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At least 667 records · Page 37Linked to original sources
PubMed1997

Identification of a genetic locus for familial atrial fibrillation.

BACKGROUND: Atrial fibrillation, the most common sustained cardiac-rhythm disturbance, affects over 2 million Americans and accounts for one third of all strokes in patients over 65 years of age. The molecular basis for atrial fibrillation is unknown, and palliative therapy is used to control the ventricular rate and prevent systemic emboli. We identified a family of 26 members of whom 10 had atrial fibrillation which segregated as an autosomal dominant disease. We subsequently identified two additional families in which the disease was linked to the same locus. METHODS: We screened the human genome with 300 polymorphic dinucleotide-repeat markers using an unconventional strategy of pooling the DNA samples into two groups (affected and unaffected), which reduced the sample size by approximately 90 percent, before performing linkage analysis to map the locus. This made it possible to identify potential loci within a few weeks. RESULTS: The lod scores for markers D10S569 and D10S607, located at 10q22-q24, were 3.60 in Family 1. The disease locus in Families 2 and 3 was also linked to the same markers, with lod scores of 6.02 and 5.35 for markers D10S569 and D10S607, respectively, when data on all three families were combined. Haplotype analysis of the three families showed that the locus was between D10S1694 and D10S1786, an interval of 11.3 centimorgans. CONCLUSIONS: Identification of the gene for familial atrial fibrillation will help to elucidate the molecular basis of the disease and provide insights into acquired forms. The strategy of pooling DNA samples for analysis is more time and cost effective than conventional screening and should accelerate the process of gene mapping in the future.

Adult↗
PubMed1993

Cloning, overexpression, and genomic mapping of the 14-kDa subunit of human replication protein A.

Replication protein A (RPA) is a three-subunit protein that plays a central role in eukaryotic DNA replication, recombination, and repair. We have previously reported the cloning and bacterial expression of the 70- and 32-kDa subunits of human RPA (hRPA). We have now cloned the 14-kDa subunit (hRPA3) from a HeLa cell cDNA library. The hRPA3 cDNA is a 692-base pair sequence that contains an open reading frame encoding a protein of 121 amino acids with a calculated molecular mass of 13.6 kDa. The deduced amino acid sequence shows only limited similarity to the small subunit of yeast RPA and is unrelated to any other protein in the current data banks. A recombinant protein containing a short histidine tag at the NH2 terminus has been purified in good yield from Escherichia coli by metal-chelate affinity chromatography. Antibodies prepared against recombinant hRPA3 recognize the native protein and inhibit SV40 DNA replication in vitro. We have localized the genes for the 70-, 32-, and 14-kDa subunits to chromosomes 17, 1, and 7, respectively, using polymerase chain reaction amplification of genomic DNA from rodent-human hybrid cell lines. Since RPA appears to be involved in several fundamental cellular processes, the physical mapping of the RPA genes may be useful in identifying possible human genetic defects associated with RPA deficiency or dysfunction.

Amino Acid Sequence↗
PubMed2005

Brain maps, great and small: lessons from comparative studies of primate visual cortical organization.

In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for "core" fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey "third tier" visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.

Anatomy, Comparative↗
PubMed2000

Trimeric ring-like structure of ArsA ATPase.

ArsA protein is the soluble subunit of the Ars anion pump in the Escherichia coli membrane which extrudes arsenite or antimonite from the cytoplasm. The molecular weight of the subunit is 63 kDa. In the cell it hydrolyzes ATP, and the energy released is used by the membrane-bound subunit ArsB to transport the substrates across the membrane. We have obtained two-dimensional crystals of ArsA in the presence of arsenite on negatively-charged lipid monolayer composed of DMPS and DOPC. These crystals have been studied using electron microscopy of negatively-stained specimens followed by image processing. The projection map obtained at 2.4 nm resolution reveals a ring-like structure with threefold symmetry. Many molecular assemblies with the same ring-shape and dimensions were also seen dispersed on electron microscopy grids, prepared directly from purified ArsA protein solution. Size-exclusion chromatography of the protein sample with arsenite present revealed that the majority of the protein particles in solution have a molecular weight of about 180 kDa. Based on these experiments, we conclude that in solution the ArsA ATPase with substrate bound is mainly in a trimeric form.

Adenosine Triphosphatases↗
PubMed2004

Using CISMeF MeSH "Encapsulated" terminology and a categorization algorithm for health resources.

INTRODUCTION: CISMeF is a Quality Controlled Health Gateway using a terminology based on the Medical Subject Headings (MeSH) thesaurus that displays medical specialties (metaterms) and the relationships existing between them and MeSH terms. OBJECTIVE: The need to classify the resources within the catalogue has led us to combine this type of semantic information with domain expert knowledge for health resources categorization purposes. MATERIAL AND METHODS: A two-step categorization process consisting of mapping resource keywords to CISMeF metaterms and ranking metaterms by decreasing coverage in the resource has been developed. We evaluate this algorithm on a random set of 123 resources extracted from the CISMeF catalogue. Our gold standard for this evaluation is the manual classification provided by a domain expert, viz. a librarian of the team. RESULTS: The CISMeF algorithm shows 81% precision and 93% recall, and 62% of the resources were assigned a "fully relevant" or "fairly relevant" categorization according to strict standards. DISCUSSION: A thorough analysis of the results has enabled us to find gaps in the knowledge modeling of the CISMeF terminology. The necessary adjustments having been made, the algorithm is currently used in CISMeF for resource categorization.

Abstracting and Indexing↗
PubMed2004

Graphical modeling of the joint distribution of alleles at associated loci.

Pairwise linkage disequilibrium, haplotype blocks, and recombination hotspots provide only a partial description of the patterns of dependences and independences between the allelic states at proximal loci. On the gross scale, where recombination and spatial relationships dominate, the associations can be reasonably described in these terms. However, on the fine scale of current high-density maps, the mutation process is also important and creates associations between loci that are independent of the physical ordering and that can not be summarized with pairwise measures of association. Graphical modeling provides a standard statistical framework for characterizing precisely these sorts of complex stochastic data. Although graphical models are often used in situations in which assumptions lead naturally to specific models, it is less well known that estimation of graphical models is also a developed field. We show how decomposable graphical models can be fitted to dense genetic data. The objective function is the maximized log likelihood for the model penalized by a multiple of the model's degrees of freedom. We also describe how this can be modified to incorporate prior information of locus position. Simulated annealing is used to find good solutions. Part of the appeal of this approach is that categorical phenotypes can be included in the same analysis and association with polymorphisms can be assessed jointly with the interlocus associations. We illustrate our method with genotypic data from 25 loci in the ELAC2 gene. The results contain third- and fourth-order locus interactions and show that, at this density of markers, linkage disequilibrium is not a simple function of physical distance. Graphical models provide more flexibility to express these features of the joint distribution of alleles than do monotonic functions connecting physical and genetic maps.

Alleles↗
PubMed2006

Mapping racism.

The author uses the metaphor of mapping to illuminate a structural feature of racist thought, locating the degraded object along vertical and horizontal axes. These axes establish coordinates of hierarchy and of distance. With the coordinates in place, racist thought begins to seem grounded in natural processes. The other's identity becomes consolidated, and parochialism results. The use of this kind of mapping is illustrated via two patient vignettes. The author presents Freud's (1905, 1927) views in relation to such a "mapping" process, as well as Adorno's (1951) and Baldwin's (1965). Finally, the author conceptualizes the crucial status of primitivity in the workings of racist thought.

Adult↗
PubMed1992

Using knowledge maps and scripted cooperation to inform college students about patterns of behavior related to recurring abuse of alcohol.

Objectives of this study were to determine the effectiveness of using a specific information format--graphic representations called knowledge maps--and an information processing strategy--scripted cooperation--in teaching college students about behavior patterns that underlie recurring abuse of alcohol. Participants in this three-session, 6-hour study were 111 Texas Christian University students recruited from undergraduate psychology classes. Participants were randomly assigned to one of two materials format conditions (map vs. text format) and to one of two processing strategy conditions (individual processing vs. scripted interaction with a partner). Results indicate that map format facilitated recall of the pattern information; processing with a partner appeared to enhance perception of the multidimensional nature of behavior that supports alcohol use.

Adult↗
PubMed1999

Integrating neuromorphic action-oriented perceptual inputs to generate a navigation behaviour for a robot.

