Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.

Genes for autism spectrum disorders (ASDs) are also implicated in fragile X syndrome (FXS), intellectual disabilities (ID) or schizophrenia (SCZ), and converge on neuronal function and differentiation. The SH-SY5Y neuroblastoma cell line, the most widely used system to study neurodevelopment, is currently discussed for its applicability to model cortical development. We implemented an optimal neuronal differentiation protocol of this system and evaluated neurodevelopment at the transcriptomic level using the CoNTeXT framework, a machine-learning algorithm based on human post-mortem brain data estimating developmental stage and regional identity of transcriptomic signatures. Our improved model in contrast to currently used SH-SY5Y models does capture early neurodevelopmental processes with high fidelity. We applied regression modelling, dynamic time warping analysis, parallel independent component analysis and weighted gene co-expression network analysis to identify activated gene sets and networks. Finally, we tested and compared these sets for enrichment of risk genes for neuropsychiatric disorders. We confirm a significant overlap of genes implicated in ASD with FXS, ID and SCZ. However, counterintuitive to this observation, we report that risk genes affect pathways specific for each disorder during early neurodevelopment. Genes implicated in ASD, ID, FXS and SCZ were enriched among the positive regulators, but only ID-implicated genes were also negative regulators of neuronal differentiation. ASD and ID genes were involved in dendritic branching modules, but only ASD risk genes were implicated in histone modification or axonal guidance. Only ID genes were over-represented among cell cycle modules. We conclude that the underlying signatures are disorder-specific and that the shared genetic architecture results in overlaps across disorders such as ID in ASD. Thus, adding developmental network context to genetic analyses will aid differentiating the pathophysiology of neuropsychiatric disorders

Observation of the second harmonic in superconducting current-phase relation of Nb/Au/(001)YBa2Cu3Ox heterojunctions

The superconducting current-phase relation (CPR) of Nb/Au/(001)YBa2Cu3Ox heterojunctions prepared on epitaxial c-axis oriented YBa2Cu3Ox thin films has been measured in a single-junction interferometer. For the first time, the second harmonic of the CPR of such junctions has been observed. The appearance of the second harmonic and the relative sign of the first and second harmonics of the CPR can be explained assuming, that the macroscopic pairing symmetry of our YBa2Cu3Ox thin films is of the d+s typeComment: 11 pages, 4 figure

A parallel evolutionary algorithm for prioritized pairwise testing of software product lines

Lopez-Herrejon, R. Erick, Ferrer J., Chicano F., Haslinger E. Nicole, Egyed A., & Alba E. (2014). A parallel evolutionary algorithm for prioritized pairwise testing of software product lines. (Arnold, D. V., Ed.).Genetic and Evolutionary Computation Conference, GECCO '14, Vancouver, BC, Canada, July 12-16, 2014. 1255–1262.Software Product Lines (SPLs) are families of related software systems, which provide different feature combinations. Different SPL testing approaches have been proposed. However, despite the extensive and successful use of evolutionary computation techniques for software testing, their application to SPL testing remains largely unexplored. In this paper we present the Parallel Prioritized product line Genetic Solver (PPGS), a parallel genetic algorithm for the generation of prioritized pairwise testing suites for SPLs. We perform an extensive and comprehensive analysis of PPGS with 235 feature models from a wide range of number of features and products, using 3 different priority assignment schemes and 5 product prioritization selection strategies. We also compare PPGS with the greedy algorithm prioritized-ICPL. Our study reveals that overall PPGS obtains smaller covering arrays with an acceptable performance difference with prioritized-ICPL.Austrian Science Fund (FWF) project P25289-N15 and Lise Meitner Fellowship M1421-N15. Spanish Ministry of Economy and Competitiveness and FEDER under contract TIN2011-28194 and fellowship Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.BES-2012-055967. Project 8.06/5.47.4142 in collaboration with the VSB-Tech. Univ. of Ostrava and Universidad de Málaga, Andalucía Tech

