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The deformation and damage laws of non-homogeneous irregular structural planes in rocks are the basis for studying the stability of rock engineering. To investigate the damage characteristics of rock containing non-parallel fissures, uniaxial compression tests and numerical simulations were conducted on sandstone specimens containing three non-parallel fissures inclined at 0°, 45° and 90° in this study. The characteristics of crack initiation and crack evolution of fissures with different inclinations were analyzed. A constitutive model for the discontinuous fractures of fissured sandstone was proposed. The results show that the fracture behaviors of fissured sandstone specimens are discontinuous. The stress–strain curves are non-smooth and can be divided into nonlinear crack closure stage, linear elastic stage, plastic stage and brittle failure stage, of which the plastic stage contains discontinuous stress drops. During the uniaxial compression test, the middle or ends of 0° fissures were the first to crack compared to 45° and 90° fissures. The end with small distance between 0° and 45° fissures cracked first, and the end with large distance cracked later. After the final failure, 0° fissures in all specimens were fractured, while 45° and 90° fissures were not necessarily fractured. Numerical simulation results show that the concentration of compressive stress at the tips of 0°, 45° and 90° fissures, as well as the concentration of tensile stress on both sides, decreased with the increase of the inclination angle. A constitutive model for the discontinuous fractures of fissured sandstone specimens was derived by combining the logistic model and damage mechanic theory. This model can well describe the discontinuous drops of stress and agrees well with the whole processes of the stress–strain curves of the fissured sandstone specimens.
Frequency mixing magnetic detection (FMMD) is a sensitive and selective technique to detect magnetic nanoparticles (MNPs) serving as probes for binding biological targets. Its principle relies on the nonlinear magnetic relaxation dynamics of a particle ensemble interacting with a dual frequency external magnetic field. In order to increase its sensitivity, lower its limit of detection and overall improve its applicability in biosensing, matching combinations of external field parameters and internal particle properties are being sought to advance FMMD. In this study, we systematically probe the aforementioned interaction with coupled Néel–Brownian dynamic relaxation simulations to examine how key MNP properties as well as applied field parameters affect the frequency mixing signal generation. It is found that the core size of MNPs dominates their nonlinear magnetic response, with the strongest contributions from the largest particles. The drive field amplitude dominates the shape of the field-dependent response, whereas effective anisotropy and hydrodynamic size of the particles only weakly influence the signal generation in FMMD. For tailoring the MNP properties and parameters of the setup towards optimal FMMD signal generation, our findings suggest choosing large particles of core sizes dc > 25 nm nm with narrow size distributions (σ < 0.1) to minimize the required drive field amplitude. This allows potential improvements of FMMD as a stand-alone application, as well as advances in magnetic particle imaging, hyperthermia and magnetic immunoassays.
Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate inflight assessment to inform exercise programmes is critical due to lack of technologies suitable for spaceflight. Changes in mechanical properties indicate muscle health status and can be measured rapidly and non-invasively using novel technology. A hand-held MyotonPRO device enabled monitoring of muscle health for the first time in spaceflight (> 180 days). Greater/maintained stiffness indicated countermeasures were effective. Tissue stiffness was preserved in the majority of muscles (neck, shoulder, back, thigh) but Tibialis Anterior (foot lever muscle) stiffness decreased inflight vs. preflight (p < 0.0001; mean difference 149 N/m) in all 12 crewmembers. The calf muscles showed opposing effects, Gastrocnemius increasing in stiffness Soleus decreasing. Selective stiffness decrements indicate lack of preservation despite daily inflight countermeasures. This calls for more targeted exercises for lower leg muscles with vital roles as ankle joint stabilizers and in gait. Muscle stiffness is a digital biomarker for risk monitoring during future planetary explorations (Moon, Mars), for healthcare management in challenging environments or clinical disorders in people on Earth, to enable effective tailored exercise programmes.
