Programming Molecular Devices using Nucleic Acid Hairpins

Nucleic Acid hairpins have been a subject of study for the last four decades. They are composed of single strand that is

hybridized to itself, and the central section forming an unhybridized loop. In nature, they stabilize single stranded RNA, serve as nucleation

sites for RNA folding, protein recognition signals, mRNA localization and regulation of mRNA degradation. On the other hand,

DNA hairpins in biological contexts have been studied with respect to forming cruciform structures that can regulate gene expression.

The use of DNA hairpins as fuel for synthetic molecular devices, including locomotion, was proposed and experimental demonstrated in 2003. They

were interesting because they bring to the table an on-demand energy/information supply mechanism.

The energy/information is hidden (from hybridization) in the hairpin’s loop, until required.

The energy/information is harnessed by opening the stem region, and exposing the single stranded loop section.

The loop region is now free for possible hybridization and help move the system into a thermodynamically favourable state.

The hidden energy and information coupled with

programmability provides another functionality, of selectively choosing what reactions to hide and

what reactions to allow to proceed, that helps develop a topological sequence of events.

Hairpins have been utilized as a source of fuel for many different DNA devices. In this thesis, we program four different

molecular devices using DNA hairpins, and experimentally validate them in the

laboratory. 1) The first device: A

novel enzyme-free autocatalytic self-replicating system composed entirely of DNA that operates isothermally. 2) The second

device: Time-Responsive Circuits using DNA have two properties: a) asynchronous: the final output is always correct

regardless of differences in the arrival time of different inputs.

b) renewable circuits which can be used multiple times without major degradation of the gate motifs

(so if the inputs change over time, the DNA-based circuit can re-compute the output correctly based on the new inputs).

3) The third device: Activatable tiles are a theoretical extension to the Tile assembly model that enhances

its robustness by protecting the sticky sides of tiles until a tile is partially incorporated into a growing assembly.

4) The fourth device: Controlled Amplification of DNA catalytic system: a device such that the amplification

of the system does not run uncontrollably until the system runs out of fuel, but instead achieves a finite

amount of gain.

Nucleic acid circuits with the ability

to perform complex logic operations have many potential practical applications, for example the ability to achieve point of care diagnostics.

We discuss the designs of our DNA Hairpin molecular devices, the results we have obtained, and the challenges we have overcome

to make these truly functional.

A green perspective on Structured parallel programming

Structured parallel programming, and in particular programming models using the algorithmic skeleton or parallel design pattern concepts, are increasingly considered to be the only viable means of supporting effective development of scalable and efficient parallel programs. Structured parallel programming models have been assessed in a number of works in the context of performance. In this paper we consider how the use of structured parallel programming models allows knowledge of the parallel patterns present to be harnessed to address both performance and energy consumption. We consider different features of structured parallel programming that may be leveraged to impact the performance/energy trade-off and we discuss a preliminary set of experiments validating our claims.

Automatically Evolving Rotation-invariant Texture Image Descriptors by Genetic Programming

In computer vision, training a model that performs classification effectively is highly dependent on the extracted features, and the number of training instances. Conventionally, feature detection and extraction are performed by a domain-expert who, in many cases, is expensive to employ and hard to find. Therefore, image descriptors have emerged to automate these tasks. However, designing an image descriptor still requires domain-expert intervention. Moreover, the majority of machine learning algorithms require a large number of training examples to perform well. However, labelled data is not always available or easy to acquire, and dealing with a large dataset can dramatically slow down the training process. In this paper, we propose a novel Genetic Programming based method that automatically synthesises a descriptor using only two training instances per class. The proposed method combines arithmetic operators to evolve a model that takes an image and generates a feature vector. The performance of the proposed method is assessed using six datasets for texture classification with different degrees of rotation, and is compared with seven domain-expert designed descriptors. The results show that the proposed method is robust to rotation, and has significantly outperformed, or achieved a comparable performance to, the baseline methods.

