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Scalable, open-access and multidisciplinary data integration pipeline for climate-sensitive diseases.

Climate-sensitive infectious diseases pose an important challenge for human, animal and environmental health and it has been estimated that over half of known human pathogenic diseases can be aggravated by climate change. While climatic and weather conditions are important drivers of transmission of vector-borne diseases, socio-economic, behavioural, and land-use factors as well as the interactions among them impact transmission dynamics. Analysis of drivers of climate-sensitive diseases require rapid integration of interdisciplinary data to be jointly analysed with epidemiological (including genomic and clinical) data. Current tools for the integration of multiple data sources are often limited to one data type or rely on proprietary data and software. To address this gap, we develop a scalable and open-access pipeline for the integration of multiple spatio-temporal datasets that requires only the declaration of the country and temporal range and resolution of the study. The tool is locally deployable and can easily be integrated into existing climate-disease-modelling applications. We demonstrate the utility of the tool for dengue modelling in Vietnam where epidemiological data are legally required to remain local. We include a pipeline for bias correction of climate data to enhance their quality for downstream modelling tasks. The Dengue Advanced Readiness Tools-Pipeline empowers users by simplifying complex download, correction, and aggregation steps, fostering data-driven discovery of relationships between infectious diseases and their drivers in space and time, and enhancing reproducibility in research. Additional modules and datasets can be added to the existing ones to make the pipeline extendable to use cases other than the ones presented here.

automated workflows↗

[Automatic analysis of gastrographies by means of optical digital equipment (author's transl)].

The present paper is concerned with problems of automatic analysis of radiograms, specially cinegastrographies. This study is connected with the utilisation of an interactive system including optical digitizer with its units of control and visualization. This system can explore the radiologic film in its current size of 30 X 40 cm. The particular interest of this application is extracting several parameters characterizing the size and the shape of the stomach. A middle axis can be extracted by computing, from this one a spatio-temporal diagram can be obtained. From this methodology of representation, several states of gastric motility could be characterized.

Analog-Digital Conversion↗

A model for processing of movement in the visual system.

Processing of spatio-temporal information in the human visual system has been investigated thoroughly during the past decade, but is still far from being properly understood. Moreover, the theory of separation of information by means of sustained and transient channels already at the retinal level is not satisfactory, as experimental results indicate that these two types of channels span a continuum of temporal characteristics. It is however obvious, that the process of pattern recognition and velocity perception calls for their separation at some level of the hierarchy. In this communication, we extend our model of three-dimensional spatio-temporal frequency expansion in the visual system (Gafni and Zeevi, 1977) to show how velocity-information extraction channels, sensitive to direction and velocity exclusively, can be formed by simple summation of signals from well-defined sets of channels representing points in the frequency space. Correspondence of these channels to characteristics of the cortical neurons is discussed.

Depth Perception↗

Spatio-temporal organization of EEG in premature infants and full-term new-borns.

Inter- and intrahemispheric EEG relationships were studied as a function of maturation in new-born infants. The spatio-temporal organization of EEG activity obtained during the two stages of sleep described in new-born infants - quiet sleep and active sleep - was analysed in 9 full-term new-born infants and 5 prematures (6 records). EEGs were recorded through transverse parietal montage made up of six bipolar derivations. Two epochs of 1.5 min each - successively obtained in both stages of sleep - were digitized, filtered in three frequency bands (beta, theta and delta) and computer-processed according to two methods, factor analysis and rhythms averaging. 1. The following EEG characteristics were found in both groups: (a) Instability of frequency within each frequency band (beta, theta and delta). However, theta activity was the most stable of the three, especially in quiet sleep. (b) Variability of topographical organization (i.e., localization of maxima of potentials) from one moment to another in both stages of sleep and in the three frequency bands. In spite of this intra-individual variability some sort of "average structure" was found in all infants; it was characterized by usually lateral and often symmetrical positions of the maxima of potential on the two hemispheres. For the same infant this structure was the same in the three frequency bands. (c) Poor interhemispheric relationships under all conditions, as well as poor interregional links in one hemisphere. 2. Some EEG characteristics differentiated the two groups and thus seemed to be related to maturation. Compared to full-term newborns the premature group showed: better stability for all three activities, especially for beta activity; higher frequency and larger amplitude of beta activity; better inter- and intrahemispheric relationships; fewer differences related to sleep stages. These results are discussed in terms of organization of the underlying cortical generators. The authors suggest that the active areas would increase in number and in surface with maturation, whereas the links between these different separate areas would remain very poor in the human full-term new-borns as well on one hemisphere as across hemispheres. This last finding would argue against the hypothesis that the corpus callosum which, as is well known, matures early, plays an important role in the establishment of interhemispheric links.

