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SummaryIntroduction There are several clinical settings and patient conditions especially in intensive care units, emergency departments, and operating theaters, where the coagulation status of a patient must be known immediately and point-of-care (POC) systems are beneficial due to low time to result. Methods This noninterventional, single-blinded, multicenter study with prospectively collected whole blood samples was performed to evaluate the diagnostic accuracy of the CoaguChek PT Test (POC PT) and CoaguChek aPTT Test (POC aPTT) compared to standard laboratory testing in patients with suspected deficiencies of coagulation factors. Results In total, 390 subjects were included. Both POC PT and POC aPTT showed concordance with the laboratory PT and aPTT. Lot-to-lot variation was below 2% both for POC PT and for POC aPTT. The mean relative difference of capillary blood compared to venous blood was 0.2 % with POC PT and 8.4% with POC aPTT. The coefficients of variation for repeatability of POC PT using whole blood were found to be between 2% and 3.6%. Conclusion Our findings suggest reliable quantitative results with this POC system to support on-site decision-making for patients with suspected deficiencies of coagulation factors in acute and intensive care.

Die vorliegende Arbeit zeigt erste Ergebnisse zur Eigenschaftsoptimierung der gemeinhin schwer umformbaren und hochfesten Aluminiumknetlegierung EN AW7075. Es werden zwei unterschiedliche Umformverfahren betrachtet: Zum Einen wird das ECAP-Verfahren (engl.: equal-channel angular pressing) mit unterschiedlichen Werkzeugen angewendet; zum Andern werden Walzversuche bei zunehmend tieferen Temperaturen (bis –196°C) durchgefuhrt. In beiden Verfahren werden unterschiedliche Umformgrade eingestellt. Durch die gezielte Variation von Umformgrad und Umformtemperatur kann die Legierung 7075 durch ECAP umgeformt werden. Dies fuhrt jedoch nur zu einer geringfugigen Verbesserung der mechanischen Eigenschaften. Durch das Tieftemperaturwalzen kann der Umformgrad noch einmal deutlich gesteigert werden, wobei es zu einer signifikanten Zunahme der Festigkeit sowie der Gleichmasdehnung kommt. Diese Ergebnisse deuten perspektivisch auf die Moglichkeit hin, durch ECAP-Umformung bei tiefen Temperaturen weitere Eigenschaftsverbesserungen zu erhalten. Sowohl das ECAP-Verfahren als auch die Tieftemperaturumformung bieten ein Potenzial zur Herstellung ultrafeinkorniger, hochfester Aluminiumlegierungen mit neuen Eigenschaftsprofilen. The present study shows first results on the optimization of the mechanical properties of the high strength 7075 aluminium alloy, which is generally regarded as hard to deform. Two different deformation/ processing approaches are considered: On the one hand, the equal-channel angular pressing (ECAP) with different types of dies is utilized. On the other hand, (cold) rolling is performed with different, low temperatures (down to –196°C). Various degrees of deformation are realized with both methods. By systematically adjusting the degree of deformation and the deformation temperature, the AA7075 alloy can be processed by ECAP. However, only minor improvements of the mechanical properties can be achieved by this approach. Cryogenic rolling results in a further increase of the degree of deformation, and also of strength and ductility. These results indicate that further improvements of the mechanical properties may well be achieved by ECAP processing at low temperatures. Both ECAP and cryogenic rolling offer a high potential for the production of ultrafine-grained high-strength aluminium alloys with novel properties.

