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The safety approval of Highly Automated Vehicles (HAV) still faces the automotive industry with economic and legal challenges. For verification and validation, it is essential to describe the intended behavior of an HAV in the development process in order to prove safety. The demand for this behavior comes from the traffic rules which are instantiated by the present scenery around the vehicle (e.g. traffic signs or road markings). The Operational Design Domain (ODD) specifies the scenery in which an HAV may operate, but current descriptions fail to explicitly represent the associated behavioral demand of the scenery. We propose a new approach for a Behavior-Semantic Scenery Description (BSSD) in order to describe the behavior space of a present scenery. A behavior space represents the delimitation of the legally possible behavior. The BSSD explicitly links the scenery with the behavioral demand for HAV. Based on identified goals and challenges for such an approach, we derive requirements for a generic structure of the description for complete road networks. All required elements to represent the behavior space of the scenery are identified. Within real world examples, we present an instance of the BSSD integrated into the HD-map framework Lanelet2 to prove the applicability of the description. The presented approach supports development, test and operation of HAV by closing the knowledge gap of where a vehicle has to behave in which limits within an ODD.

Sunlight is the primary source of energy in forest ecosystems and subcanopy light regimes largely determine the establishment, growth and dispersal of plants and thus forest floor plant communities. Subcanopy light regimes are highly variable in both space and time, which makes monitoring them challenging. In this study, we assess the potential of Sentinel-1 and Sentinel-2 time series for predicting subcanopy light regimes in temperate mountain forests. We trained different random forest regression models predicting field-measured total site factor (TSF, proportion of potential direct and diffuse solar radiation reaching the forest floor, here defined as the transition zone between belowground and aboveground biomass) from a set of metrics derived from Sentinel-1 and Sentinel-2 time series. Model performance was benchmarked against a model based on structural metrics derived from Airborne Laser Scanning (ALS) data, serving as an empirical gold-standard in modelling subcanopy light regimes. We found that Sentinel-1 and Sentinel-2 time series performed nearly as good as the model based on high-resolution ALS data (R2/RMSE of 0.80/0.11 for Sentinel-1/2 compared to R2/RMSE of 0.90/0.08 for ALS). We furthermore tested the generalizability of the trained models to two new sites not used for training for which field data was available for validation. Prediction accuracy for the ALS model decreased substantially for the two independent test sites due to variable ALS data quality and acquisition date (ΔR2/ΔRMSE of 0.29/0.05 and 0.11/0.03 for both independent test sites). The prediction accuracy of the Sentinel-1/2 model, however, remained more stable (ΔR2/ΔRMSE of 0.13/0.02 and 0.13/0.04). We therefore conclude that a combination of Sentinel-1 and Sentinel-2 time series has the potential to map subcanopy light conditions spatially and temporally independent of the availability of high-resolution ALS data. This has important implications for the operational monitoring of forest ecosystems across large scales, which is often limited by the challenges related to acquiring airborne datasets.

New mobility concepts are needed as cities become ever more congested and polluted by traffic. One factor for the growing traffic volume is the increasing delivery traffic leading to a need for sustainable concepts for urban logistics and last-mile delivery. Innovative vehicle concepts, like automated micro-vehicles, present one promising approach. However, not much is yet known about drivers and barriers for the acceptance of these vehicles from the perspective of other road users – i.e. those people sharing traffic space with automated micro-vehicles. In two consecutive animation-based experiments (n = 107, n = 543), we analysed the effect of varying behaviour and design of automated micro-vehicles on other road users’ risk perception, trust, and acceptance. Speed, braking behaviour, automation mode, number of vehicles in convoy, distance between vehicles as well as colour design significantly affect risk perceptions, trust, and partly acceptance. The results inform the development and regulation of automated micro-vehicles.

Abstract Background Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention. Case presentation We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer–BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient’s symptoms. Conclusions Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.

