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- avalanche (5)
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- LAPS (4)
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Introduction: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions.
Methods: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch.
Results: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume.
Conclusions: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.
Prosthetic textile implants of different shapes, sizes and polymers are used to correct the apical prolapse after hysterectomy (removal of the uterus). The selection of the implant before or during minimally invasive surgery depends on the patient’s anatomical defect, intended function after reconstruction and most importantly the surgeon’s preference. Weakness or damage of the supporting tissues during childbirth, menopause or previous pelvic surgeries may put females in higher risk of prolapse. Numerical simulations of reconstructed pelvic floor with weakened tissues and organ supported by textile product models: DynaMesh®-PRS soft, DynaMesh®-PRP soft and DynaMesh®-CESA from FEG Textiletechnik mbH, Germany are compared.
This paper presents a novel numerical procedure for computing limit and shakedown loads of structures using a node-based smoothed FEM in combination with a primal–dual algorithm. An associated primal–dual form based on the von Mises yield criterion is adopted. The primal-dual algorithm together with a Newton-like iteration are then used to solve this associated primal–dual form to determine simultaneously both approximate upper and quasi-lower bounds of the plastic collapse limit and the shakedown limit. The present formulation uses only linear approximations and its implementation into finite element programs is quite simple. Several numerical examples are given to show the reliability, accuracy, and generality of the present formulation compared with other available methods.
The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation.
Aircraft configurations with propellers have been drawing more attention in recent times, partly due to new propulsion concepts based on hydrogen fuel cells and electric motors. These configurations are prone to whirl flutter, which is an aeroelastic instability affecting airframes with elastically supported propellers. It commonly needs to be mitigated already during the design phase of such configurations, requiring, among other things, unsteady aerodynamic transfer functions for the propeller. However, no comprehensive assessment of unsteady propeller aerodynamics for aeroelastic analysis is available in the literature. This paper provides a detailed comparison of nine different low- to mid-fidelity aerodynamic methods, demonstrating their impact on linear, unsteady aerodynamics, as well as whirl flutter stability prediction. Quasi-steady and unsteady methods for blade lift with or without coupling to blade element momentum theory are evaluated and compared to mid-fidelity potential flow solvers (UPM and DUST) and classical, derivative-based methods. Time-domain identification of frequency-domain transfer functions for the unsteady propeller hub loads is used to compare the different methods. Predictions of the minimum required pylon stiffness for stability show good agreement among the mid-fidelity methods. The differences in the stability predictions for the low-fidelity methods are higher. Most methods studied yield a more unstable system than classical, derivative-based whirl flutter analysis, indicating that the use of more sophisticated aerodynamic modeling techniques might be required for accurate whirl flutter prediction.
Comparison of solar hot water systems in solar settlements - decentralized or centralized systems?
(2004)
Comparison of single point and equipotential bonding for I&C systems of large-area industrial sites
(1994)
The Dry-Low-NOx (DLN) Micromix combustion technology has been developed as low emission combustion principle for industrial gas turbines fueled with hydrogen or syngas. The combustion process is based on the phenomenon of jet-in-crossflow-mixing (JICF). Fuel is injected perpendicular into the air-cross-flow and burned in a multitude of miniaturized, diffusion-like flames. The miniaturization of the flames leads to a significant reduction of NOx emissions due to the very short residence time of reactants in the flame. In the Micromix research approach, computational fluid dynamics (CFD) analyses are validated toward experimental results. The combination of numerical and experimental methods allows an efficient design and optimization of DLN Micromix combustors concerning combustion stability and low NOx emissions. The paper presents a comparison of several numerical combustion models for hydrogen and hydrogen-rich syngas. They differ in the complexity of the underlying reaction mechanism and the associated computational effort. The performance of a hybrid eddy-break-up (EBU) model with a one-step global reaction is compared to a complex chemistry model and a flamelet generated manifolds (FGM) model, both using detailed reaction schemes for hydrogen or syngas combustion. Validation of numerical results is based on exhaust gas compositions available from experimental investigation on DLN Micromix combustors. The conducted evaluation confirms that the applied detailed combustion mechanisms are able to predict the general physics of the DLN-Micromix combustion process accurately. The FGM method proved to be generally suitable to reduce the computational effort while maintaining the accuracy of detailed chemistry.
