GRB 180620A: Evidence for Late-time Energy Injection

The early optical emission of gamma-ray bursts (GRBs) gives an opportunity to understand the central engine and first stages of these events. About 30% of GRBs present flares whose origin is still a subject of discussion. We present optical photometry of GRB 180620A with the COATLI telescope and RATIR instrument. COATLI started to observe from the end of prompt emission at T + 39.3 s and RATIR from T + 121.4 s. We supplement the optical data with the X-ray light curve from Swift/XRT. We observe an optical flare from T + 110 s to T + 550 s, with a temporal index decay α O,decay = 1.32 ± 0.01, and Δt/t = 1.63, which we interpret as the signature of a reverse shock component. After the initial normal decay the light curves show a long plateau from T + 500 s to T + 7800 s in both X-rays and the optical before decaying again after an achromatic jet break at T + 7800 s. Fluctuations are seen during the plateau phase in the optical. Adding to the complexity of GRB afterglows, the plateau phase (typically associated with the coasting phase of the jet) is seen in this object after the "normal" decay phase (associated with the deceleration phase of the jet), and the jet break phase occurs directly after the plateau. We suggest that this sequence of events can be explained by a rapid deceleration of the jet with t d ≲ 40 s due to the high density of the environment (≈100 cm-3) followed by reactivation of the central engine, which causes the flare and powers the plateau phase

The host galaxies and explosion sites of long-duration gamma-ray bursts: Hubble Space Telescope near-infrared imaging

We present the results of a Hubble Space Telescope WFC3/F160WSnapshot survey of the host galaxies of 39 long-duration gamma-ray bursts (LGRBs) at z < 3. We have non-detections of hosts at the locations of four bursts. Sufficient accuracy to astrometrically align optical afterglowimages and determine the location of the LGRB within its hostwas possible for 31/35 detected hosts. In agreement with other work, we find the luminosity distribution of LGRB hosts is significantly fainter than that of a star formation rate-weighted field galaxy sample over the same redshift range, indicating LGRBs are not unbiasedly tracing the star formation rate. Morphologically, the sample of LGRB hosts is dominated by spiral-like or irregular galaxies. We find evidence for evolution of the population of LGRB hosts towards lower luminosity, higher concentrated hosts at lower redshifts. Their half-light radii are consistent with other LGRB host samples where measurements were made on rest-frame UV observations. In agreement with recent work, we find their 80 per cent enclosed flux radii distribution to be more extended than previously thought, making them intermediate between core-collapse supernova (CCSN) and superluminous supernova (SLSN) hosts. The galactocentric projectedoffset distribution confirms LGRBs as centrally concentrated, much more so than CCSNe and similar to SLSNe. LGRBs are strongly biased towards the brighter regions in their host light distributions, regardless of their offset. We find a correlation between the luminosity of the LGRB explosion site and the intrinsic column density, NH, towards the burst. © 2017 The Authors

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.&#xd;&#xa;&#xd;&#xa;*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. &#xd;&#xa;&#xd;&#xa;*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from &#x22;http://www-huber.embl.de/users/anders/DESeq&#x22;:http://www-huber.embl.de/users/anders/DESeq

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Duckietown: An Innovative Way to Teach Autonomy

Teaching robotics is challenging because it is a multidisciplinary, rapidly evolving and experimental discipline that integrates cutting-edge hardware and software. This paper describes the course design and first implementation of Duckietown, a vehicle autonomy class that experiments with teaching innovations in addition to leveraging modern educational theory for improving student learning. We provide a robot to every student, thanks to a minimalist platform design, to maximize active learning; and introduce a role-play aspect to increase team spirit, by modeling the entire class as a fictional start-up (Duckietown Engineering Co.). The course formulation leverages backward design by formalizing intended learning outcomes (ILOs) enabling students to appreciate the challenges of: (a) heterogeneous disciplines converging in the design of a minimal self-driving car, (b) integrating subsystems to create complex system behaviors, and (c) allocating constrained computational resources. Students learn how to assemble, program, test and operate a self-driving car (Duckiebot) in a model urban environment (Duckietown), as well as how to implement and document new features in the system. Traditional course assessment tools are complemented by a full scale demonstration to the general public. The “duckie” theme was chosen to give a gender-neutral, friendly identity to the robots so as to improve student involvement and outreach possibilities. All of the teaching materials and code is released online in the hope that other institutions will adopt the platform and continue to evolve and improve it, so to keep pace with the fast evolution of the field.National Science Foundation (U.S.) (Award IIS #1318392)National Science Foundation (U.S.) (Award #1405259

