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At least 919 records · Page 51Linked to original sources
PubMed1998

A randomized controlled trial of automated term composition.

OBJECTIVE: To compare the ability of an Automated Term Composition (ATC) algorithm with non-compositional mappings to provide coverage (exact mappings to a controlled vocabulary) for a randomly selected set of free text entries which were entered as headings to the Impression section of the clinical notes system at the Mayo Foundation. We also compare the results of four evaluators to determine the inter-observer variability and the variance between term sets, with respect to the accuracy of the mappings and the reliability of the failure analysis. METHODS: From a corpus of approximately 1,000,000 unique terms entered into the Impression/Report/Plan section of the clinical notes system in the calendar year 1997, we randomly selected 1,000 terms. We then further randomized these 1,000 terms into two groups of 500 (Sets A and B). We constructed two copies of the same term matching interface, one without ATC (alpha) and one with ATC (beta). We took four expert Indexers and assigned them to one of the following tasks. The first reviewer (R1) compared set A using the alpha program and then set B using the beta program (R1(Aalpha + Bbeta)). The second compared set A using the alpha program and then set B using the alpha program (R2(A + B) alpha). The third compared set B using the beta program and then set A using the beta program (R3(B + A) beta). The fourth compared set A using the beta program and then set B using the alpha program (R4(Abeta + Balpha)). RESULTS: The program with Automated Term Composition mapped 540 out of the 1,000 Concepts correctly (54.0%). The same program without ATC mapped only 276 out of the 1,000 Concepts correctly (27.6%). Therefore the program with ATC was significantly more effective at matching concepts in our problem lists than the same search engine without ATC (p < 0.0001; McNemar Method). These figures result from the comparison of the alpha program with the beta program by reviewers one and four. Failure analysis showed that with the alpha version 425 out of the 724 mismatches were because a base concept was missing from the retrieval set (58.7%) and 299 mismatches were from missing qualifiers or modifiers or both (41.3%). In the beta version of the program (with ATC) 340 out of the 460 mismatches were secondary to there being a missing base concept in the retrieval set (73.9%) and only 120 mismatches due to missing modifiers and or qualifiers (26.1%). CONCLUSIONS: Automated term composition provided significantly better coverage of a randomly chosen set of patient problems, diagnosed at the Mayo Clinic during the 1997 calendar year, when compared with the same information retrieval system without ATC. We believe that these results speak further to the excellent content coverage provided by the UMLS metathesaurus. These authors believe that increased structure, normalization of UMLS content and semantics, and better tools to make use of the currently available content such as automated term composition, are what is needed to leverage the production of commercially viable tools that provide access to controlled vocabularies for medicine.

Abstracting and Indexing↗
PubMed2005

Tissue engineering of bone: search for a better scaffold.

BACKGROUND: Large bone defects still represent a major problem in orthopedics. Traditional bone-repair treatments can be divided into two groups: the bone transport (Ilizarov technology) and the graft transplant (autologous or allogeneic bone grafts). Thus far, none of these strategies have proven to be always resolving. As an alternative, a tissue engineering approach has been proposed where osteogenic cells, bioceramic scaffolds, growth factors and physical forces concur to the bone defect repair. Different sources of osteoprogenitor cells have been suggested, bone marrow stromal cells (BMSC) being in most cases the first choice. METHODS AND RESULTS: In association with mineral tridimensional scaffolds, BMSC form a primary bone tissue which is highly vascularized and colonized by host hemopoietic marrow. The chemical composition of the scaffold is crucial for the osteoconductive properties and the resorbability of the material. In addition, scaffolds should have an internal structure permissive for vascular invasion. Porous bioceramics [hydroxyapatite (HA) and tricalcium phosphate] are osteoconductive and are particularly advantageous for bone tissue engineering application as they induce neither an immune nor an inflammatory response in the implanted host. Earlier, we first reported a cell-based tissue engineering procedure to treat three patients with long bone segmental defects. Cells were loaded on a 100% HA porous ceramic. These scaffolds proved to have good osteoconductive properties resulting in a good functional recovery, but they have not been resorbed after more than 5 years from the implant. In addition, due to the high density of the mineral and the relatively low porosity (50-60%), it was very difficult to monitor the patient recovery during the post-surgery time using X-rays. CONCLUSIONS: We report here some pre-clinical testing of new scaffolds. To compare these second generation ceramic scaffolds more suitable for a tissue engineering approach we had to first establish animal models and analysis procedures including the use of X-ray-computed microtomography associated with X-rays synchroton radiation.

