Application of Software Engineering Principles to Synthetic Biology and Emerging Regulatory Concerns

As the science of synthetic biology matures, engineers have begun to deliver real-world applications which are the beginning of what could radically transform our lives. Recent progress indicates synthetic biology will produce transformative breakthroughs. Examples include: 1) synthesizing chemicals for medicines which are expensive and difficult to produce; 2) producing protein alternatives; 3) altering genomes to combat deadly diseases; 4) killing antibiotic-resistant pathogens; and 5) speeding up vaccine production. Although synthetic biology promises great benefits, many stakeholders have expressed concerns over safety and security risks from creating biological behavior never seen before in nature. As with any emerging technology, there is the risk of malicious use known as the dual-use problem. The technology is becoming democratized and de-skilled, and people in do-it-yourself communities can tinker with genetic code, similar to how programming has become prevalent through the ease of using macros in spreadsheets. While easy to program, it may be non-trivial to validate novel biological behavior. Nevertheless, we must be able to certify synthetically engineered organisms behave as expected, and be confident they will not harm natural life or the environment. Synthetic biology is an interdisciplinary engineering domain, and interdisciplinary problems require interdisciplinary solutions. Using an interdisciplinary approach, this dissertation lays foundations for verifying, validating, and certifying safety and security of synthetic biology applications through traditional software engineering concepts about safety, security, and reliability of systems. These techniques can help stakeholders navigate what is currently a confusing regulatory process. The contributions of this dissertation are: 1) creation of domain-specific patterns to help synthetic biologists develop assurance cases using evidence and arguments to validate safety and security of designs; 2) application of software product lines and feature models to the modular DNA parts of synthetic biology commonly known as BioBricks, making it easier to find safety features during design; 3) a technique for analyzing DNA sequence motifs to help characterize proteins as toxins or non-toxins; 4) a legal investigation regarding what makes regulating synthetic biology challenging; and 5) a repeatable workflow for leveraging safety and security artifacts to develop assurance cases for synthetic biology systems. Advisers: Myra B. Cohen and Brittany A. Dunca

National Aeronautics and Space Administration (NASA)/American Society for Engineering Education (ASEE) Summer Faculty Fellowship Program: 1996

The objectives of the program, which began nationally in 1964 and at JSC in 1965 are to (1) further the professional knowledge qualified engineering and science faculty members, (2) stimulate an exchange of ideas between participants and NASA, (3) and refresh the research and teaching activities of participants' institutions, and (4) contribute to the research objectives of NASA centers. Each faculty fellow spent at least 10 weeks at JSC engaged in a research project in collaboration with a NASA JSC colleague

Management Aspects of Software Clone Detection and Analysis

Copying a code fragment and reusing it by pasting with or without minor modifications is a common practice in software development for improved productivity. As a result, software systems often have similar segments of code, called software clones or code clones. Due to many reasons, unintentional clones may also appear in the source code without awareness of the developer. Studies report that significant fractions (5% to 50%) of the code in typical software systems are cloned. Although code cloning may increase initial productivity, it may cause fault propagation, inflate the code base and increase maintenance overhead. Thus, it is believed that code clones should be identified and carefully managed. This Ph.D. thesis contributes in clone management with techniques realized into tools and large-scale in-depth analyses of clones to inform clone management in devising effective techniques and strategies. To support proactive clone management, we have developed a clone detector as a plug-in to the Eclipse IDE. For clone detection, we used a hybrid approach that combines the strength of both parser-based and text-based techniques. To capture clones that are similar but not exact duplicates, we adopted a novel approach that applies a suffix-tree-based k-difference hybrid algorithm, borrowed from the area of computational biology. Instead of targeting all clones from the entire code base, our tool aids clone-aware development by allowing focused search for clones of any code fragment of the developer's interest. A good understanding on the code cloning phenomenon is a prerequisite to devise efficient clone management strategies. The second phase of the thesis includes large-scale empirical studies on the characteristics (e.g., proportion, types of similarity, change patterns) of code clones in evolving software systems. Applying statistical techniques, we also made fairly accurate forecast on the proportion of code clones in the future versions of software projects. The outcome of these studies expose useful insights into the characteristics of evolving clones and their management implications. Upon identification of the code clones, their management often necessitates careful refactoring, which is dealt with at the third phase of the thesis. Given a large number of clones, it is difficult to optimally decide what to refactor and what not, especially when there are dependencies among clones and the objective remains the minimization of refactoring efforts and risks while maximizing benefits. In this regard, we developed a novel clone refactoring scheduler that applies a constraint programming approach. We also introduced a novel effort model for the estimation of efforts needed to refactor clones in source code. We evaluated our clone detector, scheduler and effort model through comparative empirical studies and user studies. Finally, based on our experience and in-depth analysis of the present state of the art, we expose avenues for further research and development towards a versatile clone management system that we envision

