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The steel industry in the European Union (EU), important for the economy as a whole, faces various challenges. These are inter alia volatile prices for relevant input factors, uncertainties concerning the regulation of CO₂-emissions and market shocks caused by the recently introduced additional import duties in the US, which is an important sales market. We examine primary and secondary effects of these challenges on the steel industry in the EU and their impacts on European and global level. Developing and using a suitable meta-model, we analyze the competitiveness of key steel producing countries with respect to floor prices depending on selected cost factors and draw conclusions on the impacts in the trade of steel on emissions, energy demand, on the involvement of developing countries in the value chain as well on the need for innovations to avoid relocations of production. Hence, our study contributes to the assessment of sustainable industrial development, which is aimed by the Sustainability Development Goal “Build resilient infrastructure, promote inclusive and sustainable industrialization and foster innovation countries”. By applying information on country-specific Human Development Indexes (reflecting aspects of life expectancy, education, and per capita income), we show that relocating energy-intensive industries from the EU may not only increase global energy demand and CO₂-emissions, but may also be to the disadvantage of developing countries.
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.
After a short introduction of a new nonconforming linear finite element on quadrilaterals recently developed by Park, we derive a dual weighted residual-based a posteriori error estimator (in the sense of Becker and Rannacher) for this finite element. By computing a corresponding dual solution we estimate the error with respect to a given target error functional. The reliability and efficiency of this estimator is analyzed in several numerical experiments.
Recently, we introduced and mathematically analysed a new method for grid deformation (Grajewski et al., 2009) [15] we call basic deformation method (BDM) here. It generalises the method proposed by Liao et al. (Bochev et al., 1996; Cai et al., 2004; Liao and Anderson, 1992) [4], [6], [20]. In this article, we employ the BDM as core of a new multilevel deformation method (MDM) which leads to vast improvements regarding robustness, accuracy and speed. We achieve this by splitting up the deformation process in a sequence of easier subproblems and by exploiting grid hierarchy. Being of optimal asymptotic complexity, we experience speed-ups up to a factor of 15 in our test cases compared to the BDM. This gives our MDM the potential for tackling large grids and time-dependent problems, where possibly the grid must be dynamically deformed once per time step according to the user's needs. Moreover, we elaborate on implementational aspects, in particular efficient grid searching, which is a key ingredient of the BDM.
Three-dimensional (3D) full-field measurements provide a comprehensive and accurate validation of finite element (FE) models. For the validation, the result of the model and measurements are compared based on two respective point-sets and this requires the point-sets to be registered in one coordinate system. Point-set registration is a non-convex optimization problem that has widely been solved by the ordinary iterative closest point algorithm. However, this approach necessitates a good initialization without which it easily returns a local optimum, i.e. an erroneous registration. The globally optimal iterative closest point (Go-ICP) algorithm has overcome this drawback and forms the basis for the presented open-source tool that can be used for the validation of FE models using 3D full-field measurements. The capability of the tool is demonstrated using an application example from the field of biomechanics. Methodological problems that arise in real-world data and the respective implemented solution approaches are discussed.
Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels
(2019)
A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions
(2019)
Hydrogen peroxide (H2O2) is a typical surface sterilization agent for packaging materials used in the pharmaceutical, food and beverage industries. We use the finite-elements method to analyze the conceptual design of an in-line thermal evaporation unit to produce a heated gas mixture of air and evaporated H2O2 solution. For the numerical model, the required phase-transition variables of pure H2O2 solution and of the aerosol mixture are acquired from vapor-liquid equilibrium (VLE) diagrams derived from vapor-pressure formulations. This work combines homogeneous single-phase turbulent flow with heat-transfer physics to describe the operation of the evaporation unit. We introduce the apparent heat-capacity concept to approximate the non-isothermal phase-transition process of the H2O2-containing aerosol. Empirical and analytical functions are defined to represent the temperature- and pressure-dependent material properties of the aqueous H2O2 solution, the aerosol and the gas mixture. To validate the numerical model, the simulation results are compared to experimental data on the heating power required to produce the gas mixture. This shows good agreement with the deviations below 10%. Experimental observations on the formation of deposits due to the evaporation of stabilized H2O2 solution fits the prediction made from simulation results.
Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives.
An overview on dry low NOx micromix combustor development for hydrogen-rich gas turbine applications
(2019)
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 Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
(2017)
Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition.
Divided government is often thought of as causing legislative deadlock. I investigate the link between divided government and economic reforms using a novel data set on welfare reforms in US states between 1978 and 2010. Panel data regressions show that, under divided government, a US state is around 25% more likely to adopt a welfare reform than under unified government. Several robustness checks confirm this counter-intuitive finding. Case study evidence suggests an explanation based on policy competition between governor, senate, and house.
