical results indicate that the parameters of the models are reliably estimated and consistent with values reported in previous work. In particular, both the volatility risk premium and the jump risk premium are found to be significant.

Compositional agent-based models for electricity distribution networks

This thesis presents a novel approach to building large-scale agent-based models of networked physical systems using a compositional approach to provide extensibility and flexibility in building the models and simulations. A software framework (MODAM - MODular Agent-based Model) was implemented for this purpose, and validated through simulations. These simulations allow assessment of the impact of technological change on the electricity distribution network looking at the trajectories of electricity consumption at key locations over many years.

Homogeneous isotropic turbulence: large momentum expansion

High temperature expansion is an effective tool for studying second order phase transitions. With this in mind, we have looked at a high momentum expansion for homogeneous isotropic turbulence. Combining our results with those of the inertial range, we give another view of extended self-similarity (ESS).

Multiphase models for simulating hot and slightly miscible DNAPL (dense non-aqueous phase fluids) in a saturated rock fracture under deformation

In the present study a two dimensional model is first developed to show the behaviour of dense non-aqueous phase liquids (DNAPL) within a rough fracture. To consider the rough fracture, the fracture is imposed with variable apertures along its plane. It is found that DNAPL follows preferential pathways. In next part of the study the above model is further extended for non-isothermal DNAPL flow and DNAPL-water interphase mass transfer phenomenon. These two models are then coupled with joint deformation due to normal stresses. The primary focus of these models is specifically to elucidate the influence of joint alteration due to external stress and fluid pressures on flow driven energy transport and interphase mass transfer. For this, it is assumed that the critical value for joint alteration is associated with external stress and average of water and DNAPL pressures in multiphase system and the temporal and spatial evolution of joint alteration are determined for its further influence on energy transport and miscible phase transfer. The developed model has been studied to show the influence of deformation on DNAPL flow. Further this preliminary study demonstrates the influence of joint deformation on heat transport and phase miscibility via multiphase flow velocities. It is seen that the temperature profile changes and shows higher diffusivity due to deformation and although the interphase miscibility value decreases but the lateral dispersion increases to a considerably higher extent.

Axially homogeneous, zero mean flow buoyancy-driven turbulence in a vertical pipe

We report an experimental study of a new type of turbulent flow that is driven purely by buoyancy. The flow is due to an unstable density difference, created using brine and water, across the ends of a long (length/diameter = 9) vertical pipe. The Schmidt number Sc is 670, and the Rayleigh number (Ra) based on the density gradient and diameter is about 10(8). Under these conditions the convection is turbulent, and the time-averaged velocity at any point is `zero'. The Reynolds number based on the Taylor microscale, Re-lambda, is about 65. The pipe is long enough for there to be an axially homogeneous region, with a linear density gradient, about 6-7 diameters long in the midlength of the pipe. In the absence of a mean flow and, therefore, mean shear, turbulence is sustained just by buoyancy. The flow can be thus considered to be an axially homogeneous turbulent natural convection driven by a constant (unstable) density gradient. We characterize the flow using flow visualization and particle image velocimetry (PIV). Measurements show that the mean velocities and the Reynolds shear stresses are zero across the cross-section; the root mean squared (r.m.s.) of the vertical velocity is larger than those of the lateral velocities (by about one and half times at the pipe axis). We identify some features of the turbulent flow using velocity correlation maps and the probability density functions of velocities and velocity differences. The flow away from the wall, affected mainly by buoyancy, consists of vertically moving fluid masses continually colliding and interacting, while the flow near the wall appears similar to that in wall-bound shear-free turbulence. The turbulence is anisotropic, with the anisotropy increasing to large values as the wall is approached. A mixing length model with the diameter of the pipe as the length scale predicts well the scalings for velocity fluctuations and the flux. This model implies that the Nusselt number would scale as (RaSc1/2)-Sc-1/2, and the Reynolds number would scale as (RaSc-1/2)-Sc-1/2. The velocity and the flux measurements appear to be consistent with the Ra-1/2 scaling, although it must be pointed out that the Rayleigh number range was less than 10. The Schmidt number was not varied to check the Sc scaling. The fluxes and the Reynolds numbers obtained in the present configuration are Much higher compared to what would be obtained in Rayleigh-Benard (R-B) convection for similar density differences.

