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The sequence asymmetry of the Escherichia coli chromosome appears to be independent of strand or function and may be evolutionarily conserved.

I have examined potential determinants of the asymmetric distribution of nucleotide sequences in the genome of Escherichia coli as cataloged in GenBank release 44. I have used the frequency of occurrence of all possible tetranucleotides in a given sequence catalog or derivative as a comparative measure of asymmetry. The GenBank-cataloged strand and its complement show statistically similar (not complementary) distributions. The distribution is statistically similar in comparisons between the protein coding subset and the total genome, the coding subset and selected non-coding genes, the coding subset and the remainder of the DNA, and the coding subset and stable RNA sequences. I have compared the distribution in the genome of E. coli with the distributions found in the cataloged genomes of Salmonella typhimurium, Bacillus subtilis, and of coliphages lambda and T7. The distribution summed in both strands of the cataloged DNA differs statistically only in comparisons with lytic bacteriophage T7 because only the two strands of T7 show statistically dissimilar distributions. Despite similarities in tetranucleotide distribution, the pattern of codon complementarity in B. subtilis is different than that documented for E. coli. Thus, sequence asymmetry does not seem related to specific DNA function or to documented similarities or differences in codon bias. The sequence asymmetry of the E. coli genome may thus reflect a hitherto unsuspected pattern impressed on both strands of DNA which is or can be packaged into bacterial genomes.

Bacillus subtilis↗

The rat blood-brain barrier transcriptome.

The blood-brain barrier (BBB) is the cellular interface between the circulating blood and neural environment, and is created by apposed endothelial cells and their intercellular tight junctions. Many aspects of how the BBB functions at the molecular level remain unresolved; therefore, we report for the first time a comprehensive gene expression profile of rat brain microvessels using serial analysis of gene expression (SAGE). We assembled a full and quantitative SAGE catalog containing 101,364 tags, of which 33% of the tags matched known genes, 51% matched expressed sequence tags (ESTs) in the Unigene database, and 16% of the tags were unassigned. The transcriptome catalog contains many new and novel transcripts among known BBB genes. A large compliment of junctional proteins and an extensive assortment of facilitated carrier and ATP-dependent transporters are included. To identify microvessel-enriched transcripts, we compared the microvessel SAGE catalog to cortex and hippocampus SAGE catalogs. This resulted in identification of 864 genes, including several known for their abundant expression at the BBB, such as the transferrin receptor (TrnR). Sorting enriched genes based on function revealed groups that encode transporters (11%), receptors (5%), proteins involved in vesicle trafficking (4%), structural proteins (10%), and components of signal transduction pathways (17%). This genomic repertoire emphasizes the unique cellular phenotype existing within the brain and further implicates the BBB as a mediator between the brain and periphery. These results may provide a useful resource and reference point from which to determine the effects of different physiological, developmental, and disease processes on BBB gene expression.

Animals↗

Reclassification and documentation in talog cards and a computer stored record.

A project to recatalog and reclassify the book collection of the Bowman Gray School of Medicine Library utilizing the Magnetic Tape/Selectric Typwriter system for simultaneous catalog card production and computer stored data acquisition marks the beginning of eventual computerization of all library operations. A keyboard optical display system will be added by late 1970. Major input operations requiring the creation of "hard copy" will continue via the MTST system. Updating, editing and retrieval operations as well as input without hard copy production will be done through the "on-line" keyboard optical display system. Once the library's first data bank, the book catalog, has been established the computer may be consulted directly for library holdings from any optical display terminal throughout the medical center. Three basic information retrieval operations may be carried out through "on-line" optical display terminals. Output options include the reproduction of part or all of a given document, or the generation of statistical data, which are derived from two Acquisition Code lines. The creation of a central bibliographic record of Bowman Gray Faculty publications patterned after the cataloging program is presently under way. The cataloging and computer storage of serial holdings records will begin after completion of the reclassification project. All acquisitions added to the collection since October 1967 are computer-stored and fully retrievable. Reclassification of older titles will be completed in early 1971.

Book Classification↗

Automated hospital information system functions for dietetics.

