Observational Signatures of Carbon-Oxygen White Dwarf Merger Remnants

Many double white dwarf (WD) mergers likely do not lead to a prompt thermonuclear explosion. We investigate the prospects for observationally detecting the surviving remnants of such mergers, focusing on the case of mergers of Carbon-Oxygen WDs. For $\sim 10^4$ yr, the merger remnant is observationally similar to an extreme AGB star evolving to become a massive WD. Identifying merger remnants is thus easiest in galaxies with high stellar masses (high WD merger rate) and low star formation rates (low birth rate of $\sim 6-10 \,{\rm M_{\odot}}$ stars). Photometrically identifying merger remnants is challenging even in these cases because the merger remnants appear similar to He stars and post-outburst classical novae. We propose that the most promising technique for discovering WD merger remnants is through their unusual surrounding photoionized nebulae. We use CLOUDY photoionization calculations to investigate their unique spectral features. Merger remnants should produce weak hydrogen lines and strong carbon and oxygen recombination and fine-structure lines in the UV, optical and IR. With integral field spectrographs, we predict that hundreds of candidates are detectable in M87 and other nearby massive galaxies. Dust somewhat reduces the optical line emission for nebula radii $\lesssim 10^{17}$ cm, but the sources spend most of their time with larger radii when dust is less important. Our models roughly reproduce the WISE nebula surrounding the Galactic WD merger candidate IRAS 00500+6713; we predict detectable [Ne VI] and [Mg VII] lines with JWST but that the mid-IR WISE emission is dominated by dust not fine-structure lines.Comment: 12 pages, 8 figures, 2 tables, submitted to MNRA

A Negative Long Lag from the Optical to the UV Continuum in Fairall 9

We report the detection of a long-timescale negative lag, where the blue bands lag the red bands, in the nearby Seyfert 1 galaxy Fairall 9. Active Galactic Nuclei (AGN) light curves show variability over a wide range of timescales. By measuring time lags between different wavelengths, the otherwise inaccessible structure and kinematics of the accretion disk can be studied. One common approach, reverberation mapping, quantifies the continuum and line lags moving outwards through the disk at the light-travel time, revealing the size and temperature profile of the disk. Inspired by numerical simulations, we expect longer lags to exist in AGN light curves that travel inward on longer timescales, tracing the accretion process itself. By analyzing AGN light curves in both temporal and frequency space, we report the detection of long-timescale lags ($\sim -70$ days) in Fairall 9 which propagate in the opposite direction to the reverberation lag. The short continuum lag ($<10$ days) is also detected and is consistent with reverberation lags reported in the literature. When fitting the longer lag as a function of frequency with a model motivated by the thin disk model, we find that the disk scale height likely increases outward in the disk. This detection raises the exciting prospect of mapping accretion disk structures across a wide range of AGN parameters.Comment: 24 pages, 14 figures, submitted to Ap

Negative Lags on the Viscous Timescale in Quasar Photometry and Prospects for Detecting More with LSST

The variability of quasar light curves can be used to study the structure of quasar accretion disks. For example, continuum reverberation mapping uses delays between variability in short and long wavelength bands ("short" lags) to measure the radial extent and temperature profile of the disk. Recently, a potential reverse lag, where variations in shorter wavelength bands lag the longer wavelength bands at the much longer viscous timescale, was detected for Fairall 9. Inspired by this detection, we derive a timescale for these "long" negative lags from fluctuation propagation models and recent simulations. We use this timescale to forecast our ability to detect long lags using the Vera Rubin Legacy Survey of Space and Time (LSST). After exploring several methods, including the interpolated cross-correlation function, a Von-Neumann estimator, javelin, and a maximum-likelihood Fourier method, we find that our two main methods, javelin and the maximum-likelihood method, can together detect long lags of up to several hundred days in mock LSST light curves. Our methods work best on proposed LSST cadences with long season lengths, but can also work for the current baseline LSST cadence, especially if we add observations from other optical telescopes during seasonal gaps. We find that LSST has the potential to detect dozens to hundreds of additional long lags. Detecting these long lags can teach us about the vertical structure of quasar disks and how it scales with different quasar properties.Comment: 40 pages, 36 figures, submitted to Ap

