Greater repertoire and temporal variability of cross-frequency coupling (CFC) modes in resting-state neuromagnetic recordings among children with reading difficulties

Cross-frequency, phase-to-amplitude coupling (PAC) between neuronal oscillations at rest may serve as the substrate that supports information exchange between functionally specialized neuronal populations both within and between cortical regions. The study utilizes novel algorithms to identify prominent instantaneous modes of cross-frequency coupling and their temporal stability in resting state magnetoencephalography (MEG) data from 25 students experiencing severe reading difficulties (RD) and 27 age-matched non-impaired readers (NI). Phase coherence estimates were computed in order to identify the prominent mode of PAC interaction for each sensor, sensor pair, and pair of frequency bands (from δ to γ) at successive time windows of the continuous MEG record. The degree of variability in the characteristic frequency-pair PACf1−f2 modes over time was also estimated. Results revealed a wider repertoire of prominent PAC interactions in RD as compared to NI students, suggesting an altered functional substrate for information exchange between neuronal assemblies in the former group. Moreover, RD students showed significant variability in PAC modes over time. This temporal instability of PAC values was particularly prominent: (a) within and between right hemisphere temporo-parietal and occipito-temporal sensors and, (b) between left hemisphere frontal, temporal, and occipito-temporal sensors and corresponding right hemisphere sites. Altered modes of neuronal population coupling may help account for extant data revealing reduced, task-related neurophysiological and hemodynamic activation in left hemisphere regions involved in the reading network in RD. Moreover, the spatial distribution of pronounced instability of cross-frequency coupling modes in this group may provide an explanation for previous reports suggesting the presence of inefficient compensatory mechanisms to support reading

Model-Driven Simulation-Based Analysis for Multi-Robot Systems

Multi-robot systems are increasingly deployed to provide services and accomplish missions whose complexity or cost is too high for a single robot to achieve on its own. Although multi-robot systems offer increased reliability via redundancy and enable the execution of more challenging missions, engineering these systems is very complex. This complexity affects not only the architecture modelling of the robotic team but also the modelling and analysis of the collaborative intelligence enabling the team to complete its mission. Existing approaches for the development of multi-robot applications do not provide a systematic mechanism for capturing these aspects and assessing the robustness of multi-robot systems. We address this gap by introducing ATLAS, a novel model-driven approach supporting the systematic robustness analysis of multi-robot systems in simulation. The ATLAS domain-specific language enables modelling the architecture of the robotic team and its mission, and facilitates the specification of the team’s intelligence. We evaluate ATLAS and demonstrate its effectiveness on two oceanic exploration missions performed by a team of unmanned underwater vehicles developed using the MOOS-IvP robotic simulator

Classifying children with reading difficulties from non-impaired readers via symbolic dynamics and complexity analysis of MEG resting-state data

Magnetoencephalography (MEG) is a brain imaging method affording real-time temporal, and adequate spatial resolution to reveal aberrant neurophysiological function associated with dyslexia. In this study we analyzed sensor-level resting-state neuromagnetic recordings from 25 reading-disabled children and 27 non-impaired readers under the notion of symbolic dynamics and complexity analysis. We compared two techniques for estimating the complexity of MEG time-series in each of 8 frequency bands based on symbolic dynamics: (a) Lempel-Ziv complexity (LZC) entailing binarization of each MEG time series using the mean amplitude as a threshold, and (b) An approach based on the neural-gas algorithm (NG) which has been used by our group in the context of various symbolization schemes. The NG approach transforms each MEG time series to more than two symbols by learning the reconstructed manifold of each time series with a small error. Using this algorithm we computed a complexity index (CI) based on the distribution of words up to a predetermined length. The relative performance of the two complexity indexes was assessed using a classification procedure based on k-NN and Support Vector Machines. Results revealed the capacity of CI to discriminate impaired from non-impaired readers with 80% accuracy. Corresponding performance of LZC values did not exceed 55%. These findings indicate that symbolization of MEG recordings with an appropriate neuroinformatic approach, such as the proposed CI metric, may be of value in understanding the neural dynamics of dyslexia

CK1δ restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1α/ARNT complex formation.

