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Thrombin is the pivotal enzyme in the biochemistry of secondary hemostasis crucial to maintaining homeostasis of hemostasis. In contrast to routine coagulation tests (PT or aPTT) or procoagulant or anticoagulant factor assays (e.g. fibrinogen, factor VIII, antithrombin or protein C), the thrombin generation assay (TGA), also named thrombin generation test (TGT) is a so-called "global assay" that provides a picture of the hemostasis balance though a continuous and simultaneous measurement of thrombin formation and inhibition. First described in the early 1950s, as a manual assay, efforts have been made in order to standardize and automate the assay to offer researchers, clinical laboratories and the pharmaceutical industry a versatile tool covering a wide range of clinical and non-clinical applications. This review describes technical options offered to properly run TGA, including a review of preanalytical and analytical items, performance, interpretation, and applications in physiology research and pharmacy.

Determining patient's coagulation profile, i.e. detecting a bleeding tendency or the opposite, a thrombotic risk, is crucial for clinicians in many situations. Routine coagulation assays and even more specialized tests may not allow a relevant characterization of the hemostatic balance. In contrast, thrombin generation assay (TGA) is a global assay allowing the dynamic continuous and simultaneous recording of the combined effects of both thrombin generation and thrombin inactivation. TGA thus reflects the result of procoagulant and anticoagulant activities in blood and plasma. Because of this unique feature, TGA has been widely used in a wide array of settings from both research, clinical and pharmaceutical perspectives. This includes diagnosis, prognosis, prophylaxis, and treatment of inherited and acquired bleeding and thrombotic disorders. In addition, TGA has been shown to provide relevant information for the diagnosis of coagulopathies induced by infectious diseases, comprising also disturbance of the coagulation system in COVID-19, or for the assessment of early recurrence in breast cancer. This review article aims to document most clinical applications of TGA.

Understanding the isomeric behavior of active ingredients in the soil and water environment is the first and a major part of deriving an exposure assessment. Whilst a variety of approaches have been taken previously, with the new regulatory framework for the risk assessment of isomeric plant protection compounds recently published by EFSA, (European Food Safety Authority) there will in future be a more consistent approach which has been taken here. For indaziflam (IAF), the alkylazine, cross spectrum residual herbicide which has a cellulose biosynthesis inhibition mode of action, there was no published data on the isomeric degradation behavior in soil and water. The results of measuring the isomeric stability of [14C]-radiolabeled 437-IAF, the major stereoisomer of indaziflam (AE 1170437, [1R,2S,6R] configuration) during its degradation in an aerobic soil metabolism study with four EU soils, an aerobic aquatic metabolism study with two natural water/sediment test systems, as well as an aqueous photolysis study are reported. To sum up, it was shown that in the different environmental conditions under abiotic as well as biotic degradation processes, indaziflam was not subject to isomeric interconversion to diastereoisomers 435-IAF (RRR), 438-IAF (RSS), or 439-IAF (SSR). Thus, all three chiral centers of indaziflam can be considered isomerically stable. In addition, no isomeric interconversion was observed at the 1-fluoroethyl position for the major degradation products IAF-indanone and IAF-carboxylic acid to the RSS-configuration as well as IAF-diaminotriazine from the R- to the S-configuration.

We have developed innovative multilayer composite grids as engineered materials, which are produced in the form of grid strip in a single, highly efficient, multistage electrodeposition process. In the present paper, we are reporting, how the individual requirements for grid properties can be satisfied and optimised individually and then combined simultaneously to an overall optimum in this new family of composite grid materials. The multilayer composite materials are composed of different layers of different structures and properties, which can provide a combination of different functional properties to satisfy a more demanding total specification of mechanical behaviour, electrical performance, corrosion resistance and cycling behaviour. The paper deals with the improvement of these properties in detail and with the overall simultaneous engineering of the grid material.

