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Biocomposite Materials Based on Carbonized Rice Husk in Biomedicine and Environmental Applications
(2020)
This chapter describes the prospects for biomedical and environmental engineering applications of heterogeneous materials based on nanostructured carbonized rice husk. Efforts in engineering enzymology are focused on the following directions: development and optimization of immobilization methods leading to novel biotechnological and biomedical applications; construction of biocomposite materials based on individual enzymes, multi-enzyme complexes and whole cells, targeted on realization of specific industrial processes. Molecular biological and biochemical studies on cell adhesion focus predominantly on identification, isolation and structural analysis of attachment-responsible biological molecules and their genetic determinants. The chapter provides a short overview of applications of the biocomposite materials based of nanostructured carbonized adsorbents. It emphasizes that further studies and better understanding of the interactions between CNS and microbial cells are necessary. The future use of living cells as biocatalysts, especially in the environmental field, needs more systematic investigations of the microbial adsorption phenomenon.
Bacterial cellulose (BC) is a promising material for biomedical applications due to its unique properties such as high mechanical strength and biocompatibility. This article describes the microbiological synthesis, modification, and characterization of the obtained BC-nanocomposites originating from symbiotic consortium Medusomyces gisevii. Two BC-modifications have been obtained: BC-Ag and BC-calcium phosphate (BC-Ca3(PO4)2). Structure and physicochemical properties of the BC and its modifications were investigated by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), atomic force microscopy (AFM), and infrared Fourier spectroscopy as well as by measurements of mechanical and water holding/absorbing capacities. Topographic analysis of the surface revealed multicomponent thick fibrils (150–160 nm in diameter and about 15 µm in length) constituted by 50–60 nm nanofibrils weaved into a left-hand helix. Distinctive features of Ca-phosphate-modified BC samples were (a) the presence of 500–700 nm entanglements and (b) inclusions of Ca3(PO4)2 crystals. The samples impregnated with Ag nanoparticles exhibited numerous roundish inclusions, about 110 nm in diameter. The boundaries between the organic and inorganic phases were very distinct in both cases. The Ag-modified samples also showed a prominent waving pattern in the packing of nanofibrils. The obtained BC gel films possessed water-holding capacity of about 62.35 g/g. However, the dried (to a constant mass) BC-films later exhibited a low water absorption capacity (3.82 g/g). It was found that decellularized BC samples had 2.4 times larger Young’s modulus and 2.2 times greater tensile strength as compared to dehydrated native BC films. We presume that this was caused by molecular compaction of the BC structure.
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.
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.
Humic substances originating from various organic matters can ameliorate soil properties, stimulate plant growth, and improve nutrient uptake. Due to the low calorific heating value, leonardite is rather unsuitable as fuel. However, it may serve as a potential source of humic substances. This study was aimed at characterizing the leonardite-based soil amendments and examining the effect of their application on the soil microbial community, as well as on potato growth and tuber yield. A high yield (71.1%) of humic acid (LHA) from leonardite has been demonstrated. Parental leonardite (PL) and LHA were applied to soil prior to potato cultivation. The 16S rRNA sequencing of soil samples revealed distinct relationships between microbial community composition and the application of leonardite-based soil amendments. Potato tubers were planted in pots in greenhouse conditions. The tubers were harvested at the mature stage for the determination of growth and yield parameters. The results demonstrated that the LHA treatments had a significant effect on increasing potato growth (54.9%) and tuber yield (66.4%) when compared to the control. The findings highlight the importance of amending leonardite-based humic products for maintaining the biogeochemical stability of soils, for keeping their healthy microbial community structure, and for increasing the agronomic productivity of potato plants.
We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements.
Electrolyte-insulator-semiconductor (EIS) field-effect sensors belong to a new generation of electronic chips for biochemical sensing, enabling a direct electronic readout. The review gives an overview on recent advances and current trends in the research and development of chemical sensors and biosensors based on the capacitive field-effect EIS structure—the simplest field-effect device, which represents a biochemically sensitive capacitor. Fundamental concepts, physicochemical phenomena underlying the transduction mechanism and application of capacitive EIS sensors for the detection of pH, ion concentrations, and enzymatic reactions, as well as the label-free detection of charged molecules (nucleic acids, proteins, and polyelectrolytes) and nanoparticles, are presented and discussed.
Coronavirus disease 2019 (COVID-19) is a novel human infectious disease provoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific vaccines or drugs against COVID-19 are available. Therefore, early diagnosis and treatment are essential in order to slow the virus spread and to contain the disease outbreak. Hence, new diagnostic tests and devices for virus detection in clinical samples that are faster, more accurate and reliable, easier and cost-efficient than existing ones are needed. Due to the small sizes, fast response time, label-free operation without the need for expensive and time-consuming labeling steps, the possibility of real-time and multiplexed measurements, robustness and portability (point-of-care and on-site testing), biosensors based on semiconductor field-effect devices (FEDs) are one of the most attractive platforms for an electrical detection of charged biomolecules and bioparticles by their intrinsic charge. In this review, recent advances and key developments in the field of label-free detection of viruses (including plant viruses) with various types of FEDs are presented. In recent years, however, certain plant viruses have also attracted additional interest for biosensor layouts: Their repetitive protein subunits arranged at nanometric spacing can be employed for coupling functional molecules. If used as adapters on sensor chip surfaces, they allow an efficient immobilization of analyte-specific recognition and detector elements such as antibodies and enzymes at highest surface densities. The display on plant viral bionanoparticles may also lead to long-time stabilization of sensor molecules upon repeated uses and has the potential to increase sensor performance substantially, compared to conventional layouts. This has been demonstrated in different proof-of-concept biosensor devices. Therefore, richly available plant viral particles, non-pathogenic for animals or humans, might gain novel importance if applied in receptor layers of FEDs. These perspectives are explained and discussed with regard to future detection strategies for COVID-19 and related viral diseases.
Extracellular acidification is a basic indicator for alterations in two vital metabolic pathways: glycolysis and cellular respiration. Measuring these alterations by monitoring extracellular acidification using cell-based biosensors such as LAPS plays an important role in studying these pathways whose disorders are associated with numerous diseases including cancer. However, the surface of the biosensors must be specially tailored to ensure high cell compatibility so that cells can represent more in vivo-like behavior, which is critical to gain more realistic in vitro results from the analyses, e.g., drug discovery experiments. In this work, O2 plasma patterning on the LAPS surface is studied to enhance surface features of the sensor chip, e.g., wettability and biofunctionality. The surface treated with O2 plasma for 30 s exhibits enhanced cytocompatibility for adherent CHO–K1 cells, which promotes cell spreading and proliferation. The plasma-modified LAPS chip is then integrated into a microfluidic system, which provides two identical channels to facilitate differential measurements of the extracellular acidification of CHO–K1 cells. To the best of our knowledge, it is the first time that extracellular acidification within microfluidic channels is quantitatively visualized as differential (bio-)chemical images.
In collaborative research projects, both researchers and practitioners work together solving business-critical challenges. These projects often deal with ETL processes, in which humans extract information from non-machine-readable documents by hand. AI-based machine learning models can help to solve this problem.
Since machine learning approaches are not deterministic, their quality of output may decrease over time. This fact leads to an overall quality loss of the application which embeds machine learning models. Hence, the software qualities in development and production may differ.
Machine learning models are black boxes. That makes practitioners skeptical and increases the inhibition threshold for early productive use of research prototypes. Continuous monitoring of software quality in production offers an early response capability on quality loss and encourages the use of machine learning approaches. Furthermore, experts have to ensure that they integrate possible new inputs into the model training as quickly as possible.
In this paper, we introduce an architecture pattern with a reference implementation that extends the concept of Metrics Driven Research Collaboration with an automated software quality monitoring in productive use and a possibility to auto-generate new test data coming from processed documents in production.
Through automated monitoring of the software quality and auto-generated test data, this approach ensures that the software quality meets and keeps requested thresholds in productive use, even during further continuous deployment and changing input data.
There is a very large number of very important situations which can be modeled with nonlinear parabolic partial differential equations (PDEs) in several dimensions. In general, these PDEs can be solved by discretizing in the spatial variables and transforming them into huge systems of ordinary differential equations (ODEs), which are very stiff. Therefore, standard explicit methods require a large number of iterations to solve stiff problems. But implicit schemes are computationally very expensive when solving huge systems of nonlinear ODEs. Several families of Extrapolated Stabilized Explicit Runge-Kutta schemes (ESERK) with different order of accuracy (3 to 6) are derived and analyzed in this work. They are explicit methods, with stability regions extended, along the negative real semi-axis, quadratically with respect to the number of stages s, hence they can be considered to solve stiff problems much faster than traditional explicit schemes. Additionally, they allow the adaptation of the step length easily with a very small cost.