From Kandinsky to Java (The Use of 20th Century Abstract Art in Learning Programming)

At the University of Worcester we are continually striving to find new approaches to the learning and teaching of programming, to improve the quality of learning and the student experience. Over the past three years we have used the contexts of robotics, computer games, and most recently a study of Abstract Art to this end. This paper discusses our motivation for using Abstract Art as a context, details our principles and methodology, and reports on an evaluation of the student experience. Our basic tenet is that one can view the works of artists such as Kandinsky, Klee and Malevich as Object-Oriented (OO) constructions. Discussion of these works can therefore be used to introduce OO principles, to explore the meaning of classes, methods and attributes and finally to synthesize new works of art through Java code. This research has been conducted during delivery of an “Advanced OOP (Java)” programming module at final-year Undergraduate level, and during a Masters’ OO-Programming (Java) module. This allows a comparative evaluation of novice and experienced programmers’ learning. In this paper, we identify several instructional factors which emerge from our approach, and reflect upon the associated pedagogy. A Catalogue of ArtApplets is provided at the associated web-site.

Student attitudes to plagiarism and collusion within computer science

There is a widespread perception among staff in Computer Science that plagiarism is a major problem particularly in the form of collusion in programming exercises. While departments often make use of electronic detection measures, the time consumed prosecuting plagiarism offences remains a problem. As a result departments continue to seek ways to reduce the amount of plagiarism and collusion that occurs. This paper reports the findings of a questionnaire based study which attempted to assess the students' attitudes to the issues involved in the hope that such an understanding might result in practical measures for minimizing the problem. The study revealed that while students did understand the definition of plagiarism in its most extreme cases they were often confused about less clear-cut situations. Changes in the previous experience of incoming students meeting modules originally designed on the assumption that students already had some programming background and were equipped for self-directed study would also appear to be a contributory factor in the extent of collusion in programming exercises.

GPRM: a high performance programming framework for manycore processors

Processors with large numbers of cores are becoming commonplace. In order to utilise the available resources in such systems, the programming paradigm has to move towards increased parallelism. However, increased parallelism does not necessarily lead to better performance. Parallel programming models have to provide not only flexible ways of defining parallel tasks, but also efficient methods to manage the created tasks. Moreover, in a general-purpose system, applications residing in the system compete for the shared resources. Thread and task scheduling in such a multiprogrammed multithreaded environment is a significant challenge. In this thesis, we introduce a new task-based parallel reduction model, called the Glasgow Parallel Reduction Machine (GPRM). Our main objective is to provide high performance while maintaining ease of programming. GPRM supports native parallelism; it provides a modular way of expressing parallel tasks and the communication patterns between them. Compiling a GPRM program results in an Intermediate Representation (IR) containing useful information about tasks, their dependencies, as well as the initial mapping information. This compile-time information helps reduce the overhead of runtime task scheduling and is key to high performance. Generally speaking, the granularity and the number of tasks are major factors in achieving high performance. These factors are even more important in the case of GPRM, as it is highly dependent on tasks, rather than threads. We use three basic benchmarks to provide a detailed comparison of GPRM with Intel OpenMP, Cilk Plus, and Threading Building Blocks (TBB) on the Intel Xeon Phi, and with GNU OpenMP on the Tilera TILEPro64. GPRM shows superior performance in almost all cases, only by controlling the number of tasks. GPRM also provides a low-overhead mechanism, called “Global Sharing”, which improves performance in multiprogramming situations. We use OpenMP, as the most popular model for shared-memory parallel programming as the main GPRM competitor for solving three well-known problems on both platforms: LU factorisation of Sparse Matrices, Image Convolution, and Linked List Processing. We focus on proposing solutions that best fit into the GPRM’s model of execution. GPRM outperforms OpenMP in all cases on the TILEPro64. On the Xeon Phi, our solution for the LU Factorisation results in notable performance improvement for sparse matrices with large numbers of small blocks. We investigate the overhead of GPRM’s task creation and distribution for very short computations using the Image Convolution benchmark. We show that this overhead can be mitigated by combining smaller tasks into larger ones. As a result, GPRM can outperform OpenMP for convolving large 2D matrices on the Xeon Phi. Finally, we demonstrate that our parallel worksharing construct provides an efficient solution for Linked List processing and performs better than OpenMP implementations on the Xeon Phi. The results are very promising, as they verify that our parallel programming framework for manycore processors is flexible and scalable, and can provide high performance without sacrificing productivity.

