bluuebunny/crossref_metadata_2025 huggingface dataset:
Carer knowledge of dysphagia management strategies
Authors: Chadwick Darren D. , Jolliffe Jane , Goldbart Juliet
Published: September 2002

Dysphagia can have many negative health consequences for people with learning disabilities, including dehydration, aspiration and asphyxiation. Few studies have investigated dysphagia management among adults with learning disabilities. This study aims to contribute to the existing knowledge by investigating carer knowledge of speech and language therapists' (SLTs) recommendations regarding dysphagia management, and by comparing carer knowledge with their behavioural adherence to SLT recommendations. An exploratory study was undertaken investigating carer knowledge of dysphagia management strategies, along with a within‐participants' study comparing carer knowledge and adherence. Structured interviews were conducted with carers supporting adults with learning disabilities and dysphagia to explore and ascertain their knowledge of dysphagia management. These data were then compared with observational data gathered in naturalistic contexts, assessing the behavioural adherence of these same carers. Recommendations pertaining to altering consistency and using specialized equipment and utensils were recalled significantly more readily than those concerning support and prompting for the dysphagic persons. Moreover, carers adhered to management strategies to a significantly greater degree than they could recall the details of the written guidelines containing the dysphagia management strategies. The findings suggest that tangible and routinely used management strategies, e.g. food and drink consistency, and use of specialized utensils, are easier for carers to adhere to and remember than support‐based strategies such as verbal prompting and pacing. The discrepancy between compliance and knowledge can be explained by calling upon cognitive theories of memory and skill acquisition. This has implications for the selection of relevant outcomes of dysphagia training of direct care staff. Knowledge does not necessarily predict actual behavioural adherence and, though desirable, does not appear to be an adequate outcome indicator if the goal is behavioural adherence. Practice implications for SLTs training carers in dysphagia management strategies include combating fossilization of incorrect knowledge; encouraging carers to refamiliarize themselves with management strategies and their rationales periodically following initial training; and providing more specific contingency information for support and prompting in the guideline documentation.
Speech and language therapy services to education in England and Wales
Authors: Lindsay Geoff , Soloff Nina , Law James , Band Sue , Peacey Nick , Gascoigne Marie , Radford Julie
Published: September 2002

Services for children with speech and language needs in England and Wales are in a period of change. The context is subject to major systemic pressures deriving from government policies. These include the development of inclusive education and encouragement of multiprofessional collaboration in policy development and practice (‘joined up thinking’). In addition, structures at local level are changing with the establishment of unitary authorities and the change from Health Trusts to Primary Care Trusts. Professional practice is also changing with a shift from clinical to community settings for speech and language therapists working with children. The present study reports on a survey sponsored by the Department for Education and Employment, Department of Health and the Welsh Assembly to identify the nature of speech and language therapy (SLT) services provided to education in England and Wales. The sample comprised all SLT service managers (n = 133, response rate 74%). The results indicate that services vary greatly in size and in their SLT: child ratio, with a mean of one SLT to 4257 child population. The caseload was highest for the 5‐10 age group, and service delivery was targeted at these children, with low levels of work with secondary aged pupils. Most provision in educational settings was made to mainstream schools, but the provision of SLT time per child was substantially higher in specialist language resources. Apart from the preschool phase, most SLT provision was for children with statements of special educational needs. Prioritization of service delivery was usually by severity of need. The provision of bilingual SLT services was very limited, with only 14.0 full‐time equivalents SLTs fluent in a community language, other than Welsh, where proportionately availability was much greater. Most LEAs funded SLT posts, although these were usually employed as part of the SLT service, with only about 10% of LEAs employing SLTs direct. However, 55.5% of SLT managers reported that recruitment and retention were problematic, resulting in gaps in the service. These findings are discussed with respect to changes driven by professional judgements on the nature of optimal service delivery, and government policy, with particular reference to inclusion and equity of service delivery.
Speech and language skills and cognitive functioning in children with Apert syndrome: A pilot study
Authors: Shipster C. , Hearst D. , Dockrell J. E. , Kilby E. , Hayward R.
Published: September 2002

There are few studies that report findings on the speech and language characteristics of Apert syndrome and little is known about the cognitive profile of the syndrome. The current study addresses this gap and explores speech, language, resonance/voice, attention oro‐motor and cognitive skills in a group of 10 children (4;1‐5;11) with Apert syndrome. The speech and language battery included: the CELF‐Pre‐school, the PLS‐3, the Vocal Profile Analysis, GOS.SP.ASS, PACS; and the Brodsky Drooling Scale. Subscales of the BAS II‐Early Years Version were used to assess cognition. Data were also collected on other factors that could influence developmental outcome such as audiological history and management; occlusion/dentition; respiratory problems and management; neuroanatomical abnormalities; the number and nature of cranial surgeries; and the occurrence of raised intracranial pressure. All children for whom a Performance IQ was obtained (n = 8) had abilities within the average range and IQ scores were considerably higher than those reported in previous studies. Eight children had moderate or severe language difficulties and expressive language difficulties were the most frequent. These language difficulties were not associated with a general cognitive deficit. All the children had problems with attention, speech and oro‐motor skills. Nine had abnormal voice. In addition, a range of other associated factors that could affect functioning were identified. The discrepancies between the current study and previous investigations are outlined. Parameters for assessment are considered. The implications of these findings for valid assessments of children with Apert syndrome are discussed. Multidisciplinary assessment of children with Apert syndrome across a broad range of dimensions is recommended to obtain a profile of each child's strengths and weaknesses to ensure that appropriate educational placements and early interventions are implemented. Considering patterns of development over time at key ages is also argued to be of central importance.
β-Catenin–induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor
Authors: Widlund Hans R. , Horstmann Martin A. , Price E. Roydon , Cui Junqing , Lessnick Stephen L. , Wu Min , He Xi , Fisher David E.
Published: September 2002

The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of β-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that β-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF. Moreover, suppression of melanoma clonogenic growth by disruption of β-catenin–T-cell transcription factor/LEF is rescued by constitutive MITF. This rescue occurs largely through a prosurvival mechanism. Thus, β-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm.
Genome structures embossed by oligonucleotide-stickiness
Authors: Nishigaki Koichi , Saito Ayumu
Published: September 2002

Motivation: An unmanageably large amount of data on genome sequences is accumulating, prompting researchers to develop new methods to analyze them. We have devised a novel method designated oligostickiness, a measure roughly proportional to the binding affinity of an oligonucleotide to a DNA of interest, in order to analyze genome sequences as a whole.

Results: Fifteen representative genomes such as Bacillus subtilis, Escherichia coli, Saccharomyces cerevisiae, Caenorhabditis elegans, H. sapiens and others were analyzed by this method using more than 50 probe dodecanucleotides, offering the following findings: (i) Genome sequences can be specifically featured by way of oligostickiness maps. (ii) Oligostickiness analysis, which is similar to but more informative than (G + C) content or repetitive sequence analysis, can reveal intra-genomic structures such as mosaic structures (E. coli and B. subtilis) and highly sticky/non-sticky regions of biological meanings. (iii) Some probe oligonucleotides such as dC12 and dT12 can be used for classifying genomes, clearly discriminating prokaryotes and eukaryotes. (iv) Based on global oligostickiness, which is the average value of the local oligostickinesses, the features of a genome could be visualized in spider web mode. The pattern of a spider web as well as a set of oligostickiness maps is highly characteristic to each genome or chromosome. Thus, we called it as chromosome texture, leading to a finding that all the chromosomes contained in a cell, so far investigated, have a common texture.

Availability: Oligostickinesses maps used in this work are available at http://gp.fms.saitama-u.ac.jp/

Contact: koichi@fms.saitama-u.ac.jp

* To whom correspondence should be addressed.
Pooled library tissue tags for EST-based gene discovery
Authors: Gavin A. J. , Scheetz T. E. , Roberts C. A. , O'Leary B. , Braun T. A. , Sheffield V. C. , Soares M. B. , Robinson J. P. , Casavant T. L.
Published: September 2002

Motivation: In gene discovery projects based on EST sequencing, effective post-sequencing identification methods are important in determining tissue sources of ESTs within pooled cDNA libraries. In the past, such identification efforts have been characterized by higher than necessary failure rates due to the presence of errors within the subsequence containing the oligo tag intended to define the tissue source for each EST.

Results: A large-scale EST-based gene discovery program at The University of Iowa has led to the creation of a unique software method named UITagCreator usable in the creation of large sets of synthetic tissue identification tags. The identification tags provide error detection and correction capability and, in conjunction with automated annotation software, result in a substantial improvement in the accurate identification of the tissue source in the presence of sequencing and base-calling errors. These identification rates are favorable, relative to past paradigms.

Availability: The UITagCreator source code and installation instructions, along with detection software usable in concert with created tag sets, is freely available at http://genome.uiowa.edu/pubsoft/software.html

Contact: tomc@eng.uiowa.edu

* To whom correspondence should be addressed.
Identification of regulatory elements using a feature
selection method
Authors: Keleş Sündüz , van der Laan Mark , Eisen Michael B.
Published: September 2002

Motivation: Many methods have been described to identify regulatory motifs in the transcription control regions of genes that exhibit similar patterns of gene expression across a variety of experimental conditions. Here we focus on a single experimental condition, and utilize gene expression data to identify sequence motifs associated with genes that are activated under this experimental condition. We use a linear model with two-way interactions to model gene expression as a function of sequence features (words) present in presumptive transcription control regions. The most relevant features are selected by a feature selection method called stepwise selection with monte carlo cross validation. We apply this method to a publicly available dataset of the yeast Saccharomyces cerevisiae, focussing on the 800 basepairs immediately upstream of each gene's translation start site (the upstream control region (UCR)).