This paper investigates the extent to which corporate governance affects the cost of debt and equity capital of German exchange-listed companies. I examine corporate governance along three dimensions: financial information quality, ownership structure and board structure. The results suggest that firms with high levels of financial transparency and bonus compensations face lower cost of equity. In addition, block ownership is negatively related to firms' cost of equity when the blockholders are other firms, managers or founding-family members. Consistent with the conjecture that agency costs increase with firm size, I find significant cost of debt effects only in the largest German companies. Here, the creditors demand lower cost of debt from firms with block ownerships held by corporations or banks. My findings demonstrate that a uniform set of governance attributes is unlikely to satisfy suppliers of debt and equity capital equally.
Postural and metabolic benefits of using a forearm support walker in older adults with impairments
(2019)
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.
Objective
To investigate whether functional brain networks of epilepsy patients treated with antiepileptic medication differ from networks of healthy controls even during the seizure-free interval.
Methods
We applied different rules to construct binary and weighted networks from EEG and MEG data recorded under a resting-state eyes-open and eyes-closed condition from 21 epilepsy patients and 23 healthy controls. The average shortest path length and the clustering coefficient served as global statistical network characteristics.
Results
Independent on the behavioral condition, epileptic brains exhibited a more regular functional network structure. Similarly, the eyes-closed condition was characterized by a more regular functional network structure in both groups. The amount of network reorganization due to behavioral state changes was similar in both groups. Consistent findings could be achieved for networks derived from EEG but hardly from MEG recordings, and network construction rules had a rather strong impact on our findings.
Conclusions
Despite the locality of the investigated processes epileptic brain networks differ in their global characteristics from non-epileptic brain networks. Further methodological developments are necessary to improve the characterization of disturbed and normal functional networks.
Significance
An increased regularity and a diminished modulation capability appear characteristic of epileptic brain networks.
Network theory provides novel concepts that promise an improved characterization of interacting dynamical systems. Within this framework, evolving networks can be considered as being composed of nodes, representing systems, and of time-varying edges, representing interactions between these systems. This approach is highly attractive to further our understanding of the physiological and pathophysiological dynamics in human brain networks. Indeed, there is growing evidence that the epileptic process can be regarded as a large-scale network phenomenon. We here review methodologies for inferring networks from empirical time series and for a characterization of these evolving networks. We summarize recent findings derived from studies that investigate human epileptic brain networks evolving on timescales ranging from few seconds to weeks. We point to possible pitfalls and open issues, and discuss future perspectives.
We investigate the suitability of selected measures of complexity based on recurrence quantification analysis and recurrence networks for an identification of pre-seizure states in multi-day, multi-channel, invasive electroencephalographic recordings from five epilepsy patients. We employ several statistical techniques to avoid spurious findings due to various influencing factors and due to multiple comparisons and observe precursory structures in three patients. Our findings indicate a high congruence among measures in identifying seizure precursors and emphasize the current notion of seizure generation in large-scale epileptic networks. A final judgment of the suitability for field studies, however, requires evaluation on a larger database.
68Ga-radiopharmaceuticals are common in the field of Nuclear Medicine to visualize receptor-mediated processes. In contrast to straightforward labeling procedures for clinical applications, preclinical in vitro and in vivo applications are hampered for reasons like e.g. volume
restriction, activity concentration, molar activity and osmolality. Therefore, we developed a semiautomatic system specifically to overcome these problems. A difficulty appeared unexpectedly, as intrinsic trace metals derived from eluate (Zn, Fe and Cu) are concentrated as well in amounts that influence radiochemical yield and thus lower molar activity.
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 capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples.
Wind is closely associated with the discussion of fairness in ski jumping. To counter-act its influence on the jump length, the International Ski Federation (FIS) has introduced a wind compensation approach. We applied three differently accurate computer models of the flight phase with wind (M1, M2, and M3) to study the jump length effects of various wind scenarios. The previously used model M1 is accurate for wind blowing in direction of the flight path, but inaccuracies are to be expected for wind directions deviating from the tangent to the flight path. M2 considers the change of airflow direction, but it does not consider the associated change in the angle of attack of the skis which additionally modifies drag and lift area time functions. M3 predicts the length effect for all wind directions within the plane of the flight trajectory without any mathematical simplification. Prediction errors of M3 are determined only by the quality of the input data: wind velocity, drag and lift area functions, take-off velocity, and weight. For comparing the three models, drag and lift area functions of an optimized reference jump were used. Results obtained with M2, which is much easier to handle than M3, did not deviate noticeably when compared to predictions of the reference model M3. Therefore, we suggest to use M2 in future applications. A comparison of M2 predictions with the FIS wind compensation system showed substantial discrepancies, for instance: in the first flight phase, tailwind can increase jump length, and headwind can decrease it; this is opposite of what had been anticipated before and is not considered in the current wind compensation system in ski jumping.
Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system.
Accurate determination of free-surface dynamics has attracted much research attention during the past decade and has important applications in many environmental and water related areas. In this study, the free-surface dynamics in several turbulent flows commonly found in nature were investigated using a synchronised setup consisting of an ultrasonic sensor and a high-speed video camera. Basic sensor capabilities were examined in dry conditions to allow for a better characterisation of the present sensor model. The ultrasonic sensor was found to adequately reproduce free-surface dynamics up to the second order, especially in two-dimensional scenarios with the most energetic modes in the low frequency range. The sensor frequency response was satisfactory in the sub-20 Hz band, and its signal quality may be further improved by low-pass filtering prior to digitisation. The application of the USS to characterise entrapped air in high-velocity flows is also discussed.
Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate.
A field-effect biosensor employing tobacco mosaic virus (TMV) particles as scaffolds for enzyme immobilization is presented. Nanotubular TMV scaffolds allow a dense immobilization of precisely positioned enzymes with retained activity. To demonstrate feasibility of this new strategy, a penicillin sensor has been developed by coupling a penicillinase with virus particles as a model system. The developed field-effect penicillin biosensor consists of an Al-p-Si-SiO₂-Ta₂O₅-TMV structure and has been electrochemically characterized in buffer solutions containing different concentrations of penicillin G. In addition, the morphology of the biosensor surface with virus particles was characterized by scanning electron microscopy and atomic force microscopy methods. The sensors possessed a high penicillin sensitivity of ~ 92 mV/dec in a nearly-linear range from 0.1 mM to 10 mM, and a low detection limit of about 50 µM. The long-term stability of the penicillin biosensor was periodically tested over a time period of about one year without any significant loss of sensitivity. The biosensor has also been successfully applied for penicillin detection in bovine milk samples.
The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy.
Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations.
Production of Y-86 and other radiometals for research purposes using a solution target system
(2015)
[⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.
N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core.
A new formulation for the prediction of free surface dynamics related to the turbulence occurring nearby is proposed. This formulation, altogether with a breakup criterion, can be used to compute the inception of self-aeration in high velocity flows like those occurring in hydraulic structures. Assuming a simple perturbation geometry, a kinematic and a non-linear momentum-based dynamic equation are formulated and forces acting on a control volume are approximated. Limiting steepness is proposed as an adequate breakup criterion. Role of the velocity fluctuations normal to the free surface is shown to be the main turbulence quantity related to self-aeration and the role of the scales contained in the turbulence spectrum are depicted. Surface tension force is integrated accounting for large displacements by using differential geometry for the curvature estimation. Gravity and pressure effects are also contemplated in the proposed formulation. The obtained equations can be numerically integrated for each wavelength, hence resulting in different growth rates and allowing computation of the free surface roughness wavelength distribution. Application to a prototype scale spillway (at the Aviemore dam) revealed that most unstable wavelength was close to the Taylor lengthscale. Amplitude distributions have been also obtained observing different scaling for perturbations stabilized by gravity or surface tension. The proposed theoretical framework represents a new conceptualization of self-aeration which explains the characteristic rough surface at the non-aerated region as well as other previous experimental observations which remained unresolved for several decades.
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.
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.
The immobilization of NAD+-dependent dehydrogenases, in combination with a diaphorase, enables the facile development of multiparametric sensing devices. In this work, an amperometric biosensor array for simultaneous determination of ethanol, formate, d- and l-lactate is presented. Enzyme immobilization on platinum thin-film electrodes was realized by chemical cross-linking with glutaraldehyde. The optimization of the sensor performance was investigated with regard to enzyme loading, glutaraldehyde concentration, pH, cofactor concentration and temperature. Under optimal working conditions (potassium phosphate buffer with pH 7.5, 2.5 mmol L-1 NAD+, 2.0 mmol L-1 ferricyanide, 25 °C and 0.4% glutaraldehyde) the linear working range and sensitivity of the four sensor elements was improved. Simultaneous and cross-talk free measurements of four different metabolic parameters were performed successfully. The reliable analytical performance of the biosensor array was demonstrated by application in a clarified sample of inoculum sludge. Thereby, a promising approach for on-site monitoring of fermentation processes is provided.