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

Comparison between computational models of abdominal aortic aneurysm

Objective: To compare the differences in the hemodynamic parameters of abdominal aortic aneurysm (AAA) between fluid-structure interaction model (FSIM) and fluid-only model (FM), so as to discuss their application in the research of AAA. Methods: An idealized AAA model was created based on patient-specific AAA data. In FM, the flow, pressure and wall shear stress (WSS) were computed using finite volume method. In FSIM, an Arbitrary Lagrangian-Eulerian algorithm was used to solve the flow in a continuously deforming geometry. The hemodynamic parameters of both models were obtained for discussion. Results: Under the same inlet velocity, there were only two symmetrical vortexes in the AAA dilation area for FSIM. In contrast, four recirculation areas existed in FM; two were main vortexes and the other two were secondary flow, which were located between the main recirculation area and the arterial wall. Six local pressure concentrations occurred in the distal end of AAA and the recirculation area for FM. However, there were only two local pressure concentrations in FSIM. The vortex center of the recirculation area in FSIM was much more close to the distal end of AAA and the area was much larger because of AAA expansion. Four extreme values of WSS existed at the proximal of AAA, the point of boundary layer separation, the point of flow reattachment and the distal end of AAA, respectively, in both FM and FSIM. The maximum wall stress and the largest wall deformation were both located at the proximal and distal end of AAA. Conclusions: The number and center of the recirculation area for both models are different, while the change of vortex is closely associated with the AAA growth. The largest WSS of FSIM is 36% smaller than that of FM. Both the maximum wall stress and largest wall displacement shall increase with the outlet pressure increasing. FSIM needs to be considered for studying the relationship between AAA growth and shear stress.

Electrochemical phase formation (ECPF): Nucleation growth vis-a-vis adsorption models

The nucleataon growth model of electrochemical phase formation is analysed for the hnear potential sweep input Apart from deducing diagnostic criteria and method~ of estimating model parameters, the predictions of the nucleation growth model are compared and contrasted with those of a sample adsorption model A dastlnCtlOn is made possible between adsorption and phase transition, which seems useful for understanding the nature of ECPF phenomena, especially underpotentlal deposition (UPD).

Comparison of Interproton Distances in DNA Models with Nuclear Overhauser Enhancement Data

The conformational flexibility inherent in the polynucleotide chain plays an important role in deciding its three-dimensonal structure and enables it to undergo structural transitions in order to fulfil all its functions. Following certain stereochemical guidelines, both right and left handed double-helical models have been built in our laboratory and they are in reasonably good agreement with the fibre patterns for various polymorphous forms of DNA. Recently, nuclear magnetic resonance spectroscopy has become an important technique for studying the solution conformation and polymorphism of nucleic acids. Several workers have used 1H nuclear magnetic resonance nuclear Overhauser enhancement measurements to estimate the interproton distances for the various DNA oligomers and compared them with the interproton distances for particular models of A and Β form DNA. In some cases the solution conformation does not seem to fit either of these models. We have been studying various models for DNA with a view to exploring the full conformational space allowed for nucleic acid polymers. In this paper, the interproton distances calculated for the different stereochemically feasible models of DNA are presented and they are compared and correlated against those obtained from 1Η nuclear magnetic resonance nuclear Overhauser enhancement measurements of various nucleic acid oligomers.

Relativistic particle models with separable interactions

We present relativistic, classical particle models that possess Poincaré invariance, invariant world lines, particle interaction, and separability.

Designing innovative business models with a framework that promotes experimentation

Purpose – Business models to date have remained the creation of management, however, it is the belief of the authors that designers should be critically approaching, challenging and creating new business models as part of their practice. This belief portrays a new era where business model constructs become the new design brief of the future and fuel design and innovation to work together at the strategic level of an organisation. Design/methodology/approach – The purpose of this paper is to explore and investigate business model design. The research followed a deductive structured qualitative content analysis approach utilizing a predetermined categorization matrix. The analysis of forty business cases uncovered commonalities of key strategic drivers behind these innovative business models. Findings – Five business model typologies were derived from this content analysis, from which quick prototypes of new business models can be created. Research limitations/implications – Implications from this research suggest there is no “one right” model, but rather through experimentation, the generation of many unique and diverse concepts can result in greater possibilities for future innovation and sustained competitive advantage. Originality/value – This paper builds upon the emerging research and exploration into the importance and relevance of dynamic, design-driven approaches to the creation of innovative business models. These models aim to synthesize knowledge gained from real world examples into a tangible, accessible and provoking framework that provide new prototyping templates to aid the process of business model experimentation.

Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy

The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R2=99.9% and R2=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment.

Generalised growth models for aquatic species with an application to blacklip abalone (Haliotis rubra)

This paper presents a maximum likelihood method for estimating growth parameters for an aquatic species that incorporates growth covariates, and takes into consideration multiple tag-recapture data. Individual variability in asymptotic length, age-at-tagging, and measurement error are also considered in the model structure. Using distribution theory, the log-likelihood function is derived under a generalised framework for the von Bertalanffy and Gompertz growth models. Due to the generality of the derivation, covariate effects can be included for both models with seasonality and tagging effects investigated. Method robustness is established via comparison with the Fabens, improved Fabens, James and a non-linear mixed-effects growth models, with the maximum likelihood method performing the best. The method is illustrated further with an application to blacklip abalone (Haliotis rubra) for which a strong growth-retarding tagging effect that persisted for several months was detected