Age Factors↗

Automated interictal EEG spike detection using artificial neural networks.

Feed-forward, error-back-propagation artificial neural networks were applied to recognition of epileptiform patterns in the EEG. The inherent network properties of generalization and variability tolerance were effective in identifying wave forms that differed from the training patterns but still maintained 'epileptiform' spatio-temporal characteristics. The certainty of recognition was measured as a continuous function with a range of 0-1. Two levels of certainty (0.825 and 0.900) were used to indicate recognition of spikes and sharp waves (SSW). An average 94.2% (+/- 7.3) of the SSW were recognized; 20.9% (+/- 22.9) of all recognized SSW were false-positive recognitions. The time required for pattern recognition was well within the time required for digitizing the analogue data. This study provides evidence that neural network technology is, in principle, an effective pattern recognition strategy for identification of epileptiform transients in the EEG. The analysis is sufficiently rapid to be of potential value as a strategy for data reduction of long recordings stored on bulk media.

Electroencephalography↗

Hox-3.6: isolation and characterization of a new murine homeobox gene located in the 5' region of the Hox-3 cluster.

Most members of the murine Hox gene system can be grouped into two subclasses based on their structural similarity to either one of the Drosophila homeotic genes Antennapedia (Antp) or Abdominal B (AbdB). All the AbdB-like genes reported thus far are located in the 5' region of their respective cluster. We describe here the isolation, structural characterization and spatio-temporal expression pattern of a new AbdB-like homeobox gene designated Hox-3.6 that is located in the 5' region of the Hox-3 cluster. Hox-3.6 has an extreme posterior expression domain in embryos of 12.5 days of gestation, a feature that has thus far only been observed for the 5' most genes of the Hox-4 cluster. Like the other members of the AbdB subfamily, Hox-3.6 exhibits spatially restricted expression in the hindlimb bud, but the expression domain is antero-proximal in contrast to the postero-distal domain reported for its cognate gene Hox-4.5. Structural analysis of the 5' region revealed the presence of a 35 bp sequence which shares homology and relative 5' position with an upstream sequence present in its two nearest downstream neighbors, Hox-3.2 and -3.1.

Amino Acid Sequence↗

Multiple dipole modeling and localization from spatio-temporal MEG data.

An array of biomagnetometers may be used to measure the spatio-temporal neuromagnetic field or magnetoencephalogram (MEG) produced by neural activity in the brain. A popular model for the neural activity produced in response to a given sensory stimulus is a set of current dipoles, where each dipole represents the primary current associated with the combined activation of a large number of neurons located in a small volume of the brain. An important problem in the interpretation of MEG data from evoked response experiments is the localization of these neural current dipoles. We present here a linear algebraic framework for three common spatio-temporal dipole models: i) unconstrained dipoles, ii) dipoles with a fixed location, and iii) dipoles with a fixed orientation and location. In all cases, we assume that the location, orientation, and magnitude of the dipoles are unknown. With a common model, we show how the parameter estimation problem may be decomposed into the estimation of the time invariant parameters using nonlinear least-squares minimization, followed by linear estimation of the associated time varying parameters. A subspace formulation is presented and used to derive a suboptimal least-squares subspace scanning method. The resulting algorithm is a special case of the well-known MUltiple SIgnal Classification (MUSIC) method, in which the solution (multiple dipole locations) is found by scanning potential locations using a simple one dipole model. Principal components analysis (PCA) dipole fitting has also been used to individually fit single dipoles in a multiple dipole problem. Analysis is presented here to show why PCA dipole fitting will fail in general, whereas the subspace method presented here will generally succeed. Numerically efficient means of calculating the cost functions are presented, and problems of model order selection and missing moments are discussed. Results from a simulation and a somatosensory experiment are presented.

Algorithms↗

Epigenetically regulated digital signaling defines epithelial innate immunity at the tissue level.