The Dry-Low-NOₓ (DLN) Micromix combustion technology has been developed as low emission combustion principle for industrial gas turbines fueled with hydrogen or syngas. The combustion process is based on the phenomenon of jet-in-crossflow-mixing. Fuel is injected perpendicular into the air-cross-flow and burned in a multitude of miniaturized, diffusion-like flames. The miniaturization of the flames leads to a significant reduction of NOₓ emissions due to the very short residence time of reactants in the flame.
In the Micromix research approach, CFD analyses are validated towards experimental results. The combination of numerical and experimental methods allows an efficient design and optimization of DLN Micromix combustors concerning combustion stability and low NOₓ emissions.
The paper presents a comparison of several numerical combustion models for hydrogen and hydrogen-rich syngas. They differ in the complexity of the underlying reaction mechanism and the associated computational effort.
For pure hydrogen combustion a one-step global reaction is applied using a hybrid Eddy-Break-up model that incorporates finite rate kinetics. The model is evaluated and compared to a detailed hydrogen combustion mechanism derived by Li et al. including 9 species and 19 reversible elementary reactions. Based on this mechanism, reduction of the computational effort is achieved by applying the Flamelet Generated Manifolds (FGM) method while the accuracy of the detailed reaction scheme is maintained.
For hydrogen-rich syngas combustion (H₂-CO) numerical analyses based on a skeletal H₂/CO reaction mechanism derived by Hawkes et al. and a detailed reaction mechanism provided by Ranzi et al. are performed.
The comparison between combustion models and the validation of numerical results is based on exhaust gas compositions available from experimental investigation on DLN Micromix combustors.
The conducted evaluation confirms that the applied detailed combustion mechanisms are able to predict the general physics of the DLN-Micromix combustion process accurately. The Flamelet Generated Manifolds method proved to be generally suitable to reduce the computational effort while maintaining the accuracy of detailed chemistry.
Especially for reaction mechanisms with a high number of species accuracy and computational effort can be balanced using the FGM model.
Objective: As high-field cardiac MRI (CMR) becomes more widespread the propensity of ECG to interference from electromagnetic fields (EMF) and to magneto-hydrodynamic (MHD) effects increases and with it the motivation for a CMR triggering alternative. This study explores the suitability of acoustic cardiac triggering (ACT) for left ventricular (LV) function assessment in healthy subjects (n=14). Methods: Quantitative analysis of 2D CINE steady-state free precession (SSFP) images was conducted to compare ACT’s performance with vector ECG (VCG). Endocardial border sharpness (EBS) was examined paralleled by quantitative LV function assessment. Results: Unlike VCG, ACT provided signal traces free of interference from EMF or MHD effects. In the case of correct Rwave recognition, VCG-triggered 2D CINE SSFP was immune to cardiac motion effects—even at 3.0 T. However, VCG-triggered 2D SSFP CINE imaging was prone to cardiac motion and EBS degradation if R-wave misregistration occurred. ACT-triggered acquisitions yielded LV parameters (end-diastolic volume (EDV), endsystolic volume (ESV), stroke volume (SV), ejection fraction (EF) and left ventricular mass (LVM)) comparable with those derived fromVCG-triggered acquisitions (1.5 T: ESVVCG=(56± 17) ml, EDVVCG=(151±32)ml, LVMVCG=(97±27) g, SVVCG=(94± 19)ml, EFVCG=(63±5)% cf. ESVACT= (56±18) ml, EDVACT=(147±36) ml, LVMACT=(102±29) g, SVACT=(91± 22) ml, EFACT=(62±6)%; 3.0 T: ESVVCG=(55±21) ml, EDVVCG=(151±32) ml, LVMVCG=(101±27) g, SVVCG=(96±15) ml, EFVCG=(65±7)% cf. ESVACT=(54±20) ml, EDVACT=(146±35) ml, LVMACT= (101±30) g, SVACT=(92±17) ml, EFACT=(64±6)%). Conclusions: ACT’s intrinsic insensitivity to interference from electromagnetic fields renders
Semiconductor-based chemical imaging sensors, like the light-addressable potentiometric sensor (LAPS) or the pH-imaging sensor based on a charge-coupled device (CCD), are becoming a powerful tool for label-free imaging of biological phenomena. We have proposed a polyion-based enzymatic membrane to develop an acetylcholine (ACh) imaging sensor for neural cell-activity observations. In this study, a CCD-type ACh-imaging sensor and a LAPS-type ACh-imaging sensor were fabricated and the prospect of both sensors was clarified by making a comparison of their basic characteristics.