Proliferation of cells under hypoxia is facilitated by metabolic adaptation, mediated by the transcriptional activator Hypoxia Inducible Factor-1 (HIF-1). HIF-1α, the inducible subunit of HIF-1 is regulated by oxygen as well as by oxygen-independent mechanisms involving phosphorylation. We have previously shown that CK1δ phosphorylates HIF-1α in its N-terminus and reduces its affinity for its heterodimerization partner ARNT. To investigate the importance of this mechanism for cell proliferation under hypoxia, we visually monitored HIF-1α interactions within the cell nucleus using the in situ proximity ligation assay (PLA) and fluorescence recovery after photobleaching (FRAP). Both methods show that CK1δ-dependent modification of HIF-1α impairs the formation of a chromatin binding HIF-1 complex. This is confirmed by analyzing expression of lipin-1, a direct target of HIF-1 that mediates hypoxic neutral lipid accumulation. Inhibition of CK1δ increases lipid droplet formation and proliferation of both cancer and normal cells specifically under hypoxia and in an HIF-1α- and lipin-1-dependent manner. These data reveal a novel role for CK1δ in regulating lipid metabolism and, through it, cell adaptation to low oxygen conditions.This work was supported by the “ARISTEIA ΙΙ” Action of the “OPERATIONAL PROGRAMME EDUCATION AND LIFELONG LEARNING” and was co-funded by the European Social Fund (ESF) and National Resources. Partial support was provided by the Proof of Concept Studies for the ESFRI project Euro-BioImaging (Greek BioImaging Facility, PCS facility Nr. 9, Unit 2). N.-N.G., M.A.R. and Z.L. were supported by a grant from the European Research Council and S.S. was supported by a Medical Research Council Senior Fellowship (grant number G0701446).This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0898656815000637

Synthesis, Characterization, and Biological Studies of Organotin(IV) Derivatives with o- or p-hydroxybenzoic Acids

Organotin(IV) complexes with o- or p-hydroxybenzoic acids (o-H2BZA or p-H2BZA) of formulae [R2Sn(HL)2] (where H2L = o-H2BZA and R = Me- (1), n-Bu- (2)); [R3Sn(HL)] (where H2L = o-H2BZA and R = n-Bu- (3), Ph- (4) or H2L = p-H2BZA and R = n-Bu- (5), Ph- (6)) were synthesized by reacting a methanolic solution of di- and triorganotin(IV) compounds with an aqueous solution of the ligand (o-H2BZA or p-H2BZA) containing equimolar amounts of potassium hydroxide. The complexes were characterized by elemental analysis, FT-IR, Far-IR, TGA-DTA, FT-Raman, Mössbauer spectroscopy, 1H, 119Sn-NMR, UV/Vis spectroscopy, and Mass spectroscopy. The X-ray crystal structures of complexes 1 and 2 have also been determined. Finally, the influence of these complexes 1–6 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically studied and the results showed that triorganotin(IV) complex 6 has the lowest IC50 value. Also complexes 1–6 were studied for their in vitro cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, and the results showed that the complexes have high activity against these cell lines with triphenyltin((IV) complex 4 to be the most active one

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Collimation for the LHC high intensity beams

The unprecedented design intensities of the LHC require several important advances in beam collimation. With its more than 100 collimators, acting on various planes and beams, the LHC collimation system is the biggest and most performing such system ever designed and constructed. The solution for LHC collimation is explained, the technical components are introduced and the initial performance is presented. Residual beam leakage from the system is analysed. Measurements and simulations are presented which show that collimation efficiencies of better than 99.97 % have been measured with the 3.5 TeV proton beams of the LHC, in excellent agreement with expectations.peer-reviewe