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Patients after coarctation repair still have an increased risk of cardiovascular or cerebrovascular events. This has been explained by the persisting hypertension and alterations in the peripheral vessels. However, involvement of the central vessels such as the retinal arteries is virtually unknown. A total of 34 patients after coarctation repair (22 men and 12 women; 23 to 58 years old, age range 0 to 32 years at surgical repair) and 34 nonhypertensive controls underwent structural and functional retinal vessel analysis. Using structural analysis, the vessel diameters were measured. Using functional analysis, the endothelium-dependent vessel dilation in response to flicker light stimulation was assessed. In the patients after coarctation repair, the retinal arteriolar diameter was significantly reduced compared to that of the controls (median 182 μm, first to third quartile 171 to 197; vs 197 μm, first to third quartile 193 to 206; p <0.001). These findings were independent of the peripheral blood pressure and age at intervention. No differences were found for venules. The functional analysis findings were not different between the patients and controls (maximum dilation 3.5%, first to third quartile 2.1% to 4.5% vs 3.6%, first to third quartile 2.2% to 4.3%; p = 0.81), indicating preserved autoregulative mechanisms. In conclusion, the retinal artery diameter is reduced in patients after coarctation repair, independent of their current blood pressure level and age at intervention. As a structural marker of chronic vessel damage associated with past, current, or future hypertension, retinal arteriolar narrowing has been linked to stroke incidence. These results indicate an involvement of cerebral microcirculation in aortic coarctation, despite timely repair, and might contribute to explain the increased rate of cerebrovascular events in such patients.
Bead-on-plate butt joints of 2.5 mm hot rolled DP600/DP600 and 1.2 mm cold rolled TRIP700/TRIP700 steel sheets were performed using 6 kW CO2 laser beam welding. The welding speed ranged from 1.5 to 3.0 and from 2.1 to 3.9 m/min in DP/DP and TRIP/TRIP steel weldments respectively. A top surface helium gas was used as a shielding gas at a flow rate of 20 l/min. Metallographic examinations and transverse tensile testing (DIN EN 895: 1995) were carried out to characterize the weldments. The formability of base metals and weldments were investigated by standard Erichsen test (DIN EN ISO 20482). It was found that the uniaxial plastic behavior of both DP600 and TRIP700 base metals was in agreement with Swift and modified Mecking–Kocks models respectively. In a perpendicular tensile test to the weld line, all specimens were fractured at the base metal however the strengths were somewhat higher than those of base metal. There was a significant reduction in formability caused by welding of both DP/DP and TRIP/TRIP steel weldments and the formability has been improved with the increase of the welding speed.
Shielding gas influences on laser weldability of tailored blanks of advanced automotive steels
(2010)
The effects of shielding gas types and flow rates on CO2 laser weldability of DP600/TRIP700 steel sheets were studied in this work. The evaluated shielding gases were helium (He), argon (Ar) and different mixtures of He and Ar. Weld penetration, tensile strength and formability (Erichsen test) of laser welds were found to be strongly dependent upon the shielding gas types. The ability of shielding gas in removing plasma plume and thus increasing weld penetration is believed to be closely related to ionization potential and atomic weight which determine the period of plasma formation and disappearance. It was found that the higher helium shielding gas flow rate, the deeper weld penetration and the lower weld width.
C-terminal truncation of a metagenome-derived detergent protease for effective expression in E. coli
(2010)
Recently, a new alkaline protease named HP70 showing highest homology to extracellular serine proteases of Stenotrophomonas maltophilia and Xanthomonas campestris was found in the course of a metagenome screening for detergent proteases (Niehaus et al., submitted for publication). Attempts to efficiently express the enzyme in common expression hosts had failed. This study reports on the realization of overexpression in Escherichia coli after structural modification of HP70. Modelling of HP70 resulted in a two-domain structure, comprising the catalytic domain and a C-terminal domain which includes about 100 amino acids. On the basis of the modelled structure the enzyme was truncated by deletion of most of the C-terminal domain yielding HP70-C477.
This structural modification allowed effective expression of active enzyme using E. coli BL21-Gold as the host. Specific activity of HP70-C477 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 30 ± 5 U/mg compared to 8 ± 1 U/mg of the native enzyme. HP70-C477 was most active at 40 °C and pH 7–11; these conditions are prerequisite for a potential application as detergent enzyme. Determination of kinetic parameters at 40 °C and pH = 9.5 resulted in KM = 0.23 ± 0.01 mM and kcat = 167.5 ± 3.6 s⁻¹. MS-analysis of peptide fragments obtained from incubation of HP70 and HP70-C477 with insulin B indicated that the C-terminal domain influences the cleavage preferences of the enzyme. Washing experiments confirmed the high potential of HP70-C477 as detergent protease.
