Magnetic monolayer Li2_{2}N: Density Functional Theory Calculations

Density functional theory (DFT) calculations are used to investigate the electronic and magnetic structures of a two-dimensional (2D) monolayer Li$_{2}$N. It is shown that bulk Li$_{3}$N is a non-magnetic semiconductor. The non-spinpolarized DFT calculations show that $p$ electrons of N in 2D Li$_{2}$N form a narrow band at the Fermi energy $E_{\rm{F}}$ due to a low coordination number, and the density of states at the Fermi energy ($g(E_{\rm{F}}$)) is increased as compared with bulk Li$_{3}$N. The large $g(E_{\rm{F}}$) shows instability towards magnetism in Stoner's mean field model. The spin-polarized calculations reveal that 2D Li$_{2}$N is magnetic without intrinsic or impurity defects. The magnetic moment of 1.0\,$\mu_{\rm{B}}$ in 2D Li$_{2}$N is mainly contributed by the $p_{z}$ electrons of N, and the band structure shows half-metallic behavior. {Dynamic instability in planar Li$_{2}$N monolayer is observed, but a buckled Li$_{2}$N monolayer is found to be dynamically stable.} The ferromagnetic (FM) and antiferromagnetic (AFM) coupling between the N atoms is also investigated to access the exchange field strength. {We found that planar (buckled) 2D Li$_{2}$N is a ferromagnetic material with Curie temperature $T_{c}$ of 161 (572) K.}Comment: Euro Phys. Lett. 2017 (Accepted

Plane Strain Polar Elasticity Of Fibre-Reinforced Functionally Graded Materials and Structures

This study investigates the flexural response of a linearly elastic rectangular strip reinforced in a functionally graded manner by a single family of straight fibres resistant in bending. Fibre bending resistance is associated with the thickness of fibres which, in turn, is considered measurable through use of some intrinsic material length parameter involved in the definition of a corresponding elastic modulus. Solution of the relevant set of governing differential equations is achieved computationally, with the use of a well-established semi-analytical mathematical method. A connection of this solution with its homogeneous fibre-reinforced material counterpart enables the corresponding homogeneous fibrous composite to be regarded as a source of a set of equivalent functionally graded structures, each one of which is formed through inhomogeneous redistribution of the same volume of fibres within the same matrix material. A subsequent stress and couple-stress analysis provides details of the manner in which the flexural response of the polar structural component of interest is affected by certain types of inhomogeneous fibre distribution

The β-blocker Nebivolol Is a GRK/β-arrestin Biased Agonist

Nebivolol, a third generation β-adrenoceptor (β-AR) antagonist (β-blocker), causes vasodilation by inducing nitric oxide (NO) production. The mechanism via which nebivolol induces NO production remains unknown, resulting in the genesis of much of the controversy regarding the pharmacological action of nebivolol. Carvedilol is another β-blocker that induces NO production. A prominent pharmacological mechanism of carvedilol is biased agonism that is independent of Gαs and involves G protein-coupled receptor kinase (GRK)/β-arrestin signaling with downstream activation of the epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase (ERK). Due to the pharmacological similarities between nebivolol and carvedilol, we hypothesized that nebivolol is also a GRK/β-arrestin biased agonist. We tested this hypothesis utilizing mouse embryonic fibroblasts (MEFs) that solely express β2-ARs, and HL-1 cardiac myocytes that express β1- and β2-ARs and no detectable β3-ARs. We confirmed previous reports that nebivolol does not significantly alter cAMP levels and thus is not a classical agonist. Moreover, in both cell types, nebivolol induced rapid internalization of β-ARs indicating that nebivolol is also not a classical β-blocker. Furthermore, nebivolol treatment resulted in a time-dependent phosphorylation of ERK that was indistinguishable from carvedilol and similar in duration, but not amplitude, to isoproterenol. Nebivolol-mediated phosphorylation of ERK was sensitive to propranolol (non-selective β-AR-blocker), AG1478 (EGFR inhibitor), indicating that the signaling emanates from β-ARs and involves the EGFR. Furthermore, in MEFs, nebivolol-mediated phosphorylation of ERK was sensitive to pharmacological inhibition of GRK2 as well as siRNA knockdown of β-arrestin 1/2. Additionally, nebivolol induced redistribution of β-arrestin 2 from a diffuse staining pattern into more intense punctate spots. We conclude that nebivolol is a β2-AR, and likely β1-AR, GRK/β-arrestin biased agonist, which suggests that some of the unique clinically beneficial effects of nebivolol may be due to biased agonism at β1- and/or β2-ARs. © 2013 Erickson et al

Predicting Successful Tapering of Biologic Therapy for Patients with Rheumatoid Arthritis in Remission – Why are we still using clinical remission criteria to inform decisions?

