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PubMed1996

Physical mapping of chromosome 6: a strategy for the rapid generation of sequence-ready contigs.

The development of radiation hybrid (RH) mapping (Cox et al., 1990) and the availability of large numbers of STS markers, together with extensive bacterial clone resources provided a means to accelerate the process of mapping a human chromosome and preparing bacterial clone contigs ready to sequence. Our aim is to construct physical clone maps covering those regions of chromosome 6 that are not currently extensively mapped, and use these to determine the DNA sequence of the whole chromosome. We report here a strategy which initially involves establishing a high density framework map using RH mapping. The framework markers are then used for the identification of bacterial genomic clones covering the chromosome. The bacterial clones are analysed by restriction enzyme fingerprinting and STS-content analysis to identify sequence-ready contigs. Contig gap closure will also be performed by clone walking.

Chromosome Mapping↗

PubMed1997

The nature of memory processes underlying recognition judgments in the process dissociation procedure.

The hypothesis is tested that the memory processes involved in recognition judgments in the process dissociation procedure are the same as those involved in standard source-monitoring tasks. It is shown how source-monitoring response categories can be mapped onto process dissociation response categories. On the basis of this abbreviation, an experiment was conducted in which it was possible to compare, using a multinomial modeling approach, the parameters representing memory processes in the process dissociation procedure with those involved in source monitoring. For the two different encoding conditions realized, the results are compatible with the hypothesis that the same processes are involved in source monitoring and in recognition judgments in the process dissociation procedure. Implications for the interpretation of the model's parameters are discussed.

Adolescent↗

PubMedDate not supplied

Championship management for healthcare organizations.

Stakeholders will put increasing pressure on integrated health systems (IHS) for measured performance, demanding data on quality and patient satisfaction, while simultaneously pressing for lower cost. The changes to Joint Commission on Accreditation of Healthcare Organizations (Joint Commission) and the growing importance of the National Committee on Quality Assurance (NCQA) are simply forerunners of an intensifying trend. Quality of care in particular will face increasing scrutiny. Achieving competitive targets in these areas will also require measures addressing demand and worker satisfaction. "Balanced scorecard" approaches will allow IHS and their accountable work groups to track performance on several dimensions and establish integrated goals or targets. Those with consistently good scores will be labeled "champions." Champions will support the multidimensional measures with improved decision processes. About eight major processes will be central--governance/strategic management, clinical quality, clinical organization, financial planning, planning and marketing, information services, human resources, and plant services. It is possible to map these processes to the criteria of the Joint Commission, NCQA, and Malcolm Baldrige Quality Award. The processes themselves can be measured and common weaknesses identified and corrected. Champions share some common characteristics that seem to arise from the combination of processes and measures. Among these characteristics are service line orientation, extensive partnering with other organizations, and the possibility of outsourcing organizational components.

Decision Making, Organizational↗

PubMed1992

Networks formed by dorsal root ganglion neurites within spinal cord explants: a computer-aided analysis of HRP intracellularly labeled neurons.

Dorsal root ganglion (DRG) neurons from rat embryos were explanted either alone or with the attached spinal cord (SC). Neuritic processes were mapped out histologically using an intracellular iontophoretic HRP method. Computer reconstructions and morphometric parameters allowed a comparative quantitative analysis of the DRG neurons and of their neuritic processes in both models. The first model, strongly dependent on nerve growth factor (NGF) for its survival, developed large multidirectional processes. The second model showed a bipolar distribution of its neuritic processes, the central one entering predominantly the dorsolateral part of the cord explant and ramifying both homo- and heterolaterally. The quantitative data revealed a significant decrease in the overall size of the neuritic networks of the second model (with attached SC). A discriminant analysis permitted the recognition of these two populations of DRG neurons. The role of the spinal cord explant, and more precisely the target cells of the dorsal horn, was considered to be a prominent factor in the development of the DRG neuritic networks.

