Genetic studies of IgA nephropathy: past, present, and future

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN

Increased cardiovascular risk in rats with primary renal dysfunction; mediating role for vascular endothelial function

Primary chronic kidney disease is associated with high cardiovascular risk. However, the exact mechanisms behind this cardiorenal interaction remain unclear. We investigated the interaction between heart and kidneys in novel animal model for cardiorenal interaction. Normal Wistar rats and Munich Wistar Fromter rats, spontaneously developing renal dysfunction, were subjected to experimental myocardial infarction to induce cardiac dysfunction (CD) and combined cardiorenal dysfunction (CRD), respectively (N = 5–10). Twelve weeks later, cardiac- and renal parameters were evaluated. Cardiac, but not renal dysfunction was exaggerated in CRD. Accelerated cardiac dysfunction in CRD was indicated by decreased cardiac output (CD 109 ± 10 vs. CRD 79 ± 8 ml/min), diastolic dysfunction (E/e′) (CD 26 ± 2 vs. CRD 50 ± 5) and left ventricular overload (LVEDP CD 10.8 ± 2.8 vs. CRD 21.6 ± 1.7 mmHg). Congestion in CRD was confirmed by increased lung and atrial weights, as well as exaggerated right ventricular hypertrophy. Absence of accelerated renal dysfunction, measured by increased proteinuria, was supported by absence of additional focal glomerulosclerosis or further decline of renal blood flow in CRD. Only advanced peripheral endothelial dysfunction, as found in CRD, appeared to correlate with both renal and cardiac dysfunction parameters. Thus, proteinuric rats with myocardial infarction showed accelerated cardiac but not renal dysfunction. As parameters mimic the cardiorenal syndrome, these rats may provide a clinically relevant model to study increased cardiovascular risk due to renal dysfunction. Peripheral endothelial dysfunction was the only parameter that correlated with both renal and cardiac dysfunction, which may indicate a mediating role in cardiorenal interaction

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Bifurcation of magnetorheological film–substrate elastomers subjected to biaxial pre-compression and transverse magnetic fields

International audienceThis work investigates the primary sinusoidal bifurcation wrinkling response of single-and multi-layered magne-torheological elastomer (MRE) film-substrate systems subjected to combined transverse applied magnetic fields and in-plane biaxial pre-compression. A recently proposed continuum model that includes the volume fraction of soft-magnetic particles is employed to analyze the effect of the magnetic properties upon the bifurcation response of the system. The analysis is built in a highly versatile manner using a finite-element discretization approach along the direction of the applied magnetic field and Fourier expansions along the infinite in-plane layer directions. This allows for a seamless investigation of various multi-layered structures. First, we analyze the effect of biaxial pre-compression upon the critical magnetic field for a film-substrate system and for various mechanical stiffness ratios. We observe a kink in the critical magnetic curves and a reflection in the corresponding wave numbers as they cross the equi-biaxial pre-compression regime. Subsequently, we consider a MRE film bonded to a MRE substrate and study the effect of the particle volume fraction ratios in those two parts. As a result, we obtain sharp pattern transitions, i.e., long to short wavelengths changes with only minor perturbations of the applied pre-compression. The presence of a magnetic sub-strate changes qualitatively and quantitatively the bifurcation response of the film/substrate system. Finally, we carry out a data-mining exercise to minimize the critical magnetic field at bifurcation by using three different topologies, i.e., a monolayer, a bilayer and a sandwich film. We find that the topologies resembling closely the monolayer one lead to the lowest critical magnetic fields for a given biaxial pre-compression

