123,217 research outputs found
Resolvin D1 receptor stereoselectivity and regulation of inflammation and proresolving microRNAs.
Resolution of acute inflammation is an active process that involves the biosynthesis of specialized proresolving lipid mediators. Among them, resolvin D1 (RvD1) actions are mediated by two G protein-coupled receptors (GPCRs), ALX/FPR2 and GPR32, that also regulate specific microRNAs (miRNAs) and their target genes in novel resolution circuits. We report the ligand selectivity of RvD1 activation of ALX/FPR2 and GPR32. In addition to RvD1, its aspirin-triggered epimer and RvD1 analogs each dose dependently and effectively activated ALX/FPR2 and GPR32 in GPCR-overexpressing β-arrestin systems using luminescence and electric cell-substrate impedance sensing. To corroborate these findings in vivo, neutrophil infiltration in self-limited peritonitis was reduced in human ALX/FPR2-overexpressing transgenic mice that was further limited to 50% by RvD1 treatment with as little as 10 ng of RvD1 per mouse. Analysis of miRNA expression revealed that RvD1 administration significantly up-regulated miR-208a and miR-219 in exudates isolated from ALX/FPR2 transgenic mice compared with littermates. Overexpression of miR-208a in human macrophages up-regulated IL-10. In comparison, in ALX/FPR2 knockout mice, RvD1 neither significantly reduced leukocyte infiltration in zymosan-induced peritonitis nor regulated miR-208a and IL-10 in these mice. Together, these results demonstrate the selectivity of RvD1 interactions with receptors ALX/FPR2 and GPR32. Moreover, they establish a new molecular circuit that is operative in the resolution of acute inflammation activated by the proresolving mediator RvD1 involving specific GPCRs and miRNAs
Reconfigurable hyperbolic metamaterial with negative refraction
Relying on the phase change property of GST chalcogenide glass, we demonstrate a novel reconfigurable hyperbolic metamaterial in which the spectral region of negative refraction can be switched from near infra-red to visible
Endoscopic Vein Harvesting Is Associated With Increased Endothelial Microparticle Secretion:A Randomised Ex-Vivo Analysis
Objectives: Endoscopic vein harvesting (EVH) for coronary artery bypass graft surgery has been associated with both positive and negative clinical outcome in a range of studies. In the worst cases, relationships with increased occlusion, myocardial infarction and mortality have been described. EVH could induce endothelial damage leading to loss of graft function. In an attempt to assess endothelial integrity, this study was designed to compare endothelial injury using endothelial microparticle (EMP) secretion as a sensitive marker of dysfunction in vessels harvested using endoscopic versus standard techniques.Methods: A prospective randomised and technician-blinded study design was used to compare standard open technique (SOT, n = 10) vs EVH (n = 5). Once the vein had been harvested, 2 cm was cut after being filled with heparinised patient serum and clipped on either end. All the solution in the vein lumen was washed out using PBS and analysed using flow cytometry to quantify EMPs.Results: There were significantly more Annexin V + CD31 + EMPs in the EVH group compared to the SOT group (mean number of events = 4558.4 vs 86.5, P = 0.001), and also a significant increase in Annexin V + MPs in the EVH group (mean number of events = 4558.4 vs 1238.3, P = 0.027).Conclusion: In this ex-vivo study, EMP secretion was elevated in vessels harvested using endoscopic compared to standard open techniques, which is indicative of endothelial injury. This could contribute to the negative associations with EVH. Long-term clinical data is clearly warranted to translate these findings
A Multi-Language Comparison of Influences on Author Verification using Character N-Grams
We create a new multi-language corpus for author verification based on Wikipedia talkpages, and evaluate the influence that differences in topic and time have on character n-gram author profiles. Topic alignment between two texts is found to increase author verification precision, and an authors writing style is found to change over time, but not more significantly after 3 years than after 1 year.Information ArchitectureWISElectrical Engineering, Mathematics and Computer Scienc
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Gastrointestinal complications associated with catheter ablation for atrial fibrillation
MicroRNAs in resolution of acute inflammation: identification of novel resolvin Dl‐miRNA circuits
