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[Further development of the program system for lung function diagnostics running on minicomputer C 8205 (author's transl)].

Starting from the level of 1972 the development is characterized in view of -- general technical, psychological and economical problems -- completion of the program library and the -- technique of semi-on-line data collection. The last point describes experiences using the system of VEB Funkwert Erfurt. Different levels of automatization in lung function labs are discussed.

Computers↗

Emerging systems: between vertebrates and arthropods, the Lophotrochozoa.

Novel molecular model organisms for the study of development and regeneration are emerging among the Lophotrochozoa, the third major branch of bilaterian animals. The polychaete Platynereis, the leech Helobdella, the snail Ilyanassa, and several planarians are efficiently accessed for molecular techniques including large-scale whole-mount in situ hybridization screening, RNA interference or morpholino knock-down. Joint efforts include the generation of genomic resources in the form of expressed sequence tag collections and bacterial artificial chromosome libraries. Current research focuses on early pattern formation during cleavage, the emergence and diversification of body segments, and the formation of photoreceptor cells and eyes. Several lophotrochozoan groups (in particular nereid polychaetes) exhibit modes of development, organ design, or body plans that are considered ancestral in many respects. This is also reflected in the level of genes, making these groups ideally suited for developmental comparative studies.

Animals↗

Global analysis of gene expression patterns in developing mouse neocortex using serial analysis of gene expression.

Molecular inventories of the developing mouse neocortex before and after birth were generated using the global gene expression profiling tool serial analysis of gene expression (SAGE). Libraries were generated from embryonic day 15 and postnatal day 1 mouse neocortex and more than 40,000 tags were collected (20,211 and 22,001 tags, representing 11,706 and 12,402 transcripts, respectively). Comparison of the two libraries resulted in the identification of 321 transcripts that were differentially expressed (P < 0.05). Differential expression was independently verified for selected genes by Northern blotting, and in situ hybridization revealed spatial expression patterns in the neocortex. Differentially expressed transcripts included genes known to be important in neocortical development (e.g., brain factor 1, neuroD2, and Id2), genes not previously associated with neocortical development (such as brahma-related gene 1, receptor for activated C-kinase I, hypermethylated in cancer 2, and Evi9), and genes of unknown identity or function.

Animals↗

DNA display II. Genetic manipulation of combinatorial chemistry libraries for small-molecule evolution.

Biological in vitro selection techniques, such as RNA aptamer methods and mRNA display, have proven to be powerful approaches for engineering molecules with novel functions. These techniques are based on iterative amplification of biopolymer libraries, interposed by selection for a desired functional property. Rare, promising compounds are enriched over multiple generations of a constantly replicating molecular population, and subsequently identified. The restriction of such methods to DNA, RNA, and polypeptides precludes their use for small-molecule discovery. To overcome this limitation, we have directed the synthesis of combinatorial chemistry libraries with DNA "genes," making possible iterative amplification of a nonbiological molecular species. By differential hybridization during the course of a traditional split-and-pool combinatorial synthesis, the DNA sequence of each gene is read out and translated into a unique small-molecule structure. This "chemical translation" provides practical access to synthetic compound populations 1 million-fold more complex than state-of-the-art combinatorial libraries. We carried out an in vitro selection experiment (iterated chemical translation, selection, and amplification) on a library of 10(6) nonnatural peptides. The library converged over three generations to a high-affinity protein ligand. The ability to genetically encode diverse classes of synthetic transformations enables the in vitro selection and potential evolution of an essentially limitless collection of compound families, opening new avenues to drug discovery, catalyst design, and the development of a materials science "biology."

Catalysis↗

Use of a large-scale Triticeae expressed sequence tag resource to reveal gene expression profiles in hexaploid wheat (Triticum aestivum L.).

The US Wheat Genome Project, funded by the National Science Foundation, developed the first large public Triticeae expressed sequence tag (EST) resource. Altogether, 116,272 ESTs were produced, comprising 100,674 5' ESTs and 15 598 3' ESTs. These ESTs were derived from 42 cDNA libraries, which were created from hexaploid bread wheat (Triticum aestivum L.) and its close relatives, including diploid wheat (T. monococcum L. and Aegilops speltoides L.), tetraploid wheat (T. turgidum L.), and rye (Secale cereale L.), using tissues collected from various stages of plant growth and development and under diverse regimes of abiotic and biotic stress treatments. ESTs were assembled into 18,876 contigs and 23,034 singletons, or 41,910 wheat unigenes. Over 90% of the contigs contained fewer than 10 EST members, implying that the ESTs represented a diverse selection of genes and that genes expressed at low and moderate to high levels were well sampled. Statistical methods were used to study the correlation of gene expression patterns, based on the ESTs clustered in the 1536 contigs that contained at least 10 5' EST members and thus representing the most abundant genes expressed in wheat. Analysis further identified genes in wheat that were significantly upregulated (p < 0.05) in tissues under various abiotic stresses when compared with control tissues. Though the function annotation cannot be assigned for many of these genes, it is likely that they play a role associated with the stress response. This study predicted the possible functionality for 4% of total wheat unigenes, which leaves the remaining 96% with their functional roles and expression patterns largely unknown. Nonetheless, the EST data generated in this project provide a diverse and rich source for gene discovery in wheat.