Advances in polymer science have significantly increased polymer applications in life sciences. We report the use of free-standing, ultra-thin polydimethylsiloxane (PDMS) membranes, called CellDrum, as cell culture substrates for an in vitro wound model. Dermal fibroblast monolayers from 28- and 88-year-old donors were cultured on CellDrums. By using stainless steel balls, circular cell-free areas were created in the cell layer (wounding). Sinusoidal strain of 1 Hz, 5% strain, was applied to membranes for 30 min in 4 sessions. The gap circumference and closure rate of un-stretched samples (controls) and stretched samples were monitored over 4 days to investigate the effects of donor age and mechanical strain on wound closure. A significant decrease in gap circumference and an increase in gap closure rate were observed in trained samples from younger donors and control samples from older donors. In contrast, a significant decrease in gap closure rate and an increase in wound circumference were observed in the trained samples from older donors. Through these results, we propose the model of a cell monolayer on stretchable CellDrums as a practical tool for wound healing research. The combination of biomechanical cell loading in conjunction with analyses such as gene/protein expression seems promising beyond the scope published here.
During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.
Comparison of different training algorithms for the leg extension training with an industrial robot
(2018)
In the past, different training scenarios have been developed and implemented on robotic research platforms, but no systematic analysis and comparison have been done so far. This paper deals with the comparison of an isokinematic (motion with constant velocity) and an isotonic (motion against constant weight) training algorithm. Both algorithms are designed for a robotic research platform consisting of a 3D force plate and a high payload industrial robot, which allows leg extension training with arbitrary six-dimensional motion trajectories. In the isokinematic as well as the isotonic training algorithm, individual paths are defined i n C artesian s pace by sufficient s upport p oses. I n t he i sotonic t raining s cenario, the trajectory is adapted to the measured force as the robot should only move along the trajectory as long as the force applied by the user exceeds a minimum threshold. In the isotonic training scenario however, the robot’s acceleration is a function of the force applied by the user. To validate these findings, a simulative experiment with a simple linear trajectory is performed. For this purpose, the same force path is applied in both training scenarios. The results illustrate that the algorithms differ in the force dependent trajectory adaption.
Training-induced increase in Achilles tendon stiffness affects tendon strain pattern during running
(2019)
Background
During the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.
Methods
Eleven subjects were assigned to a training group performing isometric singleleg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.
Results
Achilles tendon stiffness increased by 18% (P <0:01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P <0:01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.
Discussion
These results show that a training-induced increase in Achilles tendon
stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple inseries models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.
Neuromuscular strength training of the leg extensor muscles plays an important role in the rehabilitation and prevention of age and wealth related diseases. In this paper, we focus on the design and implementation of a Cartesian admittance control scheme for isotonic training, i.e. leg extension and flexion against a predefined weight. For preliminary testing and validation of the designed algorithm an experimental research and development platform consisting of an
industrial robot and a force plate mounted at its end-effector has been used. Linear, diagonal and arbitrary two-dimensional motion trajectories with different weights for the leg extension and flexion part are applied. The proposed algorithm is easily adaptable to trajectories consisting of arbitrary six-dimensional poses and allows the implementation of individualized trajectories.
To prevent the reduction of muscle mass and loss of strength coming along with the human aging process, regular training with e.g. a leg press is suitable. However, the risk of training-induced injuries requires the continuous monitoring and controlling of the forces applied to the musculoskeletal system as well as the velocity along the motion trajectory and the range of motion. In this paper, an adaptive norm-optimal iterative learning control algorithm to minimize the knee joint loadings during the leg extension training with an industrial robot is proposed. The response of the algorithm is tested in simulation for patients with varus, normal and valgus alignment of the knee and compared to the results of a higher-order iterative learning control algorithm, a robust iterative learning control and a recently proposed conventional norm-optimal iterative learning control algorithm. Although significant improvements in performance are made compared to the conventional norm-optimal iterative learning control algorithm with a small learning factor, for the developed approach as well as the robust iterative learning control algorithm small steady state errors occur.
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.
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.
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.
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.
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.
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.