Language-based Techniques for Practical and Trustworthy Secure Multi-party Computations

Secure Multi-party Computation (MPC) enables a set of parties to collaboratively compute, using cryptographic protocols, a function over their private data in a way that the participants do not see each other's data, they only see the final output. Typical MPC examples include statistical computations over joint private data, private set intersection, and auctions. While these applications are examples of monolithic MPC, richer MPC applications move between "normal" (i.e., per-party local) and "secure" (i.e., joint, multi-party secure) modes repeatedly, resulting overall in mixed-mode computations. For example, we might use MPC to implement the role of the dealer in a game of mental poker -- the game will be divided into rounds of local decision-making (e.g. bidding) and joint interaction (e.g. dealing). Mixed-mode computations are also used to improve performance over monolithic secure computations. Starting with the Fairplay project, several MPC frameworks have been proposed in the last decade to help programmers write MPC applications in a high-level language, while the toolchain manages the low-level details. However, these frameworks are either not expressive enough to allow writing mixed-mode applications or lack formal specification, and reasoning capabilities, thereby diminishing the parties' trust in such tools, and the programs written using them. Furthermore, none of the frameworks provides a verified toolchain to run the MPC programs, leaving the potential of security holes that can compromise the privacy of parties' data. This dissertation presents language-based techniques to make MPC more practical and trustworthy. First, it presents the design and implementation of a new MPC Domain Specific Language, called Wysteria, for writing rich mixed-mode MPC applications. Wysteria provides several benefits over previous languages, including a conceptual single thread of control, generic support for more than two parties, high-level abstractions for secret shares, and a fully formalized type system and operational semantics. Using Wysteria, we have implemented several MPC applications, including, for the first time, a card dealing application. The dissertation next presents Wys*, an embedding of Wysteria in F*, a full-featured verification oriented programming language. Wys* improves on Wysteria along three lines: (a) It enables programmers to formally verify the correctness and security properties of their programs. As far as we know, Wys* is the first language to provide verification capabilities for MPC programs. (b) It provides a partially verified toolchain to run MPC programs, and finally (c) It enables the MPC programs to use, with no extra effort, standard language constructs from the host language F*, thereby making it more usable and scalable. Finally, the dissertation develops static analyses that help optimize monolithic MPC programs into mixed-mode MPC programs, while providing similar privacy guarantees as the monolithic versions.

Mathematical Programming Models for Influence Maximization on Social Networks

In this dissertation, we apply mathematical programming techniques (i.e., integer programming and polyhedral combinatorics) to develop exact approaches for influence maximization on social networks. We study four combinatorial optimization problems that deal with maximizing influence at minimum cost over a social network. To our knowl- edge, all previous work to date involving influence maximization problems has focused on heuristics and approximation. We start with the following viral marketing problem that has attracted a significant amount of interest from the computer science literature. Given a social network, find a target set of customers to seed with a product. Then, a cascade will be caused by these initial adopters and other people start to adopt this product due to the influence they re- ceive from earlier adopters. The idea is to find the minimum cost that results in the entire network adopting the product. We first study a problem called the Weighted Target Set Selection (WTSS) Prob- lem. In the WTSS problem, the diffusion can take place over as many time periods as needed and a free product is given out to the individuals in the target set. Restricting the number of time periods that the diffusion takes place over to be one, we obtain a problem called the Positive Influence Dominating Set (PIDS) problem. Next, incorporating partial incentives, we consider a problem called the Least Cost Influence Problem (LCIP). The fourth problem studied is the One Time Period Least Cost Influence Problem (1TPLCIP) which is identical to the LCIP except that we restrict the number of time periods that the diffusion takes place over to be one. We apply a common research paradigm to each of these four problems. First, we work on special graphs: trees and cycles. Based on the insights we obtain from special graphs, we develop efficient methods for general graphs. On trees, first, we propose a polynomial time algorithm. More importantly, we present a tight and compact extended formulation. We also project the extended formulation onto the space of the natural vari- ables that gives the polytope on trees. Next, building upon the result for trees---we derive the polytope on cycles for the WTSS problem; as well as a polynomial time algorithm on cycles. This leads to our contribution on general graphs. For the WTSS problem and the LCIP, using the observation that the influence propagation network must be a directed acyclic graph (DAG), the strong formulation for trees can be embedded into a formulation on general graphs. We use this to design and implement a branch-and-cut approach for the WTSS problem and the LCIP. In our computational study, we are able to obtain high quality solutions for random graph instances with up to 10,000 nodes and 20,000 edges (40,000 arcs) within a reasonable amount of time.