Mechanisms controlling resolution of acute inflammation are of wide interest. Here, we investigated microRNAs (miRNAs) in self-limited acute inflammatory exudates and their regulation by resolvin D1 (RvD1). Using real-time PCR analysis, we found in resolving exudates that miR-21, miR-146b, miR-208a, miR-203, miR-142, miR-302d, and miR-219 were selectively regulated (P<0.05) in self-limited murine peritonitis. RvD1 (300 ng/mouse or 15 μg kg(-1)) reduced zymosan-elicited neutrophil infiltration into the peritoneum 25-50% and shortened the resolution interval (R(i)) by ∼4 h. In peritonitis at 12 h, RvD1 up-regulated miR-21, miR-146b, and miR-219 and down-regulated miR-208a in vivo. In human macrophages overexpressing recombinant RvD1 receptors ALX/FPR2 or GPR32, these same miRNAs were significantly regulated (P<0.05) by RvD1 at concentrations as low as 10 nM, recapitulating the in vivo circuit. In addition, RvD1-miRNAs identified herein target cytokines and proteins involved in the immune system, e.g., miR-146b targeted NF-κB signaling, and miR-219 targeted 5-lipoxygenase and reduced leukotriene production. RvD1 also reduced nuclear translocation of NF-κB and SMAD and down-regulated phospho-IκB. Taken together, these results indicate that resolvin-regulated specific miRNAs target genes involved in resolution and establish a novel resolution circuit involving RvD1 receptor-dependent regulation of specific miRNAs
A Prospective Survey Comparing Patients’ Experience of a Nurse-Led Clinic and Consultant-Led Clinic for Surveillance of Patients with Dilatation of the Intrathoracic Aorta
Background: Increasing workload in consultant-led clinics often means patients to wait a long time for clinic appointments. To address this, there is an increasing trend in developing nurse-led clinics across many specialities in the National Health Service. This study aims to assess whether the implementation of a nurse-led clinic in thoracic aortic surgery will optimise the utilisation of health care services and improve overall patient satisfaction. Methods: 80 follow-up patients were asked to complete a questionnaire following their appointment in an aortic clinic, which was led either by a consultant (n = 40) or an aortic specialist nurse (n = 40). All patients seen by a nurse in the clinic were assessed by a consultant surgeon prior to the clinic for suitability. No new patients were seen by a nurse. Any patient with an aortic dimension of 5 cm or greater was seen by the consultant. If there were any complicated clinical features, the patient was seen in the consultant-led clinic. Patients were asked questions about their time spent with the respective health care professionals across 12 categories (punctuality, preparedness, understanding of concerns, clarity of speech, listening, respect, explaining, letting you talk, putting you at ease, emotional support, advice and advice for next follow-up). Patients rated each category using an ordinal scale from 0 - 10. Results: Patient scores were greater in nurse-led clinics compared to consultant-led clinics across a number of categories although only punctuality reached significance (mean 9.2 vs. 6.8, p 0.05). Conclusion: Patients were highly satisfied with the nurse-led clinic across all categories, with greater satisfaction for punctuality. These findings suggest that a nurse-led clinic can be implemented for the management of carefully selected thoracic aortic surgery patient without reduction in patient satisfaction
The vanishing author in computer-generated works: a critical analysis of recent Australian case law
Abstract
The use of software is ubiquitous in the creation of many copyright works, yet the requirement in copyright law that every work have a human author who engages in independent intellectual effort means that its use may prevent copyright subsistence. Several recent Australian cases have refocused attention on authorship as an essential criterion of copyright subsistence, and these cases suggest that much computer-produced output may be authorless and thus lack copyright protection. This article, the first in a two-part series, analyses how each case deals with the question of authorship of computer-produced works and why the use of software diminishes copyright protection for a significant number of computer-generated works. The article critiques the application of conventional notions of human authorship developed in the pre-computer age to modern productions and suggests alternative approaches to authorship that satisfy both the major objectives of copyright policy and the need to adapt to the computer age. The article argues that, without a broader judicial approach to authorship of computer-generated works, Parliament must remedy the lacuna in protection for these ‘authorless’ works. Possible solutions for reform are suggested. In a forthcoming article, the author comprehensively examines those reform proposals
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