47,338 research outputs found

    Adenosine to inosine editing by ADAR2 requires formation of a ternary complex on the GluR-B R/G site

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    RNA editing by members of the ADAR (adenosine deaminase that acts on RNA) enzyme family involves hydrolytic deamination of adenosine to inosine within the context of a double-stranded pre-mRNA substrate. Editing of the human GluR-B transcript is catalyzed by, the enzyme ADAR2 at the Q/R and R/G sites. We have established a minimal RNA substrate for editing based on the RIG site and have characterized the interaction of ADAR2 with this RNA by gel shift, kinetic, and cross-linking analyses. Gel shift analysis revealed that two complexes are formed on the RNA as protein concentration is increased; the ADAR monomers can be crosslinked to one another in an RNA-dependent fashion. We performed a detailed kinetic study of the editing reaction; the data from this study are consistent with a reaction scheme in which formation of an ADAR2.RNA ternary complex is required for efficient RNA editing and in which formation of this complex is rate determining. These observations suggest that RNA adenosine deaminases function as homodimers on their RNA substrates and may partially explain regulation of RNA editing in these systems

    Functional programming framework for GRworkbench

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    The software tool GRworkbench is an ongoing project in visual, numerical General Relativity at The Australian National University. Recently, the numerical differential geometric engine of GRworkbench has been rewritten using functional programming techniques. By allowing functions to be directly represented as program variables in C++ code, the functional framework enables the mathematical formalism of Differential Geometry to be more closely reflected in GRworkbench . The powerful technique of `automatic differentiation' has replaced numerical differentiation of the metric components, resulting in more accurate derivatives and an order-of-magnitude performance increase for operations relying on differentiation

    Advancing imaging technologies for patients with spinal pain : with a focus on whiplash injury

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    Background: Radiological observations of soft-tissue changes that may relate to clinical symptoms in patients with traumatic and non-traumatic spinal disorders are highly controversial. Studies are often of poor quality and findings are inconsistent. A plethora of evidence suggests some pathoanatomical findings from traditional imaging applications are common in asymptomatic participants across the life span, which further questions the diagnostic, prognostic, and theranostic value of traditional imaging. Although we do not dispute the limited evidence for the clinical importance of most imaging findings, we contend that the disparate findings across studies may in part be due to limitations in the approaches used in assessment and analysis of imaging findings. Purpose: This clinical commentary aimed to (1) briefly detail available imaging guidelines, (2) detail research-based evidence around the clinical use of findings from advanced, but available, imaging applications (eg, fat and water magnetic resonance imaging and magnetization transfer imaging), and (3) introduce how evolving imaging technologies may improve our mechanistic understanding of pain and disability, leading to improved treatments and outcomes. Study Design/Setting: A non-systematic review of the literature is carried out. Methods: A narrative summary (including studies from the authors' own work in whiplash injuries) of the available literature is provided. Results: An emerging body of evidence suggests that the combination of existing imaging sequences or the use of developing imaging technologies in tandem with a good clinical assessment of modifiable risk factors may provide important diagnostic information toward the exploration and development of more informed and effective treatment options for some patients with traumatic neck pain. Conclusions: Advancing imaging technologies may help to explain the seemingly disconnected spectrum of biopsychosocial signs and symptoms of traumatic neck pain

    Optically induced spin to charge transduction in donor spin read-out

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    The proposed read-out configuration D+D- for the Kane Si:P architecture[Nature 393, 133 (1998)] depends on spin-dependent electron tunneling between donors, induced adiabatically by surface gates. However, previous work has shown that since the doubly occupied donor state is so shallow the dwell-time of the read-out state is less than the required time for measurement using a single electron transistor (SET). We propose and analyse single-spin read-out using optically induced spin to charge transduction, and show that the top gate biases, required for qubit selection, are significantly less than those demanded by the Kane scheme, thereby increasing the D+D- lifetime. Implications for singlet-triplet discrimination for electron spin qubits are also discussed.Comment: 8 pages, 10 figures; added reference, corrected typ
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