An enzyme-based reversible Controlled NOT (CNOT) logic gate operating on a semiconductor transducer
(2017)
An enzyme-based biocatalytic system mimicking operation of a logically reversible Controlled NOT (CNOT) gate has been interfaced with semiconductor electronic transducers. Electrolyte–insulator–semiconductor (EIS) structures have been used to transduce chemical changes produced by the enzyme system to an electronically readable capacitive output signal using field-effect features of the EIS device. Two enzymes, urease and esterase, were immobilized on the insulating interface of EIS structure producing local pH changes performing XOR logic operation controlled by various combinations of the input signals represented by urea and ethyl butyrate. Another EIS transducer was functionalized with esterase only, thus performing Identity (ID) logic operation for the ethyl butyrate input. Both semiconductor devices assembled in parallel operated as a logically reversible CNOT gate. The present system, despite its simplicity, demonstrated for the first time logically reversible function of the enzyme system transduced electronically with the semiconductor devices. The biomolecular realization of a CNOT gate interfaced with semiconductors is promising for integration into complex biomolecular networks and future biosensor/biomedical applications.
To study chemical and biological processes, spatially resolved determination of the concentrations of one or more analyte species is of distinct interest. With a light-addressable potentiometric sensor (LAPS), chemical images can be created, which visualize the concentration distribution above the sensor plate. One important challenge is to achieve a good lateral resolution in order to detect events that take place in a small and limited region. LAPS utilizes a focused light spot to address the measurement region. By moving this light spot along the semiconductor sensor plate, the concentration distribution can be observed. In this study, we show that utilizing a pulse as light excitation instead of a traditionally used continuously modulated light excitation, the lateral resolution can be improved by a factor of 6 or more.
A high-Q resonance-mode measurement of EIS capacitive sensor by elimination of series resistance
(2017)
An EIS capacitive sensor is a semiconductor-based potentiometric sensor, which is sensitive to the ion concentration or pH value of the solution in contact with the sensing surface. To detect a small change in the ion concentration or pH, a small capacitance change must be detected. Recently, a resonance-mode measurement was proposed, in which an inductor was connected to the EIS capacitive sensor and the resonant frequency was correlated with the pH value. In this study, the Q factor of the resonant circuit was enhanced by canceling the internal resistance of the reference electrode and the internal resistance of the inductor coil with the help of a bypass capacitor and a negative impedance converter, respectively. 1% variation of the signal in the developed system corresponded to a pH change of 3.93 mpH, which was about 1/12 of the conventional method, suggesting a better performance in detection of a small pH change.
A light-addressable potentiometric sensor (LAPS) is a field-effect-based potentiometric sensor with an electrolyte/insulator/semiconductor (EIS) structure, which is able to monitor analyte concentrations of (bio-)chemical species in aqueous solutions in a spatially resolved way. Therefore, it is also an appropriate tool to record 2D-chemical images of concentration variations on the sensor surface. In the present work, two differential, LAPS-based measurement principles are introduced to determine the metabolic activity of Escherichia coli (E. coli) K12 and Chinese hamster ovary (CHO) cells as test microorganisms. Hereby, we focus on i) the determination of the extracellular acidification rate (ΔpH/min) after adding glucose solutions to the cell suspensions; and ii) recording the amplitude increase of the photocurrent (Iph) related to the produced acids from E. coli K12 bacteria and CHO cells on the sensor surface by 2D-chemical imaging. For this purpose, 3D-printed multi-chamber structures were developed and mounted on the planar sensor-chip surface to define four independent compartments, enabling differential measurements with varying cell concentrations. The differential concept allows eliminating unwanted drift effects and, with the four-chamber structures, measurements on the different cell concentrations were performed simultaneously, thus reducing also the overall measuring time.
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 gene encoding a putative (R,R)-butane-2,3-diol dehydrogenase (bdhA) from Bacillus clausii DSM 8716T was isolated, sequenced and expressed in Escherichia coli. The amino acid sequence of the encoded protein is only distantly related to previously studied enzymes (identity 33–43%) and exhibited some uncharted peculiarities. An N-terminally StrepII-tagged enzyme variant was purified and initially characterized. The isolated enzyme catalyzed the (R)-specific oxidation of (R,R)- and meso-butane-2,3-diol to (R)- and (S)-acetoin with specific activities of 12 U/mg and 23 U/mg, respectively. Likewise, racemic acetoin was reduced with a specific activity of up to 115 U/mg yielding a mixture of (R,R)- and meso-butane-2,3-diol, while the enzyme reduced butane-2,3-dione (Vmax 74 U/mg) solely to (R,R)-butane-2,3-diol via (R)-acetoin. For these reactions only activity with the co-substrates NADH/NAD+ was observed. The enzyme accepted a selection of vicinal diketones, α-hydroxy ketones and vicinal diols as alternative substrates. Although the physiological function of the enzyme in B. clausii remains elusive, the data presented herein clearly demonstrates that the encoded enzyme is a genuine (R,R)-butane-2,3-diol dehydrogenase with potential for applications in biocatalysis and sensor development.