Results: We successfully identify regulatory motifs that are known to be active under the experimental conditions analyzed, and find additional significant sequences that may represent novel regulatory motifs. We also discuss a complementary method that utilizes gene expression data from a single microarray experiment and allows averaging over variety of experimental conditions as an alternative to motif finding methods that act on clusters of co-expressed genes.

Availability: The software is available upon request from the first author or may be downloaded from http://www.stat.berkeley.edu/~sunduz.

Contact: keles@stat.berkeley.edu

* To whom correspondence should be addressed.
Geometry of gene expression dynamics
Authors: Rifkin S. A. , Kim J.
Published: September 2002

Motivation: A gene expression trajectory moves through a high dimensional space where each axis represents the mRNA abundance of a different gene. Genome wide gene expression has a dynamic structure, especially in studies of development and temporal response. Both visualization and analyses of such data require an explicit attention to the temporal structure.

Results: Using three cell cycle trajectories from Saccharomyces cerevisiae to illustrate, we present several techniques which reveal the geometry of the data. We import phase-delay time plots from chaotic systems theory as a dynamic data visualization device and show how these plots capture important aspects of the trajectories. We construct an objective function to find an optimal two-dimensional projection of the cell cycle, demonstrate that the system returns to this plane after three different initial perturbations, and explore the conditions under which this geometric approach outperforms standard approaches such as singular value decomposition and Fourier analysis. Finally, we show how a geometric analysis can isolate distinct parts of the trajectories, in this case the initial perturbation versus the cell cycle.

Contact: junhyong.kim@yale.edu

* To whom correspondence should be addressed.
Determination of minimum sample size and discriminatory expression
patterns in microarray data
Authors: Hwang Daehee , Schmitt William A. , Stephanopoulos George , Stephanopoulos Gregory
Published: September 2002

Motivation: Transcriptional profiling using microarrays can reveal important information about cellular and tissue expression phenotypes, but these measurements are costly and time consuming. Additionally, tissue sample availability poses further constraints on the number of arrays that can be analyzed in connection with a particular disease or state of interest. It is therefore important to provide a method for the determination of the minimum number of microarrays required to separate, with statistical reliability, distinct disease states or other physiological differences.

Results: Power analysis was applied to estimate the minimum sample size required for two-class and multi-class discrimination. The power analysis algorithm calculates the appropriate sample size for discrimination of phenotypic subtypes in a reduced dimensional space obtained by Fisher discriminant analysis (FDA). This approach was tested by applying the algorithm to existing data sets for estimation of the minimum sample size required for drawing certain conclusions on multi-class distinction with statistical reliability. It was confirmed that when the minimum number of samples estimated from power analysis is used, group means in the FDA discrimination space are statistically different.

Contact: gregstep@mit.edu

* To whom correspondence should be addressed.
Bayesian infinite mixture model based clustering of gene expression profiles
Authors: Medvedovic Mario , Sivaganesan Siva
Published: September 2002

Motivation: The biologic significance of results obtained through cluster analyses of gene expression data generated in microarray experiments have been demonstrated in many studies. In this article we focus on the development of a clustering procedure based on the concept of Bayesian model-averaging and a precise statistical model of expression data.

Results: We developed a clustering procedure based on the Bayesian infinite mixture model and applied it to clustering gene expression profiles. Clusters of genes with similar expression patterns are identified from the posterior distribution of clusterings defined implicitly by the stochastic data-generation model. The posterior distribution of clusterings is estimated by a Gibbs sampler. We summarized the posterior distribution of clusterings by calculating posterior pairwise probabilities of co-expression and used the complete linkage principle to create clusters. This approach has several advantages over usual clustering procedures. The analysis allows for incorporation of a reasonable probabilistic model for generating data. The method does not require specifying the number of clusters and resulting optimal clustering is obtained by averaging over models with all possible numbers of clusters. Expression profiles that are not similar to any other profile are automatically detected, the method incorporates experimental replicates, and it can be extended to accommodate missing data. This approach represents a qualitative shift in the model-based cluster analysis of expression data because it allows for incorporation of uncertainties involved in the model selection in the final assessment of confidence in similarities of expression profiles. We also demonstrated the importance of incorporating the information on experimental variability into the clustering model.