Animals↗

PubMed1997

Multiple-complete-digest restriction fragment mapping: generating sequence-ready maps for large-scale DNA sequencing.

Multiple-complete-digest mapping is a DNA mapping technique based on complete-restriction-digest fingerprints of a set of clones that provides highly redundant coverage of the mapping target. The maps assembled from these fingerprints order both the clones and the restriction fragments. Maps are coordinated across three enzymes in the examples presented. Starting with yeast artificial chromosome contigs from the 7q31.3 and 7p14 regions of the human genome, we have produced cosmid-based maps spanning more than one million base pairs. Each yeast artificial chromosome is first subcloned into cosmids at a redundancy of x15-30. Complete-digest fragments are electrophoresed on agarose gels, poststained, and imaged on a fluorescent scanner. Aberrant clones that are not representative of the underlying genome are rejected in the map construction process. Almost every restriction fragment is ordered, allowing selection of minimal tiling paths with clone-to-clone overlaps of only a few thousand base pairs. These maps demonstrate the practicality of applying the experimental and software-based steps in multiple-complete-digest mapping to a target of significant size and complexity. We present evidence that the maps are sufficiently accurate to validate both the clones selected for sequencing and the sequence assemblies obtained once these clones have been sequenced by a "shotgun" method.

Base Composition↗

PubMed1995

Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart.

BACKGROUND: Ventricular tachycardia may result from vortexlike reentrant excitation of the myocardium. Our general hypothesis is that in the structurally normal heart, these arrhythmias are the result of one or two nonstationary three-dimensional electrical scroll waves activating the heart muscle at very high frequencies. METHODS AND RESULTS: We used a combination of high-resolution video imaging, electrocardiography, and image processing in the isolated rabbit heart, together with mathematical modeling. We characterized the dynamics of changes in transmembrane potential patterns on the epicardial surface of the ventricles using optical mapping. Image processing techniques were used to identify the surface manifestation of the reentrant organizing centers, and the location of these centers was used to determine the movement of the reentrant pathway. We also used numerical simulations incorporating Fitzhugh-Nagumo kinetics and realistic heart geometry to study how stationary and nonstationary scroll waves are manifest on the epicardial surface and in the simulated ECG. We present epicardial surface manifestations (reentrant spiral waves) and ECG patterns of nonstationary reentrant activity that are consistent with those generated by scroll waves established at the right and left ventricles. We identified the organizing centers of the reentrant circuits on the epicardial surface during polymorphic tachycardia, and these centers moved during the episodes. In addition, the arrhythmias that showed the greatest movement of the reentrant centers displayed the largest changes in QRS morphology. The numerical simulations showed that stationary scroll waves give rise to monomorphic ECG signals, but nonstationary meandering scroll waves give rise to undulating ECGs characteristic of torsade de pointes. CONCLUSIONS: Polymorphic ventricular tachycardia in the healthy, isolated rabbit heart is the result of either a single or paired ("figure-of-eight") nonstationary scroll waves. The extent of the scroll wave movement corresponds to the degree of polymorphism in the ECG. These results are consistent with our numerical simulations that showed monomorphic ECG patterns of activity for stationary scroll waves but polymorphic patterns for scroll waves that were nonstationary.

Animals↗

PubMed1994

Genetic map construction with constraints.

A pilot program, CME, is described for generating a physical genetic map from hybridization fingerprinting data. CME is implemented in the parallel constraint logic programming language ElipSys. The features of constraint logic programming are used to enable the integration of pre-existing mapping information (partial probe orders from cytogenetic maps and local physical maps) into the global map generation process, while parallelism enables the search space to be traversed more efficiently. CME was tested using data from chromosome 2 of Schizosaccharomyces pombe and was found able to generate maps as well as (and sometimes better than) a more traditional method. This paper illustrates the practical benefits of using a symbolic logic programming language and shows that the features of constraint handling and parallel execution bring the development of practical systems based on AI programming technologies nearer to being a reality.

