The Burn: A novel

The Burn: A Novel tells the story of Richie Thornton, a 21-year-old former petty criminal and minor drug dealer. He\u27s left his sordid often violent past behind him, and now lives with his college-age girlfriend, Laurel Metti, and her parents. It\u27s a strained existence, primarily because Richie doesn\u27t feel he belongs, but he makes do, working as a stockman at an organic food store; Then he discovers that his cousin, Robert, has been released from prison early. Robert had been put in prison for attacking Laurel one year ago, and his release spells trouble for the new life Richie and Laurel have established for themselves. Richie ultimately decides it\u27s either Robert or him, and sets about attempting to locate his elusive cousin and put him out of commission

RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling http://www.tandfonline.com/doi/pdf/10.4161/15384101.2014.967076

The ATR-Chk1 signaling pathway mediates cellular responses to DNA damage and replication stress and is composed of a number of core factors that are conserved throughout eukaryotic organisms. However, humans and other higher eukaryotic species possess additional factors that are implicated in the regulation of this signaling network but that have not been extensively studied. Here we show that RHINO (for Rad9, Rad1, Hus1 interacting nuclear orphan) forms complexes with both the 9-1-1 checkpoint clamp and TopBP1 in human cells even in the absence of treatments with DNA damaging agents via direct interactions with the Rad9 and Rad1 subunits of the 9-1-1 checkpoint clamp and with the ATR kinase activator TopBP1. The interaction of RHINO with 9-1-1 was of sufficient affinity to allow for the purification of a stable heterotetrameric RHINO-Rad9-Hus1-Rad1 complex in vitro. In human cells, a portion of RHINO localizes to chromatin in the absence of DNA damage, and this association is enriched following UV irradiation. Furthermore, we find that the tethering of a Lac Repressor (LacR)-RHINO fusion protein to LacO repeats in chromatin of mammalian cells induces Chk1 phosphorylation in a Rad9- and Claspin-dependent manner. Lastly, the loss of RHINO partially abrogates ATR-Chk1 signaling following UV irradiation without impacting the interaction of the 9-1-1 clamp with TopBP1 or the loading of 9-1-1 onto chromatin. We conclude that RHINO is a bona fide regulator of ATR-Chk1 signaling in mammalian cells

Automated deep learning segmentation of high-resolution 7 T postmortem MRI for quantitative analysis of structure-pathology correlations in neurodegenerative diseases

Postmortem MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high resolution of 135 postmortem human brain tissue specimens imaged at 0.3 mm$^{3}$ isotropic using a T2w sequence on a 7T whole-body MRI scanner. We developed a deep learning pipeline to segment the cortical mantle by benchmarking the performance of nine deep neural architectures, followed by post-hoc topological correction. We then segment four subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities, and the normal appearing white matter. We show generalizing capabilities across whole brain hemispheres in different specimens, and also on unseen images acquired at 0.28 mm^3 and 0.16 mm^3 isotropic T2*w FLASH sequence at 7T. We then compute localized cortical thickness and volumetric measurements across key regions, and link them with semi-quantitative neuropathological ratings. Our code, Jupyter notebooks, and the containerized executables are publicly available at: https://pulkit-khandelwal.github.io/exvivo-brain-upennComment: Preprint submitted to NeuroImage Project website: https://pulkit-khandelwal.github.io/exvivo-brain-upen

AVONET: morphological, ecological and geographical data for all birds

Functional traits offer a rich quantitative framework for developing and testing theories in evolutionary biology, ecology and ecosystem science. However, the potential of functional traits to drive theoretical advances and refine models of global change can only be fully realised when species‐level information is complete. Here we present the AVONET dataset containing comprehensive functional trait data for all birds, including six ecological variables, 11 continuous morphological traits, and information on range size and location. Raw morphological measurements are presented from 90,020 individuals of 11,009 extant bird species sampled from 181 countries. These data are also summarised as species averages in three taxonomic formats, allowing integration with a global phylogeny, geographical range maps, IUCN Red List data and the eBird citizen science database. The AVONET dataset provides the most detailed picture of continuous trait variation for any major radiation of organisms, offering a global template for testing hypotheses and exploring the evolutionary origins, structure and functioning of biodiversity

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Exploration of a biologically inspired model for sound source localization in 3D space

Sound localization in 3D space relies on a variety of auditory cues resulting from the encoding provided by the lower and higher regions of the auditory path. During the last 50 years different theories and models have been developed to describe psychoacoustic phenomena in sound localization inspired by the processing that is undertaken in the human auditory system. In this paper, a biologically inspired model of human sound localization is described and the encoding of the known auditory cues by the model is explored. In particular, the model takes as an input binaural and monaural stationary signals that carry information about the Interaural Time Difference (ITD), the Interaural Level Difference (ILD) and the spectral variation of the Head Related Transfer Function (HRTF). The model processes these cues through a series of linear and nonlinear units, that simulate the peripheral and the pre-processing stages of the auditory system. The encoded cues, which in the model are represented by excitation-inhibition (EI) and the time average (TA) activity patterns, are then decoded by a central processing unit to estimate the final location of the sound source

Alternative approaches to optophonic mappings

This thesis presents a number of modifications to a blind aid, known as the video optophone, which enables a blind user to more readily interpret their local environment for enhanced mobility and navigation. Versions of this form of blind aid are generally both difficult to use and interpret, and are therefore inadequate for safe mobility. The reason for this severe problem lies in the complexity and excessive bandwidth of the optophonic output after the conversion from scene-to-sound. The work herein describes a number of modifications that can be applied to the current optophonic process to make more efficient use of the limited bandwidth provided by the auditory system when converting scene images to sound. Various image processing and stereo techniques have been employed to artificially emulate the human visual system through the use of depth maps that successfully fade out the quantity of relatively unimportant image features, whilst emphasising the more significant regions such as nearby obstacles. A series of experiments were designed to test these various modifications to the optophonic mapping by studying important factors of mobility and subject response whilst going about everyday life. The devised system, labelled DeLIA for the Detection, Location, Identification, and Avoidance (or Action) of obstacles, provided a means for gathering statistical data on users’ interpretation of the optophonic output. An analysis of this data demonstrated a significant improvement when using the stereo cartooning technique, developed as part of this work, over the more conventional plain image as an input to an optophonic mapping from scene-to-sound. Lastly, conclusions were drawn from the results, which indicated that the use of a stereo depth map as an input to a video optophone would improve its usefulness as an aid to general mobility. For the purposes of detecting and determining text or similar detail, either a plain unmodified image or some form of edge (depth) image were found to produce the best result