Background Only monopolar systems have thus far been available for radiofrequency ablation of liver tumors, whose application is restricted because of the incalculable energy flow, reduction of electrical tissue conduction, and limited lesion size. The aim of this study was to evaluate a novel internally cooled bipolar radiofrequency application device under in vivo conditions and to compare the effect of this system on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. Materials and methods In a porcine liver model, RFA (60 W, 12 min) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle’s maneuver, n = 12). RFA parameters (impedance, power output, temperature, applied energy) were determined continuously during therapy. RFA lesions were macroscopically assessed after liver dissection. Results Bipolar RFA induced clinical relevant ellipsoid thermal lesions without complications. Hepatic inflow occlusion led to a 4.3-fold increase in lesion volume after arterial microembolization and a 5.8-fold increase after complete interruption (7.4 cm3versus 31.9 cm3versus 42.6 cm3, P < 0.01). Conclusions The novel bipolar RFA device is a safe and effective alternative to monopolar RFA-systems. Interrupting hepatic perfusion significantly increases lesion volumes in bipolar RFA. This beneficial effect can also be achieved in the percutaneous application mode by RFA combined with arterial microembolization via a hepatic artery catheter.

The microscopic and macroscopic properties of a series of thermoplastic polyurethane (TPU) samples with different content in the hard segments and different molecular weight of the soft segments were investigated. Proton NMR transverse magnetization relaxation, DSC and rebound resilience techniques were used to characterize their molecular chain mobility, phase composition, glass transition temperature and angle of rebound. The increase of the hard segments content at the same molecular weight soft segments leads to an increase of the glass transition temperature as determined by DSC and to a decrease of the angle of rebound as determined by rebound resilience. These quantities can be correlated to the decrease in the effective transverse relaxation rates of the soft segments and to the increase of the relative fraction of the hard segments as determined by NMR. By increasing the molecular weight of the soft segments at the same content of the hard segments, the glass transition temperature and the angle of rebound decrease and the effective transverse relaxation time of the soft phase increases.

The segmental orientation of a series of thermoplastic polyurethane (TPU) samples with different content in hard segments and different number average molecular weights of soft segments was investigated by 1 H double-quantum (DQ) NMR. The residual dipolar couplings of the hard segments were measured via the residual second van Vleck moments. A simple theoretical approach based on Rouse modes was developed to explain the orientation dependence of the hard segments on the number average molecular weight of the soft segments. The effective transverse relaxation rates of the hard segments were correlated to the 1 H residual dipolar couplings. Moreover, the correlation between the segmental orientation of the hard segments and the thermodynamic and mechanical properties of the TPU samples is investigated. The glass transition temperatures of the soft segments represent the relevant thermodynamic quantities. The mechanical parameters used for discussing the correlations are Young's modulus, yield stress, and rebound resilience angles from tensile testing and rebound resilience measurements.

A new technology for grid production by electroforming is found to improve grid properties and thus, to increase cycle-life, save costs, and increase the ecological efficiency of lead–acid batteries beyond the corresponding features of competing designs. The particular aspects of the superior corrosion behaviour of the new grids are addressed with respect to the effects of chemical and anodic processes, microstructure, corrosion-induced creep and grid growth, and adherence of the positive active-mass. Along with each of these factors of influence, the prospects for improving battery behaviour and lowering cost is also discussed. The properties achievable by using electroformed grids are presented in terms of experimental results from a comparison with the properties of conventional grids, and by modelling and simulation.

This paper presents a brief description of the GALILEO services and summarizes the main performance parameters. The current status of the system architecture definition is presented in a concise overall view on the various elements of the system and their functions with a main focus on the GALILEO ground segment.

The objective of this study was to investigate spectral Doppler ultrasound (US) for monitoring extracorporeal shock-wave lithotripsy (ESWL). In vitro experiments with model stones showed that Doppler spectra acquired after a shock wave hit result in a high peak followed by a decaying signal. The duration of decay was dependent on shock-wave energy, stone size, gas content of the water and the level of disintegration. It typically ranged from 30 ms to 150 ms. It was found, by comparison with optical high-speed imaging and US B-scan imaging, that the signal originated from fragments released by the stone and cavitation. If the monitored volume contained no target, the signal duration was significantly shorter. By this means, hits were reliably distinguished from misses. The results of clinical treatments were highly consistent with those of in vitro experiments. Therefore, spectral Doppler US is an excellent tool for hit/miss monitoring in ESWL.