An Investigation of Factors Influencing Algorithm Selection for High Dimensional Continuous Optimisation Problems

The problem of algorithm selection is of great importance to the optimisation community, with a number of publications present in the Body-of-Knowledge. This importance stems from the consequences of the No-Free-Lunch Theorem which states that there cannot exist a single algorithm capable of solving all possible problems. However, despite this importance, the algorithm selection problem has of yet failed to gain widespread attention . In particular, little to no work in this area has been carried out with a focus on large-scale optimisation; a field quickly gaining momentum in line with advancements and influence of big data processing. As such, it is not as yet clear as to what factors, if any, influence the selection of algorithms for very high-dimensional problems (> 1000) - and it is entirely possible that algorithms that may not work well in lower dimensions may in fact work well in much higher dimensional spaces and vice-versa. This work therefore aims to begin addressing this knowledge gap by investigating some of these influencing factors for some common metaheuristic variants. To this end, typical parameters native to several metaheuristic algorithms are firstly tuned using the state-of-the-art automatic parameter tuner, SMAC. Tuning produces separate parameter configurations of each metaheuristic for each of a set of continuous benchmark functions; specifically, for every algorithm-function pairing, configurations are found for each dimensionality of the function from a geometrically increasing scale (from 2 to 1500 dimensions). The nature of this tuning is therefore highly computationally expensive necessitating the use of SMAC. Using these sets of parameter configurations, a vast amount of performance data relating to the large-scale optimisation of our benchmark suite by each metaheuristic was subsequently generated. From the generated data and its analysis, several behaviours presented by the metaheuristics as applied to large-scale optimisation have been identified and discussed. Further, this thesis provides a concise review of the relevant literature for the consumption of other researchers looking to progress in this area in addition to the large volume of data produced, relevant to the large-scale optimisation of our benchmark suite by the applied set of common metaheuristics. All work presented in this thesis was funded by EPSRC grant: EP/J017515/1 through the DAASE project

Energy efficient hardware acceleration of multimedia processing tools

The world of mobile devices is experiencing an ongoing trend of feature enhancement and generalpurpose multimedia platform convergence. This trend poses many grand challenges, the most pressing being their limited battery life as a consequence of delivering computationally demanding features. The envisaged mobile application features can be considered to be accelerated by a set of underpinning hardware blocks Based on the survey that this thesis presents on modem video compression standards and their associated enabling technologies, it is concluded that tight energy and throughput constraints can still be effectively tackled at algorithmic level in order to design re-usable optimised hardware acceleration cores. To prove these conclusions, the work m this thesis is focused on two of the basic enabling technologies that support mobile video applications, namely the Shape Adaptive Discrete Cosine Transform (SA-DCT) and its inverse, the SA-IDCT. The hardware architectures presented in this work have been designed with energy efficiency in mind. This goal is achieved by employing high level techniques such as redundant computation elimination, parallelism and low switching computation structures. Both architectures compare favourably against the relevant pnor art in the literature. The SA-DCT/IDCT technologies are instances of a more general computation - namely, both are Constant Matrix Multiplication (CMM) operations. Thus, this thesis also proposes an algorithm for the efficient hardware design of any general CMM-based enabling technology. The proposed algorithm leverages the effective solution search capability of genetic programming. A bonus feature of the proposed modelling approach is that it is further amenable to hardware acceleration. Another bonus feature is an early exit mechanism that achieves large search space reductions .Results show an improvement on state of the art algorithms with future potential for even greater savings

Complexity, Emergent Systems and Complex Biological Systems:\ud Complex Systems Theory and Biodynamics. [Edited book by I.C. Baianu, with listed contributors (2011)]

An overview is presented of System dynamics, the study of the behaviour of complex systems, Dynamical system in mathematics Dynamic programming in computer science and control theory, Complex systems biology, Neurodynamics and Psychodynamics.\u