The study deals with the optimisation of medium- to high-strength aluminium wrought alloys. The goal is to define processing routes in order to improve the mechanical properties if compared to their commercial counterparts. It is shown for the Al-Mg-Si and the Al-Cu-Mg-Si system that the application of ECAP enables a significant increase in strength. The strengthening as well as the grain size reduction respectively, benefit from increasing alloying as well as from the degree of aging. It is also shown that the presence of a considerably fine particulate reinforcement hardens the material tremendously during ECAP. The combination of a pre- or post-ECAP heat treatment enables the improvement of the workability on the one hand, reducing the loads on the die, and also gives a better ductility on the other hand. This positive effect is particularly pronounced for low alloying contents and high aging temperatures and can be attributed to the interaction of deformation induced defects and the precipitation activity. The combination of an appropriate set of ECAP parameters (heat treatment condition, ECAP-strain, -temperature, -backpressure) enables the efficient production of outstanding properties. Due to the low workability of AA7075 (Al-Zn-Mg-Cu system) no significant improvement in properties was achieved. (Abstract Copyright [2009], Wiley Periodicals, Inc.) [German] Die Studie befasst sich mit der Eigenschaftsoptimierung verschiedener mittel- und hochfester Aluminiumknetlegierungen. Im Fokus steht die Optimierung von Prozessabfolgen mit denen im Vergleich zu den kommerziell verfuegbaren Referenzzustaenden deutlich bessere mechanische Eigenschaften eingestellt werden koennen. Fuer das Al-Mg-Si- und das Al-Cu-Mg-Si-System wird gezeigt, dass die ECAP-Umformung sehr hohe Festigkeiten ermoeglicht. Je groesser der Legierungsgehalt bzw. Aushaertegrad ist, desto hoehere Festigkeiten und geringere Korngroessen koennen durch ECAP erreicht werden. Ebenso extrem verfestigend wirkt sich das Vorhandensein einer keramischen Verstaerkungskomponente in Partikelform aus. Durch die Kombination der ECAP-Umformung mit einer vor- bzw. nachgelagerten Waermebehandlung kann einerseits die Umformbarkeit verbessert werden, was die Werkzeugbelastungen reduziert, und andererseits die Duktilitaet des Werkstoffes angehoben werden. Dieser positive Effekt wird insbesondere bei niedrigen Legierungsgehalten bzw. hohen Auslagerungstemperaturen beobachtet und kann mit der Wechselwirkung von verformungsinduzierten Gitterdefekten und Ausscheidungen erklaert werden. Durch eine geeignete Wahl der Prozessparameter (Waermebehandlungszustand, ECAP-Umformgrad, -temperatur, -gegendruck) laesst sich so eine optimale Kombination von Festigkeit und Duktilitaet mit herausragenden Eigenschaftswerten sehr wirtschaftlich einstellen. Aufgrund der allgemein schlechten Umformbarkeit der hoechstfesten Legierung EN AW-7075 (Al-Zn-Mg-Cu - System) konnte mit Hilfe der ECAP-Umformung bisher keine signifikante Eigenschaftsverbesserung erzielt werden. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

The Escherichia coli K-12 gene coding for a component of a type II export system was identified and characterized. The HopG protein contains a typical prepilin peptidase cleavage site and has a high degree of homology with proteins PulG, OutG, and ExeG, which are components of type II secretion systems from Klebsiella pneumoniae, Erwinia carotovora, and Aeromonas hydrophila.

In production industry modern machines include a great number of feedback controlled drives. The reliable operation of these mechatronic systems including the requested function of the control loops are essential requirements for failure-free processes. In current systems, the observation of the control-loops is mostly restricted to basic monitoring functions, such as the supervision of limits. Yet, in the process- and facility-automation various methods of control loop performance monitoring (CLPM) have successfully been applied. The implementation and adaptation of these methods into the field of controlling electrical drives is considered to be a great contribution to a higher process reliability and efficiency of machines in production industry. Detecting oscillations automatically in the inner circuits of cascaded control loops is of great importance concerning process reliability and efficiency. The objective of this study is to monitor all major signals within the cascaded position control loop during operation in order to detect disadvantageous oscillations. As a first step, procedures for detecting oscillations were applied to the speed controller of electrical servo-drives.

In einer retrospektiven Studie wurden die klinischen und radiologischen Ergebnisse nach Implantation einer STAR-Sprunggelenkprothese untersucht. 49 Patienten mit einem Durchschnittsalter von 62,5 Jahren wurden zwischen Januar 2000 und September 2004 mit einer Sprunggelenkprothese vom Typ STAR versorgt. Nach durchschnittlich 30,4 Monaten wurden 48 Patienten klinisch und radiologisch nachuntersucht und der Kofoed-Ankle-Score sowie die subjektive Zufriedenheit ermittelt. Der Kofoed-Ankle-Score konnte durch die Operation signifikant von 28 auf 86 Punkte verbessert werden. 90% der Patienten waren mit dem Operationsergebnis subjektiv zufrieden. Die Revisionsrate betrug 10%. Die Fruhergebnisse nach Implantation einer STAR-Sprunggelenkprothese sind ermutigend. Bei korrekter Indikationsstellung kann mit groser Wahrscheinlichkeit eine deutliche Schmerzreduktion und eine hohe Patientenzufriedenheit erzielt werden. Ob sich die OSG-Prothesen im langfristigen Verlauf bewahren, bleibt abzuwarten.