To prevent damage to the host or its commensal microbiota, epithelial tissues must match the intensity of the immune response to the severity of a biological threat. Toll-like receptors allow epithelial cells to identify microbe associated molecular patterns. However, the mechanisms that mitigate biological noise in single cells to ensure quantitatively appropriate responses remain unclear. Here we address this question using single cell and single molecule approaches in mammary epithelial cells and primary organoids. We find that epithelial tissues respond to bacterial microbe associated molecular patterns by activating a subset of cells in an all-or-nothing (i.e. digital) manner. The maximum fraction of responsive cells is regulated by a bimodal epigenetic switch that licenses the TLR2 promoter for transcription across multiple generations. This mechanism confers a flexible memory of inflammatory events as well as unique spatio-temporal control of epithelial tissue-level immune responses. We propose that epigenetic licensing in individual cells allows for long-term, quantitative fine-tuning of population-level responses.

Animals↗

A model for the estimate of local image velocity by cells in the visual cortex.

Some computational theories of motion perception assume that the first stage en route to this perception is the local estimate of image velocity. However, this assumption is not supported by data from the primary visual cortex. Its motion sensitive cells are not selective to velocity, but rather are directionally selective and tuned to spatio-temporal frequencies. Accordingly, physiologically based theories start with filters selective to oriented spatio-temporal frequencies. This paper shows that computational and physiological theories do not necessarily conflict, because such filters may, as a population, compute velocity locally. To prove this point, we show how to combine the outputs of a class of frequency tuned filters to detect local image velocity. Furthermore, we show that the combination of filters may simulate 'Pattern' cells in the middle temporal area (MT), whereas each filter simulates primary visual cortex cells. These simulations include three properties of the primary cortex. First, the spatio-temporal frequency tuning curves of the individual filters display approximate space-time separability. Secondly, their direction-of-motion tuning curves depend on the distribution of orientations of the components of the Fourier decomposition and speed of the stimulus. Thirdly, the filters show facilitation and suppression for responses to apparent motions in the preferred and null directions, respectively. It is suggested that the MT's role is not to solve the aperture problem, but to estimate velocities from primary cortex information. The spatial integration that accounts for motion coherence may be postponed to a later cortical stage.

Animals↗

The effects of maturation on spontaneous eye movements in the macaque monkey.

The spontaneous eye movements of infant and adult monkeys were studied both in the dark and in the laboratory light by a magnetic search-coil technique and analysed comparatively. The spatio-temporal organization of the infant monkey's eye movements is predominantly vertical; by contrast it is predominantly horizontal in adults. Moreover, the infant monkey's eye movements have smaller amplitudes and slower velocities than adult's in both visual conditions. The linear relationships between amplitude and maximum velocity suggest that rapid eye movements of the infant monkey are saccades but with a lower rate of velocity increase than the adult's. We conclude that the eye movements in the infant and in the adult monkeys differ in many aspects and that maturation acts on both the static and dynamic characteristics of ocular motility.

Aging↗

Immunocytochemical analysis of embryonic compartmentation with a monoclonal antibody against a cytokeratin-related antigen.

Mab 113F4, a monoclonal antibody recognizing an antigen in the outer synaptic layer of the chick neural retina, also recognizes an antigen appearing in all three germ layers of the gastrulating chick embryo. However, as neurulation proceeds, the antigen is down-regulated in three distinct patterns. First, the antigen is lost specifically from those trunk ectodermal cells destined to form the neural plate and, later, the neural tube. It remains absent from any neural derivative until day 13 when it appears in the outer synaptic layer of the neural retina, coincident with synaptogenesis in this region. Second, the entirety of the head ectoderm loses this antigen as the head lifts off the blastoderm. This down-regulation is followed later by a similar loss of antigen expression in the trunk ectoderm. Third, expression in the mesoderm becomes limited to the lateral plate and extraembryonic epithelia. Endodermal derivatives continue to express the antigen throughout development. Antigen 113F4 is localized within the cytoplasm and is organized in a fibrillar pattern. The intracellular localization of this antigen and its characteristic spatio-temporal tissue distribution are consistent with the antigen being a cytokeratin or cytokeratin-related antigen. The changes in tissue distribution suggest a possible role in tissue modelling in response to inductive interactions during development.

Animals↗

Dipole modelling of eye activity and its application to the removal of eye artefacts from the EEG and MEG.