Two new families of ESERK schemes (ESERK3 and ESERK6) are derived, and analyzed, in this work. Each family has more than 50 new schemes, with up to 84.000 stages in the case of ESERK6. For the first time, we also parallelized all these new variable step length and variable number of stages algorithms (ESERK3, ESERK4, ESERK5, and ESERK6). These parallelized strategies allow to decrease times significantly, as it is discussed and also shown numerically in two problems. Thus, the new codes provide very good results compared to other well-known ODE solvers. Finally, a new strategy is proposed to increase the efficiency of these schemes, and it is discussed the idea of combining ESERK families in one code, because typically, stiff problems have different zones and according to them and the requested tolerance the optimum order of convergence is different.
The Rothman–Woodroofe symmetry test statistic is revisited on the basis of independent but not necessarily identically distributed random variables. The distribution-freeness if the underlying distributions are all symmetric and continuous is obtained. The results are applied for testing symmetry in a meta-analysis random effects model. The consistency of the procedure is discussed in this situation as well. A comparison with an alternative proposal from the literature is conducted via simulations. Real data are analyzed to demonstrate how the new approach works in practice.
We discuss the testing problem of homogeneity of the marginal distributions of a continuous bivariate distribution based on a paired sample with possibly missing components (missing completely at random). Applying the well-known two-sample Crámer–von-Mises distance to the remaining data, we determine the limiting null distribution of our test statistic in this situation. It is seen that a new resampling approach is appropriate for the approximation of the unknown null distribution. We prove that the resulting test asymptotically reaches the significance level and is consistent. Properties of the test under local alternatives are pointed out as well. Simulations investigate the quality of the approximation and the power of the new approach in the finite sample case. As an illustration we apply the test to real data sets.
Elastic transmission eigenvalues and their computation via the method of fundamental solutions
(2020)
A stabilized version of the fundamental solution method to catch ill-conditioning effects is investigated with focus on the computation of complex-valued elastic interior transmission eigenvalues in two dimensions for homogeneous and isotropic media. Its algorithm can be implemented very shortly and adopts to many similar partial differential equation-based eigenproblems as long as the underlying fundamental solution function can be easily generated. We develop a corroborative approximation analysis which also implicates new basic results for transmission eigenfunctions and present some numerical examples which together prove successful feasibility of our eigenvalue recovery approach.
In this article, a concept of implicit methods for scalar conservation laws in one or more spatial dimensions allowing also for source terms of various types is presented. This material is a significant extension of previous work of the first author (Breuß SIAM J. Numer. Anal. 43(3), 970–986 2005). Implicit notions are developed that are centered around a monotonicity criterion. We demonstrate a connection between a numerical scheme and a discrete entropy inequality, which is based on a classical approach by Crandall and Majda. Additionally, three implicit methods are investigated using the developed notions. Next, we conduct a convergence proof which is not based on a classical compactness argument. Finally, the theoretical results are confirmed by various numerical tests.
The established Hoeffding-Blum-Kiefer-Rosenblatt independence test statistic is investigated for partly not identically distributed data. Surprisingly, it turns out that the statistic has the well-known distribution-free limiting null distribution of the classical criterion under standard regularity conditions. An application is testing goodness-of-fit for the regression function in a non parametric random effects meta-regression model, where the consistency is obtained as well. Simulations investigate size and power of the approach for small and moderate sample sizes. A real data example based on clinical trials illustrates how the test can be used in applications.
Interior transmission eigenvalue problems for the Helmholtz equation play an important role in inverse wave scattering. Some distribution properties of those eigenvalues in the complex plane are reviewed. Further, a new scattering model for the interior transmission eigenvalue problem with mixed boundary conditions is described and an efficient algorithm for computing the interior transmission eigenvalues is proposed. Finally, extensive numerical results for a variety of two-dimensional scatterers are presented to show the validity of the proposed scheme.
We present new numerical results for shape optimization problems of interior Neumann eigenvalues. This field is not well understood from a theoretical standpoint. The existence of shape maximizers is not proven beyond the first two eigenvalues, so we study the problem numerically. We describe a method to compute the eigenvalues for a given shape that combines the boundary element method with an algorithm for nonlinear eigenvalues. As numerical optimization requires many such evaluations, we put a focus on the efficiency of the method and the implemented routine. The method is well suited for parallelization. Using the resulting fast routines and a specialized parametrization of the shapes, we found improved maxima for several eigenvalues.
Motile cilia are hair-like cell extensions present in multiple organs of the body. How cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine here experiments, novel analysis tools, and theory to address this knowledge gap. We investigate collective dynamics of cilia in the zebrafish nose, due to its conserved properties with other ciliated tissues and its superior accessibility for non-invasive imaging. We revealed that cilia are synchronized only locally and that the size of local synchronization domains increases with the viscosity of the surrounding medium. Despite the fact that synchronization is local only, we observed global patterns of traveling metachronal waves across the multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right nose, unveiling a chiral asymmetry of metachronal coordination. To understand the implications of synchronization for fluid pumping, we used a computational model of a regular array of cilia. We found that local metachronal synchronization prevents steric collisions and improves fluid pumping in dense cilia carpets, but hardly affects the direction of fluid flow. In conclusion, we show that local synchronization together with tissue-scale cilia alignment are sufficient to generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.
Lignite biosolubilization and bioconversion by Bacillus sp.: the collation of analytical data
(2021)
The vast metabolic potential of microbes in brown coal (lignite) processing and utilization can greatly contribute to innovative approaches to sustainable production of high-value products from coal. In this study, the multi-faceted and complex coal biosolubilization process by Bacillus sp. RKB 7 isolate from the Kazakhstan coal-mining soil is reported, and the derived products are characterized. Lignite solubilization tests performed for surface and suspension cultures testify to the formation of numerous soluble lignite-derived substances. Almost 24% of crude lignite (5% w/v) was solubilized within 14 days under slightly alkaline conditions (pH 8.2). FTIR analysis revealed various functional groups in the obtained biosolubilization products. Analyses of the lignite-derived humic products by UV-Vis and fluorescence spectrometry as well as elemental analysis yielded compatible results indicating the emerging products had a lower molecular weight and degree of aromaticity. Furthermore, XRD and SEM analyses were used to evaluate the biosolubilization processes from mineralogical and microscopic points of view. The findings not only contribute to a deeper understanding of microbe–mineral interactions in coal environments, but also contribute to knowledge of coal biosolubilization and bioconversion with regard to sustainable production of humic substances. The detailed and comprehensive analyses demonstrate the huge biotechnological potential of Bacillus sp. for agricultural productivity and environmental health.
An acetoin biosensor based on a capacitive electrolyte–insulator–semiconductor (EIS) structure modified with the enzyme acetoin reductase, also known as butane-2,3-diol dehydrogenase (Bacillus clausii DSM 8716ᵀ), is applied for acetoin detection in beer, red wine, and fermentation broth samples for the first time. The EIS sensor consists of an Al/p-Si/SiO₂/Ta₂O₅ layer structure with immobilized acetoin reductase on top of the Ta₂O₅ transducer layer by means of crosslinking via glutaraldehyde. The unmodified and enzyme-modified sensors are electrochemically characterized by means of leakage current, capacitance–voltage, and constant capacitance methods, respectively.
A new formulation to calculate the shakedown limit load of Kirchhoff plates under stochastic conditions of strength is developed. Direct structural reliability design by chance con-strained programming is based on the prescribed failure probabilities, which is an effective approach of stochastic programming if it can be formulated as an equivalent deterministic optimization problem. We restrict uncertainty to strength, the loading is still deterministic. A new formulation is derived in case of random strength with lognormal distribution. Upper bound and lower bound shakedown load factors are calculated simultaneously by a dual algorithm.
Cardiopulmonary bypass (CPB) is a standard technique for cardiac surgery, but comes with the risk of severe neurological complications (e.g. stroke) caused by embolisms and/or reduced cerebral perfusion. We report on an aortic cannula prototype design (optiCAN) with helical outflow and jet-splitting dispersion tip that could reduce the risk of embolic events and restores cerebral perfusion to 97.5% of physiological flow during CPB in vivo, whereas a commercial curved-tip cannula yields 74.6%. In further in vitro comparison, pressure loss and hemolysis parameters of optiCAN remain unaffected. Results are reproducibly confirmed in silico for an exemplary human aortic anatomy via computational fluid dynamics (CFD) simulations. Based on CFD simulations, we firstly show that optiCAN design improves aortic root washout, which reduces the risk of thromboembolism. Secondly, we identify regions of the aortic intima with increased risk of plaque release by correlating areas of enhanced plaque growth and high wall shear stresses (WSS). From this we propose another easy-to-manufacture cannula design (opti2CAN) that decreases areas burdened by high WSS, while preserving physiological cerebral flow and favorable hemodynamics. With this novel cannula design, we propose a cannulation option to reduce neurological complications and the prevalence of stroke in high-risk patients after CPB.
Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.
In positron emission tomography improving time, energy and spatial detector resolutions and using Compton kinematics introduces the possibility to reconstruct a radioactivity distribution image from scatter coincidences, thereby enhancing image quality. The number of single scattered coincidences alone is in the same order of magnitude as true coincidences. In this work, a compact Compton camera module based on monolithic scintillation material is investigated as a detector ring module. The detector interactions are simulated with Monte Carlo package GATE. The scattering angle inside the tissue is derived from the energy of the scattered photon, which results in a set of possible scattering trajectories or broken line of response. The Compton kinematics collimation reduces the number of solutions. Additionally, the time of flight information helps localize the position of the annihilation. One of the questions of this investigation is related to how the energy, spatial and temporal resolutions help confine the possible annihilation volume. A comparison of currently technically feasible detector resolutions (under laboratory conditions) demonstrates the influence on this annihilation volume and shows that energy and coincidence time resolution have a significant impact. An enhancement of the latter from 400 ps to 100 ps leads to a smaller annihilation volume of around 50%, while a change of the energy resolution in the absorber layer from 12% to 4.5% results in a reduction of 60%. The inclusion of single tissue-scattered data has the potential to increase the sensitivity of a scanner by a factor of 2 to 3 times. The concept can be further optimized and extended for multiple scatter coincidences and subsequently validated by a reconstruction algorithm.
Modern industry and multi-discipline projects require highly trained individuals with resilient science and engineering back-grounds. Graduates must be able to agilely apply excellent theoretical knowledge in their subject matter as well as essential practical “hands-on” knowledge of diverse working processes to solve complex problems. To meet these demands, university education follows the concept of Constructive Alignment and thus increasingly adopts the teaching of necessary practical skills to the actual industry requirements and assessment routines. However, a systematic approach to coherently align these three central teaching demands is strangely absent from current university curricula. We demonstrate the feasibility of implementing practical assessments in a regular theory-based examination, thus defining the term “blended assessment”. We assessed a course for natural science and engineering students pursuing a career in biomedical engineering, and evaluated the benefit of blended assessment exams for students and lecturers. Our controlled study assessed the physiological background of electrocardiograms (ECGs), the practical measurement of ECG curves, and their interpretation of basic pathologic alterations. To study on long time effects, students have been assessed on the topic twice with a time lag of 6 months. Our findings suggest a significant improvement in student gain with respect to practical skills and theoretical knowledge. The results of the reassessments support these outcomes. From the lecturers ́ point of view, blended assessment complements practical training courses while keeping organizational effort manageable. We consider blended assessment a viable tool for providing an improved student gain, industry-ready education format that should be evaluated and established further to prepare university graduates optimally for their future careers.
A new functionalization method to modify capacitive electrolyte–insulator–semiconductor (EIS) structures with nanofilms is presented. Layers of polyallylamine hydrochloride (PAH) and graphene oxide (GO) with the compound polyaniline:poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PANI:PAAMPSA) are deposited onto a p-Si/SiO2 chip using the layer-by-layer technique (LbL). Two different enzymes (urease and penicillinase) are separately immobilized on top of a five-bilayer stack of the PAH:GO/PANI:PAAMPSA-modified EIS chip, forming a biosensor for detection of urea and penicillin, respectively. Electrochemical characterization is performed by constant capacitance (ConCap) measurements, and the film morphology is characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). An increase in the average sensitivity of the modified biosensors (EIS–nanofilm–enzyme) of around 15% is found in relation to sensors, only carrying the enzyme but without the nanofilm (EIS–enzyme). In this sense, the nanofilm acts as a stable bioreceptor onto the EIS chip improving the output signal in terms of sensitivity and stability.
Photoelectrochemical (PEC) biosensors are a rather novel type of biosensors thatutilizelighttoprovideinformationaboutthecompositionofananalyte,enablinglight-controlled multi-analyte measurements. For enzymatic PEC biosensors,amperometric detection principles are already known in the literature. In con-trast, there is only a little information on H+-ion sensitive PEC biosensors. Inthis work, we demonstrate the detection of H+ions emerged by H+-generatingenzymes, exemplarily demonstrated with penicillinase as a model enzyme on atitanium dioxide photoanode. First, we describe the pH sensitivity of the sensorand study possible photoelectrocatalytic reactions with penicillin. Second, weshow the enzymatic PEC detection of penicillin.
Contractile behavior of the gastrocnemius medialis muscle during running in simulated hypogravity
(2021)
Vigorous exercise countermeasures in microgravity can largely attenuate muscular degeneration, albeit the extent of applied loading is key for the extent of muscle wasting. Running on the International Space Station is usually performed with maximum loads of 70% body weight (0.7 g). However, it has not been investigated how the reduced musculoskeletal loading affects muscle and series elastic element dynamics, and thereby force and power generation. Therefore, this study examined the effects of running on the vertical treadmill facility, a ground-based analog, at simulated 0.7 g on gastrocnemius medialis contractile behavior. The results reveal that fascicle−series elastic element behavior differs between simulated hypogravity and 1 g running. Whilst shorter peak series elastic element lengths at simulated 0.7 g appear to be the result of lower muscular and gravitational forces acting on it, increased fascicle lengths and decreased velocities could not be anticipated, but may inform the development of optimized running training in hypogravity. However, whether the alterations in contractile behavior precipitate musculoskeletal degeneration warrants further study.
Conventional EEG devices cannot be used in everyday life and hence, past decade research has been focused on Ear-EEG for mobile, at-home monitoring for various applications ranging from emotion detection to sleep monitoring. As the area available for electrode contact in the ear is limited, the electrode size and location play a vital role for an Ear-EEG system. In this investigation, we present a quantitative study of ear-electrodes with two electrode sizes at different locations in a wet and dry configuration. Electrode impedance scales inversely with size and ranges from 450 kΩ to 1.29 MΩ for dry and from 22 kΩ to 42 kΩ for wet contact at 10 Hz. For any size, the location in the ear canal with the lowest impedance is ELE (Left Ear Superior), presumably due to increased contact pressure caused by the outer-ear anatomy. The results can be used to optimize signal pickup and SNR for specific applications. We demonstrate this by recording sleep spindles during sleep onset with high quality (5.27 μVrms).
Test-retest reliability of the internal shoulder rotator muscles' stretch reflex in healthy men
(2021)
Until now the reproducibility of the short latency stretch reflex of the internal rotator muscles of the glenohumeral joint has not been identified. Twenty-three healthy male participants performed three sets of external shoulder rotation stretches with various pre-activation levels on two different dates of measurement to assess test-retest reliability. All stretches were applied with a dynamometer acceleration of 104°/s2 and a velocity of 150°/s. Electromyographical response was measured via surface EMG. Reflex latencies showed a pre-activation effect (ƞ2 = 0,355). ICC ranged from 0,735 to 0,909 indicating an overall “good” relative reliability. SRD 95% lay between ±7,0 to ±12,3 ms.. The reflex gain showed overall poor test-retest reproducibility. The chosen methodological approach presented a suitable test protocol for shoulder muscles stretch reflex latency evaluation. A proof-of-concept study to validate the presented methodical approach in shoulder involvement including subjects with clinically relevant conditions is recommended.
This book provides a compact introduction to the bootstrap method. In addition to classical results on point estimation and test theory, multivariate linear regression models and generalized linear models are covered in detail. Special attention is given to the use of bootstrap procedures to perform goodness-of-fit tests to validate model or distributional assumptions. In some cases, new methods are presented here for the first time.
The text is motivated by practical examples and the implementations of the corresponding algorithms are always given directly in R in a comprehensible form. Overall, R is given great importance throughout. Each chapter includes a section of exercises and, for the more mathematically inclined readers, concludes with rigorous proofs. The intended audience is graduate students who already have a prior knowledge of probability theory and mathematical statistics.
We consider a binary multivariate regression model where the conditional expectation of a binary variable given a higher-dimensional input variable belongs to a parametric family. Based on this, we introduce a model-based bootstrap (MBB) for higher-dimensional input variables. This test can be used to check whether a sequence of independent and identically distributed observations belongs to such a parametric family. The approach is based on the empirical residual process introduced by Stute (Ann Statist 25:613–641, 1997). In contrast to Stute and Zhu’s approach (2002) Stute & Zhu (Scandinavian J Statist 29:535–545, 2002), a transformation is not required. Thus, any problems associated with non-parametric regression estimation are avoided. As a result, the MBB method is much easier for users to implement. To illustrate the power of the MBB based tests, a small simulation study is performed. Compared to the approach of Stute & Zhu (Scandinavian J Statist 29:535–545, 2002), the simulations indicate a slightly improved power of the MBB based method. Finally, both methods are applied to a real data set.
