Symptomatic adrenal insufficiency during inhaled corticosteroid treatment

Symptomatic adrenal insufficiency, presenting as hypoglycaemia or poor weight gain, may occur on withdrawal of corticosteroid treatment but has not previously been reported during inhaled corticosteroid treatment. This case series illustrates the occurence of clinically significant adrenal insufficiency in asthmatic children while patients were on inhaled corticosteroid treatment and the unexpected modes of presentation. General practitioners and paediatricians need to be aware that this unusual but acute serious complication may occur in patients treated

Energy Landscape and Global Optimization for a Frustrated Model Protein

The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding. We investigate the energy landscape of this protein using disconnectivity graphs and compare it to a Go model, which is designed to reduce the frustration by removing all non-native attractive interactions. Finding the global minimum on a frustrated energy landscape is a good test of global optimization techniques, and we present calculations evaluating the performance of basin-hopping and genetic algorithms for this system.Comparisons are made with the widely studied 46-residue BLN protein.We show that the energy landscape of the 69-residue BLN protein contains several deep funnels, each of which corresponds to a different β-barrel structure

Topological methods for searching barriers and reaction paths

We present a family of algorithms for the fast determination of reaction paths and barriers in phase space and the computation of the corresponding rates. The method requires the reaction times be large compared to the microscopic time, irrespective of the origin - energetic, entropic, cooperative - of the timescale separation. It lends itself to temperature cycling as in simulated annealing and to activation-relaxation routines. The dynamics is ultimately based on supersymmetry methods used years ago to derive Morse theory. Thus, the formalism automatically incorporates all relevant topological information.Comment: 4 pages, 4 figures, RevTex

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Are there localized saddles behind the heterogeneous dynamics of supercooled liquids?

We numerically study the interplay between heterogeneous dynamics and properties of negatively curved regions of the potential energy surface in a model glassy system. We find that the unstable modes of saddles and quasi-saddles undergo a localization transition close to the Mode-Coupling critical temperature. We also find evidence of a positive spatial correlation between clusters of particles having large displacements in the unstable modes and dynamical heterogeneities.Comment: 7 pages, 3 figures, submitted to Europhys. Let

Local Properties of the Potential Energy Landscape of a Model Glass: Understanding the Low Temperature Anomalies

Though the existence of two-level systems (TLS) is widely accepted to explain low temperature anomalies in the sound absorption, heat capacity, thermal conductivity and other quantities, an exact description of their microscopic nature is still lacking. We performed computer simulations for a binary Lennard-Jones system, using a newly developed algorithm to locate double-well potentials (DWP) and thus two-level systems on a systematic basis. We show that the intrinsic limitations of computer simulations like finite time and finite size problems do not hamper this analysis. We discuss how the DWP are embedded in the total potential energy landscape. It turns out that most DWP are connected to the dynamics of the smaller particles and that these DWP are rather localized. However, DWP related to the larger particles are more collective

Why do gallium clusters have a higher melting point than the bulk?

Density functional molecular dynamical simulations have been performed on Ga$_{17}$ and Ga$_{13}$ clusters to understand the recently observed higher-than-bulk melting temperatures in small gallium clusters [Breaux {\em et al.}, Phys. Rev. Lett. {\bf 91}, 215508 (2003)]. The specific-heat curve, calculated with the multiple-histogram technique, shows the melting temperature to be well above the bulk melting point of 303 K, viz. around 650 K and 1400 K for Ga$_{17}$ and Ga$_{13}$, respectively. The higher-than-bulk melting temperatures are attributed mainly to the covalent bonding in these clusters, in contrast with the covalent-metallic bonding in the bulk.Comment: 4 pages, including 6 figures. accepted for publication in Phys. Rev. Let

Elementary transitions and magnetic correlations in two-dimensional disordered nanoparticle ensembles

The magnetic relaxation processes in disordered two-dimensional ensembles of dipole-coupled magnetic nanoparticles are theoretically investigated by performing numerical simulations. The energy landscape of the system is explored by determining saddle points, adjacent local minima, energy barriers, and the associated minimum energy paths (MEPs) as functions of the structural disorder and particle density. The changes in the magnetic order of the nanostructure along the MEPs connecting adjacent minima are analyzed from a local perspective. In particular, we determine the extension of the correlated region where the directions of the particle magnetic moments vary significantly. It is shown that with increasing degree of disorder the magnetic correlation range decreases, i.e., the elementary relaxation processes become more localized. The distribution of the energy barriers, and their relation to the changes in the magnetic configurations are quantified. Finally, some implications for the long-time magnetic relaxation dynamics of nanostructures are discussed.Comment: 19 pages, 6 figure

Hysteretic Optimization For Spin Glasses

The recently proposed Hysteretic Optimization (HO) procedure is applied to the 1D Ising spin chain with long range interactions. To study its effectiveness, the quality of ground state energies found as a function of the distance dependence exponent, $\sigma$, is assessed. It is found that the transition from an infinite-range to a long-range interaction at $\sigma=0.5$ is accompanied by a sharp decrease in the performance . The transition is signaled by a change in the scaling behavior of the average avalanche size observed during the hysteresis process. This indicates that HO requires the system to be infinite-range, with a high degree of interconnectivity between variables leading to large avalanches, in order to function properly. An analysis of the way auto-correlations evolve during the optimization procedure confirm that the search of phase space is less efficient, with the system becoming effectively stuck in suboptimal configurations much earlier. These observations explain the poor performance that HO obtained for the Edwards-Anderson spin glass on finite-dimensional lattices, and suggest that its usefulness might be limited in many combinatorial optimization problems.Comment: 6 pages, 9 figures. To appear in JSTAT. Author website: http://www.bgoncalves.co

How glassy are orientational dynamics of rodlike molecules near the isotropic-nematic transition?

In an attempt to quantitatively characterize the recently observed slow dynamics in the isotropic and nematic phase of liquid crystals, we investigate the single-particle orientational dynamics of rodlike molecules across the isotropic-nematic transition in computer simulations of a family of model systems of thermotropic liquid crystals. Several remarkable features of glassy dynamics are on display including non-exponential relaxation, dynamical heterogeneity, and non-Arrhenius temperature dependence of the orientational relaxation time. In order to obtain a quantitative measure of glassy dynamics in line with the estbalished methods in supercooled liquids, we construct a relaxation time versus scaled inverse temperature plot, and demonstrate that one can indeed define a 'fragility index' for thermotropic liquid crystals, that depends on density and aspect ratio. The values of the fragility parameter are surprisingly in the range one observed for glass forming liquids. A plausible correlation between the energy landscape features and the observed fragility is discussed.Comment: 7 figures and 8 page