20 research outputs found
Microwave Current Imaging in Passive HTS Components by Low-Temperature Laser Scanning Microscopy (LTLSM)
We have used the LTLSM technique for a spatially resolved investigation of
the microwave transport properties, nonlinearities and material inhomogeneities
in an operating coplanar waveguide YBa_2Cu_3O_{7-\delta} (YBCO) microwave
resonator on an LaAlO_3 (LAO) substrate. The influence of twin-domain blocks,
in-plane rotated grains, and micro-cracks in the YBCO film on the nonuniform rf
current distribution were measured with a micrometer-scale spatial resolution.
The impact of the peaked edge currents and rf field penetration into weak links
on the linear device performance were studied as well. The LTLSM capabilities
and its future potential for non-destructive characterization of the microwave
properties of superconducting circuits are discussed.Comment: 8 pages, 9 figures, 2-column format, presented at High Temperature
Superconductors in High Frequency Fields 2004, Journal of Superconductivity
(in press
Mu Insertions Are Repaired by the Double-Strand Break Repair Pathway of Escherichia coli
Mu is both a transposable element and a temperate bacteriophage. During lytic growth, it amplifies its genome by replicative transposition. During infection, it integrates into the Escherichia coli chromosome through a mechanism not requiring extensive DNA replication. In the latter pathway, the transposition intermediate is repaired by transposase-mediated resecting of the 5′ flaps attached to the ends of the incoming Mu genome, followed by filling the remaining 5 bp gaps at each end of the Mu insertion. It is widely assumed that the gaps are repaired by a gap-filling host polymerase. Using the E. coli Keio Collection to screen for mutants defective in recovery of stable Mu insertions, we show in this study that the gaps are repaired by the machinery responsible for the repair of double-strand breaks in E. coli—the replication restart proteins PriA-DnaT and homologous recombination proteins RecABC. We discuss alternate models for recombinational repair of the Mu gaps
Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
Background:
Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.
Methods:
We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.
Findings:
Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group.
Interpretation:
In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes.
Funding:
GlaxoSmithKline
The madness of microbiome: Attempting to find consensus “best practice” for 16S microbiome studies
Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy
Expression of J chain mRNA in duodenal IgA plasma cells in IgA nephropathy. Glomerular IgA in IgA nephropathy (IgAN) is at least in part polymeric, and is thought to derive from the mucosal IgA system in view of the association between mucosal infection and haematuria in this condition. To investigate this hypothesis, an in situ hybridization (ISH) technique was developed for the detection of J chain mRNA, the expression of which has been correlated with the secretion of high level polymeric immunoglobulin (pIg). Endoscopic duodenal biopsies from ten patients and matched controls were examined by: (i) two color immunofluorescence (IF); (ii) ISH; and (iii) combined ISH and IF, to permit simultaneous identification of plasma cell type. IF revealed a reduction in the percentage of IgA plasma cells (P < 0.02) and increased absolute numbers of IgG cells (P < 0.02) in patient biopsies. ISH demonstrated fewer J chain mRNA expressing plasma cells (P < 0.005) with lower signal intensity (P < 0.002) in patients' biopsies compared with controls. Combined ISH and IF confirmed a reduction in J chain mRNA-positive IgA plasma cells in the patient biopsies (P < 0.02). The reduction in J chain mRNA expression in duodenal IgA plasma cells in IgAN argues against the gastrointestinal lamina propria as the source of glomerular pIgA
The forces exerted by aquatic suction feeders on their prey
Successful prey capture by aquatic suction feeders depends on the ability of the predator to generate a flow of water external to the mouth that overcomes any movements and forces that the prey uses to resist the suction flow. Elucidating the nature and magnitude of these forces is a key to understanding what limits suction feeding performance. We identify three potential forces produced by the suction flow field: drag, acceleration reaction and the fluid pressure gradient. Using a mathematical model parametrized with empirical data from feeding bluegill, Lepomis macrochirus, we explore the relative magnitude of these forces under three encounter scenarios with a 5 mm diameter, spherical prey: an immobile mid-water prey; a similar prey that executes an escape response; and a prey item that grips a substratum. Contrary to the almost exclusive emphasis on drag in the suction feeding literature, it made a minor contribution to the total forces in all three cases. In all three scenarios, the pressure gradient is the largest of the three forces. These results are important because previous researchers have emphasized drag and have not explicitly recognized a role for the pressure gradient force in suction feeding. The simulations suggest previously unrecognized mechanisms that suction feeders can use to enhance the forces that they exert, by increasing the steepness of the pressure gradient that the prey item is exposed to. This can be accomplished either by increasing the rate of increase in fluid velocity or by restricting the size of the mouth aperture, which creates a steeper spatial gradient in pressure
The hydrology and long-term geomorphic significance of a flash flood in the Cairngorm mountains, Scotland
Detection of active proteasome structures in brain extracts: proteasome features of August rat brain with violations in monoamine metabolism
Just imaginary: delimiting social inclusion in higher education
This paper explores the notion of a ‘just imaginary’ for social inclusion in higher education. It responds to the current strategy of OECD nations to expand higher education and increase graduate numbers, as a way of securing a competitive advantage in the global knowledge economy. The Australian higher education system provides the case for analysis. Three dilemmas for social inclusion policy in this context are identified: questions of sustainability, aspiration and opportunity. The paper argues that while social inclusion policy has ‘first-order’ effects in higher education, a just imaginary is required for more inclusive ‘second-order’ effects to be realized. It concludes that transformation of the current imaginary will require a more robust theorization of relations between social inclusion and higher education, to give new and unifying meaning to existing practices and to generate new ones. Short of this, social inclusion may be little more than just imaginary