Comparison of Intravenous Immunoglobulins for Naturally Occurring Autoantibodies against Amyloid-β
(2010)
Differential multiplicities of forward produced hadrons in deep inelastic muon scattering on nuclear targets have been compared with those from deuterium. The ratios are observed to increase towards unity as the virtual photon energy increases with no significant dependence on the other muon kinematic variables. The hadron transverse momentum distribution is observed to be broadened in nuclear targets. The dependence on the remaining hadron variables is investigated and the results are discussed in the framework of intranuclear interaction models and in the context of the EMC effect.
Comparison of different training algorithms for the leg extension training with an industrial robot
(2018)
In the past, different training scenarios have been developed and implemented on robotic research platforms, but no systematic analysis and comparison have been done so far. This paper deals with the comparison of an isokinematic (motion with constant velocity) and an isotonic (motion against constant weight) training algorithm. Both algorithms are designed for a robotic research platform consisting of a 3D force plate and a high payload industrial robot, which allows leg extension training with arbitrary six-dimensional motion trajectories. In the isokinematic as well as the isotonic training algorithm, individual paths are defined i n C artesian s pace by sufficient s upport p oses. I n t he i sotonic t raining s cenario, the trajectory is adapted to the measured force as the robot should only move along the trajectory as long as the force applied by the user exceeds a minimum threshold. In the isotonic training scenario however, the robot’s acceleration is a function of the force applied by the user. To validate these findings, a simulative experiment with a simple linear trajectory is performed. For this purpose, the same force path is applied in both training scenarios. The results illustrate that the algorithms differ in the force dependent trajectory adaption.
Dual frequency magnetic excitation of magnetic nanoparticles (MNP) enables enhanced biosensing applications. This was studied from an experimental and theoretical perspective: nonlinear sum-frequency components of MNP exposed to dual-frequency magnetic excitation were measured as a function of static magnetic offset field. The Langevin model in thermodynamic equilibrium was fitted to the experimental data to derive parameters of the lognormal core size distribution. These parameters were subsequently used as inputs for micromagnetic Monte-Carlo (MC)-simulations. From the hysteresis loops obtained from MC-simulations, sum-frequency components were numerically demodulated and compared with both experiment and Langevin model predictions. From the latter, we derived that approximately 90% of the frequency mixing magnetic response signal is generated by the largest 10% of MNP. We therefore suggest that small particles do not contribute to the frequency mixing signal, which is supported by MC-simulation results. Both theoretical approaches describe the experimental signal shapes well, but with notable differences between experiment and micromagnetic simulations. These deviations could result from Brownian relaxations which are, albeit experimentally inhibited, included in MC-simulation, or (yet unconsidered) cluster-effects of MNP, or inaccurately derived input for MC-simulations, because the largest particles dominate the experimental signal but concurrently do not fulfill the precondition of thermodynamic equilibrium required by Langevin theory.