Advanced glycation end products (AGEs) are formed during the nonenzymatic reaction of sugars with proteins. Conventional peritoneal dialysis fluids (PDFs) lead to the formation of AGEs in the peritoneal membrane that are associated with histopathologic changes and loss of ultrafiltration. PDFs may cause AGE formation because of a high glucose concentration or reactive glucose degradation products (GDPs), which are formed during heat sterilization of PDFs. This formation of GDPs is strongly pH dependent, which is exploited in newly developed double-chamber bag PDFs. Accordingly, 3-deoxyglucosone levels in double-chamber bag PDFs are reduced by approximately 80%, and levels of the GDPs acetaldehyde, formaldehyde, and methylglyoxal are less than the detection limit. Using an in vitro model that mimics regular changes in PDFs during continuous ambulatory peritoneal dialysis treatment, the contribution of high glucose versus GDP concentrations to AGE formation was investigated. The latter was determined by measuring protein bound N ϵ -(carboxymethyl)-lysine (CML) and imidazolone by enzyme-linked immunosorbent assay. In this model, more than 85% of imidazolone and more than 70% of CML were formed by GDPs, whereas only a minor part resulted from a high glucose concentration per se. New in vivo investigations suggest that GDPs from PDFs also can exert systemic effects after absorption into the blood circulation. Imidazolone levels in blood serum decrease significantly after switching from single- to double-chamber PDFs. In summary, the use of double-chamber PDFs may decrease not only local, but also systemic AGE formation. Am J Kidney Dis 41(S1):S57-S60. © 2003 by the National Kidney Foundation, Inc.

The principle of Doppler global velocimetry (DGV) and a DGV system optimized for time averaged three-component velocity measurements is described in this paper. Furthermore, the design of the different components of the DGV-system as well as the manner of its operation is presented. The volumetric, time averaged, three-component velocity distribution was acquired in the isothermal flow of a low NOx, staged combustion chamber sector from Rolls-Royce Deutschland. The combustor was developed within the German public-funded Engine 3E program. On the basis of the collected data, the complex flow phenomena in the combustor could be analyzed in detail and supported by CFD calculations. A recently developed, pulsed Nd:YAG laser now enables planar, time-averaged, three-component DGV application in combusting flow fields. Measurements were carried out in a single-nozzle, kerosene combustion chamber model, operated under atmospheric pressure. The successful measurements demonstrated the capability of DGV as a new tool for combustion research. It was possible to separately measure the gas velocity and the velocity of the fuel droplets, a promising capability of DGV for two phase flow analysis.

The Catamaran - Measuring Dolphin (MESSIN) is an unmanned and independently operated craft having been designed for carrying out multiple measuring tasks in the field of marine research and water monitoring especially in shallow waters. An introduction to the navigation, steering and safety systems is given. Furthermore the main components of the track control system and the electronic chart system used here are shown. Results of manoeuvring tests of the MESSIN are represented. This paper gives a contribution to the field of research„ autonomous and full automated vehicle“.

The Catamaran - Measuring Dolphin (MESSIN) is an unmanned and independently operated craft having been designed for carrying out multiple measuring tasks in the field of marine research and water monitoring especially in shallow waters. An introduction to the navigation, steering and safety systems is given. Furthermore the main components of the track control system and the electronic chart system used here are shown. Results of manoeuvring tests of the MESSIN are represented. This paper gives a contribution to the field of research „autonomous and full automated vehicle“.

A new low power integrated pressure sensor system with digital output (1 bit PDM signal) for medical applications is presented. The absolute pressure sensor comprising 400 nm thick surface micromachined polysilicon membranes for capacitive pressure detection and a monolithic integrated 2nd order sigma–delta-modulator including voltage reference and timing generator is extremely miniaturized on an area of approximately 3 mm 2 . For protection and biocompatibility reasons the sensor is coated with a silicone elastomer of up to 100 μm thickness, which does not influence the sensor's performance. The sensor system was tested in vitro in physiological NaCl solution, showing excellent results compared to a commercial available reference sensor. The sensor system is working well down to a supply voltage of 2.2 V with a power consumption of 0.5 mW. The resolution is better than 12 bit. Due to the small chip area, low power consumption and cost effective production process, the sensor is ideal for medical applications, e.g., in combination with telemetric power and data transmission [J. Zacheja, B. Clasbrummel, J. Binder, U. Steinau, Implantable Telemetric Endosystem for Minimal Invasive Pressure Measurements, MedTech95, Berlin, Germany, (1995)] as an implantable sensor to reduce the mortality risk of intensive care patients.