Cell spraying has become a feasible application method for cell therapy and tissue engineering approaches. Different devices have been used with varying success. Often, twin-fluid atomizers are used, which require a high gas velocity for optimal aerosolization characteristics. To decrease the amount and velocity of required air, a custom-made atomizer was designed based on the effervescent principle. Different designs were evaluated regarding spray characteristics and their influence on human adipose-derived mesenchymal stromal cells. The arithmetic mean diameters of the droplets were 15.4–33.5 µm with decreasing diameters for increasing gas-to-liquid ratios. The survival rate was >90% of the control for the lowest gas-to-liquid ratio. For higher ratios, cell survival decreased to approximately 50%. Further experiments were performed with the design, which had shown the highest survival rates. After seven days, no significant differences in metabolic activity were observed. The apoptosis rates were not influenced by aerosolization, while high gas-to-liquid ratios caused increased necrosis levels. Tri-lineage differentiation potential into adipocytes, chondrocytes, and osteoblasts was not negatively influenced by aerosolization. Thus, the effervescent aerosolization principle was proven suitable for cell applications requiring reduced amounts of supplied air. This is the first time an effervescent atomizer was used for cell processing.
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.
Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of Staphylococcus aureus protein A (PA) on every coat protein (CP) subunit (TVCVPA) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCVPA and the wild-type subgroup 3 tobamovirus. TVCVPA could be loaded with more than 500 IgGs per virion, which mediated the immunocapture of fluorescent dyes, GFP, and active enzymes. Bi-enzyme ensembles of cooperating glucose oxidase and horseradish peroxidase were tethered together on the TVCVPA carriers via a single antibody type, with one enzyme conjugated chemically to its Fc region, and the other one bound as a target, yielding synthetic multi-enzyme complexes. In microtiter plates, the TVCVPA-displayed sugar-sensing system possessed a considerably increased reusability upon repeated testing, compared to the IgG-bound enzyme pair in the absence of the virus. A high coverage of the viral adapters was also achieved on Ta2O5 sensor chip surfaces coated with a polyelectrolyte interlayer, as a prerequisite for durable TVCVPA-assisted electrochemical biosensing via modularly IgG-assembled sensor enzymes.
Hydrogen peroxide (H₂O₂), a strong oxidizer, is a commonly used sterilization agent employed during aseptic food processing and medical applications. To assess the sterilization efficiency with H₂O₂, bacterial spores are common microbial systems due to their remarkable robustness against a wide variety of decontamination strategies. Despite their widespread use, there is, however, only little information about the detailed time-resolved mechanism underlying the oxidative spore death by H₂O₂. In this work, we investigate chemical and morphological changes of individual Bacillus atrophaeus spores undergoing oxidative damage using optical sensing with trapping Raman microscopy in real-time. The time-resolved experiments reveal that spore death involves two distinct phases: (i) an initial phase dominated by the fast release of dipicolinic acid (DPA), a major spore biomarker, which indicates the rupture of the spore’s core; and (ii) the oxidation of the remaining spore material resulting in the subsequent fragmentation of the spores’ coat. Simultaneous observation of the spore morphology by optical microscopy corroborates these mechanisms. The dependence of the onset of DPA release and the time constant of spore fragmentation on H₂O₂ shows that the formation of reactive oxygen species from H₂O₂ is the rate-limiting factor of oxidative spore death.
Lead and nickel, as heavy metals, are still used in industrial processes, and are classified as “environmental health hazards” due to their toxicity and polluting potential. The detection of heavy metals can prevent environmental pollution at toxic levels that are critical to human health. In this sense, the electrolyte–insulator–semiconductor (EIS) field-effect sensor is an attractive sensing platform concerning the fabrication of reusable and robust sensors to detect such substances. This study is aimed to fabricate a sensing unit on an EIS device based on Sn₃O₄ nanobelts embedded in a polyelectrolyte matrix of polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) using the layer-by-layer (LbL) technique. The EIS-Sn₃O₄ sensor exhibited enhanced electrochemical performance for detecting Pb²⁺ and Ni²⁺ ions, revealing a higher affinity for Pb²⁺ ions, with sensitivities of ca. 25.8 mV/decade and 2.4 mV/decade, respectively. Such results indicate that Sn₃O₄ nanobelts can contemplate a feasible proof-of-concept capacitive field-effect sensor for heavy metal detection, envisaging other future studies focusing on environmental monitoring.
Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n = 41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vFID; 3.42% ± 1.77% vs. 4.64% ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5–190.2] vs. 189.1 [179.4–197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8–0.9] vs. 0.88 [0.8–0.9], p = 0.007). When combining AVR and vFID, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R = − 0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
Using scenarios is vital in identifying and specifying measures for successfully transforming the energy system. Such transformations can be particularly challenging and require the support of a broader set of stakeholders. Otherwise, there will be opposition in the form of reluctance to adopt the necessary technologies. Usually, processes for considering stakeholders' perspectives are very time-consuming and costly. In particular, there are uncertainties about how to deal with modifications in the scenarios. In principle, new consulting processes will be required. In our study, we show how multi-criteria decision analysis can be used to analyze stakeholders' attitudes toward transition paths. Since stakeholders differ regarding their preferences and time horizons, we employ a multi-criteria decision analysis approach to identify which stakeholders will support or oppose a transition path. We provide a flexible template for analyzing stakeholder preferences toward transition paths. This flexibility comes from the fact that our multi-criteria decision aid-based approach does not involve intensive empirical work with stakeholders. Instead, it involves subjecting assumptions to robustness analysis, which can help identify options to influence stakeholders' attitudes toward transitions.
This study evaluates neuromechanical control and muscle-tendon interaction during energy storage and dissipation tasks in hypergravity. During parabolic flights, while 17 subjects performed drop jumps (DJs) and drop landings (DLs), electromyography (EMG) of the lower limb muscles was combined with in vivo fascicle dynamics of the gastrocnemius medialis, two-dimensional (2D) kinematics, and kinetics to measure and analyze changes in energy management. Comparisons were made between movement modalities executed in hypergravity (1.8 G) and gravity on ground (1 G). In 1.8 G, ankle dorsiflexion, knee joint flexion, and vertical center of mass (COM) displacement are lower in DJs than in DLs; within each movement modality, joint flexion amplitudes and COM displacement demonstrate higher values in 1.8 G than in 1 G. Concomitantly, negative peak ankle joint power, vertical ground reaction forces, and leg stiffness are similar between both movement modalities (1.8 G). In DJs, EMG activity in 1.8 G is lower during the COM deceleration phase than in 1 G, thus impairing quasi-isometric fascicle behavior. In DLs, EMG activity before and during the COM deceleration phase is higher, and fascicles are stretched less in 1.8 G than in 1 G. Compared with the situation in 1 G, highly task-specific neuromuscular activity is diminished in 1.8 G, resulting in fascicle lengthening in both movement modalities. Specifically, in DJs, a high magnitude of neuromuscular activity is impaired, resulting in altered energy storage. In contrast, in DLs, linear stiffening of the system due to higher neuromuscular activity combined with lower fascicle stretch enhances the buffering function of the tendon, and thus the capacity to safely dissipate energy.
Magnetic detection structure for Lab-on-Chip applications based on the frequency mixing technique
(2018)
A magnetic frequency mixing technique with a set of miniaturized planar coils was investigated for use with a completely integrated Lab-on-Chip (LoC) pathogen sensing system. The system allows the detection and quantification of superparamagnetic beads. Additionally, in terms of magnetic nanoparticle characterization ability, the system can be used for immunoassays using the beads as markers. Analytical calculations and simulations for both excitation and pick-up coils are presented; the goal was to investigate the miniaturization of simple and cost-effective planar spiral coils. Following these calculations, a Printed Circuit Board (PCB) prototype was designed, manufactured, and tested for limit of detection, linear response, and validation of theoretical concepts. Using the magnetic frequency mixing technique, a limit of detection of 15 µg/mL of 20 nm core-sized nanoparticles was achieved without any shielding.
The movement of magnetic beads due to a magnetic field gradient is of great interest in different application fields. In this report we present a technique based on a magnetic tweezers setup to measure the velocity factor of magnetically actuated individual superparamagnetic beads in a fluidic environment. Several beads can be tracked simultaneously in order to gain and improve statistics. Furthermore we show our results for different beads with hydrodynamic diameters between 200 and 1000 nm from diverse manufacturers. These measurement data can, for example, be used to determine design parameters for a magnetic separation system, like maximum flow rate and minimum separation time, or to select suitable beads for fixed experimental requirements.