The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹.
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.
The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase.
In the present work, surface functionalization of different sensor materials was studied. Organosilanes are well known to serve as coupling agent for biomolecules or cells on inorganic materials. 3-aminopropyltriethoxysilane (APTES) was used to attach microbiological spores time to an interdigitated sensor surface. The functionality and physical properties of APTES were studied on isolated sensor materials, namely silicon dioxide (SiO2) and platinum (Pt) as well as the combined material on sensor level. A predominant immobilization of spores could be demonstrated on SiO2 surfaces. Additionally, the impedance signal of APTES-functionalized biosensor chips has been investigated.
Short term effects of magnetic resonance imaging on excitability of the motor cortex at 1.5T and 7T
(2010)
Rationale and Objectives
The increasing spread of high-field and ultra-high-field magnetic resonance imaging (MRI) scanners has encouraged new discussion of the safety aspects of MRI. Few studies have been published on possible cognitive effects of MRI examinations. The aim of this study was to examine whether changes are measurable after MRI examinations at 1.5 and 7 T by means of transcranial magnetic stimulation (TMS).
Materials and Methods
TMS was performed in 12 healthy, right-handed male volunteers. First the individual motor threshold was specified, and then the cortical silent period (SP) was measured. Subsequently, the volunteers were exposed to the 1.5-T MRI scanner for 63 minutes using standard sequences. The MRI examination was immediately followed by another TMS session. Fifteen minutes later, TMS was repeated. Four weeks later, the complete setting was repeated using a 7-T scanner. Control conditions included lying in the 1.5-T scanner for 63 minutes without scanning and lying in a separate room for 63 minutes. TMS was performed in the same way in each case. For statistical analysis, Wilcoxon's rank test was performed.
Results
Immediately after MRI exposure, the SP was highly significantly prolonged in all 12 subjects at 1.5 and 7 T. The motor threshold was significantly increased. Fifteen minutes after the examination, the measured value tended toward normal again. Control conditions revealed no significant differences.
Conclusion
MRI examinations lead to a transient and highly significant alteration in cortical excitability. This effect does not seem to depend on the strength of the static magnetic field.
Compared to peripheral pain, trigeminal pain elicits higher levels of fear, which is assumed to enhance the interruptive effects of pain on concomitant cognitive processes. In this fMRI study we examined the behavioral and neural effects of trigeminal (forehead) and peripheral (hand) pain on visual processing and memory encoding. Cerebral activity was measured in 23 healthy subjects performing a visual categorization task that was immediately followed by a surprise recognition task. During the categorization task subjects received concomitant noxious electrical stimulation on the forehead or hand. Our data show that fear ratings were significantly higher for trigeminal pain. Categorization and recognition performance did not differ between pictures that were presented with trigeminal and peripheral pain. However, object categorization in the presence of trigeminal pain was associated with stronger activity in task-relevant visual areas (lateral occipital complex, LOC), memory encoding areas (hippocampus and parahippocampus) and areas implicated in emotional processing (amygdala) compared to peripheral pain. Further, individual differences in neural activation between the trigeminal and the peripheral condition were positively related to differences in fear ratings between both conditions. Functional connectivity between amygdala and LOC was increased during trigeminal compared to peripheral painful stimulation. Fear-driven compensatory resource activation seems to be enhanced for trigeminal stimuli, presumably due to their exceptional biological relevance.
SAR Simulations & Safety
(2017)
The LAPS (light-addressable potentiometric sensor) platform is one of the most attractive approaches for chemical and biological sensing with many applications ranging from pH and ion/analyte concentration measurements up to cell metabolism detection and chemical imaging. However, although it is generally accepted that LAPS measurements are spatially resolved, the light-addressability feature of LAPS devices has not been discussed in detail so far. In this work, an extended electrical equivalent-circuit model of the LAPS has been presented, which takes into account possible cross-talk effects due to the capacitive coupling of the non-illuminated region. A shunting effect of the non-illuminated area on the measured photocurrent and addressability of LAPS devices has been studied. It has been shown, that the measured photocurrent will be determined not only by the local interfacial potential in the illuminated region but also by possible interfacial potential changes in the non-illuminated region, yielding cross-talk effects. These findings were supported by the experimental investigations of a penicillin-sensitive multi-spot LAPS and a metal-insulator-semiconductor LAPS as model systems.
