Vortices in the presence of a nonmagnetic atom impurity in 2D XY ferromagnets

Using a model of nonmagnetic impurity potential, we have examined the behavior of planar vortex solutions in the classical two-dimensional XY ferromagnets in the presence of a spin vacancy localized out of the vortex core. Our results show that a spinless atom impurity gives rise to an effective potential that repels the vortex structure.Comment: 6 pages, 2 figures, RevTex

Ligand-Induced Modulation of the Free-Energy Landscape of G Protein-Coupled Receptors Explored by Adaptive Biasing Techniques

Extensive experimental information supports the formation of ligand-specific conformations of G protein-coupled receptors (GPCRs) as a possible molecular basis for their functional selectivity for signaling pathways. Taking advantage of the recently published inactive and active crystal structures of GPCRs, we have implemented an all-atom computational strategy that combines different adaptive biasing techniques to identify ligand-specific conformations along pre-determined activation pathways. Using the prototypic GPCR β2-adrenergic receptor as a suitable test case for validation, we show that ligands with different efficacies (either inverse agonists, neutral antagonists, or agonists) modulate the free-energy landscape of the receptor by shifting the conformational equilibrium towards active or inactive conformations depending on their elicited physiological response. Notably, we provide for the first time a quantitative description of the thermodynamics of the receptor in an explicit atomistic environment, which accounts for the receptor basal activity and the stabilization of different active-like states by differently potent agonists. Structural inspection of these metastable states reveals unique conformations of the receptor that may have been difficult to retrieve experimentally

Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. Funding: Galderma International S.A.S., Paris, France

All for Texas : a story of Texas Liberation

140 p. : map ; 22 c

The Application of the Probabilistic Collocation Method to a Transonic Axial Flow Compressor

In this paper the Probabilistic Collocation method is used for uncertainty quantification of operational uncertainties in a transonic axial flow compressor (i.e. NASA Rotor 37). Compressor rotors are components of a gas turbine that are highly sensitive to operational and geometrical uncertainties. Validation of the Probabilistic Collocation method with a Monte Carlo simulation using 10,000 Latin Hypercube samples demonstrated that the Probabilistic Collocation method can successfully be applied to a turbomachinery case. The flow through the rotor is characterized by a bow shock in front of the leading edge, which interacts with the boundary layer of the next blade. The total pressure profile at the inlet of the rotor is assumed to be uncertain. A symmetric beta distribution was used for the pressure profile, with the standard deviation such that the uncertainty is in the same order of the measurement accuracy reported in literature. The mass flow was shown to be the most sensitive to the uncertainty, while the efficiency is least affected. It was shown by the compressor maps that is important to take the uncertainty in the total pressure profile at the inlet into account. The standard deviation of the static pressure field showed that the largest variation is present near the shock wave and mainly in the region of the strongest shock, which is near the tip of the blade.Aerospace Engineerin