Heavy-duty trucks are one of the main contributors to greenhouse gas emissions in German traffic. Drivetrain electrification is an option to reduce tailpipe emissions by increasing energy conversion efficiency. To evaluate the vehicle’s environmental impacts, it is necessary to consider the entire life cycle. In addition to the daily use, it is also necessary to include the impact of production and disposal. This study presents the comparative life cycle analysis of a parallel hybrid and a conventional heavy-duty truck in long-haul operation. Assuming a uniform vehicle glider, only the differing parts of both drivetrains are taken into account to calculate the environmental burdens of the production. The use phase is modeled by a backward simulation in MATLAB/Simulink considering a characteristic driving cycle. A break-even analysis is conducted to show at what mileage the larger CO2eq emissions due to the production of the electric drivetrain are compensated. The effect of parameter variation on the break-even mileage is investigated by a sensitivity analysis. The results of this analysis show the difference in CO2eq/t km is negative, indicating that the hybrid vehicle releases 4.34 g CO2eq/t km over a lifetime fewer emissions compared to the diesel truck. The break-even analysis also emphasizes the advantages of the electrified drivetrain, compensating the larger emissions generated during production after already a distance of 15,800 km (approx. 1.5 months of operation time). The intersection coordinates, distance, and CO2eq, strongly depend on fuel, emissions for battery production and the driving profile, which lead to nearly all parameter variations showing an increase in break-even distance.
Comparative assessment of parallel-hybrid-electric propulsion systems for four different aircraft
(2020)
Until electric energy storage systems are ready to allow fully electric aircraft, the combination of combustion engine and electric motor as a hybrid-electric propulsion system seems to be a promising intermediate solution. Consequently, the design space for future aircraft is expanded considerably, as serial hybrid-electric, parallel hybrid-electric, fully electric, and conventional propulsion systems must all be considered. While the best propulsion system depends on a multitude of requirements and considerations, trends can be observed for certain types of aircraft and certain types of missions. This Paper provides insight into some factors that drive a new design toward either conventional or hybrid propulsion systems. General aviation aircraft, regional transport aircraft vertical takeoff and landing air taxis, and unmanned aerial vehicles are chosen as case studies. Typical missions for each class are considered, and the aircraft are analyzed regarding their takeoff mass and primary energy consumption. For these case studies, a high-level approach is chosen, using an initial sizing methodology. Only parallel-hybrid-electric powertrains are taken into account. Aeropropulsive interaction effects are neglected. Results indicate that hybrid-electric propulsion systems should be considered if the propulsion system is sized by short-duration power constraints. However, if the propulsion system is sized by a continuous power requirement, hybrid-electric systems offer hardly any benefit.
Combining physiological relevance and throughput for in vitro cardiac contractility measurement
(2020)
Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these.
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.
Unravelling the factors determining the allocation of carbon to various plant organs is one of the great challenges of modern plant biology. Studying allocation under close to natural conditions requires non-invasive methods, which are now becoming available for measuring plants on a par with those developed for humans. By combining magnetic resonance imaging (MRI) and positron emission tomography (PET), we investigated three contrasting root/shoot systems growing in sand or soil, with respect to their structures, transport routes and the translocation dynamics of recently fixed photoassimilates labelled with the short-lived radioactive carbon isotope 11C. Storage organs of sugar beet (Beta vulgaris) and radish plants (Raphanus sativus) were assessed using MRI, providing images of the internal structures of the organs with high spatial resolution, and while species-specific transport sectoralities, properties of assimilate allocation and unloading characteristics were measured using PET. Growth and carbon allocation within complex root systems were monitored in maize plants (Zea mays), and the results may be used to identify factors affecting root growth in natural substrates or in competition with roots of other plants. MRI–PET co-registration opens the door for non-invasive analysis of plant structures and transport processes that may change in response to genomic, developmental or environmental challenges. It is our aim to make the methods applicable for quantitative analyses of plant traits in phenotyping as well as in understanding the dynamics of key processes that are essential to plant performance.