Goodness-of-fit tests for neural population models: the multivariate time-rescaling theorem

Poster Presentation from Nineteenth Annual Computational Neuroscience Meeting: CNS*2010 San Antonio, TX, USA. 24-30 July 2010 Statistical models of neural activity are at the core of the field of modern computational neuroscience. The activity of single neurons has been modeled to successfully explain dependencies of neural dynamics to its own spiking history, to external stimuli or other covariates [1]. Recently, there has been a growing interest in modeling spiking activity of a population of simultaneously recorded neurons to study the effects of correlations and functional connectivity on neural information processing (existing models include generalized linear models [2,3] or maximum-entropy approaches [4]). For point-process-based models of single neurons, the time-rescaling theorem has proven to be a useful toolbox to assess goodness-of-fit. In its univariate form, the time-rescaling theorem states that if the conditional intensity function of a point process is known, then its inter-spike intervals can be transformed or “rescaled” so that they are independent and exponentially distributed [5]. However, the theorem in its original form lacks sensitivity to detect even strong dependencies between neurons. Here, we present how the theorem can be extended to be applied to neural population models and we provide a step-by-step procedure to perform the statistical tests. We then apply both the univariate and multivariate tests to simplified toy models, but also to more complicated many-neuron models and to neuronal populations recorded in V1 of awake monkey during natural scenes stimulation. We demonstrate that important features of the population activity can only be detected using the multivariate extension of the test. ..

Acoustic tests of Lorentz symmetry using quartz oscillators

We propose and demonstrate a test of Lorentz symmetry based on new, compact, and reliable quartz oscillator technology. Violations of Lorentz invariance in the matter and photon-sector of the standard model extension (SME) generate anisotropies in particles' inertial masses and the elastic constants, giving rise to measurable anisotopies in the resonance frequencies of acoustic modes in solids. A first realization of such a "phonon-sector" test of Lorentz symmetry using room-temperature SC-cut crystals provides a limit of $\tilde c_Q^{\rm n}=(-1.8 \pm 2.2)\times 10^{-14}$\,GeV on the most weakly constrained neutron-sector $c-$coefficient of the SME. Future experiments with cryogenic oscillators promise significant improvements in accuracy, opening up the potential for improved limits on Lorentz violation in the neutron, proton, electron and photon sector.Comment: 11 pages, 5 figures. Added reference

Concept of an ionizing time-domain matter-wave interferometer

We discuss the concept of an all-optical and ionizing matter-wave interferometer in the time domain. The proposed setup aims at testing the wave nature of highly massive clusters and molecules, and it will enable new precision experiments with a broad class of atoms, using the same laser system. The propagating particles are illuminated by three pulses of a standing ultraviolet laser beam, which detaches an electron via efficient single photon-absorption. Optical gratings may have periods as small as 80 nm, leading to wide diffraction angles for cold atoms and to compact setups even for very massive clusters. Accounting for the coherent and the incoherent parts of the particle-light interaction, we show that the combined effect of phase and amplitude modulation of the matter waves gives rise to a Talbot-Lau-like interference effect with a characteristic dependence on the pulse delay time.Comment: 25 pages, 5 figure

Colloquium: Quantum interference of clusters and molecules

We review recent progress and future prospects of matter wave interferometry with complex organic molecules and inorganic clusters. Three variants of a near-field interference effect, based on diffraction by material nanostructures, at optical phase gratings, and at ionizing laser fields are considered. We discuss the theoretical concepts underlying these experiments and the experimental challenges. This includes optimizing interferometer designs as well as understanding the role of decoherence. The high sensitivity of matter wave interference experiments to external perturbations is demonstrated to be useful for accurately measuring internal properties of delocalized nanoparticles. We conclude by investigating the prospects for probing the quantum superposition principle in the limit of high particle mass and complexity.Comment: 19 pages, 13 figures; v2: corresponds to published versio