Increasing Scots pine (Pinus sylvestris L.) mortality has been recently observed in the dry inner valleys of the European Alps. Besides drought, infection with pine mistletoe (Viscum album ssp. austriacum) seems to play an important role in the mortality dynamics of Scots pines, but how mistletoes promote pine decline remains unclear. To verify whether pine mistletoe infection weakens the host via crown degradation, as observed for dwarf mistletoes, we studied the negative effects of pine mistletoe infestation on the photosynthetic tissues and branch growth of pairs of infested and non-infested branches. Pine mistletoe infection leads to crown degradation in its host by reducing the length, the radial increment, the ramification, the needle length and the number of needle years of the infested branches. This massive loss in photosynthetic tissue results in a reduction in primary production and a subsequent decrease in carbohydrate availability. The significant reduction in needle length due to mistletoe infection is an indication for a lower water and nutrient availability in infested branches. Thus, mistletoe infection might lead to a decrease in the availability of water and carbohydrates, the two most important growth factors, which are already shortened due to the chronic drought situation in the area. Therefore, pine mistletoe increases the risk of drought-induced mortality of its host when growing in a xeric environment.
Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained.
Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound.
Purpose
To assess potential cognitive deficits under the influence of static magnetic fields at various field strengths some studies already exist. These studies were not focused on attention as the most vulnerable cognitive function. Additionally, mostly no magnetic resonance imaging (MRI) sequences were performed.
Materials and Methods
In all, 25 right-handed men were enrolled in this study. All subjects underwent one MRI examination of 63 minutes at 1.5 T and one at 7 T within an interval of 10 to 30 days. The order of the examinations was randomized. Subjects were referred to six standardized neuropsychological tests strictly focused on attention immediately before and after each MRI examination. Differences in neuropsychological variables between the timepoints before and after each MRI examination were assessed and P-values were calculated
Results
Only six subtests revealed significant differences between pre- and post-MRI. In these tests the subjects achieved better results in post-MRI testing than in pre-MRI testing (P = 0.013–0.032). The other tests revealed no significant results.
Conclusion
The improvement in post-MRI testing is only explicable as a result of learning effects. MRI examinations, even in ultrahigh-field scanners, do not seem to have any persisting influence on the attention networks of human cognition immediately after exposure.
Short term effects of magnetic resonance imaging on excitability of the motor cortex at 1.5T and 7T
(2010)
Rationale and Objectives
The increasing spread of high-field and ultra-high-field magnetic resonance imaging (MRI) scanners has encouraged new discussion of the safety aspects of MRI. Few studies have been published on possible cognitive effects of MRI examinations. The aim of this study was to examine whether changes are measurable after MRI examinations at 1.5 and 7 T by means of transcranial magnetic stimulation (TMS).
Materials and Methods
TMS was performed in 12 healthy, right-handed male volunteers. First the individual motor threshold was specified, and then the cortical silent period (SP) was measured. Subsequently, the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using standard sequences. The MRI examination was immediately followed by another TMS session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete setting was repeated using a 7-T scanner. Control conditions included lying in the 1.5-T scanner for 63 minutes without scanning and lying in a separate room for 63 minutes. TMS was performed in the same way in each case. For statistical analysis, Wilcoxon's rank test was performed.
Results
Immediately after MRI exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and 7 T. The motor threshold was significantly increased. Fifteen minutes after the examination, the measured value tended toward normal again. Control conditions revealed no significant differences.
Conclusion
MRI examinations lead to a transient and highly significant alteration in cortical excitability. This effect does not seem to depend on the strength of the static magnetic field.
Gas sensor investigation based on a catalytically activated thin-film thermopile for H2O2 detection
(2010)
Paracoccus denitrificans for the effluent recycling during continuous denitrification of liquid food
(2010)
Nitrate is an undesirable component of several foods. A typical case of contamination with high nitrate contents is whey concentrate, containing nitrate in concentrations up to 25 l. The microbiological removal of nitrate by Paracoccus denitrificans under formation of harmless nitrogen in combination with a cell retention reactor is described here. Focus lies on the resource-conserving design of a microbal denitrification process. Two methods are compared. The application of polyvinyl alcohol-immobilized cells, which can be applied several times in whey feed, is compared with the implementation of a two step denitrification system. First, the whey concentrate's nitrate is removed by ion exchange and subsequently the eluent regenerated by microorganisms under their retention by crossflow filtration. Nitrite and nitrate concentrations were determined by reflectometric color measurement with a commercially available Reflectoquant® device. Correction factors for these media had to be determined. During the pilot development, bioreactors from 4 to 250 mg·L-1 and crossflow units with membrane areas from 0.02 to 0.80 m2 were examined. Based on the results of the pilot plants, a scaling for the exemplary process of denitrifying 1,000 tons per day is discussed.