Cluster Analysis↗

Online journals: impact on print journal usage.

PURPOSE: The research sought to determine the impact of online journals on the use of print journals and interlibrary loan (ILL). SETTING: The Library of the Health Sciences-Peoria is a regional site of the University of Illinois at Chicago (UIC) Library with a print journal collection of approximately 400 titles. Since 1999, UIC site licenses have given students and faculty affiliated with UIC-Peoria access to more than 4,000 online full-text journal titles through the Internet. METHODOLOGY: The Library of the Health Sciences-Peoria has conducted a journal-use study over an extended period of time. The information collected from this study was used to assess the impact of 104 online journals, added to the collection in January 1999, on the use of print journals. RESULTS: Results of the statistical analysis showed print journal usage decreased significantly since the introduction of online journals (F(1,147) = 12.10, P < 0.001). This decrease occurred regardless of whether a journal was available only in print or both online and in print. Interlibrary loan requests have also significantly decreased since the introduction of online journals (F(2,30) = 4.46, P < 0.02). CONCLUSIONS: The decrease in use of the print collection suggests that many patrons prefer to access journals online. The negative impact the online journals have had on the use of the journal titles available only in print suggests users may be compromising quality for convenience when selecting journal articles. Possible implications for collection development are discussed.

Analysis of Variance↗

Parallel construction of orthologous sequence-ready clone contig maps in multiple species.

Comparison is a fundamental tool for analyzing DNA sequence. Interspecies sequence comparison is particularly powerful for inferring genome function and is based on the simple premise that conserved sequences are likely to be important. Thus, the comparison of a genomic sequence with its orthologous counterpart from another species is increasingly becoming an integral component of genome analysis. In ideal situations, such comparisons are performed with orthologous sequences from multiple species. To facilitate multispecies comparative sequence analysis, a robust and scalable strategy for simultaneously constructing sequence-ready bacterial artificial chromosome (BAC) contig maps from targeted genomic regions has been developed. Central to this approach is the generation and utilization of "universal" oligonucleotide-based hybridization probes ("overgo" probes), which are designed from sequences that are highly conserved between distantly related species. Large collections of these probes are used en masse to screen BAC libraries from multiple species in parallel, with the isolated clones assembled into physical contig maps. To validate the effectiveness of this strategy, efforts were focused on the construction of BAC-based physical maps from multiple mammalian species (chimpanzee, baboon, cat, dog, cow, and pig). Using available human and mouse genomic sequence and a newly developed computer program to design the requisite probes, sequence-ready maps were constructed in all species for a series of targeted regions totaling approximately 16 Mb in the human genome. The described approach can be used to facilitate the multispecies comparative sequencing of targeted genomic regions and can be adapted for constructing BAC contig maps in other vertebrates.

Animals↗

Protein expression clone repositories for functional proteomics.

The information generated from the sequence of the human genome has inspired efforts to systematically develop organized collections of human cDNA clones for use in expression screens in mammalian cells. These high-throughput cloning initiatives offer significant advantages over the cDNA libraries that have been used in the past, including greater experimental flexibility, immediate identification of hits, information regarding all tested proteins (even for those giving no response) and eventually more comprehensive coverage. Some of the lessons learned and the considerations that underlie the creation of genome-wide cDNA repositories are discussed here. Although still inchoate, these resources are already impacting the manner in which high-throughput functional screens are performed.

Animals↗

Health care machine-readable data files: secondary analysis, access, and the role of the library.

Access to health care machine-readable data files (MRDF) is becoming increasingly important to students and researchers in the health care field who use the data in secondary analysis. Health sciences libraries must play a role in providing such access, and this role should consist primarily in providing users with information about the identity and contents of available MRDF and about how they may be obtained. Libraries should therefore collect extensive materials containing information about the MRDF that may be of interest to their users. Many such materials are available in print, and their quality may be expected to improve as newly developed methods and procedures for constructing bibliographic citations, abstracts, and catalog entries for MRDF are put into practice. Also, it is now feasible to incorporate data file abstracts into existing online bibliographic databases.

Health Services Research↗

Creation of an online collection of emergency medicine literature.

