Insight into High-quality Aerodynamic Design Spaces through Multi-objective Optimization

An approach to support the computational aerodynamic design process is presented and demonstrated through the application of a novel multi-objective variant of the Tabu Search optimization algorithm for continuous problems to the aerodynamic design optimization of turbomachinery blades. The aim is to improve the performance of a specific stage and ultimately of the whole engine. The integrated system developed for this purpose is described. This combines the optimizer with an existing geometry parameterization scheme and a well- established CFD package. The system’s performance is illustrated through case studies – one two-dimensional, one three-dimensional – in which flow characteristics important to the overall performance of turbomachinery blades are optimized. By showing the designer the trade-off surfaces between the competing objectives, this approach provides considerable insight into the design space under consideration and presents the designer with a range of different Pareto-optimal designs for further consideration. Special emphasis is given to the dimensionality in objective function space of the optimization problem, which seeks designs that perform well for a range of flow performance metrics. The resulting compressor blades achieve their high performance by exploiting complicated physical mechanisms successfully identified through the design process. The system can readily be run on parallel computers, substantially reducing wall-clock run times – a significant benefit when tackling computationally demanding design problems. Overall optimal performance is offered by compromise designs on the Pareto trade-off surface revealed through a true multi-objective design optimization test case. Bearing in mind the continuing rapid advances in computing power and the benefits discussed, this approach brings the adoption of such techniques in real-world engineering design practice a ste

Control of epidermal stem cell clusters by Notch-mediated lateral induction☆☆Supplementary data associated with this article can be found at doi:10.1016/S0012-1606(03)00107-6.

AbstractStem cells in the basal layer of human interfollicular epidermis form clusters that can be reconstituted in vitro. In order to supply the interfollicular epidermis with differentiated cells, the size of these clusters must be controlled. Evidence suggests that control is regulated via differentiation of stem cells on the periphery of the clusters. Moreover, there is growing evidence that this regulation is mediated by the Notch signalling pathway. In this paper, we develop theoretical arguments, in conjunction with computer simulations of a model of the basal layer, to show that regulation of differentiation is the most likely mechanism for cluster control. In addition, we show that stem cells must adhere more strongly to each other than they do to differentiated cells. Developing our model further we show that lateral-induction, mediated by the Notch signalling pathway, is a natural mechanism for cluster control. It can not only indicate to cells the size of the cluster they are in and their position within it, but it can also control the cluster size. This can only be achieved by postulating a secondary, cluster wide, differentiation signal, and cells with high Delta expression being deaf to this signal

Enhanced Accessibility for People with Disabilities Living in Urban Areas

[Excerpt] People with disabilities constitute a significant proportion of the poor in developing countries. If internationally agreed targets on reducing poverty are to be reached, it is critical that specific measures be taken to reduce the societal discrimination and isolation that people with disabilities continue to face. Transport is an important enabler of strategies to fight poverty through enhancing access to education, employment, and social services. This project aims to further the understanding of the mobility and access issues experienced by people with disabilities in developing countries, and to identify specific steps that can be taken to start addressing problems. A major objective of the project is to compile a compendium of guidelines that can be used by government authorities, advocacy groups, and donor/loan agencies to improve the access of people with disabilities to transport and other services in urban areas

Topographic determinants of foot and mouth disease transmission in the UK 2001 epidemic

Background A key challenge for modelling infectious disease dynamics is to understand the spatial spread of infection in real landscapes. This ideally requires a parallel record of spatial epidemic spread and a detailed map of susceptible host density along with relevant transport links and geographical features. Results Here we analyse the most detailed such data to date arising from the UK 2001 foot and mouth epidemic. We show that Euclidean distance between infectious and susceptible premises is a better predictor of transmission risk than shortest and quickest routes via road, except where major geographical features intervene. Conclusion Thus, a simple spatial transmission kernel based on Euclidean distance suffices in most regions, probably reflecting the multiplicity of transmission routes during the epidemic

rTMS evidence for a dissociation in short-term memory for spoken words and nonwords

