The Intermediate Luminosity Optical Transient SN 2010da: The Progenitor, Eruption and Aftermath of a Peculiar Supergiant High-mass X-ray Binary

We present optical spectroscopy, ultraviolet to infrared imaging and X-ray observations of the intermediate luminosity optical transient (ILOT) SN 2010da in NGC 300 (d=1.86 Mpc) spanning from -6 to +6 years relative to the time of outburst in 2010. Based on the light curve and multi-epoch SEDs of SN 2010da, we conclude that the progenitor of SN 2010da is a ~10-12 Msol yellow supergiant possibly transitioning into a blue loop phase. During outburst, SN 2010da had a peak absolute magnitude of M<-10.4 mag, dimmer than other ILOTs and supernova impostors. We detect multi-component hydrogen Balmer, Paschen, and Ca II emission lines in our high-resolution spectra, which indicate a dusty and complex circumstellar environment. Since the 2010 eruption, the star has brightened by a factor of ~5 and remains highly variable in the optical. Furthermore, we detect SN 2010da in archival Swift and Chandra observations as an ultraluminous X-ray source (L~6x10^{39} erg/s). We additionally attribute He II 4686 Angstrom and coronal Fe emission lines in addition to a steady X-ray luminosity of ~10^{37} erg/s to the presence of a compact companion.Comment: published; updated citations and other minor edit

The Unusually Luminous Extragalactic Nova SN 2010U

We present observations of the unusual optical transient SN 2010U, including spectra taken 1.03 days to 15.3 days after maximum light that identify it as a fast and luminous Fe II type nova. Our multi-band light curve traces the fast decline (t_2 = 3.5 days) from maximum light (M_V = -10.2 mag), placing SN 2010U in the top 0.5% of the most luminous novae ever observed. We find typical ejecta velocities of approximately 1100 km/s and that SN 2010U shares many spectral and photometric characteristics with two other fast and luminous Fe II type novae, including Nova LMC 1991 and M31N-2007-11d. For the extreme luminosity of this nova, the maximum magnitude vs. rate of decline relationship indicates a massive white dwarf progenitor with a low pre-outburst accretion rate. However, this prediction is in conflict with emerging theories of nova populations, which predict that luminous novae from massive white dwarfs should preferentially exhibit an alternate spectral type (He/N) near maximum light.Comment: 16 pages, 16 figures. Submitted to the Astrophysical Journa

A response to “Likelihood ratio as weight of evidence: a closer look” by Lund and Iyer

Recently, Lund and Iyer (L&amp;I) raised an argument regarding the use of likelihood ratios in court. In our view, their argument is based on a lack of understanding of the paradigm. L&amp;I argue that the decision maker should not accept the expert’s likelihood ratio without further consideration. This is agreed by all parties. In normal practice, there is often considerable and proper exploration in court of the basis for any probabilistic statement. We conclude that L&amp;I argue against a practice that does not exist and which no one advocates. Further we conclude that the most informative summary of evidential weight is the likelihood ratio. We state that this is the summary that should be presented to a court in every scientific assessment of evidential weight with supporting information about how it was constructed and on what it was based

An integrative approach to ortholog prediction for disease-focused and other functional studies

Background Mapping of orthologous genes among species serves an important role in functional genomics by allowing researchers to develop hypotheses about gene function in one species based on what is known about the functions of orthologs in other species. Several tools for predicting orthologous gene relationships are available. However, these tools can give different results and identification of predicted orthologs is not always straightforward. Results We report a simple but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog Prediction Tool (DIOPT; http://www.flyrnai.org/diopt webcite), for rapid identification of orthologs. DIOPT integrates existing approaches, facilitating rapid identification of orthologs among human, mouse, zebrafish, C. elegans, Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows increased sensitivity with only a modest decrease in specificity. Moreover, the flexibility built into the DIOPT graphical user interface allows researchers with different goals to appropriately 'cast a wide net' or limit results to highest confidence predictions. DIOPT also displays protein and domain alignments, including percent amino acid identity, for predicted ortholog pairs. This helps users identify the most appropriate matches among multiple possible orthologs. To facilitate using model organisms for functional analysis of human disease-associated genes, we used DIOPT to predict high-confidence orthologs of disease genes in Online Mendelian Inheritance in Man (OMIM) and genes in genome-wide association study (GWAS) data sets. The results are accessible through the DIOPT diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist webcite). Conclusions DIOPT and DIOPT-DIST are useful resources for researchers working with model organisms, especially those who are interested in exploiting model organisms such as Drosophila to study the functions of human disease genes.Harvard CatalystNational Institutes of Health (U.S.) (NIH R01 GM067761)National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (5K08DK78361)Dana-Farber/Harvard Cancer Cente

Concurrent MEK targeted therapy prevents MAPK pathway reactivation during BRAFV600E targeted inhibition in a novel syngeneic murine glioma model.