For performing point-of-care molecular diagnostics, magnetic immunoassays constitute a promising alternative to established enzyme-linked immunosorbent assays (ELISA) because they are fast, robust and sensitive. Simultaneous detection of multiple biomolecular targets from one body fluid sample is desired. The aim of this work is to show that multiplex magnetic immunodetection based on magnetic frequency mixing by means of modular immunofiltration columns prepared for different targets is feasible. By calculations of the magnetic response signal, the required spacing between the modules was determined. Immunofiltration columns were manufactured by 3D printing and antibody immobilization was performed in a batch approach. It was shown experimentally that two different target molecules in a sample solution could be individually detected in a single assaying step with magnetic measurements of the corresponding immobilization filters. The arrangement order of the filters and of a negative control did not influence the results. Thus, a simple and reliable approach to multi-target magnetic immunodetection was demonstrated.
In modern bioanalytical methods, it is often desired to detect several targets in one sample within one measurement. Immunological methods including those that use superparamagnetic beads are an important group of techniques for these applications. The goal of this work is to investigate the feasibility of simultaneously detecting different superparamagnetic beads acting as markers using the magnetic frequency mixing technique. The frequency of the magnetic excitation field is scanned while the lower driving frequency is kept constant. Due to the particles’ nonlinear magnetization, mixing frequencies are generated. To record their amplitude and phase information, a direct digitization of the pickup-coil’s signal with subsequent Fast Fourier Transformation is performed. By synchronizing both magnetic beads using frequency scanning in magnetic frequency mixing technique magnetic fields, a stable phase information is gained. In this research, it is shown that the amplitude of the dominant mixing component is proportional to the amount of superparamagnetic beads inside a sample. Additionally, it is shown that the phase does not show this behaviour. Excitation frequency scans of different bead types were performed, showing different phases, without correlation to their diverse amplitudes. Two commercially available beads were selected and a determination of their amount in a mixture is performed as a demonstration for multiplex measurements.
Sensitive and rapid detection of cholera toxin subunit B using magnetic frequency mixing detection
(2019)
Cholera is a life-threatening disease caused by the cholera toxin (CT) as produced by some Vibrio cholerae serogroups. In this research we present a method which directly detects the toxin’s B subunit (CTB) in drinking water. For this purpose we performed a magnetic sandwich immunoassay inside a 3D immunofiltration column. We used two different commercially available antibodies to capture CTB and for binding to superparamagnetic beads. ELISA experiments were performed to select the antibody combination. The beads act as labels for the magnetic frequency mixing detection technique. We show that the limit of detection depends on the type of magnetic beads. A nonlinear Hill curve was fitted to the calibration measurements by means of a custom-written python software. We achieved a sensitive and rapid detection of CTB within a broad concentration range from 0.2 ng/ml to more
than 700 ng/ml.
It has been shown that muscle fascicle curvature increases with increasing contraction level and decreasing muscle–tendon complex length. The analyses were done with limited examination windows concerning contraction level, muscle–tendon complex length, and/or intramuscular position of ultrasound imaging. With this study we aimed to investigate the correlation between fascicle arching and contraction, muscle–tendon complex length and their associated architectural parameters in gastrocnemius muscles to develop hypotheses concerning the fundamental mechanism of fascicle curving. Twelve participants were tested in five different positions (90°/105°*, 90°/90°*, 135°/90°*, 170°/90°*, and 170°/75°*; *knee/ankle angle). They performed isometric contractions at four different contraction levels (5%, 25%, 50%, and 75% of maximum voluntary contraction) in each position. Panoramic ultrasound images of gastrocnemius muscles were collected at rest and during constant contraction. Aponeuroses and fascicles were tracked in all ultrasound images and the parameters fascicle curvature, muscle–tendon complex strain, contraction level, pennation angle, fascicle length, fascicle strain, intramuscular position, sex and age group were analyzed by linear mixed effect models. Mean fascicle curvature of the medial gastrocnemius increased with contraction level (+5 m−1 from 0% to 100%; p = 0.006). Muscle–tendon complex length had no significant impact on mean fascicle curvature. Mean pennation angle (2.2 m−1 per 10°; p < 0.001), inverse mean fascicle length (20 m−1 per cm−1; p = 0.003), and mean fascicle strain (−0.07 m−1 per +10%; p = 0.004) correlated with mean fascicle curvature. Evidence has also been found for intermuscular, intramuscular, and sex-specific intramuscular differences of fascicle curving. Pennation angle and the inverse fascicle length show the highest predictive capacities for fascicle curving. Due to the strong correlations between pennation angle and fascicle curvature and the intramuscular pattern of curving we suggest for future studies to examine correlations between fascicle curvature and intramuscular fluid pressure.
