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A light-addressable potentiometric sensor (LAPS) is a field-effect-based potentiometric device, which detects concentration changes of an analyte solution on the sensor surface in a spatially resolved way. It uses a light source to generate electron–hole pairs inside the semiconductor, which are separated in the depletion region due to an applied bias voltage across the sensor structure and hence, a surface-potential-dependent photocurrent can be read out. However, depending on the beam angle of the light source, scattering effects can occur, which influence the recorded signal in LAPS-based differential measurements. To solve this problem, a novel illumination unit based on a field programmable gate array (FPGA) consisting of 16 small-sized tunable infrared laser-diode modules (LDMs) is developed. Due to the improved focus of the LDMs with a beam angle of only 2 mrad, undesirable scattering effects are minimized. Escherichia coli (E. coli) K12 bacteria are used as a test microorganism to study the extracellular acidification on the sensor surface. Furthermore, a salt bridge chamber is built up and integrated with the LAPS system enabling multi-chamber differential measurements with a single Ag/AgCl reference electrode.
In this study, flexible calorimetric gas sensors are developed for specificdetection of gaseous hydrogen peroxide (H₂O₂) over a wide concentrationrange, which is used in sterilization processes for aseptic packaging industry.The flexibility of these sensors is an advantage for identifying the chemical components of the sterilant on the corners of the food boxes, so-called “coldspots”, as critical locations in aseptic packaging, which are of great importance. These sensors are fabricated on flexible polyimide films by means of thin-film technique. Thin layers of titanium and platinum have been deposited on polyimide to define the conductive structures of the sensors. To detect the high-temperature evaporated H₂O₂, a differential temperature set-up is proposed. The sensors are evaluated in a laboratory-scaled sterilizationsystem to simulate the sterilization process. The concentration range of the evaporated H₂O₂ from 0 to 7.7% v/v was defined and the sensors have successfully detected high as well as low H₂O₂ concentrations with a sensitivity of 5.04 °C/% v/v. The characterizations of the sensors confirm their precise fabrication, high sensitivity and the novelty of low H₂O₂ concentration detections for future inline monitoring of food-package sterilization.
The rail business is challenged by long product life cycles and a broad spectrum of assembly groups and single parts. When spare part obsolescence occurs, quick solutions are needed. A reproduction of obsolete parts is often connected to long waiting times and minimum lot quantities that need to be purchased and stored. Spare part storage is therefore challenged by growing stocks, bound capital and issues of part ageing. A possible solution could be a virtual storage of spare parts which will be 3D printed through additive manufacturing technologies in case of sudden demand. As mechanical properties of additive manufactured parts are neither guaranteed by machine manufacturers nor by service providers, the utilization of this relatively young technology is impeded and research is required to address these issues. This paper presents an examination of mechanical properties of specimens manufactured from stainless steel through the selective laser melting (SLM) process. The specimens were produced in multiple batches. This paper interrogates the question if the test results follow a normal distribution pattern and if mechanical property predictions can be made. The results will be put opposite existing threshold values provided as the industrial standard. Furthermore, probability predictions will be made in order to examine the potential of the SLM process to maintain state-of-the-art mechanical property requirements.
The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
(2018)
The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells.
Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23% for agglomerated MNP in suspension and a decrease by up to 28% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy.
Impaired cerebral autoregulation and neurovascular coupling (NVC) contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). Retinal vessel analysis (RVA) allows non-invasive assessment of vessel dimension and NVC hereby demonstrating a predictive value in the context of various neurovascular diseases. Using RVA as a translational approach, we aimed to assess the retinal vessels in patients with SAH. RVA was performed prospectively in 24 patients with acute SAH (group A: day 5–14), in 11 patients 3 months after ictus (group B: day 90 ± 35), and in 35 age-matched healthy controls (group C). Data was acquired using a Retinal Vessel Analyzer (Imedos Systems UG, Jena) for examination of retinal vessel dimension and NVC using flicker-light excitation. Diameter of retinal vessels—central retinal arteriolar and venular equivalent—was significantly reduced in the acute phase (p < 0.001) with gradual improvement in group B (p < 0.05). Arterial NVC of group A was significantly impaired with diminished dilatation (p < 0.001) and reduced area under the curve (p < 0.01) when compared to group C. Group B showed persistent prolonged latency of arterial dilation (p < 0.05). Venous NVC was significantly delayed after SAH compared to group C (A p < 0.001; B p < 0.05). To our knowledge, this is the first clinical study to document retinal vasoconstriction and impairment of NVC in patients with SAH. Using non-invasive RVA as a translational approach, characteristic patterns of compromise were detected for the arterial and venous compartment of the neurovascular unit in a time-dependent fashion. Recruitment will continue to facilitate a correlation analysis with clinical course and outcome.