Animals↗
PubMed2003

Optimizing the search algorithm for protein engineering by directed evolution.

An in silico protein model based on the Kauffman NK-landscape, where N is the number of variable positions in a protein and K is the degree of coupling between variable positions, was used to compare alternative search strategies for directed evolution. A simple genetic algorithm (GA) was used to model the performance of a standard DNA shuffling protocol. The search effectiveness of the GA was compared to that of a statistical approach called the protein sequence activity relationship (ProSAR) algorithm, which consists of two steps: model building and library design. A number of parameters were investigated and found to be important for the comparison, including the value of K, the screening size, the system noise and the number of replicates. The statistical model was found to accurately predict the measured activities for small values of the coupling between amino acids, K <or= 1. The ProSAR strategy was found to perform well for small to moderate values of coupling, 0 <or= K <or= 3, and was found to be robust to noise. Some implications for protein engineering are discussed.

Algorithms↗
PubMed2004

Systematic peptide engineering and structural characterization to search for the shortest antimicrobial peptide analogue of gaegurin 5.

As part of an effort to develop new, low molecular mass peptide antibiotics, we searched for the shortest bioactive analogue of gaegurin 5 (GGN5), a 24-residue antimicrobial peptide. Thirty-one kinds of GGN5 analogues were synthesized, and their biological activities were analyzed against diverse microorganisms and human erythrocytes. The structural properties of the peptides in various solutions were characterized by spectroscopic methods. The N-terminal 13 residues of GGN5 were identified as the minimal requirement for biological activity. The helical stability, the amphipathic property, and the hydrophobic N terminus were characterized as the important structural factors driving the activity. To develop shorter antibiotic peptides, amino acid substitutions in an inactive 11-residue analogue were examined. Single tryptophanyl substitutions at certain positions yielded some active 11-residue analogues. The most effective site for the substitution was the hydrophobic-hydrophilic interface in the amphipathic helical structure. At this position, tryptophan was the most useful amino acid conferring favorable activity to the peptide. The introduced tryptophan played an important anchoring role for the membrane interaction of the peptides. Finally, two 11-residue analogues of GGN5, which exhibited strong bactericidal activity with little hemolytic activity, were obtained as property-optimized candidates for new peptide antibiotic development. Altogether, the present approach not only characterized some important factors for the antimicrobial activity but also provided useful information about peptide engineering to search for potent lead molecules for new peptide antibiotic development.

Acrylamide↗
PubMed1993

Searching sequence space to engineer proteins: exponential ensemble mutagenesis.

We describe an efficient method for generating combinatorial libraries with a high percentage of unique and functional mutants. Combinatorial libraries have been successfully used in the past to express ensembles of mutant proteins in which all possible amino acids are encoded at a few positions in the sequence. However, as more positions are mutagenized the proportion of functional mutants is expected to decrease exponentially. Small groups of residues were randomized in parallel to identify, at each altered position, amino acids which lead to functional proteins. By using optimized nucleotide mixtures deduced from the sequences selected from the random libraries, we have simultaneously altered 16 sites in a model pigment binding protein: approximately one percent of the observed mutants were functional. Mathematical formalization and extrapolation of our experimental data suggests that a 10(7)-fold increase in the throughput of functional mutants has been obtained relative to the expected frequency from a random combinatorial library. Exponential ensemble mutagenesis should be advantageous in cases where many residues must be changed simultaneously to achieve a specific engineering goal, as in the combinatorial mutagenesis of phage displayed antibodies. With the enhanced functional mutant frequencies obtained by this method, entire proteins could be mutagenized combinatorially.

Amino Acid Sequence↗
PubMed2006

Web-based information search and retrieval: effects of strategy use and age on search success.