Residents and medical students are challenged to incorporate the latest medical literature into their clinical practice. However, retrieving influential articles in a timely manner can be difficult. To address this, the authors created a collection of influential primary research literature relevant to the practice of emergency medicine. The authors surveyed local experts as to the most influential articles in their area of expertise and then linked articles in the literature collection to full-text versions available through the medical school's digital library. A total of 154 articles were included in the literature collection. These were organized into 23 subject headings and 23 subheadings. Fifty-two residents were surveyed one month after the collection became available; 18 residents (35%) had used the literature collection at that time. An online collection has several advantages: it makes the most relevant literature immediately available during clinical care and allows residents to elaborate on their own knowledge when clinical problems arise. It also can be easily updated and password protected. Similar collections may be developed for use in other educational settings.

Bibliometrics↗

Clinical Features and Outcome Measures Across Still Disease (Systemic Juvenile Idiopathic Arthritis and Adult-Onset Still Disease) Cohorts Worldwide: A Systematic Literature Review.

OBJECTIVE: Multinational research is essential to improve recognition and management of systemic juvenile idiopathic arthritis (sJIA). Current cohorts vary in the clinical variables and outcome measures collected. Adult-onset Still disease (AOSD) and sJIA are widely considered to comprise a single disease spectrum; however, classification criteria and clinical tools differ between groups. This systematic literature review aimed to identify clinical features and outcome measures collected across sJIA and AOSD cohorts worldwide to guide the development of a minimal dataset for Still disease. METHODS: A literature search was conducted from 2000 to 2024 using Ovid MEDLINE, Embase, and Wiley Cochrane Library (Trials). Included articles were in English and described sJIA or AOSD cohorts of &#x2265; 20 patients, reporting patient characteristics, clinical and laboratory features, and outcome measures. RESULTS: A total of 240 articles were included (95 sJIA, 134 AOSD, 11 mixed), from 37 countries, describing 23,136 patients. International League of Associations for Rheumatology classification was used in 77.9% of sJIA studies, whereas 98.5% of AOSD studies used Yamaguchi criteria. There was no clear consensus on the definition of macrophage activation syndrome. Race and ethnicity were only reported in 11.7% of articles. Cohorts evaluated aligned on the most commonly collected laboratory items for both AOSD and sJIA, with some agreement among clinical features, whereas disease outcome measures used to evaluate and follow disease trajectory were variable. CONCLUSION: Data reporting across sJIA and AOSD cohorts for clinical characteristics and outcome measures is widely heterogeneous. Consensus on the identification of a standardized minimal dataset for Still disease cohorts is needed to foster future collaboration and improve patient outcomes.

Humans↗

MEDLINE end-user survey: the University of Florida experience.

The University of Florida Health Science Center Library (UF-HSCL) surveyed MEDLINE end-user activities of the faculty from the six colleges which the UF-HSCL serves. A questionnaire was developed and sent to all faculty members. The Basic SAS program was used to analyze the collected data. This survey was intended to identify the users, the reasons for faculty members not being end users, the purpose for searching MEDLINE, the information retrieval methods, the level of end-user satisfaction, and the librarian's role in information retrieval activities. Many findings from this survey were in agreement with those of the 1988 study by the National Library of Medicine.

Attitude to Computers↗

A collection of bovine cDNA probes for gene expression profiling in muscle.

Array technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to muscle development and pathology as well as meat production in livestock species have been hampered by the lack of appropriate cDNA collections. To overcome this problem, a directed cDNA library was constructed starting from 23 muscles of meat-producing bovines to derive a collection of 3573 clones. A preliminary sequence characterization of this collection indicated that the most abundant transcripts correspond to genes encoding proteins involved in energy metabolism (COX and NADH dehydrogenase subunits) and belonging to the contractile apparatus (myosin chains and troponin isoforms). From this cDNA library, we selected a set of 435 clones representing 340 unique genes, of which 24 were novel. This collection was subsequently completed with 75 specific cDNA probes for genes of interest already studied in our laboratory. The bovine 'muscle' cDNA repertoire thus designed was spotted onto a nylon membrane (macroarray) in order to test its utility to further investigate the transcriptome of bovine muscles in relation to meat quality traits. It is also anticipated that this type of collection might be useful for the study of chronic myologic diseases in other mammalian species, including humans.

Animals↗

Actinobacterial 16S rRNA genes from freshwater habitats cluster in four distinct lineages.