Virtual Reality Games for Motor Rehabilitation

This paper presents a fuzzy logic based method to track user satisfaction without the need for devices to monitor users physiological conditions. User satisfaction is the key to any product’s acceptance; computer applications and video games provide a unique opportunity to provide a tailored environment for each user to better suit their needs. We have implemented a non-adaptive fuzzy logic model of emotion, based on the emotional component of the Fuzzy Logic Adaptive Model of Emotion (FLAME) proposed by El-Nasr, to estimate player emotion in UnrealTournament 2004. In this paper we describe the implementation of this system and present the results of one of several play tests. Our research contradicts the current literature that suggests physiological measurements are needed. We show that it is possible to use a software only method to estimate user emotion

Probabilistic and artificial intelligence modelling of drought and agricultural crop yield in Pakistan

Pakistan is a drought-prone, agricultural nation with hydro-meteorological imbalances that increase the scarcity of water resources, thus, constraining water availability and leading major risks to the agricultural productivity sector and food security. Rainfall and drought are imperative matters of consideration, both for hydrological and agricultural applications. The aim of this doctoral thesis is to advance new knowledge in designing hybridized probabilistic and artificial intelligence forecasts models for rainfall, drought and crop yield within the agricultural hubs in Pakistan. The choice of these study regions is a strategic decision, to focus on precision agriculture given the importance of rainfall and drought events on agricultural crops in socioeconomic activities of Pakistan. The outcomes of this PhD contribute to efficient modelling of seasonal rainfall, drought and crop yield to assist farmers and other stakeholders to promote more strategic decisions for better management of climate risk for agriculturalreliant nations

Using MapReduce Streaming for Distributed Life Simulation on the Cloud

Distributed software simulations are indispensable in the study of large-scale life models but often require the use of technically complex lower-level distributed computing frameworks, such as MPI. We propose to overcome the complexity challenge by applying the emerging MapReduce (MR) model to distributed life simulations and by running such simulations on the cloud. Technically, we design optimized MR streaming algorithms for discrete and continuous versions of Conway’s life according to a general MR streaming pattern. We chose life because it is simple enough as a testbed for MR’s applicability to a-life simulations and general enough to make our results applicable to various lattice-based a-life models. We implement and empirically evaluate our algorithms’ performance on Amazon’s Elastic MR cloud. Our experiments demonstrate that a single MR optimization technique called strip partitioning can reduce the execution time of continuous life simulations by 64%. To the best of our knowledge, we are the first to propose and evaluate MR streaming algorithms for lattice-based simulations. Our algorithms can serve as prototypes in the development of novel MR simulation algorithms for large-scale lattice-based a-life models.https://digitalcommons.chapman.edu/scs_books/1014/thumbnail.jp

The Unbalanced Classification Problem: Detecting Breaches in Security

This research proposes several methods designed to improve solutions for security classification problems. The security classification problem involves unbalanced, high-dimensional, binary classification problems that are prevalent today. The imbalance within this data involves a significant majority of the negative class and a minority positive class. Any system that needs protection from malicious activity, intruders, theft, or other types of breaches in security must address this problem. These breaches in security are considered instances of the positive class. Given numerical data that represent observations or instances which require classification, state of the art machine learning algorithms can be applied. However, the unbalanced and high-dimensional structure of the data must be considered prior to applying these learning methods. High-dimensional data poses a “curse of dimensionality” which can be overcome through the analysis of subspaces. Exploration of intelligent subspace modeling and the fusion of subspace models is proposed. Detailed analysis of the one-class support vector machine, as well as its weaknesses and proposals to overcome these shortcomings are included. A fundamental method for evaluation of the binary classification model is the receiver operating characteristic (ROC) curve and the area under the curve (AUC). This work details the underlying statistics involved with ROC curves, contributing a comprehensive review of ROC curve construction and analysis techniques to include a novel graphic for illustrating the connection between ROC curves and classifier decision values. The major innovations of this work include synergistic classifier fusion through the analysis of ROC curves and rankings, insight into the statistical behavior of the Gaussian kernel, and novel methods for applying machine learning techniques to defend against computer intrusion detection. The primary empirical vehicle for this research is computer intrusion detection data, and both host-based intrusion detection systems (HIDS) and network-based intrusion detection systems (NIDS) are addressed. Empirical studies also include military tactical scenarios