Programming chemical kinetics: engineering dynamic reaction networks with DNA strand displacement

Over the last century, the silicon revolution has enabled us to build faster, smaller and more sophisticated computers. Today, these computers control phones, cars, satellites, assembly lines, and other electromechanical devices. Just as electrical wiring controls electromechanical devices, living organisms employ "chemical wiring" to make decisions about their environment and control physical processes. Currently, the big difference between these two substrates is that while we have the abstractions, design principles, verification and fabrication techniques in place for programming with silicon, we have no comparable understanding or expertise for programming chemistry.

In this thesis we take a small step towards the goal of learning how to systematically engineer prescribed non-equilibrium dynamical behaviors in chemical systems. We use the formalism of chemical reaction networks (CRNs), combined with mass-action kinetics, as our programming language for specifying dynamical behaviors. Leveraging the tools of nucleic acid nanotechnology (introduced in Chapter 1), we employ synthetic DNA molecules as our molecular architecture and toehold-mediated DNA strand displacement as our reaction primitive.

Abstraction, modular design and systematic fabrication can work only with well-understood and quantitatively characterized tools. Therefore, we embark on a detailed study of the "device physics" of DNA strand displacement (Chapter 2). We present a unified view of strand displacement biophysics and kinetics by studying the process at multiple levels of detail, using an intuitive model of a random walk on a 1-dimensional energy landscape, a secondary structure kinetics model with single base-pair steps, and a coarse-grained molecular model that incorporates three-dimensional geometric and steric effects. Further, we experimentally investigate the thermodynamics of three-way branch migration. Our findings are consistent with previously measured or inferred rates for hybridization, fraying, and branch migration, and provide a biophysical explanation of strand displacement kinetics. Our work paves the way for accurate modeling of strand displacement cascades, which would facilitate the simulation and construction of more complex molecular systems.

In Chapters 3 and 4, we identify and overcome the crucial experimental challenges involved in using our general DNA-based technology for engineering dynamical behaviors in the test tube. In this process, we identify important design rules that inform our choice of molecular motifs and our algorithms for designing and verifying DNA sequences for our molecular implementation. We also develop flexible molecular strategies for "tuning" our reaction rates and stoichiometries in order to compensate for unavoidable non-idealities in the molecular implementation, such as imperfectly synthesized molecules and spurious "leak" pathways that compete with desired pathways.

We successfully implement three distinct autocatalytic reactions, which we then combine into a de novo chemical oscillator. Unlike biological networks, which use sophisticated evolved molecules (like proteins) to realize such behavior, our test tube realization is the first to demonstrate that Watson-Crick base pairing interactions alone suffice for oscillatory dynamics. Since our design pipeline is general and applicable to any CRN, our experimental demonstration of a de novo chemical oscillator could enable the systematic construction of CRNs with other dynamic behaviors.

A brief study of economic Penstock design : Supplementary to Course 800, Department of Civil Engineering

No abstract.

Grants for Libraries

More and more libraries, museums and cultural institutions rely on fundraising and grant writing to sustain their services, special projects, or new initiatives Since most MLIS programs do not include grant project planning and proposal writing as part of their curriculum, librarians learn the process through trial and error, or continuing education classes. There are numerous books and websites that can assist the novice grant writer. We hope to provide beginners with basic information on the types of grants available, where to look for funding agencies, selected grant writing resources, and a few helpful grant writing hints to get you started. The presentation will be a three-person panel providing a short overview of the areas mentioned above, and discussion of sample grants submitted or received. The overview will be presented in Power Point format with an accompanying handout for each attendee.

Genetic engineering of microorganisms: free release into the environment

Genetic engineering now makes possible the insertion of DNA from many organisms into other prokaryotic, eukaryotic and viral hosts. This technology has been used to construct a variety of such genetically engineered microorganisms (GEMs). The possibility of accidental or deliberate release of GEMs into the natural environment has recently raised much public concern. The prospect of deliberate release of these microorganisms has prompted an increased need to understand the processes of survival, expression, transfer and rearrangement of recombinant DNA molecules in microbial communities. The methodology which is being developed to investigate these processes will greatly enhance our ability to study microbial population ecology.

Some engineering issues of an FBG sensor with the dual gratings parallel matched interrogation method

The key issues of engineering application of the dual gratings parallel matched interrogation method are expanding the measurable range, improving the usability, and lowering the cost by adopting a compact and simple setup based on existing conditions and improving the precision of the data-processing scheme. A credible and effective data-processing scheme based on a novel divisional look-up table is proposed based on the advantages of other schemes. Any undetermined data is belonged to a certain section, which can be confirmed at first, then it can be looked up in the table to correspond to microstrain by the scheme. It not only solves inherent problems of the traditional one (double value and small measurable range) but also enhances the precision, which improves the performance of the system. From the experimental results, the measurable range of the system is 525 mu epsilon, and the precision is +/- 1 mu epsilon based on normal matched gratings. The system works in real time, which is competent for most engineering measurement requirements. (C) 2007 Elsevier GmbH. All rights reserved.