User-centered, research-based design of futuristic intensive care units

Towards the Knowledge-based Design of Universal Influenza Epitope Ensemble Vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highlyconserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes.

Reconciling Function- and Affordance-Based Design

Traditional engineering design methods are based on Simon's (1969) use of the concept function, and as such collectively suffer from both theoretical and practical shortcomings. Researchers in the field of affordance-based design have borrowed from ecological psychology in an attempt to address the blind spots of function-based design, developing alternative ontologies and design processes. This dissertation presents function and affordance theory as both compatible and complimentary. We first present a hybrid approach to design for technology change, followed by a reconciliation and integration of function and affordance ontologies for use in design. We explore the integration of a standard function-based design method with an affordance-based design method, and demonstrate how affordance theory can guide the early application of function-based design. Finally, we discuss the practical and philosophical ramifications of embracing affordance theory's roots in ecology and ecological psychology, and explore the insights and opportunities made possible by an ecological approach to engineering design. The primary contribution of this research is the development of an integrated ontology for describing and designing technological systems using both function- and affordance-based methods.

A hardware-based multi-disciplinary design optimization method for aeronautical applications

There are many applications in aeronautics where there exist strong couplings between disciplines. One practical example is within the context of Unmanned Aerial Vehicle(UAV) automation where there exists strong coupling between operation constraints, aerodynamics, vehicle dynamics, mission and path planning. UAV path planning can be done either online or offline. The current state of path planning optimisation online UAVs with high performance computation is not at the same level as its ground-based offline optimizer's counterpart, this is mainly due to the volume, power and weight limitations on the UAV; some small UAVs do not have the computational power needed for some optimisation and path planning task. In this paper, we describe an optimisation method which can be applied to Multi-disciplinary Design Optimisation problems and UAV path planning problems. Hardware-based design optimisation techniques are used. The power and physical limitations of UAV, which may not be a problem in PC-based solutions, can be approached by utilizing a Field Programmable Gate Array (FPGA) as an algorithm accelerator. The inevitable latency produced by the iterative process of an Evolutionary Algorithm (EA) is concealed by exploiting the parallelism component within the dataflow paradigm of the EA on an FPGA architecture. Results compare software PC-based solutions and the hardware-based solutions for benchmark mathematical problems as well as a simple real world engineering problem. Results also indicate the practicality of the method which can be used for more complex single and multi objective coupled problems in aeronautical applications.

Paper-based mixed reality sketch augmentation as a conceptual design support tool

This undergraduate student paper explores usage of mixed reality techniques as support tools for conceptual design. A proof-of-concept was developed to illustrate this principle. Using this as an example, a small group of designers was interviewed to determine their views on the use of this technology. These interviews are the main contribution of this paper. Several interesting applications were determined, suggesting possible usage in a wide range of domains. Paper-based sketching, mixed reality and sketch augmentation techniques complement each other, and the combination results in a highly intuitive interface.

Design of laterally loaded piles in clays based on cone penetration test data: a reliability-based approach

The behaviour of laterally loaded piles is considerably influenced by the uncertainties in soil properties. Hence probabilistic models for assessment of allowable lateral load are necessary. Cone penetration test (CPT) data are often used to determine soil strength parameters, whereby the allowable lateral load of the pile is computed. In the present study, the maximum lateral displacement and moment of the pile are obtained based on the coefficient of subgrade reaction approach, considering the nonlinear soil behaviour in undrained clay. The coefficient of subgrade reaction is related to the undrained shear strength of soil, which can be obtained from CPT data. The soil medium is modelled as a one-dimensional random field along the depth, and it is described by the standard deviation and scale of fluctuation of the undrained shear strength of soil. Inherent soil variability, measurement uncertainty and transformation uncertainty are taken into consideration. The statistics of maximum lateral deflection and moment are obtained using the first-order, second-moment technique. Hasofer-Lind reliability indices for component and system failure criteria, based on the allowable lateral displacement and moment capacity of the pile section, are evaluated. The geotechnical database from the Konaseema site in India is used as a case example. It is shown that the reliability-based design approach for pile foundations, considering the spatial variability of soil, permits a rational choice of allowable lateral loads.

Optimum Design of Bridge Abutments under Seismic Conditions: Reliability-Based Approach

The paper focuses on the reliability-based design optimization of gravity wall bridge abutments when subjected to active condition during earthquakes. An analytical study considering the effect of uncertainties in the seismic analysis of bridge abutments is presented. Planar failure surface has been considered in conjunction with the pseudostatic limit equilibrium method for the calculation of the seismic active earth pressure. Analysis is conducted to evaluate the external stability of bridge abutments when subjected to earthquake loads. Reliability analysis is used to estimate the probability of failure in three modes of failure viz. sliding failure of the wall on its base, overturning failure about its toe (or eccentricity failure of the resultant force) and bearing failure of foundation soil below the base of wall. The properties of backfill and foundation soil below the base of abutment are treated as random variables. In addition, the uncertainties associated with characteristics of earthquake ground motions such as horizontal seismic acceleration and shear wave velocity propagating through backfill soil are considered. The optimum proportions of the abutment needed to maintain the stability are obtained against three modes of failure by targeting various component and system reliability indices. Studies have also been made to study the influence of various parameters on the seismic stability.