Due to the Renewable Energy Act, in Germany it is planned to increase the amount of renewable energy carriers up to 60%. One of the main problems is the fluctuating supply of wind and solar energy. Here biogas plants provide a solution, because a demand-driven supply is possible. Before running such a plant, it is necessary to simulate and optimize the process. This paper provides a new model of a biogas plant, which is as accurate as the standard ADM1 model. The advantage compared to ADM1 is that it is based on only four parameters compared to 28. Applying this model, an optimization was installed, which allows a demand-driven supply by biogas plants. Finally the results are confirmed by several experiments and measurements with a real test plant.
In this work, a spore-based biosensor is evaluated to monitor the microbicidal efficacy of sterilization processes applying gaseous hydrogen peroxide (H2O2). The sensor is based on interdigitated electrode structures (IDEs) that have been fabricated by means of thin-film technologies. Impedimetric measurements are applied to study the effect of sterilization process on spores of Bacillus atrophaeus. This resilient microorganism is commonly used in industry to proof the sterilization efficiency. The sensor measurements are accompanied by conventional microbiological challenge tests, as well as morphological characterizations with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The sensor measurements are correlated with the microbiological test routines. In both methods, namely the sensor-based and microbiological one, a tailing effect has been observed. The results are evaluated and discussed in a three-dimensional calibration plot demonstrating the sensor's suitability to enable a rapid process decision in terms of a successfully performed sterilization.
After a liver tumor intervention the medical doctor has to compare both pre and postoperative CT acquisitions to ensure that all carcinogenic cells are destroyed. A correct assessment of the intervention is of vital importance, since it will reduce the probability of tumor recurrence. Some methods have been proposed to support the medical doctors during the assessment process, however, all of them focus on secondary tumors. In this paper a tool is presented that enables the outcome validation for both primary and secondary tumors. Therefore, a multiphase registration (preoperative arterial and portal phases) followed by a registration between the pre and postoperative CT images is carried out. The first registration is in charge of the primary tumors that are only visible in the arterial phase. The secondary tumors will be incorporated in the second registration step. Finally, the part of the tumor that was not covered by the necrosis is quantified and visualized. The method has been tested in 9 patients, with an average registration error of 1.41 mm.
BACKGROUND: Muscle stretch reflexes are widely considered to beneficially influence joint stability and power generation in the lower limbs. While in the upper limbs and especially in the muscles surrounding the shoulder joint such evidence is lacking. OBJECTIVE: To quantify the electromyographical response in the muscles crossing the shoulder of specifically trained overhead athletes to an anterior perturbation force. METHODS: Twenty healthy male participants performed six sets of different external shoulder rotation stretches on an isokinetic dynamometer over a range of amplitudes and muscle pre-activation moment levels. All stretches were applied with a dynamometer acceleration of 10,000∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexes were not observed in all experimental conditions. The reflex latencies revealed a significant muscle main effect (F (2,228) = 99.31, p< 0.001; η2= 0.466; f= 0.934) and a pre-activation main effect (F (1,228) = 142.21, p< 0.001; η2= 0.384; f= 1.418). The stretch reflex amplitude yielded a significant pre-activation main effect (F (1,222) = 470.373, p< 0.001; η2= 0.679; f= 1.454). CONCLUSION: Short latency muscle reflexes showed a tendency to an anterior to posterior muscle recruitment whereby the main internal rotator muscles of the shoulder revealed the most consistent results.
For smaller railway operators or those with a diverse fleet, it can be difficult to collect sufficient data to improve maintenance programs. At the same time, new rules such as entity in charge of maintenance – ECM – regulations impose an additional workload by requiring a dedicated maintenance management system and specific reports. The RailCrowd platform sets out to facilitate compliance with ECM and similar regulations while at the same time pooling anonymised fleet data across operators to form virtual fleets, providing greater data insights.
Slot die coating is applied to deposit thin and homogenous films in roll-to-roll and sheet-to-sheet applications. The critical step in operation is to choose suitable process parameters within the process window. In this work, we investigate an upper limit for stripe coatings. This maximum film thickness is characterized by stripe merging which needs to be avoided in a stable process. It is shown that the upper limit reduces the process window for stripe coatings to a major extent. As a result, stripe coatings at large coating gaps and low viscosities are only possible for relatively thick films. Explaining the upper limit, a theory of balancing the side pressure in the gap region in the cross-web direction has been developed.
Given industrial applications, the costs for the operation and maintenance of a pump system typically far exceed its purchase price. For finding an optimal pump configuration which minimizes not only investment, but life-cycle costs, methods like Technical Operations Research which is based on Mixed-Integer Programming can be applied. However, during the planning phase, the designer is often faced with uncertain input data, e.g. future load demands can only be estimated. In this work, we deal with this uncertainty by developing a chance-constrained two-stage (CCTS) stochastic program. The design and operation of a booster station working under uncertain load demand are optimized to minimize total cost including purchase price, operation cost incurred by energy consumption and penalty cost resulting from water shortage. We find optimized system layouts using a sample average approximation (SAA) algorithm, and analyze the results for different risk levels of water shortage. By adjusting the risk level, the costs and performance range of the system can be balanced, and thus the
system’s resilience can be engineered
Resilience as a concept has found its way into different disciplines to describe the ability of an individual or system to withstand and adapt to changes in its environment. In this paper, we provide an overview of the concept in different communities and extend it to the area of mechanical engineering. Furthermore, we present metrics to measure resilience in technical systems and illustrate them by applying them to load-carrying structures. By giving application examples from the Collaborative Research Centre (CRC) 805, we show how the concept of resilience can be used to control uncertainty during different stages of product life.