Germany is a frontrunner in setting frameworks for the transition to a low-carbon system. The mobility sector plays a significant role in this shift, affecting different people and groups on multiple levels. Without acceptance from these stakeholders, emission targets are out of reach. This research analyzes how the heterogeneous preferences of various stakeholders align with the transformation of the mobility sector, looking at the extent to which the German transformation paths are supported and where stakeholders are located.
Under the research objective of comparing stakeholders' preferences to identify which car segments require additional support for a successful climate transition, a status quo of stakeholders and car performance criteria is the foundation for the analysis. Stakeholders' hidden preferences hinder the derivation of criteria weightings from stakeholders; therefore, a ranking from observed preferences is used. This study's inverse multi-criteria decision analysis means that weightings can be predicted and used together with a recalibrated performance matrix to explore future preferences toward car segments.
Results show that stakeholders prefer medium-sized cars, with the trend pointing towards the increased potential for alternative propulsion technologies and electrified vehicles. These insights can guide the improved targeting of policy supporting the energy and mobility transformation. Additionally, the method proposed in this work can fully handle subjective approaches while incorporating a priori information. A software implementation of the proposed method completes this work and is made publicly available.
On the applicability of several tests to models with not identically distributed random effects
(2023)
We consider Kolmogorov–Smirnov and Cramér–von-Mises type tests for testing central symmetry, exchangeability, and independence. In the standard case, the tests are intended for the application to independent and identically distributed data with unknown distribution. The tests are available for multivariate data and bootstrap procedures are suitable to obtain critical values. We discuss the applicability of the tests to random effects models, where the random effects are independent but not necessarily identically distributed and with possibly unknown distributions. Theoretical results show the adequacy of the tests in this situation. The quality of the tests in models with random effects is investigated by simulations. Empirical results obtained confirm the theoretical findings. A real data example illustrates the application.
We consider time-dependent portfolios and discuss the allocation of changes in the risk of a portfolio to changes in the portfolio’s components. For this purpose we adopt established allocation principles. We also use our approach to obtain forecasts for changes in the risk of the portfolio’s components. To put the approach into practice we present an implementation based on the output of a simulation. Allocation is illustrated with an example portfolio in the context of Solvency II. The quality of the forecasts is investigated with an empirical study.
Motile cilia are hair-like cell extensions that beat periodically to generate fluid flow along various epithelial tissues within the body. In dense multiciliated carpets, cilia were shown to exhibit a remarkable coordination of their beat in the form of traveling metachronal waves, a phenomenon which supposedly enhances fluid transport. Yet, how cilia coordinate their regular beat in multiciliated epithelia to move fluids remains insufficiently understood, particularly due to lack of rigorous quantification. We combine experiments, novel analysis tools, and theory to address this knowledge gap. To investigate collective dynamics of cilia, we studied zebrafish multiciliated epithelia in the nose and the brain. We focused mainly on 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. Even though synchronization is local only, we observed global patterns of traveling metachronal waves across the zebrafish multiciliated epithelium. Intriguingly, these global wave direction patterns are conserved across individual fish, but different for left and right noses, 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, i.e., cilia colliding with each other, 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 coincide and generate metachronal wave patterns in multiciliated epithelia, which enhance their physiological function of fluid pumping.