Remission is the optimum treatment target for patients with rheumatoid arthritis. With the advent of biologic therapies, and the use of treat to target strategies, many more patients are achieving remission. Once a patient has achieved a period of sustained remission, there is little to guide subsequent management and patients usually continue treatment long-term. This may be inappropriate. Recent evidence suggests that some patients may be able to reduce or even stop therapy however, the ideal patient profile is yet to be determined. Potential predictors have been identified, however have not entered routine clinical practice. There is a need for robust biomarkers to facilitate the prediction of successful tapering

The Combinatorial World (of Auctions) According to GARP

Revealed preference techniques are used to test whether a data set is compatible with rational behaviour. They are also incorporated as constraints in mechanism design to encourage truthful behaviour in applications such as combinatorial auctions. In the auction setting, we present an efficient combinatorial algorithm to find a virtual valuation function with the optimal (additive) rationality guarantee. Moreover, we show that there exists such a valuation function that both is individually rational and is minimum (that is, it is component-wise dominated by any other individually rational, virtual valuation function that approximately fits the data). Similarly, given upper bound constraints on the valuation function, we show how to fit the maximum virtual valuation function with the optimal additive rationality guarantee. In practice, revealed preference bidding constraints are very demanding. We explain how approximate rationality can be used to create relaxed revealed preference constraints in an auction. We then show how combinatorial methods can be used to implement these relaxed constraints. Worst/best-case welfare guarantees that result from the use of such mechanisms can be quantified via the minimum/maximum virtual valuation function

Diagnostic imaging in congenital adrenal hyperplasia – how does it help?

The phenotypic manifestation of congenital adrenal hyperplasia (CAH) is variable, and this largely depends on the extent of 21-Hydroxylase enzyme deficiency. In non- classic CAH (NCCAH), the clinical features predominantly reflect the androgen excess rather than adrenal insufficiency. In boys, the condition may not present until much later in childhood, where the diagnosis is made following presentation with precocious puberty, features of aldosterone insufficiency, or this condition may be detected during fertility workup Imaging is generally not used in the evaluation of CAH, but may be helpful for the diagnosis, management, and follow-up of these patients. CAH can result in adrenal enlargement in both classic and non-classic forms of adrenal hyperplasia. The so-called adrenal rest tissue may be seen at several sites throughout the body, including the celiac plexus region, broad ligaments, normal ovaries, and testes. Sustained elevation of adrenocorticotropic hormone (ACTH) in patients with CAH has been postulated to cause adrenal rest cells to grow and become functionally active. The discovery of bilateral adrenal enlargement during radiologic evaluation for unrelated disease processes might serve as a mode of presentation for clinically not apparent or non- classical congenital adrenal hyperplasia (NCCAH)

Efficacy of Vancomycin, Teicoplanin and Fusidic Acid as Prophylactic Agents in Prevention of Vascular Graft Infection: An Experimental Study in Rat

AbstractObjectivesTo compare the efficacy of a single prophylactic dose of intra-peritoneal vancomycin and teicoplanin with anti-biotic treated Dacron grafts (vancomycin, teicoplanin, 10 or 40% fusidic acid-soaked grafts) in preventing vascular graft infections in a rat model.DesignProspective, randomized, controlled animal study.Materials and methodsThe graft infections were established in the subcutaneous tissues of 80 female Sprague–Dawley rats by the implantation of Dacron prostheses followed by the topical inoculation with methicillin-resistant Staphylococcus aureus. The study groups were as follows: (1) uncontaminated control group, (2) untreated contaminated group, (3) contaminated group with intra-peritoneal vancomycin, (4) contaminated group with intra-peritoneal teicoplanin, (5) contaminated group received vancomycin-soaked Dacron graft, (6) contaminated group received teicoplanin-soaked Dacron graft, (7) contaminated group received 40% fusidic acid-soaked Dacron graft, and (8) contaminated group received 10% fusidic acid-soaked Dacron graft prophylaxis. The grafts were removed after 7 days and evaluated by a quantitative culture analysis.ResultsNo infection was detected in controls. The untreated contaminated group had a high bacteria count (6.0×104CFU/cm2 Dacron graft). Groups that received intra-peritoneal vancomycin or teicoplanin had less bacterial growth (4.8×103 and 3.9×103CFU/cm2 Dacron graft, respectively). Similarly, the group that received 10% fusidic acid-soaked graft showed less bacterial growth (3.6×103CFU/cm2 Dacron graft). The groups with vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts showed no evidence of infection. Statistical analyses demonstrated that intra-peritoneal prophylactic antibiotic treatment was less effective in inhibiting bacterial growth than high concentration antimicrobial-soaking of grafts.ConclusionThe use of vancomycin-, teicoplanin- and 40% fusidic acid-soaked grafts was effective in preventing primary prosthetic vascular graft infection