Biomedical subjects

Scott Brown

Publications and source records attributed to Scott Brown.

27 records · Page 2Linked to original sources

PubMed2003

Minimalist models for protein folding and design.

Protein folding research during the past decade has emphasized the dominant role of native state topology in determining the speed and mechanism of folding for small proteins; this has been illustrated by simulations using minimalist protein models. The advantages of minimalist protein models lie in their ability to rapidly collect meaningful statistics about folding pathways and kinetics, their ease of characterization with coarse-grained order parameters and their concentration on the essential physics of the problem to connect with experimental observables for a target protein. The maturation of experimental protein folding has driven the need for more quantitative protein simulations to better understand the balance between sequence details and fold topology. In the past year, we have seen the emergence of more complex minimalist models, ranging from all-atom Gō potentials to coarse-grained bead models in which Gō interactions are replaced or supplemented by more physically motivated potentials. The reduced computational cost at the coarse-grained level of abstraction will potentially enable both folding studies on a genomic scale and systematic application in protein design.

Bacterial Proteins↗

PubMed2003

Constituents within pulp mill effluent deplete retinoid stores in white sucker and bind to rainbow trout retinoic acid receptors and retinoid X receptors.

Wild female and male white sucker (Catostomus commersoni) inhabiting an area receiving pulp mill effluent had reduced hepatic levels of retinol, didehydroretinol, retinyl esters, and didehydroretinyl esters, while vitamin E levels were unaffected. This disruption of the retinoid system led us to test methanol and dichloromethane extracts from the effluent of 11 pulp mills from across Canada for their ability to bind to rainbow trout (Oncorhynchus mykiss) retinoic acid receptors (RARs) from the gill and retinoid X receptors (RXRs) from the liver. Concentrated extracts of the final effluent from 6 of the 11 pulp mills were able to displace greater than 25% of the receptor-bound [3H]all-trans retinoic acid (RA) or [3H]9-cis RA from trout RARs and RXRs, respectively. The ability of the extracts to displace retinoic acid did not appear to be linked to the pulping or treatment processes. Moreover, extracts with the greatest activity came from thermomechanical mills, suggesting the compounds may originate from the wood furnish. In addition, extracts prepared from wood furnish (wood chips: white spruce [50%], lodgepole pine [47%], and balsam fir [3%]) from one mill were able to displace [3H]RA from the RARs and RXRs. The 4-hydroxy RA, a metabolite of RA that has been shown to be generated in greater quantities in fish exposed to P450-inducing xenobiotics, was able to displace [3H]all-trans RA from trout RARs as effectively as unlabeled all-trans RA. These results suggest that pulp mill effluent may impact the retinoid system of fish at multiple sites, either by decreasing hepatic retinoid stores or through contributing additional ligands (from the wood furnish) that can bind to RA receptors.

Animals↗

PubMed2003

Averaging learning curves across and within participants.

We examine recent concerns that averaged learning curves can present a distorted picture of individual learning. Analyses of practice curve data from a range of paradigms demonstrate that such concerns are well founded for fits of power and exponential functions when the arithmetic average is computed over participants. We also demonstrate that geometric averaging over participants does not, in general, avoid distortion. By contrast, we show that block averages of individual curves and similar smoothing techniques cause little or no distortion of functional form, while still providing the noise reduction benefits that motivate the use of averages. Our analyses are concerned mainly with the effects of averaging on the fit of exponential and power functions, but we also define general conditions that must be met by any set of functions to avoid distortion from averaging.

Algorithms↗

PubMed2003

QMLE: fast, robust, and efficient estimation of distribution functions based on quantiles.

Quantile maximum likelihood (QML) is an estimation technique, proposed by Heathcote, Brown, and Mewhort (2002), that provides robust and efficient estimates of distribution parameters, typically for response time data, in sample sizes as small as 40 observations. In view of the computational difficulty inherent in implementing QML, we provide open-source Fortran 90 code that calculates QML estimates for parameters of the ex-Gaussian distribution, as well as standard maximum likelihood estimates. We show that parameter estimates from QML are asymptotically unbiased and normally distributed. Our software provides asymptotically correct standard error and parameter intercorrelation estimates, as well as producing the outputs required for constructing quantile-quantile plots. The code is parallelizable and can easily be modified to estimate parameters from other distributions. Compiled binaries, as well as the source code, example analysis files, and a detailed manual, are available for free on the Internet.

Data Interpretation, Statistical↗

PubMed2003

Bias in exponential and power function fits due to noise: comment on Myung, Kim, and Pitt.

