Searching the World-Wide-Web using nucleotide and peptide sequences

*Background:* No approaches have yet been developed to allow instant searching of the World-Wide-Web by just entering a string of sequence data. Though general search engines can be tuned to accept ‘processed’ queries, the burden of preparing such ‘search strings’ simply defeats the purpose of quickly locating highly relevant information. Unlike ‘sequence similarity’ searches that employ dedicated algorithms (like BLAST) to compare an input sequence from defined databases, a direct ‘sequence based’ search simply locates quick and relevant information about a blunt piece of nucleotide or peptide sequence. This approach is particularly invaluable to all biomedical researchers who would often like to enter a sequence and quickly locate any pertinent information before proceeding to carry out detailed sequence alignment. 

*Results:* Here, we describe the theory and implementation of a web-based front-end for a search engine, like Google, which accepts sequence fragments and interactively retrieves a collection of highly relevant links and documents, in real-time. e.g. flat files like patent records, privately hosted sequence documents and regular databases. 

*Conclusions:* The importance of this simple yet highly relevant tool will be evident when with a little bit of tweaking, the tool can be engineered to carry out searches on all kinds of hosted documents in the World-Wide-Web.

*Availability:* Instaseq is free web based service that can be accessed by visiting the following hyperlink on the WWW
http://instaseq.georgetown.edu 
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A Top-Down LC-FTICR MS-Based Strategy for Characterizing Oxidized Calmodulin in Activated Macrophages

A liquid chromatography-mass spectrometry (LC-MS)-based approach for characterizing the degree of nitration and oxidation of intact calmodulin (CaM) has been used to resolve ∼250 CaM oxiforms using only 500 ng of protein. The analysis was based on high-resolution data of the intact CaM isoforms obtained by Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) coupled with an on-line reversed-phase LC separation. Tentative identifications of post-translational modifications (PTMs), such as oxidation or nitration, have been assigned by matching observed protein mass to a database containing all theoretically predicted oxidation products of CaM and verified through a combination of tryptic peptide information (generated from bottom-up analyses) and on-line collisionally induced dissociation (CID) tandem mass spectrometry (MS/MS) at the intact protein level. The reduction in abundance and diversity of oxidatively modified CaM (i.e., nitrated tyrosines and oxidized methionines) induced by macrophage activation has been explored and semiquantified for different oxidation degrees (i.e., no oxidation, moderate, and high oxidation). This work demonstrates the power of the top-down approach to identify and quantify hundreds of combinations of PTMs for single protein target such as CaM and implicate competing repair and peptidase activities to modulate cellular metabolism in response to oxidative stress

Medical communication and technology: a video-based process study of the use of decision aids in primary care

Background: much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.Methods: a video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.Results: median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19–26) minutes to work through compared to 31 (16–41) minutes for the implicit tool; and 44 (39–55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58–66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversationConclusion: irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary car

Implementation of Parallel Arithmetic In a Cellular Automaton

We describe an approach to parallel computation using particle propagation and collisions in a one-dimensional cellular automaton using a particle model ---a Particle Machine (PM). Such a machine has the parallelism, structural regularity, and local connectivity of systolic arrays, but is general and programmable. It contains no explicit multipliers, adders, or other fixed arithmetic operations; these are implemented using fine-grain interactions of logical particles which are injected into the medium of the cellular automaton, and which represent both data and processors. We sketch a VLSI implementation of a PM, and estimate its speed and size. We next discuss the problem of determining whether a rule set for a PM is free of conflicts. In general, the question is undecidable, but enough side information is available in practice to answer the question in polynomial time. We then show how to implement division in time linear in the number of significant bits of the result, complementing previous results for fixed-point addition and multiplication. The precision of the arithmetic is arbitrary, being determined by the particle groups used as input