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PubMed2006

A sound and complete fuzzy temporal constraint logic.

In this work, we define an extended fuzzy temporal constraint logic (EFTCL) based on possibilistic logic. EFTCL allows us to handle fuzzy temporal constraints between temporal variables and, therefore, enables us to express interrelated events through fuzzy temporal constraints. EFTCL is compatible with a theoretical temporal reasoning model: the fuzzy temporal constraint networks (FTCN). The syntax, the semantics and the deduction and refutation theorems for EFTCL are similar to those defined for the sound and noncomplete fuzzy temporal constraint logic (FTCL). In this paper, a resolution principle for performing inferences which take these constraints into account is proposed for EFTCL. Moreover, we prove the soundness and the completeness of the refutation by resolution in EFTCL.

Algorithms↗

PubMed2004

The antisaccade task and neuropsychological tests of prefrontal cortical integrity in schizophrenia: empirical findings and interpretative considerations.

To date, every published study of the antisaccade task has replicated the finding that schizophrenia patients make an increased number of errors. This finding has been interpreted as support for frontal and/or basal ganglia dysfunction in schizophrenia, primarily because neurological patients with pathology in these brain regions also make large numbers of errors on the antisaccade task. Here, we compared the performance of schizophrenia patients and nonpsychiatric controls on an antisaccade task and on two neuropsychological tests, the Wisconsin Card Sorting Test, which is assumed to tap frontal lobe functioning, and the interference condition of the Stroop Test, which is thought to tap dorsolateral prefrontal cortex/anterior cingulate functioning. We examined the pattern of intercorrelations among these tasks. Schizophrenia patients made significantly more errors on the antisaccade task, made more perseverative errors and achieved fewer categories on the Wisconsin Card Sorting Test, and were significantly slower during the interference condition of the Stroop Test than were nonpsychiatric controls. Antisaccade errors were significantly correlated with interference performance on the Stroop in schizophrenia patients and in controls, but were not significantly correlated with the measures of Wisconsin Card Sorting Test performance in either group. The pattern of intercorrelation suggests that these tasks should not be thought of as representing a unitary variable of "frontal cortical integrity". Although aspects of these tasks tap the ability to inhibit prepotent responses, each task is also behaviorally complex. The multifaceted nature of these tasks makes it difficult to isolate which brain regions are part of the network underlying the specific act of inhibiting a prepotent response (for example, the reflexive saccade toward the novel peripheral target) and which regions participate in aspects of task performance that are related to non-inhibitory components (for example, executing an antisaccade). A broadly distributed network is undoubtedly involved in both processes. Parsing the various components of cognitively complex tasks may help to clarify both the specific behaviors that are anomalous and their underlying neural substrates. We also address the complexity of inferring localized brain dysfunction in schizophrenia patients based on seemingly analogous behavioral deficits in neurological populations.

Journal Article↗

PubMed1998

Scattered Golgi elements during microtubule disruption are initially enriched in trans-Golgi proteins.

We have addressed the question of whether or not Golgi fragmentation, as exemplified by that occurring during drug-induced microtubule depolymerization, is accompanied by the separation of Golgi subcompartments one from another. Scattering kinetics of Golgi subcompartments during microtubule disassembly and reassembly following reversible nocodazole exposure was inferred from multimarker analysis of protein distribution. Stably expressed alpha-2,6-sialyltransferase and N-acetylglucosaminyltransferase-I (NAGT-I), both C-terminally tagged with the myc epitope, provided markers for the trans-Golgi/trans-Golgi network (TGN) and medial-Golgi, respectively, in Vero cells. Using immunogold labeling, the chimeric proteins were polarized within the Golgi stack. Total cellular distributions of recombinant proteins were assessed by immunofluorescence (anti-myc monoclonal antibody) with respect to the endogenous protein, beta-1,4-galactosyltransferase (GalT, trans-Golgi/TGN, polyclonal antibody). ERGIC-53 served as a marker for the intermediate compartment). In HeLa cells, distribution of endogenous GalT was compared with transfected rat alpha-mannosidase II (medial-Golgi, polyclonal antibody). After a 1-h nocodazole treatment, Vero alpha-2,6-sialyltransferase and GalT were found in scattered cytoplasmic patches that increased in number over time. Initially these structures were often negative for NAGT-I, but over a two- to threefold slower time course, NAGT-I colocalized with alpha-2,6-sialyltransferase and GalT. Scattered Golgi elements were located in proximity to ERGIC-53-positive structures. Similar trans-first scattering kinetics was seen with the HeLa GalT/alpha-mannosidase II pairing. Following nocodazole removal, all cisternal markers accumulated at the same rate in a juxtanuclear Golgi. Accumulation of cisternal proteins in scattered Golgi elements was not blocked by microinjected GTPgammaS at a concentration sufficient to inhibit secretory processes. Redistribution of Golgi proteins from endoplasmic reticulum to scattered structures following brefeldin A removal in the presence of nocodazole was not blocked by GTPgammaS. We conclude that Golgi subcompartments can separate one from the other. We discuss how direct trafficking of Golgi proteins from the TGN/trans-Golgi to endoplasmic reticulum may explain the observed trans-first scattering of Golgi transferases in response to microtubule depolymerization.