Integer Linear Programming for Sequence Problems: A general approach to reduce the problem size

Sequence problems belong to the most challenging interdisciplinary topics of the actuality. They are ubiquitous in science and daily life and occur, for example, in form of DNA sequences encoding all information of an organism, as a text (natural or formal) or in form of a computer program. Therefore, sequence problems occur in many variations in computational biology (drug development), coding theory, data compression, quantitative and computational linguistics (e.g. machine translation). In recent years appeared some proposals to formulate sequence problems like the closest string problem (CSP) and the farthest string problem (FSP) as an Integer Linear Programming Problem (ILPP). In the present talk we present a general novel approach to reduce the size of the ILPP by grouping isomorphous columns of the string matrix together. The approach is of practical use, since the solution of sequence problems is very time consuming, in particular when the sequences are long.

Constraint Programming-based Job Dispatching for Modern HPC Applications

A High-Performance Computing job dispatcher is a critical software that assigns the finite computing resources to submitted jobs. This resource assignment over time is known as the on-line job dispatching problem in HPC systems. The fact the problem is on-line means that solutions must be computed in real-time, and their required time cannot exceed some threshold to do not affect the normal system functioning. In addition, a job dispatcher must deal with a lot of uncertainty: submission times, the number of requested resources, and duration of jobs. Heuristic-based techniques have been broadly used in HPC systems, at the cost of achieving (sub-)optimal solutions in a short time. However, the scheduling and resource allocation components are separated, thus generates a decoupled decision that may cause a performance loss. Optimization-based techniques are less used for this problem, although they can significantly improve the performance of HPC systems at the expense of higher computation time. Nowadays, HPC systems are being used for modern applications, such as big data analytics and predictive model building, that employ, in general, many short jobs. However, this information is unknown at dispatching time, and job dispatchers need to process large numbers of them quickly while ensuring high Quality-of-Service (QoS) levels. Constraint Programming (CP) has been shown to be an effective approach to tackle job dispatching problems. However, state-of-the-art CP-based job dispatchers are unable to satisfy the challenges of on-line dispatching, such as generate dispatching decisions in a brief period and integrate current and past information of the housing system. Given the previous reasons, we propose CP-based dispatchers that are more suitable for HPC systems running modern applications, generating on-line dispatching decisions in a proper time and are able to make effective use of job duration predictions to improve QoS levels, especially for workloads dominated by short jobs.

Architecture for machining process and production monitoring based in open computer numerical control

This paper proposes an architecture for machining process and production monitoring to be applied in machine tools with open Computer numerical control (CNC). A brief description of the advantages of using open CNC for machining process and production monitoring is presented with an emphasis on the CNC architecture using a personal computer (PC)-based human-machine interface. The proposed architecture uses the CNC data and sensors to gather information about the machining process and production. It allows the development of different levels of monitoring systems with mininium investment, minimum need for sensor installation, and low intrusiveness to the process. Successful examples of the utilization of this architecture in a laboratory environment are briefly described. As a Conclusion, it is shown that a wide range of monitoring solutions can be implemented in production processes using the proposed architecture.

Dynamical models for computer viruses propagation

Nowadays, digital computer systems and networks are the main engineering tools, being used in planning, design, operation, and control of all sizes of building, transportation, machinery, business, and life maintaining devices. Consequently, computer viruses became one of the most important sources of uncertainty, contributing to decrease the reliability of vital activities. A lot of antivirus programs have been developed, but they are limited to detecting and removing infections, based on previous knowledge of the virus code. In spite of having good adaptation capability, these programs work just as vaccines against diseases and are not able to prevent new infections based on the network state. Here, a trial on modeling computer viruses propagation dynamics relates it to other notable events occurring in the network permitting to establish preventive policies in the network management. Data from three different viruses are collected in the Internet and two different identification techniques, autoregressive and Fourier analyses, are applied showing that it is possible to forecast the dynamics of a new virus propagation by using the data collected from other viruses that formerly infected the network. Copyright (c) 2008 J. R. C. Piqueira and F. B. Cesar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.