The spatio-temporal dipole model approach has been used to identify the difference dipoles arising from changes in the ocular dipoles due to eye movements and blinks. Based on these results a method has been developed to remove eye artefacts from electrical or magnetic data. The method avoids distortions due to the head model by determining the spatial distribution of the signals from the eyes empirically. Using simultaneous modelling of the EEG or MEG activity with dipole sources distributed within the head together with the empirically determined spatial eye components, the eye activity can be estimated and removed from the EEG or MEG. This greatly reduces the distortion to the topography that is a concomitant of previous eye artefact correction methods. The advantages of the method are illustrated using simulated and real electrical data.

Analysis of Variance↗

Kinetic depth effect and optic flow--I. 3D shape from Fourier motion.

Fifty-three different 3D shapes were defined by sequences of 2D views (frames) of dots on a rotating 3D surface. (1) Subjects' accuracy of shape identifications dropped from over 90% to less than 10% when either the polarity of the stimulus dots was alternated from light-on-gray to dark-on-gray on successive frames or when neutral gray interframe intervals were interposed. Both manipulations interfere with motion extraction by spatio-temporal (Fourier) and gradient first-order detectors. Second-order (non-Fourier) detectors that use full-wave rectification are unaffected by alternating-polarity but disrupted by interposed gray frames. (2) To equate the accuracy of two-alternative forced-choice (2AFC) planar direction-of-motion discrimination in standard and polarity-alternated stimuli, standard contrast was reduced. 3D shape discrimination survived contrast reduction in standard stimuli whereas it failed completely with polarity-alternation even at full contrast. (3) When individual dots were permitted to remain in the image sequence for only two frames, performance showed little loss compared to standard displays where individual dots had an expected lifetime of 20 frames, showing that 3D shape identification does not require continuity of stimulus tokens. (4) Performance in all discrimination tasks is predicted (up to a monotone transformation) by considering the quality of first-order information (as given by a simple computation on Fourier power) and the number of locations at which motion information is required. Perceptual first-order analysis of optic flow is the primary substrate for structure-from-motion computations in random dot displays because only it offers sufficient quality of perceptual motion at a sufficient number of locations.

Depth Perception↗

Ultrastructure of giant and small thalamic terminals of cortical origin: a study of the projections from the barrel cortex in mice using Phaseolus vulgaris leuco-agglutinin (PHA-L).

By means of tracing with the lectin Phaseolus-vulgaris leucoagglutinin (PHA-L), we examined in the thalamus of the mouse, the axon terminals of fibers originating in the barrel cortex. Vibratome sections of the brain were subjected to PHA-L immunocytochemistry and processed for light and electron microscopy. We observed small (0.5-0.8 microns in diameter) varicosities of labeled fibers in the nucleus ventrobasalis (VB) and the nucleus posterior (PO) as well as labeled giant terminals (3-5 microns in diameter) in PO. The analysis involved examination of serial sections and computer-aided reconstruction of several terminals. The small varicosities in VB appear to be small axon terminals forming distinct asymmetric synapses with small dendritic profiles. Some labeled terminals are apposed to, but not synaptically related with, the cell bodies of neurons in VB that are retrogradely labeled with PHA-L. The small varicosities seen with the light microscope in PO are terminals forming asymmetric synapses with dendritic shafts. The giant terminals in PO appear as large, vesicle-filled profiles forming part of synaptic glomeruli, i.e. complexes of one corticothalamic terminal engulfing several excrescences of a single dendrite. A giant terminal forms several asymmetric synapses (about 8) with these excrescences, as well as numerous (up to 15) puncta adhaerentia. The glomeruli are enveloped in glial lamellae, and they are often found at the bifurcations of primary dendritic segments. We suggest that the small terminals in VB are in the service of feedback signalling from the barrel cortex to its principal thalamic relay nucleus; the functional importance of this projection may reside in increased spatio-temporal discrimination. We interpret the giant terminals in PO as elements serving feed-forward processing, allowing the barrel cortex to influence, via PO, parts of the motor pathway modulating the animal's ongoing behavior.

Animals↗

Expression of various NCAM isoforms in human embryonic muscles: correlation with myosin heavy chain phenotypes.

Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.

Aging↗

Training-stage related neuronal plasticity in limbic thalamus and cingulate cortex during learning: a possible key to mnemonic retrieval.