Animals↗

PubMed2005

Genome-wide analysis of hydrogen peroxide-regulated gene expression in Arabidopsis reveals a high light-induced transcriptional cluster involved in anthocyanin biosynthesis.

In plants, reactive oxygen species and, more particularly, hydrogen peroxide (H(2)O(2)) play a dual role as toxic by-products of normal cell metabolism and as regulatory molecules in stress perception and signal transduction. Peroxisomal catalases are an important sink for photorespiratory H(2)O(2). Using ATH1 Affymetrix microarrays, expression profiles were compared between control and catalase-deficient Arabidopsis (Arabidopsis thaliana) plants. Reduced catalase levels already provoked differences in nuclear gene expression under ambient growth conditions, and these effects were amplified by high light exposure in a sun simulator for 3 and 8 h. This genome-wide expression analysis allowed us to reveal the expression characteristics of complete pathways and functional categories during H(2)O(2) stress. In total, 349 transcripts were significantly up-regulated by high light in catalase-deficient plants and 88 were down-regulated. From this data set, H(2)O(2) was inferred to play a key role in the transcriptional up-regulation of small heat shock proteins during high light stress. In addition, several transcription factors and candidate regulatory genes involved in H(2)O(2) transcriptional gene networks were identified. Comparisons with other publicly available transcriptome data sets of abiotically stressed Arabidopsis revealed an important intersection with H(2)O(2)-deregulated genes, positioning elevated H(2)O(2) levels as an important signal within abiotic stress-induced gene expression. Finally, analysis of transcriptional changes in a combination of a genetic (catalase deficiency) and an environmental (high light) perturbation identified a transcriptional cluster that was strongly and rapidly induced by high light in control plants, but impaired in catalase-deficient plants. This cluster comprises the complete known anthocyanin regulatory and biosynthetic pathway, together with genes encoding unknown proteins.

Anthocyanins↗

PubMed1985

Vasculogenesis in the chick embryo optic tectum.

The initial formation and further development of the intraneural blood vessel network in the tectum opticum of the chick from the 4th to the 14th incubation day have been analyzed and some quantitative data morphometrically recorded. Vessels have been filled by intracardial injection of India ink in vivo. As inferred from our previous investigations on the vasculogenesis of several districts of the central and peripheral nervous system in the chick embryo, also in the developing optic tectum growth and distribution pattern of the vessels seem to unfold step by step under the local influence of earlier occurring morpho-histogenetic processes of the corresponding neural substratum.

Animals↗

PubMed2006

Developmental constraints vs. variational properties: How pattern formation can help to understand evolution and development.