We report a novel process for the full integration of surface-micromachined pressure-sensor cells into a standard BiCMOS process. Only the standard layers of the BiCMOS process are used to build up the sensor and only one additional photolithography step is necessary to achieve the micromachined structures. The application of the process is demonstrated by means of an integrated pressure-sensor system at a working range of 0.1 to 1.1 bar of absolute pressure. The influence of process parameters and tolerances of the VLSI process on the sensor performance are examined. To examine the long-term stability, the sensors are electrically deflected at the resonance frequency applying 4 × 10 11 load cycles. The measurements do not show any changes in the mechanical behaviour, so a very high long-term stability can be proven. In contrast to all integrated micromechanical systems presented so far, neither prenor post-processing of the system is necessary. Compared to conventional surface micromachining, the additional processing effort for the sensor realization is reduced dramatically to about 5% of the BiCMOS process.

The electrical properties of a Switchable Flux-Flow Resistor (SFFR) have been investigated. The maximum superconducting current in the channel can reversibly be varied by gate voltages in the range 2.5–7 V. Gate voltages above a threshold voltage yield a depression of the pinning force in the channel. The SFFR allows for three different operation modes, which have been characterized by static and transient measurements. A special layout for transient measurements with high resolution was developed. Possible applications of superconducting three-terminal devices are discussed.

The supervised working FuzzyARTMAP pattern recognition algorithm has been applied to automated identification of post-consumer plastics by near-infrared spectroscopy (NIRS). Experimentally, a remote operating parallel multisensor device, based on a rapid InGaAs diode array detector combined with new collimation optics, has been used. The laboratory setup allows on-line identification of more than 100 spectra per second. Internal parameter settings of FuzzyARTMAP were varied to explore their influence on the classifier’s behavior. Discrimination results obtained were better than those from an optimized multilayer feedforward backpropagation artificial neural network (MLF-BP) and significantly better than those provided by the partial least squares method (PLSZ). Additional advantages of FuzzyARTMAP compared to these two classifiers are a significantly higher speed of calibration, the chemical interpretability of network weight coefficients and a built-in detector against extrapolations.

Supported PtCoCr alloy catalysts on graphitized carbon black showing increased activity and stability as electrode catalysts for oxygen-reduction reaction in phosphoric acid fuel cells have been developed by co-precipitation of the corresponding metal nitrates. XRD investigations showed that a tetragonal ordered structure was formed upon thermal treatment. The formation of this structure required temperatures above 873 K. Although two-step and other sequential methods are known for the preparation of such catalysts, the newly developed method described here will led more efficiently to catalysts, having a small particle size, of the platinum cobalt chromium alloy.

Results on a new approach for the monolithic integration of micromechanics and electronics are presented. The same process steps and layers can be used for both the mechanical and the electronic elements. This is a promising process concept for integrated microelectromechanical systems with a minimum of additional costs compared to the standard electronics process. Results on the fabrication of micromechanical structures using the process steps of a 0.8 μm CMOS process are given. The sublimation technique is used to dry the released surface-micromachined structures and different sublimating chemicals are compared. The influences of polycrystalline and amorphous deposition as well as diffusion doping and ion implantation on the strain gradients of the structural layers are presented. A fabricated electrostatically deflectable and capacitively detectable cantilever is presented and the dependence of the capacitance on the drive voltage is shown. By using the presented theory and fitting calculations to the measured non-linear characteristic, a value of 170 GPa for Young's modulus of the polysilicon film is extracted.

