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.

Losing their marbles : syntax-free programming for assessing problem-solving skills

Novice programmers have difficulty developing an algorithmic solution while simultaneously obeying the syntactic constraints of the target programming language. To see how students fare in algorithmic problem solving when not burdened by syntax, we conducted an experiment in which a large class of beginning programmers were required to write a solution to a computational problem in structured English, as if instructing a child, without reference to program code at all. The students produced an unexpectedly wide range of correct, and attempted, solutions, some of which had not occurred to their teachers. We also found that many common programming errors were evident in the natural language algorithms, including failure to ensure loop termination, hardwiring of solutions, failure to properly initialise the computation, and use of unnecessary temporary variables, suggesting that these mistakes are caused by inexperience at thinking algorithmically, rather than difficulties in expressing solutions as program code.

Further evidence of a relationship between explaining, tracing and writing skills in introductory programming

This paper reports on a replication of earlier studies into a possible hierarchy of programming skills. In this study, the students from whom data was collected were at a university that had not provided data for earlier studies. Also, the students were taught the programming language Python, which had not been used in earlier studies. Thus this study serves as a test of whether the findings in the earlier studies were specific to certain institutions, student cohorts, and programming languages. Also, we used a non–parametric approach to the analysis, rather than the linear approach of earlier studies. Our results are consistent with the earlier studies. We found that students who cannot trace code usually cannot explain code, and also that students who tend to perform reasonably well at code writing tasks have also usually acquired the ability to both trace code and explain code.

Ownerships for reasoning about parallelism : type system and semantics

Technical Report to accompany Ownership for Reasoning About Parallelism. Documents type system which captures effects and the operational semantics for the language which is presented as part of the paper.

Seeing is understanding : the effect of visualisation in understanding programming concepts

How and why visualisations support learning was the subject of this qualitative instrumental collective case study. Five computer programming languages (PHP, Visual Basic, Alice, GameMaker, and RoboLab) supporting differing degrees of visualisation were used as cases to explore the effectiveness of software visualisation to develop fundamental computer programming concepts (sequence, iteration, selection, and modularity). Cognitive theories of visual and auditory processing, cognitive load, and mental models provided a framework in which student cognitive development was tracked and measured by thirty-one 15-17 year old students drawn from a Queensland metropolitan secondary private girls’ school, as active participants in the research. Seventeen findings in three sections increase our understanding of the effects of visualisation on the learning process. The study extended the use of mental model theory to track the learning process, and demonstrated application of student research based metacognitive analysis on individual and peer cognitive development as a means to support research and as an approach to teaching. The findings also forward an explanation for failures in previous software visualisation studies, in particular the study has demonstrated that for the cases examined, where complex concepts are being developed, the mixing of auditory (or text) and visual elements can result in excessive cognitive load and impede learning. This finding provides a framework for selecting the most appropriate instructional programming language based on the cognitive complexity of the concepts under study.

Engaging students in programming

Poor student engagement and high failure rates in first year units were addressed at the Queensland University of Technology (QUT) with a course restructure involving a fresh approach to introducing programming. Students’ first taste of programming in the new course focused less on the language and syntax, and more on problem solving and design, and the role of programming in relation to other technologies they are likely to encounter in their studies. In effect, several technologies that have historically been compartmentalised and taught in isolation have been brought together as a breadth-first introduction to IT. Incorporating databases and Web development technologies into what used to be a purely programming unit gave students a very short introduction to each technology, with programming acting as the glue between each of them. As a result, students not only had a clearer understanding of the application of programming in the real world, but were able to determine their preference or otherwise for each of the technologies introduced, which will help them when the time comes for choosing a course major. Students engaged well in an intensely collaborative learning environment for this unit which was designed to both support the needs of students and meet industry expectations. Attrition from the unit was low, with computer laboratory practical attendance rates for the first time remaining high throughout semester, and the failure rate falling to a single figure percentage.