Availability: The MS Windows™ based program implementing the Gibbs sampler and supplemental material is available at http://homepages.uc.edu/~medvedm/BioinformaticsSupplement.htm

Contact: medvedm@email.uc.edu

* To whom correspondence should be addressed.
Ratio statistics of gene expression levels and applications to
microarray data analysis
Authors: Chen Yidong , Kamat Vishnu , Dougherty Edward R. , Bittner Michael L. , Meltzer Paul S. , Trent Jeffery M.
Published: September 2002

Motivation: Expression-based analysis for large families of genes has recently become possible owing to the development of cDNA microarrays, which allow simultaneous measurement of transcript levels for thousands of genes. For each spot on a microarray, signals in two channels must be extracted from their backgrounds. This requires algorithms to extract signals arising from tagged mRNA hybridized to arrayed cDNA locations and algorithms to determine the significance of signal ratios.

Results: This paper focuses on estimation of signal ratios from the two channels, and the significance of those ratios. The key issue is the determination of whether a ratio is significantly high or low in order to conclude whether the gene is upregulated or downregulated. The paper builds on an earlier study that involved a hypothesis test based on a ratio statistic under the supposition that the measured fluorescent intensities subsequent to image processing can be assumed to reflect the signal intensities. Here, a refined hypothesis test is considered in which the measured intensities forming the ratio are assumed to be combinations of signal and background. The new method involves a signal-to-noise ratio, and for a high signal-to-noise ratio the new test reduces (with close approximation) to the original test. The effect of low signal-to-noise ratio on the ratio statistics constitutes the main theme of the paper. Finally, and in this vein, a quality metric is formulated for spots. This measure can be used to decide whether or not a spot ratio should be deleted, or to adjust various measurements to reflect confidence in the quality of the measurement.

Contact: e-dougherty@tamu.edu

* To whom correspondence should be addressed.
Multi-class cancer classification via partial least
squares with gene expression profiles
Authors: Nguyen Danh V. , Rocke David M.
Published: September 2002

Motivation: Discrimination between two classes such as normal and cancer samples and between two types of cancers based on gene expression profiles is an important problem which has practical implications as well as the potential to further our understanding of gene expression of various cancer cells. Classification or discrimination of more than two groups or classes (multi-class) is also needed. The need for multi-class discrimination methodologies is apparent in many microarray experiments where various cancer types are considered simultaneously.

Results: Thus, in this paper we present the extension to the classification methodology proposed earlier Nguyen and Rocke (2002b; Bioinformatics, 18, 39–50) to classify cancer samples from multiple classes. The methodologies proposed in this paper are applied to four gene expression data sets with multiple classes: (a) a hereditary breast cancer data set with (1) BRCA1-mutation, (2) BRCA2-mutation and (3) sporadic breast cancer samples, (b) an acute leukemia data set with (1) acute myeloid leukemia (AML), (2) T-cell acute lymphoblastic leukemia (T-ALL) and (3) B-cell acute lymphoblastic leukemia (B-ALL) samples, (c) a lymphoma data set with (1) diffuse large B-cell lymphoma (DLBCL), (2) B-cell chronic lymphocytic leukemia (BCLL) and (3) follicular lymphoma (FL) samples, and (d) the NCI60 data set with cell lines derived from cancers of various sites of origin. In addition, we evaluated the classification algorithms and examined the variability of the error rates using simulations based on randomization of the real data sets. We note that there are other methods for addressing multi-class prediction recently and our approach is along the line of Nguyen and Rocke (2002b; Bioinformatics, 18, 39–50).

Contact: dnguyen@stat.tamu.edudmrocke@ucdavis.edu
Optimal enhancement of immune response
Authors: Stengel Robert F. , Ghigliazza Raffaele M. , Kulkarni Nilesh V.
Published: September 2002

Motivation: Therapeutic enhancement of innate immune response to microbial attack is addressed as the optimal control of a dynamic system. Interactions between an invading pathogen and the innate immune system are characterized by four non-linear, ordinary differential equations that describe rates of change of pathogen, plasma cell, and antibody concentrations, and of an indicator of organic health. Without therapy, the dynamic model evidences sub-clinical or clinical decay, chronic stabilization, or unrestrained lethal growth of the pathogen; the response pattern depends on the initial concentration of pathogens in the simulated attack. In the model, immune response can be augmented by therapeutic agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. A previous paper demonstrated open-loop optimal control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal (Stengel et al. (2002)). Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and control usage, providing implicit control over harmful side effects.

Results: We demonstrate the ability of neighboring–optimal feedback control to account for a range of unknown initial conditions and persistent input of pathogens by adjusting the therapy to account for perturbations from the nominal-optimal response history. We examine therapies that combine open-loop control of one agent with closed-loop control of another. We show that optimal control theory points the way toward new protocols for treatment and cure of human diseases.