Tailoring the atomic structure of graphene nanoribbons by STM lithography

The practical realization of nano-scale electronics faces two major challenges: the precise engineering of the building blocks and their assembly into functional circuits. In spite of the exceptional electronic properties of carbon nanotubes only basic demonstration-devices have been realized by time-consuming processes. This is mainly due to the lack of selective growth and reliable assembly processes for nanotubes. However, graphene offers an attractive alternative. Here we report the patterning of graphene nanoribbons (GNRs) and bent junctions with nanometer precision, well-defined widths and predetermined crystallographic orientations allowing us to fully engineer their electronic structure using scanning tunneling microscope (STM) lithography. The atomic structure and electronic properties of the ribbons have been investigated by STM and tunneling spectroscopy measurements. Opening of confinement gaps up to 0.5 eV, allowing room temperature operation of GNR-based devices, is reported. This method avoids the difficulties of assembling nano-scale components and allows the realization of complete integrated circuits, operating as room temperature ballistic electronic devices.Comment: 8 pages text, 5 figures, Nature Nanotechnology, in pres

Development of pig welfare assessment protocol integrating animal-, environment-, and management-based measures

Abstract Background Due to increased interest in animal welfare, there is now a need for a comprehensive assessment protocol to be used in intensive pig farming systems. There are two current welfare assessment protocols for pigs: Welfare Quality&#174; Assessment Protocols (applicable in the Europe Union), that mostly focuses on animal-based measures, and the Swine Welfare Assurance Program (applicable in the United States), that mostly focuses on management- and environment-based measures. In certain cases, however, animal-based measures might not be adequate for properly assessing pig welfare status. Similarly, welfare assessment that relies only on environment- and management-based measures might not represent the actual welfare status of pigs. Therefore, the objective of this paper was to develop a new welfare protocol by integrating animal-, environment-, and management-based measures. The background for selection of certain welfare criteria and modification of the scoring systems from existing welfare assessment protocols are described. Methods The developed pig welfare assessment protocol consists of 17 criteria that are related to four main principles of welfare (good feeding, good housing, good health, and appropriate behavior). Good feeding, good housing, and good health were assessed using a 3-point scale: 0 (good welfare), 1 (moderate welfare), and 2 (poor welfare). In certain cases, only a 2-point scale was used: 0 (certain condition is present) or 2 (certain condition is absent). Appropriate behavior was assessed by scan sampling of positive and negative social behaviors based on qualitative behavior assessment and human-animal relationship tests. Results Modification of the body condition score into a 3-point scale revealed pigs with a moderate body condition (score 1). Moreover, additional criteria such as feed quality confirmed that farms had moderate (score 1) or poor feed quality (score 2), especially those farms located in a high relative humidity region. Conclusions The developed protocol can be utilized to assess welfare status in an intensive pig farming system. Although further improvements are still needed, this study is a first step in developing a pig welfare assessment protocol that combines animal-, environment-, and management-based measures

Hypoxia leads to significant changes in alternative splicing and elevated expression of CLK splice factor kinases in PC3 prostate cancer cells