Utilization of computer technology in health care is expanding, and managers need information regarding existing automated functions when making decisions relative to system design or acquisition. The Automated Hospital Information System (AHIS) Component Catalog, compiled by the Health Services Research Center/Health Care Technology Center (HSRC/HCTC) at the University of Missouri-Columbia, describes the features of software packages offered by vendors and utilized in hospitals. On the basis of an analysis of the contents of the Catalog relative to automated functions for dietetic departments, charge capturing and diet change notification were the functions used most frequently in hospitals. Although a stores inventory was not included as a component offered by any of the responding vendors, 23 of the hospital systems described in the catalog included a stores inventory component. Menu planning and meal scheduling were functions which were both available from vendors and utilized in hospitals. The nutrient analysis function was implemented in some of the larger hospitals. The information in the Catalog reflects the availability and adoption of automated hospital information system components for dietetic functions.

Dietetics↗

Three-way division combined with conversion to Medical Subject Headings(MeSH) in a medium-sized medical library.

Conversion to MeSH and other reasons are enumerated for the division of an undivided dictionary card catalog into a three-way divided catalog, consisting of Proper Names, Titles, and Topical Subjects sections. Methodology of division is described. Conversion from Library of Congress Subject Headings to Medical Subject Headings (MeSH) as an authority list stimulated such concurrent changes as (1) the introduction of a guide card system that eliminates typing of subject headings on catalog cards and (2) the adoption of a filing system that employs reverse chronological order for all types of sequential material in the Proper Names and Titles sections and for all material in the Topical Subjects section. The ancillary decisions, procedures, and methods necessitated by these major conversions are also described.

Catalogs, Library↗

Mechanization of library procedures in the medium-sized medical library. 8. Suspension of computer atalog.

A system for the substitution of a computer-printed book catalog for a card catalog was put to the test by making the former the sole means of locating material in the library, after four years of being used merely as an adjunct to the card catalog. It was found not suitable, and a new system is being devised in the light of the difficulties encountered. The reasons why the system broke down and the plans for the new one are described.

Catalogs, Library↗

IDID: inherited diseases in dogs: web-based information for canine inherited disease genetics.

The domestic dog ( Canis familiaris) shows greater phenotypic variation than any other mammal. A corollary of this variation has been the recognition of more naturally occurring inherited diseases in dogs than have been cataloged in any other species apart from man. Recent catalogs list more than 370. A searchable Web-based database "Inherited Diseases in Dogs" (http://www.vet.cam.ac.uk/idid) has been developed. It catalogs diseases and conditions of dogs which are likely to be transmitted wholly or partly through a genetic mechanism, together with breeds in which they have been described. It contains disease listings and short descriptions, genetic and molecular genetic summaries where known, and connects to entry points to the literature on each disease.

Animals↗

Comparison of the NCI open database with seven large chemical structural databases.

Eight large chemical databases have been analyzed and compared to each other. Central to this comparison is the open National Cancer Institute (NCI) database, consisting of approximately 250 000 structures. The other databases analyzed are the Available Chemicals Directory ("ACD," from MDL, release 1.99, 3D-version); the ChemACX ("ACX," from CamSoft, Version 4.5); the Maybridge Catalog and the Asinex database (both as distributed by CamSoft as part of ChemInfo 4.5); the Sigma-Aldrich Catalog (CD-ROM, 1999 Version); the World Drug Index ("WDI," Derwent, version 1999.03); and the organic part of the Cambridge Crystallographic Database ("CSD," from Cambridge Crystallographic Data Center, 1999 Version 5.18). The database properties analyzed are internal duplication rates; compounds unique to each database; cumulative occurrence of compounds in an increasing number of databases; overlap of identical compounds between two databases; similarity overlap; diversity; and others. The crystallographic database CSD and the WDI show somewhat less overlap with the other databases than those with each other. In particular the collections of commercial compounds and compilations of vendor catalogs have a substantial degree of overlap among each other. Still, no database is completely a subset of any other, and each appears to have its own niche and thus "raison d'être". The NCI database has by far the highest number of compounds that are unique to it. Approximately 200 000 of the NCI structures were not found in any of the other analyzed databases.

Cluster Analysis↗

[Forensic evaluation of physical damage in the early Middle Ages--a comparison with current occupational disability guidelines].

The legal systems of the Germanic tribes in the early Middle Ages elaborated detailed catalogs of forfeits in compensation for certain physical injuries. The perpetrator had to pay the forfeit to the injured person, or in case of manslaughter, to the tribe of the dead. By doing so he could avert the feud which otherwise faced him. These catalogs of forfeits exactly reflect the relative value that was appointed to certain parts of the body and to sensory functions. The catalog of the Lex Saxonum (c. 802), in which physical injuries are listed, ranging from loss of single phalanges, differentiated between thumb, forefinger, small finger, and the other fingers, to death, is compared with modern grades of disability. There are surprising parallels and interesting contrasts. Bilateral deafness is put on a level with bilateral blindness, the loss of both hands, both feet, both testicles, and death.

