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PubMed1980

[Analysis of paracentral scotomata with spatially adaptive computer methods].

Flexible computer programs have been developed which are capable of distinguishing between normal and defective areas in the visual field, in that the computer logic only grossly probes normal areas and concentrates on the abnormal areas. As soon as a defect is discovered, it is analyzed with greater accuracy. In this way, no time is wasted analyzing and confirming normal conditions. At the same time, the system is highly effective in respect of pathologically defective areas of the visual field. The principle is described and illustrated with some clinical examples (paracentral scotomata).

Computers↗
PubMed1995

More about the difference between men and women: evidence from linear neural networks and the principal-component approach.

The ability of a statistical/neural network to classify faces by sex by means of a pixel-based representation has not been fully investigated. Simulations with pixel-based codes have provided sex-classification results that are less impressive than those reported for measurement-based codes. In no case, however, have the reported pixel-based simulations been optimized for the task of classifying faces by sex. A series of simulations is described in which four network models were applied to the same pixel-based face code. These simulations involved either a radial basis function network or a perceptron as a classifier, preceded or not by a preprocessing step of eigendecomposition. It is shown that performance comparable to that of the measurement-based models can be achieved with pixel-based input (90%) when the data are preprocessed. The effect of the eigendecomposition preprocessing of the faces is then compared with spatial-frequency analysis of face images and analyzed in terms of the perceptual information it captures. It is shown that such an examination may offer insight into the facial aspects important to the sex-classification process. Finally, the contribution of hair information to the performance of the model is evaluated. It is shown that, although the hair contributes to the sex-classification process, it is not the only important contributor.

Algorithms↗
PubMed2006

Discrete and analogue quantity processing in the parietal lobe: a functional MRI study.

The human intraparietal sulcus (IPS) is implicated in processing symbolic number information and possibly in nonsymbolic number information. Specific IPS activity for discrete quantities (numerosities) as compared with continuous, analogue quantity has not been demonstrated. Here we use a stimulus-driven paradigm to distinguish automatic estimation of "how many things" from "how much" and "how long." The discrete analogue response task (DART) uses the perception of hues which can change either abruptly (discrete, numerous stimuli) or smoothly (analogue, nonnumerous stimuli) in space or in time. Subjects decide whether they saw more green or more blue. A conjunction analysis of spatial and temporal conditions revealed that bilateral IPS was significantly more active during the processing of discrete stimuli than during analogue stimuli, as was a parietal-occipital transition zone. We suggest that processing numerosity is a distinct process from processing analogue quantity, whether extended in space or time, and that an intraparietal network connects objects' segmentation to the estimation of their numerosity.

Adolescent↗
PubMed1990

Hypercolumns in primate visual cortex can develop in the absence of cues from photoreceptors.

The visual cortex in primates consists of an array of anatomically and chemically identifiable cellular modules (hypercolumns) with distinct physiological properties. For example, layers II/III in the macaque monkey contain a regular array of cytochrome oxidase-rich blobs. Furthermore, the surrounding cytochrome oxidase-poor interblob regions have a higher density of neuropeptide Y-positive aspiny stellate cells. Neurons in the blobs are thought to mediate predominantly low spatial frequencies and color vision, while those in the interblobs appear to be engaged in pattern vision and high spatial frequency analysis. In this study we examined the role of the retina in the development of hypercolumns. A bilateral retinal ablation was performed in embryos at midgestation, before any photoreceptors had established contacts with other retinal neurons and before layers II/III of the cortex--or their synaptic connection--had been generated. We found that the cortex in operated animals had cytochrome oxidase blobs and that their size and spacing were normal. In addition, neuropeptide Y-containing neurons were preferentially distributed in the interblob region as in control animals. Our findings indicate that some basic aspects of the cyto- and chemoarchitectonic organization of the cerebral cortex, which presumably evolved for the analysis of form and color, can emerge in the absence of cues from the retinal photoreceptors that mediate these attributes of vision.

Aging↗
PubMed1996

Probing the structure and function of the tachykinin neurokinin-2 receptor through biosynthetic incorporation of fluorescent amino acids at specific sites.