Contact: stengel@princeton.edurghiglia@princeton.edunkulkarn@princeton.edu

* To whom correspondence should be addressed.
The correlation error and finite-size correction in an ungapped
sequence alignment
Authors: Park Yonil , Spouge John L.
Published: September 2002

Motivation: The BLAST program for comparing two sequences assumes independent sequences in its random model. The resulting random alignment matrices have correlations across their diagonals. Analytic formulas for the BLAST p-value essentially neglect these correlations and are equivalent to a random model with independent diagonals. Progress on the independent diagonals model has been surprisingly rapid, but the practical magnitude of the correlations it neglects remains unknown. In addition, BLAST uses a finite-size correction that is particularly important when either of the sequences being compared is short. Several formulas for the finite-size correction have now been given, but the corresponding errors in the BLAST p-values have not been quantified. As the lengths of compared sequences tend to infinity, it is also theoretically unknown whether the neglected correlations vanish faster than the finite-size correction.

Results: Because we required certain analytic formulas, our study restricted its computer experiments to ungapped sequence alignment. We expect some of our conclusions to extend qualitatively to gapped sequence alignment, however. With this caveat, the finite-size correction appeared to vanish faster than the neglected correlations. Although the finite-size correction underestimated the BLAST p-value, it improved the approximation substantially for all but very short sequences. In practice, the Altschul–Gish finite-size correction was superior to Spouge's. The independent diagonals model was always within a factor of 2 of the true BLAST p-value, although fitting p-value parameters from it probably is unwise.

Contact: spouge@ncbi.nlm.nih.gov

* To whom correspondence should be addressed.
The use of structure information to increase alignment
accuracy does not aid homologue detection with profile HMMs
Authors: Griffiths-Jones Sam , Bateman Alex
Published: September 2002

Motivation: The best quality multiple sequence alignments are generally considered to derive from structural superposition. However, no previous work has studied the relative performance of profile hidden Markov models (HMMs) derived from such alignments. Therefore several alignment methods have been used to generate multiple sequence alignments from 348 structurally aligned families in the HOMSTRAD database. The performance of profile HMMs derived from the structural and sequence-based alignments has been assessed for homologue detection.

Results: The best alignment methods studied here correctly align nearly 80% of residues with respect to structure alignments. Alignment quality and model sensitivity are found to be dependent on average number, length, and identity of sequences in the alignment. The striking conclusion is that, although structural data may improve the quality of multiple sequence alignments, this does not add to the ability of the derived profile HMMs to find sequence homologues.

Supplementary information: A list of HOMSTRAD families used in this study and the corresponding Pfam families is available at http://www.sanger.ac.uk/Users/sgj/alignments/map.html

Contact: sgj@sanger.ac.uk

* To whom correspondence should be addressed.
ESyPred3D: Prediction of proteins 3D structures
Authors: Lambert Christophe , Léonard Nadia , De Bolle Xavier , Depiereux Eric
Published: September 2002

Motivation: Homology or comparative modeling is currently the most accurate method to predict the three-dimensional structure of proteins. It generally consists in four steps: (1) databanks searching to identify the structural homolog, (2) target–template alignment, (3) model building and optimization, and (4) model evaluation. The target–template alignment step is generally accepted as the most critical step in homology modeling.

Results: We present here ESyPred3D, a new automated homology modeling program. The method gets benefit of the increased alignment performances of a new alignment strategy. Alignments are obtained by combining, weighting and screening the results of several multiple alignment programs. The final three-dimensional structure is build using the modeling package MODELLER. ESyPred3D was tested on 13 targets in the CASP4 experiment (Critical Assessment of Techniques for Proteins Structural Prediction). Our alignment strategy obtains better results compared to PSI-BLAST alignments and ESyPred3D alignments are among the most accurate compared to those of participants having used the same template.

Availability: ESyPred3D is available through its web site at http://www.fundp.ac.be/urbm/bioinfo/esypred/

Contact: christophe.lambert@fundp.ac.behttp://www.fundp.ac.be/~lambertc

* To whom correspondence should be addressed.
A dissimilarity matrix between protein atom classes based
on Gaussian mixtures
Authors: Rantanen Ville-Veikko , Gyllenberg Mats , Koski Timo , Johnson Mark S.
Published: September 2002

Motivation: Previously, Rantanen et al. (2001; J. Mol. Biol., 313, 197–214) constructed a protein atom–ligand fragment interaction library embodying experimentally solved, high-resolution three-dimensional (3D) structural data from the Protein Data Bank (PDB). The spatial locations of protein atoms that surround ligand fragments were modeled with Gaussian mixture models, the parameters of which were estimated with the expectation-maximization (EM) algorithm. In the validation analysis of this library, there was strong indication that the protein atom classification, 24 classes, was too large and that a reduction in the classes would lead to improved predictions.

