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PubMed1975

Quantification of ventricular performance: a computer-based system for the analysis of angiographic data.

A computer-based quantitative angiography system for the acquisition and analysis of ventriculographic data has been developed. In addition to the apparatus normally required for angiography and left ventricular pressure recording, a digitizing tablet, PDP 11/20 mini computer, and TV monitor with a hard-copy device is employed. Four modes of operation are currently in use: data acquisition, analysis, mini cine, and data tape editor. Data acquisition facilitates forming a magnetic tape record of the digitized pressure, timing, and event identification, together with anywhere from 4 to 100 digitilized LV contours. A number of error checks and feedbacks are incorporated to provide some measure of quality control. In the event an error is written onto the magnetic tape record, the data tape editor can be used to review the record and correct most errors. Analysis of the generated data tape consists of several options which include: pump function, muscle function, pressure derived indices of contractility and systolic time intervals, and contour pattern recognition which is still under development. If the complete analysis option is chosen, a summary of the analysis, referred to as the quick-sight list, is also presented. The so called mini cine option employs a separate and independent acquisition-analysis program. This requires only the end-diastolic (with a segment of wall) and end-systolic contours (without pressure data) to extract the most essential parameters (EDV, EF, CI, HR, and wall mass). As a result of the relative straightforward processing and inherent simplicity, the mini cine option is most frequently used. This system has done much to reduce the time required for analysis of angiographic data, while at the same time maintaining and even improving the quality of the results. Other less tangible benefits include: the possibility to build a readily accessible library of patient data files facilitating a posteriori studies, precise and uniform definition of the rules to input and analyze data, and finally providing a useful step towards fully automatic ventriculographic processing.

Angiocardiography↗
PubMed2006

Neural lineages of the Drosophila brain: a three-dimensional digital atlas of the pattern of lineage location and projection at the late larval stage.

The late larval brain consists of embryonically produced primary neurons forming a deep core cortex, surrounded at the surface by approximately 100 secondary lineages. Each secondary lineage forms a tract (secondary lineage tract) with an invariant and characteristic trajectory. Within the neuropile, tracts of neighboring lineages bundle together to form secondary tract systems. In this paper, we visualized secondary lineages by the global marker BP106 (neurotactin), as well as green fluorescent protein-labeled clones and thereby establish a comprehensive digital atlas of secondary lineages. The information contained in this atlas is the location of the lineage within the cortex, the neuropile compartment contacted by the lineage tract, and the projection pattern of the lineage tract within the neuropile. We have digitally mapped the expression pattern of three genes, sine oculis, period, and engrailed into the lineage atlas. The atlas will enable us and others to analyze the phenotype of mutant clones in the larval brain. Mutant clones can only be interpreted if the corresponding wild-type clone is well characterized, and our lineage atlas, which visualizes all wild-type lineages, will provide this information. Secondly, secondary lineage tracts form a scaffold of connections in the neuropile that foreshadows adult nerve connections. Thus, starting from the larval atlas and proceeding forward through pupal development, one will be able to reconstruct adult brain connectivity at a high level of resolution. Third, the atlas can serve as a repository for genes expressed in lineage-specific patterns.

Anatomy, Artistic↗
PubMed1998

High-fidelity digital hybridization screening.

We developed a highly efficient screening method for minimizing the hybridization of high-density replica (HDR) filters and for allowing simultaneous use of numerous oligonucleotide probes for STS markers. We designated this method "digital hybridization (DH) screening," in which a binary n-bit ID number is given to each probe, and a series of probe mixtures is prepared in an arranged combination. The matrix pattern between probe mixtures and hybridization signals determines the relation between a particular STS marker(s) and the corresponding DNA clone(s). Here, we describe a successful DH screening of over 15,000 human BAC clones with 126 STS marker probes with 7-bit ID numbers, which required only 8 sets of HDR filter hybridizations. Our results indicate that DH screening can be performed with more than 1000 STS marker probes with only 10-bit ID numbers. The DH screening method is convenient, economical, and of high fidelity, and thus it should facilitate the construction of sequence-ready DNA contigs for the human genome as well as for genomes of various species. The principle of DH screening has various applications to the biological sciences.

