Electroosmotic flow has been monitored in a capillary using a method based on periodic photobleaching of a neutral, fluorescent buffer additive. Rhodamine B was determined to be neutral between pH 6.0 and 10.8 and was added to the running buffer at a concentration of 400 nM. Rhodamine B was photobleached by opening a shutter under computer control for 250 ms every 5.00 s, to expose the dye to a laser beam and create a photobleached zone. The time was measured for the photobleached zone to migrate 6.13 mm to a downstream laser-induced fluorescence detector, to determine the rate of electroosmotic flow in the entire capillary. The flow rate was sampled every 5.00 s, and the precision of the flow measurements was 0.7% or better. Three fluorescent compounds were separated and detected by capillary electrophoresis with laser-induced fluorescence detection, while simultaneously monitoring the electroosmotic flow rate.

Biosequence similarity search is an important application in modern molecular biology. Search algorithms aim to identify sets of sequences whose extensional similarity suggests a common evolutionary origin or function. The most widely used similarity search tool for biosequences is BLAST, a program designed to compare query sequences to a database. Here, we present the design of BLASTN, the version of BLAST that searches DNA sequences, on the Mercury system, an architecture that supports high-volume, high-throughput data movement off a data store and into reconfigurable hardware. An important component of application deployment on the Mercury system is the functional decomposition of the application onto both the reconfigurable hardware and the traditional processor. Both the Mercury BLASTN application design and its performance analysis are described. 1: IntroductionComputational search through large databases of DNA and protein sequence is a fundamental tool of modern molecular biology. Rapid advances in the speed and cost-effectiveness of DNA sequencing have led to an explosion in the rate at which new sequences, including entire mammalian genomes [35], are being generated. To understand the function and evolutionary history of an organism, biologists now seek to identify discrete biologically meaningful features in its genome sequence. A powerful approach to identify such features is comparative annotation, in which a query sequence, such as new genome, is compared to a large database of known biosequences. Database sequences exhibiting high similarity to the query, as measured by string edit distance [31], are hypothesized to derive from the same ancestral sequence as the query and in many cases to have the same biological function.BLAST, the Basic Local Alignment Search Tool [1], is the most widely used software for rapidly comparing a query sequence to a biosequence database. Although BLAST's algorithms are highly optimized for efficient similarity search, growth in the databases it uses is outpacing speed improvements in general-purpose computing hardware. For example, the National Center for Biological Information (NCBI) Genbank database grew exponentially between 1992 and 2003 with a doubling time of 12-16 months [24]. The problem is particularly acute for BLASTN, the BLAST variant used to compare DNA sequences, because each new genome sequenced from animals or higher plants produces between 10 8 and 10 10 bytes of new DNA sequence.One response to runaway growth in biosequence databases has been to distribute BLAST searches across multiple computers, each responsible for searching only part of a database. This approach requires both a substantial hardware investment and the ability to coordinate a {praveenk, jbuhler, roger, jbf, kg2, jarpith, jmlancas}@cse.wustl.edu. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript search across processors. An alternate approach that makes more parsimonious use of hardware is to build a specialized BLAST accelerator. By using an applic...

Noise may play a pivotal role in gene circuit functionality, as demonstrated for the genetic switch in the bacterial phage lambda. Like the lambda switch, bacterial quorum sensing (QS) systems operate within a population and contain a bistable switching element, making it likely that noise plays a functional role in QS circuit operation. Therefore, a detailed analysis of the noise behavior of QS systems is needed. We have developed a set of tools generally applicable to the analysis of gene circuits, with an emphasis on investigations in the frequency domain (FD), that we apply here to the QS system in the marine bacterium Vibrio fischeri. We demonstrate that a tight coupling between exact stochastic simulation and FD analysis provides insights into the structure/function relationships in the QS circuit. Furthermore, we argue that a noise analysis is incomplete without consideration of the power spectral densities (PSDs) of the important molecular output signals. As an example we consider reversible reactions in the QS circuit, and show through analysis and exact stochastic simulation that these circuits make significant and dynamic modifications to the noise spectra. In particular, we demonstrate a "whitening" effect, which occurs as the noise is processed through these reversible reactions.

In modeling and simulation tools, random numbers lrom a variety of probability distribution lunctions are generated to simulate the behavior 01 random events. lnellicient generation of these nnmbers can be a significant bottleneck lor simulation applications. Generating these random numbers imprecisely can skew results. An ellicient and scalable fire& point method for generating random numbers for any probability distribution function in a Field Programmable Gate Array (FPGA) is developed. A Pi estimator, a Monte Carlo integrator, and a stochastic simulator lor chemical species are developed in soltware. Estimates are made regarding their potential to be accelerated using the designed FPG.4. Results are presented which examine lrade-ofls between the number ol gates used by the FPGA and the accuracy 01 the random numbers generated. The work shows that generating random numbers using the designed hardware can signilicantly increase the perlormance of simulation applications that require many random numbers.

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