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Providing healthcare services frequently involves cognitively demanding tasks, including diagnoses and analyses as well as complex decisions about treatments and therapy. From a global perspective, ethically significant inequalities exist between regions where the expert knowledge required for these tasks is scarce or abundant. One possible strategy to diminish such inequalities and increase healthcare opportunities in expert-scarce settings is to provide healthcare solutions involving digital technologies that do not necessarily require the presence of a human expert, e.g., in the form of artificial intelligent decision-support systems (AI-DSS). Such algorithmic decision-making, however, is mostly developed in resource- and expert-abundant settings to support healthcare experts in their work. As a practical consequence, the normative standards and requirements for such algorithmic decision-making in healthcare require the technology to be at least as explainable as the decisions made by the experts themselves. The goal of providing healthcare in settings where resources and expertise are scarce might come with a normative pull to lower the normative standards of using digital technologies in order to provide at least some healthcare in the first place. We scrutinize this tendency to lower standards in particular settings from a normative perspective, distinguish between different types of absolute and relative, local and global standards of explainability, and conclude by defending an ambitious and practicable standard of local relative explainability.
The downsizing of spark ignition engines in conjunction with turbocharging is considered to be a promising method for reducing CO₂ emissions. Using this concept, FEV has developed a new, highly efficient drivetrain to demonstrate fuel consumption reduction and drivability in a vehicle based on the Ford Focus ST. The newly designed 1.8L turbocharged gasoline engine incorporates infinitely variable intake and outlet control timing and direct fuel injection utilizing piezo injectors centrally located. In addition, this engine uses a prototype FEV engine control system, with software that was developed and adapted entirely by FEV. The vehicle features a 160 kW engine with a maximum mean effective pressure of 22.4 bar and 34 % savings in simulated fuel consumption. During the first stage, a new electrohydraulically actuated hybrid transmission with seven forward gears and one reverse gear and a single dry starting clutch will be integrated. The electric motor of the hybrid is directly connected to the gear set of the transmission. Utilizing the special gear set layout, the electric motor can provide boost during a change of gears, so that there is no interruption in traction. Therefore, the transmission system combines the advantages of a double clutch controlled gear change (gear change without an interruption in traction) with the efficient, cost-effective design of an automated manual transmission system. Additionally, the transmission provides a purely electric drive system and the operation of an air-conditioning compressor during the engine stop phases. One other alternative is through the use of CAI (Controlled Auto Ignition), which incorporates a process developed by FEV for controlled compression ignition.
SHEMAT-Suite: An open-source code for simulating flow, heat and species transport in porous media
(2020)
SHEMAT-Suite is a finite-difference open-source code for simulating coupled flow, heat and species transport in porous media. The code, written in Fortran-95, originates from geoscientific research in the fields of geothermics and hydrogeology. It comprises: (1) a versatile handling of input and output, (2) a modular framework for subsurface parameter modeling, (3) a multi-level OpenMP parallelization, (4) parameter estimation and data assimilation by stochastic approaches (Monte Carlo, Ensemble Kalman filter) and by deterministic Bayesian approaches based on automatic differentiation for calculating exact (truncation error-free) derivatives of the forward code.
Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism
(2019)
Sleep spindles are neurophysiological phenomena that appear to be linked to memory formation and other functions of the central nervous system, and that can be observed in electroencephalographic recordings (EEG) during sleep. Manually identified spindle annotations in EEG recordings suffer from substantial intra- and inter-rater variability, even if raters have been highly trained, which reduces the reliability of spindle measures as a research and diagnostic tool. The Massive Online Data Annotation (MODA) project has recently addressed this problem by forming a consensus from multiple such rating experts, thus providing a corpus of spindle annotations of enhanced quality. Based on this dataset, we present a U-Net-type deep neural network model to automatically detect sleep spindles. Our model’s performance exceeds that of the state-of-the-art detector and of most experts in the MODA dataset. We observed improved detection accuracy in subjects of all ages, including older individuals whose spindles are particularly challenging to detect reliably. Our results underline the potential of automated methods to do repetitive cumbersome tasks with super-human performance.
Enzyme-based logic gates and circuits - analytical applications and interfacing with electronics
(2017)
The paper is an overview of enzyme-based logic gates and their short circuits, with specific examples of Boolean AND and OR gates, and concatenated logic gates composed of multi-step enzyme-biocatalyzed reactions. Noise formation in the biocatalytic reactions and its decrease by adding a “filter” system, converting convex to sigmoid response function, are discussed. Despite the fact that the enzyme-based logic gates are primarily considered as components of future biomolecular computing systems, their biosensing applications are promising for immediate practical use. Analytical use of the enzyme logic systems in biomedical and forensic applications is discussed and exemplified with the logic analysis of biomarkers of various injuries, e.g., liver injury, and with analysis of biomarkers characteristic of different ethnicity found in blood samples on a crime scene. Interfacing of enzyme logic systems with modified electrodes and semiconductor devices is discussed, giving particular attention to the interfaces functionalized with signal-responsive materials. Future perspectives in the design of the biomolecular logic systems and their applications are discussed in the conclusion.
