Contributions to Bayesian experimental design

This thesis progresses Bayesian experimental design by developing novel methodologies and extensions to existing algorithms. Through these advancements, this thesis provides solutions to several important and complex experimental design problems, many of which have applications in biology and medicine. This thesis consists of a series of published and submitted papers. In the first paper, we provide a comprehensive literature review on Bayesian design. In the second paper, we discuss methods which may be used to solve design problems in which one is interested in finding a large number of (near) optimal design points. The third paper presents methods for finding fully Bayesian experimental designs for nonlinear mixed effects models, and the fourth paper investigates methods to rapidly approximate the posterior distribution for use in Bayesian utility functions.

Evolutionary optimization and game strategies for advanced multi-disciplinary design : applications to aeronautics and UAV design

Many complex aeronautical design problems can be formulated with efficient multi-objective evolutionary optimization methods and game strategies. This book describes the role of advanced innovative evolution tools in the solution, or the set of solutions of single or multi disciplinary optimization. These tools use the concept of multi-population, asynchronous parallelization and hierarchical topology which allows different models including precise, intermediate and approximate models with each node belonging to the different hierarchical layer handled by a different Evolutionary Algorithm. The efficiency of evolutionary algorithms for both single and multi-objective optimization problems are significantly improved by the coupling of EAs with games and in particular by a new dynamic methodology named “Hybridized Nash-Pareto games”. Multi objective Optimization techniques and robust design problems taking into account uncertainties are introduced and explained in detail. Several applications dealing with civil aircraft and UAV, UCAV systems are implemented numerically and discussed. Applications of increasing optimization complexity are presented as well as two hands-on test cases problems. These examples focus on aeronautical applications and will be useful to the practitioner in the laboratory or in industrial design environments. The evolutionary methods coupled with games presented in this volume can be applied to other areas including surface and marine transport, structures, biomedical engineering, renewable energy and environmental problems.

Stream power criterion and design of sand bed channels at incipient motion

The critical stream power criterion may be used to describe the incipient motion of cohesionless particles of plane sediment beds. The governing equation relating ``critical stream power'' to ``shear Reynolds number'' is developed by using the present experimental data as well as the data from several other sources. Simultaneously, a resistance equation, relating the ``particle Reynolds number'' to the``shear Reynolds number'' is developed for plane sediment beds in wide channels with little or no transport. By making use of these relations, a procedure is developed to design plane sediment beds such that any two of the four design variables, including particle size, energy/friction slope, flow depth, and discharge per unit width in the channel should be known to predict the remaining two variables. Finally, a straightforward design procedure using design tables/design curves and analytical methods is presented to solve six possible design problems.

Investigating novelty-outcome relationships in engineering design

Design creativity involves developing novel and useful solutions to design problems The research in this article is an attempt to understand how novelty of a design resulting from a design process is related to the kind of outcomes. described here as constructs, involved in the design process A model of causality, the SAPPhIRE model, is used as the basis of the analysis The analysis is based on previous research that shows that designing involves development and exploration of the seven basic constructs of the SAPPhIRE model that constitute the causal connection between the various levels of abstraction at which a design can be described The constructs am state change, action, parts. phenomenon. input. organs. and effect The following two questions are asked. Is there a relationship between novelty and the constructs? If them is a relationship, what is the degree of this relationship? A hypothesis is developed to answer the questions an increase in the number and variety of ideas explored while designing should enhance the variety of concept space. leading to an increase in the novelty of the concept space Eight existing observational studies of designing sessions are used to empirically validate the hypothesis Each designing session involves an individual designer. experienced or novice. solving a design problem by producing concepts and following a think-aloud protocol. The results indicate dependence of novelty of concept space on variety of concept space and dependence of variety of concept space on variety of idea space. thereby validating the hypothesis The Jesuits also reveal a strong correlation between novelty and the constructs, correlation value decreases as the abstraction level of the constructs reduces. signifying the importance of using constructs at higher abstraction levels for enhancing novelty