Animals↗
PubMed2026

Associations between smart infusion pump-electronic health record interoperability and healthcare outcomes: A systematic review.

OBJECTIVE: This study synthesized available evidence on the associations between smart infusion pump-electronic health record (EHR) interoperability and healthcare outcomes. METHODS: A systematic review of PubMed, CINAHL, Embase, and Scopus databases identified 901 records, which were imported into Rayyan® for duplicate removal, independent screening by three reviewers, and resolution of discrepancies. Eligible studies were peer-reviewed, data-driven, and reported associations between smart infusion pump-EHR interoperability and healthcare outcomes. Studies focused solely on technical validation or interoperability prototypes were excluded. A backward citation search identified additional studies. Two reviewers independently extracted and cross-validated study characteristics using standardized templates. Methodological quality was assessed with the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Twenty records of 14 full-text studies and 6 conference proceedings were included. Most records reported positive associations between smart infusion pump-EHR interoperability and outcomes related to safety (e.g., medication administration errors, safety-reported events, pump alerts, and compliance with interoperability and drug library), operational efficiency (e.g., programming and documentation time and technical issues), financial performance (e.g., charges captured, and cost avoided), and user experience domains. Most studies used observational designs, reflecting real-world interoperability implementations, where controlling confounding factors is challenging. Limited reporting of baseline characteristics, pump type, and sample sizes limited comparability across studies. CONCLUSIONS: Smart infusion pump-EHR interoperability was associated with improvements in patient safety, efficiency, charge capture, and user experience, with variable findings across studies. Future research should use rigorous methodologies and standardized measures, examine relationships across outcome domains, assess limitations of pump-EHR interoperability, and evaluate underexplored outcomes, including team communication, cognitive workload, and AI-enabled pumps. IMPLICATIONS FOR CLINICAL PRACTICE: Interoperability should be viewed as a component of a broader sociotechnical system, in which technology, user, workflow, clinical content, and organizational practices collectively determine overall effectiveness.

Humans↗
PubMed2002

HUGE: a database for human large proteins identified in the Kazusa cDNA sequencing project.

We have been developing a HUGE database to summarize results from the sequence analysis of human novel large (>4 kb) cDNAs identified in the Kazusa cDNA sequencing project, systematically designated KIAA plus a four-digit number. HUGE currently contains nearly 2000 gene/protein characteristic tables harboring the results of the computer-assisted analysis of the cDNA and the predicted protein sequences together with those of expression profiling and chromosomal mapping. In the updated version of HUGE, we made it possible to compare each KIAA cDNA sequence with the corresponding entry in the human draft genome sequence that was published recently. Approximately 90% of KIAA cDNAs in HUGE can be localized along the human genome for at least half or more of the cDNA's length. Any nucleotide differences between the cDNA and the corresponding genomic sequences are also presented in detail. This new version of HUGE greatly helps us evaluate the completeness of cDNA clones and the accuracy of cDNA/genomic sequences. More interestingly, in some cases, the ability to compare cDNA with genomic sequences allows us to identify candidate sites of RNA editing. HUGE is available on the World Wide Web at http://www.kazusa.or.jp/huge.

Amino Acid Sequence↗
PubMed1995

Monoclonal antibody MT2 identifies the urodele alpha 1 chain of type XII collagen, a developmentally regulated extracellular matrix protein in regenerating newt limbs.