Results: Here, a dissimilarity (distance) matrix that is suitable for comparison and fusion of 24 pre-defined protein atom classes has been derived. Jeffreys' distances between Gaussian mixture models are used as a basis to estimate dissimilarities between protein atom classes. The dissimilarity data are analyzed both with a hierarchical clustering method and independently by using multidimensional scaling analysis. The results provide additional insight into the relationships between different protein atom classes, giving us guidance on, for example, how to readjust protein atom classification and, thus, they will help us to improve protein--ligand interaction predictions.

Contact: vira@utu.fi

* To whom correspondence should be addressed.
VIZARD: analysis of Affymetrix Arabidopsis
GeneChip® data
Authors: Moseyko Nick , Feldman Lewis J.
Published: September 2002

Summary: The Affymetrix GeneChip® Arabidopsis genome array has proved to be a very powerful tool for the analysis of gene expression in Arabidopsis thaliana, the most commonly studied plant model organism. VIZARD is a Java program created at the University of California, Berkeley, to facilitate analysis of Arabidopsis GeneChip® data. It includes several integrated tools for filtering, sorting, clustering and visualization of gene expression data as well as tools for the discovery of regulatory motifs in upstream sequences. VIZARD also includes annotation and upstream sequence databases for the majority of genes represented on the Affymetrix Arabidopsis GeneChip® array.

Availability: VIZARD is available free of charge for educational, research, and not-for-profit purposes, and can be downloaded at http://www.anm.f2s.com/research/vizard/

Contact: moseyko@uclink4.berkeley.edu

* To whom correspondence should be addressed.
SEGE: A database on ‘intron less/single exonic’ genes from eukaryotes
Authors: Sakharkar Meena K. , Kangueane Pandjassarame , Petrov Dmitri A. , Kolaskar A. S. , Subbiah S.
Published: September 2002

Summary: Eukaryotes have both ‘intron containing’ and ‘intron less’ genes. Several databases are available for ‘intron containing’ genes in eukaryotes. In this note, we describe a database for‘ intron less’ genes from eukaryotes. ‘Intron less’ eukaryotic genes having prokaryotic architecture will help to understand gene evolution in a much simpler way unlike ‘intron containing’ genes.

Availability: SEGE is available at http://intron.bic.nus.edu.sg/seg/

Contact: mmeena@ntu.edu.sg

* To whom correspondence should be addressed.
UniBLAST: a system to filter, cluster, and display BLAST
results and assign unique gene annotation
Authors: Zhou Yan , Huang Guyang Matthew , Wei Liping
Published: September 2002

Motivation: More and more often, a gene is epitomized by a large number of sequences in GenBank. This high redundancy makes it very difficult to identify a unique best match for a query sequence from its BLAST results. We developed a novel program UniBLAST that filters out uninformative hits, clusters the redundant hits, groups the hits by LocusLink, and graphically displays the results. We also implemented a scoring function in UniBLAST to assign a unique gene name to a query sequence. UniBLAST significantly increases the efficiency of gene annotation.

Availability: The program is available at http://south.genomics.org.cn/software/uniblast/index.html

Contact: uniblast@genomics.org.cnwei@nexusgenomics.com

* To whom correspondence should be addressed.
Parallelized multiple alignment
Authors: Kleinjung Jens , Douglas Nigel , Heringa Jaap
Published: September 2002

Summary: Multiple sequence alignment is a frequently used technique for analyzing sequence relationships. Compilation of large alignments is computationally expensive, but processing time can be considerably reduced when the computational load is distributed over many processors. Parallel processing functionality in the form of single-instruction multiple-data (SIMD) technology was implemented into the multiple alignment program Praline by using ‘message passing interface’ (MPI) routines. Over the alignments tested here, the parallelized program performed up to ten times faster on 25 processors compared to the single processor version.

Availability: Example program code for parallelizing pairwise alignment loops is available from http://mathbio.nimr.mrc.ac.uk/~jkleinj/tools/mpicode. The‘ message passing interface’ package (MPICH) is available from http:/www.unix.mcs.anl.gov/mpi/mpich.

Contact: jhering@nimr.mrc.ac.uk

Supplementary information: Praline is accessible at http://mathbio.nimr.mrc.ac.uk/praline.

* To whom correspondence should be addressed.
OrthoGUI: graphical presentation of Orthostrapper results
Authors: Hollich Volker , Storm Christian E. V. , Sonnhammer Erik L. L
Published: September 2002

Summary: Orthostrapper is a program that calculates orthology support values for pairs of sequences in a multiple alignment (Storm and Sonnhammer, Bioinformatics, 18, 92–99, 2002). Here we present OrthoGUI, a web interface and display tool for Orthostrapper analysis. OrthoGUI visualizes the Orthostrapper output in both tabular and tree representations, and can also apply a clustering algorithm to identify groups of multiple orthologs, which are indicated by colour coding.