Multi-attribute relation extraction (MARE): simplifying the application of relation extraction
(2021)
Natural language understanding’s relation extraction makes innovative and encouraging novel business concepts possible and facilitates new digitilized decision-making processes. Current approaches allow the extraction of relations with a fixed number of entities as attributes. Extracting relations with an arbitrary amount of attributes requires complex systems and costly relation-trigger annotations to assist these systems. We introduce multi-attribute relation extraction (MARE) as an assumption-less problem formulation with two approaches, facilitating an explicit mapping from business use cases to the data annotations. Avoiding elaborated annotation constraints simplifies the application of relation extraction approaches. The evaluation compares our models to current state-of-the-art event extraction and binary relation extraction methods. Our approaches show improvement compared to these on the extraction of general multi-attribute relations.
The progress in natural language processing (NLP) research over the last years, offers novel business opportunities for companies, as automated user interaction or improved data analysis. Building sophisticated NLP applications requires dealing with modern machine learning (ML) technologies, which impedes enterprises from establishing successful NLP projects. Our experience in applied NLP research projects shows that the continuous integration of research prototypes in production-like environments with quality assurance builds trust in the software and shows convenience and usefulness regarding the business goal. We introduce STAMP 4 NLP as an iterative and incremental process model for developing NLP applications. With STAMP 4 NLP, we merge software engineering principles with best practices from data science. Instantiating our process model allows efficiently creating prototypes by utilizing templates, conventions, and implementations, enabling developers and data scientists to focus on the business goals. Due to our iterative-incremental approach, businesses can deploy an enhanced version of the prototype to their software environment after every iteration, maximizing potential business value and trust early and avoiding the cost of successful yet never deployed experiments.
The integration of frequently changing, volatile product data from different manufacturers into a single catalog is a significant challenge for small and medium-sized e-commerce companies. They rely on timely integrating product data to present them aggregated in an online shop without knowing format specifications, concept understanding of manufacturers, and data quality. Furthermore, format, concepts, and data quality may change at any time. Consequently, integrating product catalogs into a single standardized catalog is often a laborious manual task. Current strategies to streamline or automate catalog integration use techniques based on machine learning, word vectorization, or semantic similarity. However, most approaches struggle with low-quality or real-world data. We propose Attribute Label Ranking (ALR) as a recommendation engine to simplify the integration process of previously unknown, proprietary tabular format into a standardized catalog for practitioners. We evaluate ALR by focusing on the impact of different neural network architectures, language features, and semantic similarity. Additionally, we consider metrics for industrial application and present the impact of ALR in production and its limitations.
The treatment method to deactivate viable microorganisms from objects or products is termed sterilization. There are multiple forms of sterilization, each intended to be applied for a specific target, which depends on—but not limited to—the thermal, physical, and chemical stability of that target. Herein, an overview on the currently used sterilization processes in the global market is provided. Different sterilization techniques are grouped under a category that describes the method of treatment: radiation (gamma, electron beam, X-ray, and ultraviolet), thermal (dry and moist heat), and chemical (ethylene oxide, ozone, chlorine dioxide, and hydrogen peroxide). For each sterilization process, the typical process parameters as defined by regulations and the mode of antimicrobial activity are summarized. Finally, the recommended microorganisms that are used as biological indicators to validate sterilization processes in accordance with the rules that are established by various regulatory agencies are summarized.
Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating.
Stretch-shortening type actions are characterized by lengthening of the pre-activated muscle-tendon unit (MTU) in the eccentric phase immediately followed by muscle shortening. Under 1 g, pre-activity before and muscle activity after ground contact, scale muscle stiffness, which is crucial for the recoil properties of the MTU in the subsequent push-off. This study aimed to examine the neuro-mechanical coupling of the stretch-shortening cycle in response to gravity levels ranging from 0.1 to 2 g. During parabolic flights, 17 subjects performed drop jumps while electromyography (EMG) of the lower limb muscles was combined with ultrasound images of the gastrocnemius medialis, 2D kinematics and kinetics to depict changes in energy management and performance. Neuro-mechanical coupling in 1 g was characterized by high magnitudes of pre-activity and eccentric muscle activity allowing an isometric muscle behavior during ground contact. EMG during pre-activity and the concentric phase systematically increased from 0.1 to 1 g. Below 1 g the EMG in the eccentric phase was diminished, leading to muscle lengthening and reduced MTU stretches. Kinetic energy at take-off and performance were decreased compared to 1 g. Above 1 g, reduced EMG in the eccentric phase was accompanied by large MTU and muscle stretch, increased joint flexion amplitudes, energy loss and reduced performance. The energy outcome function established by linear mixed model reveals that the central nervous system regulates the extensor muscles phase- and load-specifically. In conclusion, neuro-mechanical coupling appears to be optimized in 1 g. Below 1 g, the energy outcome is compromised by reduced muscle stiffness. Above 1 g, loading progressively induces muscle lengthening, thus facilitating energy dissipation.
The international partnership of space agencies has agreed to proceed forward to the Moon sustainably. Activities on the Lunar surface (0.16 g) will allow crewmembers to advance the exploration skills needed when expanding human presence to Mars (0.38 g). Whilst data from actual hypogravity activities are limited to the Apollo missions, simulation studies have indicated that ground reaction forces, mechanical work, muscle activation, and joint angles decrease with declining gravity level. However, these alterations in locomotion biomechanics do not necessarily scale to the gravity level, the reduction in gastrocnemius medialis activation even appears to level off around 0.2 g, while muscle activation pattern remains similar. Thus, it is difficult to predict whether gastrocnemius medialis contractile behavior during running on Moon will basically be the same as on Mars. Therefore, this study investigated lower limb joint kinematics and gastrocnemius medialis behavior during running at 1 g, simulated Martian gravity, and simulated Lunar gravity on the vertical treadmill facility. The results indicate that hypogravity-induced alterations in joint kinematics and contractile behavior still persist between simulated running on the Moon and Mars. This contrasts with the concept of a ceiling effect and should be carefully considered when evaluating exercise prescriptions and the transferability of locomotion practiced in Lunar gravity to Martian gravity.
The compliant nature of distal limb muscle-tendon units is traditionally considered suboptimal in explosive movements when positive joint work is required. However, during accelerative running, ankle joint net mechanical work is positive. Therefore, this study aims to investigate how plantar flexor muscle-tendon behavior is modulated during fast accelerations. Eleven female sprinters performed maximum sprint accelerations from starting blocks, while gastrocnemius muscle fascicle lengths were estimated using ultrasonography. We combined motion analysis and ground reaction force measurements to assess lower limb joint kinematics and kinetics, and to estimate gastrocnemius muscle-tendon unit length during the first two acceleration steps. Outcome variables were resampled to the stance phase and averaged across three to five trials. Relevant scalars were extracted and analyzed using one-sample and two-sample t-tests, and vector trajectories were compared using statistical parametric mapping. We found that an uncoupling of muscle fascicle behavior from muscle-tendon unit behavior is effectively used to produce net positive mechanical work at the joint during maximum sprint acceleration. Muscle fascicles shortened throughout the first and second steps, while shortening occurred earlier during the first step, where negative joint work was lower compared with the second step. Elastic strain energy may be stored during dorsiflexion after touchdown since fascicles did not lengthen at the same time to dissipate energy. Thus, net positive work generation is accommodated by the reuse of elastic strain energy along with positive gastrocnemius fascicle work. Our results show a mechanism of how muscles with high in-series compliance can contribute to net positive joint work.
Performing tasks, such as running and jumping, requires activation of the agonist and antagonist muscles before (motor unit pre-activation) and during movement performance (Santello and Mcdonagh, 1998). A well-timed and regulated muscle activation elicits a stretch-shortening cycle (SSC) response, naturally occurring in bouncing movements (Ishikawa and Komi, 2004; Taube et al., 2012). By definition, the SSC describes the stretching of a pre-activated muscle-tendon complex immediately followed by a muscle shortening in the concentric push-off phase (Komi, 1984).
Given the importance of SSC actions for human movement, it is not surprising that many studies investigated the biomechanics of this phenomenon; in particular, drop jumps (DJs) represent a good paradigm to study muscle fascicle and tendon behavior in ballistic movements involving the SSC.