Real-time and reliable monitoring of the biogas process is crucial for a stable and efficient operation of biogas production in order to avoid digester breakdowns. The concentration of dissolved hydrogen (H₂) represents one of the key parameters for biogas process control. In this work, a one-chip integrated combined amperometric/field-effect sensor for monitoring the dissolved H₂ concentration has been developed for biogas applications. The combination of two different transducer principles might allow a more accurate and reliable measurement of dissolved H₂ as an early warning indicator of digester failures. The feasibility of the approach has been demonstrated by simultaneous amperometric/field-effect measurements of dissolved H₂ concentrations in electrolyte solutions. Both, the amperometric and the field-effect transducer show a linear response behaviour in the H₂ concentration range from 0.1 to 3% (v/v) with a slope of 198.4 ± 13.7 nA/% (v/v) and 14.9 ± 0.5 mV/% (v/v), respectively.
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.
Coincident events in two scintillator crystals coupled to photomultipliers (PMT) are detected by processing just the digital data of the recorded pulses. For this purpose the signals from both PMTs are continuously sampled by free-running ADCs at a sampling rate of 40 MHz. For each sampled pulse the starting time is determined by processing the pulse data. Even a fairly simple interpolating algorithm results in a FWHM of about 2 ns.
Objective
Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels.
Methods
152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions.
Results
In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained.
Conclusion
This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.
Bacterial cell appendix formation supports cell-cell interaction, cell adhesion and cell movement. Additionally, in bioelectrochemical systems (BES), cell appendages have been shown to participate in extracellular electron transfer. In this work, the cell appendix formation of Clostridium acetobutylicum in biofilms of a BES are imaged and compared with conventional biofilms. Under all observed conditions, the cells possess filamentous appendages with a higher number and density in the BES. Differences in the amount of extracellular polymeric substance in the biofilms of the electrodes lead to the conclusion that the cathode can be used as electron donor and the anode as electron acceptor by C. acetobutylicum. When using conductive atomic force microscopy, a current response of about 15 nA is found for the cell appendages from the BES. This is the first report of conductivity for clostridial cell appendices and represents the basis for further studies on their role for biofilm formation and electron transfer.
NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.
The manufacturing share of laser powder bed fusion (L-PBF) increases in industrial application, but still many process steps are manually operated. Additionally, it is not possible to achieve tight dimensional tolerances or low surfaces roughness. Hence, a process chain has to be set up to combine additive manufacturing (AM) with further machining technologies. To achieve a continuous workpiece flow as basis for further industrialization of L-PBF, the paper presents a novel substrate system and its application on L-PBF machines and post-processing. The substrate system consists of a zero-point clamping system and a matrix-like interface of contact pins to be substantially connected to the workpiece within the L-PBF process.
A chip-based amperometric biosensor referring on using the bioelectrocatalytical amplification principle for the detection of low adrenaline concentrations is presented. The adrenaline biosensor has been prepared by modification of a platinum thin-film electrode with an enzyme membrane containing the pyrroloquinoline quinone-dependent glucose dehydrogenase and glutaraldehyde. Measuring conditions such as temperature, pH value, and glucose concentration have been optimized to achieve a high sensitivity and a low detection limit of about 1 nM adrenaline measured in phosphate buffer at neutral pH value. The response of the biosensor to different catecholamines has also been proven. Long-term stability of the adrenaline biosensor has been studied over 10 days. In addition, the biosensor has been successfully applied for adrenaline detection in human blood plasma for future biomedical applications. Furthermore, preliminary experiments have been carried to detect the adrenaline-concentration difference measured in peripheral blood and adrenal venous blood, representing the adrenal vein sampling procedure of a physician.