Algorithms↗

PubMed1994

Ambiguity resolution while mapping free text to the UMLS Metathesaurus.

We propose a method for resolving ambiguities encountered when mapping free text to the UMLS Metathesaurus. Much of the research in medical informatics involves the manipulation of free text. The Metathesaurus contains extensive information which supports solutions to problems encountered while processing such text. After discussing the process of mapping free text to the Metathesaurus and describing the ambiguities which are often the result of such mapping, we provide examples of rules designed to eliminate mapping ambiguities. These rules refer to the context in which the ambiguity occurs and crucially depend on semantic types obtained from the Metathesaurus. We have conducted a preliminary test of the methodology and the results obtained indicate that the rules successfully resolve ambiguity around 80% of the time.

Abstracting and Indexing↗

PubMed1991

The extracellular domain of p185/neu is released from the surface of human breast carcinoma cells, SK-BR-3.

The human breast carcinoma cell line SK-BR-3, expresses the neu oncogene product, p185, which is a receptor tyrosine kinase. Using a double monoclonal antibody capture enzyme-linked immunosorbent assay for p185, activity was detected in conditioned media from cultures of SK-BR-3 cells. Two monoclonal antibodies specific for the extracellular domain of p185/neu immunoprecipitated a protein with a molecular mass of approximately 105 kDa. p105 was further shown to compete with p185 for binding to monoclonal antibodies and pulse-chase experiments indicate that it was generated by post-translational processing. Peptide maps showed that p105 and p185 are related polypeptides. Since p105 is close to the predicted size for the extracellular domain of p185/neu, we propose that SK-BR-3 cells specifically process and release this portion of the receptor into the medium. The release of the extracellular domain may have implications in oncogenesis and its detection could prove useful as a cancer diagnostic.

Adenocarcinoma↗

PubMed2001

Automated three-dimensional signature model for assessing brain injury in emergent stroke.

This presentation will focus on the value of established and newer MR methods that can be applied to the diagnosis and management of ischemic stroke with emphasis on future applications of MR to provide previously unmet needs of the treating clinician and clinical trials. Time alone is an inadequate indicator of the therapeutic window, especially when the time of stroke onset is uncertain. Thus, there is a need to predict the evolution of stroke in a way that more precisely and with greater resolution identifies the progression of cellular damage at the moment of investigation. This also would be of value for thrombolysis when knowledge of the degree and extent of tissue necrosis and the consequent potential for brain hemorrhage is of the utmost importance. To provide this, we perform postprocessing of diffusion-, T(1)- and T(2)-weighted images to produce the apparent diffusion coefficient of water, and T(1) and T(2) maps that are then further processed to provide maps and quantitation of the tissue signatures of ischemic histopathology. By these means, we can accomplish objective volumetric analysis of infarct size and of the proportions of potentially viable and salvageable tissue. We will show how this has the potential to predict long-term stroke outcome and facilitate decision-making in terms of safety of reperfusion strategies and the appropriateness of cytoprotective treatment. The value of our approach is to replace time as the therapeutic window and extend the opportunity of treatment to those patients presenting beyond the stringent time limits employed in current investigative clinical trials. Further, used as a surrogate marker of clinical outcome, this form of stroke analysis may speed proof of principle clinical trials in small numbers of stroke patients.

Brain↗

PubMed1998

Development of an intervention map for a parent education intervention to prevent violence among Hispanic middle school students.

This paper describes development of Padres Trabajando por la Paz, a violence prevention intervention for Hispanic parents to increase parental monitoring. The intervention was developed using an innovative new program planning process: intervention mapping. Theory and empirical evidence broadly defined performance objectives and determinants of parental monitoring. These objectives were further refined through group and individual interviews with the target parent group. Learning objectives for the intervention guided the content of the intervention that used modeling as the primary method and role model stories as a strategy delivered through newsletters. Stage-matching members of the target population for their readiness to implement the parental monitoring behaviors further refined the social cognitive message design strategies. Intervention mapping provides an explicit theory- and data-driven guide for intervention development that maximizes intervention impact for a specific target population.