We analysed the phylogenetic relatedness of 16S rRNA genes from freshwater bacteria affiliated with the class Actinobacteria. A polymerase chain reaction assay was developed to identify reliably rare Actinobacteria-related inserts within 16S rRNA gene clone libraries. In 18 libraries constructed from seven freshwater systems, altogether 63 actinobacterial sequence types were collected from a total of > 1800 clones. Sixty of the newly obtained sequences grouped within four distinct phylogenetic lineages. They constitute approximately 75% of the nearly complete sequences within these clusters that are presently available. A comparison with > 300 sequences from various soil habitats revealed that two of these monophyletic actinobacterial clades (acI and acII) almost exclusively harbour 16S rRNA sequence types from freshwaters and estuaries. This may indicate that such bacteria are not inoculated to freshwaters from terrestrial sources, but are autochthonous components of freshwater microbial assemblages. In contrast, sequence types from freshwaters, marine sediments and soils were clearly mixed in another of the actinobacterial lineages (acIV). Sequence divergence within acIV was the highest of all four lineages (88% minimum similarity), which potentially reflects its radiation across several habitat types. Within the freshwater lineages, groups of essentially identical sequence types were retrieved from geographically distant aquatic systems with strikingly different hydrological and limnological characteristics. This points to the necessity to investigate genotypic variability, in situ abundances and activities of these Actinobacteria in freshwater plankton in greater detail by cultivation-independent techniques.

Actinobacteria↗

Measuring contextual characteristics for community health.

OBJECTIVE: To conceptualize and measure community contextual influences on population health and health disparities. DATA SOURCES: We use traditional and nontraditional secondary sources of data comprising a comprehensive array of community characteristics. STUDY DESIGN: Using a consultative process, we identify 12 overarching dimensions of contextual characteristics that may affect community health, as well as specific subcomponents relating to each dimension. DATA COLLECTION: An extensive geocoded library of data indicators relating to each dimension and subcomponent for metropolitan areas in the United States is assembled. PRINCIPAL FINDINGS: We describe the development of community contextual health profiles, present the rationale supporting each of the profile dimensions, and provide examples of relevant data sources. CONCLUSIONS: Our conceptual framework for community contextual characteristics, including a specified set of dimensions and components, can provide practical ways to monitor health-related aspects of the economic, social, and physical environments in which people live. We suggest several guiding principles useful for understanding how aspects of contextual characteristics can affect health and health disparities.

Community Health Planning↗

Isolation and characterization of a diverse set of genes from carrot somatic embryos.

The early events in plant embryogenesis are critical for pattern formation, since it is during this process that the primary apical meristems and the embryo polarity axis are established. However, little is known about the molecular events that are unique to the early stages of embryogenesis. This study of gene expression during plant embryogenesis is focused on identifying molecular markers from carrot (Daucus carota) somatic embryos and characterizing the expression and regulation of these genes through embryo development. A cDNA library, prepared from polysomal mRNA of globular embryos, was screened using a subtracted probe; 49 clones were isolated and preliminarily characterized. Sequence analysis revealed a large set of genes, including many new genes, that are expressed in a variety of patterns during embryogenesis and may be regulated by different molecular mechanisms. To our knowledge, this group of clones represents the largest collection of embryo-enhanced genes isolated thus far, and demonstrates the utility of the subtracted-probe approach to the somatic embryo system. It is anticipated that many of these genes may serve as useful molecular markers for early embryo development.

Animals↗

The NLM Indexing Initiative's Medical Text Indexer.

The Medical Text Indexer (MTI) is a program for producing MeSH indexing recommendations. It is the major product of NLM's Indexing Initiative and has been used in both semi-automated and fully automated indexing environments at the Library since mid 2002. We report here on an experiment conducted with MEDLINE indexers to evaluate MTI's performance and to generate ideas for its improvement as a tool for user-assisted indexing. We also discuss some filtering techniques developed to improve MTI's accuracy for use primarily in automatically producing the indexing for several abstracts collections.

Abstracting and Indexing↗

Enhanced dead-end elimination in the search for the global minimum energy conformation of a collection of protein side chains.

Although the conformational states of protein side chains can be described using a library of rotamers, the determination of the global minimum energy conformation (GMEC) of a large collection of side chains, given fixed backbone coordinates, represents a challenging combinatorial problem with important applications in the field of homology modelling. Recently, we have developed a theoretical framework, called the dead-end elimination method, which allows us to identify efficiently rotamers that cannot be members of the GMEC. Such dead-ending rotamers can be iteratively removed from the system under study thereby tracking down the size of the combinatorial problem. Here we present new developments to the dead-end elimination method that allow us to handle larger proteins and more extensive rotamer libraries. These developments encompass (i) a procedure to determine weight factors in the generalized dead-end elimination theorem thereby enhancing the elimination of dead-ending rotamers and (ii) a novel strategy, mainly based on logical arguments derived from the logic pairs theorem, to use dead-ending rotamer pairs in the efficient elimination of single rotamers. These developments are illustrated for proteins of various sizes and the flow of the current method is discussed in detail. The effectiveness of dead-end elimination is increased by two orders of magnitude as compared with previous work. In addition, it now becomes feasible to use extremely detailed libraries. We also provide an appendix in which the validity of the generalized dead-end criterion is shown. Finally, perspectives for further applications which may now become within reach are discussed.

Aprotinin↗