Disability Evaluation↗

The magnitude distribution of declustered earthquakes in Southern California.

The binned distribution densities of magnitudes in both the complete and the declustered catalogs of earthquakes in the Southern California region have two significantly different branches with crossover magnitude near M = 4.8. In the case of declustered earthquakes, the b-values on the two branches differ significantly from each other by a factor of about two. The absence of self-similarity across a broad range of magnitudes in the distribution of declustered earthquakes is an argument against the application of an assumption of scale-independence to models of main-shock earthquake occurrence, and in turn to the use of such models to justify the assertion that earthquakes are unpredictable. The presumption of scale-independence for complete local earthquake catalogs is attributable, not to a universal process of self-organization leading to future large earthquakes, but to the universality of the process that produces aftershocks, which dominate complete catalogs.

Journal Article↗

Wheat embryo mitochondrial 18S ribosomal RNA: evidence for its prokaryotic nature.

We present a catalog of sequences of oligonucleotides produced by T1 ribonuclease digestion of 32P-labeled small-ribosomal-subunit RNA ("18S rRNA) isolated from purified wheat embryo mitochondria. This catalog is compared to catalogs published for prokaryotic and chloroplast 16S rRNAs and to preliminary results for wheat cytosol 18S rRNA. These comparisons indicate that: (1) wheat mitochondrial 18S rRNA is clearly prokaryotic in nature, showing significantly more sequence homology with 16S rRNAs than can be expected to arise by chance (p less than 0.000001); (2) shared oligonucleotide sequences include an especially high proportion of those identified as conserved in the evolution of prokaryotic rRNAs; and (3) wheat embryo mitochondrial and cytosol 18S rRNAs retain no more, and perhaps less, than the minimum sequence homology detectable by this sensitive method. These results argue in favor of an endosymbiotic origin for mitochondria.

Base Sequence↗

A survey and evaluation of human genetic traits used in classroom laboratory studies.

Twenty-six selected introductory biology and genetics laboratory manuals were examined and were found to include 57 human "inherited" traits as examples for classroom study. Forty-three of these 57 traits are included in McKusick's catalog of human inherited characteristics, Mendelian Inheritance in Man. Of these 43 traits, 26 are annotated with an asterisk, indicating that their modes of inheritance are well documented, while 17 traits are not so annotated, suggesting uncertain mechanisms of inheritance. Fourteen of the 57 traits are not found in McKusick's catalog, implying that they may not be inherited traits at all or that their modes of inheritance may be polygenic. Current literature also suggest that certain traits included in the McKusick catalog may, in fact, not have a genetic basis. Notable examples of such questionable traits are handedness, hand clasping, and tongue rolling. Clearly, a need exists for reliable morphological and easily detected biochemical human genetic traits for use in classroom instruction. Authors preparing instructional manuals for introductory biology and genetics laboratory studies should carefully select the traits with which they illustrate human inheritance. A first requisite for selection of such characteristics must be conclusive evidence that the trait does, indeed, have an established genetic basis. Additional criteria for selection of such traits are also discussed.

Bibliographies as Topic↗

Genome annotation past, present, and future: how to define an ORF at each locus.

Driven by competition, automation, and technology, the genomics community has far exceeded its ambition to sequence the human genome by 2005. By analyzing mammalian genomes, we have shed light on the history of our DNA sequence, determined that alternatively spliced RNAs and retroposed pseudogenes are incredibly abundant, and glimpsed the apparently huge number of non-coding RNAs that play significant roles in gene regulation. Ultimately, genome science is likely to provide comprehensive catalogs of these elements. However, the methods we have been using for most of the last 10 years will not yield even one complete open reading frame (ORF) for every gene--the first plateau on the long climb toward a comprehensive catalog. These strategies--sequencing randomly selected cDNA clones, aligning protein sequences identified in other organisms, sequencing more genomes, and manual curation--will have to be supplemented by large-scale amplification and sequencing of specific predicted mRNAs. The steady improvements in gene prediction that have occurred over the last 10 years have increased the efficacy of this approach and decreased its cost. In this Perspective, I review the state of gene prediction roughly 10 years ago, summarize the progress that has been made since, argue that the primary ORF identification methods we have relied on so far are inadequate, and recommend a path toward completing the Catalog of Protein Coding Genes, Version 1.0.

