Mining for viral fragments in methylation enriched sequencing data

Most next generation sequencing experiments generate more data than is required for the experimental set up. For example, methyl-CpG binding domain (MBD) affinity purification based sequencing is often used for DNA-methylation profiling, but up to 30% of the sequenced fragments cannot be mapped uniquely to the reference genome. Here we present and evaluate a methodology for the identification of viruses in these otherwise unused paired-end MBD-seq data. Viral detection is accomplished by mapping non-reference alignable reads to a comprehensive set of viral genomes. As viruses play an important role in epigenetics and cancer development, 92 (pre)malignant and benign samples, originating from two different collections of cervical samples and related cell lines, were used in this study. These samples include primary carcinomas (n=22), low- & high-grade cervical intrapeithelial neoplasia (CIN1 & CIN2/3 - n=2/n=30) and normal tissue (n=20), as well as control samples (n=17). Viruses that were detected include phages, adenoviruses, herpesviridae and HPV. HPV, which causes virtually all cervical cancers, was identified in 95% of the carcinomas, 100% of the CIN2/3 samples, both CIN1 samples and in 55% of the normal samples. Comparing the amount of mapped fragments on HPV for each HPV-infected sample yielded a significant difference between normal samples and carcinomas or CIN2/3 samples (adjusted p-values resp. < 10^-5, < 10^-5), reflecting different viral loads and/or methylation degrees in non-normal samples. Fragments originating from different HPV types could be distinguished and were independently validated by PCR-based assays with a specificity of 98% and a sensitivitity of 66%. In conclusion, although limited by the a priori knowledge of viral reference genome sequences, the proposed methodology can provide a first but substantial insight into the presence, concentration and types of methylated viral sequences in MBD-seq data without additional costs

False-negative upper extremity ultrasound in the initial evaluation of patients with suspected subclavian vein thrombosis due to thoracic outlet syndrome (Paget-Schroetter syndrome)

OBJECTIVE: To assess the utilization and consequences of upper extremity Duplex ultrasound in the initial diagnostic evaluation of patients with suspected subclavian vein (SCV) thrombosis and venous thoracic outlet syndrome (VTOS). METHODS: A retrospective single-center review was conducted for patients that underwent primary surgical treatment for VTOS between 2008 and 2017, in whom an upper extremity ultrasound had been performed as the initial diagnostic test (n = 214). Clinical and treatment characteristics were compared between patients with positive and false-negative ultrasound studies. RESULTS: There were 122 men (57%) and 92 women (43%) that had presented with spontaneous idiopathic arm swelling, including 28 (13%) with proven pulmonary embolism, at a mean age of 30.7 ± 0.8 years (range 14-69). Upper extremity ultrasound had been performed 23.8 ± 12.2 days after the onset of symptoms, with confirmation of axillary-SCV thrombosis in 169 patients (79%) and negative results in 45 (21%). Of the false-negative ultrasound study reports, only 8 (18%) acknowledged limitations in visualizing the central SCV. Definitive diagnostic imaging (DDI) had been obtained by upper extremity venography in 175 (82%), computed tomography angiography in 24 (11%), and magnetic resonance angiography in 15 (7%), with 142 (66%) undergoing catheter-directed axillary-SCV thrombolysis. The mean interval between initial ultrasound and DDI was 48.9 ± 14.2 days with no significant difference between groups, but patients with a positive ultrasound were more likely to have DDI within 48 hours than those with a false-negative ultrasound (44% vs 24%; P = .02). At the time of surgical treatment, the SCV was widely patent following paraclavicular decompression and external venolysis alone in 74 patients (35%). Patch angioplasty was performed for focal SCV stenosis in 76 (36%) and bypass graft reconstruction for long-segment axillary-SCV occlusion in 63 (29%). Patients with false-negative initial ultrasound studies were significantly more likely to require SCV bypass reconstruction than those with a positive ultrasound (44% vs 25%; P = .02). CONCLUSIONS: Duplex ultrasound has significant limitations in the initial evaluation of patients with suspected SCV thrombosis, with false-negative results in 21% of patients with proven VTOS. This is rarely acknowledged in ultrasound reports, but false-negative ultrasound studies have the potential to delay definitive imaging, thrombolysis, and further treatment for VTOS. Initial false-negative ultrasound results are associated with progressive thrombus extension and a more frequent need for SCV bypass reconstruction at the time of surgical treatment

Higher-order spin effects in the amplitude and phase of gravitational waveforms emitted by inspiraling compact binaries: Ready-to-use gravitational waveforms