We use neural networks with pointer map architectures to provide simple attentional processing in a robotic task. A pointer map comprises a map of neurons that encode a stimulus. Besides global feedback inhibition, the map receives feedback excitation via a small group of pointer neurons that encode the location of a salient stimulus on the map as a vectorial representation. The pointer neurons are able to apply selective processing to a particular region of the network. The robot uses these properties to manoeuver in relation to an attended object. We implemented a controller composed of two pointer maps, and a motor map. The first pointer map reports the direction of a salient obstacle in a one-dimensional map of distance derived from infrared sensors. The second pointer map reports the direction to potential obstacles in a two-dimensional edge-enhanced image derived from a forward looking CCD-camera. These outputs are applied to a motor map, where they bias the motor control signals issued to the robots wheels, according to navigational intentions.

Avoidance Learning↗
PubMed2002

Involvement of MAP kinase in the regulation of amyloid precursor protein processing by novel cholinesterase inhibitors derived from rasagiline.

Two novel neuroprotective cholinesterase (ChE) inhibitors, TV3326, (N-propargyl-(3R) aminoindan-5-yl)-ethyl methyl carbamate, and TV3279, (N-propargyl-(3S) aminoindan-5-yl)-ethyl methyl carbamate, were derived from rasagiline for the treatment of Alzheimer's disease (AD). TV3326 also inhibits monoamine oxidase (MAO)-A and -B, whereas its S-isomer, TV3279, lacks MAO inhibitory activity. The action of these drugs in the regulation of amyloid precursor protein (APP) processing, using rat PC12 and human SH-SY5Y neuroblastoma cells, was examined. Both isomers stimulated the release of the non-amyloidogenic a-secretase form of soluble APP (sAPPalpha) from these cell lines. The increases in sAPPalpha, induced by TV3326 and TV3279, were dose-dependent (0.1-100 mM) and blocked by the hydroxamic acid-based metalloprotease inhibitor, Ro31-9790, suggesting mediation via a-secretase activity. Using several signal transduction inhibitors, we identified the involvement of protein kinase C (PKC), mitogen-activated protein (MAP) kinase, and tyrosine kinase-dependent pathways in the enhancement of sAPPalpha release by TV3326 and TV3279. In addition, both drugs directly induced the phosphorylation of p44 and p42 MAP kinase, which was abolished by the specific inhibitors of MAP kinase activation, PD98059 and U0126. These data suggest a novel pharmacological mechanism whereby these ChE inhibitors regulate the secretory processes of APP via activation of the MAP kinase pathway.

Amyloid beta-Protein Precursor↗
PubMed2002

Segregated processing of auditory motion and auditory location: an ERP mapping study.

Recent studies have revealed a distinct cortical network activated during the analysis of sounds' spatial properties. Whether common brain regions in this auditory where pathway are involved in both auditory motion and location processing is unresolved. We investigated this question with multichannel auditory evoked potentials (AEPs) in 11 subjects. Stimuli were binaural 500-ms white noise bursts. Interaural time differences (ITD) created the sensation of moving or stationary sounds within each auditory hemifield, and subjects discriminated either their position or direction of motion in a blocked design. Scalp potential distributions (AEP maps) differentiated electric field configurations across stimulus classes. The initial approximately 250-ms poststimulus yielded common topographies for both stimulus classes and hemifields. After approximately 250-ms, moving and stationary sounds engaged distinct cortical networks at two time periods, again with no differences observed between hemifields. The first ( approximately 250- to 350-ms poststimulus onset) was during stimulus presentation, and the second ( approximately 550- to 900-ms poststimulus onset) occurred after stimulus offset. Distributed linear inverse solutions of the maps over the 250- to 350-ms time period revealed not only bilateral inferior frontal activation for both types of auditory spatial processing, but also strong right inferior parietal activation in the case of auditory motion discrimination. During the later 550-to 900-ms time period, right inferior parietal and bilateral inferior frontal activity was again observed for moving sounds, whereas strong bilateral superior frontal activity was seen in the case of stationary sounds. Collectively, the evidence supports the existence of partly segregated networks within the auditory where pathway for auditory location and auditory motion processing.

Acoustic Stimulation↗
PubMed1992

Mutational analysis of essential IncP alpha plasmid transfer genes traF and traG and involvement of traF in phage sensitivity.