Type-I phosphoinositide 3-kinases (PI3Ks) were characterized as a group of intracellular signalling proteins expressing both protein and lipid kinase activities. Recent studies implicate PI3Ks as mediators of oocyte maturation, but the molecular mechanisms are poorly defined. Here we used the Xenopus oocyte expression system as a model to investigate a possible contribution of the gamma-isoform of PI3K (PI3Kgamma) in the different pathways leading to cell-cycle progression by monitoring the time course of germinal vesicle breakdown (GVBD). Expression of a constitutive active PI3Kgamma (PI3Kgamma-CAAX) induced GVBD and increased the levels of phosphorylated Akt/protein kinase B and mitogen-activated protein kinase (MAPK). Furthermore, PI3Kgamma-CAAX accelerated progesterone-induced GVBD, but had no effect on GVBD induced by insulin. The effects of PI3Kgamma-CAAX could be suppressed by pre-incubation of the oocytes with LY294002, PD98059 or roscovitine, inhibitors of PI3K, MEK (MAPK/extracellular-signal-regulated protein kinase kinase) and cdc2/cyclin B kinase, respectively. Mutants of PI3Kgamma-CAAX, in which either lipid kinase or both lipid and protein kinase activities were altered or eliminated, did not induce significant GVBD. Our data demonstrate that expression of PI3Kgamma in Xenopus oocytes accelerates their progesterone-induced maturation and that lipid kinase activity is required to induce this effect.

ERG (ether-à-go-go-related gene) K+ channels are crucial in human heart physiology (h-ERG), but are also found in neuronal cells and are impaired in Drosophila 'seizure' mutants. Their biophysical properties include the relatively fast kinetics of the inactivation gate and much slower kinetics of the activation gate. In order to elucidate how the complex time- and voltage-dependent activation properties of ERG channels underlies distinct roles in excitability, we investigated different types of ERG channels intrinsically present in cells or heterologously expressed in mammalian cells or Xenopus oocytes. Voltage-dependent activation curves were highly dependent on the features of the eliciting protocols. Only very long preconditioning times produced true steady-state relationships, a fact that has been largely neglected in the past, hampering the comparison of published data on ERG channels. Beyond this technical aspect, the slow activation property of ERG can be responsible for unsuspected physiological roles. We found that around the midpoint of the activation curve, the time constant of ERG open-close kinetics is of the order of 10-15 s. During sustained trains of depolarizations, e.g. those produced in neuronal firing, this leads to the use-dependent accumulation of open-state ERG channels. Accumulation is not observed in a mutant with a fast activation gate. In conclusion, it is well established that other K+ channels (i.e. Ca2+-activated and M) control the spike-frequency adaptation, but our results support the notion that the purely voltage-dependent activation property of ERG channels would allow a slow inhibitory physiological role in rapid neuronal signalling.

Background. Renal functional prognosis is consistently more adverse in male individuals with renal disease. Male animals develop more marked proteinuria and glomerulosclerosis in several models of renal damage. Renal and glomerular growth are important permissive factors for progression of renal failure. Purpose of the study. To investigate the influence of testosterone on renal and glomerular growth. Design. Renal compensatory growth after uninephrectomy (UNX) was chosen as a model of renal growth. The effect of testosterone was assessed in control male, in orchidectomized (OX) male, and in ovariectomized (OV ) female SD rats. Observation time was 10 months. Measurements. Albuminuria by nephelometry; glomerular diameter, glomerular tuft area, renal zonal analysis by quantitative stereology. Testosterone and dihydroxytestosterone by gas chromatography and RIA. Results. In sham-operated male rats, testosterone administration did not change the (left) kidney:bodyweight ratio after uninephrectomy. In contrast, in OX male rats, testosterone administration caused a significant increase in kidney:body-weight ratio and in albuminuria. In these animals, glomerular diameter and outer stripe width were significantly lower in OX rats than in sham-operated controls. Glomerular volume and outer stripe width in OX animals were significantly higher after uninephrectomy (UNX) and were further increased in OX-UNX animals by administration of testosterone. Similar effects on glomerular diameter, cortical width (single) kidney:body-weight ratio were seen when OV female rats were treated with testosterone. Conclusion. After gonadal ablation, administration of testosterone amplifies compensatory glomerular and tubular growth in uninephrectomized male and female rats, i.e. testosterone is a permissive factor. Stimulation of glomerular growth may favour development of glomerulosclerosis.

1. The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K+ channels, including the human ether-a-go-go related gene (HERG) channels, in Xenopus oocytes and tested them for their haloperidol sensitivity. 2. Haloperidol had only little effects on the delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 and IsK, the A-type channel Kv1.4 and the inward rectifier channel Kir2.1 (inhibition6% at 3 microM haloperidol). 3. In contrast, haloperidol blocked HERG channels potently with an IC50 value of approximately 1 microM. Reduced haloperidol, the primary metabolite of haloperidol, produced a block with an IC50 value of 2.6 microM. 4. Haloperidol block was use- and voltage-dependent, suggesting that it binds preferentially to either open or inactivated HERG channels. As haloperidol increased the degree and rate of HERG inactivation, binding to inactivated HERG channels is suggested. 5. The channel mutant HERG S631A has been shown to exhibit greatly reduced C-type inactivation which occurs only at potentials greater than 0 mV. Haloperidol block of HERG S631A at 0 mV was four fold weaker than for HERG wild-type channels. Haloperidol affinity for HERG S631A was increased four fold at +40 mV compared to 0 mV. 6. In summary, the data suggest that HERG channel blockade is involved in the arrhythmogenic side effects of haloperidol. The mechanism of haloperidol block involves binding to inactivated HERG channels.