Shakedown analysis of two dimensional structures by an edge-based smoothed finite element method
(2010)
Simultaneous detection of cyanide and heavy metals for environmental analysis by means of µISEs
(2010)
The determination of spacing, edge and end distance requirements for self-tapping screws requires numerous and comprehensive insertion tests. Yet the results of such tests cannot be transferred to other types of screws or even to screws of different diameter because of differences in shape or geometry. To reduce the effort of insertion tests a new method was developed which allows the estimation of required spacings, distances and timber thickness.
Quantifying and minimizing uncertainty is vital for simulating technically and economically successful geothermal reservoirs. To this end, we apply a stochastic modelling sequence, a Monte Carlo study, based on (i) creating an ensemble of possible realizations of a reservoir model, (ii) forward simulation of fluid flow and heat transport, and (iii) constraining post-processing using observed state variables. To generate the ensemble, we use the stochastic algorithm of Sequential Gaussian Simulation and test its potential fitting rock properties, such as thermal conductivity and permeability, of a synthetic reference model and—performing a corresponding forward simulation—state variables such as temperature. The ensemble yields probability distributions of rock properties and state variables at any location inside the reservoir. In addition, we perform a constraining post-processing in order to minimize the uncertainty of the obtained distributions by conditioning the ensemble to observed state variables, in this case temperature. This constraining post-processing works particularly well on systems dominated by fluid flow. The stochastic modelling sequence is applied to a large, steady-state 3-D heat flow model of a reservoir in The Hague, Netherlands. The spatial thermal conductivity distribution is simulated stochastically based on available logging data. Errors of bottom-hole temperatures provide thresholds for the constraining technique performed afterwards. This reduce the temperature uncertainty for the proposed target location significantly from 25 to 12 K (full distribution width) in a depth of 2300 m. Assuming a Gaussian shape of the temperature distribution, the standard deviation is 1.8 K. To allow a more comprehensive approach to quantify uncertainty, we also implement the stochastic simulation of boundary conditions and demonstrate this for the basal specific heat flow in the reservoir of The Hague. As expected, this results in a larger distribution width and hence, a larger, but more realistic uncertainty estimate. However, applying the constraining post-processing the uncertainty is again reduced to the level of the post-processing without stochastic boundary simulation. Thus, constraining post-processing is a suitable tool for reducing uncertainty estimates by observed state variables.
Objectives
Interest in cardiovascular magnetic resonance (CMR) at 7 T is motivated by the expected increase in spatial and temporal resolution, but the method is technically challenging. We examined the feasibility of cardiac chamber quantification at 7 T.
Methods
A stack of short axes covering the left ventricle was obtained in nine healthy male volunteers. At 1.5 T, steady-state free precession (SSFP) and fast gradient echo (FGRE) cine imaging with 7 mm slice thickness (STH) were used. At 7 T, FGRE with 7 mm and 4 mm STH were applied. End-diastolic volume, end-systolic volume, ejection fraction and mass were calculated.
Results
All 7 T examinations provided excellent blood/myocardium contrast for all slice directions. No significant difference was found regarding ejection fraction and cardiac volumes between SSFP at 1.5 T and FGRE at 7 T, while volumes obtained from FGRE at 1.5 T were underestimated. Cardiac mass derived from FGRE at 1.5 and 7 T was larger than obtained from SSFP at 1.5 T. Agreement of volumes and mass between SSFP at 1.5 T and FGRE improved for FGRE at 7 T when combined with an STH reduction to 4 mm.
Conclusions
This pilot study demonstrates that cardiac chamber quantification at 7 T using FGRE is feasible and agrees closely with SSFP at 1.5 T.
Bacterial lipopolysaccharides (endotoxins) show strong biological effects at very low concentrations in human beings and many animals when entering the blood stream. These include affecting structure and function of organs and cells, changing metabolic functions, raising body temperature, triggering the coagulation cascade, modifying hemodynamics and causing septic shock. Because of this toxicity, the removal of even minute amounts is essential for safe parenteral administration of drugs and also for septic shock patients' care. The absence of a general method for endotoxin removal from liquid interfaces urgently requires finding new methods and materials to overcome this gap. Nanostructured carbonized plant parts is a promising material that showed good adsorption properties due to its vast pore network and high surface area. The aim of this study was comparative measurement of endotoxin- and blood proteins-related adsorption rate and adsorption capacity for different carboneous materials produced at different temperatures and under different surface modifications. As a main surface modificator, positively cbarged polymer, polyethileneimine (PEl) was used. Activated carbon materials showed good adsorption properties for LPS and some proteins used in the experiments. During the batch experiments, several techniques (dust removal, autoclaving) were used and optimized for improving the material's adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics. Modification of the surface apparently has not affected hemoglobin binding to the adsorbent's surface. Obtained adsorption isotherms can be used as a powerful tool for designing of future column-based setups for blood purification from LPS, which is especially important for septic shock treatment.