Abstract Aims We continuously monitored right ventricular pressures and the estimated diastolic pulmonary artery pressure (ePAD) for up to 30 days in mechanically ventilated patients with severe COVID‐19 acute respiratory distress syndrome in order to detect and treat right ventricular and pulmonary artery hypertension. Methods and Results We retrospectively evaluated right ventricular pressures and the ePAD measured in 30 invasively ventilated COVID‐19 acute respiratory distress syndrome patients between 1 October 2020 and 31 March 2021. We divided the patients into two groups, survivors and non‐survivors based on their 60 day mortality. Primary outcome variables were the values of right ventricular pressures and the ePAD over time after insertion of the right ventricular probe. Right ventricular systolic pressure [RVSP, (IQR; 25th to 75th percentile)] was significantly lower on the first and the last measurement day in the survivors compared with the non‐survivors [Day 1: 38 (27–45) vs. 46 (44–49), P = 0.036; last day: 36 (27–44) vs. 51 (40–57) mmHg, P = 0.006]. 16/22 survivors and 7/8 non‐survivors received sildenafil orally, one survivor received additionally inhaled nitric oxide and one survivor and one non‐survivor each inhaled iloprost. On the last measurement day, both right ventricular pressure amplitude [31 (26–37) vs. 38 (35–47) mmHg, P = 0.027] and ePAD [22 (16–26) vs. 31 (23–34) mmHg, P = 0.043] were significantly lower in the survivors compared with the non‐survivors. Four patients in the survivor group developed excessive high RVSP in the course of their disease (peak: 57/61/78/105 mmHg). After sildenafil 20 mg every 8 h, additional inhaled nitric oxide (20 ppm) in one and additional inhaled iloprost 20 μg every 4 h in another patient RVSP consecutively decreased substantially in all four patients until the end of the measurement period (47/23/42/47 mmHg). Conclusions The RVSP and right ventricular pressure amplitude both were significantly lower in the survivors compared with those in the non‐survivors with a significant decrease in RVSP over time in the survivors suggesting successful lowering by pulmonary vasodilators. The ePAD as an indicator of left heart failure was significantly higher in non‐survivors compared to the surviving patients.

Abstract We evaluated pressure‐based right ventricular ejection fraction (RVEF) and diastolic isovolumetric relaxation time constant (Tau) from continuously (up to 30 days) invasive measured right ventricular pressures in mechanically ventilated patients with severe COVID‐19 acute respiratory distress syndrome (ARDS). We retrospectively calculated beat‐to‐beat ejection fraction from right ventricular pressures and dp/dt maximum and minimum in 39 patients treated between October 1st, 2020 and June 30th, 2021. After performing a stepwise logistic regression with survival as a dependent variable, we divided the patients into survivors and nonsurvivors based on their 60‐day mortality. Independent outcome variables were the values of RVEF and Tau over time after insertion of the right ventricular probe along with right ventricular systolic and diastolic pressures (RVSP) and the estimated pulmonary artery diastolic pressure (ePAD). RVEF increased significantly over time in the survivors (estimate: 0.354; 95% confidence interval, CI: 0.18–0.53; p

Abstract Non-small cell lung cancer (NSCLC) has a poor prognosis with a 5 year survival rate of only ~ 10%. Important driver mutations underlying NSCLC affect the epidermal growth factor receptor (EGFR) causing the constitutive activation of its tyrosine kinase domain. There are efficient EGFR tyrosine kinase inhibitors (TKIs), but patients develop inevitably a resistance against these drugs. On the other hand, KCa3.1 channels contribute to NSCLC progression so that elevated KCa3.1 expression is a strong predictor of poor NSCLC patient prognosis. The present study tests whether blocking KCa3.1 channels increases the sensitivity of NSCLC cells towards the EGFR TKI erlotinib and overcomes drug resistance. mRNA expression of KCa3.1 channels in erlotinib-sensitive and -resistant NSCLC cells was analysed in datasets from Gene expression omnibus (GEO) and ArrayExpress. We assessed proliferation and migration of NSCLC cells. These (live cell-imaging) experiments were complemented by patch clamp experiments and Western blot analyses. We identified three out of four datasets comparing erlotinib-sensitive and -resistant NSCLC cells which revealed an altered expression of KCa3.1 mRNA in erlotinib-resistant NSCLC cells. Therefore, we evaluated the combined effect of erlotinib and the KCa3.1 channel inhibition with sencapoc. Erlotinib elicits a dose-dependent inhibition of migration and proliferation of NSCLC cells. The simultaneous application of the KCa3.1 channel blocker senicapoc increases the sensitivity towards a low dose of erlotinib (300 nmol/L) which by itself has no effect on migration and proliferation. Partial erlotinib resistance can be overcome by KCa3.1 channel blockade. The sensitivity towards erlotinib as well as the potentiating effect of KCa3.1 blockade is further increased by mimicking hypoxia. Our results suggest that KCa3.1 channel blockade may constitute a therapeutic concept for treating NSCLC and overcome EGFR TKI resistance. We propose that this is due to complementary mechanisms of action of both blockers.