OBJECTIVE: The purpose of this study was to investigate the relationship between strategy use and search success on the World Wide Web (i.e., the Web) for experienced Web users. An additional goal was to extend understanding of how the age of the searcher may influence strategy use. BACKGROUND: Current investigations of information search and retrieval on the Web have provided an incomplete picture of Web strategy use because participants have not been given the opportunity to demonstrate their knowledge of Web strategies while also searching for information on the Web. METHODS: Using both behavioral and knowledge-engineering methods, we investigated searching behavior and system knowledge for 16 younger adults (M = 20.88 years of age) and 16 older adults (M = 67.88 years). RESULTS: Older adults were less successful than younger adults in finding correct answers to the search tasks. Knowledge engineering revealed that the age-related effect resulted from ineffective search strategies and amount of Web experience rather than age per se. Our analysis led to the development of a decision-action diagram representing search behavior for both age groups. CONCLUSION: Older adults had more difficulty than younger adults when searching for information on the Web. However, this difficulty was related to the selection of inefficient search strategies, which may have been attributable to a lack of knowledge about available Web search strategies. APPLICATION: Actual or potential applications of this research include training Web users to search more effectively and suggestions to improve the design of search engines.

Adult↗
PubMed2003

An automated program to screen databases for members of protein families.

We have developed a program, ScreenTransporter (ST), to screen for potential members of recognized transporter families. This program uses Blastpgp as the engine to search a nonredundant database, NRDB90, based on an adjustable E-value cut-off as well as adjustable protein size criteria. Additional parameters can be integrated in later versions. ST is convenient for easily obtaining nonredundant members of transporter families starting from several homologous query sequences. The program can be applied to any protein family.

Computational Biology↗
PubMed2005

Ranking the whole MEDLINE database according to a large training set using text indexing.

BACKGROUND: The MEDLINE database contains over 12 million references to scientific literature, with about 3/4 of recent articles including an abstract of the publication. Retrieval of entries using queries with keywords is useful for human users that need to obtain small selections. However, particular analyses of the literature or database developments may need the complete ranking of all the references in the MEDLINE database as to their relevance to a topic of interest. This report describes a method that does this ranking using the differences in word content between MEDLINE entries related to a topic and the whole of MEDLINE, in a computational time appropriate for an article search query engine. RESULTS: We tested the capabilities of our system to retrieve MEDLINE references which are relevant to the subject of stem cells. We took advantage of the existing annotation of references with terms from the MeSH hierarchical vocabulary (Medical Subject Headings, developed at the National Library of Medicine). A training set of 81,416 references was constructed by selecting entries annotated with the MeSH term stem cells or some child in its sub tree. Frequencies of all nouns, verbs, and adjectives in the training set were computed and the ratios of word frequencies in the training set to those in the entire MEDLINE were used to score references. Self-consistency of the algorithm, benchmarked with a test set containing the training set and an equal number of references randomly selected from MEDLINE was better using nouns (79%) than adjectives (73%) or verbs (70%). The evaluation of the system with 6,923 references not used for training, containing 204 articles relevant to stem cells according to a human expert, indicated a recall of 65% for a precision of 65%. CONCLUSION: This strategy appears to be useful for predicting the relevance of MEDLINE references to a given concept. The method is simple and can be used with any user-defined training set. Choice of the part of speech of the words used for classification has important effects on performance. Lists of words, scripts, and additional information are available from the web address http://www.ogic.ca/projects/ks2004/.

Abstracting and Indexing↗
PubMed2004

Internet usage by low-literacy adults seeking health information: an observational analysis.

BACKGROUND: Adults with low literacy may encounter informational obstacles on the Internet when searching for health information, in part because most health Web sites require at least a high-school reading proficiency for optimal access. OBJECTIVE: The purpose of this study was to 1) determine how low-literacy adults independently access and evaluate health information on the Internet, 2) identify challenges and areas of proficiency in the Internet-searching skills of low-literacy adults. METHODS: Subjects (n=8) were enrolled in a reading assistance program at Bidwell Training Center in Pittsburgh, PA, and read at a 3rd to 8th grade level. Subjects conducted self-directed Internet searches for designated health topics while utilizing a think-aloud protocol. Subjects' keystrokes and comments were recorded using Camtasia Studio screen-capture software. The search terms used to find health information, the amount of time spent on each Web site, the number of Web sites accessed, the reading level of Web sites accessed, and the responses of subjects to questionnaires were assessed. RESULTS: Subjects collectively answered 8 out of 24 questions correctly. Seven out of 8 subjects selected "sponsored sites"-paid Web advertisements-over search engine-generated links when answering health questions. On average, subjects accessed health Web sites written at or above a 10th grade reading level. Standard methodologies used for measuring health literacy and for promoting subjects to verbalize responses to Web-site form and content had limited utility in this population. CONCLUSION: This study demonstrates that Web health information requires a reading level that prohibits optimal access by some low-literacy adults. These results highlight the low-literacy adult population as a potential audience for Web health information, and indicate some areas of difficulty that these individuals face when using the Internet and health Web sites to find information on specific health topics.