Protein sequence design on the basis of topology optimization techniques -Using continuous modeling of discrete amino acid types

The notion of optimization is inherent in protein design. A long linear chain of twenty types of amino acid residues are known to fold to a 3-D conformation that minimizes the combined inter-residue energy interactions. There are two distinct protein design problems, viz. predicting the folded structure from a given sequence of amino acid monomers (folding problem) and determining a sequence for a given folded structure (inverse folding problem). These two problems have much similarity to engineering structural analysis and structural optimization problems respectively. In the folding problem, a protein chain with a given sequence folds to a conformation, called a native state, which has a unique global minimum energy value when compared to all other unfolded conformations. This involves a search in the conformation space. This is somewhat akin to the principle of minimum potential energy that determines the deformed static equilibrium configuration of an elastic structure of given topology, shape, and size that is subjected to certain boundary conditions. In the inverse-folding problem, one has to design a sequence with some objectives (having a specific feature of the folded structure, docking with another protein, etc.) and constraints (sequence being fixed in some portion, a particular composition of amino acid types, etc.) while obtaining a sequence that would fold to the desired conformation satisfying the criteria of folding. This requires a search in the sequence space. This is similar to structural optimization in the design-variable space wherein a certain feature of structural response is optimized subject to some constraints while satisfying the governing static or dynamic equilibrium equations. Based on this similarity, in this work we apply the topology optimization methods to protein design, discuss modeling issues and present some initial results.

An empirical evaluation of a framework for design for variety and novelty

The objective of this paper is to empirically evaluate a framework for designing – GEMS of SAPPhIRE as req-sol – to check if it supports design for variety and novelty. A set of observational studies is designed where three teams of two designers each, solve three different design problems in the following order: without any support, using the framework, and using a combination of the framework and a catalogue. Results from the studies reveal that both variety and novelty of the concept space increases with the use of the framework or the framework and the catalogue. However, the number of concepts and the time taken by the designers decreases with the use of the framework and, the framework and the catalogue. Based on the results and the interview sessions with the designers, an interactive framework for designing to be supported on a computer is proposed as future work.

Evaluating FuncSION: A software for automated synthesis of design solutions for stimulating ideation during mechanical conceptual design

The goal of the work reported in this paper is to use automated, combinatorial synthesis to generate alternative solutions to be used as stimuli by designers for ideation. FuncSION, a computational synthesis tool that can automatically synthesize solution concepts for mechanical devices by combining building blocks from a library, is used for this purpose. The objectives of FuncSION are to help generate a variety of functional requirements for a given problem and a variety of concepts to fulfill these functions. A distinctive feature of FuncSION is its focus on automated generation of spatial configurations, an aspect rarely addressed by other computational synthesis programs. This paper provides an overview of FuncSION in terms of representation of design problems, representation of building blocks, and rules with which building blocks are combined to generate concepts at three levels of abstraction: topological, spatial, and physical. The paper then provides a detailed account of evaluating FuncSION for its effectiveness in providing stimuli for enhanced ideation.

Application of Qualitative Imaging Methods to Electrical Performance-Aware Package Board Design

Package-board co-design plays a crucial role in determining the performance of high-speed systems. Although there exist several commercial solutions for electromagnetic analysis and verification, lack of Computer Aided Design (CAD) tools for SI aware design and synthesis lead to longer design cycles and non-optimal package-board interconnect geometries. In this work, the functional similarities between package-board design and radio-frequency (RF) imaging are explored. Consequently, qualitative methods common to the imaging community, like Tikhonov Regularization (TR) and Landweber method are applied to solve multi-objective, multi-variable package design problems. In addition, a new hierarchical iterative piecewise linear algorithm is developed as a wrapper over LBP for an efficient solution in the design space.