In this work, the image formation in a confocal laser scanning microscope (CLSM) is investigated for custom-made multi-cylinder phantoms. The cylinder structures were fabricated using 3D direct laser writing and consist of parallel cylinders with radii of 5 and 10 μm for the respective multi-cylinder phantom, with overall dimensions of about 200×200×200 μm3. Measurements were performed for different refractive index differences and by varying other parameters of the measurement system, such as pinhole size or numerical aperture (NA). For theoretical comparison, the confocal setup was implemented in an in-house developed tetrahedron-based and GPU-accelerated Monte Carlo (MC) software. The simulation results for a cylindrical single scatterer were first compared with the analytical solution of Maxwell’s equations in two dimensions for prior validation. Subsequently, the more complex multi-cylinder structures were simulated using the MC software and compared with the experimental results. For the largest refractive index difference, i.e., air as the surrounding medium, the simulated and measured data show a high degree of agreement, with all the key features of the CLSM image being reproduced by the simulation. Even with a significant reduction in the refractive index difference by the use of immersion oil to values as low as 0.005, a good agreement between simulation and measurement was observed, particularly with respect to the increase in penetration depth.

The pollution of the environment with microplastics in general, and in particular, the contamination of our drinking water and other food items, has increasingly become the focus of public attention in recent years. In order to better understand the entry pathways into the human food chain and thus prevent them if possible, a precise characterization of the particles concerning their size and material is indispensable. Particularly small plastic particles pose a special challenge since their material can only be determined by means of large experimental effort. In this work, we present a proof of principle experiment that allows the precise determination of the plastic type and the particle size in a single step. The experiment combines elastic light scattering (Mie scattering) with inelastic light scattering (Raman scattering), the latter being used to determine the plastic type. We conducted Monte Carlo simluations for the elastically scattered light for different kinds of plastics in a microfluidic cuvette which we could reproduce in the experiment. We were able to measure the Raman signals for different microplastics in the same measurement as the elastically scattered light and thereby determine their material. This information was used to select the appropriate Monte Carlo simulation data and to assign the correct particle size to different materials with only one calibration measurement.

BackgroundWhile cerebral lesions are common in Fabry disease (FD), spinal lesions have not been described, and their presence was suggested to be indicative of multiple sclerosis. Here, we present a FD patient with histopathological confirmed spinal ischemic stroke.Case presentationA patient with genetically and biochemically diagnosed FD and characteristic manifestations (acroparesthesia, angiokeratomas, hypohidrosis, microalbuminuria, myocardial hypertrophy) presented with paraplegia, loss of all sensory modalities below Th9, and loss of bowel and bladder function. While cranial MRI was inconspicuous, spinal MRI showed a T2 hyperintense, non-contrast-enhancing lesion of the thoracic spinal cord. Lumbar puncture revealed mild pleocytosis, increased total protein and lactate levels, decreased glucose ratio, and negative oligoclonal bands. Rheumatic, neoplastic, and infectious disorders were excluded. The patient received intravenous and intrathecal methylprednisolone, plasmapheresis, intravenous immunoglobulins, and cyclophosphamide without clinical improvement. A biopsy of the thoracic lesion was performed. A histopathological examination revealed necrotic tissue consistent with spinal cord ischemia. Diagnostic work-up for stroke etiology clarification was not conspicuous. Two years onward, the patient suffered from a pontine infarction and a transient ischemic attack.ConclusionThe current case highlights the possible occurrence of spinal ischemic lesions in FD. Thus, the diagnosis of FD should not be prematurely discarded in the presence of spinal lesions.