The purpose of the current study was to examine the reproducibility of fascicle length and pennation angle of gastrocnemius medialis while human walking. To the best of our knowledge, this is the first study of the reproducibility of fascicle length and pennation angle of gastrocnemius medialis in vivo during human gait. Twelve males performed 10 gait trials on a treadmill, in 2 separate days. B-mode ultrasonography, with the ultrasound probe firmly adjusted in the transverse and frontal planes using a special cast, was used to measure the fascicle length and the pennation angle of the gastrocnemius medialis (GM). A Vicon 624 system with three cameras operating at 120 Hz was also used to record the ankle and knee joint angles. The results showed that measurements of fascicle length and pennation angle showed high reproducibility during the gait cycle, both within the same day and between different days. Moreover, the root mean square differences between the repeated waveforms of both variables were very small, compared with their ranges (fascicle length: RMS = ∼3 mm, range: 38–63 mm; pennation angle: RMS = ∼1.5°, range: 22–32°). However, their reproducibility was lower compared to the joint angles. It was found that representative data have to be derived by a wide number of gait trials (fascicle length ∼six trials, pennation angle more than 10 trials), to assure the reliability of the fascicle length and pennation angle in human gait.
The purpose of the current study in combination with our previous published data (Arampatzis et al., 2007) was to examine the effects of a controlled modulation of strain magnitude and strain frequency applied to the Achilles tendon on the plasticity of tendon mechanical and morphological properties. Eleven male adults (23.9±2.2 yr) participated in the study. The participants exercised one leg at low magnitude tendon strain (2.97±0.47%), and the other leg at high tendon strain magnitude (4.72±1.08%) of similar frequency (0.5 Hz, 1 s loading, 1 s relaxation) and exercise volume (integral of the plantar flexion moment over time) for 14 weeks, 4 days per week, 5 sets per session. The exercise volume was similar to the intervention of our earlier study (0.17 Hz frequency; 3 s loading, 3 s relaxation) allowing a direct comparison of the results. Before and after the intervention ankle joint moment has been measured by a dynamometer, tendon–aponeurosis elongation by ultrasound and cross-sectional area of the Achilles tendon by magnet resonance images (MRI). We found a decrease in strain at a given tendon force, an increase in tendon–aponeurosis stiffness and tendon elastic modulus of the Achilles tendon only in the leg exercised at high strain magnitude. The cross-sectional area (CSA) of the Achilles tendon did not show any statistically significant (P>0.05) differences to the pre-exercise values in both legs. The results indicate a superior improvement in tendon properties (stiffness, elastic modulus and CSA) at the low frequency (0.17 Hz) compared to the high strain frequency (0.5 Hz) protocol. These findings provide evidence that the strain magnitude applied to the Achilles tendon should exceed the value, which occurs during habitual activities to trigger adaptational effects and that higher tendon strain duration per contraction leads to superior tendon adaptational responses.
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.
Background and Objective
Effective leg extension training at a leg press requires high forces, which need to be controlled to avoid training-induced damage. In order to avoid high external knee adduction moments, which are one reason for unphysiological loadings on knee joint structures, both training movements and the whole reaction force vector need to be observed. In this study, the applicability of lateral and medial changes in foot orientation and position as possible manipulated variables to control external knee adduction moments is investigated. As secondary parameters both the medio-lateral position of the center of pressure and the frontal-plane orientation of the reaction force vector are analyzed.
Methods
Knee adduction moments are estimated using a dynamic model of the musculoskeletal system together with the measured reaction force vector and the motion of the subject by solving the inverse kinematic and dynamic problem. Six different foot conditions with varying positions and orientations of the foot in a static leg press are evaluated and compared to a neutral foot position.
Results
Both lateral and medial wedges under the foot and medial and lateral shifts of the foot can influence external knee adduction moments in the presented study with six healthy subjects. Different effects are observed with the varying conditions: the pose of the leg is changed and the direction and center of pressure of the reaction force vector is influenced. Each effect results in a different direction or center of pressure of the reaction force vector.
Conclusions
The results allow the conclusion that foot position and orientation can be used as manipulated variables in a control loop to actively control knee adduction moments in leg extension training.
