Canonical Particle Acceleration in FRI Radio Galaxies

Matched resolution multi-frequency VLA observations of four radio galaxies are used to derive the asymptotic low energy slope of the relativistic electron distribution. Where available, low energy slopes are also determined for other sources in the literature. They provide information on the acceleration physics independent of radiative and other losses, which confuse measurements of the synchrotron spectra in most radio, optical and X-ray studies. We find a narrow range of inferred low energy electron energy slopes, n(E)=const*E^-2.1 for the currently small sample of lower luminosity sources classified as FRI (not classical doubles). This distribution is close to, but apparently inconsistent with, the test particle limit of n(E)=const*E^-2.0 expected from strong diffusive shock acceleration in the non-relativistic limit. Relativistic shocks or those modified by the back-pressure of efficiently accelerated cosmic rays are two alternatives to produce somewhat steeper spectra. We note for further study the possiblity of acceleration through shocks, turbulence or shear in the flaring/brightening regions in FRI jets as they move away from the nucleus. Jets on pc scales and the collimated jets and hot spots of FRII (classical double) sources would be governed by different acceleration sites and mechanisms; they appear to show a much wider range of spectra than for FRI sources.Comment: 16 figures, including 5 color. Accepted to Astrophysical Journa

Risk analysis of animal–vehicle crashes: a hierarchical Bayesian approach to spatial modelling

Driving along any rural road within Western Australia involves some level of uncertainty about encountering an animal whether it is wildlife, farm stock or domestic. This level of uncertainty can vary depending on factors such as the surrounding land use, water source, geometry of the road, speed limits and signage. This paper aims to model the risk of animal–vehicle crashes (AVCs) on a segmented highway. A hierarchical Bayesian model involving multivariate Poisson lognormal regression is used in establishing the relationship between AVCs and the contributing factors. Findings of this study show that farming on both sides of a road, a mixture of farming and forest roadside vegetation and roadside vegetation have significant positive effect on AVCs, while speed limits and horizontal curves indicate a negative effect. AVCs consist of both spatial- and segment-specific contributions, even though the spatial random error does not dominate model variability. Segment 15 is identified as the highest risk segment and its nearby segments also exhibit high risk

A Green Bank Telescope search for narrowband technosignatures between 1.1-1.9 GHz during 12 Kepler planetary transits

A growing avenue for determining the prevalence of life beyond Earth is to search for "technosignatures" from extraterrestrial intelligences/agents. Technosignatures require significant energy to be visible across interstellar space and thus intentional signals might be concentrated in frequency, in time, or in space, to be found in mutually obvious places. Therefore, it could be advantageous to search for technosignatures in parts of parameter space that are mutually-derivable to an observer on Earth and a distant transmitter. In this work, we used the L-band (1.1-1.9 GHz) receiver on the Robert C. Byrd Green Bank Telescope (GBT) to perform the first technosignature search pre-synchronized with exoplanet transits, covering 12 Kepler systems. We used the Breakthrough Listen turboSETI pipeline to flag narrowband hits ($\sim$3 Hz) using a maximum drift rate of $\pm$614.4 Hz/s and a signal-to-noise threshold of 5 - the pipeline returned $\sim 3.4 \times 10^5$ apparently-localized features. Visual inspection by a team of citizen scientists ruled out 99.6% of them. Further analysis found 2 signals-of-interest that warrant follow-up, but no technosignatures. If the signals-of-interest are not re-detected in future work, it will imply that the 12 targets in the search are not producing transit-aligned signals from 1.1-1.9 GHz with transmitter powers $>$60 times that of the former Arecibo radar. This search debuts a range of innovative technosignature techniques: citizen science vetting of potential signals-of-interest, a sensitivity-aware search out to extremely high drift rates, a more flexible method of analyzing on-off cadences, and an extremely low signal-to-noise threshold.Comment: 18 pages, 11 figure

TCR-engineered adoptive cell therapy effectively treats intracranial murine glioblastoma

BACKGROUND: Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. As an alternative, T cell receptor (TCR)-engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma. METHODS: We employed single-cell PCR to isolate a TCR specific for the Imp3 RESULTS: We isolated and characterized the 3×1.1C TCR that displayed a high affinity for mImp3 but no wild-type cross-reactivity. To provide a source of mImp3-specific T cells, we generated the MISTIC mouse. In a model of adoptive cellular therapy, the infusion of activated MISTIC T cells resulted in rapid intratumoral infiltration and profound antitumor effects with long-term cures in a majority of GL261-bearing mice. The subset of mice that did not respond to the adoptive cell therapy showed evidence of retained neoantigen expression but intratumoral MISTIC T cell dysfunction. The efficacy of MISTIC T cell therapy was lost in mice bearing a tumor with heterogeneous mImp3 expression, showcasing the barriers to targeted therapy in polyclonal human tumors. CONCLUSIONS: We generated and characterized the first TCR transgenic against an endogenous neoantigen within a preclinical glioma model and demonstrated the therapeutic potential of adoptively transferred neoantigen-specific T cells. The MISTIC mouse provides a powerful novel platform for basic and translational studies of antitumor T-cell responses in glioblastoma