Inhibitors of BRAFV600E kinase are currently under investigations in preclinical and clinical studies involving BRAFV600E glioma. Studies demonstrated clinical response to such individualized therapy in the majority of patients whereas in some patients tumors continue to grow despite treatment. To study resistance mechanisms, which include feedback activation of mitogen-activated protein kinase (MAPK) signaling in melanoma, we developed a luciferase-modified cell line (2341luc) from a BrafV600E mutant and Cdkn2a- deficient murine high-grade glioma, and analyzed its molecular responses to BRAFV600E- and MAPK kinase (MEK)-targeted inhibition. Immunocompetent, syngeneic FVB/N mice with intracranial grafts of 2341luc were tested for effects of BRAFV600E and MEK inhibitor treatments, with bioluminescence imaging up to 14-days after start of treatment and survival analysis as primary indicators of inhibitor activity. Intracranial injected tumor cells consistently generated high-grade glioma-like tumors in syngeneic mice. Intraperitoneal daily delivery of BRAFV600E inhibitor dabrafenib only transiently suppressed MAPK signaling, and rather increased Akt signaling and failed to extend survival for mice with intracranial 2341luc tumor. MEK inhibitor trametinib delivered by oral gavage daily suppressed MAPK pathway more effectively and had a more durable anti-growth effect than dabrafenib as well as a significant survival benefit. Compared with either agent alone, combined BRAFV600E and MEK inhibitor treatment was more effective in reducing tumor growth and extending animal subject survival, as corresponding to sustained MAPK pathway inhibition. Results derived from the 2341luc engraftment model application have clinical implications for the management of BRAFV600E glioma

A GPU Spatial Processing System for CHIME

We present an overview of the Graphics Processing Unit (GPU) based spatial processing system created for the Canadian Hydrogen Intensity Mapping Experiment (CHIME). The design employs AMD S9300x2 GPUs and readily-available commercial hardware in its processing nodes to provide a cost- and power-efficient processing substrate. These nodes are supported by a liquid-cooling system which allows continuous operation with modest power consumption and in all but the most adverse conditions. Capable of continuously correlating 2048 receiver-polarizations across 400\,MHz of bandwidth, the CHIME X-engine constitutes the most powerful radio correlator currently in existence. It receives $6.6$\,Tb/s of channelized data from CHIME's FPGA-based F-engine, and the primary correlation task requires $8.39\times10^{14}$ complex multiply-and-accumulate operations per second. The same system also provides formed-beam data products to commensal FRB and Pulsar experiments; it constitutes a general spatial-processing system of unprecedented scale and capability, with correspondingly great challenges in computation, data transport, heat dissipation, and interference shielding

The Dynamics of Rayleigh-Taylor Stable and Unstable Contact Discontinuities with Anisotropic Thermal Conduction

We study the effects of anisotropic thermal conduction along magnetic field lines on an accelerated contact discontinuity in a weakly collisional plasma. We first perform a linear stability analysis similar to that used to derive the Rayleigh-Taylor instability (RTI) dispersion relation. We find that anisotropic conduction is only important for compressible modes, as incompressible modes are isothermal. Modes grow faster in the presence of anisotropic conduction, but growth rates do not change by more than a factor of order unity. We next run fully non-linear numerical simulations of a contact discontinuity with anisotropic conduction. The non-linear evolution can be thought of as a superposition of three physical effects: temperature diffusion due to vertical conduction, the RTI, and the heat flux driven buoyancy instability (HBI). In simulations with RTI-stable contact discontinuities, the temperature discontinuity spreads due to vertical heat conduction. This occurs even for initially horizontal magnetic fields due to the initial vertical velocity perturbation and numerical mixing across the interface. The HBI slows this temperature diffusion by reorienting initially vertical magnetic field lines to a more horizontal geometry. In simulations with RTI-unstable contact discontinuities, the dynamics are initially governed by temperature diffusion, but the RTI becomes increasingly important at late times. We discuss the possible application of these results to supernova remnants, solar prominences, and cold fronts in galaxy clusters.Comment: 18 pages, 15 figures, submitted to MNRA

AVENUE21. Connected and Automated Driving: Prospects for Urban Europe

This open access publication examines the impact of connected and automated vehicles on the European city and the conditions that can enable this technology to make a positive contribution to urban development. The authors argue for two theses that have thus far received little attention in scientific discourse: as connected and automated vehicles will not be ready for use in all parts of the city for a long time, previously assumed effects – from traffic safety to traffic performance as well as spatial effects – will need to be re-evaluated. To ensure this technology has a positive impact on the mobility of the future, transport and settlement policy regulations must be adapted and further developed. Established territorial, institutional and organizational boundaries must be investigated and challenged quickly. Despite – or, indeed, because of – the many uncertainties, we find ourselves at the beginning of a new design phase, not only in terms of technology development, but also regarding politics, urban planning, administration and civil society