Although the broad-host-range IncP plasmids can vegetatively replicate in diverse gram-negative bacteria, the development of shuttle vector systems has established that the host range for IncP plasmid conjugative transfer is greater than the range of bacteria that sustain IncP replicons. Towards understanding IncP plasmid conjugation and the connection between IncP conjugation and Agrobacterium tumefaciens T-DNA transfer to plants, two sets of mutants were generated in the larger transfer region (Tra1) of the IncP alpha plasmid RK2. Mutagenesis strategies were chosen to minimize transcriptional polar effects. Mutant Tra1 clones were mapped, sequenced, and processed to reconstruct 49.5-kb Tra2-containing plasmid derivatives in order to assay for transfer activity and IncP plasmid-specific phage sensitivity. Focusing on the activities of the gene products of traF and traG in Escherichia coli, we found that mutations in traF abolished transfer activity and rendered the host cells phage resistant and mutations in traG abolished transfer activity but had no effect on phage sensitivity. Complementation of these mutant derivatives with corresponding trans-acting clones carrying traF or traG restored transfer activity and, in the case of the traF mutant, the phage sensitivity of the host cell. We conclude that in E. coli, both TraF and TraG are essential for IncP plasmid transfer and that TraF is necessary (but not sufficient) for donor-specific phage sensitivity, and sequencing data suggest that both TraF and TraG are membrane spanning.

Amino Acid Sequence↗
PubMed2005

Mining for diagnostic information in body surface potential maps: a comparison of feature selection techniques.

BACKGROUND: In body surface potential mapping, increased spatial sampling is used to allow more accurate detection of a cardiac abnormality. Although diagnostically superior to more conventional electrocardiographic techniques, the perceived complexity of the Body Surface Potential Map (BSPM) acquisition process has prohibited its acceptance in clinical practice. For this reason there is an interest in striking a compromise between the minimum number of electrocardiographic recording sites required to sample the maximum electrocardiographic information. METHODS: In the current study, several techniques widely used in the domains of data mining and knowledge discovery have been employed to mine for diagnostic information in 192 lead BSPMs. In particular, the Single Variable Classifier (SVC) based filter and Sequential Forward Selection (SFS) based wrapper approaches to feature selection have been implemented and evaluated. Using a set of recordings from 116 subjects, the diagnostic ability of subsets of 3, 6, 9, 12, 24 and 32 electrocardiographic recording sites have been evaluated based on their ability to correctly asses the presence or absence of Myocardial Infarction (MI). RESULTS: It was observed that the wrapper approach, using sequential forward selection and a 5 nearest neighbour classifier, was capable of choosing a set of 24 recording sites that could correctly classify 82.8% of BSPMs. Although the filter method performed slightly less favourably, the performance was comparable with a classification accuracy of 79.3%. In addition, experiments were conducted to show how (a) features chosen using the wrapper approach were specific to the classifier used in the selection model, and (b) lead subsets chosen were not necessarily unique. CONCLUSION: It was concluded that both the filter and wrapper approaches adopted were suitable for guiding the choice of recording sites useful for determining the presence of MI. It should be noted however that in this study recording sites have been suggested on their ability to detect disease and such sites may not be optimal for estimating body surface potential distributions.

Algorithms↗
PubMed2000

A sensitive mapping strategy for monitoring the reproducibility of glycan processing in an HIV vaccine, RGP-160, expressed in a mammalian cell line.

The external envelope glycoprotein (gp160) of HIV-1 is a candidate for vaccines against AIDS. Most of the surface of the molecule is shielded by carbohydrate and the structures and locations of these glycans may be important in defining the immunogenicity of the viral coat. Here we report a sensitive mapping strategy for profiling and analysing the N-glycosylation of gp160, based on chemical release of glycans, fluorescent labelling and HPLC analysis. This approach has been validated in terms of establishing the reproducibility of all steps in the analytical procedure and on overall reproducibility on a run-to-run and day-to-day basis. The validated analysis technique was used to monitor the consistency of N-glycosylation of one rgp 160 vaccine candidate produced in baby hamster kidney (BHK) cell culture. It was demonstrated that the variation in the glycan profiles of 6 different lots was not statistically significant.

AIDS Vaccines↗
PubMed2005

New adaptive color quantization method based on self-organizing maps.

