Effect of the laser fluence on the microstructure and the relating magnetic properties of BaFe₁₂O₁₉ films grown on YSZ(111) by PLD for optimized perpendicular recording

High-quality BaFe$_{12}$O$_{19}$ (BaM) films with high uniaxial anisotropy fields of H$_A$ = 17.5 and 18.5 kOe were obtained by pulsed laser deposition (PLD) at two fluences of 1.5 and 5.1 J/cm$^2$ on YSZ(111) substrate, using a platinum interlayer for reducing lattice mismatch. We demonstrated that the microstructure, morphology, and stoichiometry of the hexaferrite BaFe$_{12}$O$_{19}$ films can be affected by raising the corresponding energy per pulse from 25 to 75 mJ. However, we also concluded that the increase of fluence leads to the formation of a non-stoichiometric BaM film through two nucleation steps and an output growth of small grains in addition to the increase of the defect density. In turn, this has contributed to the enhancement of the coercive field from H$_c$ = 1769 Oe to H$_c$ = 2166 Oe as it is required for the improvement of perpendicular recording resolution. We found that both the lateral coherent block size and misorientation of mosaic blocks are remarkably affected by the growth kinetics, which itself depends on the energy per pulse. For a deep understanding of the effect of laser fluence on the microstructure, chemical composition, and on the magnetic properties of thin BaM films, the results of complementary methods are combined. These methods comprise high-resolution X-ray diffraction, atomic force microscopy, high-resolution transmission electron microscopy (TEM), scanning TEM combined with energy-dispersive X-ray spectroscopy, and vibrating sample magnetometer

Proteostasis regulators modulate proteasomal activity and gene expression to attenuate multiple phenotypes in Fabry disease

The lysosomal storage disorder Fabry disease is characterized by a deficiency of the lysosomal enzyme \u3b1-Galactosidase A. The observation that missense variants in the encoding GLA gene often lead to structural destabilization, endoplasmic reticulum retention and proteasomal degradation of the misfolded, but otherwise catalytically functional enzyme has resulted in the exploration of alternative therapeutic approaches. In this context, we have investigated proteostasis regulators (PRs) for their potential to increase cellular enzyme activity, and to reduce the disease-specific accumulation of the biomarker globotriaosylsphingosine in patient-derived cell culture. The PRs also acted synergistically with the clinically approved 1-deoxygalactonojirimycine, demonstrating the potential of combination treatment in a therapeutic application. Extensive characterization of the effective PRs revealed inhibition of the proteasome and elevation of GLA gene expression as paramount effects. Further analysis of transcriptional patterns of the PRs exposed a variety of genes involved in proteostasis as potential modulators. We propose that addressing proteostasis is an effective approach to discover new therapeutic targets for diseases involving folding and trafficking-deficient protein mutants

Universality and beyond in Optical Microcavity Billiards with Source-Induced Dynamics

Optical microcavity billiards are a paradigm of a mesoscopic model system for quantum chaos. We demonstrate the action and origin of ray-wave correspondence in real and phase space using far-field emission characteristics and Husimi functions. Whereas universality induced by the invariant-measure dominated far-field emission is known to be a feature shaping the properties of many lasing optical microcavities, the situation changes in the presence of sources that we discuss here. We investigate the source-induced dynamics and the resulting limits of universality while we find ray-picture results to remain a useful tool in order to understand the wave behaviour of optical microcavities with sources. We demonstrate the source-induced dynamics in phase space from the source ignition until a stationary regime is reached comparing results from ray, ray-with-phase, and wave simulations and explore ray–wave correspondence

Universality and beyond in Optical Microcavity Billiards with Source-Induced Dynamics

Optical microcavity billiards are a paradigm of a mesoscopic model system for quantum chaos. We demonstrate the action and origin of ray-wave correspondence in real and phase space using far-field emission characteristics and Husimi functions. Whereas universality induced by the invariant-measure dominated far-field emission is known to be a feature shaping the properties of many lasing optical microcavities, the situation changes in the presence of sources that we discuss here. We investigate the source-induced dynamics and the resulting limits of universality while we find ray-picture results to remain a useful tool in order to understand the wave behaviour of optical microcavities with sources. We demonstrate the source-induced dynamics in phase space from the source ignition until a stationary regime is reached comparing results from ray, ray-with-phase, and wave simulations and explore ray–wave correspondence

Trajectory tracing dynamics in anisotropic microcavities

Ray-wave correspondence has proven a powerful tool in mesoscopic optics, in particular in the description of deformed microdisc cavities with a versatile application potential ranging from microlasers to sensors. New material classes such as graphene-based systems have enriched the field by adding Dirac Fermion optics as well as anisotropic material properties as further system parameters. The trigonally warped dispersion relation in bilayer-graphene billiards generalizes the concept of birefringence and opens unconventional ways of trajectory control in the interplay of dispersion relation and the cavity geometry as we illustrate in this contribution

Biocompatible, 3D Printable Magnetic Soft Actuators – Ink Formulation, Rheological Characterization and Hydrogel Actuator Prototypes