A novel modeling approach for design studies of brushless doubly fed induction generator based on magnetic equivalent circuit

Brushless doubly fed induction generator (BDFIG) has substantial benefits, which make it an attractive alternative as a wind turbine generator. However, it suffers from lower efficiency and larger dimensions in comparison to DFIG. Hence, optimizing the BDFIG structure is necessary for enhancing its situation commercially. In previous studies, a simple model has been used in BDFIG design procedure that is insufficiently accurate. Furthermore, magnetic saturation and iron loss are not considered because of difficulties in determination of flux density distributions. The aim of this paper is to establish an accurate yet computationally fast model suitable for BDFIG design studies. The proposed approach combines three equivalent circuits including electric, magnetic and thermal models. Utilizing electric equivalent circuit makes it possible to apply static form of magnetic equivalent circuit, because the elapsed time to reach steady-state results in the dynamic form is too long for using in population-based design studies. The operating characteristics, which are necessary for evaluating the objective function and constraints values of the optimization problem, can be calculated using the presented approach considering iron loss, saturation, and geometrical details. The simulation results of a D-180 prototype BDFIG are compared with measured data in order to validate the developed model. © 1986-2012 IEEE.

An approach for reliability-based robust design optimisation of angle-ply composites

Variations of manufacturing process parameters and environmental aspects may affect the quality and performance of composite materials, which consequently affects their structural behaviour. Reliability-based design optimisation (RBDO) and robust design optimisation (RDO) searches for safe structural systems with minimal variability of response when subjected to uncertainties in material design parameters. An approach that simultaneously considers reliability and robustness is proposed in this paper. Depending on a given reliability index imposed on composite structures, a trade-off is established between the performance targets and robustness. Robustness is expressed in terms of the coefficient of variation of the constrained structural response weighted by its nominal value. The Pareto normed front is built and the nearest point to the origin is estimated as the best solution of the bi-objective optimisation problem.

PRACTICAL LAND GRADING BASED ON LEAST SQUARES.

Practical methods for land grading design of a plane surface for rectangular and irregularly shaped fields based on a least squares analysis are presented. The least squares procedure leads to a system of three linear equations with three unknowns for determination of the best-fit plane. The equations can be solved by determinants (Cramer's rule) using a procedure capable of solution by many programmable calculators. The detailed computational process for determining the equation of the plane and a simple method to find the centroid location of an irregular field are also given. An illustrative example and design instructions are included to demonstrate the application of the design procedure.

Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay

The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit telomerase activity. We used a fluorescence assay to identify molecules that stabilize G-quadruplexes. Intramolecular folding of an oligonucleotide with four repeats of the human telomeric sequence into a G-quadruplex structure led to fluorescence excitation energy transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5′ and 3′ ends of the oligonucleotide, respectively. The melting of the G-quadruplex was monitored in the presence of putative G-quadruplex-binding molecules by measuring the fluorescence emission of the donor. A series of compounds (pentacyclic crescent-shaped dibenzophenanthroline derivatives) was shown to increase the melting temperature of the G-quadruplex by 2–20°C at 1 μM dye concentration. This increase in Tm value was well correlated with an increase in the efficiency of telomerase inhibition in vitro. The best telomerase inhibitor showed an IC50 value of 28 nM in a standard telomerase repeat amplification protocol assay. Fluorescence energy transfer can thus be used to reveal the formation of four-stranded DNA structures, and its stabilization by quadruplex-binding agents, in an effort to discover new potent telomerase inhibitors.

Abstraction versus case based:A comparative study of two approaches to support Parametric Design

We describe an experimental study testing the reuse of design knowledge as a method to support learning and use of parametric design in architecture.The use of parametric design systems and programming environments offer architects new opportunities, providing a powerful means to create geometries and allowing dynamic design exploration, but it can also impose substantial challenges.The proposition tested in this study is that the reuse of design knowledge can improve architects’ ability to use parametric modelling, and reduce the barriers to using programming in a design context.The paper explores and compares two approaches as a means of accessing and reusing existing design solutions: the reuse of abstract parametric ‘Design Patterns’ [1]; and secondly the reuse of parametric solutions from specific design cases (Case- Based Design).This paper outlines the principles and methods of ‘abstract’ versus ‘case-based’ approaches to reuse parametric solutions; and focuses on the results of their practical implementation through the statistical analysis of a comparative study involving 126 designers. In conclusion, it is proposed the outcomes from this study can be applied to inform the methodology for introducing parametric design in architecture and design disciplines.

Urban codes : abstraction and case-based approaches to algorithmic design and implications for the design of contemporary cities

This paper reports on a comparative study that evaluates two approaches to support the learning and use of algorithmic design in architecture, and extrapolates from this to consider applications for the algorithmic design of cities. The study explored two methods to reduce the barriers of using programming and potentially improve design performance. The first is the reuse of abstract algorithmic ‘patterns’. The second approach is the reuse of algorithmic solutions from specific design cases (case-based design). Reflecting on this research we outline how our findings discussed in relation to alternate thinking on the use of pattern, might inform a hybrid approach to the algorithmic design of cities.