We prove characterizations of the existence of perfect ƒ-matchings in uniform mengerian and perfect hypergraphs. Moreover, we investigate the ƒ-factor problem in balanced hypergraphs. For uniform balanced hypergraphs we prove two existence theorems with purely combinatorial arguments, whereas for non-uniform balanced hypergraphs we show that the ƒ-factor problem is NP-hard.
The conjunction of (bio-)chemical recognition elements with nanoscale biological building blocks such as virus particles is considered as a very promising strategy for the creation of biohybrids opening novel opportunities for label-free biosensing. This work presents a new approach for the development of biosensors using tobacco mosaic virus (TMV) nanotubes or coat proteins (CPs) as enzyme nanocarriers. Sensor chips combining an array of Pt electrodes loaded with glucose oxidase (GOD)-modified TMV nanotubes or CP aggregates were used for amperometric detection of glucose as a model system for the first time. The presence of TMV nanotubes or CPs on the sensor surface allows binding of a high amount of precisely positioned enzymes without substantial loss of their activity, and may also ensure accessibility of their active centers for analyte molecules. Specific and efficient immobilization of streptavidin-conjugated GOD ([SA]-GOD) complexes on biotinylated TMV nanotubes or CPs was achieved via bioaffinity binding. These layouts were tested in parallel with glucose sensors with adsorptively immobilized [SA]-GOD, as well as [SA]-GOD crosslinked with glutardialdehyde, and came out to exhibit superior sensor performance. The achieved results underline a great potential of an integration of virus/biomolecule hybrids with electronic transducers for future applications in biosensorics and biochips.
Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃–(CH₂CH (OCO(CH₂)ₘCH₃))ₙ–Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated.
All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain.
Sensitivity of turbulent Schmidt number and turbulence model to simulations of jets in crossflow
(2016)
Environmental discharges have been traditionally designed by means of cost-intensive and time-consuming experimental studies. Some extensively validated models based on an integral approach have been often employed for water quality problems, as recommended by USEPA (i.e.: CORMIX). In this study, FLOW-3D is employed for a full 3D RANS modelling of two turbulent jet-to-crossflow cases, including free surface jet impingement. Results are compared to both physical modelling and CORMIX to better assess model performance. Turbulence measurements have been collected for a better understanding of turbulent diffusion's parameter sensitivity. Although both studied models are generally able to reproduce jet trajectory, jet separation downstream of the impingement has been reproduced only by RANS modelling. Additionally, concentrations are better reproduced by FLOW-3D when the proper turbulent Schmidt number is used. This study provides a recommendation on the selection of the turbulence model and the turbulent Schmidt number for future outfall structures design studies.
Self-aeration is traditionally explained by the water turbulent boundary layer outer edge intersection with the free surface. This paper presents a discussion on the commonly accepted hypothesis behind the computation of the critical point of self-aeration in spillway flows and a new formulation is proposed based on the existence of a developing air flow over the free surface. Upstream of the inception point of self-aeration, some surface roughening has been often reported in previous studies which consequently implies some entrapped air transport and air–water flows coupling. Such air flow is proven in this study by presenting measured air velocities and computing the air boundary layer thickness for a 1V:2H smooth chute flow. Additionally, the growth rate of free surface waves has been analysed by means of Ultrasonic Sensors measurements, obtaining also the entrapped air concentration. High-speed camera imaging has been used for qualitative study of the flow perturbations.
An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.
The light-addressable potentiometric sensor (LAPS) has the unique feature to address different regions of a sensor surface without the need of complex structures. Measurements at different locations on the sensor surface can be performed in a common analyte solution, which distinctly simplifies the fluidic set-up. However, the measurement in a single analyte chamber prevents the application of different drugs or different concentrations of a drug to each measurement spot at the same time as in the case of multi-reservoir-based set-ups. In this work, the authors designed a LAPS-based set-up for cell culture screening that utilises magnetic beads loaded with the endotoxin (lipopolysaccharides, LPS), to generate a spatially distributed gradient of analyte concentration. Different external magnetic fields can be adjusted to move the magnetic beads loaded with a specific drug within the measurement cell. By recording the metabolic activities of a cell layer cultured on top of the LAPS surface, this work shows the possibility to apply different concentrations of a sample along the LAPS measurement spots within a common analyte solution.