We previously described the upregulation of the MT2 antigen during urodele limb regeneration and characterized the MT2 antigen as a 310- to 325-kDa chondroitin-sulfated glycoprotein with a core protein of 285-300 kDa. In this study, we screened a newt blastema cDNA library using monoclonal antibody (mAb) MT2 and obtained a 1-kb cDNA fragment, designated Isolate (IS)-1. Subsequent screening of the same library using IS-1 cDNA as a probe provided IS-2, a 2.8-kb cDNA. IS-2 overlaps IS-1 at its 5' end, is highly homologous to a portion of the alpha 1 chain of the chicken type XII collagen cDNA (alpha 1[XII]), and spans a third of the chicken alpha 1[XII] cDNA, from the last 62 amino acids of the second A domain of von Willebrand factor to the first two repeats of the fourth fibronectin type III domain. The peptide sequence deduced from cDNA IS-2 demonstrates invariable tryptophan, leucine, threonine, and tyrosine residues that are highly conserved among all the fibronectin type III domains within IS-2 and between corresponding sequences of IS-2 and chicken alpha 1[XII]. A Northern blot showed a 10-kb band that corresponds to the size of the chicken alpha 1[XII] mRNA. A fusion gene was constructed by inserting the IS-2 cDNA downstream from the malE gene of Escherichia coli, which encodes maltose-binding protein (MBP). The isopropyl beta-D-thiogalactoside-induced fusion protein had the expected molecular weight and reacted to both mAb MT2 and rabbit anti-MBP serum. We conclude that mAb MT2 identifies the urodele alpha 1[XII]. The expression pattern of the type XII collagen gene in newt limb regenerates was examined by in situ hybridization. Type XII collagen transcripts first appeared at 3 days after amputation in cells of the basal layer of the wound epithelium. At Day 10, both the basal wound epithelial cells and the distal mesenchyme cells were highly transcriptionally active. At mid-bud and late-bud blastema stages, wound epithelium expression had decreased, whereas the mesenchyme remained strongly active in transcription and showed a tendency toward distal regionalization. Condensing cartilage showed no signal. Finally, at the late digit stage, hybridization became largely restricted to the perichondrium. The in situ results suggest a developmental role for type XII collagen in regeneration.

Amino Acid Sequence↗
PubMed2001

Matrix-assisted laser desorption/ionization coupled with quadrupole/orthogonal acceleration time-of-flight mass spectrometry for protein discovery, identification, and structural analysis.

The design and operation of a novel UV-MALDI ionization source on a commercial QqoaTOF mass spectrometer (Applied Biosystem/MDS Sciex QSTAR Pulsar) is described. Samples are loaded on a 96-well target plate, the movement of which is under software control and can be readily automated. Unlike conventional high-energy MALDI-TOF, the ions are produced with low energies (5-10 eV) in a region of relatively low vacuum (8 mTorr). Thus, they are cooled by extensive low-energy collisions before selection in the quadrupole mass analyzer (Q1), potentially giving a quasi-continuous ion beam ideally suited to the oaTOF used for mass analysis of the fragment ions, although ion yields from individual laser shots may vary widely. Ion dissociation is induced by collisions with argon in an rf-only quadrupole cell, giving typical low-energy CID spectra for protonated peptide ions. Ions separated in the oaTOF are registered by a four-anode detector and time-to-digital converter and accumulated in "bins" that are 625 ps wide. Peak shapes depend upon the number of ion counts in adjacent bins. As expected, the accuracy of mass measurement is shown to be dependent upon the number of ions recorded for a particular peak. With internal calibration, mass accuracy better than 10 ppm is attainable for peaks that contain sufficient ions to give well-defined Gaussian profiles. By virtue of its high resolution, capability for accurate mass measurements, and sensitivity in the low-femotomole range, this instrument is ideally suited to protein identification for proteomic applications by generation of peptide tags, manual sequence interpretation, identification of modifications such as phosphorylation, and protein structural elucidation. Unlike the multiply charged ions typical of electrospray ionization, the singly charged MALDI-generated peptide ions show a linear dependence of optimal collision energy upon molecular mass, which is advantageous for automated operation. It is shown that the novel pulsing technique of this instrument that increases the sensitivity for precursor ions scans is applicable to the identification of peptides labeled with isotope-coded affinity tags.

Databases, Factual↗
PubMed2004

Digital karyotyping identifies thymidylate synthase amplification as a mechanism of resistance to 5-fluorouracil in metastatic colorectal cancer patients.

Resistance to chemotherapy is a major cause of mortality in advanced cancer patients. In this study, digital karyotyping was used to search for genomic alterations in liver metastases that were clinically resistant to 5-fluorouracil (5-FU). In two of four patients, we identified amplification of an approximately 100-kb region on 18p11.32 that was of particular interest because it contained the gene encoding thymidylate synthase (TYMS), a molecular target of 5-FU. Analysis of TYMS by fluorescence in situ hybridization identified TYMS gene amplification in 23% of 31 5-FU-treated cancers, whereas no amplification was observed in metastases of patients that had not been treated with 5-FU. Patients with metastases containing TYMS amplification had a substantially shorter median survival (329 days) than those without amplification (1,021 days, P <0.01). These data suggest that genetic amplification of TYMS is a major mechanism of 5-FU resistance in vivo and have important implications for the management of colorectal cancer patients with recurrent disease.