Hydrophobic magnetic nanoparticles (NPs) consisting of undecanoate-capped magnetite (Fe3O4, average diameter ca. 5 nm) are used to control quantized electron transfer to surface-confined redox units and metal NPs. A two-phase system consisting of an aqueous electrolyte solution and a toluene phase that includes the suspended undecanoatecapped magnetic NPs is used to control the interfacial properties of the electrode surface. The attracted magnetic NPs form a hydrophobic layer on the electrode surface resulting in the change of the mechanisms of the surface-confined electrochemical processes. A quinone-monolayer modified Au electrode demonstrates an aqueous-type of the electrochemical process (2e-+2H+ redox mechanism) for the quinone units in the absence of the hydrophobic magnetic NPs, while the attraction of the magnetic NPs to the surface results in the stepwise single-electron transfer mechanism characteristic of a dry nonaqueous medium. Also, the attraction of the hydrophobic magnetic NPs to the Au electrode surface modified with Au NPs (ca. 1.4 nm) yields a microenvironment with a low dielectric constant that results in the single-electron quantum charging of the Au NPs.
In the study, the process chain of additive manufacturing by means of powder bed fusion will be presented based on the material glass. In order to reliably process components additively, new concepts with different solutions were developed and investigated.
Compared to established metallic materials, the properties of glass materials differ significantly. Therefore, the process control was adapted to the material glass in the investigations. With extensive parameter studies based on various glass powders such as borosilicate glass and quartz glass, scientifically proven results on powder bed fusion of glass are presented. Based on the determination of the particle properties with different methods, extensive investigations are made regarding the melting behavior of glass by means of laser beams. Furthermore, the experimental setup was steadily expanded. In addition to the integration of coaxial temperature measurement and regulation, preheating of the building platform is of major importance. This offers the possibility to perform 3D printing at the transformation temperatures of the glass materials. To improve the component’s properties, the influence of a subsequent heat treatment was also investigated.
The experience gained was incorporated into a new experimental system, which allows a much better exploration of the 3D printing of glass. Currently, studies are being conducted to improve surface texture, building accuracy, and geometrical capabilities using three-dimensional specimen.
The contribution shows the development of research in the field of 3D printing of glass, gives an insight into the machine and process engineering as well as an outlook on the possibilities and applications.
In comparison to single-analyte devices, multiplexed systems for a multianalyte detection offer a reduced assay time and sample volume, low cost, and high throughput. Herein, a multiplexing platform for an automated quasi-simultaneous characterization of multiple (up to 16) capacitive field-effect sensors by the capacitive–voltage (C–V) and the constant-capacitance (ConCap) mode is presented. The sensors are mounted in a newly designed multicell arrangement with one common reference electrode and are electrically connected to the impedance analyzer via the base station. A Python script for the automated characterization of the sensors executes the user-defined measurement protocol. The developed multiplexing system is tested for pH measurements and the label-free detection of ligand-stabilized, charged gold nanoparticles.
Electrolyte-insulator-semiconductor capacitors (EISCAP) belong to field-effect sensors having an attractive transducer architecture for constructing various biochemical sensors. In this study, a capacitive model of enzyme-modified EISCAPs has been developed and the impact of the surface coverage of immobilized enzymes on its capacitance-voltage and constant-capacitance characteristics was studied theoretically and experimentally. The used multicell arrangement enables a multiplexed electrochemical characterization of up to sixteen EISCAPs. Different enzyme coverages have been achieved by means of parallel electrical connection of bare and enzyme-covered single EISCAPs in diverse combinations. As predicted by the model, with increasing the enzyme coverage, both the shift of capacitance-voltage curves and the amplitude of the constant-capacitance signal increase, resulting in an enhancement of analyte sensitivity of the EISCAP biosensor. In addition, the capability of the multicell arrangement with multi-enzyme covered EISCAPs for sequentially detecting multianalytes (penicillin and urea) utilizing the enzymes penicillinase and urease has been experimentally demonstrated and discussed.