3D printable inks for the preparation of magnetic hydrogel actuators are difficult to formulate because magnetic nanoparticles tend to aggregate without stabilization through other ink components. At the same time, such inks need to be shear-thinning and recover their high viscosity state sufficiently fast to be suitable for the printing process. Here, the use of chitosan as dispersing agent for Fe2O3 nanoparticles is reported. Combined with Pluronic F127 as a rheology modifier and acrylamide as the base monomer, thermoresponsive and shear-thinning magnetic inks containing well-dispersed particles are obtained. The ink viscosity is tuned over two orders of magnitude by varying the chitosan and Pluronics F127 content. 3D-printed shapes with good shape fidelity are obtained at a print bed temperature of 50 °C, where aggregation of the Pluoronics F127 micelles occurs. This leads to a fast recovery of the high viscosity state of the material, so that the printed shape can then be locked in by UV cross-linking. This treatment yielded magneto-responsive prototypes which are promising for soft robotics applications. Thanks to the simplicity of the ink formulation, it is easily transferable also to nonspecialist laboratories, and the concept is potentially applicable also to other types of nanoparticles

Biocompatible, 3D Printable Magnetic Soft Actuators – Ink Formulation, Rheological Characterization and Hydrogel Actuator Prototypes

Abstract 3D printable inks for the preparation of magnetic hydrogel actuators are difficult to formulate because magnetic nanoparticles tend to aggregate without stabilization through other ink components. At the same time, such inks need to be shear‐thinning and recover their high viscosity state sufficiently fast to be suitable for the printing process. Here, the use of chitosan as dispersing agent for Fe2O3 nanoparticles is reported. Combined with Pluronic F127 as a rheology modifier and acrylamide as the base monomer, thermoresponsive and shear‐thinning magnetic inks containing well‐dispersed particles are obtained. The ink viscosity is tuned over two orders of magnitude by varying the chitosan and Pluronics F127 content. 3D‐printed shapes with good shape fidelity are obtained at a print bed temperature of 50 °C, where aggregation of the Pluoronics F127 micelles occurs. This leads to a fast recovery of the high viscosity state of the material, so that the printed shape can then be locked in by UV cross‐linking. This treatment yielded magneto‐responsive prototypes which are promising for soft robotics applications. Thanks to the simplicity of the ink formulation, it is easily transferable also to nonspecialist laboratories, and the concept is potentially applicable also to other types of nanoparticles

In vitro enzyme measurement to test pharmacological chaperone responsiveness in fabry and pompe disease

The use of personalized medicine to treat rare monogenic diseases like lysosomal storage disorders (LSDs) is challenged by complex clinical trial designs, high costs, and low patient numbers. Hundreds of mutant alleles are implicated in most of the LSDs. The diseases are typically classified into 2 to 3 different clinical types according to severity. Moreover, molecular characterization of the genotype can help predict clinical outcomes and inform patient care. Therefore, we developed a simple cell culture assay based on HEK293H cells heterologously over-expressing the mutations identified in Fabry and Pompe disease. A similar assay has recently been introduced as a preclinical test to identify amenable mutations for Pharmacological Chaperone Therapy (PCT) in Fabry disease. This manuscript describes an amended cell culture assay which enables rapid phenotypic assessment of allelic variants in Fabry and Pompe disease to identify eligible patients for PCT and may aid in the development of novel pharmacochaperones

Influence of left atrial size on P-wave morphology : differential effects of dilation and hypertrophy

Aims: Chronic left atrial enlargement (LAE) increases the risk of atrial fibrillation. Electrocardiogram (ECG) criteria might provide a means to diagnose LAE and identify patients at risk; however, current criteria perform poorly. We seek to characterize the potentially differential effects of atrial dilation vs. hypertrophy on the ECG P-wave. Methods and results: We predict effects on the P-wave of (i) left atrial dilation (LAD), i.e. an increase of LA cavity volume without an increase in myocardial volume, (ii) left atrial concentric hypertrophy (LACH), i.e. a thickened myocardial wall, and (iii) a combination of the two. We performed a computational study in a cohort of 72 anatomical variants, derived from four human atrial anatomies. To model LAD, pressure was applied to the LA endocardium increasing cavity volume by up to 100%. For LACH, the LA wall was thickened by up to 3.3 mm. P-waves were derived by simulating atrial excitation propagation and computing the body surface ECG. The sensitivity regarding changes beyond purely anatomical effects was analysed by altering conduction velocity by 25% in 96 additional model variants. Left atrial dilation prolonged P-wave duration (PWd) in two of four subjects; in one subject a shortening, and in the other a variable change were seen. Left atrial concentric hypertrophy, in contrast, consistently increased P-wave terminal force in lead V1 (PTF-V1) in all subjects through an enlarged amplitude while PWd was unaffected. Combined hypertrophy and dilation generally enhanced the effect of hypertrophy on PTF-V1. Conclusion: Isolated LAD has moderate effects on the currently used P-wave criteria, explaining the limited utility of PWd and PTF-V1 in detecting LAE in clinical practice. In contrast, PTF-V1 may be a more sensitive indicator of LA myocardial hypertrophy

ADAM23 promotes neuronal differentiation of human neural progenitor cells

Abstract Background ADAM23 is widely expressed in the embryonic central nervous system and plays an important role in tissue formation. Results In this study, we showed that ADAM23 contributes to cell survival and is involved in neuronal differentiation during the differentiation of human neural progenitor cells (hNPCs). Upregulation of ADAM23 in hNPCs was found to increase the number of neurons and the length of neurite, while its downregulation decreases them and triggers cell apoptosis. RNA microarray analysis revealed mechanistic insights into genes and pathways that may become involved in multiple cellular processes upon up- or downregulation of ADAM23. Conclusions Our results suggest that ADAM23 regulates neuronal differentiation by triggering specific signaling pathways during hNPC differentiation