Based on the European Space Agency (ESA) Science in Space Environment (SciSpacE) community White Paper “Human Physiology – Musculoskeletal system”, this perspective highlights unmet needs and suggests new avenues for future studies in musculoskeletal research to enable crewed exploration missions. The musculoskeletal system is essential for sustaining physical function and energy metabolism, and the maintenance of health during exploration missions, and consequently mission success, will be tightly linked to musculoskeletal function. Data collection from current space missions from pre-, during-, and post-flight periods would provide important information to understand and ultimately offset musculoskeletal alterations during long-term spaceflight. In addition, understanding the kinetics of the different components of the musculoskeletal system in parallel with a detailed description of the molecular mechanisms driving these alterations appears to be the best approach to address potential musculoskeletal problems that future exploratory-mission crew will face. These research efforts should be accompanied by technical advances in molecular and phenotypic monitoring tools to provide in-flight real-time feedback.
The Cramér-von-Mises distance is applied to the distribution of the excess over a confidence level. Asymptotics of related statistics are investigated, and it is seen that the obtained limit distributions differ from the classical ones. For that reason, quantiles of the new limit distributions are given and new bootstrap techniques for approximation purposes are introduced and justified. The results motivate new one-sample goodness-of-fit tests for the distribution of the excess over a confidence level and a new confidence interval for the related fitting error. Simulation studies investigate size and power of the tests as well as coverage probabilities of the confidence interval in the finite sample case. A practice-oriented application of the Cramér-von-Mises tests is the determination of an appropriate confidence level for the fitting approach. The adoption of the idea to the well-known problem of threshold detection in the context of peaks over threshold modelling is sketched and illustrated by data examples.
In this paper, we provide an analytical study of the transmission eigenvalue problem with two conductivity parameters. We will assume that the underlying physical model is given by the scattering of a plane wave for an isotropic scatterer. In previous studies, this eigenvalue problem was analyzed with one conductive boundary parameter whereas we will consider the case of two parameters. We prove the existence and discreteness of the transmission eigenvalues as well as study the dependence on the physical parameters. We are able to prove monotonicity of the first transmission eigenvalue with respect to the parameters and consider the limiting procedure as the second boundary parameter vanishes. Lastly, we provide extensive numerical experiments to validate the theoretical work.
Field-effect EIS (electrolyte-insulator-semiconductor) sensors modified with a positively charged weak polyelectrolyte layer have been applied for the electrical detection of DNA (deoxyribonucleic acid) immobilization and hybridization by the intrinsic molecular charge. The EIS sensors are able to detect the existence of target DNA amplicons in PCR (polymerase chain reaction) samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process. Due to their miniaturized setup, compatibility with advanced micro- and nanotechnologies, and ability to detect biomolecules by their intrinsic molecular charge, those sensors can serve as possible platform for the development of label-free DNA chips. Possible application fields as well as challenges and limitations will be discussed.
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.
It was generally believed that coal sources are not favorable as live-in habitats for microorganisms due to their recalcitrant chemical nature and negligible decomposition. However, accumulating evidence has revealed the presence of diverse microbial groups in coal environments and their significant metabolic role in coal biogeochemical dynamics and ecosystem functioning. The high oxygen content, organic fractions, and lignin-like structures of lower-rank coals may provide effective means for microbial attack, still representing a greatly unexplored frontier in microbiology. Coal degradation/conversion technology by native bacterial and fungal species has great potential in agricultural development, chemical industry production, and environmental rehabilitation. Furthermore, native microalgal species can offer a sustainable energy source and an excellent bioremediation strategy applicable to coal spill/seam waters. Additionally, the measures of the fate of the microbial community would serve as an indicator of restoration progress on post-coal-mining sites. This review puts forward a comprehensive vision of coal biodegradation and bioprocessing by microorganisms native to coal environments for determining their biotechnological potential and possible applications.
Ambitious climate targets affect the competitiveness of industries in the international market. To prevent such industries from moving to other countries in the wake of increased climate protection efforts, cost adjustments may become necessary. Their design requires knowledge of country-specific production costs. Here, we present country-specific cost figures for different production routes of steel, paying particular attention to transportation costs. The data can be used in floor price models aiming to assess the competitiveness of different steel production routes in different countries (Rübbelke, 2022).