An empirical understanding of use of internal analogies in conceptual design

Internal analogies are created if the knowledge of source domain is obtained only from the cognition of designers. In this paper, an understanding of the use of internal analogies in conceptual design is developed by studying: the types of internal analogies; the roles of internal analogies; the influence of design problems on the creation of internal analogies; the role of experience of designers on the use of internal analogies; the levels of abstraction at which internal analogies are searched in target domain, identified in source domain, and realized in the target domain; and the effect of internal analogies from the natural and artificial domains on the solution space created using these analogies. To facilitate this understanding, empirical studies of design sessions from earlier research, each involving a designer solving a design problem by identifying requirements and developing conceptual solutions, without using any support, are used. The following are the important findings: designers use analogies from the natural and artificial domains; analogies are used for generating requirements and solutions; the nature of the design problem influences the use of analogies; the role of experience of designers on the use of analogies is not clearly ascertained; analogical transfer is observed only at few levels of abstraction while many levels remain unexplored; and analogies from the natural domain seem to have more positive influence than the artificial domain on the number of ideas and variety of idea space.

Towards the development of an integrated design framework using the Blackboard model

Current research into the process of engineering design is extending the use of computers towards the acquisition, representation and application of design process knowledge in addition to the existing storage and manipulation of product-based models of design objects. This is a difficult task because the design of mechanical systems is a complex, often unpredictable process involving ill-structured problem solving skills and large amounts of knowledge, some which may be of an incomplete and subjective nature. Design problems require the integration of a variety of modes of working such as numerical, graphical, algorithmic or heuristic and demand products through synthesis, analysis and evaluation activities.

This report presents the results of a feasibility study into the blackboard approach and discusses the development of an initial prototype system that will enable an alphanumeric design dialogue between a designer and an expert to be analysed in a formal way, thus providing real-life protocol data on which to base the blackboard message structures.

An approach to functional synthesis of solutions in mechanical conceptual design. Part III: Spatial configuration

These three papers describe an approach to the synthesis of solutions to a class of mechanical design problems; these involve transmission and transformation of mechanical forces and motion, and can be described by a set of inputs and outputs. The approach involves (1) identifying a set of primary functional elements and rules of combining them, and (2) developing appropriate representations and reasoning procedures for synthesising solution concepts using these elements and their combination rules; these synthesis procedures can produce an exhaustive set of solution concepts, in terms of their topological as well as spatial configurations, to a given design problem. This paper (Part III) describes a constraint propagation procedure which, using a knowledge base of spatial information about a set of primary functional elements, can produce possible spatial configurations of solution concepts generated in Part II.

Fertile-free fuels in pressurized water reactors: Design challenges and solutions

This paper investigates the basic feasibility of using reactor-grade Pu in fertile-free fuel (FFF) matrix in pressurized water reactors (PWRs). Several important issues were investigated in this work: the Pu loading required to achieve a specific interrefueling interval, the impact of inert matrix composition on reactivity constrained length of cycle, and the potential of utilizing burnable poisons (BPs) to alleviate degradation of the reactivity control mechanism and temperature coefficients. Although the subject was addressed in the past, no systematic approach for assessment of BP utilization in FFF cores was published. In this work, we examine all commercially available BP materials in all geometrical arrangements currently used by the nuclear industry with regards to their potential to alleviate the problems associated with the use of FFF in PWRs. The recently proposed MgO-ZrO2 solid-state solution fuel matrix, which appears to be very promising in terms of thermal properties and radiation damage resistance, was used as a reference matrix material in this work. The neutronic impact of the relative amounts of MgO and ZrO2 in the matrix were also studied. The analysis was performed with a neutron transport and fuel assembly burnup code BOXER. A modified linear reactivity model was applied to the two-dimensional single fuel assembly results to approximate the full core characteristics. Based on the results of the performed analyses, the Pu-loaded FFF core demonstrated potential feasibility to be used in existing PWRs. Major FFF core design problems may be significantly mitigated through the correct choice of BP design. It was found that a combination of BP materials and geometries may be required to meet all FFF design goals. The use of enriched (in most effective isotope) BPs, such as 167Er and 157Gd, may further improve the BP effectiveness and reduce the fuel cycle length penalty associated with their use.

