Structure and energetics of ammonia clusters (NH3)n (n=3-20) investigated using a rigid-polarizable model derived from ab initio calculations

An analytical model has been developed to describe the interaction between rigid ammonia molecules including the explicit description of induction. The parameters of the model potential were chosen by fitting high quality ab initio data obtained using second-order Moller-Plesset (MP2) perturbation theory and extended basis sets. The description of polarization effects is introduced by using a noniterative form of the "charge on spring model", the latter accounting for more than 95% of the dipole induction energy and of the increased molecular dipole. Putative global minima for (NH3)(n) (n = 3-20) have been optimized using this new model, the structure and energetics of the clusters with n = 3-5 being found in good agreement with previous ab initio results including electronic correlation. Results for larger species have been compared with previous structural studies where only nonpolarizable models were employed. Our model predicts larger binding energies for any cluster size than previous analytical surfaces, the results often suggesting a reorganization of the relative energy ranking and a different structure for the global minimum

Quantifying entropy production in active fluctuations of the hair-cell bundle from time irreversibility and uncertainty relations

We introduce lower bounds for the rate of entropy production of an active stochastic process by quantifying the irreversibility of stochastic traces obtained from mesoscopic degrees of freedom. Our measures of irreversibility reveal signatures of time's arrow and provide bounds for entropy production even in the case of active fluctuations that have no drift. We apply these irreversibility measures to experimental recordings of spontaneous hair-bundle oscillations in mechanosensory hair cells from the ear of the bullfrog. By analyzing the fluctuations of only the tip position of hair bundles, we reveal irreversibility in active oscillations and estimate an associated rate of entropy production of at least similar to 3k (B)/s, on average. Applying thermodynamic uncertainty relations, we predict that measuring both the tip position of the hair bundle and the mechano-electrical transduction current that enters the hair cell leads to tighter lower bounds for the rate of entropy production, up to similar to 10(3) k (B)/s in the oscillatory regime

Lognormal scale invariant random measures

In this article, we consider the continuous analog of the celebrated Mandelbrot star equation with lognormal weights. Mandelbrot introduced this equation to characterize the law of multiplicative cascades. We show existence and uniqueness of measures satisfying the aforementioned continuous equation; these measures fall under the scope of the Gaussian multiplicative chaos theory developed by J.P. Kahane in 1985 (or possibly extensions of this theory). As a by product, we also obtain an explicit characterization of the covariance structure of these measures. We also prove that qualitative properties such as long-range independence or isotropy can be read off the equation.Comment: 31 pages; Probability Theory and Related Fields (2012) electronic versio

Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis

BACKGROUND: Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis. METHODS: To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels. RESULTS: Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients. CONCLUSION: Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used

Three-dimensional CFD simulations with large displacement of the geometries using a connectivity-change moving mesh approach

This paper deals with three-dimensional (3D) numerical simulations involving 3D moving geometries with large displacements on unstructured meshes. Such simulations are of great value to industry, but remain very time-consuming. A robust moving mesh algorithm coupling an elasticity-like mesh deformation solution and mesh optimizations was proposed in previous works, which removes the need for global remeshing when performing large displacements. The optimizations, and in particular generalized edge/face swapping, preserve the initial quality of the mesh throughout the simulation. We propose to integrate an Arbitrary Lagrangian Eulerian compressible flow solver into this process to demonstrate its capabilities in a full CFD computation context. This solver relies on a local enforcement of the discrete geometric conservation law to preserve the order of accuracy of the time integration. The displacement of the geometries is either imposed, or driven by fluid–structure interaction (FSI). In the latter case, the six degrees of freedom approach for rigid bodies is considered. Finally, several 3D imposed-motion and FSI examples are given to validate the proposed approach, both in academic and industrial configurations

Whole lifespan microscopic observation of budding yeast aging through a microfluidic dissection platform

Important insights into aging have been generated with the genetically tractable and short-lived budding yeast. However, it is still impossible today to continuously track cells by high-resolution microscopic imaging (e.g., fluorescent imaging) throughout their entire lifespan. Instead, the field still needs to rely on a 50-y-old laborious and time-consuming method to assess the lifespan of yeast cells and to isolate differentially aged cells for microscopic snapshots via manual dissection of daughter cells from the larger mother cell. Here, we are unique in achieving continuous and high-resolution microscopic imaging of the entire replicative lifespan of single yeast cells. Our microfluidic dissection platform features an optically prealigned single focal plane and an integrated array of soft elastomer-based micropads, used together to allow for trapping of mother cells, removal of daughter cells, monitoring gradual changes in aging, and unprecedented microscopic imaging of the whole aging process. Using the platform, we found remarkable age-associated changes in phenotypes (e.g., that cells can show strikingly differential cell and vacuole morphologies at the moment of their deaths), indicating substantial heterogeneity in cell aging and death. We envision the microfluidic dissection platform to become a major tool in aging research.

Controllable adhesion using field-activated fluids

We demonstrate that field-responsive magnetorheological fluids can be used for variable-strength controllable adhesion. The adhesive performance is measured experimentally in tensile tests (a.k.a. probe-tack experiments) in which the magnetic field is provided by a cylindrical permanent magnet. Increasing the magnetic field strength induces higher peak adhesive forces. We hypothesize that the adhesion mechanism arises from the shear resistance of a yield stress fluid in a thin gap. This hypothesis is supported by comparing the experimentally measured adhesive performance to the response predicted by a lubrication model for a non-Newtonian fluid with a field-dependent yield stress. The model predictions are in agreement with experimental data up to moderate field strengths. Above a critical magnetic field strength the model over-predicts the experimentally measured values indicating non-ideal conditions such as local fluid dewetting from the surface.U.S. Army Research Laboratory (United States. Army Research Office Contract/Grant W911NF-08-C-0055

Targeted re-sequencing of linkage region on 2q21 identifies a novel functional variant for hip and knee osteoarthritis

Objective: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families. Methods: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score. In addition, exome sequencing was performed in three family members from the same family. Results: Genome wide linkage analysis identified a susceptibility locus on chromosome 2q21 with a multipoint LOD score of 3.91. Targeted re-sequencing and subsequent linkage analysis revealed a susceptibility insertion variant rs11446594. It locates in a predicted strong enhancer element region with maximum LOD score 3.42 under dominant model of inheritance. Insertion creates a recognition sequence for ELF3 and HMGA1 transcription factors. Their DNA-binding affinity is highly increased in the presence of A-allele compared to wild type null allele. Conclusion: A potentially novel functional OA susceptibility variant was identified by targeted resequencing. This variant locates in a predicted regulatory site and creates a recognition sequence for ELF3 and HMGA1 transcription factors that are predicted to play a significant role in articular cartilage homeostasis. (C) 2015 The Authors. Published by Elsevier Ltd and Osteoarthritis Research Society International.Peer reviewe