On the Hybrid Extension of CTL and CTL+

The paper studies the expressivity, relative succinctness and complexity of satisfiability for hybrid extensions of the branching-time logics CTL and CTL+ by variables. Previous complexity results show that only fragments with one variable do have elementary complexity. It is shown that H1CTL+ and H1CTL, the hybrid extensions with one variable of CTL+ and CTL, respectively, are expressively equivalent but H1CTL+ is exponentially more succinct than H1CTL. On the other hand, HCTL+, the hybrid extension of CTL with arbitrarily many variables does not capture CTL*, as it even cannot express the simple CTL* property EGFp. The satisfiability problem for H1CTL+ is complete for triply exponential time, this remains true for quite weak fragments and quite strong extensions of the logic

Neural Connectivity with Hidden Gaussian Graphical State-Model

The noninvasive procedures for neural connectivity are under questioning. Theoretical models sustain that the electromagnetic field registered at external sensors is elicited by currents at neural space. Nevertheless, what we observe at the sensor space is a superposition of projected fields, from the whole gray-matter. This is the reason for a major pitfall of noninvasive Electrophysiology methods: distorted reconstruction of neural activity and its connectivity or leakage. It has been proven that current methods produce incorrect connectomes. Somewhat related to the incorrect connectivity modelling, they disregard either Systems Theory and Bayesian Information Theory. We introduce a new formalism that attains for it, Hidden Gaussian Graphical State-Model (HIGGS). A neural Gaussian Graphical Model (GGM) hidden by the observation equation of Magneto-encephalographic (MEEG) signals. HIGGS is equivalent to a frequency domain Linear State Space Model (LSSM) but with sparse connectivity prior. The mathematical contribution here is the theory for high-dimensional and frequency-domain HIGGS solvers. We demonstrate that HIGGS can attenuate the leakage effect in the most critical case: the distortion EEG signal due to head volume conduction heterogeneities. Its application in EEG is illustrated with retrieved connectivity patterns from human Steady State Visual Evoked Potentials (SSVEP). We provide for the first time confirmatory evidence for noninvasive procedures of neural connectivity: concurrent EEG and Electrocorticography (ECoG) recordings on monkey. Open source packages are freely available online, to reproduce the results presented in this paper and to analyze external MEEG databases

Reactive models for biological regulatory networks

A reactive model, as studied by D. Gabbay and his collaborators, can be regarded as a graph whose set of edges may be altered whenever one of them is crossed. In this paper we show how reactive models can describe biological regulatory networks and compare them to Boolean networks and piecewise-linear models, which are some of the most common kinds of models used nowadays. In particular, we show that, with respect to the identification of steady states, reactive Boolean networks lie between piecewise linear models and the usual, plain Boolean networks. We also show this ability is preserved by a suitable notion of bisimulation, and, therefore, by network minimisation.ERDF - The European Regional Development Fund through the Operational Programme for Competitiveness and Internationalisation - COMPETE 2020 Programme and by National Funds through the Portuguese funding agency, FCT - Fundação para a Ciência e a Tecnologia, within project POCI-01-0145-FEDER-030947. and project with reference UID/MAT/04106/2019 at CIDMA. D. Figueiredo also acknowledges the support given by FCT via the PhD scholarship PD/BD/114186/201

Effects of sleep on the academic performance of children with attention deficit and hyperactivity disorder

Attention deficit and hyperactivity disorder (ADHD) is commonly associated with disordered or disturbed sleep and the association of sleep problems with ADHD is complex and multidirectional. The purpose of this study was to analyze the relationship between sleep and academic performance, comparing children with ADHD and a control group without ADHD. Academic performance in Spanish, mathematics, and a foreign language (English) was evaluated. Different presentations of ADHD were considered as well as the potential difference between weekday and weekend sleep habits. The sample consisted of 75 children aged 6–12 in primary education. Accelerometry was used to study sleep, and school grades were used to gather information about academic performance. The results showed that ADHD influenced the amount of sleep during weekends, the time getting up at the weekends, weekday sleep efficiency, as well as academic performance. Given the effects that were seen in the variables linked to the weekend, it is necessary to consider a longitudinal design with which to determine if there is a cause and effect relationship

Completeness in hybrid type theory

We show that basic hybridization (adding nominals and @ operators) makes it possible to give straightforward Henkin-style completeness proofs even when the modal logic being hybridized is higher-order. The key ideas are to add nominals as expressions of type t, and to extend to arbitrary types the way we interpret @i in propositional and first-order hybrid logic. This means: interpret @iαa, where αa is an expression of any type a, as an expression of type a that rigidly returns the value that αa receives at the i-world. The axiomatization and completeness proofs are generalizations of those found in propositional and first-order hybrid logic, and (as is usual in hybrid logic) we automatically obtain a wide range of completeness results for stronger logics and languages. Our approach is deliberately low-tech. We don’t, for example, make use of Montague’s intensional type s, or Fitting-style intensional models; we build, as simply as we can, hybrid logic over Henkin’s logic.submittedVersionFil: Areces, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Blackburn, Patrick. University of Roskilde. Centre for Culture and Identity. Department of Philosophy and Science Studies; Dinamarca.Fil: Huertas, Antonia. Universitat Oberta de Catalunya; España.Fil: Manzano, María. Universidad de Salamanca; España.Ciencias de la Computació