In a special paired sample case, Hotelling’s T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given.
Hotelling’s T² tests in paired and independent survey samples are compared using the traditional asymptotic efficiency concepts of Hodges–Lehmann, Bahadur and Pitman, as well as through criteria based on the volumes of corresponding confidence regions. Conditions characterizing the superiority of a procedure are given in terms of population canonical correlation type coefficients. Statistical tests for checking these conditions are developed. Test statistics based on the eigenvalues of a symmetrized sample cross-covariance matrix are suggested, as well as test statistics based on sample canonical correlation type coefficients.
The paper deals with the asymptotic behaviour of estimators, statistical tests and confidence intervals for L²-distances to uniformity based on the empirical distribution function, the integrated empirical distribution function and the integrated empirical survival function. Approximations of power functions, confidence intervals for the L²-distances and statistical neighbourhood-of-uniformity validation tests are obtained as main applications. The finite sample behaviour of the procedures is illustrated by a simulation study.
Suppose we have k samples X₁,₁,…,X₁,ₙ₁,…,Xₖ,₁,…,Xₖ,ₙₖ with different sample sizes ₙ₁,…,ₙₖ and unknown underlying distribution functions F₁,…,Fₖ as observations plus k families of distribution functions {G₁(⋅,ϑ);ϑ∈Θ},…,{Gₖ(⋅,ϑ);ϑ∈Θ}, each indexed by elements ϑ from the same parameter set Θ, we consider the new goodness-of-fit problem whether or not (F₁,…,Fₖ) belongs to the parametric family {(G₁(⋅,ϑ),…,Gₖ(⋅,ϑ));ϑ∈Θ}. New test statistics are presented and a parametric bootstrap procedure for the approximation of the unknown null distributions is discussed. Under regularity assumptions, it is proved that the approximation works asymptotically, and the limiting distributions of the test statistics in the null hypothesis case are determined. Simulation studies investigate the quality of the new approach for small and moderate sample sizes. Applications to real-data sets illustrate how the idea can be used for verifying model assumptions.
A nonparametric goodness-of-fit test for random variables with values in a separable Hilbert space is investigated. To verify the null hypothesis that the data come from a specific distribution, an integral type test based on a Cramér-von-Mises statistic is suggested. The convergence in distribution of the test statistic under the null hypothesis is proved and the test's consistency is concluded. Moreover, properties under local alternatives are discussed. Applications are given for data of huge but finite dimension and for functional data in infinite dimensional spaces. A general approach enables the treatment of incomplete data. In simulation studies the test competes with alternative proposals.
The paper deals with an asymptotic relative efficiency concept for confidence regions of multidimensional parameters that is based on the expected volumes of the confidence regions. Under standard conditions the asymptotic relative efficiencies of confidence regions are seen to be certain powers of the ratio of the limits of the expected volumes. These limits are explicitly derived for confidence regions associated with certain plugin estimators, likelihood ratio tests and Wald tests. Under regularity conditions, the asymptotic relative efficiency of each of these procedures with respect to each one of its competitors is equal to 1. The results are applied to multivariate normal distributions and multinomial distributions in a fairly general setting.
Let X₁,…,Xₙ be independent and identically distributed random variables with distribution F. Assuming that there are measurable functions f:R²→R and g:R²→R characterizing a family F of distributions on the Borel sets of R in the way that the random variables f(X₁,X₂),g(X₁,X₂) are independent, if and only if F∈F, we propose to treat the testing problem H:F∈F,K:F∉F by applying a consistent nonparametric independence test to the bivariate sample variables (f(Xᵢ,Xⱼ),g(Xᵢ,Xⱼ)),1⩽i,j⩽n,i≠j. A parametric bootstrap procedure needed to get critical values is shown to work. The consistency of the test is discussed. The power performance of the procedure is compared with that of the classical tests of Kolmogorov–Smirnov and Cramér–von Mises in the special cases where F is the family of gamma distributions or the family of inverse Gaussian distributions.
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.
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.