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In this paper we present an extension of the action language Golog that allows for using fuzzy notions in non-deterministic argument choices and the reward function in decision-theoretic planning. Often, in decision-theoretic planning, it is cumbersome to specify the set of values to pick from in the non-deterministic-choice-of-argument statement. Also, even for domain experts, it is not always easy to specify a reward function. Instead of providing a finite domain for values in the non-deterministic-choice-of-argument statement in Golog, we now allow for stating the argument domain by simply providing a formula over linguistic terms and fuzzy uents. In Golog’s forward-search DT planning algorithm, these formulas are evaluated in order to find the agent’s optimal policy. We illustrate this in the Diner Domain where the agent needs to calculate the optimal serving order.
In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.
Density Operator
(2009)
With the variety of toothbrushes on the market, the question arises, which toothbrush is best suited to maintain oral health? This thematic review focuses first on plaque formation mechanisms and then on the plaque removal effectiveness of ultrasonic toothbrushes and their potential in preventing oral diseases like periodontitis, gingivitis, and caries. We overviewed the physical effects that occurred during brushing and tried to address the question of whether ultrasonic toothbrushes effectively reduced the microbial burden by increasing the hydrodynamic forces. The results of published studies show that electric toothbrushes, which combine ultrasonic and sonic (or acoustic and mechanic) actions, may have the most promising effect on good oral health. Existing ultrasonic/sonic toothbrush models do not significantly differ regarding the removal of dental biofilm and the reduction of gingival inflammation compared with other electrically powered toothbrushes, whereas the manual toothbrushes show a lower effectiveness.
The increasing share of renewable electricity in the grid drives the need for sufficient storage capacity. Especially for seasonal storage, power-to-gas can be a promising approach. Biologically produced methane from hydrogen produced from surplus electricity can be used to substitute natural gas in the existing infrastructure. Current reactor types are not or are poorly optimized for flexible methanation. Therefore, this work proposes a new reactor type with a plug flow reactor (PFR) design. Simulations in COMSOL Multiphysics ® showed promising properties for operation in laminar flow. An experiment was conducted to support the simulation results and to determine the gas fraction of the novel reactor, which was measured to be 29%. Based on these simulations and experimental results, the reactor was constructed as a 14 m long, 50 mm diameter tube with a meandering orientation. Data processing was established, and a step experiment was performed. In addition, a kLa of 1 h−1 was determined. The results revealed that the experimental outcomes of the type of flow and gas fractions are in line with the theoretical simulation. The new design shows promising properties for flexible methanation and will be tested.
Design and initial performance of PlanTIS: a high-resolution positron emission tomograph for plants
(2010)
Positron emitters such as 11C, 13N and 18F and their labelled compounds are widely used in clinical diagnosis and animal studies, but can also be used to study metabolic and physiological functions in plants dynamically and in vivo. A very particular tracer molecule is 11CO2 since it can be applied to a leaf as a gas. We have developed a Plant Tomographic Imaging System (PlanTIS), a high-resolution PET scanner for plant studies. Detectors, front-end electronics and data acquisition architecture of the scanner are based on the ClearPET™ system. The detectors consist of LSO and LuYAP crystals in phoswich configuration which are coupled to position-sensitive photomultiplier tubes. Signals are continuously sampled by free running ADCs, and data are stored in a list mode format. The detectors are arranged in a horizontal plane to allow the plants to be measured in the natural upright position. Two groups of four detector modules stand face-to-face and rotate around the field-of-view. This special system geometry requires dedicated image reconstruction and normalization procedures. We present the initial performance of the detector system and first phantom and plant measurements.
Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.
