Physical activity and lipoprotein metabolism: epidemiological evidence and clinical trials

Twenty cases with patellar luxation in dogs and cats, in which a sulcoplasty and cranialisation of the tuberositas tibiae were performed, were investigated and reviewed retrospectively. Twelve knees were available for follow-up after a mean period of 15 months. Clinical scoring of patients showed eight with no lameness, three with an occasional weightbearing lameness, and one with a frequent weightbearing lameness. The patella was stable and could not be luxated in ten out of twelve cases. Degenerative joint disease was slightly progressive in the postoperative period. It did not impair the outcome of the procedure.     

Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains

From each of two AIDS patients with oropharyngeal candidiasis, five Candida albicans isolates from recurrent episodes of infection which became gradually resistant against fluconazole during antimycotic treatment were analyzed for molecular changes responsible for drug resistance. In both patients, a single C. albicans strain was responsible for the recurrent infections, but the CARE-2 fingerprint pattern of the isolates exhibited minor genetic alterations, indicating that microevolution of the strains took place during fluconazole therapy. In the isolates from patient 1, enhanced mRNA levels of the MDR1 gene, encoding a multiple drug resistance protein from the superfamily of major facilitators, and constitutive high expression of the ERG11 gene, coding for the drug target enzyme sterol 14alpha-demethylase, correlated with a stepwise development of fluconazole resistance. The resistant strains exhibited reduced accumulation of fluconazole and, for the last in the series, a slight increase in drug needed to inhibit sterol 14alpha-demethylation in vitro. In the isolates from patient 2, increased MDR1 mRNA levels and the change from heterozygosity to homozygosity for a mutant form of the ERG11 gene correlated with continuously decreased drug susceptibility. In this series, reduced drug accumulation and increased resistance in the target enzyme activity, sterol 14alpha-demethylase, were observed. These results demonstrate that different molecular mechanisms contribute to a gradual development of fluconazole resistance in C. albicans.     

Model experiments of mixing in steel ladles with continuous addition of the substance to be mixed

The process of alloying steel melts in ladles consists of the three partial steps alloy addition, alloy solution, and alloy mixing. Addition and dissolution together can be simulated approximately by continuous addition of a dissolved substance to be mixed. In this way, the mixing process during alloying can be captured separately. The process was studied in model experiments with continuous addition of NaCl solution to water in a 0.18 m³ cylindrical acrylic glass vessel. The water was stirred by air injection through an eccentrically positioned nozzle in the bottom. The added amount of NaCl was 40 cm³ of a 20% aqueous solution. The addition time was varied. The NaCI concentration in the water vessel was continuously measured with electrical conductivity probes at 12 different positions. From the thus obtained concentration-vs.-time curves, the mixing times were determined. They were studied for stirring gas rates between 100 and 700 cm³/min(STP) and for various addition times of the indicator. The measured mixing times depended on the gas stirring rate. They were also functions of the indicator addition time and decreased with increasing addition time until they became zero or negative. Trials where NaCI was added in form of a melting, NaCI containing ice sphere, yielded negative mixing times, which means that melting is slower than mixing. A theoretical model to describe mixing with continuous addition is presented. Besides the measurement of the mixing process, the three main flow directions of the indicator solution when it leaves the injection nozzle were documented by a video camera. They were associated to the concentration curves measured at the conductivity probes to which the flow was directed. It was found that concentration maxima occurred on the curves when the flow was directed to the respective measuring probe. The duration of the maxima coincided almost always with the duration of the flow directions.     

Phase angle convergence of multiple monophasic action potential recordings precedes spontaneous termination of ventricular fibrillation

Cell-surface expression of endothelial P-selectin increases adhesion and migration of leukocytes and thus may participate in the pathogenesis of reperfusion injury and atherosclerosis. Angiotensin II (Ang II) is also thought to be involved in such disease states. Nitric oxide (NO) downregulates P-selectin expression, and bradykinin (BK) is known to stimulate NO release from endothelial cells. The objective of this study was to determine the effects of 10-min stimulation of cultured human umbilical endothelial cells (HUVECs) with Ang II, BK, or both on P-selectin expression. Ang II (10(-9)-10(-5) M) stimulated P-selectin expression in a concentration-dependent manner, exhibiting a significant effect at 10(-7) M and reaching a plateau at 5 x 10(-5) M. Pretreatment of HUVECs with the AT1 antagonist losartan and the AT1/AT2 antagonist saralasin but not the AT2 antagonist PD123319 (all at 10(-5) M) markedly attenuated the effect of 10(-7) M Ang II. The effects of Ang II on P-selectin expression were not affected by the presence of the NO synthase inhibitor nitro-L-arginine (L-NA, 5 x 10(-4) M) but were abolished by pretreatment with superoxide dismutase (SOD). BK (10(-6) M) abolished the effects of 10(-7) M Ang II on P-selectin expression but did not affect P-selectin expression induced by desmopressin (0.01-10 microM). L-NA obliterated the blunting effect of BK on the Ang II-induced P-selectin membrane expression. BK alone slightly stimulated P-selectin expression, but in the presence of L-NA, BK markedly enhanced P-selectin expression. The effects of BK in the presence of NA were not altered by SOD, indicating that at difference with Ang II, it acts by a mechanism other than superoxide generation. Thus, Ang II acting on AT1 receptors stimulates superoxide generation, which, in turn, induces expression of P-selectin on the endothelial cell surface. BK inhibits the effects of Ang II, likely acting via NO. We conclude that the balance between Ang II, BK, and NO can regulate P-selectin expression on the endothelial cell membrane, an important component of the cascade leading to leukocyte adhesion to the vascular endothelium.     

Optimized evaluation of a large sum of functions using a three-grid approach

The efficient evaluation of numerous values of functions that vary rapidly only in a small part of the region of interest is presented. An optimized algorithm using a sequence of grids with increasing resolution is developed. The algorithm does not make any assumptions about special properties of the function to be evaluated, e.g., symmetry. An additional speed-up is obtained by exploiting the asymptotic behaviour of the functions to be summed. Two applications from high resolution atmospheric radiative transfer modelling in the infrared and microwave are presented. In a third example asymmetric Rautian line shapes important for high resolution molecular spectroscopy are considered. Computational gains by more than two orders of magnitude with relative errors less than 10⁻³ have been achieved.     

Ensuring the long-term functionality of passive auto-catalytic recombiners under operational containment atmosphere conditions—An interdisciplinary investigation

In order to sustain the structural integrity of the containment and other safety relevant components i.e. to avoid a detonation of the hydrogen-air mixture generated during a severe accident in light water reactors, passive auto-catalytic recombiners (PAR) are used for hydrogen removal in many European nuclear power plants (NPP). In 1999, the German NPP Emsland (KKE) was equipped with 58 PAR of AREVA design as an internal accident management measure for a beyond-design accident. Since that time the recombiners are in a stand-by state. As the catalyst elements are exposed to various airborne substances during normal plant operation their function is controlled periodically by testing selected catalyst sheets in a specially designed device. Under the conservative test conditions during this procedure some catalyst sheets showed a delayed responding behavior. First internal analysis gave indication of a beginning fouling on the catalytic surface.The aim of a precautionary investigation performed in cooperation between KKE, Forschungszentrum Juelich and RWTH Aachen University was to characterize the composition of the fouling and to correlate it with potential sources within the containment.In the framework of the investigation the reports of the periodic inspections were analyzed and appropriate sample sheets were selected from the installation. These samples were subjected to a comprehensive chemical surface analysis in order to identify effects like thermal sintering, poisoning or a blocking of the catalytic surface (Baerns, M., 2004. Basic Principles in Applied Catalysis, Springer Verlag). Along with the chemical analysis the catalytic activity of the samples was assessed in several test series in order to correlate the chemically quantified deposition on the catalyst samples with the characteristics of the start-up and the steady-state performance of the recombination reaction. In a final step, possible sources of the fouling were analyzed with regard to their possible contribution to the phenomena. According to the results achieved, measures have been implemented at KKE in order to optimize procedures and to enhance the performance of the PARs.     

Development of an ELISA technique for serodiagnosis of bovine paratuberculosis

In Japan, ortho-phenylphenol (OPP), biphenyl (BP), and thiabendazole (2-(4'-thiazolyl)benzimidazole, TBZ) are commonly used as a postharvest treatment to preserve imported citrus fruits during transport and storage. We used a modification of the alkaline single cell gel electrophoresis (SCG) (Comet) assay to test the in vivo genotoxicity of those agents in mouse stomach, liver, kidney, bladder, lung, brain, and bone marrow. CD-1 male mice were sacrificed 3, 8, and 24 h after oral administration of the test compounds. OPP (2000 mg/kg) induced DNA damage in the stomach, liver, kidney, bladder, and lung, BP (2000 mg/kg) and TBZ (200 mg/kg) induced DNA damage in all the organs studied. For OPP, increased DNA damage peaked at 3-8 h and tended to decrease at 24 h. For BP, on the contrary, increased DNA migration peaked at 24 h. That delay may have been due to the fact that OPP is metabolized by cytochrome 450 and prostaglandin H synthase to phenylbenzoquinone (PBQ), a DNA binding metabolite, and BP is metabolized to PBQ via OPP and m-phenylphenol. The positive response to TBZ, an aneugen, supports the in vivo DNA-damaging action of TBZ.     

Using metrics in management decision making

The amount of code in NASA systems has continued to grow over the past 30 years. This growth brings with it the increased risk of system failure caused by software. Thus, managing the risks inherent in software development and maintenance is becoming a highly visible and important field. The metrics effort within NASA's Mission Operations Directorate has helped managers and engineers better understand their processes and products. The toolkit helps ensure consistent data collection across projects and increases the number and types of analysis options available to project personnel. The decisions made on the basis of metrics analysis have helped project engineers make decisions about project and mission readiness by removing the inherent optimism of “engineering judgment”     

Design of masonry buildings of three‐layered units according to Eurocode 6 / Bemessung von Mauerwerksbauten aus Dreischichtsteinen nach Eurocode 6

In the recent past, the masonry industry has developed many different solutions for optimising the heat protection of buildings. This took place for the building materials, geometric design, but also by development of multiple layered stones in which the components masonry unit, insulation and outer shell have been integrated into a block.