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"Hill, Chris"
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What does it mean to be global?
Teaches children about respecting other countries and cultures and what it means to be a community.
Book
Coherent Focused Lidars for Doppler Sensing of Aerosols and Wind
Many coherent lidars are used today with aerosol targets for detailed studies of e.g., local wind speed and turbulence. Fibre-optic lidars operating near 1.5 μm dominate the wind energy market, with hundreds now installed worldwide. Here, we review some of the beam/target physics for these lidars and discuss practical problems. In a monostatic Doppler lidar with matched local oscillator and transmit beams, focusing of the beam gives rise to a spatial sensitivity along the beam direction that depends on the inverse of beam area; for Gaussian beams, this sensitivity follows a Lorentzian function. At short range, the associated probe volume can be extremely small and contain very few scatterers; we describe predictions and simulations for few-scatterer and multi-scatterer sensing. We review the single-particle mode (SPM) and volume mode (VM) modelling of Frehlich et al. and some numerical modelling of lidar detector time series and statistics. Interesting behaviour may be observed from a modern coherent lidar used at short ranges (e.g., in a wind tunnel) and/or with weak aerosol seeding. We also review some problems (and solutions) for Doppler-sign-insensitive lidars.
Journal Article
Insights from structural studies of the cardiovirus 2A protein
Cardioviruses are single-stranded RNA viruses of the family Picornaviridae. In addition to being the first example of internal ribosome entry site (IRES) utilization, cardioviruses also employ a series of alternative translation strategies, such as Stop-Go translation and programmed ribosome frameshifting. Here, we focus on cardiovirus 2A protein, which is not only a primary virulence factor, but also exerts crucial regulatory functions during translation, including activation of viral ribosome frameshifting and inhibition of host cap-dependent translation. Only recently, biochemical and structural studies have allowed us to close the gaps in our knowledge of how cardiovirus 2A is able to act in diverse translation-related processes as a novel RNA-binding protein. This review will summarize these findings, which ultimately may lead to the discovery of other RNA-mediated gene expression strategies across a broad range of RNA viruses.
Journal Article
ما معنى أن أكون عالميا ؟
مجموعة من المفاهيم البسيطة التي تساعد الطفل على أن يدرك كيف يكون عالميا من خلال أن لغته ليست سوى واحدة من بين آلاف اللغات وأن هناك اختلافات كبيرة بين الأفراد في بقاع الأرض كافة من حيث المأكولات والتقاليد والأديان، فعلينا أن نتقبل هذا الاختلاف وأن نكون منفتحين على العالم بأكمله فأن أكون عالميا يعني أن أكون مواطنا من العالم.
BOOK
Architecture of eukaryotic mRNA 3′-end processing machinery
Newly transcribed eukaryotic precursor messenger RNAs (pre-mRNAs) are processed at their 3′ ends by the ~1-megadalton multiprotein cleavage and polyadenylation factor (CPF). CPF cleaves pre-mRNAs, adds a polyadenylate tail, and triggers transcription termination, but it is unclear how its various enzymes are coordinated and assembled. Here, we show that the nuclease, polymerase, and phosphatase activities of yeast CPF are organized into three modules. Using electron cryomicroscopy, we determined a 3.5-angstrom-resolution structure of the ~200-kilodalton polymerase module. This revealed four β propellers, in an assembly markedly similar to those of other protein complexes that bind nucleic acid. Combined with in vitro reconstitution experiments, our data show that the polymerase module brings together factors required for specific and efficient polyadenylation, to help coordinate mRNA 3′-end processing.
Journal Article
Structural and molecular basis for Cardiovirus 2A protein as a viral gene expression switch
Programmed –1 ribosomal frameshifting (PRF) in cardioviruses is activated by the 2A protein, a multi-functional virulence factor that also inhibits cap-dependent translational initiation. Here we present the X-ray crystal structure of 2A and show that it selectively binds to a pseudoknot-like conformation of the PRF stimulatory RNA element in the viral genome. Using optical tweezers, we demonstrate that 2A stabilises this RNA element, likely explaining the increase in PRF efficiency in the presence of 2A. Next, we demonstrate a strong interaction between 2A and the small ribosomal subunit and present a cryo-EM structure of 2A bound to initiated 70S ribosomes. Multiple copies of 2A bind to the 16S rRNA where they may compete for binding with initiation and elongation factors. Together, these results define the structural basis for RNA recognition by 2A, show how 2A-mediated stabilisation of an RNA pseudoknot promotes PRF, and reveal how 2A accumulation may shut down translation during virus infection.
Many RNA viruses employ programmed –1 ribosomal frameshifting (PRF) to expand their coding capacity and optimize production of viral proteins. Here, the authors report structural and biophysical analysis of protein 2A from a cardiovirus, with insights into the mechanism of its PRF-stimulatory function.
Journal Article
Absolute Batman Incorporated
\"Grant Morrison's epic saga is collected here in its entirety, in this beautiful new Absolute edition. Bruce Wayne publicly announces that he is the financial backer of Batman and establishes a worldwide franchise of Batmen that will protect the entire globe. Joining him are strange heroes such as Knight & Squire, El Gaucho and Batwing, as well as allies Nightwing and his own son, Robin. However, it seems that as soon as Batman creates his own crimefighting force, another organization rises to challenge him: Leviathan. As the war between the two forces reaches its apex, Bruce Wayne will face the greatest tragedy of his life. This New York Times best-selling epic is given the Absolute treatment, formatted as an oversized slip cased edition with extra bonus materials. Collects BATMAN, INCORPORATED #1-8, BATMAN, INCORPORATED LEVIATHAN RISES #1, BATMAN, INCORPORATED VOL. 2 #1-13, BATMAN, INCORPORATED SPECIAL #1\"-- Provided by publisher.
BOOK
Structurally heterogeneous ribosomes cooperate in protein synthesis in bacterial cells
Ribosome heterogeneity is a paradigm in biology, pertaining to the existence of structurally distinct populations of ribosomes within a single organism or cell. This concept suggests that structurally distinct pools of ribosomes have different functional properties and may be used to translate specific mRNAs. However, it is unknown to what extent structural heterogeneity reflects genuine functional specialization rather than stochastic variations in ribosome assembly. Here, we address this question by combining cryo-electron microscopy and tomography to observe individual structurally heterogeneous ribosomes in bacterial cells. We show that 70% of ribosomes in
Psychrobacter urativorans
contain a second copy of the ribosomal protein bS20 at a previously unknown binding site on the large ribosomal subunit. We then determine that this second bS20 copy appears to be functionally neutral. This demonstrates that ribosome heterogeneity does not necessarily lead to functional specialization, even when it involves significant variations such as the presence or absence of a ribosomal protein. Instead, we show that heterogeneous ribosomes can cooperate in general protein synthesis rather than specialize in translating discrete populations of mRNA.
Cells can simultaneously produce structurally dissimilar ribosomes, suggesting functional specialization of distinct ribosome populations. Here, the authors show that distinct ribosomes cooperate rather than specialize in protein synthesis.
Journal Article