Color quantization (CQ) is an image processing task popularly used to convert true color images to palletized images for limited color display devices. To minimize the contouring artifacts introduced by the reduction of colors, a new competitive learning (CL) based scheme called the frequency sensitive self-organizing maps (FS-SOMs) is proposed to optimize the color palette design for CQ. FS-SOM harmonically blends the neighborhood adaptation of the well-known self-organizing maps (SOMs) with the neuron dependent frequency sensitive learning model, the global butterfly permutation sequence for input randomization, and the reinitialization of dead neurons to harness effective utilization of neurons. The net effect is an improvement in adaptation, a well-ordered color palette, and the alleviation of underutilization problem, which is the main cause of visually perceivable artifacts of CQ. Extensive simulations have been performed to analyze and compare the learning behavior and performance of FS-SOM against other vector quantization (VQ) algorithms. The results show that the proposed FS-SOM outperforms classical CL, Linde, Buzo, and Gray (LBG), and SOM algorithms. More importantly, FS-SOM achieves its superiority in reconstruction quality and topological ordering with a much greater robustness against variations in network parameters than the current art SOM algorithm for CQ. A most significant bit (MSB) biased encoding scheme is also introduced to reduce the number of parallel processing units. By mapping the pixel values as sign-magnitude numbers and biasing the magnitudes according to their sign bits, eight lattice points in the color space are condensed into one common point density function. Consequently, the same processing element can be used to map several color clusters and the entire FS-SOM network can be substantially scaled down without severely scarifying the quality of the displayed image. The drawback of this encoding scheme is the additional storage overhead, which can be cut down by leveraging on existing encoder in an overall lossy compression scheme.

Algorithms↗
PubMed1999

Distribution of Epi Info software: an evaluation using the Internet.

INTRODUCTION: Epi Info and Epi Map are computer programs for word processing, database management, epidemiologic statistics, and mapping designed for public health professionals. The programs are in the public domain, and distribution outside the Centers for Disease Control and Prevention (CDC) has been through a variety of informal channels. METHOD: Individuals and organizations known to have distributed Epi Info or Epi Map since 1987 provided information. Distributors included CDC, the World Health Organization (WHO), commercial vendors, translators, instructors in university and public health settings, and other public health professionals. Reports documented a minimum number of 145,320 copies distributed. CONCLUSIONS: Since 1994, the Internet has become a major means of propagation, accounting for 66% of the copies for which the method of distribution was known. The Internet also was a major information source for this study.

Centers for Disease Control and Prevention, U.S.↗
PubMed1987

Computational maps in the brain.

The nervous system performs computations to process information that is biologically important. Some of these computations occur in maps--arrays of neurons in which the tuning of neighboring neurons for a particular parameter value varies systematically. Computational maps transform the representation of information into a place-coded probability distribution that represents the computed values of parameters by sites of maximum relative activity. Numerous computational maps have been discovered, including visual maps of line orientation and direction of motion, auditory maps of amplitude spectrum and time interval, and motor maps of orienting movements. The construction of the auditory map of space is the most thoroughly understood: information about interaural delays and interaural intensity differences is processed in parallel by separate computational maps, and the outputs of these maps feed into a higher order processor that integrates sets of cues corresponding to sound source locations and creates a map of auditory space. Computational maps represent ranges of parameter values that are relevant to the animal, and may differentially magnify the representation of values that are of particular importance. The tuning of individual neurons for values of a mapped parameter is broad relative to the range of the map. Consequently, neurons throughout a large portion of a computational map are activated by any given stimulus, and precise information about the mapped parameter is coded by the locations of peak activity. There are a number of advantages of performing computations in maps. First, information is processed rapidly because the computations are preset and are executed in parallel. Second, maps simplify the schemes of connectivity required for processing and utilizing the information. Third, a common, mapped representation of the results of different kinds of computations allows the nervous system to employ a single strategy for reading the information. Finally, maps enable several classes of neuronal mechanisms to sharpen tuning in a manner not possible for information that is represented in a non-topographic code.

Animals↗
PubMed1996

Memory for places: a navigational model in support of Marr's theory of hippocampal function.

In this report we describe a model that applies Marr's theory of hippocampal function to the problem of map-based navigation. Like many others we attribute a spatial memory function to the hippocampus, but we suggest that the additional functional components required for map-based navigation are located elsewhere in the brain. One of the key functional components in this model is an egocentric map of space, located in the neocortex, that is continuously updated using ideothetic (self-motion) information. The hippocampus stores snapshots of this egocentric map. The modeled activity pattern of head direction cells is used to set the best egocentric map rotation to match the snapshots stored in the hippocampus, resulting in place cells with a nondirectional firing pattern. We describe an evaluation of this model using a mobile robot and demonstrate that with this model the robot can recognize an environment and find a hidden goal. This model is discussed in the context of prior experiments that were designed to discover the map-based spatial processing of animals. We also predict the results of further experiments.

Animals↗