© 2018 The Author(s). Background: Mounting evidence suggests that one of the ways that cells adapt to hypoxia is through alternative splicing. The aim of this study was firstly to examine the effect of hypoxia on the alternative splicing of cancer associated genes using the prostate cancer cell line PC3 as a model. Secondly, the effect of hypoxia on the expression of several regulators of splicing was examined. Methods: PC3 cells were grown in 1% oxygen in a hypoxic chamber for 48 h, RNA extracted and sent for high throughput PCR analysis at the RNomics platform at the University of Sherbrooke, Canada. Genes whose exon inclusion rate PSI (ψ) changed significantly were identified, and their altered exon inclusion rates verified by RT-PCR in three cell lines. The expression of splice factors and splice factor kinases in response to hypoxia was examined by qPCR and western blotting. The splice factor kinase CLK1 was inhibited with the benzothiazole TG003. Results: In PC3 cells the exon inclusion rate PSI (ψ) was seen to change by >25% in 12 cancer-associated genes; MBP, APAF1, PUF60, SYNE2, CDC42BPA, FGFR10P, BTN2A2, UTRN, RAP1GDS1, PTPN13, TTC23 and CASP9 (caspase 9). The expression of the splice factors SRSF1, SRSF2, SRSF3, SAM68, HuR, hnRNPA1, and of the splice factor kinases SRPK1 and CLK1 increased significantly in hypoxia. We also observed that the splice factor kinase CLK3, but not CLK2 and CLK4, was also induced in hypoxic DU145 prostate, HT29 colon and MCF7 breast cancer cell lines. Lastly, we show that the inhibition of CLK1 in PC3 cells with the benzothiazole TG003 increased expression of the anti-apoptotic isoform caspase 9b. Conclusions: Significant changes in alternative splicing of cancer associated genes occur in prostate cancer cells in hypoxic conditions. The expression of several splice factors and splice factor kinases increases during hypoxia, in particular the Cdc-like splice factor kinases CLK1 and CLK3. We suggest that in hypoxia the elevated expression of these regulators of splicing helps cells adapt through alternative splicing of key cancer-associated genes. We suggest that the CLK splice factor kinases could be targeted in cancers in which hypoxia contributes to resistance to therapy

Modulation of transforming growth factor beta signalling pathway genes by transforming growth factor beta in human osteoarthritic chondrocytes: involvement of Sp1 in both early and late response cells to transforming growth factor beta

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Biophysical Property and Broad Anti-HIV Activity of Albuvirtide, a 3-Maleimimidopropionic Acid-Modified Peptide Fusion Inhibitor

Albuvirtide (ABT) is a 3-maleimimidopropionic acid (MPA)-modified peptide HIV fusion inhibitor that can irreversibly conjugate to serum albumin. Previous studies demonstrated its in vivo long half-life and potent anti-HIV activity. Here, we focused to characterize its biophysical properties and evaluate its antiviral spectrum. In contrast to T20 (Enfuvirtide, Fuzeon), ABT was able to form a stable α-helical conformation with the target sequence and block the fusion-active six-helix bundle (6-HB) formation in a dominant-negative manner. It efficiently inhibited HIV-1 Env-mediated cell membrane fusion and virus entry. A large panel of 42 HIV-1 pseudoviruses with different genotypes were constructed and used for the antiviral evaluation. The results showed that ABT had potent inhibitory activity against the subtypes A, B and C that predominate the worldwide AIDS epidemics, and subtype B′, CRF07_BC and CRF01_AE recombinants that are currently circulating in China. Furthermore, ABT was also highly effective against HIV-1 variants resistant to T20. Taken together, our data indicate that the chemically modified peptide ABT can serve as an ideal HIV-1 fusion inhibitor

Oscillations by Minimal Bacterial Suicide Circuits Reveal Hidden Facets of Host-Circuit Physiology

Synthetic biology seeks to enable programmed control of cellular behavior though engineered biological systems. These systems typically consist of synthetic circuits that function inside, and interact with, complex host cells possessing pre-existing metabolic and regulatory networks. Nevertheless, while designing systems, a simple well-defined interface between the synthetic gene circuit and the host is frequently assumed. We describe the generation of robust but unexpected oscillations in the densities of bacterium Escherichia coli populations by simple synthetic suicide circuits containing quorum components and a lysis gene. Contrary to design expectations, oscillations required neither the quorum sensing genes (luxR and luxI) nor known regulatory elements in the PluxI promoter. Instead, oscillations were likely due to density-dependent plasmid amplification that established a population-level negative feedback. A mathematical model based on this mechanism captures the key characteristics of oscillations, and model predictions regarding perturbations to plasmid amplification were experimentally validated. Our results underscore the importance of plasmid copy number and potential impact of “hidden interactions” on the behavior of engineered gene circuits - a major challenge for standardizing biological parts. As synthetic biology grows as a discipline, increasing value may be derived from tools that enable the assessment of parts in their final context