This study is part of an ongoing project concerned with the analysis of the neural substrates of discriminative avoidance learning in rabbits. Multi-unit activity was recorded in 5 anterior and lateral thalamic nuclei and in 4 layers of 2 posterior cingulate cortical areas (29c/d and 29b) during learning. The rabbits learned to step in response to a warning tone to avoid a foot-shock, and to ignore a different tone not followed by shock. Excitatory training-induced unit activity (TIA, increased tone-elicited activity during training relative to a pretraining session with unpaired tone-shock presentations) and/or discriminative TIA (greater discharges to the warning than to the safe tone) developed during training in 11 of the 13 areas. Discriminative TIA in the thalamic nuclei increased monotonically as learning occurred. Anterodorsal (AD) thalamic excitatory TIA peaked in an early stage (the first session of training), laterodorsal thalamic and parvocellular anteroventral (AVp) excitatory TIA peaked in an intermediate stage (the session of the first behavioral discrimination), and magnocellular anteroventral (AVm) and anteromedial (AM) thalamic excitatory TIA peaked in a late stage (the session in which asymptotic behavioral discrimination first occurred). The excitatory TIA in these nuclei declined as training continued beyond the stage in which the peak occurred. Peaks of excitatory TIA developed in area 29c/d of posterior cingulate cortex in the early (layer IV), intermediate (layers I-III and V) and late (layer IV) training stages, as just defined. Only layer IV in area 29b of posterior cingulate cortex exhibited a peak of excitatory TIA, which occurred in the early and intermediate training stages. As in limbic thalamus, discriminative TIA increased monotonically over training stages in layers V and VI of areas 29c/d and in layer VI of area 29b. However, layers I-III and IV in area 29c exhibited peak discriminative TIA in the intermediate and late training stages, respectively. Lesion studies indicate that limbic thalamus and cingulate cortex are essential for learning. The peaks represent a unique topographic pattern of thalamic and cortical excitation elicited by the CS+. It is proposed that the peaks constitute a retrieval pattern, i.e. a unique topographic array of excitation. This pattern encodes the spatio-temporal context which defines the learning situation and is necessary for recall and output of the learned response.

Animals↗

Axial responses in visual cortical cells: spatio-temporal mechanisms quantified by Fourier components of cortical tuning curves.

The responses of 81 cells from area 17 in paralysed and anaesthetized cats were studied with moving spots and moving bars of different lengths. Tuning curves were measured and plotted as polar-plots. The strongest response of visual cortical cells to a moving bar occurs when the stimulus trajectory crosses the long axis of the receptive field (Hubel and Wiesel 1962). The optimal orientation for a moving and a flashing bar are identical, so that this response-type has been called the orientational component. For a moving spot, however, in most cases the strongest response occurs for motion along the receptive field long axis (axial component). Thus, the axial and orientational components are orthogonal (Wörgötter and Eysel 1989). It is shown that orientational and axial components can display direction selectivity and for short bar stimuli a superposition of the two orthogonal components is demonstrated. Such a superposition in general, resulted in a polar-plot with four peaks 90 degrees apart from each other (four-symmetrical polar-plot). Polar-plots with three or two response peaks were also found; the actual number of response peaks depending on the direction selectivity of the components. In many cells pure axial responses could be elicited with a light spot which stimulates only motion dependent mechanisms. Thus, it was concluded that temporal facilitation is strongly involved in the generation of axial responses. Fourier analysis of polar-plots (SDO-analysis, Wörgötter and Eysel 1987; Wörgötter et al. 1990) was applied to determine the tuning strengths of the different components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of spatial frequency and handedness on hemispheric asymmetry in visually steady-state evoked potentials.

Recent suggestions on the involvement of the spatial frequency of visual stimuli in the hemispheric lateralization were investigated by recording steady-state evoked potentials in two groups of subjects: five right-handers and five left-handers. Sinusoidal gratings at spatial frequency of 0.5, 1, 3, 4, 6, 8, 10, 12 or 16 cpd were phase reversed at 4 Hz or 12 Hz. Evoked potentials recorded from temporal leads over each hemisphere were submitted to a FFT analysis. Results concern the amplitude of the fundamental component. In right-handers, the temporal frequency was the deciding factor of the lateralization: the evoked activities were greatest in the RH at 4 Hz and in the LH at 12 Hz. This effect was obvious for the range of spatial frequencies from 3-12 cpd. Results, discussed in terms of global/local information, suggested the existence of two transient and sustained systems. In left-handers, both the spatial and temporal parameters were relevant to the lateralization. A spatio-temporal interaction was observed which was reversed at 6 cpd.

Adult↗