Eggshell Calcification of the Heart

   A case of a patient with extensive egg-shell calcification of the pericardium is presented without signs of constriction. This was imaged by fluoroscopy during an ablation procedure performed for persistent atrial fibrillation.  Rhythmos 2022; 17(1):105-106

Dynamics of Alpha-Helix Formation in the CSAW Model

We study the folding dynamics of polyalanine (Ala$_{20}$), a protein fragment with 20 residues whose native state is a single alpha helix. We use the CSAW model (conditioned self-avoiding walk), which treats the protein molecule as a chain in Brownian motion, with interactions that include hydrophobic forces and internal hydrogen bonding. We find that large scale structures form before small scale structures, and obtain the relevant relaxation times. We find that helix nucleation occurs at two separate points on the protein chain. The evolution of small and large scale structures involve different mechanisms. While the former can be describe by rate equations governing the growth of helical content, the latter is akin to the relaxation of an elastic solid.Comment: 18 pages, 10 figure

Improving statistical power of glaucoma clinical trials using an ensemble of cyclical generative adversarial networks

Albeit spectral-domain OCT (SDOCT) is now in clinical use for glaucoma management, published clinical trials relied on time-domain OCT (TDOCT) which is characterized by low signal-to-noise ratio, leading to low statistical power. For this reason, such trials require large numbers of patients observed over long intervals and become more costly. We propose a probabilistic ensemble model and a cycle-consistent perceptual loss for improving the statistical power of trials utilizing TDOCT. TDOCT are converted to synthesized SDOCT and segmented via Bayesian fusion of an ensemble of GANs. The final retinal nerve fibre layer segmentation is obtained automatically on an averaged synthesized image using label fusion. We benchmark different networks using i) GAN, ii) Wasserstein GAN (WGAN) (iii) GAN + perceptual loss and iv) WGAN + perceptual loss. For training and validation, an independent dataset is used, while testing is performed on the UK Glaucoma Treatment Study (UKGTS), i.e. a TDOCT-based trial. We quantify the statistical power of the measurements obtained with our method, as compared with those derived from the original TDOCT. The results provide new insights into the UKGTS, showing a significantly better separation between treatment arms, while improving the statistical power of TDOCT on par with visual field measurements

Common denominators in the immunobiology of IgG4 autoimmune diseases: What do glomerulonephritis, pemphigus vulgaris, myasthenia gravis, thrombotic thrombocytopenic purpura and autoimmune encephalitis have in common?

IgG4 autoimmune diseases (IgG4-AID) are an emerging group of autoimmune diseases that are caused by pathogenic autoantibodies of the IgG4 subclass. It has only recently been appreciated, that members of this group share relevant immunobiological and therapeutic aspects even though different antigens, tissues and organs are affected: glomerulonephritis (kidney), pemphigus vulgaris (skin), thrombotic thrombocytopenic purpura (hematologic system) muscle-specific kinase (MuSK) in myasthenia gravis (peripheral nervous system) and autoimmune encephalitis (central nervous system) to give some examples. In all these diseases, patients’ IgG4 subclass autoantibodies block protein-protein interactions instead of causing complement mediated tissue injury, patients respond favorably to rituximab and share a genetic predisposition: at least five HLA class II genes have been reported in individual studies to be associated with several different IgG4-AID. This suggests a role for the HLA class II region and specifically the DRβ1 chain for aberrant priming of autoreactive T-cells toward a chronic immune response skewed toward the production of IgG4 subclass autoantibodies. The aim of this review is to provide an update on findings arguing for a common pathogenic mechanism in IgG4-AID in general and to provide hypotheses about the role of distinct HLA haplotypes, T-cells and cytokines in IgG4-AID

CMS Monte Carlo production in the WLCG computing Grid

Monte Carlo production in CMS has received a major boost in performance and scale since the past CHEP06 conference. The production system has been re-engineered in order to incorporate the experience gained in running the previous system and to integrate production with the new CMS event data model, data management system and data processing framework. The system is interfaced to the two major computing Grids used by CMS, the LHC Computing Grid (LCG) and the Open Science Grid (OSG). Operational experience and integration aspects of the new CMS Monte Carlo production system is presented together with an analysis of production statistics. The new system automatically handles job submission, resource monitoring, job queuing, job distribution according to the available resources, data merging, registration of data into the data bookkeeping, data location, data transfer and placement systems. Compared to the previous production system automation, reliability and performance have been considerably improved. A more efficient use of computing resources and a better handling of the inherent Grid unreliability have resulted in an increase of production scale by about an order of magnitude, capable of running in parallel at the order of ten thousand jobs and yielding more than two million events per day

Investigation of routes and funnels in protein folding by free energy functional methods

