A new method has been developed to compute the probability that each amino acid in a protein sequence is in a particular secondary structural element. Each of these probabilities is computed using the entire sequence and a set of predefined structural class models. This set of structural classes is patterned after Jane Richardson's taxonomy for the domains of globular proteins. For each structural class considered, a mathematical model is constructed to represent constraints on the pattern of secondary structural elements characteristic of that class. These are stochastic models having discrete state spaces (referred to as hidden Markov models by researchers in signal processing and automatic speech recognition). Each model is a mathematical generator of amino acid sequences; the sequence under consideration is modeled as having been generated by one model in the set of candidates. The probability that each model generated the given sequence is computed using a filtering algorithm. The protein is then classified as belonging to the structural class having the most probable model. The secondary structure of the sequence is then analyzed using a "smoothing" algorithm that is optimal for that structural class model. For each residue position in the sequence, the smoother computes the probability that the residue is contained within each of the defined secondary structural elements of the model. This method has two important advantages: (1) the probability of each residue being in each of the modeled secondary structural elements is computed using the totality of the amino acid sequence, and (2) these probabilities are consistent with prior knowledge of realizable domain folds as encoded in each model. As an example of the method's utility, we present its application to flavodoxin, a prototypical a//3 protein having a central &sheet, and to thioredoxin, which belongs to a similar structural class but shares no significant sequence similarity.Keywords: flavodoxin; hidden Markov model; secondary structure; state space modeling; tertiary structure classification; thioredoxin The number of known protein sequences greatly exceeds the number of directly determined structures. This is due in part to the relative ease of protein sequence determination by DNA sequencing as compared to the difficulty and expense of structure determination by X-ray crystallography and NMR spectroscopy. Although the number of known structures continues to grow, the number of protein sequences is expected to greatly exceed the number of known structures for the foreseeable future. Because knowledge of the structure of a protein is essential to understanding its function, the elucidation of any aspect of a protein's structure from the sequence information alone is potentially useful.Although there are over 600 structures in the Brookhaven protein structural database (Bernstein et al., 1977;

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The Gene Ontology (GO) Consortium has produced a controlled vocabulary for annotation of gene function that is used in many organism-specific gene annotation databases. This allows the prediction of gene function based on patterns of annotation. For example, if annotations for two attributes tend to occur together in a database, then a gene holding one attribute is likely to hold the other as well. We modeled the relationships among GO attributes with decision trees and Bayesian networks, using the annotations in the Saccharomyces Genome Database (SGD) and in FlyBase as training data. We tested the models using cross-validation, and we manually assessed 100 gene-attribute associations that were predicted by the models but that were not present in the SGD or FlyBase databases. Of the 100 manually assessed associations, 41 were judged to be true, and another 42 were judged to be plausible.[Detailed lists of hypotheses including the curators' comments on each hypothesis, are available at

Non-invasive treatment of brain disorders using ultrasound would require a transducer array that can propagate ultrasound through the skull and still produce sufficient acoustic pressure at a specific location within the brain. Additionally, the array must not cause excessive heating near the skull or in other regions of the brain. A hemisphere-shaped transducer is proposed which disperses the ultrasound over a large region of the skull. The large surface area covered allows maximum ultrasound gain while minimizing undesired heating. To test the feasibility of the transducer two virtual arrays are simulated by superposition of multiple measurements from an 11-element and a 40-element spherically concave test array. Each array is focused through an ex vivo human skull at four separate locations around the skull surface. The resultant ultrasound field is calculated by combining measurements taken with a polyvinylidene difluoride needle hydrophone providing the fields from a 44-element and a 160-element virtual array covering 88% and 33% of a hemisphere respectively. Measurements are repeated after the phase of each array element is adjusted to maximize the constructive interference at the transducer's geometric focus. An investigation of mechanical and electronic beam steering through the skull is also performed with the 160-element virtual array, phasing it such that the focus of the transducer is located 14 mm from the geometric centre. Results indicate the feasibility of focusing and beam steering through the skull using an array spread over a large surface area. Further, it is demonstrated that beam steering through the skull is plausible.

Introduction: Focus groups are an important learning tool in HIV prevention research among U.S. Black men who have sex with men (BMSM), for whom incidence persists.Focus groups are useful in designing interventions, but many have struggled to engage BMSM in research. To optimize the utility of focus group methodology on HIV prevention among BMSM, this paper offers methodological considerations for conducting and managing focus groups with BMSM.Methods: Perspectives come from the process of conducting nine focus groups (N = 52) to explore the role of religion and spirituality in the lives of BMSM in Baltimore City and how these concepts could be used to inform local HIV prevention interventions. Results:Themes from field notes captured important concepts to consider regarding the following: recruitment and retention, recruiting from within the social network, screening for HIV status, focus group stratification, and focus group facilitation.Discussion: Considerations and recommendations for mitigating the challenges in focus group research and enriching data collection with BMSM are outlined. K E Y W O R D SBlack MSM, culture, focus groups, HIV prevention

This study was set up to examine factors affecting adherence to highly active antiretroviral therapy (HAART) by substance abusing women and to conduct a pilot study of a reminder device intervention. Three focus groups totaling 24 HIV-positive women developed priority lists of issues affecting adherence. Another group of 24 HIV-positive women received a timer-reminder with structured interviews on adherence at baseline and two monthly follow up intervals. Focus groups described key barriers to HAART adherence as substance abuse, forgetting, feeling ill, others' negative attitudes, obtaining refills and confidentiality. Primary disadvantages to HAART were side effects, pill-taking schedule and burden of taking medications. Facilitators included reminders (e.g. pill boxes) and spirituality. After receiving the reminder, missing a dose was less common (p < 0.05) due to sleeping through dose, being busy and feeling too good while a favourable trend (p = 0.07) was seen for change in daily routine and having too many pills to take. Although well accepted, the reminder did not affect the proportion missing a dose in the past two weeks: baseline (33%), first follow-up (30%) and second follow-up (30%). Forgetting to take HAART was only one of many cited barriers to adherence in these HIV-positive women; well-received reminder devices did not affect adherence. To improve substance-abusing women's adherence, multidimensional interventions are warranted.

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