SInC: An accurate and fast error-model based simulator for SNPs, Indels and CNVs coupled with a read generator for short-read sequence data

We report SInC (SNV, Indel and CNV) simulator and read generator, an open-source tool capable of simulating biological variants taking into account a platform-specific error model. SInC is capable of simulating and generating single- and paired-end reads with user-defined insert size with high efficiency compared to the other existing tools. SInC, due to its multi-threaded capability during read generation, has a low time footprint. SInC is currently optimised to work in limited infrastructure setup and can efficiently exploit the commonly used quad-core desktop architecture to simulate short sequence reads with deep coverage for large genomes. Sinc can be downloaded from https://sourceforge.net/projects/sincsimulator/

Rattus Model Utilizing Selective Pulmonary Ischemia Induces Bronchiolitis Obliterans Organizing Pneumonia

Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. Studies were performed 7 days later. Relative pulmonary and systemic flow to each lung was measured by injection of technetium Tc 99m macroaggregated albumin. Histological sections were examined for structure and necrosis and scored for BOOP. Apoptosis was detected by immunohistochemistry with an antibody against cleaved caspase 3. Pulmonary artery blood flow to left lungs was less than 0.1% of the cardiac output, and bronchial artery circulation was ~2% of aortic artery flow. Histological sections from ischemic left lungs consistently showed Masson bodies, inflammation, and young fibroblasts filling the distal airways and alveoli, consistent with BOOP. In quantitative evaluation of BOOP using epithelial changes, inflammation and fibrosis were higher in ischemic left lungs than right or sham-operated left lungs. Apoptosis was increased in areas exhibiting histological BOOP, but there was no histological evidence of necrosis. Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP

Predicting molecular vibronic spectra using time-domain analog quantum simulation

Spectroscopy is one of the most accurate probes of the molecular world. However, predicting molecular spectra accurately is computationally difficult because of the presence of entanglement between electronic and nuclear degrees of freedom. Although quantum computers promise to reduce this computational cost, existing quantum approaches rely on combining signals from individual eigenstates, an approach that is difficult to scale because the number of eigenstates grows exponentially with molecule size. Here, we introduce a method for scalable analog quantum simulation of molecular spectroscopy, by performing simulations in the time domain. Our approach can treat more complicated molecular models than previous ones, requires fewer approximations, and can be extended to open quantum systems with minimal overhead. We present a direct mapping of the underlying problem of time-domain simulation of molecular spectra to the degrees of freedom and control fields available in a trapped-ion quantum simulator. We experimentally demonstrate our algorithm on a trapped-ion device, exploiting both intrinsic electronic and motional degrees of freedom, showing excellent quantitative agreement for a single-mode vibronic photoelectron spectrum of SO$_2$.Comment: 13 pages, 8 figure

Electronic Devices Based on Purified Carbon Nanotubes Grown By High Pressure Decomposition of Carbon Monoxide

The excellent properties of transistors, wires, and sensors made from single-walled carbon nanotubes (SWNTs) make them promising candidates for use in advanced nanoelectronic systems. Gas-phase growth procedures such as the high pressure decomposition of carbon monoxide (HiPCO) method yield large quantities of small diameter semiconducting SWNTs, which are ideal for use in nanoelectronic circuits. As-grown HiPCO material, however, commonly contains a large fraction of carbonaceous impurities that degrade properties of SWNT devices. Here we demonstrate a purification, deposition, and fabrication process that yields devices consisting of metallic and semiconducting nanotubes with electronic characteristics vastly superior to those of circuits made from raw HiPCO. Source-drain current measurements on the circuits as a function of temperature and backgate voltage are used to quantify the energy gap of semiconducting nanotubes in a field effect transistor geometry. This work demonstrates significant progress towards the goal of producing complex integrated circuits from bulk-grown SWNT material.Comment: 6 pages, 4 figures, to appear in Nature Material

Production of Magnetic Arsenic–Phosphorus Alloy Nanoribbons with Small Band Gaps and High Hole Conductivities

Quasi-1D nanoribbons provide a unique route to diversifying the properties of their parent 2D nanomaterial, introducing lateral quantum confinement and an abundance of edge sites. Here, a new family of nanomaterials is opened with the creation of arsenic–phosphorus alloy nanoribbons (AsPNRs). By ionically etching the layered crystal black arsenic–phosphorus using lithium electride followed by dissolution in amidic solvents, solutions of AsPNRs are formed. The ribbons are typically few-layered, several micrometers long with widths tens of nanometers across, and both highly flexible and crystalline. The AsPNRs are highly electrically conducting above 130 K due to their small band gap (ca. 0.035 eV), paramagnetic in nature, and have high hole mobilities, as measured with the first generation of AsP devices, directly highlighting their properties and utility in electronic devices such as near-infrared detectors, quantum computing, and charge carrier layers in solar cells

Room Temperature Optically and Magnetically Active Edges in Phosphorene Nanoribbons