Adult↗
PubMed2003

[Preliminary research for constructing tissue-engineered oral mucosa].

OBJECTIVE: To search for a method of constructing tissue-engineered oral mucosa. METHODS: Hard palate mucoperiosteum were excised and extracted from raw SD milk rat. Tissue-engineered oral mucosa was made with the cultured oral keratinocytes that had been digested by Dispase and cultured in the serum-free keratinocytes medium, the supportive membrane being made from sodium alginate. RESULTS: Rat oral mucosal epithelial cells could be obtained with Dispase digestion. It was found that the best time for oral mucosa membrane to be digested to independent cells by Dispase again is ten minutes after the mucosa membrane has been obtained by Dispase; the best density of rat oral mucosa cells cultured is 1.5 x 10(5)/cm2, and the mucosa cells will be difficult to form the colon if the density of cells is too low. The keratinocytes can be cultured in serum-free keratinocytes medium without fibroblast contamination; the mucosa cells grow well on the sodium alginate membrane. CONCLUSION: Tissue-engineered oral mucosa can be constructed with the cultured oral keratinocytes in the serum-free keratinocytes medium and the self-made sodium alginate membrane.

Alginates↗
PubMed1998

CyanoBase, a www database containing the complete nucleotide sequence of the genome of Synechocystis sp. strain PCC6803.

CyanoBase (http://www.kazusa.or.jp/cyano/) is a database containing genomic information on the cyanobacterium Synechocystis sp. strain PCC6803. It furnishes an annotation to each of the 3168 protein genes deduced from the entire nucleotide sequence of this genome. Information on the genome can be directly accessed through three different menus: a clickable physical map of the genome, a gene classification list, and a keyword search menu, all of which are accessible from the main page of the database. The entry page for a gene annotation contains the following information: the location of the gene on the genome, the nucleotide and deduced amino acid sequence of the gene, the result of a similarity search, and the classification of the deduced gene product according to its function. This page has reverse-links to the local physical map and gene classification list so that relevant genes can be searched in terms of their location on the genome and their function. In addition, the main page of CyanoBase provides engines for similarity searches between a query sequence and the entire genome sequence and for keyword searches, in addition to numerous links to pages containing related information.

Bacterial Proteins↗
PubMed1996

An engineering challenge: incontinence.

The search for better incontinence products is under way. This article reports on issues that have inhibited new developments until now and the areas that offer the greatest potential. A diversity of views are aired on this unexplored product sector.

Biomedical Engineering↗
PubMed1988

Fast atom bombardment mass spectral search for the amino terminus of genetically engineered alpha 1-antitrypsin.

Protein structure determination of genetically engineered alpha 1-antitrypsin was carried out using the technique of 'fast atom bombardment (FAB) MAPPING'. CNBr, tryptic and chymotryptic FAB MAPS were produced. The anticipated amino terminal region of the molecule was not mapped at the expected mass, raising the possibility of post-translational modification. A specific experiment was designed to isolate and identify this region by FAB mass spectral screening of high-performance liquid chromatography separated peptides. A signal at m/z 1231 was observed which could not be assigned to any sequence in the molecule using the computer program. Following CNBr treatment, this signal disappeared completely, giving rise to a new signal at m/z 1058. The amino terminus was thus found to be extended by the presence of an N-acetyl methionine residue, and this discovery is the subject of the present paper; another modification within the sequence will be reported elsewhere. Combining the FAB MAPPING data, the overall structural confirmation achieved was 93% of the recombinant alpha 1-antitrypsin molecule.

Amino Acid Sequence↗