An effector region in Eps8 is responsible for the activation of the Rac-specific GEF activity of Sos-1 and for the proper localization of the Rac-based actin-polymerizing machine

Genetic and biochemical evidence demonstrated that Eps8 is involved in the routing of signals from Ras to Rac. This is achieved through the formation of a tricomplex consisting of Eps8-E3b1-Sos-1, which is endowed with Rac guanine nucleotide exchange activity. The catalytic subunit of this complex is represented by Sos-1, a bifunctional molecule capable of catalyzing guanine nucleotide exchange on Ras and Rac. The mechanism by which Sos-1 activity is specifically directed toward Rac remains to be established. Here, by performing a structure-function analysis we show that the Eps8 output function resides in an effector region located within its COOH terminus. This effector region, when separated from the holoprotein, activates Rac and acts as a potent inducer of actin polymerization. In addition, it binds to Sos-1 and is able to induce Rac-specific, Sos-1-dependent guanine nucleotide exchange activity. Finally, the Eps8 effector region mediates a direct interaction of Eps8 with F-actin, dictating Eps8 cellular localization. We propose a model whereby the engagement of Eps8 in a tricomplex with E3b1 and Sos-1 facilitates the interaction of Eps8 with Sos-1 and the consequent activation of an Sos-1 Rac-specific catalytic ability. In this complex, determinants of Eps8 are responsible for the proper localization of the Rac-activating machine to sites of actin remodeling

Harmonized-Multinational qEEG Norms (HarMNqEEG)

This paper extends the frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. ii) We also show that the multinational harmonized Riemannian norms produce z-scores with increased diagnostic accuracy to predict brain dysfunction at school-age produced by malnutrition only in the first year of life. iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings

Formin1 Mediates the Induction of Dendritogenesis and Synaptogenesis by Neurogenin3 in Mouse Hippocampal Neurons

Neurogenin3, a proneural transcription factor controlled by Notch receptor, has been recently shown to regulate dendritogenesis and synaptogenesis in mouse hippocampal neurons. However, little is known about the molecular mechanisms involved in these actions of Ngn3. We have used a microarray analysis to identify Ngn3 regulated genes related with cytoskeleton dynamics. One of such genes is Fmn1, whose protein, Formin1, is associated with actin and microtubule cytoskeleton. Overexpression of the Fmn1 isoform-Ib in cultured mouse hippocampal neurons induced an increase in the number of primary dendrites and in the number of glutamatergic synaptic inputs at 4 days in vitro. The same changes were provoked by overexpression of Ngn3. In addition downregulation of Fmn1 by the use of Fmn1-siRNAs impaired such morphological and synaptic changes induced by Ngn3 overexpression in neurons. These results reveal a previously unknown involvement of Formin1 in dendritogenesis and synaptogenesis and indicate that this protein is a key component of the Ngn3 signaling pathway that controls neuronal differentiation

Transformation and scattering activities of the receptor tyrosine kinase RON/Stk in rodent fibroblasts and lack of regulation by the jaagsiekte sheep retrovirus receptor, Hyal2

BACKGROUND: The envelope (Env) protein of jaagsiekte sheep retrovirus (JSRV) can transform cells in culture and is likely to be the main factor responsible for lung cancer induction by JSRV in animals. A recent report indicates that the epithelial-cell transforming activity of JSRV Env depends on activation of the cell-surface receptor tyrosine kinase Mst1r (called RON for the human and Stk for the rodent orthologs). In the immortalized line of human epithelial cells used (BEAS-2B cells), the virus receptor Hyal2 was found to bind to and suppress the activity of RON. When Env was expressed it bound to Hyal2 causing its degradation, release of RON activity from Hyal2 suppression, and activation of pathways resulting in cell transformation. METHODS: Due to difficulty with reproducibility of the transformation assay in BEAS-2B cells, we have used more tractable rodent fibroblast models to further study Hyal2 modulation of RON/Stk transforming activity and potential effects of Hyal2 on RON/Stk activation by its natural ligand, macrophage stimulating protein (MSP). RESULTS: We did not detect transformation of NIH 3T3 cells by plasmids expressing RON or Stk, but did detect transformation of 208F rat fibroblasts by these plasmids at a very low rate. We were able to isolate 208F cell clones that expressed RON or Stk and that showed changes in morphology indicative of transformation. The parental 208F cells did not respond to MSP but 208F cells expressing RON or Stk showed obvious increases in scattering/transformation in response to MSP. Human Hyal2 had no effect on the basal or MSP-induced phenotypes of RON-expressing 208F cells, and human, mouse or rat Hyal2 had no effect on the basal or MSP-induced phenotypes of Stk-expressing 208F cells. CONCLUSIONS: We have shown that RON or Stk expression in 208F rat fibroblasts results in a transformed phenotype that is enhanced by addition of the natural ligand for these proteins, MSP. Hyal2 does not directly modulate the basal or MSP-induced RON/Stk activity, although it is possible that adaptor proteins might mediate such signaling in other cell types