Chromosomes, Human, Pair 18↗
PubMed2005

Differential roles for Sox15 and Sox2 in transcriptional control in mouse embryonic stem cells.

Sox family transcription factors play essential roles in cell differentiation, development, and sex determination. Sox2 was previously thought to be the sole Sox protein expressed in mouse embryonic stem (ES) cells. Sox2 associates with Oct3/4 to maintain self-renewal of ES cells. In the current study, digital differential display identified transcripts for an additional Sox family member, Sox15, enriched in mouse ES cells. Reverse transcription-PCR confirmed that Sox15 expression is highest in undifferentiated ES cells and repressed upon differentiation. Sox15 is expressed at low levels in several tissues, including testis and muscle. In vitro studies showed that Sox15, like Sox2, associated with Oct3/4 on DNA sequences containing the octamer motif and Sox-binding site. Gel mobility shift assays and SELEX analyses showed that Sox15 binds similar DNA sequences as Sox2 but with weaker affinity. In contrast to the early embryonic lethality observed in Sox2-null mice, Sox15-null ES cells and mice were grossly normal. DNA microarray analyses revealed that Otx2, Ctgf, Ebaf, and Hrc are dysregulated in Sox15-null ES cells, however. Chromatin immunoprecipitation showed that Sox15, but not Sox2, bound to a Sox consensus binding site within the Hrc gene. Taken together, these data demonstrate differential roles for Sox15 and Sox2 in transcriptional control in mouse ES cells.

Amino Acid Motifs↗
PubMed2001

Electronic teaching files: seven-year experience using a commercial picture archiving and communication system.

With the advent of electronic imaging and the internet, the ability to create, search, access, and archive digital imaging teaching files has dramatically improved. Despite the fact that a picture archival and communication system (PACS) has the potential to greatly simplify the creation of, archival, and access to a department or multifacility teaching file, this potential has not yet been satisfactorily realized in our own and most other PACS installations. Several limitations of the teaching file tools within our PACS have become apparent over time. These have, at our facility, resulted in a substantially reduced role of the teaching file tools for conferences, daily teaching, and research purposes. With the PACS at our institution, academic folders can only be created by the systems engineer, which often serves as an impediment to the teaching process. Once these folders are created, multiple steps are required to identify the appropriate folders, and subsequently save images. Difficulties exist for those attempting to search for the teaching file images. Without pre-existing knowledge of the folder name and contents, it is difficult to query the system for specific images. This is due to the fact that there is currently no fully satisfactory mechanism for categorizing, indexing, and searching cases using the PACS. There is currently no easy mechanism to save teaching, research, or clinical files onto a CD or other removable media or to automatically strip demographic or other patient information from the images. PACS vendors should provide much more sophisticated tools to create and annotate teaching file images in an easy to use but standard format (possibly Radiological Society of North America's Medical Image Resource Center [MIRC] format) that could be exchanged with other sites and other vendors' PAC systems. The privilege to create teaching or conference files should be given to the individual radiologists, technologists, and other users, and an audit should be kept of who has created these files, as well as keep track of who has accessed the files. Vendors should maintain a local PACS library of image quality phantoms, normal variants, and interesting cases and should have the capability of accessing central image repositories such as the RSNA's MIRC images. Commercial PAC systems should utilize a standard lexicon to facilitate the creation and categorization of images, as well as to facilitate sharing of images and related text with other sites. This should be combined with a very easy to use mechanism to write images and related text when appropriate onto removable media (while maintaining a high level of security and confidentiality) to make it easier to share images for teaching, research, or clinical purposes.

Computer-Assisted Instruction↗
PubMed1974

The molecular and crystal structures of 4-N-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-L-asparagine trihydrate and 4-N-(beta-D-glucopyranosyl)-L-asparagine monohydrate. The x-ray analysis of a carbohydrate-peptide linkage.