Ensuring access to water and sanitation for all is Goal No. 6 of the 17 UN Sustainability Development Goals to transform our world. As one step towards this goal, we present an approach that leverages remote sensing data to plan optimal water supply networks for informal urban settlements. The concept focuses on slums within large urban areas, which are often characterized by a lack of an appropriate water supply. We apply methods of mathematical optimization aiming to find a network describing the optimal supply infrastructure. Hereby, we choose between different decentral and central approaches combining supply by motorized vehicles with supply by pipe systems. For the purposes of illustration, we apply the approach to two small slum clusters in Dhaka and Dar es Salaam. We show our optimization results, which represent the lowest cost water supply systems possible. Additionally, we compare the optimal solutions of the two clusters (also for varying input parameters, such as population densities and slum size development over time) and describe how the result of the optimization depends on the entered remote sensing data.
On obligations in the development process of resilient systems with algorithmic design methods
(2018)
Advanced computational methods are needed both for the design of large systems and to compute high accuracy solutions. Such methods are efficient in computation, but the validation of results is very complex, and highly skilled auditors are needed to verify them. We investigate legal questions concerning obligations in the development phase, especially for technical systems developed using advanced methods. In particular, we consider methods of resilient and robust optimization. With these techniques, high performance solutions can be found, despite a high variety of input parameters. However, given the novelty of these methods, it is uncertain whether legal obligations are being met. The aim of this paper is to discuss if and how the choice of a specific computational method affects the developer’s product liability. The review of legal obligations in this paper is based on German law and focuses on the requirements that must be met during the design and development process.
Malaria infection remains a significant risk for much of the population of tropical and subtropical areas, particularly in developing countries. Therefore, it is of high importance to develop sensitive, accurate and inexpensive malaria diagnosis tests. Here, we present a novel aptamer-based electrochemical biosensor (aptasensor) for malaria detection by impedance spectroscopy, through the specific recognition between a highly discriminatory DNA aptamer and its target Plasmodium falciparum lactate dehydrogenase (PfLDH). Interestingly, due to the isoelectric point (pI) of PfLDH, the aptasensor response showed an adjustable detection range based on the different protein net-charge at variable pH environments. The specific aptamer recognition allows sensitive protein detection with an expanded detection range and a low detection limit, as well as a high specificity for PfLDH compared to analogous proteins. The specific feasibility of the aptasensor is further demonstrated by detection of the target PfLDH in human serum. Furthermore, the aptasensor can be easily regenerated and thus applied for multiple usages. The robustness, sensitivity, and reusability of the presented aptasensor make it a promising candidate for point-of-care diagnostic systems.
The chemical imaging sensor is a semiconductor-based chemical sensor capable of visualizing pH and ion distributions. The spatial resolution depends on the lateral diffusion of photocarriers generated by illumination of the semiconductor substrate. In this study, two types of optical setups, one based on a bundle of optical fibers and the other based on a binocular tube head, were developed to project a hybrid illumination of a modulated light beam and a ring-shaped constant illumination onto the sensor plate. An improved spatial resolution was realized by the ring-shaped constant illumination, which suppressed lateral diffusion of photocarriers by enhanced recombination due to the increased carrier concentration.
Synthetic mimics of natural high-performance structural materials have shown great and partly unforeseen opportunities for the design of multifunctional materials. For nacre-mimetic nanocomposites, it has remained extraordinarily challenging to make ductile materials with high stretchability at high fractions of reinforcements, which is however of crucial importance for flexible barrier materials. Here, highly ductile and tough nacre-mimetic nanocomposites are presented, by implementing weak, but many hydrogen bonds in a ternary nacre-mimetic system consisting of two polymers (poly(vinyl amine) and poly(vinyl alcohol)) and natural nanoclay (montmorillonite) to provide efficient energy dissipation and slippage at high nanoclay content (50 wt%). Tailored interactions enable exceptional combinations of ductility (close to 50% strain) and toughness (up to 27.5 MJ m⁻³). Extensive stress whitening, a clear sign of high internal dynamics at high internal cohesion, can be observed during mechanical deformation, and the materials can be folded like paper into origami planes without fracture. Overall, the new levels of ductility and toughness are unprecedented in highly reinforced bioinspired nanocomposites and are of critical importance to future applications, e.g., as barrier materials needed for encapsulation and as a printing substrate for flexible organic electronics.