This article suggests that apparent disagreements between the concept of developmental constraints and neo-Darwinian views on morphological evolution can disappear by using a different conceptualization of the interplay between development and selection. A theoretical framework based on current evolutionary and developmental biology and the concepts of variational properties, developmental patterns and developmental mechanisms is presented. In contrast with existing paradigms, the approach in this article is specifically developed to compare developmental mechanisms by the morphological variation they produce and the way in which their functioning can change due to genetic variation. A developmental mechanism is a gene network, which is able to produce patterns in space though the regulation of some cell behaviour (like signalling, mitosis, apoptosis, adhesion, etc.). The variational properties of a developmental mechanism are all the pattern transformations produced under different initial and environmental conditions or IS-mutations. IS-mutations are DNA changes that affect how two genes in a network interact, while T-mutations are mutations that affect the topology of the network itself. This article explains how this new framework allows predictions not only about how pattern formation affects variation, and thus phenotypic evolution, but also about how development evolves by replacement between pattern formation mechanisms. This article presents testable inferences about the evolution of the structure of development and the phenotype under different selective pressures. That is what kind of pattern formation mechanisms, in which relative temporal order, and which kind of phenotypic changes, are expected to be found in development.

Animals↗

PubMed2006

Decoding spike train ensembles: tracking a moving stimulus.

We consider the issue of how to read out the information from nonstationary spike train ensembles. Based on the theory of censored data in statistics, we propose a 'censored' maximum-likelihood estimator (CMLE) for decoding the input in an unbiased way when the spike activity is observed over time windows of finite length. Compared with a rate-based, moment estimator, the CMLE is proved consistently more efficient, particularly with nonstationary inputs. Using our approach, we show that a dynamical input to a group of neurons can be inferred accurately and with high temporal resolution (50 ms) using as few as about one spike per neuron within each decoding window. By applying our theoretical results to a population coding setting, we then demonstrate that a spiking neural network can encode spatial information in such a way to allow fast and precise tracking of a moving target.

Brain↗

PubMed2002

A neuro-fuzzy framework for inferencing.

Earlier we proposed a connectionist implementation of compositional rule of inference (COI) for rules with antecedents having a single clause. We first review this net, then generalize it so that it can deal with rules with antecedent having multiple clauses. We call it COIN, the compositional rule of inferencing network. Given a relational representation of a set of rules, the proposed architecture can realize the COI. The outcome of COI depends on the choice of both the implication function and the inferencing scheme. The problem of choosing an appropriate implication function is avoided through neural learning. COIN can automatically find a 'good' relation to represent a set of fuzzy rules. We model the connection weights so as to ensure learned weights lie in [0,1]. We demonstrate through extensive numerical examples that the proposed neural realization can find a much better representation of the rules than that by usual implication and hence results in much better conclusions than the usual COI.

Fuzzy Logic↗

PubMed2001

Life events and depression in a community sample of siblings.

BACKGROUND: The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices. METHODS: We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations. RESULTS: Life events showed sibling correlations of 0-37 for network events and between 0-10 and 0.19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects. CONCLUSIONS: Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.

Adult↗

PubMed2003

Can attentional theory explain the inverse base rate effect? Comment on Kruschke (2001).

In J. K. Kruschke's (2001; see record 2001-18940-005) study, it is argued that attentional theory is the sole satisfactory explanation of the inverse base rate effect and that eliminative inference (P. Juslin, P. Wennerholm, & A. Winman, 2001; see record 2001-07828-016) plays no role in the phenomenon. In this comment, the authors demonstrate that, in contrast to the central tenets of attentional theory, (a) rapid attention shifts as implemented in ADIT decelerate learning in the inverse base-rate task and (b) the claim that the inverse base-rate effect is directly caused by an attentional asymmetry is refuted by data. It is proposed that a complete account of the inverse base-rate effect needs to integrate attention effects with inference rules that are flexibly used for both induction and elimination.

Association Learning↗

PubMed2026

Mitochondria-Related Pathogenic Genes in Paediatric Asthma: A Multi-Omics Mendelian Randomization Study.