Parallel coordinates in computational engineering design

Modern Engineering Design involves the deployment of many computational tools. Re- search on challenging real-world design problems is focused on developing improvements for the engineering design process through the integration and application of advanced com- putational search/optimization and analysis tools. Successful application of these methods generates vast quantities of data on potential optimum designs. To gain maximum value from the optimization process, designers need to visualise and interpret this information leading to better understanding of the complex and multimodal relations between param- eters, objectives and decision-making of multiple and strongly conflicting criteria. Initial work by the authors has identified that the Parallel Coordinates interactive visualisation method has considerable potential in this regard. This methodology involves significant levels of user-interaction, making the engineering designer central to the process, rather than the passive recipient of a deluge of pre-formatted information. In the present work we have applied and demonstrated this methodology in two differ- ent aerodynamic turbomachinery design cases; a detailed 3D shape design for compressor blades, and a preliminary mean-line design for the whole compressor core. The first case comprises 26 design parameters for the parameterisation of the blade geometry, and we analysed the data produced from a three-objective optimization study, thus describing a design space with 29 dimensions. The latter case comprises 45 design parameters and two objective functions, hence developing a design space with 47 dimensions. In both cases the dimensionality can be managed quite easily in Parallel Coordinates space, and most importantly, we are able to identify interesting and crucial aspects of the relationships between the design parameters and optimum level of the objective functions under con- sideration. These findings guide the human designer to find answers to questions that could not even be addressed before. In this way, understanding the design leads to more intelligent decision-making and design space exploration. © 2012 AIAA.

Novel Computational Protein Design Algorithms with Applications to Cystic Fibrosis and HIV

Proteins are essential components of cells and are crucial for catalyzing reactions, signaling, recognition, motility, recycling, and structural stability. This diversity of function suggests that nature is only scratching the surface of protein functional space. Protein function is determined by structure, which in turn is determined predominantly by amino acid sequence. Protein design aims to explore protein sequence and conformational space to design novel proteins with new or improved function. The vast number of possible protein sequences makes exploring the space a challenging problem.

Computational structure-based protein design (CSPD) allows for the rational design of proteins. Because of the large search space, CSPD methods must balance search accuracy and modeling simplifications. We have developed algorithms that allow for the accurate and efficient search of protein conformational space. Specifically, we focus on algorithms that maintain provability, account for protein flexibility, and use ensemble-based rankings. We present several novel algorithms for incorporating improved flexibility into CSPD with continuous rotamers. We applied these algorithms to two biomedically important design problems. We designed peptide inhibitors of the cystic fibrosis agonist CAL that were able to restore function of the vital cystic fibrosis protein CFTR. We also designed improved HIV antibodies and nanobodies to combat HIV infections.

Design for reliability for wafer level system in package

This paper discusses the Design for Reliability modelling of several System-in-Package (SiP) structures developed by NXP and advanced on the basis of Wafer Level Packaging (WLP). Two different types of Wafer Level SiP (WLSiP) are presented and discussed. The main focus is on the modelling approach that has been adopted to investigate and analyse the board level reliability of the presented SiP configurations. Thermo-mechanical non-linear Finite Element Analysis (FEA) is used to analyse the effect of various package design parameters on the reliability of the structures and to identify design trends towards package optimisation. FEA is used also to gain knowledge on moulded wafer shrinkage and related issues during the wafer level fabrication. The paper provides a brief outline and demonstration of a design methodology for reliability driven design optimisation of SiP. The study emphasises the advantages of applying the methodology to address complex design problems where several requirements may exist and uncertainties and interactions between parameters in the design are common.