165 research outputs found

    Pupillary anomaly masquerading as a glaucomatous visual field defect: a case report

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    BACKGROUND: Patients are often referred to ophthalmologists with focal visual field defects on routine testing, possibly related to a potential diagnosis of glaucoma. However, examination of the individual patient's ocular characteristics as well as facial characteristics may often reveal a cause of the visual field defect. CASE PRESENTATION: We describe a patient who was found to have a superior visual field defect on routine testing by the optician. Repeat perimetry with pharmacological dilatation of the pupil revealed that the cause of the field defect was related to an eccentric inferiorly displaced pupil, secondary to trauma some years previously. DISCUSSION: Individual patient characteristics, including both ocular, as well as facial, need to be considered, when interpreting any visual field defect

    Autophagy of mucin granules contributes to resolution of airway mucous metaplasia

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    Abstract Exacerbations of muco-obstructive airway diseases such as COPD and asthma are associated with epithelial changes termed mucous metaplasia (MM). Many molecular pathways triggering MM have been identified; however, the factors that regulate resolution are less well understood. We hypothesized that the autophagy pathway is required for resolution of MM by eliminating excess non-secreted intracellular mucin granules. We found increased intracellular levels of mucins Muc5ac and Muc5b in mice deficient in autophagy regulatory protein, Atg16L1, and that this difference was not due to defects in the known baseline or stimulated mucin secretion pathways. Instead, we found that, in mucous secretory cells, Lc3/Lamp1 vesicles colocalized with mucin granules particularly adjacent to the nucleus, suggesting that some granules were being eliminated in the autophagy pathway rather than secreted. Using a mouse model of MM resolution, we found increased lysosomal proteolytic activity that peaked in the days after mucin production began to decline. In purified lysosomal fractions, Atg16L1-deficient mice had reduced proteolytic degradation of Lc3 and Sqstm1 and persistent accumulation of mucin granules associated with impaired resolution of mucous metaplasia. In normal and COPD derived human airway epithelial cells (AECs), activation of autophagy by mTOR inhibition led to a reduction of intracellular mucin granules in AECs. Our findings indicate that during peak and resolution phases of MM, autophagy activity rather than secretion is required for elimination of some remaining mucin granules. Manipulation of autophagy activation offers a therapeutic target to speed resolution of MM in airway disease exacerbations

    Boundary State from Ellwood Invariants

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    Boundary states are given by appropriate linear combinations of Ishibashi states. Starting from any OSFT solution and assuming Ellwood conjecture we show that every coefficient of such a linear combination is given by an Ellwood invariant, computed in a slightly modified theory where it does not trivially vanish by the on-shell condition. Unlike the previous construction of Kiermaier, Okawa and Zwiebach, ours is linear in the string field, it is manifestly gauge invariant and it is also suitable for solutions known only numerically. The correct boundary state is readily reproduced in the case of known analytic solutions and, as an example, we compute the energy momentum tensor of the rolling tachyon from the generalized invariants of the corresponding solution. We also compute the energy density profile of Siegel-gauge multiple lump solutions and show that, as the level increases, it correctly approaches a sum of delta functions. This provides a gauge invariant way of computing the separations between the lower dimensional D-branes.Comment: v2: 63 pages, 14 figures. Major improvements in section 2. Version published in JHE

    Banking union in historical perspective: the initiative of the European Commission in the 1960s-1970s

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    This article shows that planning for the organization of EU banking regulation and supervision did not just appear on the agenda in recent years with discussions over the creation of the eurozone banking union. It unveils a hitherto neglected initiative of the European Commission in the 1960s and early 1970s. Drawing on extensive archival work, this article explains that this initiative, however, rested on a number of different assumptions, and emerged in a much different context. It first explains that the Commission's initial project was not crisis-driven; that it articulated the link between monetary integration and banking regulation; and finally that it did not set out to move the supervisory framework to the supranational level, unlike present-day developments

    Energy from the gauge invariant observables

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    For a classical solution |Psi> in Witten's cubic string field theory, the gauge invariant observable is conjectured to be equal to the difference of the one-point functions of the closed string state corresponding to V, between the trivial vacuum and the one described by |Psi>. For a static solution |Psi>, if V is taken to be the graviton vertex operator with vanishing momentum, the gauge invariant observable is expected to be proportional to the energy of |Psi>. We prove this relation assuming that |Psi> satisfies equation of motion and some regularity conditions. We discuss how this relation can be applied to various solutions obtained recently.Comment: 27 pages; v5: minor revision in section 2, results unchange

    Uncertainties and opportunities in delivering environmentally sustainable surgery:the surgeons' view

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    Surgery is a carbon‐heavy activity and creates a high volume of waste. Surgical teams around the world want to deliver more environmentally sustainable surgery but are unsure what to do and how to create change. There are many interventions available, but resources and time are limited. Capital investment into healthcare and engagement of senior management are challenging. However, frontline teams can change behaviours and drive wider change. Patients have a voice here too, as they would like to ensure their surgery does not harm their local community but are concerned about the effects on them when changes are made. Environmentally sustainable surgery is at the start of its journey. Surgeons need to rapidly upskill their generic knowledge base, identify which measures they can implement locally and take part in national research programmes. Surgical teams in the NHS have the chance to create a world‐leading programme that can bring change to hospitals around the world. This article provides an overview of how surgeons see the surgical team being involved in environmentally sustainable surgery

    Gapless Assembly of Maize Chromosomes Using Long-Read Technologies

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    Creating gapless telomere-to-telomere assemblies of complex genomes is one of the ultimate challenges in genomics. We use two independent assemblies and an optical map-based merging pipeline to produce a maize genome (B73-Ab10) composed of 63 contigs and a contig N50 of 162 Mb. This genome includes gapless assemblies of chromosome 3 (236 Mb) and chromosome 9 (162 Mb), and 53 Mb of the Ab10 meiotic drive haplotype. The data also reveal the internal structure of seven centromeres and five heterochromatic knobs, showing that the major tandem repeat arrays (CentC, knob180, and TR-1) are discontinuous and frequently interspersed with retroelements

    The barley stem rust-resistance gene Rpg1 is a novel disease-resistance gene with homology to receptor kinases

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    Stem rust caused by Puccinia graminis f. sp. tritici was among the most devastating diseases of barley in the northern Great Plains of the U.S. and Canada before the deployment of the stem rust-resistance gene Rpg1 in 1942. Since then, Rpg1 has provided durable protection against stem rust losses in widely grown barley cultivars (cvs.). Extensive efforts to clone Rpg1 by synteny with rice provided excellent flanking markers but failed to yield the gene because it does not seem to exist in rice. Here we report the map-based cloning and characterization of Rpg1. A high-resolution genetic map constructed with 8,518 gametes and a 330-kb bacterial artificial chromosome contig physical map positioned the gene between two crossovers ≈0.21 centimorgan and 110 kb apart. The region including Rpg1 was searched for potential candidate genes by sequencing low-copy probes. Two receptor kinase-like genes were identified. The candidate gene alleles were sequenced from resistant and susceptible cvs. Only one of the candidate genes showed a pattern of apparently functional gene structure in the resistant cvs. and defective gene structure in the susceptible cvs. identifying it as the Rpg1 gene. Rpg1 encodes a receptor kinase-like protein with two tandem protein kinase domains, a novel structure for a plant disease-resistance gene. Thus, it may represent a new class of plant resistance genes
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