Design of a Measurement Setup for the Impedance of Low-Resistance Plate-Conductors in the RF-Range
(2006)
The maintenance of wind turbines is of growing importance considering the transition to renewable energy. This paper presents a multi-robot-approach for automated wind turbine maintenance including a novel climbing robot. Currently, wind turbine maintenance remains a manual task, which is monotonous, dangerous, and also physically demanding due to the large scale of wind turbines. Technical climbers are required to work at significant heights, even in bad weather conditions. Furthermore, a skilled labor force with sufficient knowledge in repairing fiber composite material is rare. Autonomous mobile systems enable the digitization of the maintenance process. They can be designed for weather-independent operations. This work contributes to the development and experimental validation of a maintenance system consisting of multiple robotic platforms for a variety of tasks, such as wind turbine tower and rotor blade service. In this work, multicopters with vision and LiDAR sensors for global inspection are used to guide slower climbing robots. Light-weight magnetic climbers with surface contact were used to analyze structure parts with non-destructive inspection methods and to locally repair smaller defects. Localization was enabled by adapting odometry for conical-shaped surfaces considering additional navigation sensors. Magnets were suitable for steel towers to clamp onto the surface. A friction-based climbing ring robot (SMART— Scanning, Monitoring, Analyzing, Repair and Transportation) completed the set-up for higher payload. The maintenance period could be extended by using weather-proofed maintenance robots. The multi-robot-system was running the Robot Operating System (ROS). Additionally, first steps towards machine learning would enable maintenance staff to use pattern classification for fault diagnosis in order to operate safely from the ground in the future.
Design of enzyme reactors as chromatographic columns for racemic resolution of amino acid esters
(1989)
Within the Crystal Clear Collaboration four centres are developing 2nd generation high performance small animal PET scanners for different kinds of animals and medical applications. The first prototypes are PMT-based systems including depth of interaction (DOI) detection by using a phoswich layer of LSO and LuYAP. The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in FOVs caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN) was used. The simulations have shown that all PMT designs with one-to-one coupling of crystals have a very nonlinear axial sensitivity profile. By shifting every other PMT 1/4 of a PMT length in axial direction the sampling of the FOVs became more homogeneous. At an energy threshold of 350keV the regression coefficient increases from 0.818 for the non-shifted to 0.993 for the shifted design. Simulations of a point source centred in the FOV (threshold: 350keV) resulted in sensitivities of 4.2% for a 4×20PMT (LSO/LuYAP a 10mm) and 3.8% for a 4×16PMT (LSO/LuYAP a 8mm) ring design. The 3D-MLEM reconstruction of a point source shows the enormous improvement of resolution using a crystal double layer with DOI (3.1mm at 40mm from CFOV) instead of a 20mm single layer (11.9mm).
Within the Crystal Clear Collaboration (CCC), four centers are developing second generation high performance small animal positron emission tomography (PET) scanners for different kinds of animals and medical applications. The first prototypes are photomultiplier tube (PMT)-based systems including depth of interaction (DOI) detection by using a phoswich layer of lutetium oxyorthosilicate (LSO) and lutetium yttrium aluminum perovskite (LuYAP). The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in fields of view (FOVs) caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN, Geneva, Switzerland) was used.
Design, evaluation and comparison of endorectal coils for hybrid MR-PET imaging of the prostate
(2020)
Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.
Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.
A method for detecting and approximating fault lines or surfaces, respectively, or decision curves in two and three dimensions with guaranteed accuracy is presented. Reformulated as a classification problem, our method starts from a set of scattered points along with the corresponding classification algorithm to construct a representation of a decision curve by points with prescribed maximal distance to the true decision curve. Hereby, our algorithm ensures that the representing point set covers the decision curve in its entire extent and features local refinement based on the geometric properties of the decision curve. We demonstrate applications of our method to problems related to the detection of faults, to multi-criteria decision aid and, in combination with Kirsch’s factorization method, to solving an inverse acoustic scattering problem. In all applications we considered in this work, our method requires significantly less pointwise classifications than previously employed algorithms.
Detecting synchronization clusters in multivariate time series via coarse-graining of Markov chains
(2007)
Detection and identification of free radicals in hydrocarbon pyrolysis by an iodine trapping method
(1992)
Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte–insulator–semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716ᵀ is immobilized via biotin–streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage–current, capacitance–voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.
An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied.