Perisynaptic Schwann cells of the vertebrate motor endplate bear modified cilia

Perisynaptic Schwann cells (PSCs), descendants of the myelinating Schwann cells, cover the axon terminal of the vertebrate motor endplate of the skeletal muscle fiber. PSCs are assumed to support the function of the axon terminal. This function suggests a net material transport in the direction of the axon terminal. Morphologically it is to be expected that these cells have a cytoskeleton aligned to the axon terminal. Investigations clarifying this statement have not yet been undertaken. From previous investigations we know, however, that the PSCs have a microtubule-organizing center, which is a part of this cytoskeleton. The centrioles of the organizing center may also participate in the formation of a modified cilium structure whose function is unknown. In the present investigation, characteristic ultrastructural features of the modified cilium structure and its relationship to the Golgi apparatus and the axon terminal are presented. A function for the modified cilium structure is discussed.     

Charge,mass and heat transfer interactions in solid oxide fuel cells operated with different fuel gases—A sensitivity analysis

The interaction between charge, heat and mass transfer occurring in SOFCs is investigated applying a finite-volume-based SOFC model. The strong interactions are the consequence of the high degree of integration of different processes (chemical/electrochemical reactions, diffusion, heat and mass transfer) within SOFCs. The understanding of these interactions is a key for the future development and application of SOFCs. The investigation was conducted by means of a sensitivity analysis for two different fuel gases, where one gas features a considerable amount of methane inducing steam reforming reactions as additional disturbance factor in the energy and mass balance system of SOFCs. In order to isolate the impact of the varied model parameters and the according changes in the interactions of charge, mass and heat transfer from side effects, the sensitivity analysis was conducted at constant fuel utilization. It was found that the impact of different fuel gases on the operational conditions of SOFCs dominates geometrical and material-induced phenomena. The power output was most affected by the fuel, followed by the values for the activation polarization activation energy that reflects the employed electrode catalysts activity.     

Chalcone-Supported Cardiac Mesoderm Induction in Human Pluripotent Stem Cells for Heart Muscle Engineering

Human pluripotent stem cells (hPSCs) hold great promise for applications in cell therapy and drug screening in the cardiovascular field. Bone morphogenetic protein 4 (BMP4) is key for early cardiac mesoderm induction in hPSC and subsequent cardiomyocyte derivation. Small-molecular BMP4 mimetics may help to standardize cardiomyocyte derivation from hPSCs. Based on observations that chalcones can stimulate BMP4 signaling pathways, we hypothesized their utility in cardiac mesoderm induction. To test this, we set up a two-tiered screening strategy, (1) for directed differentiation of hPSCs with commercially available chalcones (4’-hydroxychalcone [4’HC] and Isoliquiritigen) and 24 newly synthesized chalcone derivatives, and (2) a functional screen to assess the propensity of the obtained cardiomyocytes to self-organize into contractile engineered human myocardium (EHM). We identified 4’HC, 4-fluoro-4’-methoxychalcone, and 4-fluoro-4’-hydroxychalcone as similarly effective in cardiac mesoderm induction, but only 4’HC as an effective replacement for BMP4 in the derivation of contractile EHM-forming cardiomyocytes.     

Fiber-Reinforced Ceramic-Matrix Composites with a Polysiloxane/Boron-Derived Matrix

A ceramic matrix for carbon-fiber-reinforced ceramic-matrix composites (CMCs) has been developed from polysiloxane/boron mixtures. Complex geometries can be realized by using standard technologies of fiber-reinforced polymer composites. On pyrolysis, the polymer-filler mixture is converted to a ceramic matrix, consisting of silicon carbide, boron carbide, boron nitride, and a silicon oxycarbide (SiOC) glass, without reacting with the carbon fiber. Because of the large volume increase of the boron filler on nitridation (142 vol%), no multiple reinfiltration of the structure is necessary to achieve a dense matrix. Tensile strength and interlaminar shear strength exhibit maxima at a pyrolysis temperature of 1300°C, where extensive fiber pullout is observed. Thermodynamic calculations have been used to evaluate the theoretical qualitative and quantitative phase compositions at equilibrium. Thermoanalytical (thermogravimetry-mass spectroscopy) and structural analysis (X-ray diffractometry) have shown a satisfying coherence with respect to the condensed phases, whereas deviations have been noted with respect to the composition of the gas phase.     