We use a free energy functional theory to elucidate general properties of heterogeneously ordering, fast folding proteins, and we test our conclusions with lattice simulations. We find that both structural and energetic heterogeneity can lower the free energy barrier to folding. Correlating stronger contact energies with entropically likely contacts of a given native structure lowers the barrier, and anticorrelating the energies has the reverse effect. Designing in relatively mild energetic heterogeneity can eliminate the barrier completely at the transition temperature. Sequences with native energies tuned to fold uniformly, as well as sequences tuned to fold by a single or a few routes, are rare. Sequences with weak native energetic heterogeneity are more common; their folding kinetics is more strongly determined by properties of the native structure. Sequences with different distributions of stability throughout the protein may still be good folders to the same structure. A measure of folding route narrowness is introduced which correlates with rate, and which can give information about the intrinsic biases in ordering due to native topology. This theoretical framework allows us to systematically investigate the coupled effects of energy and topology in protein folding, and to interpret recent experiments which investigate these effects.Comment: 12 pages, 1 figure, to appear in Proc. Natl. Acad. Sc

Mesoscale modeling of combined aerosol and photo-oxidant processes in the Eastern Mediterranean

International audienceParticulate matter and photo-oxidant processes in the Eastern Mediterranean have been studied using the UAM-AERO mesoscale air quality model in conjunction with the NILU-CTM regional model. Meteorological data were obtained from the RAMS prognostic meteorological model. The modeling domain includes the eastern Mediterranean area between the Greek mainland and the island of Crete. The modeling system is applied to study the atmospheric processes in three periods, i.e. 13?16 July 2000, 26?30 July 2000 and 7?14 January 2001. The spatial and temporal distributions of both gaseous and particulate matter pollutants have been extensively studied together with the identification of major emission sources in the area. The modeling results were compared with field data obtained in the same period. The objective of the current modeling work was mainly to apply the UAM-AERO mesoscale model in the eastern Mediterranean in order to assess the performed field campaigns and determine that the applied mesoscale model is fit for this purpose. Comparison of the modeling results with measured data was performed for a number of gaseous and aerosol species. The UAM-AERO model underestimates the PM10 measured concentrations during summer and winter campaigns. Discrepancies between modeled and measured data are attributed to unresolved particulate matter emissions. Particulate matter in the area is mainly composed by sulphate, sea salt and crustal materials, and with significant amounts of nitrate, ammonium and organics. During winter the particulate matter and oxidant concentrations were lower than the summer values

Isomorphs in model molecular liquids

Isomorphs are curves in the phase diagram along which a number of static and dynamic quantities are invariant in reduced units. A liquid has good isomorphs if and only if it is strongly correlating, i.e., the equilibrium virial/potential energy fluctuations are more than 90% correlated in the NVT ensemble. This paper generalizes isomorphs to liquids composed of rigid molecules and study the isomorphs of two systems of small rigid molecules, the asymmetric dumbbell model and the Lewis-Wahnstrom OTP model. In particular, for both systems we find that the isochoric heat capacity, the excess entropy, the reduced molecular center-of-mass self part of the intermediate scattering function, the reduced molecular center-of-mass radial distribution function to a good approximation are invariant along an isomorph. In agreement with theory, we also find that an instantaneous change of temperature and density from an equilibrated state point to another isomorphic state point leads to no relaxation. The isomorphs of the Lewis-Wahnstrom OTP model were found to be more approximative than those of the asymmetric dumbbell model, which is consistent with the OTP model being less strongly correlating. For both models we find "master isomorphs", i.e., isomorphs have identical shape in the virial/potential energy phase diagram.Comment: 20 page

Semi-Analytic Stellar Structure in Scalar-Tensor Gravity

Precision tests of gravity can be used to constrain the properties of hypothetical very light scalar fields, but these tests depend crucially on how macroscopic astrophysical objects couple to the new scalar field. We develop quasi-analytic methods for solving the equations of stellar structure using scalar-tensor gravity, with the goal of seeing how stellar properties depend on assumptions made about the scalar coupling at a microscopic level. We illustrate these methods by applying them to Brans-Dicke scalars, and their generalization in which the scalar-matter coupling is a weak function of the scalar field. The four observable parameters that characterize the fields external to a spherically symmetric star (the stellar radius, R, mass, M, scalar `charge', Q, and the scalar's asymptotic value, phi_infty) are subject to two relations because of the matching to the interior solution, generalizing the usual mass-radius, M(R), relation of General Relativity. We identify how these relations depend on the microscopic scalar couplings, agreeing with earlier workers when comparisons are possible. Explicit analytical solutions are obtained for the instructive toy model of constant-density stars, whose properties we compare to more realistic equations of state for neutron star models.Comment: 39 pages, 9 figure

Three-Particle Correlations in Simple Liquids

We use video microscopy to follow the phase-space trajectory of a two-dimensional colloidal model liquid and calculate three-point correlation functions from the measured particle configurations. Approaching the fluid-solid transition by increasing the strength of the pair-interaction potential, one observes the gradual formation of a crystal-like local order due to triplet correlations, while being still deep inside the fluid phase. Furthermore, we show that in a strongly interacting system the Born-Green equation can be satisfied only with the full triplet correlation function but not with three-body distribution functions obtained from superposing pair-correlations (Kirkwood superposition approximation).Comment: 4 pages, submitted to PRL, experimental paper, 2nd version: Fig.1 and two new paragraphs have been adde