Mitochondrial dysfunction is implicated in asthma pathogenesis, but causal roles of mitochondrial-related genes in paediatric asthma remain unclear. We performed a multi-omics Mendelian randomization study integrating GWAS data from paediatric asthma cohorts with blood-based methylation quantitative trait loci (mQTLs), expression QTLs (eQTLs) and protein QTLs (pQTLs) datasets. Causal inference was assessed using Summary-data-based Mendelian Randomization (SMR) and HEIDI testing, complemented by colocalization analysis. Findings were validated in independent cohorts and evaluated for tissue specificity using GTEx. Functional enrichment and protein-protein interaction (PPI) network analyses were conducted. SMR analysis identified 80 methylation sites spanning 54 genes, 26 gene expressions, and three proteins significantly associated with paediatric asthma. Colocalization analysis confirmed strong evidence for 10 methylation sites (7 genes), the STX17 eQTL (PP.H4 = 0.98) and the UNG pQTL (PP.H4 = 0.84). Tissue-specific eQTL validation replicated the STX17 association. Multi-omics integration associated ALAS1 (cg13241645, cg15698299) and TXNRD1 (cg09884423) with asthma at both methylation and expression levels, with colocalization supporting both ALAS1 associations. Furthermore, integrated mQTL-eQTL analysis suggests that DNA methylation potentially regulates ALAS1 and TXNRD1 expression. Functional enrichment and network analyses revealed that these candidate genes converge on mitochondrial metabolic pathways and identified seven hub genes with potential regulatory significance (SDHB, MFN2, GLDC, PHB2, TXNRD1, ATP5MC1 and PHB). This study provides multi-omics evidence supporting a causal role for mitochondrial-related genes, particularly ALAS1 and TXNRD1, in paediatric asthma, offering new insights into pathogenesis and potential therapeutic targets.

Humans↗

PubMed2001

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: an illustration using fMRI.

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Adolescent↗

PubMed1994

Corticocortical connectivity, autonomous networks, and schizophrenia.

Dr. David hypothesizes that increased, not decreased, corticocortical connectivity causes schizophrenia. He cites studies suggesting excessive semantic priming and cross-hemispheric interference in this disorder to support his hypothesis. These findings, David suggests, reflect excessive transmission of information between neurons or within neural systems. However, considerable caution should be exercised in making neuroanatomic inferences on the basis of cognitive studies alone. There is an increasing consensus that information is represented by the brain as patterns of neural activation, where the same neuron or group of neurons participates in many different representations. Our simulations, which reflect this consensus, suggest that persistent or intrusive activation patterns do not emerge from too many neural connections, but from too few. This condition causes subgroups of neurons to disregard information processing by other neurons and to produce autonomously their own output, which interferes with the functioning of the system as a whole. Direct neuroanatomic or neurochemical studies of the cerebral cortex are needed to fully assess hypotheses regarding abnormal corticocortical connectivity in schizophrenia.

Brain Mapping↗

PubMed1985

Packing volume of sedimented microtubules: regulation and potential relationship to an intracellular matrix.

To determine the contribution of microtubules to a hypothetical intracellular matrix, we have analyzed the space occupied by microtubules in vitro. Taxol-stabilized microtubules assembled from purified (three-times-cycled) bovine brain microtubule protein were pelleted by centrifugation under standardized conditions. The specific volume of the pellet, defined as the microliter volume per milligram protein, was 22.4. As suggested by others, this volume was strongly dependent on microtubule-associated proteins (MAPs), as shown by quantitation of the effects of purified MAP supplementation on specific volume. The specific volumes of microtubule pellets stripped of MAPs by high salt or chymotryptic digestion approached the mathematically optimal (least occupied space) and increased 14-fold with the highest MAP concentrations employed. Packing was also dependent on pH. Specific volumes comparable to those of MAP-depleted microtubules were attainable at pH's from 5.5 to 6.0, and specific volumes more than doubled at pH 7.5. MAP content was unaffected by pH. We present a theoretical analysis that suggests that as microtubules are centrifuged the mixture behaves as a liquid crystal. With packing, the mixture undergoes an isotropic-nematic phase transition in which the microtubules become oriented principally as parallel rods, mimicking their orientation in vivo. From the known concentration of microtubules in vivo, it can be inferred from our measurements that in some cells a large fraction, perhaps 40-50% of the cytosolic volume, is occupied by microtubules that form a mechanically irreducible space. Further theoretical analysis employing Ogston's formulation of the penetrability of fibrous networks suggests that the space between microtubules (in contrast to the extracellular matrix) imposes little barrier to the diffusion of macromolecules. A microtubule array thus achieves mechanical stability without affecting transport by diffusion. The space can accommodate other fibrous networks that could then affect transport, and, as we show, the space itself may be regulated by MAP content and intracellular pH.