Recent trends in 3D cell culturing has placed organotypic tissue models at another level. Now, not only is the microenvironment at the cynosure of this research, but rather, microscopic geometrical parameters are also decisive for mimicking a tissue model. Over the years, technologies such as micromachining, 3D printing, and hydrogels are making the foundation of this field. However, mimicking the topography of a particular tissue-relevant substrate can be achieved relatively simply with so-called template or morphology transfer techniques. Over the last 15 years, in one such research venture, we have been investigating a micro thermoforming technique as a facile tool for generating bioinspired topographies. We call them MatriGrid®s. In this research account, we summarize our learning outcome from this technique in terms of the influence of 3D micro morphologies on different cell cultures that we have tested in our laboratory. An integral part of this research is the evolution of unavoidable aspects such as possible label-free sensing and fluidic automatization. The development in the research field is also documented in this account.

Determining the range, status, ecology and behaviour of species from areas where surveys and samplings are uncommon or difficult to conduct is a challenge, such as in the Democratic People’s Republic of Korea (DPR Korea). Here, we used genetic samples, field surveys, call recordings, photographic identification and a literature review to estimate the presence, range and status of amphibians in the DPR Korea. From our combined results and based on the IUCN Red List categories and criteria, we were able to estimate the national threat levels for most species. Our results demonstrated the presence of 18 native species and the suspected presence of Karsenia koreana and two Onychodactylus species. We reported the first record for Rana uenoi in the vicinity of Pyongyang using molecular tools and similarly confirmed the presence of Dryophytes japonicus at the same location. Based on distribution and modelling, we can expect the contact zone between species within the Rana and Onychodactylus genera to be located along the Changbai Massif, a mountain range that marks a shift in ecoregions and acts as a barrier to dispersion. The species richness was higher in the lowlands and at lower latitudes, with such areas populated by up to 11 species, while more northern regions were characterised by species richness of about half of that value. The combination of ecological models and known threats resulted in the recommendation of ten species as threatened at the national level following the IUCN Red List categories and criteria. This high number of threatened species was anticipated based on the high threat level to amphibians in bordering nations and globally. While the ecology of species in the DPR Korea is still understudied, we argue that species relying on agricultural wetlands such as rice paddies are not under imminent threat due to the enduring presence of extensive agricultural landscapes with low rates of chemical use and mechanisation. The maintenance of such landscapes is a clear benefit to amphibian species, in contrast to more industrialised agricultural landscapes in neighbouring nations. In comparison, the status of species dependent on forested habitats is unclear and threat levels are likely to be higher because of deforestation, as in neighbouring nations.

Multi-material jetting (CerAM MMJ, previously T3DP) enables the additive manufacturing of ceramics, metals, glass and hardmetals, demonstrating comparatively high solid contents of the processed materials. The material is applied drop by drop onto a substrate. The droplets can be adapted to the component to be produced by a large degree of freedom in parameterization. Thus, large volumes can be processed quickly and fine structures can be displayed in detail, based on the droplet size. Data-driven methods are applied to build process knowledge and to contribute to the optimization of CerAM MMJ manufacturing processes. As a basis for the computational exploitation of mass sensor data from the technological process chain for manufacturing a component with CerAM MMJ, a data management plan was developed with the help of an engineering workflow. Focusing on the process step of green part production, droplet structures as intermediate products of 3D generation were described by means of droplet height, droplet circularity, the number of ambient satellite particles, as well as the associated standard deviations. First of all, the weighting of the factors influencing the droplet geometry was determined by means of single factor preliminary tests, in order to be able to reduce the number of factors to be considered in the detailed test series. The identification of key influences (falling time, needle lift, rising time, air supply pressure) permitted an optimization of the droplet geometry according to the introduced target characteristics by means of a design of experiments.

Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

Like heparan sulfate proteoglycans, some monosaccharides and glycosaminoglycans, such as sulfated glucosamine (GS) and chondroitin (CS), integrate the vascular extracellular matrix and may influence vascular endothelial cell growth. To assess the effects of these substances on blood vessel formation, we used the chick yolk sac membrane (YSM) model and fractal geometry quantification, which provided an objective in vivo method for testing potential agents that promote vasculogenesis and angiogenesis. An image processing method was developed to evaluate YSM capillary vessels after they were implanted in a methylcellulose disk of GS or CS at a concentration between 0.001-0.1mg/disk (performed on 2-day old embryos). This method resulted in a binary image of the microvascular network (white vessels on a black background). Fractal box-counting (DBC) and information (DINF) dimensions were used to quantify the activity of GS and CS in vasculogenesis and angiogenesis. YSM treated with GS (0.001-0.1mg) and CS (0.03-0.1mg) showed an increase in fractal dimensions that corresponded to vitelline vessel growth compared to the control group (vehicle), with GS displaying higher fractal dimension values., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to determine the indications, the safety, and the efficacy of pediatric radiofrequency catheter ablation (RFCA) in infants., Methods and Results: Data from the pediatric RFCA registry were reviewed. Between August 1989 and January 1999, 137 infants, defined by age 0 to 1.5 years (median 0.7 years; weight 1.9 to 14.8 kg, median 10 kg), underwent 152 procedures in 27 of 49 registry centers (55%), compared with 5960 noninfants undergoing 6610 procedures during a comparable period. Structural heart disease was present in 36% of infants, compared with 11.2% of noninfants (P<0.0001). RFCA in infants was performed more commonly for drug resistance or life-threatening arrhythmias than in noninfants. No differences were found between infants and noninfants in success for all tachycardia substrates (87.6% versus 90.6%, P=0.11), for single accessory pathways (94.5% versus 91.5%, P=0.4), or for total (7.8% versus 7.4%, P=1) and major (4.6% versus 2.9%, P=0.17) complications. Neither success for infants with a single accessory pathway nor complications for the entire infant group were related to weight, age, center size, or the presence of structural heart disease. Centers that performed infant procedures, however, enrolled more patients overall in the registry than those that did not perform infant procedures, and successful procedures in infants were performed by more experienced physicians than failed procedures., Conclusions: Compared with noninfants, RFCA in infants is usually performed for drug resistance or life-threatening arrhythmias, often in the presence of structural heart disease. The data support the use of RFCA by experienced physicians in selected infants.

To determine the effects of anabolic steroids on myocardial structure, VO2max, and body composition, experienced age-matched male weight trainers (M age 26.5 yr) who either used (U) (N = 11) or did not use (NU) (N = 13) anabolic steroids were evaluated. Steroid users were tested while off cycle (U-OFF) for at least 8 wk, again at the peak (U-ON) of their subsequent cycle, and to the nonuser group of weight trainers. Echocardiographic measurements revealed significant differences in left ventricular (LV) mass (182.8 +/- 26.9 g vs 210.6 +/- 42 g; P < 0.05) and interventricular septum thickness (IVS) (10.3 +/- 1.2 mm vs 11.1 +/- 1.2 mm; P < 0.05) between U-OFF and U-ON, respectively. NU measurements were also significantly different than U-ON for LV mass and IVS (186.5 +/- 36.2 g; P < 0.05 and 9.3 +/- 1.2 mm; P < 0.05, respectively). LV diameter in diastole was significantly greater in U-ON (59.1 mm) than in NU (55.7 mm; P < 0.05). In addition, LV posterior wall thickness in diastole was greater in U-ON compared with NU (11.2 mm vs 9.5 mm; P < 0.05). VO2max values for both user groups were significantly lower than those for NU (U-OFF = 41.0 +/- 4.5 ml.kg-1.min-1, U-ON = 41.0 +/- 5.7 ml.kg-1.min-1, and NU = 50.2 +/- 6.4 ml.kg-1.min-1; P < 0.05). Despite these morphological changes within the myocardium, there were no concomitant increases in shortening fraction.

Seventeen term newborn infants (control subjects) and 17 whose mothers had been given intravaginal doses of prostaglandin E2 (PGE2) were examined serially by color Doppler echocardiography to determine whether maternal PGE2 prolonged ductal patency. No clinically relevant differences in closure times were found. Low-dose intravaginal PGE2 therapy was not associated with prolonged ductal patency in term infants.

The accuracy of duplex pulsed Doppler echocardiography (d-PDE) for detecting mitral regurgitation was evaluated in 35 patients undergoing d-PDE, cardiac auscultation, and left ventriculography. With three transducer positions, the overall d-PDE sensitivity was 95%, specificity was 100%, positive predictive value was 100%, negative predictive value was 94%, and diagnostic accuracy was 97% compared with ventriculography. This technique was superior to auscultation (sensitivity 74%, specificity 94%, positive predictive value 93%, negative predictive value 75%, diagnostic accuracy 83%). No false-positive d-PDE results occurred, but discordant false-negative results occurred frequently among the three transducer positions. If discordant negative results are considered to be false negative, then d-PDE is both sensitive and specific when mitral regurgitation is defined as systolic spectral broadening in any one transducer position.