Myung, Kim, and Pitt (2000) demonstrated that simple power functions almost always provide a better fit to purely random data than do simple exponential functions. This result has important implications, because it suggests that high noise levels, which are common in psychological experiments, may cause a bias favoring power functions. We replicate their result and extend it by showing strong bias for more realistic sample sizes. We also show that biases occur for data that contain both random and systematic components, as may be expected in real data. We then demonstrate that these biases disappear for two- or three-parameter functions that include linear parameters (in at least one parameterization). Our results suggest that one should exercise caution when proposing simple power and exponential functions as models of learning. More generally, our results suggest that linear parameters should be estimated rather than fixed when one is comparing the fit of nonlinear models to noisy data.

Data Interpretation, Statistical↗

PubMed2002

A five-residue HIV envelope helper T cell determinant: does this peptide-MHC interaction leave the binding groove half empty?

High-resolution structures have revealed major pockets in the MHC class II peptide binding groove within a region designated Pl-P9. The region can accommodate 9-mer peptides, consistent with the observation that minimal core helper T (Th) cell determinants are usually eight or nine residues in size. Here we describe mouse Th cell hybridomas that are specific for a core peptide of only five residues (NPIIL) in the HIV envelope glycoprotein. Effective Th cell stimulation requires that these MHC class II Ia(b)-presented peptides contain amino acids flanking the minimal pentamer, but the flanking residues may be located on either the N or C terminus. To explain these findings, we suggest that mini-Th cell epitopes may effectively associate with MHC when only five (or possibly fewer) of the P1-P9 positions are filled. The remaining positions may be empty, or may be associated with a second, perhaps unrelated, peptide moiety.

Amino Acid Sequence↗

PubMed2002

Transient elevation of the tumor markers CA 15-3 and CASA as markers of interstitial lung disease rather than underlying malignancy in dermatomyositis sine myositis.

A 37-year-old woman with severe interstitial lung disease associated with dermatomyositis sine myositis is reported. A thoracoscopic lung biopsy revealed organizing diffuse alveolar damage. Significantly elevated serum levels of the tumor markers CA 15-3 and CASA (cancer-associated serum antigen) were detected, but no evidence of an underlying malignancy (including breast and ovarian) was found on serial clinical and radiologic examinations. These levels gradually normalized as the interstitial lung disease responded to a combination of cyclophosphamide and corticosteroids. The use of the CA 15-3 and CASA assays to measure serum levels of the highly glycosylated, high-molecular-weight mucin MUC1 in interstitial lung disease has not been previously described. Clinicians should therefore be aware that elevation of these tumor markers may reflect the presence of interstitial lung disease rather than an underlying malignancy in patients with dermatomyositis, especially if the levels normalize after successful treatment of the lung disease.

Journal Article↗

PubMed2002

Quantile maximum likelihood estimation of response time distributions.

We introduce and evaluate via a Monte Carlo study a robust new estimation technique that fits distribution functions to grouped response time (RT) data, where the grouping is determined by sample quantiles. The new estimator, quantile maximum likelihood (QML), is more efficient and less biased than the best alternative estimation technique when fitting the commonly used ex-Gaussian distribution. Limitations of the Monte Carlo results are discussed and guidance provided for the practical application of the new technique. Because QML estimation can be computationally costly, we make fast open source code for fitting available that can be easily modified to use QML in the estimation of any distribution function.

Data Interpretation, Statistical↗

PubMedDate not supplied

Outcomes of an infection prevention project focusing on hand hygiene and isolation practices.

Nosocomial infections are a major health problem for hospitalized patients and their families. Since the 1800s, hand hygiene has been recognized as the single best method to prevent the spread of pathogens and nosocomial infections. Despite this fact, many healthcare workers do not adhere to hand hygiene policies. The Centers for Disease Control and Prevention issued a guideline for hand hygiene practices in 2002. Multifaceted approaches to improve hand hygiene have been shown to increase compliance among healthcare workers and subsequently reduce infections. A performance improvement project was initiated to implement this guideline and other strategies to prevent nosocomial infection. This article summarizes the performance improvement processes and the preliminary outcomes on adherence to infection prevention policies related to hand hygiene and isolation practices. Clinically and statistically significant increases were noted for hand hygiene prior to patient care and in wearing masks when indicated. Nurses and patient care technicians had the greatest increases in compliance. Increases in hand hygiene after patient contact and wearing of gown and gloves were also noted, but results were not statistically significant. Nosocomial infection rates from antibiotic-resistant organisms decreased in the first surveillance, but rates increased during the 1-year surveillance. Consumption of alcohol-based foam disinfectant doubled from baseline. Findings are consistent with other published studies. The project will continue with further reinforcement and education over the second year.

Centers for Disease Control and Prevention, U.S.↗