Animals↗

Vere-Jones' self-similar branching model.

Motivated by its potential application to earthquake statistics as well as for its intrinsic interest in the theory of branching processes, we study the exactly self-similar branching process introduced recently by Vere-Jones. This model extends the ETAS class of conditional self-excited branching point-processes of triggered seismicity by removing the problematic need for a minimum (as well as maximum) earthquake size. To make the theory convergent without the need for the usual ultraviolet and infrared cutoffs, the distribution of magnitudes m' of daughters of first-generation of a mother of magnitude m has two branches m < m' with exponent beta - d and m' > m with exponent beta + d, where beta and d are two positive parameters. We investigate the condition and nature of the subcritical, critical, and supercritical regime in this and in an extended version interpolating smoothly between several models. We predict that the distribution of magnitudes of events triggered by a mother of magnitude m over all generations has also two branches m' < m with exponent and with exponent beta - h, with h=d squareroot of (1-s), where s is the fraction of triggered events. This corresponds to a renormalization of the exponent d into h by the hierarchy of successive generations of triggered events. For a significant part of the parameter space, the distribution of magnitudes over a full catalog summed over an average steady flow of spontaneous sources (immigrants) reproduces the distribution of the spontaneous sources with a single branch and is blind to the exponents beta, d of the distribution of triggered events. Since the distribution of earthquake magnitudes is usually obtained with catalogs including many sequences, we conclude that the two branches of the distribution of aftershocks are not directly observable and the model is compatible with real seismic catalogs. In summary, the exactly self-similar Vere-Jones model provides an attractive new approach to model triggered seismicity, which alleviates delicate questions on the role of magnitude cutoffs in other non-self-similar models. The new prediction concerning two branches in the distribution of magnitudes of aftershocks could be tested with recently introduced stochastic reconstruction methods, tailored to disentangle the different triggered sequences.

Journal Article↗

Arabidopsis genes involved in acyl lipid metabolism. A 2003 census of the candidates, a study of the distribution of expressed sequence tags in organs, and a web-based database.

The genome of Arabidopsis has been searched for sequences of genes involved in acyl lipid metabolism. Over 600 encoded proteins have been identified, cataloged, and classified according to predicted function, subcellular location, and alternative splicing. At least one-third of these proteins were previously annotated as "unknown function" or with functions unrelated to acyl lipid metabolism; therefore, this study has improved the annotation of over 200 genes. In particular, annotation of the lipolytic enzyme group (at least 110 members total) has been improved by the critical examination of the biochemical literature and the sequences of the numerous proteins annotated as "lipases." In addition, expressed sequence tag (EST) data have been surveyed, and more than 3,700 ESTs associated with the genes were cataloged. Statistical analysis of the number of ESTs associated with specific cDNA libraries has allowed calculation of probabilities of differential expression between different organs. More than 130 genes have been identified with a statistical probability > 0.95 of preferential expression in seed, leaf, root, or flower. All the data are available as a Web-based database, the Arabidopsis Lipid Gene database (http://www.plantbiology.msu.edu/lipids/genesurvey/index.htm). The combination of the data of the Lipid Gene Catalog and the EST analysis can be used to gain insights into differential expression of gene family members and sets of pathway-specific genes, which in turn will guide studies to understand specific functions of individual genes.

Acylation↗

Trends in the measurement of health utilities in published cost-utility analyses.

OBJECTIVE: The Panel on Cost-Effectiveness in Health and Medicine recommended the compilation of a catalog of health state utility weights for use in cost-utility analyses (CUAs), and has given methodological recommendations. This study presents an update, through 2001, to our current registry of utility weights (available at http://www.tufts-nemc.org/cearegistry; previously at http://www.hsph.harvard.edu/cearegistry), and documents recent changes in methods used for utility weight elicitation. METHODS: We searched the English-language medical literature for original CUAs reporting outcomes as cost per quality-adjusted life-year (QALY). Two trained readers independently audited each article, abstracting data on the health state descriptions, corresponding utility weights, methods of elicitation, and sources of the estimates. The utility elicitation methods from 1998 to 2001 were compared with the methods used to obtain utilities before 1998. RESULTS: We identified 306 CUAs published after 1998, reporting 1210 separate health-related utility estimates, bringing the total in our catalog to 2159 weights. Most frequently, health states pertained to the circulatory system and oncology. Methods varied substantially: 36% of authors used direct elicitation (standard gamble, time trade-off or rating scale), 23% used generic health status instruments (EQ-5D, Health Utilities Index, etc.), and 25% estimated weights based on clinical judgment. Community preferences were used in 27% of the values. Compared with pre-1998, utilities published from 1998 to 2001 were more likely to be elicited using a generic instrument, more likely elicited from community samples, and less likely derived from expert opinion, with no formally employed methodology. CONCLUSIONS: Increasingly, analysts conducting CUAs are using generic, preference-weighted instruments, and relying on community-based preferences. Our catalog of utility weights provides a useful reference tool for producers and consumers of CUAs, but also highlights the continued need for improvement in methods and transparency.