Alkaloids↗

PubMed2000

The development of algorithms in electrical impedance computerized tomography.

Electrical Impedance Computerized Tomography (EICT) is an imaging method to reconstruct the impedance distribution inside of domain through the boundary injected current and display the impedance contrast ratio as an image. This paper concentrates on developing two algorithms to enhance the quality of the conductivity image. The two algorithms are "Fine-Mesh Conversion Method" and "Sub-Domain EICT Method". "Fine-Mesh Conversion Method" is a numerical calibration process to find a coarse mesh impedance network that behaves like a fine mesh network in terms of giving similar voltages under the same current excitations. "Sub-Domain EICT" solves a higher resolution EICT with the cost of a lower resolution EICT by combining "Fine-Mesh Conversion Method", and a Fuzzy Logic Inference Systems (FLIS) classifier.

Algorithms↗

PubMed2006

Comparison of protein interaction networks reveals species conservation and divergence.

BACKGROUND: Recent progresses in high-throughput proteomics have provided us with a first chance to characterize protein interaction networks (PINs), but also raised new challenges in interpreting the accumulating data. RESULTS: Motivated by the need of analyzing and interpreting the fast-growing data in the field of proteomics, we propose a comparative strategy to carry out global analysis of PINs. We compare two PINs by combining interaction topology and sequence similarity to identify conserved network substructures (CoNSs). Using this approach we perform twenty-one pairwise comparisons among the seven recently available PINs of E.coli, H.pylori, S.cerevisiae, C.elegans, D.melanogaster, M.musculus and H.sapiens. In spite of the incompleteness of data, PIN comparison discloses species conservation at the network level and the identified CoNSs are also functionally conserved and involve in basic cellular functions. We investigate the yeast CoNSs and find that many of them correspond to known complexes. We also find that different species harbor many conserved interaction regions that are topologically identical and these regions can constitute larger interaction regions that are topologically different but similar in framework. Based on the species-to-species difference in CoNSs, we infer potential species divergence. It seems that different species organize orthologs in similar but not necessarily the same topology to achieve similar or the same function. This attributes much to duplication and divergence of genes and their associated interactions. Finally, as the application of CoNSs, we predict 101 protein-protein interactions (PPIs), annotate 339 new protein functions and deduce 170 pairs of orthologs. CONCLUSION: Our result demonstrates that the cross-species comparison strategy we adopt is powerful for the exploration of biological problems from the perspective of networks.

Animals↗

PubMed2000

Structure and function of fibrinogen inferred from hereditary dysfibrinogens.

The structure-function relationships of human fibrinogen and their clinical implications are discussed on the basis of data provided by biochemical and electron microscopic analyses of normal and abnormal fibrinogen and by recent crystallographic studies on certain functional domains and segments of normal fibrinogen. Particularly, ultrastructure studies of individual fibrinogen molecules and fibrin networks of structurally elucidated dysfibrinogens enable us to understand the structure-function relationships of these dysfibrinogens more clearly than ever. Electron micrographs of some representative dysfibrinogen molecules are provided.

Binding Sites↗

PubMed1992

Toward normative expert systems: Part II. Probability-based representations for efficient knowledge acquisition and inference.

We address practical issues concerning the construction and use of decision-theoretic or normative expert systems for diagnosis. In particular, we examine Pathfinder, a normative expert system that assists surgical pathologists with the diagnosis of lymph-node diseases, and discuss the representation of dependencies among pieces of evidence within this system. We describe the belief network, a graphical representation of probabilistic dependencies. We see how Pathfinder uses a belief network to construct differential diagnosis efficiently, even when there are dependencies among pieces of evidence. In addition, we introduce an extension of the belief-network representation called a similarity network, a tool for constructing large and complex belief networks. The representation allows a user to construct independent belief networks for subsets of a given domain. A valid belief network for the entire domain can then be constructed from the individual belief networks. We also introduce the partition, a graphical representation that facilitates the assessment of probabilities associated with a belief network. We show that the similarity-network and partition representations made practical the construction of Pathfinder.

Algorithms↗