The coupling of ligand-stabilized gold nanoparticles with field-effect devices offers new possibilities for label-free biosensing. In this work, we study the immobilization of aminooctanethiol-stabilized gold nanoparticles (AuAOTs) on the silicon dioxide surface of a capacitive field-effect sensor. The terminal amino group of the AuAOT is well suited for the functionalization with biomolecules. The attachment of the positively-charged AuAOTs on a capacitive field-effect sensor was detected by direct electrical readout using capacitance-voltage and constant capacitance measurements. With a higher particle density on the sensor surface, the measured signal change was correspondingly more pronounced. The results demonstrate the ability of capacitive field-effect sensors for the non-destructive quantitative validation of nanoparticle immobilization. In addition, the electrostatic binding of the polyanion polystyrene sulfonate to the AuAOT-modified sensor surface was studied as a model system for the label-free detection of charged macromolecules. Most likely, this approach can be transferred to the label-free detection of other charged molecules such as enzymes or antibodies.
Enzyme-catalyzed reactions have been designed to mimic various Boolean logic gates in the general framework of unconventional biomolecular computing. While some of the logic gates, particularly OR, AND, are easy to realize with biocatalytic reactions and have been reported in numerous publications, some other, like NXOR, are very challenging and have not been realized yet with enzyme reactions. The paper reports on a novel approach to mimicking the NXOR logic gate using the bell-shaped enzyme activity dependent on pH values. Shifting pH from the optimum value to the acidic or basic values by using acid or base inputs (meaning 1,0 and 0,1 inputs) inhibits the enzyme reaction, while keeping the optimum pH (assuming 0,0 and 1,1 input combinations) preserves a high enzyme activity. The challenging part of the present approach is the selection of an enzyme with a well-demonstrated bell-shape activity dependence on the pH value. While many enzymes can satisfy this condition, we selected pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase as this enzyme has the optimum pH center-located on the pH scale allowing the enzyme activity change by the acidic and basic pH shift from the optimum value corresponding to the highest activity. The present NXOR gate is added to the biomolecular “toolbox” as a new example of Boolean logic gates based on enzyme reactions.
The purpose of this study was to investigate whether sprint performance is related to lower leg musculoskeletal geometry within a homogeneous group of highly trained 100-m sprinters. Using a cluster analysis, eighteen male sprinters were divided into two groups based on their personal best (fast: N = 11, 10.30 ± 0.07 s; slow: N = 7, 10.70 ± 0.08 s). Calf muscular fascicle arrangement and Achilles tendon moment arms (calculated by the gradient of tendon excursion versus ankle joint angle) were analyzed for each athlete using ultrasonography. Achilles tendon moment arm, foot and ankle skeletal geometry, fascicle arrangement as well as the ratio of fascicle length to Achilles tendon moment arm showed no significant (p > 0.05) correlation with sprint performance, nor were there any differences in the analyzed musculoskeletal parameters between the fast and slow sprinter group. Our findings provide evidence that differences in sprint ability in world-class athletes are not a result of differences in the geometrical design of the lower leg even when considering both skeletal and muscular components.
Mannoheptulose is a seven-carbon sugar. It is an inhibitor of glucose-induced insulin secretion due to its ability to selectively inhibit the enzyme glucokinase. An improved procedure for mannoheptulose isolation from avocados is described in this study (based upon the original method by La Forge). The study focuses on the combination of biotransformation and downstream processing (preparative chromatography) as an efficient method to produce a pure extract of mannoheptulose. The experiments were divided into two major phases. In the first phase, several methods and parameters were compared to optimize the mannoheptulose extraction with respect to efficiency and purity. In the second phase, a mass balance of mannoheptulose over the whole extraction process was undertaken to estimate the yield and efficiency of the total extraction process. The combination of biotransformation and preparative chromatography allowed the production of a pure mannoheptulose extract. In a biological test, the sugar inhibited the glucokinase enzyme activity efficiently.
Flow visualization by means of PIV of an artificial aortic heart valve fixed into a mock aorta
(2005)
The production and assembly of customized products increases the demand for flexible automation systems. One approach is to remove the safety fences that separate human and industrial robot to combine their skills. This collaboration possesses a certain risk for the human co-worker, leading to numerous safety concepts to protect him. The human needs to be monitored and tracked by a safety system using different sensors. The proposed system consists of a RGBD camera for surveillance of the common working area, an array of optical distance sensors to compensate shadowing effects of the RGBD camera and a laser range finder to detect the co-worker when approaching the work cell. The software for collision detection, path planning, robot control and predicting the behaviour of the co-worker is based on the Robot Operating System (ROS). A first prototype of the work cell shows that with advanced algorithms from the field of mobile robotics a very flexible safety concept can be realized: the robot not simply stops its movement when detecting a collision, but plans and executes an alternative path around the obstacle.