266 research outputs found

    Measuring Information Transfer

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    An information theoretic measure is derived that quantifies the statistical coherence between systems evolving in time. The standard time delayed mutual information fails to distinguish information that is actually exchanged from shared information due to common history and input signals. In our new approach, these influences are excluded by appropriate conditioning of transition probabilities. The resulting transfer entropy is able to distinguish driving and responding elements and to detect asymmetry in the coupling of subsystems.Comment: 4 pages, 4 Figures, Revte

    Asymptotically stable phase synchronization revealed by autoregressive circle maps

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    A new type of nonlinear time series analysis is introduced, based on phases, which are defined as polar angles in spaces spanned by a finite number of delayed coordinates. A canonical choice of the polar axis and a related implicit estimation scheme for the potentially underlying auto-regressive circle map (next phase map) guarantee the invertibility of reconstructed phase space trajectories to the original coordinates. The resulting Fourier approximated, Invertibility enforcing Phase Space map (FIPS map) is well suited to detect conditional asymptotic stability of coupled phases. This rather general synchronization criterion unites two existing generalisations of the old concept and can successfully be applied e.g. to phases obtained from ECG and airflow recordings characterizing cardio-respiratory interaction.Comment: PDF file, 232 KB, 24 pages, 3 figures; cheduled for Phys. Rev. E (Nov) 200

    FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies.

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    The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p.Arg85Cys and p.Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca(2) (+) pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition

    HERMES: Towards an Integrated Toolbox to Characterize Functional and Effective Brain Connectivity

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    The analysis of the interdependence between time series has become an important field of research in the last years, mainly as a result of advances in the characterization of dynamical systems from the signals they produce, the introduction of concepts such as generalized and phase synchronization and the application of information theory to time series analysis. In neurophysiology, different analytical tools stemming from these concepts have added to the ‘traditional’ set of linear methods, which includes the cross-correlation and the coherency function in the time and frequency domain, respectively, or more elaborated tools such as Granger Causality. This increase in the number of approaches to tackle the existence of functional (FC) or effective connectivity (EC) between two (or among many) neural networks, along with the mathematical complexity of the corresponding time series analysis tools, makes it desirable to arrange them into a unified-easy-to-use software package. The goal is to allow neuroscientists, neurophysiologists and researchers from related fields to easily access and make use of these analysis methods from a single integrated toolbox. Here we present HERMES (http://hermes.ctb.upm.es), a toolbox for the Matlab® environment (The Mathworks, Inc), which is designed to study functional and effective brain connectivity from neurophysiological data such as multivariate EEG and/or MEG records. It includes also visualization tools and statistical methods to address the problem of multiple comparisons. We believe that this toolbox will be very helpful to all the researchers working in the emerging field of brain connectivity analysis

    Manual and automated blood cells count in ocelots (Leopardus pardalis - Linnaeus, 1758)

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    Aparelhos de automação, cujo uso está estabelecido na hematologia dos animais domésticos, ainda não são empregados rotineiramente em felídeos selvagens. Esse estudo objetivou avaliar a técnica automatizada na contagem de células sanguíneas de jaguatiricas (Leopardus pardalis), comparando-a com a técnica manual. Foram coletadas amostras sanguíneas de oito jaguatiricas, que se submeteram à contagem de eritrócitos, leucócitos, plaquetas e à determinação do volume globular pelo método manual padrão e por meio do aparelho BC - 2800 VET® com a configuração para gatos domésticos. Os resultados foram avaliados por meio do teste t para dados pareados, e as técnicas submetidas à análise de correlação de Pearson. A técnica automatizada demonstrou resultados estatisticamente semelhantes para eritrócitos e leucócitos. Apenas para volume globular houve diferença significativa entre as técnicas manual e automatizada, mas a correlação foi alta. Apesar de não haver diferença significativa entre as técnicas para plaquetas, a correlação foi baixa. Conclui-se que o aparelho BC - 2800 VET® com a configuração para gatos domésticos é uma técnica confiável na realização do eritrograma e do leucograma para jaguatiricas. Para a determinação do parâmetro volume globular, o aparelho pode ser utilizado, desde que se faça a correção. Para a contagem de plaquetas, a técnica manual é recomendada.Automated equipment, whose use is established in hematology of domestic animals, is not yet routinely used in blood cells count of wildlife, due to lack of studies that validate its use. The purpose of this study was to evaluate the automated technique for blood cells count of ocelots (Leopardus pardalis), comparing it with the manual technique. Blood samples were collected from eight ocelots, which were submitted to counting of erythrocytes, leukocytes, platelets and packed cell volume by the standard manual method and by the device VET ® 2800 BC with the configuration for domestic cats. The results were evaluated using the t test for paired data and the techniques submitted to Pearson correlation. The automated technique showed statistically similar results to erythrocytes and leukocytes. Significant difference was found only for packed cell volume between the manual and automated techniques, but the correlation was high. Although there was no significant difference between the techniques for platelets, the correlation was low. We concluded that the 2800 BC VET ® device with the configuration for domestic cats is a reliable technique in performing the erythrocyte and leukocyte counts for ocelots. The device may be used to determine packed cell volume, provided the correction is made. The manual technique is recommended for the platelet count

    Characterizing global evolutions of complex systems via intermediate network representations

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    Recent developments in measurement techniques have enabled us to observe the time series of many components simultaneously. Thus, it is important to understand not only the dynamics of individual time series but also their interactions. Although there are many methods for analysing the interaction between two or more time series, there are very few methods that describe global changes of the interactions over time. Here, we propose an approach to visualise time evolution for the global changes of the interactions in complex systems. This approach consists of two steps. In the first step, we construct a meta-time series of networks. In the second step, we analyse and visualise this meta-time series by using distance and recurrence plots. Our two-step approach involving intermediate network representations elucidates the half-a-day periodicity of foreign exchange markets and a singular functional network in the brain related to perceptual alternations

    Direct Generation of Neurosphere-Like Cells from Human Dermal Fibroblasts

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    Neural stem cell (NSC) transplantation replaces damaged brain cells and provides disease-modifying effects in many neurological disorders. However, there has been no efficient way to obtain autologous NSCs in patients. Given that ectopic factors can reprogram somatic cells to be pluripotent, we attempted to generate human NSC-like cells by reprograming human fibroblasts. Fibroblasts were transfected with NSC line-derived cellular extracts and grown in neurosphere culture conditions. The cells were then analyzed for NSC characteristics, including neurosphere formation, gene expression patterns, and ability to differentiate. The obtained induced neurosphere-like cells (iNS), which formed daughter neurospheres after serial passaging, expressed neural stem cell markers, and had demethylated SOX2 regulatory regions, all characteristics of human NSCs. The iNS had gene expression patterns that were a combination of the patterns of NSCs and fibroblasts, but they could be differentiated to express neuroglial markers and neuronal sodium channels. These results show for the first time that iNS can be directly generated from human fibroblasts. Further studies on their application in neurological diseases are warranted

    Protection of Visual Functions by Human Neural Progenitors in a Rat Model of Retinal Disease

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    BACKGROUND: A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. METHODOLOGY/PRINCIPAL FINDINGS: Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. CONCLUSIONS/SIGNIFICANCE: Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo
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