X-ray analyses have shown that the glucopyranose rings of GlcNAc-Asn [4-N-(2-acetamido-2-deoxy-beta-d-glucopyranosyl)-l-asparagine] and Glc-Asn [4-N-(beta-d-glucopyranosyl)-l-asparagine] both have the C-1 chair conformation and also that the glucose-asparagine linkage of each molecule is present in the beta-anomeric configuration. The dimensions (the estimated standard deviations of the last digit are in parentheses) of the glycosidic bond in GlcNAc-Asn and Glc-Asn are, respectively, C((1))-N((1)) 0.1441(6)nm, 0.146(2)nm; angle O((5))-C((1))-N((1)) 106.8(3) degrees , 105.7(8) degrees ; angle C((2))-C((1))-N((1)) 111.1(4) degrees , 110.4(9) degrees ; angle C((1))-N((1))-C((9)) 121.4(4) degrees , 120.5(9) degrees . The glycosidic torsion angle C((9))-N((1))-C((1))-C((2)) is 141.0 degrees and 157.6 degrees in GlcNAc-Asn and Glc-Asn respectively. Hydrogen-bonding is extensive in these two crystal structures and does affect one torsion angle in particular. Two very different values of chi(1)(N-C(alpha)-C(beta)-C(gamma)) occur for the asparagine residue of the two different molecules; the values of chi(1), -69.0 degrees in GlcNAc-Asn and 61.9 degrees in Glc-Asn, correspond to two different staggered conformations about the C(alpha)-C(beta) bond as the NH(3) (+) group is adjusted to different hydrogen-bonding patterns. The two trans-peptide groups in GlcNAc-Asn show small distortions in planarity whereas that in Glc-Asn is more non-planar. The mean plane through the atoms of the amide group at C((2)) in GlcNAc-Asn is approximately perpendicular (69 degrees ) to the mean plane through the C((2)), C((3)), C((5)) and O((5)) atoms of the glucose ring and that at C((1)) is less perpendicular (65 degrees ). The mean plane through the atoms of the amide group in Glc-Asn makes an angle of only 55 degrees with the mean plane through these same four atoms of the glucose ring. The N((1))-H bond of the amide at C((1)) is trans to the C((1))-H bond in these two compounds; the N((2))-H bond of the amide at C((2)) is trans to the C((2))-H bond in GlcNAc-Asn. The values of the observed and final calculated structure amplitudes have been deposited as Supplementary Publication SUP 50035 (26 pages) at the British Library (Lending Division), (formerly the National Lending Library for Science and Technology), Boston Spa, Yorks. LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1973) 131, 5.

Aminoglycosides↗
PubMed2003

NeuroNames 2002.

NeuroNames is a nomenclature designed as a tool for indexing digital databases of neuroscientific information. It can be used, for example, as the entry point to a digital dictionary of neuroanatomy, to a brain atlas, or to a database of information referenced to specific brain structures. The user can query with terms from many different nomenclatures. One can create a neuroanatomic ontology from NeuroNames by relating an appropriate subset of terms to a conceptual model represented by structures illustrated in a brain atlas. At the conceptual core of NeuroNames are primary structures, the elementary units of the brain in the spatial domain. Each primary structure is associated with a set of synonyms that represent the structure in the symbolic domain. One of the synonyms is designated the default name for use in verbal definitions of other structures. A unique abbreviation based on the default name is provided for labeling images. Neuroscientists classify structures in different contexts reflecting different attributes of interest. Thus, the name of a given structure can appear in any number of hierarchical contexts. In NeuroNames all primary structures are now represented in at least two hierarchies. The first is a nine-level "Brain Hierarchy," in which volumetric structures are grouped by proximity to form successively larger units that represent the brain at different levels of dissection. Secondly, primary structures are categorized in a three-level "spatial attribute hierarchy" used to color- code them for visual display. Grouped structures in the nine-level volumetric hierarchy are designated superstructures, each of which has synonyms, a default term, and an abbreviation. All names of structures not in the hierarchy are designated ancillary terms and are defined in words using the default names of hierarchy structures. With NeuroNames as entry point, we have developed BrainInfo (http://braininfo.rprc.washington.edu), a website that allows searchers to proceed intuitively in a few steps to descriptions and images of specific structures. Currently NeuroNames resides in a Microsoft ACCESS database and includes some 12,200 terms in seven languages.

Abstracting and Indexing↗