Within a DJ, three main phases [pre-activation, braking, and push-off (PO; Komi, 2000)] have been recognized and extensively studied in common and challenging conditions, such as changes in load, falling height, or simulated hypo-gravity (Avela et al., 1994; Arampatzis et al., 2001; Fukashiro et al., 2005; Ishikawa et al., 2005; Sousa et al., 2007; Ritzmann et al., 2016; Helm et al., 2020).
These studies show that the timing and amount of triceps-surae muscle-tendon unit pre-activation in DJs are differentially regulated based on the load applied to the muscle, being optimal in normal “Earth” gravity conditions (Avela et al., 1994), but decreased in simulated hypo-gravity, hyper-gravity (Avela et al., 1994; Ritzmann et al., 2016), or unknown conditions (i.e., unknown falling heights; Helm et al., 2020). Some authors indicated that, when falling from heights different from the optimal one [defined as the drop height giving a maximum DJ performance indicated as peak ground reaction force (GRF) or jump high], electromyographic (EMG) activity of the plantar flexors increases from lower than optimal to higher than optimal heights (Ishikawa and Komi, 2004; Sousa et al., 2007).
These findings highlight the ability of the central nervous system to regulate the timing and amount of pre-activation according to different jumping conditions, thus regulating muscle fascicle length, tendon and joint stiffness as well as position, in order to safely land on the ground and quickly re-bounce.
Similarly, to pre-activation, also in the braking phase, the plantar flexors are differentially regulated. In optimal height (i.e., load) jumping conditions, gastrocnemius medialis (GM) fascicles shorten at early ground contact (possibly due to the intervention of the stretch reflex; Gollhofer et al., 1992) and behave quasi-isometrically in the late braking phase, enabling tendon elongation, and storage of elastic energy (Gollhofer et al., 1992; Fukashiro et al., 2005; Sousa et al., 2007). When increasing the falling height (augmenting the impact GRF), the quasi-isometric behavior of fascicles disappears, and fast fascicle lengthening occurs (Ishikawa et al., 2005; Sousa et al., 2007).
In the third and last PO phase, fascicles shorten and the tendon releases the elastic energy previously stored. Bobbert et al. (1987) reported no influence of jumping height on the work done and on the net vertical impulse assessed during PO; this observation suggests that, despite an optimal DJ performance might be achieved only in specific conditions (falling heights, loads), the central nervous system seems to be able to regulate muscle behavior in order to effectively perform the required task also in challenging situations.
Although the regulation of triceps-surae muscle-tendon unit in DJs has been extensively investigated, very few studies focused on sarcomeres behavior during the performance of this SSC movement (Kurokawa et al., 2003; Fukashiro et al., 2005, 2006). Sarcomeres represent muscle contractile units and are known to express different amounts of force depending on their length (Gordon et al., 1966; Walker and Schrodt, 1974); thus, understanding the time course of their responses during DJs is fundamental to gain further insights into muscle force-generating capacity. In vivo measurement of sarcomere length in humans has been so far been performed only in static positions and under highly controlled experimental conditions (Llewellyn et al., 2008; Sanchez et al., 2015). Instead, human sarcomere length estimation (achieved by dividing GM measured fascicle length for a fixed sarcomere number) in dynamic contractions provided an indirect measure of sarcomere operating range during squat jump, countermovement jump, and DJ (Fukashiro et al., 2005, 2006; Kurokawa et al., 2003). The results of these studies showed that sarcomeres operate in the ascending limb of their length-tension (L-T) relationship in all types of jumps, and particularly so in DJ.
However, most of the available observations on sarcomere and muscle fascicle behavior were made in condition of constant gravity. Thus, in order to understand how sarcomere and muscle fascicle length are regulated in variable gravity conditions, we performed experiments in a parabolic flight, involving variable gravity levels, ranging from about zero-g to about double the Earth’s gravity (1 g; Waldvogel et al., 2021).
Specifically, the aims of the present study were as follows:
1. To investigate the ability of the neuromuscular system in regulating fascicle length in response to conditions of variable gravity.
2. To estimate sarcomere operative length in the different DJ phases, in order to calculate its theoretical force production and its possible modulation in conditions of variable gravity.
We hypothesized that muscle fascicles would be differentially regulated in different gravity conditions compared to 1 g, particularly in anticipation of landing and re-bouncing in unknown gravity levels. In addition, we hypothesized that sarcomeres would operate in the upper part of the ascending limb of their L-T relationship, possibly lengthening during the braking phase (especially in hyper-gravity) while operating quasi-isometrically in 1 g.
Achilles tendon rupture (ATR) patients have persistent functional deficits in the triceps surae muscle–tendon unit (MTU). The complex remodeling of the MTU accompanying these deficits remains poorly understood. The purpose of the present study was to associate in vivo and in silico data to investigate the relations between changes inMTU properties and strength deficits inATR patients. Methods: Elevenmale subjects who had undergone surgical repair of complete unilateral ATR were examined 4.6 ± 2.0 (mean ± SD) yr after rupture. Gastrocnemius medialis (GM) tendon stiffness, morphology, and muscle architecture were determined using ultrasonography. The force–length relation of the plantar flexor muscles was assessed at five ankle joint angles. In addition, simulations (OpenSim) of the GM MTU force–length properties were performed with various iterations of MTU properties found between the unaffected and the affected side. Results: The affected side of the patients displayed a longer, larger, and stiffer GM tendon (13% ± 10%, 105% ± 28%, and 54% ± 24%, respectively) compared with the unaffected side. The GM muscle fascicles of the affected side were shorter (32% ± 12%) and with greater pennation angles (31% ± 26%). A mean deficit in plantarflexion moment of 31% ± 10% was measured. Simulations indicate that pairing an intact muscle with a longer tendon shifts the optimal angular range of peak force outside physiological angular ranges, whereas the shorter muscle fascicles and tendon stiffening seen in the affected side decrease this shift, albeit incompletely. Conclusions: These results suggest that the substantial changes in MTU properties found in ATR patients may partly result from compensatory remodeling, although this process appears insufficient to fully restore muscle function.
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.
Purpose Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. Methods 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 pro- found hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. Results Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p \ 0.04 and p \ 0.02 respectively) in-between the hemispheres spheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. Conclusion Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetri altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.
Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus.
The term ocular rigidity is widely used in clinical ophthalmology. Generally it is assumed as a resistance of the whole eyeball to mechanical deformation and relates to biomechanical properties of the eye and its tissues. Basic principles and formulas for clinical tonometry, tonography and pulsatile ocular blood flow measurements are based on the concept of ocular rigidity. There is evidence for altered ocular rigidity in aging, in several eye diseases and after eye surgery. Unfortunately, there is no consensual view on ocular rigidity: it used to make a quite different sense for different people but still the same name. Foremost there is no clear consent between biomechanical engineers and ophthalmologists on the concept. Moreover ocular rigidity is occasionally characterized using various parameters with their different physical dimensions. In contrast to engineering approach, clinical approach to ocular rigidity claims to characterize the total mechanical response of the eyeball to its deformation without any detailed considerations on eye morphology or material properties of its tissues. Further to the previous chapter this section aims to describe clinical approach to ocular rigidity from the perspective of an engineer in an attempt to straighten out this concept, to show its advantages, disadvantages and various applications.
Microbial diversity studies regarding the aquatic communities that experienced or are experiencing environmental problems are essential for the comprehension of the remediation dynamics. In this pilot study, we present data on the phylogenetic and ecological structure of microorganisms from epipelagic water samples collected in the Small Aral Sea (SAS). The raw data were generated by massive parallel sequencing using the shotgun approach. As expected, most of the identified DNA sequences belonged to Terrabacteria and Actinobacteria (40% and 37% of the total reads, respectively). The occurrence of Deinococcus-Thermus, Armatimonadetes, Chloroflexi in the epipelagic SAS waters was less anticipated. Surprising was also the detection of sequences, which are characteristic for strict anaerobes—Ignavibacteria, hydrogen-oxidizing bacteria, and archaeal methanogenic species. We suppose that the observed very broad range of phylogenetic and ecological features displayed by the SAS reads demonstrates a more intensive mixing of water masses originating from diverse ecological niches of the Aral-Syr Darya River basin than presumed before.
Plant viruses are major contributors to crop losses and induce high economic costs worldwide. For reliable, on-site and early detection of plant viral diseases, portable biosensors are of great interest. In this study, a field-effect SiO2-gate electrolyte-insulator-semiconductor (EIS) sensor was utilized for the label-free electrostatic detection of tobacco mosaic virus (TMV) particles as a model plant pathogen. The capacitive EIS sensor has been characterized regarding its TMV sensitivity by means of constant-capacitance method. The EIS sensor was able to detect biotinylated TMV particles from a solution with a TMV concentration as low as 0.025 nM. A good correlation between the registered EIS sensor signal and the density of adsorbed TMV particles assessed from scanning electron microscopy images of the SiO2-gate chip surface was observed. Additionally, the isoelectric point of the biotinylated TMV particles was determined via zeta potential measurements and the influence of ionic strength of the measurement solution on the TMV-modified EIS sensor signal has been studied.