A microfluidic chip integrating amperometric enzyme sensors for the detection of glucose, glutamate and glutamine in cell-culture fermentation processes has been developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were immobilized by means of cross-linking with glutaraldehyde on platinum thin-film electrodes integrated within a microfluidic channel. The biosensor chip was coupled to a flow-injection analysis system for electrochemical characterization of the sensors. The sensors have been characterized in terms of sensitivity, linear working range and detection limit. The sensitivity evaluated from the respective peak areas was 1.47, 3.68 and 0.28 μAs/mM for the glucose, glutamate and glutamine sensor, respectively. The calibration curves were linear up to a concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The lower detection limit amounted to be 0.05 mM for the glucose and glutamate sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell-culture medium have demonstrated a good correlation between the glutamate, glutamine and glucose concentrations measured with the chip-based biosensors in a differential-mode and the commercially available instrumentation. The obtained results demonstrate the feasibility of the realized microfluidic biosensor chip for monitoring of bioprocesses.
High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors for liquids. In this work, BST films have been applied as a sensitive transducer material for a label-free detection of adsorbed charged macromolecules (positively charged polyelectrolytes) and concentration of hydrogen peroxide vapor as well as protection insulator layer for a contactless electrolyte-conductivity sensor. The experimental results of characterization of individual sensors are presented. Special emphasis is devoted towards the development of a capacitively-coupled contactless electrolyte-conductivity sensor.
The chemical imaging sensor is a device to visualize the spatial distribution of chemical species based on the principle of LAPS (light-addressable potentiometric sensor), which is a field-effect chemical sensor based on semiconductor. In this study, the chemical imaging sensor has been applied to investigate the ion profile of laminar flows in a microfluidic channel. The chemical images (pH maps) were collected in a Y-shaped microfluidic channel while injecting HCl and NaCl solutions into two branches. From the chemical images, it was clearly observed that the injected solutions formed laminar flows in the channel. In addition, ion diffusion across the laminar flows was observed, and the diffusion coefficient could be derived by fitting the pH profiles to the Fick's equation.
The chemical imaging sensor is a chemical sensor which is capable of visualizing the spatial distribution of chemical species in sample solution. In this study, a novel measurement system based on the chemical imaging sensor was developed to observe the inside of a Y-shaped microfluidic channel while injecting two sample solutions from two branches. From the collected chemical images, it was clearly observed that the injected solutions formed laminar flows in the microfluidic channel. In addition, ion diffusion across the laminar flows was observed. This label-free method can acquire quantitative data of ion distribution and diffusion in microfluidic devices, which can be used to determine the diffusion coefficients, and therefore, the molecular weights of chemical species in the sample solution.
Characterizing volcanic ash elements from the 2015 eruptions of bromo and raung volcanoes, Indonesia
(2020)
The volcanic eruptions of Mt. Bromo and Mt. Raung in East Java, Indonesia, in 2015 perturbed volcanic materials and affected surface-layer air quality at surrounding locations. During the episodes, the volcanic ash from the eruptions influenced visibility, traffic accidents, flight schedules, and human health. In this research, the volcanic ash particles were collected and characterized by relying on the detail of physical observation. We performed an assessment of the volcanic ash elements to characterize the volcanic ash using two different methods which are aqua regia extracts followed by MP-AES and XRF laboratory test of bulk samples. The analysis results showed that the volcanic ash was mixed of many materials, such as Al, Si, P, K, Ca, Ti, V, Cr, Mn, Fe, Ni, and others. Fe, Si, Ca, and Al were found as the major elements, while the others were the trace elements Ba, Cr, Cu, Mn, P, Mn, Ni, Zn, Sb, Sr, and V with the minor concentrations. XRF analyses showed that Fe dominated the elements of the volcanic ash. The XRF analysis showed that Fe was at 35.40% in Bromo and 43.00% in Raung of the detected elements in bulk material. The results of aqua regia extracts analyzed by MP-AES were 1.80% and 1.70% of Fe element for Bromo and Raung volcanoes, respectively.