Generation of discrete first‐ and second‐order sensitivities for single shooting

In this work, an approach to the forward generation of discrete first‐ and second‐order sensitivities is proposed. For this purpose, an algorithm has been developed, which can basically be applied to general implicit differential‐algebraic equation (DAE) systems. Moreover, the approach has been tailored to both the generation of directional derivatives and sensitivities with respect to discontinuous control trajectories. The implementation of the method is discussed here for the orthogonal collocation method based on Legendre–Gauss–Radau points and considering the linear implicit DAE type, which arises in problems related to chemical engineering. Lastly, the approach has been applied to three case studies of different complexities. The corresponding performance for the generation of Jacobian and Hessian information is discussed in detail. © 2012 American Institute of Chemical Engineers AIChE J, 58: 3110–3122, 2012     

Clinical Phenotype of PDE6B-Associated Retinitis Pigmentosa

In this retrospective, longitudinal, observational cohort study, we investigated the phenotypic and genotypic features of retinitis pigmentosa associated with variants in the PDE6B gene. Patients underwent clinical examination and genetic testing at a single tertiary referral center, including best-corrected visual acuity (BCVA), kinetic visual field (VF), full-field electroretinography, full-field stimulus threshold, spectral domain optical coherence tomography, and fundus autofluorescence imaging. The genetic testing comprised candidate gene sequencing, inherited retinal disease gene panel sequencing, whole-genome sequencing, and testing for familial variants by Sanger sequencing. Twenty-four patients with mutations in PDE6B from 21 families were included in the study (mean age at the first visit: 32.1 ± 13.5 years). The majority of variants were putative splicing defects (8/23) and missense (7/23) mutations. Seventy-nine percent (38/48) of eyes had no visual acuity impairment at the first visit. Visual acuity impairment was mild in 4% (2/48), moderate in 13% (6/48), and severe in 4% (2/48). BCVA was symmetrical in the right and left eyes. The kinetic VF measurements were highly symmetrical in the right and left eyes, as was the horizontal ellipsoid zone (EZ) width. Regarding the genetic findings, 43% of the PDE6B variants found in our patients were novel. Thus, this study contributed substantially to the PDE6B mutation spectrum. The visual acuity impairment was mild in 83% of eyes, providing a window of opportunity for investigational new drugs. The EZ width was reduced in all patients and was highly symmetric between the eyes, making it a promising outcome measure. We expect these findings to have implications on the design of future PDE6B-related retinitis pigmentosa (RP) clinical trials.     

Phase formation and microstructure during laser sintering and crystallization of a 4.2 MgO·5.0 ZnO·44.1 CaO·26.7 Al<Subscript>2</Subscript>O<Subscript>3</Subscript>·20.0 SiO<Subscript>2</Subscript> glass

In order to produce housings for high-temperature applications, alumina is a highly advantageous material because it has a high chemical durability and withstands high temperatures. If alumina is to be sealed, materials are necessary which have an adapted coefficient of thermal expansion (8.6 × 10^?6 K^?1). If temperature-sensitive components have to be encapsulated, a rapid laser sealing process is highly advantageous. This process requires a glass which can rapidly be crystallized. In this paper, a glass powder with the composition 4.2 MgO·5.0 ZnO·44.1·CaO·26.7 Al₂O₃·20.0 SiO₂ was sintered and subsequently crystallized using a CO₂-laser. As crystalline phases, predominantly a solid solution of akermanite and gehlenite (AGSS) was formed and as phases with minor concentrations Al₂O₃, spinel/gahnite solid solution and ZnO. The AGSS grains have sizes of approximately 5 µm, and Mg and Zn are enriched at the grain boundaries. After sealing at temperatures of 985 and 1135 °C, a similar microstructure and similar grain sizes were observed. The AGSS seems to nucleate at the glass/Al₂O₃ interface but also in the bulk. The AGSS and all other phases do not show a preferred orientation. The resulting coefficients of thermal expansion fit well to that of Al₂O₃.     

Methods for determining regularization for atmospheric retrieval problems

The atmosphere of Earth has already been investigated by several spaceborne instruments, and several further instruments will be launched, e.g., NASA's Earth Observing System Aura platform and the European Space Agency's Environmental Satellite. To stabilize the results in atmospheric retrievals, constraints are used in the iteration process. Therefore hard constraints (discretization of the retrieval grid) and soft constraints (regularization operators) are included in the retrieval. Tikhonov regularization is often used as a soft constraint. In this study, different types of Tikhonov operator were compared, and several new methods were developed to determine the optimal strength of the constraint operationally. The resulting regularization parameters were applied successfully to an ozone retrieval from simulated nadir sounding spectra like those expected to be measured by the Tropospheric Emission Spectrometer, which is part of the Aura platform. Retrievals were characterized by means of estimated error, averaging kernel, vertical resolution, and degrees of freedom.     

Bayesian class discovery in microarray datasets

A novel approach to class discovery in gene expression datasets is presented. In the context of clinical diagnosis, the central goal of class discovery algorithms is to simultaneously find putative (sub-)types of diseases and to identify informative subsets of genes with disease-type specific expression profile. Contrary to many other approaches in the literature, the method presented implements a wrapper strategy for feature selection, in the sense that the features are directly selected by optimizing the discriminative power of the used partitioning algorithm. The usual combinatorial problems associated with wrapper approaches are overcome by a Bayesian inference mechanism. On the technical side, we present an efficient optimization algorithm with guaranteed local convergence property. The only free parameter of the optimization method is selected by a resampling-based stability analysis. Experiments with Leukemia and Lymphoma datasets demonstrate that our method is able to correctly infer partitions and corresponding subsets of genes which both are relevant in a biological sense. Moreover, the frequently observed problem of ambiguities caused by different but equally high-scoring partitions is successfully overcome by the model selection method proposed.