A general method for understanding the mechanisms of ligand recognition and activation of G protein-coupled receptors has been developed. A study of ligand-receptor interactions in the prototypic seven-transmembrane neurokinin-2 receptor (NK2) using this fluorescence-based approach is presented. A fluorescent unnatural amino acid was introduced at known sites into NK2 by suppression of UAG nonsense codons with the aid of a chemically misacylated synthetic tRNA specifically designed for the incorporation of unnatural amino acids during heterologous expression in Xenopus oocytes. Fluorescence-labeled NK2 mutants containing an unique 3-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-2,3-diaminopropionic acid (NBD-Dap) residue at either site 103, in the first extracellular loop, or 248, in the third cytoplasmic loop, were functionally active. The fluorescent NK2 mutants were investigated by microspectrofluorimetry in a native membrane environment. Intermolecular distances were determined by measuring the fluorescence resonance energy transfer (FRET) between the fluorescent unnatural amino acid and a fluorescently labeled NK2 heptapeptide antagonist. These distances, calculated by the theory of Förster, permit to fix the ligand in space and define the structure of the receptor in a molecular model for NK2 ligand-receptor interactions. Our data are the first report of the incorporation of a fluorescent unnatural amino acid into a membrane protein in intact cells by the method of nonsense codon suppression, as well as the first measurement of experimental distances between a G protein-coupled receptor and its ligand by FRET. The method presented here can be generally applied to the analysis of spatial relationships in integral membrane proteins such as receptors or channels.

Animals↗
PubMed2002

Optimal control strategies under different feedback schedules: kinematic evidence.

Two experiments were conducted in which participants (N = 12, Experiment 1; N = 12, Experiment 2) performed rapid aiming movements with and without visual feedback under blocked, random, and alternating feedback schedules. Prior knowledge of whether vision would be available had a significant impact on the strategies that participants adopted. When they knew that vision would be available, less time was spent preparing movements before movement initiation. Participants also reached peak deceleration sooner but spent more time after peak deceleration adjusting limb trajectories. Consistent with those findings, analysis of spatial variability at different points in the trajectory indicated that variability increased up to peak deceleration but then decreased from peak deceleration to the end of the movement.

Biomechanical Phenomena↗
PubMed2003

Online versus offline processing of visual feedback in the production of component submovements.

The present authors tested the assumptions in R. S. Woodworth's (1899) 2-component model regarding the specific roles of vision in the production of both the initial impulse and the error-correction phases of movement. Participants (N = 40) practiced a rapid aiming task (1,500 trials), with either no visual feedback, vision of only the 1st 50% of the movement, vision of only the 1st 75% of the movement, or vision of the entire movement. Consistent with previous research, the availability of vision over the 1st half of the movement had no effect on aiming accuracy during acquisition. In contrast, when visual feedback was available over the 1st 75% of the movement and the entire movement, initial impulse endpoints were less variable and the efficiency of the error-correction phase was improved. Analysis of spatial variability at various stages in the movement revealed that participants processed visual feedback offline to improve programming of the initial impulse and processed it online in regulating the deceleration of the initial impulse.

Computers↗
PubMedDate not supplied

APOE distribution in world populations with new data from India and the UK.