Geräuschemissionen von Luft/Wasser Wärmepumpen

Aufgrund der gestiegenen Heizölpreise ist die Nachfrage nach alternativen Heizsystemen in den letzten Jahren stark angestiegen. Eine Möglichkeit sind Wärmepumpen, die sowohl für Innen- und Außenaufstellung verfügbar sind. Akustisch können Wärmepumpen jedoch problematisch sein, da sie in Form von Ventilatoren und Verdichtern auch Lärmquellen enthalten, um z.B. der Außenluft die benötigte Wärmemenge zu entziehen. Am Fraunhofer-Institut für Bauphysik wurden im Rahmen einer Schallleistungsbestimmung Luft/Wasser-Wärmepumpen schalltechnisch untersucht. Ergebnisse der Untersuchung bezüglich der Hauptlärmquellen werden aufgezeigt sowie Verbesserungsmaßnahmen dargestellt

A computational framework for magnetically hard and soft viscoelastic magnetorheological elastomers

International audienceThis work deals with a comprehensive theoretical and numerical framework that allows the modeling of finite strain magnetorheological elastomers (MREs) comprising mechanically soft nonlinear elastic-viscoelastic polymer phases and magnetically hard (i.e. dissipative) or soft (i.e. purely energetic) magnetic phases. The framework is presented in a general manner and is implemented using the finite element method. Two software implementations are developed, one using FEniCS and the other in Abaqus. A detailed analysis of the numerical schemes used to model the surrounding air is made and their pros and cons are discussed. The proposed framework is used to simulate two model geometries that are directly relevant to recent applications of MREs. The first two-dimensional example simulates a mechanically soft beam consisting of a single wavy-chain of hard or soft magnetic particles. The beam is subjected to transverse magnetic actuation loads that induce important vertical deflections. Despite the overall small local strains in the beam, a significant viscoelastic effect is observed when high-rate magnetic fields are applied. A torque model for the particles is also used to analyze the beam geometry and is found to be in relatively good agreement with the rest of the approaches for small actuation fields. The second example discusses the rotation of a three-dimensional ellipsoid embedded in a cubic elastomer domain, while the ensemble lies inside a larger cubic air domain. Non-monotonic uniaxial and rotating magnetic fields are applied leading to complex, non-monotonic rotations of the ellipsoidal particle. The hard and soft magnetic cases exhibit significant differences, whereas viscoelasticity is found to induce strong coupling with the magnetization rotation but not with the dissipative magnetization amplitude. Extensive supplementary material provides all details of our implementations as well as animated visualization of results

An explicit dissipative model for isotropic hard magnetorheological elastomers

Hard magnetorheological elastomers (h-MREs) are essentially two phase composites comprising permanently magnetizable metallic inclusions suspended in a soft elastomeric matrix. This work provides a thermodynamically consistent, microstructurally-guided modeling framework for isotropic, incompressible h-MREs. Energy dissipates in such hard-magnetic composites primarily via ferromagnetic hysteresis in the underlying hard-magnetic particles. The proposed constitutive model is thus developed following the generalized standard materials framework, which necessitates suitable definitions of the energy density and the dissipation potential. Moreover, the proposed model is designed to recover several well-known homogenization results (and bounds) in the purely mechanical and purely magnetic limiting cases. The magneto–mechanical coupling response of the model, in turn, is calibrated with the aid of numerical homogenization estimates under symmetric cyclic loading. The performance of the model is then probed against several other numerical homogenization estimates considering various magneto–mechanical loading paths other than the calibration loading path. Very good agreement between the macroscopic model and the numerical homogenization estimates is observed, especially for stiff to moderately-soft matrix materials. An important outcome of the numerical simulations is the independence of the current magnetization to the stretch part of the deformation gradient. This is taken into account in the model by considering an only rotation-dependent remanent magnetic field as an internal variable. We further show that there is no need for an additional mechanical internal variable. Finally, the model is employed to solve macroscopic boundary value problems involving slender h-MRE structures and the results match excellently with experimental data from literature. Crucial differences are found between uniformly and non-uniformly pre-magnetized h-MREs in terms of their pre-magnetization and the associated self-fields

Magneto-electric coupling in terms of magnetically induced polarization from Analytical estimation of non-local deformation-mediated magneto-electric coupling in soft composites

Plots of magnetically induced polarizations and associated magneto-electric sensitivitie