Availability: http://www.cgb.ki.se/OrthoGUI

Contact: erik.sonnhammer@cgb.ki.se

* To whom correspondence should be addressed.
A kinase sequence database: sequence alignments and family assignment
Authors: Buzko Oleksandr , Shokat Kevan M.
Published: September 2002

Summary: The Kinase Sequence Database (KSD) located at http://kinase.ucsf.edu/ksd contains information on 290 protein kinase families derived by profile-based clustering of the non-redundant list of sequences obtained from a GenBank-wide search. Included in the database are a total of 5041 protein kinases from over 100 organisms. Clustering into families is based on the extent of homology within the kinase catalytic domain (250–300 residues in length). Alignments of the families are viewed by interactive Excel-based sequence spreadsheets. In addition, KSD features evolutionary trees derived for each family and detailed information on each sequence as well as links to the corresponding GenBank entries. Sequence manipulation tools, such as evolutionary tree generation, novel sequence assignment, and statistical analysis, are also provided.

Availability: The kinase sequence database is a web-based service accessible at http://kinase.ucsf.edu/ksd

Contact: buzko@cmp.ucsf.edushokat@cmp.ucsf.edu/ksd

* To whom correspondence should be addressed.
PeCoP: automatic determination of persistently conserved positions in protein families
Authors: Friedberg Iddo , Margalit Hanah
Published: September 2002

Summary: PeCoP is a WWW-based service which accepts a protein sequence, and reports positions that are conserved in close and distant sequence family members. The collation of family members is performed using iterative PSI-BLAST runs. Examining positional conservation in close and distant family members enables a better selection of positions that may play a role in determining the protein's structure and function.

Availability: http://bioinformatics.org/pecop

Contact: idoerg@burnham.org

Supplementary information: http://bioinformatics.org/pecop/about_pecop

* To whom correspondence should be addressed at present address: The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA
Applications of Tree-Maps to hierarchical biological data
Authors: McConnell Patrick , Johnson Kimberly , Lin Simon
Published: September 2002

Summary: A brief overview of Tree-Maps provides the basis for understanding two new implementations of Tree-Map methods. TreeMapClusterView provides a new way to view microarray gene expression data, and GenePlacer provides a view of gene ontology annotation data. We also discuss the benefits of Tree-Maps to visualize complex hierarchies in functional genomics.

Availability: Java class files are freely available at http://mendel.mc.duke.edu/bioinformatics/

Contact: mccon012@mc.duke.edu

Supplementary information: For more information on TreeMapClusterView (see http://mendel.mc.duke.edu/bioinformatics/software/boxclusterview/), and http://mendel.mc.duke.edu/bioinformatics/software/geneplacer/).

* To whom correspondence should be addressed.
An ontology driven architecture for derived representations of macromolecular structure
Authors: Greer Douglas S. , Westbrook John D. , Bourne Philip E.
Published: September 2002

Summary: An object metamodel based on a standard scientific ontology has been developed and used to generate a CORBA interface, an SQL schema and an XML representation for macromolecular structure (MMS) data. In addition to the interface and schema definitions, the metamodel was also used to generate the core elements of a CORBA reference server and a JDBC database loader. The Java source code which implements this metamodel, the CORBA server, database loader and XML converter along with detailed documentation and code examples are available as part of the OpenMMS toolkit.

Availability: http://openmms.sdsc.edu

Contact: dsg@sdsc.edu

* To whom correspondence should be addressed.
The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease
Authors: Weiss Robin A.
Published: September 2002

Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal–to–human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt–Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918–1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal–to–human transplants unleash further infections? Do microbes become more virulent upon cross–species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human–tohuman transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.
Catastrophes after crossing species barriers
Authors: Osterhaus Albert
Published: September 2002

Probably the most tragic examples of virus infections that have caused the deaths of many millions of people in the past century were the influenza and AIDS pandemics. These events occurred as a direct result of the introduction of animal viruses into the human population. Similarly, mass mortalities among aquatic and terrestrial mammals were caused by the introduction of viruses into species in which they had not previously been present. It seems paradoxical that at a time when we have managed to control or even eradicate major human virus infections like polio and smallpox we are increasingly confronted with new or newly emerging virus infections of humans and animals. A complex mix of social, technological and ecological changes, and the ability of certain viruses to adapt rapidly to a changing environment, seems to be at the basis of this phenomenon. Extensive diagnostic and surveillance networks, as well as novel vaccine- and antiviral development strategies should provide us with the safeguards to limit its impact.
Epidemiology and the emergence of human immunodeficiency virus and acquired immune deficiency syndrome
Authors: De Cock Kevin M.
Published: September 2002