The msprop program presented in this work is capable of solving the Maxwell–Schrödinger equations for one or several laser fields propagating through a medium of quantum optical few-level systems in one spatial dimension and in time. In particular, it allows to numerically treat systems in which a laser field interacts with the medium with both its electric and magnetic component at the same time. The internal dynamics of the few-level system is modeled by a quantum optical master equation which includes coherent processes due to optical transitions driven by the laser fields as well as incoherent processes due to decay and dephasing. The propagation dynamics of the laser fields is treated in slowly varying envelope approximation resulting in a first order wave equation for each laser field envelope function. The program employs an Adams predictor formula second order in time to integrate the quantum optical master equation and a Lax–Wendroff scheme second order in space and time to evolve the wave equations for the fields. The source function in the Lax–Wendroff scheme is specifically adapted to allow taking into account the simultaneous coupling of a laser field to the polarization and the magnetization of the medium. To reduce execution time, a customized data structure is implemented and explained. In three examples the features of the program are demonstrated and the treatment of a system with a phase-dependent cross coupling of the electric and magnetic field component of a laser field is shown.
Visualization of the recovery process of defects in a cultured cell layer by chemical imaging sensor
(2016)
The chemical imaging sensor is a field-effect sensor which is able to visualize both the distribution of ions (in LAPS mode) and the distribution of impedance (in SPIM mode) in the sample. In this study, a novel cell assay is proposed, in which the chemical imaging sensor operated in SPIM mode is applied to monitor the recovery of defects in a cell layer brought into proximity of the sensing surface. A reduced impedance at a defect formed artificially in a cell layer was successfully visualized in a photocurrent image. The cell layer was cultured over two weeks, during which the temporal change of the photocurrent distribution corresponding to the recovery of the defect was observed.
A comparative performance analysis of the CFD platforms OpenFOAM and FLOW-3D is presented, focusing on a 3D swirling turbulent flow: a steady hydraulic jump at low Reynolds number. Turbulence is treated using RANS approach RNG k-ε. A Volume Of Fluid (VOF) method is used to track the air–water interface, consequently aeration is modeled using an Eulerian–Eulerian approach. Structured meshes of cubic elements are used to discretize the channel geometry. The numerical model accuracy is assessed comparing representative hydraulic jump variables (sequent depth ratio, roller length, mean velocity profiles, velocity decay or free surface profile) to experimental data. The model results are also compared to previous studies to broaden the result validation. Both codes reproduced the phenomenon under study concurring with experimental data, although special care must be taken when swirling flows occur. Both models can be used to reproduce the hydraulic performance of energy dissipation structures at low Reynolds numbers.
A multi-spot light-addressable potentiometric sensor (LAPS), which belongs to the family of semiconductor field-effect devices, was applied for label-free detection of double-stranded deoxyribonucleic acid (dsDNA) molecules by their intrinsic molecular charge. To reduce the distance between the DNA charge and sensor surface and thus, to enhance the electrostatic coupling between the dsDNA molecules and the LAPS, the negatively charged dsDNA molecules were electrostatically adsorbed onto the gate surface of the LAPS covered with a positively charged weak polyelectrolyte layer of PAH (poly(allylamine hydrochloride)). The surface potential changes in each spot of the LAPS, induced by the layer-by-layer adsorption of a PAH/dsDNA bilayer, were recorded by means of photocurrent-voltage and constant-photocurrent measurements. In addition, the surface morphology of the gate surface before and after consecutive electrostatic adsorption of PAH and dsDNA layers was studied by atomic force microscopy measurements. Moreover, fluorescence microscopy was used to verify the successful adsorption of dsDNA molecules onto the PAH-modified LAPS surface. A high sensor signal of 25 mV was registered after adsorption of 10 nM dsDNA molecules. The lower detection limit is down to 0.1 nM dsDNA. The obtained results demonstrate that the PAH-modified LAPS device provides a convenient and rapid platform for the direct label-free electrical detection of in-solution hybridized dsDNA molecules.
Based on an identifying Volterra type integral equation for randomly right censored observations from a lifetime distribution function F, we solve the corresponding estimating equation by an explicit and implicit Euler scheme. While the first approach results in some known estimators, the second one produces new semi-parametric and pre-smoothed Kaplan–Meier estimators which are real distribution functions rather than sub-distribution functions as the former ones are. This property of the new estimators is particular useful if one wants to estimate the expected lifetime restricted to the support of the observation time.
Specifically, we focus on estimation under the semi-parametric random censorship model (SRCM), that is, a random censorship model where the conditional expectation of the censoring indicator given the observation belongs to a parametric family. We show that some estimated linear functionals which are based on the new semi-parametric estimator are strong consistent, asymptotically normal, and efficient under SRCM. In a small simulation study, the performance of the new estimator is illustrated under moderate sample sizes. Finally, we apply the new estimator to a well-known real dataset.
We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.