Biologically sensitive field-effect devices (BioFEDs) advantageously combine the electronic field-effect functionality with the (bio)chemical receptor’s recognition ability for (bio)chemical sensing. In this review, basic and widely applied device concepts of silicon-based BioFEDs (ion-sensitive field-effect transistor, silicon nanowire transistor, electrolyte-insulator-semiconductor capacitor, light-addressable potentiometric sensor) are presented and recent progress (from 2019 to early 2021) is discussed. One of the main advantages of BioFEDs is the label-free sensing principle enabling to detect a large variety of biomolecules and bioparticles by their intrinsic charge. The review encompasses applications of BioFEDs for the label-free electrical detection of clinically relevant protein biomarkers, deoxyribonucleic acid molecules and viruses, enzyme-substrate reactions as well as recording of the cell acidification rate (as an indicator of cellular metabolism) and the extracellular potential.
Reliable automation of the labor-intensive manual task of scoring animal sleep can facilitate the analysis of long-term sleep studies. In recent years, deep-learning-based systems, which learn optimal features from the data, increased scoring accuracies for the classical sleep stages of Wake, REM, and Non-REM. Meanwhile, it has been recognized that the statistics of transitional stages such as pre-REM, found between Non-REM and REM, may hold additional insight into the physiology of sleep and are now under vivid investigation. We propose a classification system based on a simple neural network architecture that scores the classical stages as well as pre-REM sleep in mice. When restricted to the classical stages, the optimized network showed state-of-the-art classification performance with an out-of-sample F1 score of 0.95 in male C57BL/6J mice. When unrestricted, the network showed lower F1 scores on pre-REM (0.5) compared to the classical stages. The result is comparable to previous attempts to score transitional stages in other species such as transition sleep in rats or N1 sleep in humans. Nevertheless, we observed that the sequence of predictions including pre-REM typically transitioned from Non-REM to REM reflecting sleep dynamics observed by human scorers. Our findings provide further evidence for the difficulty of scoring transitional sleep stages, likely because such stages of sleep are under-represented in typical data sets or show large inter-scorer variability. We further provide our source code and an online platform to run predictions with our trained network.
Plant virus-like particles, and in particular, tobacco mosaic virus (TMV) particles, are increasingly being used in nano- and biotechnology as well as for biochemical sensing purposes as nanoscaffolds for the high-density immobilization of receptor molecules. The sensitive parameters of TMV-assisted biosensors depend, among others, on the density of adsorbed TMV particles on the sensor surface, which is affected by both the adsorption conditions and surface properties of the sensor. In this work, Ta₂O₅-gate field-effect capacitive sensors have been applied for the label-free electrical detection of TMV adsorption. The impact of the TMV concentration on both the sensor signal and the density of TMV particles adsorbed onto the Ta₂O₅-gate surface has been studied systematically by means of field-effect and scanning electron microscopy methods. In addition, the surface density of TMV particles loaded under different incubation times has been investigated. Finally, the field-effect sensor also demonstrates the label-free detection of penicillinase immobilization as model bioreceptor on TMV particles.
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.
In the context of the Solvency II directive, the operation of an internal risk model is a possible way for risk assessment and for the determination of the solvency capital requirement of an insurance company in the European Union. A Monte Carlo procedure is customary to generate a model output. To be compliant with the directive, validation of the internal risk model is conducted on the basis of the model output. For this purpose, we suggest a new test for checking whether there is a significant change in the modeled solvency capital requirement. Asymptotic properties of the test statistic are investigated and a bootstrap approximation is justified. A simulation study investigates the performance of the test in the finite sample case and confirms the theoretical results. The internal risk model and the application of the test is illustrated in a simplified example. The method has more general usage for inference of a broad class of law-invariant and coherent risk measures on the basis of a paired sample.
Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating
(2021)
Rehabilitative body weight supported gait training aims at restoring walking function as a key element in activities of daily living. Studies demonstrated reductions in muscle and joint forces, while kinematic gait patterns appear to be preserved with up to 30% weight support. However, the influence of body weight support on muscle architecture, with respect to fascicle and series elastic element behavior is unknown, despite this having potential clinical implications for gait retraining. Eight males (31.9 ± 4.7 years) walked at 75% of the speed at which they typically transition to running, with 0% and 30% body weight support on a lower-body positive pressure treadmill. Gastrocnemius medialis fascicle lengths and pennation angles were measured via ultrasonography. Additionally, joint kinematics were analyzed to determine gastrocnemius medialis muscle–tendon unit lengths, consisting of the muscle's contractile and series elastic elements. Series elastic element length was assessed using a muscle–tendon unit model. Depending on whether data were normally distributed, a paired t-test or Wilcoxon signed rank test was performed to determine if body weight supported walking had any effects on joint kinematics and fascicle–series elastic element behavior. Walking with 30% body weight support had no statistically significant effect on joint kinematics and peak series elastic element length. Furthermore, at the time when peak series elastic element length was achieved, and on average across the entire stance phase, muscle–tendon unit length, fascicle length, pennation angle, and fascicle velocity were unchanged with respect to body weight support. In accordance with unchanged gait kinematics, preservation of fascicle–series elastic element behavior was observed during walking with 30% body weight support, which suggests transferability of gait patterns to subsequent unsupported walking.
The hot spots conjecture is only known to be true for special geometries. This paper shows numerically that the hot spots conjecture can fail to be true for easy to construct bounded domains with one hole. The underlying eigenvalue problem for the Laplace equation with Neumann boundary condition is solved with boundary integral equations yielding a non-linear eigenvalue problem. Its discretization via the boundary element collocation method in combination with the algorithm by Beyn yields highly accurate results both for the first non-zero eigenvalue and its corresponding eigenfunction which is due to superconvergence. Additionally, it can be shown numerically that the ratio between the maximal/minimal value inside the domain and its maximal/minimal value on the boundary can be larger than 1 + 10− 3. Finally, numerical examples for easy to construct domains with up to five holes are provided which fail the hot spots conjecture as well.
Fields of asymmetric tensors play an important role in many applications such as medical imaging (diffusion tensor magnetic resonance imaging), physics, and civil engineering (for example Cauchy-Green-deformation tensor, strain tensor with local rotations, etc.). However, such asymmetric tensors are usually symmetrized and then further processed. Using this procedure results in a loss of information. A new method for the processing of asymmetric tensor fields is proposed restricting our attention to tensors of second-order given by a 2x2 array or matrix with real entries. This is achieved by a transformation resulting in Hermitian matrices that have an eigendecomposition similar to symmetric matrices. With this new idea numerical results for real-world data arising from a deformation of an object by external forces are given. It is shown that the asymmetric part indeed contains valuable information.
The European Union's aim to become climate neutral by 2050 necessitates ambitious efforts to reduce carbon emissions. Large reductions can be attained particularly in energy intensive sectors like iron and steel. In order to prevent the relocation of such industries outside the EU in the course of tightening environmental regulations, the establishment of a climate club jointly with other large emitters and alternatively the unilateral implementation of an international cross-border carbon tax mechanism are proposed. This article focuses on the latter option choosing the steel sector as an example. In particular, we investigate the financial conditions under which a European cross border mechanism is capable to protect hydrogen-based steel production routes employed in Europe against more polluting competition from abroad. By using a floor price model, we assess the competitiveness of different steel production routes in selected countries. We evaluate the climate friendliness of steel production on the basis of specific GHG emissions. In addition, we utilize an input-output price model. It enables us to assess impacts of rising cost of steel production on commodities using steel as intermediates. Our results raise concerns that a cross-border tax mechanism will not suffice to bring about competitiveness of hydrogen-based steel production in Europe because the cost tends to remain higher than the cost of steel production in e.g. China. Steel is a classic example for a good used mainly as intermediate for other products. Therefore, a cross-border tax mechanism for steel will increase the price of products produced in the EU that require steel as an input. This can in turn adversely affect competitiveness of these sectors. Hence, the effects of higher steel costs on European exports should be borne in mind and could require the cross-border adjustment mechanism to also subsidize exports.