Although acquired immune deficiency syndrome (AIDS) was first described in the USA in 1981, there is evidence that individual cases occurred considerably earlier in Central Africa, and serological and virological data show human immunodeficiency virus (HIV) was present in the Democratic Republic of Congo (DRC) as far back as 1959. It is likely that HIV–1 infection in humans was established from cross–species transmission of simian immunodeficiency virus of chimpanzees, but the circumstances surrounding this zoonotic transfer are uncertain. This presentation will review how causality is established in epidemiology, and review the evidence (a putative ecological association) surrounding the hypothesis that early HIV–1 infections were associated with trials of oral polio vaccine (OPV) in the DRC. From an epidemiological standpoint, the OPV hypothesis is not supported by data and the ecological association proposed between OPV use and early HIV/AIDS cases is unconvincing. It is likely that Africa will continue to dominate global HIV and AIDS epidemiology in the near to medium–term future, and that the epidemic will evolve over many decades unless a preventive vaccine becomes widely available.
Update on HIV/SIV infections in Cameroon
Authors: Zekeng Leopold
Published: September 2002

The high degree of human immunodeficiency virus type 1 (HIV–1) diversity in the Cameroonian population indicates a relatively old epidemic in this country. However, studies of pygmy ‘hunter–gatherers’ show only rare HIV–1 infection, mainly after contact with Bantus rather than from contact with non–human primates.
Using human immunodeficiency virus type 1 sequences to infer historical features of the acquired immune deficiency syndrome epidemic and human immunodeficiency virus evolution
Authors: Yusim Karina , Peeters Martine , Pybus Oliver G. , Bhattacharya Tanmoy , Delaporte Eric , Mulanga Claire , Muldoon Mark , Theiler James , Korber Bette
Published: September 2002

In earlier work, human immunodeficiency virus type 1 (HIV–1) sequences were analysed to estimate the timing of the ancestral sequence of the main group of HIV–1, the virus that is responsible for the acquired immune deficiency syndrome pandemic, yielding a best estimate of 1931 (95% confidence interval of 1915–1941). That work will be briefly reviewed, outlining how phylogenetic tools were extended to incorporate improved evolutionary models, how the molecular clock model was adapted to incorporate variable periods of latency, and how the approach was validated by correctly estimating the timing of two historically documented dates. The advantages, limitations, and assumptions of the approach will be summarized, with particular consideration of the implications of branch length uncertainty and recombination. We have recently undertaken new phylogenetic analysis of an extremely diverse set of human immunodeficiency virus envelope sequences from the Democratic Republic of the Congo (the DRC, formerly Zaire). This analysis both corroborates and extends the conclusions of our original study. Coalescent methods were used to infer the demographic history of the HIV–1 epidemic in the DRC, and the results suggest an increase in the exponential growth rate of the infected population through time.
Experimental oral polio vaccines and acquired immune deficiency syndrome
Authors: Hooper Edward
Published: September 2002

The simian immunodeficiency virus (SIV) of the common chimpanzee is widely acknowledged as the direct ancestor of HIV–1. There is increasing historical evidence that during the late 1950s, kidneys were routinely excised from central African chimpanzees by scientists who were collaborating with the polio vaccine research of Dr Hilary Koprowski, and sent – inter alia – to vaccine–making laboratories in the USA and Africa, and to unspecified destinations in Belgium. While there is no direct evidence that cells from these kidneys were used as a substrate for growing Dr Koprowski's oral polio vaccines, there is a startling coincidence between places in Africa where his CHAT vaccine was fed, and the first appearances in the world of HIV–1 group M and group–M–related AIDS. Because of the enormous implications of the hypothesis that AIDS may be an unintended iatrogenic (physician–caused) disease, it is almost inevitable that this theory will engender heated opposition from many of those in the scientific establishment, and those with vested interests.
Untruths and consequences: the false hypothesis linking CHAT type 1 polio vaccination to the origin of human immunodeficiency virus
Authors: Plotkin Stanley A.
Published: September 2002

A book published in 1999 hypothesized that the scientists who worked with the CHAT type 1 attenuated polio strain tested in the former Belgian Congo in the late 1950s had covertly prepared the vaccine in chimpanzee kidney cells contaminated with a simian immunodeficiency virus, which evolved into HIV–1 group M. This paper summarizes the results of the investigation conducted by the author to determine the legitimacy of the accusation. Testimony by eyewitnesses, documents of the time, epidemiological analysis, and ancillary phylogenetic, virologic and PCR data all concur to reject the hypothesis as false and without factual foundation.
Polio vaccine and retroviruses
Authors: Beale John , Horaud Florian
Published: September 2002

In this paper we consider the main steps in the process of manufacture of oral polio vaccine and assess the probable clearance factor for HIV retrovirus at each step. We conclude that the processes employed would have eliminated retrovirus contamination for all practical purposes.