Differing patterns of verbal short-term memory (STM) impairment have provided unique insights into the relationship between STM and broader language function. Lexicality effects (i.e., better recall for words than nonwords) are larger in patients with phonological deficits following left temporoparietal lesions, and smaller in patients with semantic impairment and anterior temporal damage, supporting linguistic accounts of STM. However, interpretation of these patient dissociations are complicated by (i) non-focal damage and (ii) confounding factors and secondary impairments. This study addressed these issues by examining the impact of inhibitory transcranial magnetic stimulation (TMS) on auditory-verbal STM performance in healthy individuals. We compared the effects of TMS to left anterior supramarginal gyrus (SMG) and left anterior middle temporal gyrus (ATL) on STM for lists of nonwords and random words. SMG stimulation disrupted nonword recall, in a pattern analogous to that observed in patients, compatible with a role for this site in processing speech sounds without support from long-term lexical-semantic representations. Stimulation of ATL, a semantic site, disrupted the recall of words but not nonwords. A visual pattern memory task indicated that these effects of TMS were restricted to the verbal domain. These data provide convergent evidence for the conclusions of neuropsychological studies that support linguistic accounts of verbal STM

Explaining Observed Infection and Antibody Age-Profiles in Populations with Urogenital Schistosomiasis

Urogenital schistosomiasis is a tropical disease infecting more than 100 million people in sub-Saharan Africa. Individuals in endemic areas endure repeated infections with long-lived schistosome worms, and also encounter larval and egg stages of the life cycle. Protective immunity against infection develops slowly with age. Distinctive age-related patterns of infection and specific antibody responses are seen in endemic areas, including an infection ‘peak shift’ and a switch in the antibody types produced. Deterministic models describing changing levels of infection and antibody with age in homogeneously exposed populations were developed to identify the key mechanisms underlying the antibody switch, and to test two theories for the slow development of protective immunity: that (i) exposure to dying (long-lived) worms, or (ii) experience of a threshold level of antigen, is necessary to stimulate protective antibody. Different model structures were explored, including alternative stages of the life cycle as the main antigenic source and the principal target of protective antibody, different worm survival distributions, antigen thresholds and immune cross-regulation. Models were identified which could reproduce patterns of infection and antibody consistent with field data. Models with dying worms as the main source of protective antigen could reproduce all of these patterns, but so could some models with other continually-encountered life stages acting as the principal antigen source. An antigen threshold enhanced the ability of the model to replicate these patterns, but was not essential for it to do so. Models including either non-exponential worm survival or cross-regulation were more likely to be able to reproduce field patterns, but neither of these was absolutely required. The combination of life cycle stage stimulating, and targeted by, antibody was found to be critical in determining whether models could successfully reproduce patterns in the data, and a number of combinations were excluded as being inconsistent with field data

Sheep Movement Networks and the Transmission of Infectious Diseases

Background and Methodology: Various approaches have been used to investigate how properties of farm contact networks impact on the transmission of infectious diseases. The potential for transmission of an infection through a contact network can be evaluated in terms of the basic reproduction number, R 0. The magnitude of R 0 is related to the mean contact rate of a host, in this case a farm, and is further influenced by heterogeneities in contact rates of individual hosts. The latter can be evaluated as the second order moments of the contact matrix (variances in contact rates, and co-variance between contacts to and from individual hosts). Here we calculate these quantities for the farms in a country-wide livestock network:.15,000 Scottish sheep farms in each of 4 years from July 2003 to June 2007. The analysis is relevant to endemic and chronic infections with prolonged periods of infectivity of affected animals, and uses different weightings of contacts to address disease scenarios of low, intermediate and high animal-level prevalence. Principal Findings and Conclusions: Analysis of networks of Scottish farms via sheep movements from July 2003 to June 2007 suggests that heterogeneities in movement patterns (variances and covariances of rates of movement on and off the farms) make a substantial contribution to the potential for the transmission of infectious diseases, quantified as R 0, within the farm population. A small percentage of farms (,20%) contribute the bulk of the transmission potential (.80%) and these farms could be efficiently targeted by interventions aimed at reducing spread of diseases via animal movement