Long gamma-ray bursts and core-collapse supernovae have different environments

When massive stars exhaust their fuel they collapse and often produce the extraordinarily bright explosions known as core-collapse supernovae. On occasion, this stellar collapse also powers an even more brilliant relativistic explosion known as a long-duration gamma-ray burst. One would then expect that long gamma-ray bursts and core-collapse supernovae should be found in similar galactic environments. Here we show that this expectation is wrong. We find that the long gamma-ray bursts are far more concentrated on the very brightest regions of their host galaxies than are the core-collapse supernovae. Furthermore, the host galaxies of the long gamma-ray bursts are significantly fainter and more irregular than the hosts of the core-collapse supernovae. Together these results suggest that long-duration gamma-ray bursts are associated with the most massive stars and may be restricted to galaxies of limited chemical evolution. Our results directly imply that long gamma-ray bursts are relatively rare in galaxies such as our own Milky Way.Comment: 27 pages, 4 figures, submitted to Nature on 22 August 2005, revised 9 February 2006, online publication 10 May 2006. Supplementary material referred to in the text can be found at http://www.stsci.edu/~fruchter/GRB/locations/supplement.pdf . This new version contains minor changes to match the final published versio

Computer-assisted assessment of the Human Epidermal Growth Factor Receptor 2 immunohistochemical assay in imaged histologic sections using a membrane isolation algorithm and quantitative analysis of positive controls

<p>Abstract</p> <p>Background</p> <p>Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER2) are eligible for effective biologically targeted therapies, such as trastuzumab. However, accurately determining HER2 overexpression, especially in immunohistochemically equivocal cases, remains a challenge. Manual analysis of HER2 expression is dependent on the assessment of membrane staining as well as comparisons with positive controls. In spite of the strides that have been made to standardize the assessment process, intra- and inter-observer discrepancies in scoring is not uncommon. In this manuscript we describe a pathologist assisted, computer-based continuous scoring approach for increasing the precision and reproducibility of assessing imaged breast tissue specimens.</p> <p>Methods</p> <p>Computer-assisted analysis on HER2 IHC is compared with manual scoring and fluorescence in situ hybridization results on a test set of 99 digitally imaged breast cancer cases enriched with equivocally scored (2+) cases. Image features are generated based on the staining profile of the positive control tissue and pixels delineated by a newly developed Membrane Isolation Algorithm. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis.</p> <p>Results</p> <p>A computer-aided diagnostic approach has been developed using a membrane isolation algorithm and quantitative use of positive immunostaining controls. By incorporating internal positive controls into feature analysis a greater Area Under the Curve (AUC) in ROC analysis was achieved than feature analysis without positive controls. Evaluation of HER2 immunostaining that utilized membrane pixels, controls, and percent area stained showed significantly greater AUC than manual scoring, and significantly less false positive rate when used to evaluate immunohistochemically equivocal cases.</p> <p>Conclusion</p> <p>It has been shown that by incorporating both a membrane isolation algorithm and analysis of known positive controls a computer-assisted diagnostic algorithm was developed that can reproducibly score HER2 status in IHC stained clinical breast cancer specimens. For equivocal scoring cases, this approach performed better than standard manual evaluation as assessed by ROC analysis in our test samples. Finally, there exists potential for utilizing image-analysis techniques for improving HER2 scoring at the immunohistochemically equivocal range.</p

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope

We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently-known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi-LAT energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cut-off at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch D., Rea N., Burnett