BACKGROUND: The APOE gene and its protein product is associated with a number of plasma proteins like very-low density lipoprotein (VLDL), high density lipoprotein (HDL) chylomicrons, chylomicron remnants, and plays a crucial role in lipid metabolism. The APOE gene is polymorphic and common alleles (*E2, *E3 and *E4) have been associated with a number of common and complex diseases in different populations. Due to their crucial role in metabolism and clinical significance, it is imperative that allelic variation in different populations is analysed to evaluate the usage of APOE in an evolutionary and clinical context. AIM: We report allelic variation at the APOE locus in three European and four Indian populations and evaluate global patterns of genetic variation at this locus. The large, intricate and unexpected heterogeneity of this locus in its global perspective may have insightful consequences, which we have explored in this paper. SUBJECT AND METHODS: Apolipoprotein E genotypes were determined in four population groups (Punjabi Sikhs, Punjabi Hindus, Maria Gonds and Koch, total individuals = 497) of India and three regionally sub-divided British populations (Nottinghamshire, East Midlands and West Midlands, total individuals = 621). The extent and distribution of APOE allele frequencies were compared with 292 populations of the world using a variety of multivariate methods. RESULTS: Three alleles, APOE*E2, APOE*E3 and APOE*E4, were observed with contrasting variation, although *E4 was absent in the tribal population of Koch. Higher heterozygosities (>43%) in British populations reflected their greater genetic diversity at this locus. The overall pattern of allelic diversity among these populations is comparable to many European and Indian populations. At a global level, higher frequencies of the *E2 allele were observed in Africa and Oceania (0.099 +/- 0.083 and 0.111 +/- 0.052, respectively). Similarly, *E4 allele averages were higher in Oceania (0.221 +/- 0.149) and Africa (0.209 +/- 0.090), while Indian and Asian populations showed the highest frequencies of *E3 allele. The coefficient of gene differentiation was found to be highest in South America (9.6%), although the highest genetic diversity was observed in Oceania (48.7%) and Africa (46.3%). APOE*E2 revealed a statistically significant decreasing cline towards the north in Asia (r = -0.407, d.f. = 70, p < 0.05), which is not compatible with the coronary heart disease statistics in this continent. APOE*E4 showed a significant increasing cline in North European populations. Spatial autocorrelation analysis shows that the variation at this locus is influenced by 'isolation by distance' with a strong positive correlation for lower distances up to 1313 km. CONCLUSION: Overall APOE allelic variation in UK and Indian populations is comparable to previous studies but in tribal populations *E4 allele frequency was very low or absent. At a global level allelic variation shows that geography, isolation by distance, genetic drift and possibly pre-historical selection are responsible for shaping the spectrum of genetic variation at the APOE gene. Overall, APOE is a good anthropogenetic and clinical diagnostic marker.

Apolipoproteins E↗
PubMed2006

Counting complex dot patterns in Alzheimer's disease.

Patients affected by Alzheimer's disease (DAT) showed considerable difficulties assessing the numerosity of complex dot patterns (up to 30 dots). Patients' and controls' performance was found to be modulated by the spatial array of dot patters. Dots presented in curved lines were easier to count than dots in circle arrays or in random arrays. Highly significant between group differences were found in counting dots in circle arrays, but not in counting curved lines. Patients and controls differed in the choice of counting strategies. While controls efficiently adapted their counting strategies to the respective dot patterns, DAT patients were not able to adapt counting strategies to the requirements of the spatial arrays. Analysis of error types further evidenced the particular difficulties of patients. Several recounts in counting circle arrays reflected difficulties to stop counting, while omissions in random patterns suggested deficits in monitoring already counted items. Results of this study suggest that deficits in executive functions prevented patients from selecting and adapting counting strategies in order to keep track of already counted items, to enhance accuracy and to reduce demands on cognitive resources.

Aged↗
PubMed2001

Vectorcardiography is superior to conventional ECG for detection of myocardial injury after coronary surgery.

OBJECTIVE: The reliability of conventional scalar ECG for diagnosis of perioperative myocardial infarction (PMI) in cardiac surgery has been questioned. For the diagnosis of myocardial infarction in general vectorcardiography (VCG) is superior to ECG. Therefore, the usefulness of conventional VCG and computerized analysis of spatial VCG changes for diagnosis of PMI were studied. DESIGN: VCG registrations were obtained from 218 patients undergoing coronary surgery. The spatial QRS vector loop area of each VCG registration was calculated and the loop area before surgery compared with the loop area after surgery. Conventional VCG criteria for myocardial infarction and set values for loop area reduction were related to sustained elevation of plasma troponin-T and clinical course. RESULTS: Both conventional VCG criteria and spatial changes translated better than Q-waves on scalar ECG into elevation of biochemical markers of myocardial injury and impaired clinical course. CONCLUSION: VCG appears superior to conventional ECG as regards detection of myocardial injury in coronary surgery. Computerized programs have facilitated the registration and the interpretation of VCG and this methodology deserves further evaluation in cardiac surgery.

Cardiac Surgical Procedures↗
PubMed1999

mtDNA history of the Cayapa Amerinds of Ecuador: detection of additional founding lineages for the Native American populations.

mtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations.

Base Sequence↗
PubMed2000

Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Y-chromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift.

Africa, Northern↗
PubMed2005

Detecting small-area similarities in the epidemiology of childhood acute lymphoblastic leukemia and diabetes mellitus, type 1: a Bayesian approach.

Childhood acute lymphoblastic leukemia and diabetes mellitus, type 1, have common epidemiologic and etiologic features, including correlated international incidence and associations with infections. The authors examined whether the diseases' similar large-scale distributions are reflected in small geographic areas while also examining the influence of sociodemographic characteristics. Details of 299 children (0-14 years) with acute lymphoblastic leukemia and 1,551 children with diabetes diagnosed between 1986 and 1998 were extracted from two registers in Yorkshire, United Kingdom. Standardized incidence ratios across 532 electoral wards were compared using Poisson regression, confirming significant associations between population mixing and the geographic heterogeneity of both conditions. Bayesian methods analysis of spatial correlation between diseases by modeling a bivariate outcome based on their standardized incidence ratios was applied; spatial and heterogeneity components were included within a hierarchical random effects model. A positive correlation between diseases of 0.33 (95% credible interval: -0.20, 0.74) was observed, and this was reduced after control for population mixing (r = 0.18), population density (r = 0.14), and deprivation (r = 0.06). The Bayesian approach showed a modest but nonsignificant joint spatial correlation between diseases, only partially suggesting that the risk of both was associated within some electoral wards. With Bayesian methodology, population mixing remained significantly associated with both diseases. The links between diabetes and acute lymphoblastic leukemia observed for large regions are weaker for small areas. More powerful replications are needed for confirmation of these findings.

Adolescent↗
PubMed2006

Mechanims of aerosol particle deposition in the Oro-pharynx under non-steady airflow.

Comparison of experimental and computational results of aerosol deposition in the oro-pharyngeal cast of human published recently (Sosnowski TR, Moskal A, Gradoń L. (2006) Inhal Toxicol; 18: 773-780) demonstrated the applicability and relevance of considering realistic breathing patterns in analysis of aerosol flow and deposition within the human head airways. This issue is extended in the current paper, focused on a detailed analysis of spatial and temporal distribution of particle deposition in the oro-pharynx during inspiration. CFD modeling was used to determine both the 3D airflow structure and the local particle deposition fluxes at two different inspiratory patterns. Behavior of aerosol (particle size: 0.3-10 micro m, material density: 2200 kg m(-3)) was analyzed applying Lagrangian approach and considering Brownian effects for submicron particles. Results indicate that particles of different sizes are deposited in different parts of the oro-pharynx, depending on the point in the inspiration cycle. Larger particles (3-10 micro m) are separated efficiently in the naso-pharyngeal bend due to inertia, which predominate in the middle phase of inspiration. Submicron particles are deposited more uniformly in the oro-pharyngeal space, and their separation from the air is enhanced in a short transition period between inspiration and expiration. It suggests the importance of mixing of inspired and expired air streams for particle deposition pattern. Comparison of our computational results of deposition to the approximation derived from the in vivo data (Stahlhofen W, Rudolf G, James AC. (1989) J Aerosol Med; 2: 285-308) shows a good agreement for particles, for which the inertia is a predominant mechanism of deposition. The results of this work lead to a more detailed description of the dynamics of oro-pharyngeal aerosol deposition during inspiratory part of the breathing cycle. The recognition of that problem is essential for prediction of toxic or pharmacological local effects of inhaled aerosols.

Aerosols↗
PubMed2006

Fine-scale genetic structure among genetic individuals of the clone-forming monotypic genus Echinosophora koreensis (Fabaceae).