Reliable methods for automatic readability assessment have the potential to impact a variety of fields, ranging from machine translation to self-informed learning. Recently, large language models for the German language (such as GBERT and GPT-2-Wechsel) have become available, allowing to develop Deep Learning based approaches that promise to further improve automatic readability assessment. In this contribution, we studied the ability of ensembles of fine-tuned GBERT and GPT-2-Wechsel models to reliably predict the readability of German sentences. We combined these models with linguistic features and investigated the dependence of prediction performance on ensemble size and composition. Mixed ensembles of GBERT and GPT-2-Wechsel performed better than ensembles of the same size consisting of only GBERT or GPT-2-Wechsel models. Our models were evaluated in the GermEval 2022 Shared Task on Text Complexity Assessment on data of German sentences. On out-of-sample data, our best ensemble achieved a root mean squared error of 0:435.
Edge-based and face-based smoothed finite element methods (ES-FEM and FS-FEM, respectively) are modified versions of the finite element method allowing to achieve more accurate results and to reduce sensitivity to mesh distortion, at least for linear elements. These properties make the two methods very attractive. However, their implementation in a standard finite element code is nontrivial because it requires heavy and extensive modifications to the code architecture. In this article, we present an element-based formulation of ES-FEM and FS-FEM methods allowing to implement the two methods in a standard finite element code with no modifications to its architecture. Moreover, the element-based formulation permits to easily manage any type of element, especially in 3D models where, to the best of the authors' knowledge, only tetrahedral elements are used in FS-FEM applications found in the literature. Shape functions for non-simplex 3D elements are proposed in order to apply FS-FEM to any standard finite element.
The mechanical behavior of the large intestine beyond the ultimate stress has never been investigated. Stretching beyond the ultimate stress may drastically impair the tissue microstructure, which consequently weakens its healthy state functions of absorption, temporary storage, and transportation for defecation. Due to closely similar microstructure and function with humans, biaxial tensile experiments on the porcine large intestine have been performed in this study. In this paper, we report hyperelastic characterization of the large intestine based on experiments in 102 specimens. We also report the theoretical analysis of the experimental results, including an exponential damage evolution function. The fracture energies and the threshold stresses are set as damage material parameters for the longitudinal muscular, the circumferential muscular and the submucosal collagenous layers. A biaxial tensile simulation of a linear brick element has been performed to validate the applicability of the estimated material parameters. The model successfully simulates the biomechanical response of the large intestine under physiological and non-physiological loads.
Messenger apps like WhatsApp or Telegram are an integral part of daily communication. Besides the various positive effects, those services extend the operating range of criminals. Open trading groups with many thousand participants emerged on Telegram. Law enforcement agencies monitor suspicious users in such chat rooms. This research shows that text analysis, based on natural language processing, facilitates this through a meaningful domain overview and detailed investigations. We crawled a corpus from such self-proclaimed black markets and annotated five attribute types products, money, payment methods, user names, and locations. Based on each message a user sends, we extract and group these attributes to build profiles. Then, we build features to cluster the profiles. Pretrained word vectors yield better unsupervised clustering results than current
state-of-the-art transformer models. The result is a semantically meaningful high-level overview of the user landscape of black market chatrooms. Additionally, the extracted structured information serves as a foundation for further data exploration, for example, the most active users or preferred payment methods.
Wearable EEG has gained popularity in recent years driven by promising uses outside of clinics and research. The ubiquitous application of continuous EEG requires unobtrusive form-factors that are easily acceptable by the end-users. In this progression, wearable EEG systems have been moving from full scalp to forehead and recently to the ear. The aim of this study is to demonstrate that emerging ear-EEG provides similar impedance and signal properties as established forehead EEG. EEG data using eyes-open and closed alpha paradigm were acquired from ten healthy subjects using generic earpieces fitted with three custom-made electrodes and a forehead electrode (at Fpx) after impedance analysis. Inter-subject variability in in-ear electrode impedance ranged from 20 kΩ to 25 kΩ at 10 Hz. Signal quality was comparable with an SNR of 6 for in-ear and 8 for forehead electrodes. Alpha attenuation was significant during the eyes-open condition in all in-ear electrodes, and it followed the structure of power spectral density plots of forehead electrodes, with the Pearson correlation coefficient of 0.92 between in-ear locations ELE (Left Ear Superior) and ERE (Right Ear Superior) and forehead locations, Fp1 and Fp2, respectively. The results indicate that in-ear EEG is an unobtrusive alternative in terms of impedance, signal properties and information content to established forehead EEG.
Image reconstruction analysis for positron emission tomography with heterostructured scintillators
(2022)
The concept of structure engineering has been proposed for exploring the next generation of radiation detectors with improved performance. A TOF-PET geometry with heterostructured scintillators with a pixel size of 3.0×3.1×15 mm3 was simulated using Monte Carlo. The heterostructures consisted of alternating layers of BGO as a dense material with high stopping power and plastic (EJ232) as a fast light emitter. The detector time resolution was calculated as a function of the deposited and shared energy in both materials on an event-by-event basis. While sensitivity was reduced to 32% for 100 μm thick plastic layers and 52% for 50 μm, the CTR distribution improved to 204±49 ps and 220±41 ps respectively, compared to 276 ps that we considered for bulk BGO. The complex distribution of timing resolutions was accounted for in the reconstruction. We divided the events into three groups based on their CTR and modeled them with different Gaussian TOF kernels. On a NEMA IQ phantom, the heterostructures had better contrast recovery in early iterations. On the other hand, BGO achieved a better contrast to noise ratio (CNR) after the 15th iteration due to the higher sensitivity. The developed simulation and reconstruction methods constitute new tools for evaluating different detector designs with complex time responses.
On the basis of bivariate data, assumed to be observations of independent copies of a random vector (S,N), we consider testing the hypothesis that the distribution of (S,N) belongs to the parametric class of distributions that arise with the compound Poisson exponential model. Typically, this model is used in stochastic hydrology, with N as the number of raindays, and S as total rainfall amount during a certain time period, or in actuarial science, with N as the number of losses, and S as total loss expenditure during a certain time period. The compound Poisson exponential model is characterized in the way that a specific transform associated with the distribution of (S,N) satisfies a certain differential equation. Mimicking the function part of this equation by substituting the empirical counterparts of the transform we obtain an expression the weighted integral of the square of which is used as test statistic. We deal with two variants of the latter, one of which being invariant under scale transformations of the S-part by fixed positive constants. Critical values are obtained by using a parametric bootstrap procedure. The asymptotic behavior of the tests is discussed. A simulation study demonstrates the performance of the tests in the finite sample case. The procedure is applied to rainfall data and to an actuarial dataset. A multivariate extension is also discussed.
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.
Introduction
In regard of surgical training, the reproducible simulation of life-like proximal humerus fractures in human cadaveric specimens is desirable. The aim of the present study was to develop a technique that allows simulation of realistic proximal humerus fractures and to analyse the influence of rotator cuff preload on the generated lesions in regards of fracture configuration.
Materials and methods
Ten cadaveric specimens (6 left, 4 right) were fractured using a custom-made drop-test bench, in two groups. Five specimens were fractured without rotator cuff preload, while the other five were fractured with the tendons of the rotator cuff preloaded with 2 kg each. The humeral shaft and the shortened scapula were potted. The humerus was positioned at 90° of abduction and 10° of internal rotation to simulate a fall on the elevated arm. In two specimens of each group, the emergence of the fractures was documented with high-speed video imaging. Pre-fracture radiographs were taken to evaluate the deltoid-tuberosity index as a measure of bone density. Post-fracture X-rays and CT scans were performed to define the exact fracture configurations. Neer’s classification was used to analyse the fractures.
Results
In all ten cadaveric specimens life-like proximal humerus fractures were achieved. Two III-part and three IV-part fractures resulted in each group. The preloading of the rotator cuff muscles had no further influence on the fracture configuration. High-speed videos of the fracture simulation revealed identical fracture mechanisms for both groups. We observed a two-step fracture mechanism, with initial impaction of the head segment against the glenoid followed by fracturing of the head and the tuberosities and then with further impaction of the shaft against the acromion, which lead to separation of the tuberosities.
Conclusion
A high energetic axial impulse can reliably induce realistic proximal humerus fractures in cadaveric specimens. The preload of the rotator cuff muscles had no influence on initial fracture configuration. Therefore, fracture simulation in the proximal humerus is less elaborate. Using the presented technique, pre-fractured specimens are available for real-life surgical education.
Orthodontic treatments are concomitant with mechanical forces and thereby cause teeth movements. The applied forces are transmitted to the tooth root and the periodontal ligaments which is compressed on one side and tensed up on the other side. Indeed, strong forces can lead to tooth root resorption and the crown-to-tooth ratio is reduced with the potential for significant clinical impact. The cementum, which covers the tooth root, is a thin mineralized tissue of the periodontium that connects the periodontal ligament with the tooth and is build up by cementoblasts. The impact of tension and compression on these cells is investigated in several in vivo and in vitro studies demonstrating differences in protein expression and signaling pathways. In summary, osteogenic marker changes indicate that cyclic tensile forces support whereas static tension inhibits cementogenesis. Furthermore, cementogenesis experiences the same protein expression changes in static conditions as static tension, but cyclic compression leads to the exact opposite of cyclic tension. Consistent with marker expression changes, the singaling pathways of Wnt/ß-catenin and RANKL/OPG show that tissue compression leads to cementum degradation and tension forces to cementogenesis. However, the cementum, and in particular its cementoblasts, remain a research area which should be explored in more detail to understand the underlying mechanism of bone resorption and remodeling after orthodontic treatments.