We provide ready-to-use time-domain gravitational waveforms for spinning compact binaries with precession effects through 1.5PN order in amplitude and compute their mode decomposition using spin-weighted -2 spherical harmonics. In the presence of precession, the gravitational-wave modes (l,m) contain harmonics originating from combinations of the orbital frequency and precession frequencies. We find that the gravitational radiation from binary systems with large mass asymmetry and large inclination angle can be distributed among several modes. For example, during the last stages of inspiral, for some maximally spinning configurations, the amplitude of the (2,0) and (2,1) modes can be comparable to the amplitude of the (2,2) mode. If the mass ratio is not too extreme, the l=3 and l=4 modes are generally one or two orders of magnitude smaller than the l = 2 modes. Restricting ourselves to spinning, non-precessing compact binaries, we apply the stationary-phase approximation and derive the frequency-domain gravitational waveforms including spin-orbit and spin(1)- spin(2) effects through 1.5PN and 2PN order respectively in amplitude, and 2.5PN order in phase. Since spin effects in the amplitude through 2PN order affect only the first and second harmonics of the orbital phase, they do not extend the mass reach of gravitational-wave detectors. However, they can interfere with other harmonics and lower or raise the signal-to-noise ratio depending on the spin orientation. These ready-to-use waveforms could be employed in the data-analysis of the spinning, inspiraling binaries as well as in comparison studies at the interface between analytical and numerical relativity.Comment: 43 pages, 10 Postscript figures. submitted to Physical Review D. Includes corrections due to errat

Experimental Implementation of a Concatenated Quantum Error-Correcting Code

Concatenated coding provides a general strategy to achieve the desired level of noise protection in quantum information storage and transmission. We report the implementation of a concatenated quantum error-correcting code able to correct against phase errors with a strong correlated component. The experiment was performed using liquid-state nuclear magnetic resonance techniques on a four spin subsystem of labeled crotonic acid. Our results show that concatenation between active and passive quantum error-correcting codes offers a practical tool to handle realistic noise contributed by both independent and correlated errors.Comment: 4 pages, 2 encapsulated eps figures. REVTeX4 styl

Superconducting Diamond on Silicon Nitride for Device Applications

Chemical vapour deposition (CVD) grown nanocrystalline diamond is an attractive material for the fabrication of devices. For some device architectures, optimisation of its growth on silicon nitride is essential. Here, the effects of three pre-growth surface treatments, often employed as cleaning methods of silicon nitride, were investigated. Such treatments provide control over the surface charge of the substrate through modification of the surface functionality, allowing for the optimisation of electrostatic diamond seeding densities. Zeta potential measurements and X-ray photoelectron spectroscopy (XPS) were used to analyse the silicon nitride surface following each treatment. Exposing silicon nitride to an oxygen plasma offered optimal surface conditions for the electrostatic self-assembly of a hydrogen-terminated diamond nanoparticle monolayer. The subsequent growth of boron-doped nanocrystalline diamond thin films on modified silicon nitride substrates under CVD conditions produced coalesced films for oxygen plasma and solvent treatments, whilst pin-holing of the diamond film was observed following RCA-1 treatment. The sharpest superconducting transition was observed for diamond grown on oxygen plasma treated silicon nitride, demonstrating it to be of the least structural disorder. Modifications to the substrate surface optimise the seeding and growth processes for the fabrication of diamond on silicon nitride devices

Adjustable microchip ring trap for cold atoms and molecules

We describe the design and function of a circular magnetic waveguide produced from wires on a microchip for atom interferometry using deBroglie waves. The guide is a two-dimensional magnetic minimum for trapping weak-field seeking states of atoms or molecules with a magnetic dipole moment. The design consists of seven circular wires sharing a common radius. We describe the design, the time-dependent currents of the wires and show that it is possible to form a circular waveguide with adjustable height and gradient while minimizing perturbation resulting from leads or wire crossings. This maximal area geometry is suited for rotation sensing with atom interferometry via the Sagnac effect using either cold atoms, molecules and Bose-condensed systems

Magellan/M2FS Spectroscopy of Galaxy Clusters: Stellar Population Model and Application to Abell 267

We report the results of a pilot program to use the Magellan/M2FS spectrograph to survey the galactic populations and internal kinematics of galaxy clusters. For this initial study, we present spectroscopic measurements for $223$ quiescent galaxies observed along the line of sight to the galaxy cluster Abell 267 ($z\sim0.23$). We develop a Bayesian method for modeling the integrated light from each galaxy as a simple stellar population, with free parameters that specify redshift ($v_\mathrm{los}/c$) and characteristic age, metallicity ($\mathrm{[Fe/H]}$), alpha-abundance ($[\alpha/\mathrm{Fe}]$), and internal velocity dispersion ($\sigma_\mathrm{int}$) for individual galaxies. Parameter estimates derived from our 1.5-hour observation of A267 have median random errors of $\sigma_{v_\mathrm{los}}=20\ \mathrm{km\ s^{-1}}$, $\sigma_{\mathrm{Age}}=1.2\ \mathrm{Gyr}$, $\sigma_{\mathrm{[Fe/H]}}=0.11\ \mathrm{dex}$,$\sigma_{[\alpha/\mathrm{Fe}]}=0.07\ \mathrm{dex}$, and$\sigma_{\sigma_\mathrm{int}}=20\ \mathrm{km\ s^{-1}}$. In a companion paper, we use these results to model the structure and internal kinematics of A267.Comment: 16 pages, 11 figures, accepted for publication in The Astronomical Journa