Adolescent↗

PubMed1988

Developments in processing image sequences for elemental mapping.

Elemental mapping consists in searching the distribution of a given chemical species over an extended specimen area, with relation to topographical or structural features. It can be done with EELS core signals from a combination of several energy filtered images. One major problem encountered in the processing of such sequences of images lies in the extrapolation errors due to a difficult estimate of the background below the characteristic signal. The chosen method must be sufficiently reliable to avoid the risk of both "false positive" and "false negative" values: the first category may stem from spurious signals or from a non-satisfactory fit of the background. The second category is mainly due to a limited sensitivity. The EELS signal is often much weaker than the background intensity; an extrapolation error can therefore transform a negative value into a positive one, or vice versa. The purpose of the present contribution is to check the validity of the processing at different levels: i) different mathematical models of background; ii) different types of fitting procedures (one-parameter and two-parameters fits); iii) different fitting methods and several associated manipulations, such as a quasi local estimation of the involved fitting parameters. The statistical validity of those techniques is discussed through several tests on real images obtained from different specimens (Co/CeO2 catalysts, ferritin molecules, U and Tb staining clusters). Progress is made on the way of quantitative elemental mapping at a given confidence level, and towards the identification of single atoms.

Electron Probe Microanalysis↗

PubMed1995

Characterization and mapping of a highly conserved processed pseudogene and an intron-carrying gene of the heat shock cognate protein 70 (Hsc70) gene family in the rat.

A processed pseudogene of the rat Hsc70 gene, Hsc70-ps1, is described, which still presents the open reading frame of the original gene. The pseudogene does not appear to be expressed. It maps to rat Chromosome (Chr) 2. The intron-carrying Hsc70 gene localizes to Chr 8. Hsc70-specific probes detect a large number of more than 20 cross-hybridizing fragments, which show only limited length polymorphism among various inbred rat strains.

Animals↗

PubMed1989

Different anisotropies of movement direction in upper and lower layers of the cat's area 18 and their implications for global optic flow processing.

Cells in Area 18 of awake and behaving cats were tested for directional preference with a large visual noise pattern. Upper and lower layer cells were found to exhibit different anisotropies for movement direction, offset by 90 degrees. These findings could reflect different functions for the global mapping and processing of optic flow field in upper and lower layers.

Animals↗

PubMed2002

MAP-2e, a novel MAP-2 isoform, is expressed in gliomas and delineates tumor architecture and patterns of infiltration.

The MAP-2 isoform containing exon 13 (MAP-2e) is expressed in human fetal development as early as 15 gestational weeks and parallels oligodendrocyte maturation. MAP-2e is down-regulated following myelination and is expressed in few cells in the adult central nervous system (CNS). To determine whether CNS tumors express MAP-2e, we screened 122 archival, paraffin-embedded adult and pediatric tumors of the CNS and non-CNS. All oligodendrogliomas were positive and extensive staining was observed in glioblastomas, various malignant gliomas and dysembryoplastic neuroepithelial tumors. MAP-2e was not expressed in non-CNS tumors or neuroblastomas. Thus. neuroectodermal tumors that have glial characteristics express this developmental marker of immature glia. Analysis of oligodendrogliomas demonstrated numerous cell morphologies from round cells with no processes to cells with single or multiple processes. MAP-2e immunostaining also delineated tumor invasion into adjacent gray and white matter, indicating that MAP-2e appears to be a useful marker for examining the infiltration of malignant cells into surrounding tissue.

Alternative Splicing↗

PubMedDate not supplied

The cerebellum's role in reading: a functional MR imaging study.

BACKGROUND AND PURPOSE: Long considered to have a role limited largely to motor-related functions, the cerebellum has recently been implicated as being involved in both perceptual and cognitive processes. Our purpose was to determine whether cerebellar activation occurs during cognitive tasks that differentially engage the component processes of word identification in reading. METHODS: Forty-two neurologically normal adults underwent functional MR imaging of the cerebellum with a gradient-echo echo-planar technique while performing tasks designed to study the cognitive processing used in reading. A standard levels-of-processing paradigm was used. Participants were asked to determine whether pairs of words were written in the same case (orthographic processing), whether pairs of words and non-words rhymed with each other, respectively (phonologic assembly), and whether pairs of words belonged to the same category (semantic processing). Composite maps were generated from a general linear model based on a randomization of statistical parametric maps. RESULTS: During phonologic assembly, cerebellar activation was observed in the middle and posterior aspects of the posterior superior fissure and adjacent simple lobule and semilunar lobule bilaterally and in posterior aspects of the simple lobule, superior semilunar lobule, and inferior semilunar lobule bilaterally. Semantic processing, however, resulted in activation in the deep nuclear region on the right and in the inferior vermis, in addition to posterior areas active in phonologic assembly, including the simple, superior semilunar, and inferior semilunar lobules. CONCLUSION: The cerebellum is engaged during reading and differentially activates in response to phonologic and semantic tasks. These results indicate that the cerebellum contributes to the cognitive processes integral to reading.

Adult↗

PubMed1999

Confidence maps and confidence intervals for near infrared images in breast cancer.

This paper extends basic concepts of statistical hypothesis testing and confidence intervals to images generated by a new procedure for near infrared spectroscopic tomography being developed for use in breast cancer diagnosis. By estimating the covariance matrix of the pixels of an image from data used in the image reconstruction process, confidence maps for statistical tests on individual pixels and confidence intervals for entire images are displayed as an aid to research and clinical personnel interpreting possibly noisy images. The methods are applied to simulated and phantom-based images.

Breast Neoplasms↗

PubMed1988

Activity sharpens the regenerating retinotectal projection in goldfish: sensitive period for strobe illumination and lack of effect on synaptogenesis and on ganglion cell receptive field properties.

The regenerating optic nerve of goldfish first reestablishes a rough retinotopic map on the contralateral tectum and then sharpens it. Disruption of visual activity, either by blocking activity with intraocular tetrodotoxin (TTX; Schmidt and Edwards, 1983) or by synchronizing activity with strobe illumination (Schmidt and Eisele, 1985), disrupts the sharpening process: the map is correctly oriented but the multiunit receptive fields at each point average 25-40 degrees in diameter. In order to test whether strobe and TTX interfere with the same mechanism, we have tested whether their sensitive periods are the same, and whether strobe, like TTX treatment, does not affect either ganglion cell receptive field properties or synaptogenesis. In parallel studies, we exposed fish to 2 weeks of either strobe illumination or intraocular TTX beginning at various times after crush and determined via electrophysiological recordings that the periods of sensitivity were nearly identical. There was no effect of either treatment during the first 2 weeks (before the fibers arrive at the tectum), maximal disruption of sharpening between 14 and 50 days (the period of rapid synaptogenesis), decreasing disruption between 50 and 125 days, and no effect beyond that point or in the normal projection. In addition, long strobe exposures of up to 142 days produced no greater disruptions than shorter 2-3-week exposures, indicating no cumulative effect. The reestablishment of synaptic transmission in tectum, assayed by recording field potentials elicited by optic nerve shock, was not affected by stroboscopic illumination. Finally, individual ganglion cells, recorded intraretinally following long-term strobe exposure, had receptive fields that were normal both in size and in their characteristic responses to light-on, to light-off, or to both on and off. These findings support the hypothesis that strobe-like TTX prevents retinotopic refinement by preventing the correction of errors initially made by the ingrowing optic axons (Schmidt et al., 1988).

Animals↗