Bayesian optimization of the PC algorithm for learning Gaussian Bayesian networks

The PC algorithm is a popular method for learning the structure of Gaussian Bayesian networks. It carries out statistical tests to determine absent edges in the network. It is hence governed by two parameters: (i) The type of test, and (ii) its significance level. These parameters are usually set to values recommended by an expert. Nevertheless, such an approach can suffer from human bias, leading to suboptimal reconstruction results. In this paper we consider a more principled approach for choosing these parameters in an automatic way. For this we optimize a reconstruction score evaluated on a set of different Gaussian Bayesian networks. This objective is expensive to evaluate and lacks a closed-form expression, which means that Bayesian optimization (BO) is a natural choice. BO methods use a model to guide the search and are hence able to exploit smoothness properties of the objective surface. We show that the parameters found by a BO method outperform those found by a random search strategy and the expert recommendation. Importantly, we have found that an often overlooked statistical test provides the best over-all reconstruction results

Canonical, squeezed and fermionic coherent states in a right quaternionic Hilbert space with a left multiplication on it

Using a left multiplication defined on a right quaternionic Hilbert space, we shall demonstrate that various classes of coherent states such as the canonical coherent states, pure squeezed states, fermionic coherent states can be defined with all the desired properties on a right quaternionic Hilbert space. Further, we shall also demonstrate squeezed states can be defined on the same Hilbert space, but the noncommutativity of quaternions prevents us in getting the desired results.Comment: Conference paper. arXiv admin note: text overlap with arXiv:1704.02946; substantial text overlap with arXiv:1706.0068

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Reduced engagement with social stimuli in 6-month-old infants with later Autism Spectrum Disorder: a longitudinal prospective study of infants at high familial risk

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of the population, and close to 20% of prospectively studied infants with an older sibling with ASD. Although significant progress has been made in characterizing the emergence of behavioral symptoms of ASD, far less is known about the underlying disruptions to early learning. Recent models suggest that core aspects of the causal path to ASD may only be apparent in early infancy. Here, we investigated social attention in 6- and 12-month-old infants who did and did not meet criteria for ASD at 24 months using both cognitive and electrophysiological methods. We hypothesized that a reduction in attention engagement to faces would be associated with later ASD. Methods: In a prospective longitudinal design, we used measures of both visual attention (habituation) and brain function (event-related potentials to faces and objects) at 6 and 12 months, and investigated the relationship to ASD outcome at 24 months. Results: High-risk infants who met criteria for ASD at 24 months showed shorter epochs of visual attention, faster but less prolonged neural activation to faces, and delayed sensitization responses (increases in looking) to faces at 6 months; these differences were less apparent at 12 months. These findings are consistent with disrupted engagement of sustained attention to social stimuli. Conclusions: These findings suggest that there may be fundamental early disruptions to attention engagement that may have cascading consequences for later social functioning

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Expansion of the Multi-Link Frontier™ Coronary Bifurcation Stent: Micro-Computed Tomographic Assessment in Human Autopsy and Porcine Heart Samples

BACKGROUND: Treatment of coronary bifurcation lesions remains challenging, beyond the introduction of drug eluting stents. Dedicated stent systems are available to improve the technical approach to the treatment of these lesions. However dedicated stent systems have so far not reduced the incidence of stent restenosis. The aim of this study was to assess the expansion of the Multi-Link (ML) Frontier™ stent in human and porcine coronary arteries to provide the cardiologist with useful in-vitro information for stent implantation and selection. METHODOLOGY/PRINCIPAL FINDINGS: Nine ML Frontier™ stents were implanted in seven human autopsy heart samples with known coronary artery disease and five ML Frontier™ stents were implanted in five porcine hearts. Proximal, distal and side branch diameters (PD, DD, SBD, respectively), corresponding opening areas (PA, DA, SBA) and the mean stent length (L) were assessed by micro-computed tomography (micro-CT). PD and PA were significantly smaller in human autopsy heart samples than in porcine heart samples (3.54±0.47 mm vs. 4.04±0.22 mm, p = 0.048; 10.00±2.42 mm(2) vs. 12.84±1.38 mm(2), p = 0.034, respectively) and than those given by the manufacturer (3.54±0.47 mm vs. 4.03 mm, p = 0.014). L was smaller in human autopsy heart samples than in porcine heart samples, although data did not reach significance (16.66±1.30 mm vs. 17.30±0.51 mm, p = 0.32), and significantly smaller than that given by the manufacturer (16.66±1.30 mm vs. 18 mm, p = 0.015). CONCLUSIONS/SIGNIFICANCE: Micro-CT is a feasible tool for exact surveying of dedicated stent systems and could make a contribution to the development of these devices. The proximal diameter and proximal area of the stent system were considerably smaller in human autopsy heart samples than in porcine heart samples and than those given by the manufacturer. Special consideration should be given to the stent deployment procedure (and to the follow-up) of dedicated stent systems, considering final intravascular ultrasound or optical coherence tomography to visualize (and if necessary optimize) stent expansion

Global Array-Based Transcriptomics from Minimal Input RNA Utilising an Optimal RNA Isolation Process Combined with SPIA cDNA Probes

Technical advances in the collection of clinical material, such as laser capture microdissection and cell sorting, provide the advantage of yielding more refined and homogenous populations of cells. However, these attractive advantages are counter balanced by the significant difficultly in obtaining adequate nucleic acid yields to allow transcriptomic analyses. Established technologies are available to carry out global transcriptomics using nanograms of input RNA, however, many clinical samples of low cell content would be expected to yield RNA within the picogram range. To fully exploit these clinical samples the challenge of isolating adequate RNA yield directly and generating sufficient microarray probes for global transcriptional profiling from this low level RNA input has been addressed in the current report. We have established an optimised RNA isolation workflow specifically designed to yield maximal RNA from minimal cell numbers. This procedure obtained RNA yield sufficient for carrying out global transcriptional profiling from vascular endothelial cell biopsies, clinical material not previously amenable to global transcriptomic approaches. In addition, by assessing the performance of two linear isothermal probe generation methods at decreasing input levels of good quality RNA we demonstrated robust detection of a class of low abundance transcripts (GPCRs) at input levels within the picogram range, a lower level of RNA input (50 pg) than previously reported for global transcriptional profiling and report the ability to interrogate the transcriptome from only 10 pg of input RNA. By exploiting an optimal RNA isolation workflow specifically for samples of low cell content, and linear isothermal RNA amplification methods for low level RNA input we were able to perform global transcriptomics on valuable and potentially informative clinically derived vascular endothelial biopsies here for the first time. These workflows provide the ability to robustly exploit ever more common clinical samples yielding extremely low cell numbers and RNA yields for global transcriptomics

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT