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Old MacDino had a farm
\"Old MacDino had a farm, E-I-E-I-O! And on this farm he had a Stegosaurus! Old MacDino's farm is full of DINOSAURS! The cows, pigs, horses, and other animals are joined by a Diplodocus, a Triceratops, a Velociraptor, and more. With a Stomp! Stomp! here, and a Crash! Smash! there, they're causing chaos EVERYWHERE! What's a farmer to do?\"-- Amazon.com.
Book
Red supergiants as supernova progenitors
It is now well-established from pre-explosion imaging that red supergiants (RSGs) are the direct progenitors of Type-IIP supernovae. These images have been used to infer the physical properties of the exploding stars, yielding some surprising results. In particular, the differences between the observed and predicted mass spectrum has provided a challenge to our view of stellar evolutionary theory. However, turning what is typically a small number of pre-explosion photometric points into the physical quantities of stellar luminosity and mass requires a number of assumptions about the spectral appearance of RSGs, as well as their evolution in the last few years of life. Here I will review what we know about RSGs, with a few recent updates on how they look and how their appearance changes as they approach supernova.
This article is part of the themed issue ‘Bridging the gap: from massive stars to supernovae’.
Journal Article
Changes in political trust in Britain during the COVID-19 pandemic in 2020: integrated public opinion evidence and implications
In this paper, we document changes in political trust in the UK throughout 2020 so as to consider wider implications for the ongoing handling of the COVID-19 pandemic. We analysed data from 18 survey organisations with measures on political trust (general, leadership, and COVID-19-related) spanning the period December 2019–October 2020. We examined the percentage of trust and distrust across time, identifying where significant changes coincide with national events. Levels of political trust were low following the 2019 UK General Election. They rose at the onset of UK lockdown imposed in March 2020 but showed persistent gradual decline throughout the remainder of the year, falling to pre-COVID levels by October 2020. Inability to sustain the elevated political trust achieved at the onset of the pandemic is likely to have made the management of public confidence and behaviour increasingly challenging, pointing to the need for strategies to sustain trust levels when handling future crises.
Journal Article
Oxr1 Is Essential for Protection against Oxidative Stress-Induced Neurodegeneration
Oxidative stress is a common etiological feature of neurological disorders, although the pathways that govern defence against reactive oxygen species (ROS) in neurodegeneration remain unclear. We have identified the role of oxidation resistance 1 (Oxr1) as a vital protein that controls the sensitivity of neuronal cells to oxidative stress; mice lacking Oxr1 display cerebellar neurodegeneration, and neurons are less susceptible to exogenous stress when the gene is over-expressed. A conserved short isoform of Oxr1 is also sufficient to confer this neuroprotective property both in vitro and in vivo. In addition, biochemical assays indicate that Oxr1 itself is susceptible to cysteine-mediated oxidation. Finally we show up-regulation of Oxr1 in both human and pre-symptomatic mouse models of amyotrophic lateral sclerosis, indicating that Oxr1 is potentially a novel neuroprotective factor in neurodegenerative disease.
Journal Article
Genome-wide CRISPR/Cas9-knockout in human induced Pluripotent Stem Cell (iPSC)-derived macrophages
Genome engineering using CRISPR/Cas9 technology enables simple, efficient and precise genomic modifications in human cells. Conventional immortalized cell lines can be easily edited or screened using genome-wide libraries with lentiviral transduction. However, cell types derived from the differentiation of induced Pluripotent Stem Cells (iPSC), which often represent more relevant, patient-derived models for human pathology, are much more difficult to engineer as CRISPR/Cas9 delivery to these differentiated cells can be inefficient and toxic. Here, we present an efficient, lentiviral transduction protocol for delivery of CRISPR/Cas9 to macrophages derived from human iPSC with efficiencies close to 100%. We demonstrate CRISPR/Cas9 knockouts for three nonessential proof-of-concept genes—
HPRT1, PPIB
and
CDK4
. We then scale the protocol and validate for a genome-wide pooled CRISPR/Cas9 loss-of-function screen. This methodology enables, for the first time, systematic exploration of macrophage involvement in immune responses, chronic inflammation, neurodegenerative diseases and cancer progression, using efficient genome editing techniques.
Journal Article
The right not to know and the obligation to know
There is significant controversy over whether patients have a ‘right not to know’ information relevant to their health. Some arguments for limiting such a right appeal to potential burdens on others that a patient’s avoidable ignorance might generate. This paper develops this argument by extending it to cases where refusal of relevant information may generate greater demands on a publicly funded healthcare system. In such cases, patients may have an ‘obligation to know’. However, we cannot infer from the fact that a patient has an obligation to know that she does not also have a right not to know. The right not to know is held against medical professionals at a formal institutional level. We have reason to protect patients’ control over the information that they receive, even if in individual instances patients exercise this control in ways that violate obligations.