Nanoribbons - nanometer wide strips of a two-dimensional material - are a unique system in condensed matter physics. They combine the exotic electronic structures of low-dimensional materials with an enhanced number of exposed edges, where phenomena including ultralong spin coherence times, quantum confinement and topologically protected states can emerge. An exciting prospect for this new material concept is the potential for both a tunable semiconducting electronic structure and magnetism along the nanoribbon edge. This combination of magnetism and semiconducting properties is the first step in unlocking spin-based electronics such as non-volatile transistors, a route to low-energy computing, and has thus far typically only been observed in doped semiconductor systems and/or at low temperatures. Here, we report the magnetic and semiconducting properties of phosphorene nanoribbons (PNRs). Static (SQUID) and dynamic (EPR) magnetization probes demonstrate that at room temperature, films of PNRs exhibit macroscopic magnetic properties, arising from their edge, with internal fields of ~ 250 to 800 mT. In solution, a giant magnetic anisotropy enables the alignment of PNRs at modest sub-1T fields. By leveraging this alignment effect, we discover that upon photoexcitation, energy is rapidly funneled to a dark-exciton state that is localized to the magnetic edge and coupled to a symmetry-forbidden edge phonon mode. Our results establish PNRs as a unique candidate system for studying the interplay of magnetism and semiconducting ground states at room temperature and provide a stepping-stone towards using low-dimensional nanomaterials in quantum electronics.Comment: 18 pages, 4 figure

Immediate myeloid depot for SARS-CoV-2 in the human lung

In the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, epithelial populations in the distal lung expressing Angiotensin-converting enzyme 2 (ACE2) are infrequent, and therefore, the model of viral expansion and immune cell engagement remains incompletely understood. Using human lungs to investigate early host-viral pathogenesis, we found that SARS-CoV-2 had a rapid and specific tropism for myeloid populations. Human alveolar macrophages (AMs) reliably expressed ACE2 allowing both spike-ACE2-dependent viral entry and infection. In contrast to Influenza A virus, SARS-CoV-2 infection of AMs was productive, amplifying viral titers. While AMs generated new viruses, the interferon responses to SARS-CoV-2 were muted, hiding the viral dissemination from specific antiviral immune responses. The reliable and veiled viral depot in myeloid cells in the very early phases of SARS-CoV-2 infection of human lungs enables viral expansion in the distal lung and potentially licenses subsequent immune pathologies

A Pan-cancer analysis reveals high-frequency genetic alterations in mediators of signaling by the tgf-β superfamily

We present an integromic analysis of gene alterations that modulate transforming growth factor β (TGF-β)-Smad-mediated signaling in 9,125 tumor samples across 33 cancer types in The Cancer Genome Atlas (TCGA). Focusing on genes that encode mediators and regulators of TGF-β signaling, we found at least one genomic alteration (mutation, homozygous deletion, or amplification) in 39% of samples, with highest frequencies in gastrointestinal cancers. We identified mutation hotspots in genes that encode TGF-β ligands (BMP5), receptors (TGFBR2, AVCR2A, and BMPR2), and Smads (SMAD2 and SMAD4). Alterations in the TGF-β superfamily correlated positively with expression of metastasis-associated genes and with decreased survival. Correlation analyses showed the contributions of mutation, amplification, deletion, DNA methylation, and miRNA expression to transcriptional activity of TGF-β signaling in each cancer type. This study provides a broad molecular perspective relevant for future functional and therapeutic studies of the diverse cancer pathways mediated by the TGF-β superfamily

Microcavity-like exciton-polaritons can be the primary photoexcitation in bare organic semiconductors.

Strong-coupling between excitons and confined photonic modes can lead to the formation of new quasi-particles termed exciton-polaritons which can display a range of interesting properties such as super-fluidity, ultrafast transport and Bose-Einstein condensation. Strong-coupling typically occurs when an excitonic material is confided in a dielectric or plasmonic microcavity. Here, we show polaritons can form at room temperature in a range of chemically diverse, organic semiconductor thin films, despite the absence of an external cavity. We find evidence of strong light-matter coupling via angle-dependent peak splittings in the reflectivity spectra of the materials and emission from collective polariton states. We additionally show exciton-polaritons are the primary photoexcitation in these organic materials by directly imaging their ultrafast (5 × 106 m s-1), ultralong (~270 nm) transport. These results open-up new fundamental physics and could enable a new generation of organic optoelectronic and light harvesting devices based on cavity-free exciton-polaritons.EPSRC (EP/R025517/1), EPSRC (EP/M025330/1), ERC Horizon 2020 (grant agreements No 670405 and No 758826), ERC (ERC-2014-STG H2020 639088), Netherlands Organisation for Scientific Research, Swedish Research Council (VR, 2014-06948), Knut and Alice Wallenberg Foundation 3DEM-NATUR (no. 2012.0112), Royal Commission for the Exhibition of 1851, CNRS (France), US Department of Energy, Office of Science, Basic Energy Sciences, CPIMS Program, Early Career Research Program (DE-SC0019188)