Decoding Brain Activity Associated with Literal and Metaphoric Sentence Comprehension Using Distributional Semantic Models

Recent years have seen a growing interest within the natural language processing (NLP)community in evaluating the ability of semantic models to capture human meaning representation in the brain. Existing research has mainly focused on applying semantic models to de-code brain activity patterns associated with the meaning of individual words, and, more recently, this approach has been extended to sentences and larger text fragments. Our work is the first to investigate metaphor process-ing in the brain in this context. We evaluate a range of semantic models (word embeddings, compositional, and visual models) in their ability to decode brain activity associated with reading of both literal and metaphoric sentences. Our results suggest that compositional models and word embeddings are able to capture differences in the processing of literal and metaphoric sentences, providing sup-port for the idea that the literal meaning is not fully accessible during familiar metaphor comprehension

The Murchison Widefield Array: Design Overview

The Murchison Widefield Array (MWA) is a dipole-based aperture array synthesis telescope designed to operate in the 80-300 MHz frequency range. It is capable of a wide range of science investigations, but is initially focused on three key science projects. These are detection and characterization of 3-dimensional brightness temperature fluctuations in the 21cm line of neutral hydrogen during the Epoch of Reionization (EoR) at redshifts from 6 to 10, solar imaging and remote sensing of the inner heliosphere via propagation effects on signals from distant background sources,and high-sensitivity exploration of the variable radio sky. The array design features 8192 dual-polarization broad-band active dipoles, arranged into 512 tiles comprising 16 dipoles each. The tiles are quasi-randomly distributed over an aperture 1.5km in diameter, with a small number of outliers extending to 3km. All tile-tile baselines are correlated in custom FPGA-based hardware, yielding a Nyquist-sampled instantaneous monochromatic uv coverage and unprecedented point spread function (PSF) quality. The correlated data are calibrated in real time using novel position-dependent self-calibration algorithms. The array is located in the Murchison region of outback Western Australia. This region is characterized by extremely low population density and a superbly radio-quiet environment,allowing full exploitation of the instrumental capabilities.Comment: 9 pages, 5 figures, 1 table. Accepted for publication in Proceedings of the IEE

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren’s syndrome: results of the TRACTISS randomised double-blind multicentre substudy

Objectives To compare the effects of rituximab versus placebo on salivary gland ultrasound (SGUS) in primary Sjögren’s syndrome (PSS) in a multicentre, multiobserver phase III trial substudy. Methods Subjects consenting to SGUS were randomised to rituximab or placebo given at weeks 0, 2, 24 and 26, and scanned at baseline and weeks 16 and 48. Sonographers completed a 0–11 total ultrasound score (TUS) comprising domains of echogenicity, homogeneity, glandular definition, glands involved and hypoechoic foci size. Baseline-adjusted TUS values were analysed over time, modelling change from baseline at each time point. For each TUS domain, we fitted a repeated-measures logistic regression model to model the odds of a response in the rituximab arm (≥1-point improvement) as a function of the baseline score, age category, disease duration and time point. Results 52 patients (n=26 rituximab and n=26 placebo) from nine centres completed baseline and one or more follow-up visits. Estimated between-group differences (rituximab-placebo) in baseline-adjusted TUS were −1.2 (95% CI −2.1 to −0.3; P=0.0099) and −1.2 (95% CI −2.0 to −0.5; P=0.0023) at weeks 16 and 48. Glandular definition improved in the rituximab arm with an OR of 6.8 (95% CI 1.1 to 43.0; P=0.043) at week 16 and 10.3 (95% CI 1.0 to 105.9; P=0.050) at week 48. Conclusions We demonstrated statistically significant improvement in TUS after rituximab compared with placebo. This encourages further research into both B cell depletion therapies in PSS and SGUS as an imaging biomarker

Modern microwave methods in solid state inorganic materials chemistry: from fundamentals to manufacturing

No abstract available

Stearoyl-CoA desaturase-1 impairs the reparative properties of macrophages and microglia in the brain

Failure of remyelination underlies the progressive nature of demyelinating diseases such as multiple sclerosis. Macrophages and microglia are crucially involved in the formation and repair of demyelinated lesions. Here we show that myelin uptake temporarily skewed these phagocytes toward a disease-resolving phenotype, while sustained intracellular accumulation of myelin induced a lesion-promoting phenotype. This phenotypic shift was controlled by stearoyl-CoA desaturase-1 (SCD1), an enzyme responsible for the desaturation of saturated fatty acids. Monounsaturated fatty acids generated by SCD1 reduced the surface abundance of the cholesterol efflux transporter ABCA1, which in turn promoted lipid accumulation and induced an inflammatory phagocyte phenotype. Pharmacological inhibition or phagocyte-specific deficiency of Scd1 accelerated remyelination ex vivo and in vivo. These findings identify SCD1 as a novel therapeutic target to promote remyelination