Journal Article
Evidence for enhancer activity in intron 1 of TNFRSF1A using CRISPR/Cas9 in human induced pluripotent stem cell-derived macrophages
TNFα is a common drug target in the treatment of autoimmune diseases, with pro-inflammatory functions that are primarily mediated through its receptor, TNFRSF1A.
TNFRSF1A
has been genetically associated with many immune-mediated diseases including ankylosing spondylitis, multiple sclerosis, and inflammatory bowel disease. Many of the genetic variants within or near
TNFRSF1A
that have been associated with disease through genome-wide association studies (GWAS) lie in non-coding regions of the genome. Understanding the functional consequences of these genetic variants is limited by incomplete understanding of
TNFRSF1A
gene regulation, including for specific cellular contexts relevant to inflammation and immunity such as macrophages. This work used CRISPR/Cas9 in human induced pluripotent stem cells followed by differentiation into macrophages to investigate putative regulatory elements in the
TNFRSF1A
gene locus. Through gene editing, with functional genomic readouts including the assay for transposase-accessible chromatin using sequencing (ATAC-Seq), chromatin immunoprecipitation with sequencing (ChIP-Seq), and RNA-Seq to assess the consequences of these edits, we present evidence for an enhancer of
TNFRSF1A
contained within an intron of the gene. Understanding gene regulation and the genomic context in which GWAS variants lie could bring us closer to deconvoluting the genetic basis of common disease aetiology and uncover effective drug targets.
Journal Article
A randomised trial of the influence of racial stereotype bias on examiners’ scores, feedback and recollections in undergraduate clinical exams
Background
Asian medical students and doctors receive lower scores on average than their white counterparts in examinations in the UK and internationally (a phenomenon known as “differential attainment”). This could be due to examiner bias or to social, psychological or cultural influences on learning or performance. We investigated whether students’ scores or feedback show influence of ethnicity-related bias; whether examiners unconsciously bring to mind (activate) stereotypes when judging Asian students’ performance; whether activation depends on the stereotypicality of students’ performances; and whether stereotypes influence examiner memories of performances.
Methods
This is a randomised, double-blinded, controlled, Internet-based trial. We created near-identical videos of medical student performances on a simulated Objective Structured Clinical Exam using British Asian and white British actors. Examiners were randomly assigned to watch performances from white and Asian students that were either consistent or inconsistent with a previously described stereotype of Asian students’ performance. We compared the two examiner groups in terms of the following: the scores and feedback they gave white and Asian students; how much the Asian stereotype was activated in their minds (response times to Asian-stereotypical vs neutral words in a lexical decision task); and whether the stereotype influenced memories of student performances (recognition rates for real vs invented stereotype-consistent vs stereotype-inconsistent phrases from one of the videos).
Results
Examiners responded to Asian-stereotypical words (716 ms, 95% confidence interval (CI) 702–731 ms) faster than neutral words (769 ms, 95% CI 753–786 ms,
p
< 0.001), suggesting Asian stereotypes were activated (or at least active) in examiners’ minds. This occurred regardless of whether examiners observed stereotype-consistent or stereotype-inconsistent performances. Despite this stereotype activation, student ethnicity had no influence on examiners’ scores; on the feedback examiners gave; or on examiners’ memories for one performance.
Conclusions
Examiner bias does not appear to explain the differential attainment of Asian students in UK medical schools. Efforts to ensure equality should focus on social, psychological and cultural factors that may disadvantage learning or performance in Asian and other minority ethnic students.
Journal Article
Application of the Sensor Selection Approach in Polymer Electrolyte Membrane Fuel Cell Prognostics and Health Management
In this paper, the sensor selection approach is investigated with the aim of using fewer sensors to provide reliable fuel cell diagnostic and prognostic results. The sensitivity of sensors is firstly calculated with a developed fuel cell model. With sensor sensitivities to different fuel cell failure modes, the available sensors can be ranked. A sensor selection algorithm is used in the analysis, which considers both sensor sensitivity to fuel cell performance and resistance to noise. The performance of the selected sensors in polymer electrolyte membrane (PEM) fuel cell prognostics is also evaluated with an adaptive neuro-fuzzy inference system (ANFIS), and results show that the fuel cell voltage can be predicted with good quality using the selected sensors. Furthermore, a fuel cell test is performed to investigate the effectiveness of selected sensors in fuel cell fault diagnosis. From the results, different fuel cell states can be distinguished with good quality using the selected sensors.
Journal Article