Exposure to prolonged periods in microgravity is associated with deconditioning of the musculoskeletal system due to chronic changes in mechanical stimulation. Given astronauts will operate on the Lunar surface for extended periods of time, it is critical to quantify both external (e.g., ground reaction forces) and internal (e.g., joint reaction forces) loads of relevant movements performed during Lunar missions. Such knowledge is key to predict musculoskeletal deconditioning and determine appropriate exercise countermeasures associated with extended exposure to hypogravity.
Altered gastrocnemius contractile behavior in former achilles tendon rupture patients during walking
(2022)
Achilles tendon rupture (ATR) remains associated with functional limitations years after injury. Architectural remodeling of the gastrocnemius medialis (GM) muscle is typically observed in the affected leg and may compensate force deficits caused by a longer tendon. Yet patients seem to retain functional limitations during—low-force—walking gait. To explore the potential limits imposed by the remodeled GM muscle-tendon unit (MTU) on walking gait, we examined the contractile behavior of muscle fascicles during the stance phase. In a cross-sectional design, we studied nine former patients (males; age: 45 ± 9 years; height: 180 ± 7 cm; weight: 83 ± 6 kg) with a history of complete unilateral ATR, approximately 4 years post-surgery. Using ultrasonography, GM tendon morphology, muscle architecture at rest, and fascicular behavior were assessed during walking at 1.5 m⋅s–1 on a treadmill. Walking patterns were recorded with a motion capture system. The unaffected leg served as control. Lower limbs kinematics were largely similar between legs during walking. Typical features of ATR-related MTU remodeling were observed during the stance sub-phases corresponding to series elastic element (SEE) lengthening (energy storage) and SEE shortening (energy release), with shorter GM fascicles (36 and 36%, respectively) and greater pennation angles (8° and 12°, respectively). However, relative to the optimal fascicle length for force production, fascicles operated at comparable length in both legs. Similarly, when expressed relative to optimal fascicle length, fascicle contraction velocity was not different between sides, except at the time-point of peak series elastic element (SEE) length, where it was 39 ± 49% lower in the affected leg. Concomitantly, fascicles rotation during contraction was greater in the affected leg during the whole stance-phase, and architectural gear ratios (AGR) was larger during SEE lengthening. Under the present testing conditions, former ATR patients had recovered a relatively symmetrical walking gait pattern. Differences in seen AGR seem to accommodate the profound changes in MTU architecture, limiting the required fascicle shortening velocity. Overall, the contractile behavior of the GM fascicles does not restrict length- or velocity-dependent force potentials during this locomotor task.
This study aims to quantify the kinematics, kinetics and muscular activity of all-out handcycling exercise and examine their alterations during the course of a 15-s sprint test. Twelve able-bodied competitive triathletes performed a 15-s all-out sprint test in a recumbent racing handcycle that was attached to an ergometer. During the sprint test, tangential crank kinetics, 3D joint kinematics and muscular activity of 10 muscles of the upper extremity and trunk were examined using a power metre, motion capturing and surface electromyography (sEMG), respectively. Parameters were compared between revolution one (R1), revolution two (R2), the average of revolution 3 to 13 (R3) and the average of the remaining revolutions (R4). Shoulder abduction and internal-rotation increased, whereas maximal shoulder retroversion decreased during the sprint. Except for the wrist angles, angular velocity increased for every joint of the upper extremity. Several muscles demonstrated an increase in muscular activation, an earlier onset of muscular activation in crank cycle and an increased range of activation. During the course of a 15-s all-out sprint test in handcycling, the shoulder muscles and the muscles associated to the push phase demonstrate indications for short-duration fatigue. These findings are helpful to prevent injuries and improve performance in all-out handcycling.
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.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.
Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, <10 µm thin membranes as mechanical stress sensors of thin cell layers. For this to be successful, the properties (thickness, temperature, dust, wrinkles, etc.) must be precisely controlled. The following parameters of membrane fabrication by means of the Floating-on-Water (FoW) method were investigated: (1) PDMS volume, (2) ambient temperature, (3) membrane deflection and (4) membrane mechanical compliance. Significant differences were found between all PDMS volumes and thicknesses tested (p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3–4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications.
Useful market simulations are key to the evaluation of diferent market designs existing of multiple market mechanisms or rules. Yet a simulation framework which has a comparison of diferent market mechanisms in mind was not found. The need to create an objective view on different sets of market rules while investigating meaningful agent strategies concludes that such a simulation framework is needed to advance the research on this subject. An overview of diferent existing market simulation models is given which also shows the research gap and the missing capabilities of those systems. Finally, a methodology is outlined how a novel market simulation which can answer the research questions can be developed.
Sleep spindles are neurophysiological phenomena that appear to be linked to memory formation and other functions of the central nervous system, and that can be observed in electroencephalographic recordings (EEG) during sleep. Manually identified spindle annotations in EEG recordings suffer from substantial intra- and inter-rater variability, even if raters have been highly trained, which reduces the reliability of spindle measures as a research and diagnostic tool. The Massive Online Data Annotation (MODA) project has recently addressed this problem by forming a consensus from multiple such rating experts, thus providing a corpus of spindle annotations of enhanced quality. Based on this dataset, we present a U-Net-type deep neural network model to automatically detect sleep spindles. Our model’s performance exceeds that of the state-of-the-art detector and of most experts in the MODA dataset. We observed improved detection accuracy in subjects of all ages, including older individuals whose spindles are particularly challenging to detect reliably. Our results underline the potential of automated methods to do repetitive cumbersome tasks with super-human performance.
The recent advances in microbiology have shed light on understanding the role of vitamins beyond the nutritional range. Vitamins are critical in contributing to healthy biodiversity and maintaining the proper function of gut microbiota. The sharing of vitamins among bacterial populations promotes stability in community composition and diversity; however, this balance becomes disturbed in various pathologies. Here, we overview and analyze the ability of different vitamins to selectively and specifically induce changes in the intestinal microbial community. Some schemes and regularities become visible, which may provide new insights and avenues for therapeutic management and functional optimization of the gut microbiota.
Vitamin D plays an essential role in calcium and inorganic phosphate (Pi) homeostasis, maintaining their optimal levels to assure adequate bone mineralization. Vitamin D, as calcitriol (1,25(OH)2D), not only increases intestinal calcium and phosphate absorption but also facilitates their renal reabsorption, leading to elevated serum calcium and phosphate levels. The interaction of 1,25(OH)2D with its receptor (VDR) increases the efficiency of intestinal absorption of calcium to 30–40% and phosphate to nearly 80%. Serum phosphate levels can also influence 1,25 (OH)2D and fibroblast growth factor 23 (FGF23) levels, i.e., higher phosphate concentrations suppress vitamin D activation and stimulate parathyroid hormone (PTH) release, while a high FGF23 serum level leads to reduced vitamin D synthesis. In the vitamin D-deficient state, the intestinal calcium absorption decreases and the secretion of PTH increases, which in turn causes the stimulation of 1,25(OH)2D production, resulting in excessive urinary phosphate loss. Maintenance of phosphate homeostasis is essential as hyperphosphatemia is a risk factor of cardiovascular calcification, chronic kidney diseases (CKD), and premature aging, while hypophosphatemia is usually associated with rickets and osteomalacia. This chapter elaborates on the possible interactions between vitamin D and phosphate in health and disease.
A generalized shear-lag theory for fibres with variable radius is developed to analyse elastic fibre/matrix stress transfer. The theory accounts for the reinforcement of biological composites, such as soft tissue and bone tissue, as well as for the reinforcement of technical composite materials, such as fibre-reinforced polymers (FRP). The original shear-lag theory proposed by Cox in 1952 is generalized for fibres with variable radius and with symmetric and asymmetric ends. Analytical solutions are derived for the distribution of axial and interfacial shear stress in cylindrical and elliptical fibres, as well as conical and paraboloidal fibres with asymmetric ends. Additionally, the distribution of axial and interfacial shear stress for conical and paraboloidal fibres with symmetric ends are numerically predicted. The results are compared with solutions from axisymmetric finite element models. A parameter study is performed, to investigate the suitability of alternative fibre geometries for use in FRP.