Generation of ENU-Induced Mouse Mutants with Hypocholesterolemia: Novel Tools for Dissecting Plasma Lipoprotein Homeostasis

Pathologic plasma lipoprotein cholesterol levels play a key role in the development and pathogenesis of human atherosclerotic cardiovascular diseases. Plasma cholesterol homeostasis is regulated by genetic predispositions and environmental factors. Animal models showing aberrant plasma cholesterol levels are used for the identification and analysis of novel causative genes. Here, we searched for inherited hypocholesterolemia phenotypes in randomly mutant mice which may contribute to the detection of disease protective alleles. In the Munich ENU mouse mutagenesis project, clinical chemistry blood analysis was carried out on more than 15,500 G1 offspring and 230 G3 pedigrees of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to a decreased plasma total cholesterol level. We identified 66 animals consistently showing hypocholesterolemia. Transmission of the altered phenotype to the subsequent generations led to the successful establishment of 14 independent hypocholesterolemic lines. Line-specific differences were detected by clinical chemistry analysis of plasma HDL cholesterol, LDL cholesterol and triglycerides. Thus, we successfully established a novel panel of ENU-derived mutant mouse lines for their use in the identification of alleles selectively influencing the plasma cholesterol homeostasis. Such findings may be subsequently used for humans and other species.     

The impact of fouling on the performance of filter–evaporator combinations

This paper presents results of experiments performed on different combinations of five types of filters of varying efficiencies (MERV4, 6, 8, 11, and 14) and four types of evaporator coils with depths and fin geometries under clean and fouled conditions. The fouled conditions were obtained after injection of 600 g (1612 g/m² of coil face area) of dust upstream of the filter–coil combination, which was meant to simulate a year of operation in the field. The air-side pressure drops of the coils and filters and air-side effective heat transfer coefficients of the coils were determined from the measurements under the clean and fouled conditions. Depending upon the filter and coil, the coil pressure drops increased in the range of 6–30% for an air velocity of 2.54 m/s. The impact was significantly greater for tests performed without an upstream filter (the coil pressure drops increased from 43% to 200%). The largest relative effect of fouling on pressure drop occurs for coils with fewer rows, primarily due to higher fin densities. The impact of fouling on air-side effective heat transfer coefficients was found to be relatively small, which ranged from −14% to 4%. In some cases, heat transfer was actually enhanced due to additional turbulence caused by the presence of dust. However, with large dust deposits, heat transfer is degraded because the dust also acts as insulation and creates an uneven air velocity.     

Design,Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

The natural products rhizopodin and bistramide belong to an elite class of highly potent actin binding agents. They show powerful antiproliferative activities against a range of tumor cell lines, with IC₅₀ values in the low‐nanomolar range. At the molecular level they disrupt the actin cytoskeleton by binding specifically to a few critical sites of G‐actin, resulting in actin filament stabilization. The important biological properties of rhizopodin and bistramide, coupled with their unique and intriguing molecular architectures, render them attractive compounds for further development. However, this is severely hampered by the structural complexity of these metabolites. We initiated an interdisciplinary approach at the interface between molecular modeling, organic synthesis, and chemical biology to support further biological applications. We also wanted to expand structure–activity relationship studies with the goal of accessing simplified analogues with potent biological properties. We report computational analyses of actin–inhibitor interactions involving molecular docking, validated on known actin binding ligands, that show a close match between the crystal and modeled structures. Based on these results, the ligand shape was simplified, and more readily accessible rhizopodin–bistramide mimetics were designed. A flexible and modular strategy was applied for the synthesis of these compounds, enabling diverse access to dramatically simplified rhizopodin–bistramide hybrids. This novel analogue class was analyzed for its antiproliferative and actin binding properties.     

Oberflächenstrukturierung polymerer Fasern durch UV-Laserbestrahlung, 15. Beschreibung des Temperaturfeldes in PETP-Polymeren während und nach der Laserbestrahlung mit einem gepulsten UV-Laser

For understanding the generation of UV laser induced surface structures of PETP polymers the temperature field within the irradiated surface is calculated in dependence on the laser irradiation wavelength (193 nm, 248 nm, 308 nm), pulse time, pulse form, the irradiation intensity and depth, using temperature-independent material data of PETP polymers known from literature. For this purpose the solution function of the one-dimensional heat differential equation is used. Depending on the order of magnitude of the absorption coefficient of the polymer for UV light of different wavelengths, surface temperatures of approx. 16 000°C (193 nm), 11 000°C (248 nm) and 500°C (308 nm) are calculated at the end of the laser pulse. The temperature input within the polymer layer is limited to only a very small penetration depth. For the irradiation with the two laser wavelengths of 193 nm and 248 nm this is less then 0.4 μm. The cooling process is considerably slower, reaching the initial temperature after approx. 4 μs.     

Surface structuring of synthetic fibres by UV laser irradiation. Part III. Surface functionality changes resulting from excimer-laser irradiation

The chemical surface composition accompanying UV-laser induced surface structuring of fibrous materials such as poly(ethylene terephthalate) (PETP) is discussed. Only a few real chemical changes have been investigated up to now (formation of carboxylic groups on PETP, formation of C=O bonds on polypropylene). Much more data exist on the formation of yellow layers on the laser-treated samples, consisting of debris derived from the ablation process. Analysis by laser desorption mass spectroscopy (LD-MS) and XPS confirm the composition of those layers as highly carbonaceous. Methods for using LD-MS for fibre identification and methods for avoiding debris-layer formation are described together with some surface grafting experiments. In some cases excimer irradiation may be used to remove fabrication agents from polymer surfaces. © 1998 SCI.     

A simple approach towards fully stressed design in hyperelasticity exploiting the isoparametric finite element concept

A novel approach towards fully stressed designs in hyperelasticity is discussed leading to closed‐form expressions for the sensitivities of the objective and displacements with respect to design variations. The key idea is the modification of the classical approach coupled with a so‐called design element method offering a lot of parallelism to standard finite element methods. We bypass implicit constraints on dependent quantities and derive an explicit linearly constrained optimization problem solved by means of first‐order procedures. The results obtained with the proposed method are adequate from an engineering point of view though being computed with a simple method. Copyright © 2000 John Wiley & Sons, Ltd.     

Multifunctional FeCo/TiN Multilayer Thin Films with Combined Magnetic and Protective Properties

Coatings with thicknesses ranging from a few nanometer up to several micrometer produced by physical vapor deposition (PVD) processes have been established in engineering technologies since the early 1980s. In particular, magnetron sputtered wear resistance coatings are industrially established and capable to enhance tool lifetimes significantly. However, in cases where optical inspection of a coating in use is not possible, an intrinsic sensor function of the film would be beneficial. Therefore, the development of wear resistant coatings with an integrated sensor functionality based on the insertion of a magnetoelastic ferromagnetic phase is suggested. In combination with appropriate read‐out electronics such a film system would be ready for online monitoring of the coatings' actual state (e.g., strain, temperature, volume loss). This paper focuses on the development of wear resistance coatings which simultaneously supply beneficial mechanical properties as well as ferromagnetic properties optimized for online non‐contact read‐out applications. Multilayer coatings obtained through alternate stacking of magnetron sputtered TiN and FeCo layers with a nominal total thickness of 1000 nm were produced as a model system meeting the above conditions. The bilayer period was varied down to 2.6 nm while the individual layer thickness ratio t_TiN/t_FeCo was determined by the deposition rates and maintained constant at a value of about 3/1. The films were vacuum annealed ex situ in a static magnetic field subsequent to the deposition. The constitution of the as‐deposited and annealed coatings as well as their mechanical (nanohardness, Young's modulus) and magnetic properties (magnetization hysteresis, frequency‐dependent permeability) are described. Finally, the suitability of the coatings for the use in remote‐interrogable wear sensor applications is briefly discussed.