Australia↗

No phenotypic resistance observed for most group-3 and -4 variants in Mycobacterium tuberculosis genes related to bedaquiline, clofazimine, delamanid, and pretomanid in a Central and West African context.

The interpretation of genetic variants' association (or not) with phenotypic resistance to newly introduced and repurposed antituberculosis drugs remains challenging, as many mutations detected by whole-genome sequencing (WGS) are classified as of uncertain significance (group 3) or not associated with resistance-interim (group 4) by the World Health Organization (WHO) mutation catalog v2. We evaluated the phenotypic impact of such variants on minimum inhibitory concentrations (MICs) for bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), and pretomanid (PA) in Mycobacterium tuberculosis complex isolates from the multi-country DIAMA cohort in sub-Saharan Africa (SSA), which recruited RR/RS-TB patients na&#xef;ve to these drugs. Among 1,475 isolates with available WGS data, 163 variants met eligibility criteria; due to viable strain unavailability, 89 isolates carrying 29 unique BDQ/CFZ-related and 60 unique DLM/PA-related variants were tested for MIC determination using broth microdilution. Additional structural modeling was performed to explore potential effects of amino-acid substitutions on protein stability. Among BDQ/CFZ-related variants, MICs above the critical concentrations (CCs) were consistently associated with mmpR5 variants, whereas variants in atpE, pepQ, and Rv1979c were not. DLM/PA variants (ddn, fbiA-D, and fgd1) were frequently detected as non-fixed populations, yet rarely yielding MIC values above the CC. Predicted structural destabilization showed no consistent association with MIC values or variant fixation status. Under the conditions tested, phenotypic resistance was not detected for most group 3 and 4 variants detected by WGS. Our data provide evidence from SSA to support improved interpretation of resistance-associated mutations for new and repurposed antituberculosis drugs.IMPORTANCEWhole-genome sequencing increasingly detects Mycobacterium tuberculosis complex mutations classified by the World Health Organization (WHO) mutation catalog v2 as group 3 variants of uncertain significance or group 4 variants not associated with resistance-interim, limiting reliable prediction of resistance to new and repurposed antituberculosis drugs. By generating minimum inhibitory concentration (MIC) data for such variants identified in a multi-country sub-Saharan African cohort, this study provides phenotypic evidence to support future refinement and expansion of the WHO mutation catalog v2. Notably, mmpR5 variants associated with elevated bedaquiline/clofazimine MICs were identified in eight isolates, suggesting that some patients in this cohort may have harbored pre-existing resistance-associated variants yet remained potentially eligible for bedaquiline-containing regimens. These findings contribute to improving the interpretation of genomic resistance data and strengthening surveillance of resistance to bedaquiline, clofazimine, delamanid, and pretomanid.

Mycobacterium tuberculosis↗

Axiope tools for data management and data sharing.

Many areas of biological research generate large volumes of very diverse data. Managing this data can be a difficult and time-consuming process, particularly in an academic environment where there are very limited resources for IT support staff such as database administrators. The most economical and efficient solutions are those that enable scientists with minimal IT expertise to control and operate their own desktop systems. Axiope provides one such solution, Catalyzer, which acts as flexible cataloging system for creating structured records describing digital resources. The user is able specify both the content and structure of the information included in the catalog. Information and resources can be shared by a variety of means, including automatically generated sets of web pages. Federation and integration of this information, where needed, is handled by Axiope's Mercat server. Where there is a need for standardization or compatibility of the structures usedby different researchers this canbe achieved later by applying user-defined mappings in Mercat. In this way, large-scale data sharing can be achieved without imposing unnecessary constraints or interfering with the way in which individual scientists choose to record and catalog their work. We summarize the key technical issues involved in scientific data management and data sharing, describe the main features and functionality of Axiope Catalyzer and Axiope Mercat, and discuss future directions and requirements for an information infrastructure to support large-scale data sharing and scientific collaboration.

Animals↗