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with incomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of progression have not been elucidated. To identify some pathogenetic factors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalapril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 animals per group) S-urea at age 150 days was consistently above 300 mg/dl, while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In castrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-211) compared to sham-operated male Han: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uninephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not significantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170; 140-195 in non-enalapril controls), although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S-urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to some extent. Uninephrectomy accelerates renal failure in the rat, but not in humans. On the other hand, in contrast to human ADPKD the renin system is suppressed in the rat model and ACE inhibition does not affect the course of renal failure.

The Han: SPRD Pkd rat mutant is an autosomal dominant rat model with incomplete penetration of polycystic renal transformation. Progressive renal failure occurs in heterozygous male animals. The mechanisms of progression have not been elucidated. To identify some pathogenetic factors involved we subjected male SPRD Pkd rats (and their non-affected littermates as controls) to uninephrectomy (UNX), castration or enalapril treatment. To assess progression S-urea at age 150 days was chosen as endpoint. (i) In uninephrectomized male Han: SPRD Pkd (n = 12 animals per group) S-urea at age 150 days was consistently above 300 mg/dl, while it was 245 mg/dl (191-290) in control Han: SPRD Pkd. (ii) In castrated male Han: SPRD median S urea at 150 days was 100 mg/dl (69-211) compared to sham-operated male Han: SPRD controls (245; 191-290). Castration did not, however, prevent accelerated progression after uninephrectomy. (iii) Enalapril (50 mg/l) in the drinking fluid did not significantly lower median systolic blood pressure (by plethysmography) in animals on 0.2% sodium diet (at 185 days 160 mmHg; 140-170 versus 170; 140-195 in non-enalapril controls), although circulating ACE was significantly inhibited (17 U; 11-33 versus 89; 52-108 in controls). S-urea at age 185 days was not significantly different in the 2 groups. In conclusion, the Han: SPRD Pkd model differs from human ADPKD to some extent. Uninephrectomy accelerates renal failure in the rat, but not in humans. On the other hand, in contrast to human ADPKD the renin system is suppressed in the rat model and ACE inhibition does not affect the course of renal failure.

Since fully-dense ultrafine or nanocrystalline bulk materials can be processed, there has been an increasing scientific interest in several plastic deformation (SPD) procedures, particularly in the last decade. Especially the equal-channel angular pressing (ECAP) has widely been investigated due to its ability of producing billets sufficiently large for industrial applications in functional or structural components. The significant strength increase based on grain refinement is typically accompanied by a significant decrease in ductility and toughness. Within this work, a new methodology was applied for combining ECAP with a subsequent high-temperature short-time aging for the 6063 aluminium alloy. An increase in strength, ductility as well as impact toughness regarding its coarse grained counterparts was reached. More precisely, ultimate tensile strength, elongation to failure and impact toughness were increased by 46%, 21% and 40% respectively. This was observed after only one run of ECAP at room temperature in a solid-solution treated condition and an aging at 170? C for 18 minutes. The regular aging time for maximum strength at 170? C is around 6 hours. Longer exposure times lead to recrystallisation and, as for regular aging, it leads to overaging, both causing a decrease of properties. The work demonstrates a strategy for an efficient processing of commercial Al-Mg-Si alloys with outstanding mechanical properties.

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Behaviour of Mg and Ca content in the blood serum of 28 cattle with grass tetany and hypocalcaemia was evaluated at short time intervals after infusion of 500 ml of a solution A (containing 12 g Mg-adipat and 5 g Ca-gluconate/100 ml aqua dest.) and a solution B (containing 12 g Mg-adipate and 12 g Ca-gluconate/100 ml) respectively. After treatment with the last-named solutions there was evident a considerable increase of Mg-values in the blood serum for a longer period (up to 6 h), also in the case of distinct hypomagnesaemia while Ca-values of the circulating blood declined more quickly. Efficacy of treatment was the better the earlier infusion was performed after occurence of clinical signs. Application of solution B for treatment of grass tetany and paresis with tetany like symptoms is recommended for several reasons. Necessity of assurance the Mg and Ca supply after infusion is emphasized.