Purpose : We describe how stereo photogrammetry can be used to determine immobilization and repositioning accuracies of head holder systems used for fractionated radiotherapy of intracranial lesions. Methods and Materials : The apparatus consists of two video cameras controlled by a personal computer and a bite block based landmark system. Position and spatial orientation of the landmarks are monitored by the cameras and processed for the real-time calculation of a target point's actual position relative to its initializing position. The target's position is assumed to be invariant with respect to the landmark system. We performed two series of 30 correlated head motion measurements on two test persons. One of the series was done with a thermoplastic device, the other one with a cast device developed for stereotactic treatment at the German Cancer Research Center. Immobilization and repositioning accuracies were determined with respect to a target point situated near the base of the skull. The repositioning accuracies were described in terms of the distributions of the mean displacements of the single motion measurements. Results : Movements of the target in the order of 0.05 mm caused by breathing could be detected with a maximum resolution in time of 12 ms. The data derived from the investigation of the two test persons indicated similar immobilization accuracies for the two devices, but the repositioning errors were larger for the thermoplastic device than for the cast device. Apart from this, we found that for the thermoplastic mask the lateral repositioning error depended on the order in which the mask was closed. Conclusion : The photogrammetric apparatus is a versatile tool for accuracy measurements of head holder devices used for fractionated radiotherapy.

To reduce the number of deletion mutants from antibody (Ab) libraries that had been amplified by PCR from peripheral blood lymphocytes, we constructed the Ab expression vector, pLAB, in which DNA coding for a single-chain Ab was inserted into the gene encoding β-lactamase (Bla) at the 3′-terminus of its signal sequence. After transforming Escherichia coli with this vector, a fusion protein with a functional Bla domain was produced that was able to protect the bacteria from the action of ampicillin (Ap). Libraries can therefore be usefully propagated with this vector, since only those clones carrying inserts that are in frame with Bla will survive Ap selection, while others that carry out-of-frame deletions or internal stop codons are eliminated.

Directional coronary atherectomy has been shown to be a successful method of percutaneous coronary revascularisation, particularly in large vessels with eccentric stenoses. The application of laser technology to coronary revascularisation has not been as successful, mainly because of a relatively high rate of vessel wall perforation. We describe a combination endovascular imaging/laser atherectomy catheter (Precision Guided Directional Laser Atherectomy Catheter, PGDLAC) that may overcome these shortcomings by allowing precision guided intervention. The catheter consists of a laser cutting device with an integrated imaging system (fiberoptic or ultrasound). Fiberoptic imaging allows exact positioning and orientation of the laser tipped catheter within the vessel lumen, and visual control of plaque excision. In the second step, the vessel wall morphology is demonstrated using ultrasound, and the result of the intervention assessed without removing the catheter. Excised plaque fragments are extracted by way of the catheter, Preliminary results of in vitro experimental application of this device in human coronary arteries is promising and confirms the technical feasibility. Such a device potentially offers the advantages of effective, precision guided atherectomy in plaques of variable constitution, with a potential reduction in procedure time and radiation dose. By combining state of the art imaging and interventional technology, we have developed a precision guided directional laser atherectomy system that may provide more effective percutaneous coronary revascularisation than previously developed techniques.

Bi-2212 superconducting rings (380 mm in diameter) were processed in a rotating furnace in flowing oxygen using Ag foil as the substrate. The powder was heated to the partial melt state, cooled to 855°C to develop superconducting phase, annealed in N 2 rich atmosphere, and finally cooled in N 2 from 700°C. This process has been optimised to achieve smooth surface finish and uniform thickness in the rings. Microstructure studies suggest that the as-processed Bi-2212 rings are highly densified and consist of random oriented Bi-2212 grain bundles. The Bi-2212 rings show a high T c onset of 96K and a typical J c of 1500 Acm −2 with I c of 2500 A.

Cauliflower mosaic virus, although a DNA virus, uses RNA as a replicative intermediate and employs reverse transcriptase for genome replication. Details of this replication mode as currently known and implications for other aspects of the life cycle of this virus are presented here.

The high T c superconductors YBa 2 Cu 3 O 7−δ , prepared by conventional sintering techniques, has a critical current j c ranging between 100–1000A/cm 2 about two orders of magnitude lower than the intragrain j c . From our investigations we conclude that the sintered samples are not strictly single phase. Most impurities are CuO and BaCu-oxide, present mainly at inner surfaces (cavities) and at some grain boundaries. These results are important for practical applications to obtain a higher critical current. The role of the impurity phases in relation to j c will be discussed.