BACKGROUND AND AIMS: For rare endemics or endangered plant species that reproduce both sexually and vegetatively it is critical to understand the extent of clonality because assessment of clonal extent and distribution has important ecological and evolutionary consequences with conservation implications. A survey was undertaken to understand clonal effects on fine-scale genetic structure (FSGS) in two populations (one from a disturbed and the other from an undisturbed locality) of Echinosophora koreensis, an endangered small shrub belonging to a monotypic genus in central Korea that reproduces both sexually and vegetatively via rhizomes. METHODS: Using inter-simple sequence repeats (ISSRs) as genetic markers, the spatial distribution of individuals was evaluated using Ripley's L(d)-statistics and quantified the spatial scale of clonal spread and spatial distribution of ISSR genotypes using spatial autocorrelation analysis techniques (join-count statistics and kinship coefficient, F(ij)) for total samples and samples excluding clones. KEY RESULTS: A high degree of differentiation between populations was observed (phi(ST(g)) = 0.184, P < 0.001). Ripley's L(d)-statistics revealed a near random distribution of individuals in a disturbed population, whereas significant aggregation of individuals was found in an undisturbed site. The join-count statistics revealed that most clones significantly aggregate at < or = 6-m interplant distance. The Sp statistic reflecting patterns of correlograms revealed a strong pattern of FSGS for all four data sets (Sp = 0.072-0.154), but these patterns were not significantly different from each other. At small interplant distances (< or = 2 m), however, jackknifed 95% CIs revealed that the total samples exhibited significantly higher F(ij) values than the same samples excluding clones. CONCLUSION: The strong FSGS from genets is consistent with two biological and ecological traits of E. koreensis: bee-pollination and limited seed dispersal. Furthermore, potential clone mates over repeated generations would contribute to the observed high F(ij) values among genets at short distance. To ensure long-term ex situ genetic variability of the endangered E. koreensis, individuals located at distances of 10-12 m should be collected across entire populations of E. koreensis.

Conservation of Natural Resources↗
PubMed1990

Spatial autocorrelation of genotypes under directional selection.

The spatial distributions of genetic variation under selection-mutation equilibrium within populations that have limited dispersal are investigated. The results show that directional selection with moderate strength rapidly reduces the amount of genetic structure and spatial autocorrelations far below that predicted for selectively neutral loci. For the latter, homozygotes are spatially clustered into separate areas or patches, each consisting of several hundred homozygotes. When selection is added the patches of the deleterious homozygotes are much smaller, in the range of 25 to 50 individuals. Selection also reduces temporal correlations. Also investigated are the effects of random replacement processes, such as mutation, immigration, and long-distance migration, on spatial and temporal correlations. The detection of natural selection through spatial pattern analysis is discussed, and applied to data from populations of the morning glory, Ipomoea purpurea.

Alleles↗
PubMed2004

Photoreceptor-specific nuclear receptor NR2E3 functions as a transcriptional activator in rod photoreceptors.

NR2E3, a photoreceptor-specific orphan nuclear receptor, is believed to play a pivotal role in the differentiation of photoreceptors. Mutations in the human NR2E3 gene and its mouse ortholog are associated with enhanced S-cones and retinal degeneration. In order to gain insights into the NR2E3 function, we performed temporal and spatial expression analysis, yeast two-hybrid screening, promoter activity assays and co-immunoprecipitation studies. The Nr2e3 expression was localized preferentially to the rod, and not to the cone, photoreceptor nuclei in rodent retina. The yeast two-hybrid screening of a retinal cDNA library, using NR2E3 as the bait, identified another orphan nuclear receptor NR1D1 (Rev-erbalpha). The interaction of NR2E3 with NR1D1 was confirmed by glutathione S-transferase pulldown and co-immunoprecipitation experiments. In transient transfection studies using HEK 293 cells, both NR2E3 and NR1D1 activated the promoters of rod phototransduction genes synergistically with neural retina leucine zipper (NRL) and cone-rod homeobox (CRX). All four proteins, NR2E3, NR1D1, NRL and CRX, could be co-immunoprecipitated from the bovine retinal nuclear extract, suggesting their existence in a multi-protein transcriptional regulatory complex in vivo. Our results demonstrate that NR2E3 is involved in regulating the expression of rod photoreceptor-specific genes and support its proposed role in transcriptional regulatory network(s) during rod differentiation.

Animals↗